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  1. Central administration of nicotine suppresses tracheobronchial cough in anesthetized cats

    PubMed Central

    Rose, M. J.; Pitts, T. E.; Mortensen, A.; Corrie, L. W.; Davenport, P. W.; Bolser, D. C.

    2014-01-01

    We tested the hypothesis that nicotine, which acts peripherally to promote coughing, might inhibit reflex cough at a central site. Nicotine was administered via the vertebral artery [intra-arterial (ia)] to the brain stem circulation and by microinjections into a restricted area of the caudal ventral respiratory column in 33 pentobarbital anesthetized, spontaneously breathing cats. The number of coughs induced by mechanical stimulation of the tracheobronchial airways; amplitudes of the diaphragm, abdominal muscle, and laryngeal muscles EMGs; and several temporal characteristics of cough were analyzed after administration of nicotine and compared with those during control and recovery period. (−)Nicotine (ia) reduced cough number, cough expiratory efforts, blood pressure, and heart rate in a dose-dependent manner. (−)Nicotine did not alter temporal characteristics of the cough motor pattern. Pretreatment with mecamylamine prevented the effect of (−)nicotine on blood pressure and heart rate, but did not block the antitussive action of this drug. (+)Nicotine was less potent than (−)nicotine for inhibition of cough. Microinjections of (−)nicotine into the caudal ventral respiratory column produced similar inhibitory effects on cough as administration of this isomer by the ia route. Mecamylamine microinjected in the region just before nicotine did not significantly reduce the cough suppressant effect of nicotine. Nicotinic acetylcholine receptors significantly modulate functions of brain stem and in particular caudal ventral respiratory column neurons involved in expression of the tracheobronchial cough reflex by a mecamylamine-insensitive mechanism. PMID:25477349

  2. Central administration of nicotine suppresses tracheobronchial cough in anesthetized cats.

    PubMed

    Poliacek, I; Rose, M J; Pitts, T E; Mortensen, A; Corrie, L W; Davenport, P W; Bolser, D C

    2015-02-01

    We tested the hypothesis that nicotine, which acts peripherally to promote coughing, might inhibit reflex cough at a central site. Nicotine was administered via the vertebral artery [intra-arterial (ia)] to the brain stem circulation and by microinjections into a restricted area of the caudal ventral respiratory column in 33 pentobarbital anesthetized, spontaneously breathing cats. The number of coughs induced by mechanical stimulation of the tracheobronchial airways; amplitudes of the diaphragm, abdominal muscle, and laryngeal muscles EMGs; and several temporal characteristics of cough were analyzed after administration of nicotine and compared with those during control and recovery period. (-)Nicotine (ia) reduced cough number, cough expiratory efforts, blood pressure, and heart rate in a dose-dependent manner. (-)Nicotine did not alter temporal characteristics of the cough motor pattern. Pretreatment with mecamylamine prevented the effect of (-)nicotine on blood pressure and heart rate, but did not block the antitussive action of this drug. (+)Nicotine was less potent than (-)nicotine for inhibition of cough. Microinjections of (-)nicotine into the caudal ventral respiratory column produced similar inhibitory effects on cough as administration of this isomer by the ia route. Mecamylamine microinjected in the region just before nicotine did not significantly reduce the cough suppressant effect of nicotine. Nicotinic acetylcholine receptors significantly modulate functions of brain stem and in particular caudal ventral respiratory column neurons involved in expression of the tracheobronchial cough reflex by a mecamylamine-insensitive mechanism. PMID:25477349

  3. Jejunal administration of glucose enhances acyl ghrelin suppression in obese humans.

    PubMed

    Tamboli, Robyn A; Sidani, Reem M; Garcia, Anna E; Antoun, Joseph; Isbell, James M; Albaugh, Vance L; Abumrad, Naji N

    2016-07-01

    Ghrelin is a gastric hormone that stimulates hunger and worsens glucose metabolism. Circulating ghrelin is decreased after Roux-en-Y gastric bypass (RYGB) surgery; however, the mechanism(s) underlying this change is unknown. We tested the hypothesis that jejunal nutrient exposure plays a significant role in ghrelin suppression after RYGB. Feeding tubes were placed in the stomach or jejunum in 13 obese subjects to simulate pre-RYGB or post-RYGB glucose exposure to the gastrointestinal (GI) tract, respectively, without the confounding effects of caloric restriction, weight loss, and surgical stress. On separate study days, the plasma glucose curves obtained with either gastric or jejunal administration of glucose were replicated with intravenous (iv) infusions of glucose. These "isoglycemic clamps" enabled us to determine the contribution of the GI tract and postabsorptive plasma glucose to acyl ghrelin suppression. Plasma acyl ghrelin levels were suppressed to a greater degree with jejunal glucose administration compared with gastric glucose administration (P < 0.05). Jejunal administration of glucose also resulted in a greater suppression of acyl ghrelin than the corresponding isoglycemic glucose infusion (P ≤ 0.01). However, gastric and isoglycemic iv glucose infusions resulted in similar degrees of acyl ghrelin suppression (P > 0.05). Direct exposure of the proximal jejunum to glucose increases acyl ghrelin suppression independent of circulating glucose levels. The enhanced suppression of acyl ghrelin after RYGB may be due to a nutrient-initiated signal in the jejunum that regulates ghrelin secretion. PMID:27279247

  4. Promotion or suppression of experimental metastasis of B16 melanoma cells after oral administration of lapachol

    SciTech Connect

    Maeda, Masayo; Murakami, Manabu; Takegami, Tsutomu; Ota, Takahide

    2008-06-01

    Lapachol [2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone] is a vitamin K antagonist with antitumor activity. The effect of lapachol on the experimental metastasis of murine B16BL6 melanoma cells was examined. A single oral administration of a high toxic dose of lapachol (80-100 mg/kg) 6 h before iv injection of tumor cells drastically promoted metastasis. This promotion of metastasis was also observed in T-cell-deficient mice and NK-suppressed mice. In vitro treatment of B16BL6 cells with lapachol promoted metastasis only slightly, indicating that lapachol promotes metastasis primarily by affecting host factors other than T cells and NK cells. A single oral administration of warfarin, the most commonly used vitamin K antagonist, 6 h before iv injection of tumor cells also drastically promoted the metastasis of B16BL6 cells. The promotion of metastasis by lapachol and warfarin was almost completely suppressed by preadministration of vitamin K3, indicating that the promotion of metastasis by lapachol was derived from vitamin K antagonism. Six hours after oral administration of lapachol or warfarin, the protein C level was reduced maximally, without elongation of prothrombin time. These observations suggest that a high toxic dose of lapachol promotes metastasis by inducing a hypercoagulable state as a result of vitamin K-dependent pathway inhibition. On the other hand, serial oral administration of low non-toxic doses of lapachol (5-20 mg/kg) weakly but significantly suppressed metastasis by an unknown mechanism, suggesting the possible use of lapachol as an anti-metastatic agent.

  5. Suppression of conditioned fear by administration of CCKB receptor antagonist PD135158.

    PubMed

    Tsutsumi, T; Akiyoshi, J; Isogawa, K; Kohno, Y; Hikichi, T; Nagayama, H

    1999-12-01

    In order to examine the involvement of CCK in the formation of anxiety, we have investigated whether CCKB receptor antagonist PD135158 suppressed conditioned fear stress. Rats were individually subjected to 30 min of inescapable electric footshock in a chamber with a grid floor. First, the rats were individually subjected to 30 min of footshock. Twenty-four h after the footshock, the rats were again placed in the chamber and observed for 5 min without shocks. PD135158 was administered 30 min before placing the rats in the chamber again. Secondly, PD135158 was administered 30 min before footshock. Thirdly, PD135158 was administered 5 min after footshock. Administration of PD135158 30 min before conditioned fear stress significantly reduced freezing behavior. Administration of PD135158 30 min before footshock also significantly reduced freezing behavior. But, administration of PD135158 5 min after footshock did not significantly reduce freezing behavior. PD135158 blocked not only the acquisition but also the expression of conditioned fear. These results suggest that the CCKB receptor might play an important role in conditioned fear stress and that it might be related to anxiety. PMID:10657528

  6. [Suppression of conditioned fear by administration of CCKB receptor antagonist PD135158].

    PubMed

    Tsutsumi, T; Isogawa, K; Kouno, Y; Hikichi, T; Nagayama, H; Akiyoshi, J

    1998-02-01

    The aim of this study is to determine whether or not CCKB receptor antagonist PD135158 suppresses conditioned fear. Rats were individually subjected to 30 min of inescapable electric footshock in a chamber with a grid floor. PD135158 or the vehicle was administered 30 min before placing the rats in the shock chamber again. The rats were observed for 5 min without receiving shock. The administration of PD135158 30 min before conditioned-fear stress significantly reduced freezing behavior. PD135158 blocked the expression of conditioned fear. PD135158 was again administered 30 min before footshock. Then, the rats were individually subjected to 30 min of inescapable electric footshock in the shock chamber. Twenty-four hours after receiving footshock, the rats were again placed in the shock chamber and observed for 5 min without shock administration. The administration of PD135158 30 min before footshock significantly reduced conditioned freezing. PD135158 blocked the anxiety of conditioned fear. PD135158 blocked not only the anxiety, but also the expression of conditioned fear. These results suggest that CCKB receptor might play an important role in conditioned-fear stress. They indicate that CCKB receptor is related to anxiety. PMID:9592807

  7. In vivo MRI characteristics of lipoma arborescens utilizing fat suppression and contrast administration

    SciTech Connect

    Chaljub, G.; Johnson, P.R.

    1996-01-01

    Lipoma arborescens or villous lipomatous proliferation of the synovium is a rare lesion. We describe the in vivo imaging characteristics of lipoma arborescens of the knee utilizing fat suppression techniques and contrast medium administration. As expected, the lesion demonstrated signal loss when utilizing fat suppression. In addition, no contrast enhancement was noted. When a synovial process demonstrates isointensity with subcutaneous fat on all pulse sequences and no contrast enhancement, lipoma arborescens should be the primary diagnosis consideration. 7 refs., 4 figs.

  8. Systemic administration of resveratrol suppress the nociceptive neuronal activity of spinal trigeminal nucleus caudalis in rats.

    PubMed

    Takehana, Shiori; Sekiguchi, Kenta; Inoue, Maki; Kubota, Yoshiko; Ito, Yukihiko; Yui, Kei; Shimazu, Yoshihito; Takeda, Mamoru

    2016-01-01

    Although a modulatory role has been reported for the red wine polyphenol resveratrol on several types of ion channels and excitatory synaptic transmission in the nervous system, the acute effects of resveratrol in vivo, particularly on nociceptive transmission of the trigeminal system, remain to be determined. The aim of the present study was to investigate whether acute intravenous resveratrol administration to rats attenuates the excitability of wide dynamic range (WDR) spinal trigeminal nucleus caudalis (SpVc) neurons in response to nociceptive and non-nociceptive mechanical stimulation in vivo. Extracellular single unit recordings were made from 18 SpVc neurons in response to orofacial mechanical stimulation of pentobarbital-anesthetized rats. Responses to both non-noxious and noxious mechanical stimuli were analyzed in the present study. The mean firing frequency of SpVc WDR neurons in response to both non-noxious and noxious mechanical stimuli was inhibited by resveratrol (0.5-2 mg/kg, i.v.) and maximum inhibition of the discharge frequency of both non-noxious and noxious mechanical stimuli was seen within 10 min. These inhibitory effects were reversed after approximately 20 min. The relative magnitude of inhibition by resveratrol of SpVc WDR neuronal discharge frequency was significantly greater for noxious than non-noxious stimulation. These results suggest that, in the absence of inflammatory or neuropathic pain, acute intravenous resveratrol administration suppresses trigeminal sensory transmission, including nociception, and so resveratrol may be used as a complementary and alternative medicine therapeutic agent for the treatment of trigeminal nociceptive pain, including hyperalgesia. PMID:26608254

  9. Effective gastric acid suppression after oral administration of enteric-coated omeprazole granules.

    PubMed

    Mohiuddin, M A; Pursnani, K G; Katzka, D A; Gideon, R M; Castell, J A; Castell, D O

    1997-04-01

    Omeprazole is inactivated by exposure to gastric acid and is formulated as a gelatin capsule containing enteric-coated granules that release the drug in alkaline medium. In clinical situations where patients are unable to take the capsule orally, the optimum means of administration is uncertain. Eleven normal volunteers were given omeprazole 20 mg every day for one week before breakfast in random order as either a 20-mg capsule with water or free enteric-coated granules with either 8 oz of orange juice, 8 oz of water with 2 Alka-Seltzer antacid tablets (aspirin free), or 1 teaspoon of apple sauce. On day 7 of each regimen, an 8-hr intragastric pH study was performed following omeprazole 20 mg and standard breakfast. The median percentage of time of gastric acid pH > 4 after an omeprazole capsule was 68.5 (25-100); after granules with orange juice 59 (43-100); after granules in Alka-Seltzer solution 63 (31-100), and after granules in apple sauce 65 (30-99), with no significant differences (ANOVA). The time for the gastric pH to reach <4' after having been above was also similar for all four regimens (ANOVA). Omeprazole granules administered orally in a variety of ways achieve gastric acid suppression as effectively as the intact capsule. PMID:9125637

  10. Olanzapine-induced suppression of cocaine self-administration in rhesus monkeys.

    PubMed

    Howell, Leonard L; Wilcox, Kristin M; Lindsey, Kimberly P; Kimmel, Heather L

    2006-03-01

    The neuropharmacological profile of the atypical antipsychotic, olanzapine, is consistent with a potentially useful medication for cocaine abuse. The present study utilized an i.v. drug self-administration paradigm in nonhuman primates to obtain definitive evidence regarding the effectiveness of olanzapine to modulate the reinforcing effects of cocaine. The effects of olanzapine were compared directly to those of the neuroleptic, haloperidol. Rhesus monkeys (n=7) were trained to self-administer cocaine (0.03-0.3 mg/kg/injection) under a second-order, fixed-interval 600-s schedule with fixed ratio 20 components. Experimental sessions comprised five consecutive fixed intervals, each followed by a 1-min timeout. In drug-interaction experiments, a single dose of olanzapine (0.03-0.3 mg/kg) or haloperidol (0.01-0.03 mg/kg) was administered i.v. 15 min presession for at least three consecutive sessions. In drug-substitution experiments, different doses of olanzapine (0.01-0.1 mg/kg/injection) were substituted for cocaine until responding stabilized. Olanzapine caused dose-related decreases in cocaine self-administration at pretreatment doses that had no overt behavioral effects indicative of sedation. A dose of 0.1 mg/kg eliminated cocaine self-administration in all subjects. In contrast, doses of haloperidol that suppressed cocaine self-administration induced marked sedation and catalepsy. Olanzapine failed to maintain self-administration behavior above saline extinction levels over a range of unit doses. In vivo microdialysis experiments in a second group of awake rhesus monkeys (n=3) confirmed previous reports in rodents that olanzapine effectively increases extracellular dopamine in ventral striatum. The dose of olanzapine that markedly suppressed cocaine self-administration behavior increased dopamine to approximately 190% of control values. Lastly, pretreatment with fluoxetine had no systematic effect on olanzapine-induced increases in striatal dopamine. The

  11. 21 CFR 10.70 - Documentation of significant decisions in administrative file.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Documentation of significant decisions in administrative file. 10.70 Section 10.70 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... appropriate employees, and show all persons to whom copies were sent; (4) Avoid defamatory...

  12. Immune suppressive virus-like particles in a Drosophila parasitoid: significance of their intraspecific morphological variations.

    PubMed

    Dupas, S; Brehelin, M; Frey, F; Carton, Y

    1996-09-01

    The Eucoilid parasitoid Leptopilina boulardi is able to suppress its host Drosophila melanogaster immune reaction. Some strains, however, are non-immune suppressive to that host. Virus-like particles (VLPs) responsible for the immune suppressive ability were investigated in different strains of L. boulardi with histochemical and ultrastructural techniques. Membrane-bound particles containing vesicles were observed in the reservoir of the long gland and also in the egg canal of the ovipositor. These particles are homologous with the immune suppressive VLPs already described in the reservoir of L. heterotoma. Similarities were also observed with the L2 particles described previously around the chorion of the parasitoid egg after infestation. A weak positive DNA specific histochemical reaction was observed inside the reservoir and at the ultrastructural level. Feulgen-derived techniques demonstrated that the reaction was localized inside the particles. The morphology of the particles as well as the immune suppressive ability varied between strains. Two morphotypes of VLPs are described; the 'Is' morphotype (always observed in immune suppressive or Is strains) and the 'NIs' morphotype (observed in the non-immune suppressive or NIs strain). The hybrids between Is and NIs strains produce a third type of particle, the 'HIs' morphotype with half-immune suppressive ability and intermediate morphology. The origin of the particles' immune suppressive activity against D. melanogaster is discussed within the scope of host specificity. PMID:8811846

  13. Development of an orally-administrative MELK-targeting inhibitor that suppresses the growth of various types of human cancer.

    PubMed

    Chung, Suyoun; Suzuki, Hanae; Miyamoto, Takashi; Takamatsu, Naofumi; Tatsuguchi, Ayako; Ueda, Koji; Kijima, Kyoko; Nakamura, Yusuke; Matsuo, Yo

    2012-12-01

    We previously reported MELK (maternal embryonic leucine zipper kinase) as a novel therapeutic target for breast cancer. MELK was also reported to be highly upregulated in multiple types of human cancer. It was implied to play indispensable roles in cancer cell survival and indicated its involvement in the maintenance of tumor-initiating cells. We conducted a high-throughput screening of a compound library followed by structure-activity relationship studies, and successfully obtained a highly potent MELK inhibitor OTSSP167 with IC₅₀ of 0.41 nM. OTSSP167 inhibited the phosphorylation of PSMA1 (proteasome subunit alpha type 1) and DBNL (drebrin-like), which we identified as novel MELK substrates and are important for stem-cell characteristics and invasiveness. The compound suppressed mammosphere formation of breast cancer cells and exhibited significant tumor growth suppression in xenograft studies using breast, lung, prostate, and pancreas cancer cell lines in mice by both intravenous and oral administration. This MELK inhibitor should be a promising compound possibly to suppress the growth of tumor-initiating cells and be applied for treatment of a wide range of human cancer. PMID:23283305

  14. Inhibition of miR-29 has a significant lipid-lowering benefit through suppression of lipogenic programs in liver

    PubMed Central

    Kurtz, C. Lisa; Fannin, Emily E.; Toth, Cynthia L.; Pearson, Daniel S.; Vickers, Kasey C.; Sethupathy, Praveen

    2015-01-01

    MicroRNAs (miRNAs) are important regulators and potential therapeutic targets of metabolic disease. In this study we show by in vivo administration of locked nucleic acid (LNA) inhibitors that suppression of endogenous miR-29 lowers plasma cholesterol levels by ~40%, commensurate with the effect of statins, and reduces fatty acid content in the liver by ~20%. Whole transcriptome sequencing of the liver reveals 883 genes dysregulated (612 down, 271 up) by inhibition of miR-29. The set of 612 down-regulated genes are most significantly over-represented in lipid synthesis pathways. Among the up-regulated genes are the anti-lipogenic deacetylase sirtuin 1 (Sirt1) and the anti-lipogenic transcription factor aryl hydrocarbon receptor (Ahr), the latter of which we demonstrate is a direct target of miR-29. In vitro radiolabeled acetate incorporation assays confirm that pharmacologic inhibition of miR-29 significantly reduces de novo cholesterol and fatty acid synthesis. Our findings indicate that miR-29 controls hepatic lipogenic programs, likely in part through regulation of Ahr and Sirt1, and therefore may represent a candidate therapeutic target for metabolic disorders such as dyslipidemia. PMID:26246194

  15. Oral Administration of MBG to Modulate Immune Responses and Suppress OVA-Sensitized Allergy in a Murine Model

    PubMed Central

    Wu, Yu-Sheng; Chen, Sherwin; Wang, William; Lu, Chung-Lun; Liu, Chi-Feng; Chen, Shiu-Nan

    2014-01-01

    Recently studies performed on mushroom isolated polysaccharides demonstrated that β-(1,3)-glucan may affect the balance of Th1/Th2 cell response. Using ovalbumin (OVA) as a hypersensitivity inducer, we evaluated the ability of mushroom beta-glucan (MBG) in modulating Th1/Th2 cell responses in B6 mice. As compared to the control group, administration of MBG resulted in an increase of phagocytic activities, Th1 cytokine productions, immunoglobulins including IgG2A and IgA, and a significant expression of the splenic surface markers including CD3, CD4, CD8, and F4/80. In contrast, administration of MBG has significantly suppressed IgE and IgG1 levels and Th2 cytokines including IL-4, IL-5, and IL-6. Histopathological observation of MBG-treated followed by OVA-treated mice showed less filtration of eosinophil in pulmonary tissue sections. Our data suggested that administration of MBG treatments alters the natural course of the IgE-mediated hypersensitivities. In this investigation, we realize the mushroom beta glucan alter the Th2 response toward the Th1 in the allergic, resulting in a reduction in IgE productions which played a substantive role in reducing the severity of IgE-mediated hypersensitivity. PMID:24723960

  16. Suppression of conditioned fear by administration of CCKB receptor antisense oligodeoxynucleotide into the lateral ventricle.

    PubMed

    Tsutsumi, T; Akiyoshi, J; Hikichi, T; Kiyota, A; Kohno, Y; Katsuragi, S; Yamamoto, Y; Isogawa, K; Nagayama, H

    2001-11-01

    We investigated the role of CCK in the development of anxiety by determining whether CCKB receptor antisense suppressed intracellular Ca(2+) concentration in vitro or suppressed conditioned fear stress in vivo. First, for the in vitro studies, we used rat pituitary tumor GH3 cells since these cells have CCKB receptors. GH3 cells were stimulated by 10 microM CCK-4; intracellular Ca(2+) concentration was measured. The CCKB receptor antisense at 1 or 10 microM reduced the subsequent response to 10 microM CCK-4 in a time-dependent manner. Second, for the in vivo studies, the CCKB receptor antisense, sense, random sense, or saline was infused at a constant rate for 6 days into rat lateral ventricles via mini-osmotic pumps. Individual rats were then subjected to 30 min of inescapable electric footshock in a chamber with a grid floor. Twenty-four hours later, the rat was again placed in the chamber and observed for 5 min without shocks. This study showed that CCKB receptor antisense significantly suppressed intracellular Ca(2+) concentration in GH3 cells and significantly reduced freezing behavior in rats, indicating that the CCKB receptor plays an important role in anxiety. PMID:11778143

  17. Significance of Ovarian Function Suppression in Endocrine Therapy for Breast Cancer in Pre-Menopausal Women

    PubMed Central

    Scharl, A.; Salterberg, A.

    2016-01-01

    Ovarian function suppression (OFS) for treating breast cancer in pre-menopausal women was introduced for the first time in the late 19th century as bilateral oophorectomy. It was not until the 1960s that the oestrogen receptor was identified and a test for detecting endocrine sensitivity of the breast cancer was developed. A weakness of early trials on OFS for breast cancer treatment is therefore their failure to take receptor sensitivity into account when selecting participants. A meta-analysis performed in the early 1990s first proved that adjuvant OFS significantly improved the cure rate of oestrogen receptor-positive breast cancer in pre-menopausal women regardless of whether it was carried out through oophorectomy, radiation-induced ablation or drug therapy. In the 1970s, tamoxifen was synthesized. It became one of the most important cancer drugs and today constitutes the gold standard for endocrine adjuvant therapy. Taking tamoxifen for a five-year period lowers mortality by 30 % over 15 years. Ten years of tamoxifen therapy reduces mortality even further, with increased side effects, however. Research over the past ten years has proven that for post-menopausal women, aromatase inhibitors have benefits over tamoxifen. Current trial results have rekindled the debate about the combination of OFS with tamoxifen or with aromatase inhibitors for adjuvant breast cancer treatment of pre-menopausal women. These trials have reported an improvement in disease-free survival in patients with a high risk of recurrence when they are treated with a combination of OFS plus tamoxifen or aromatase inhibitors, especially in women younger than 35. However, combination therapy causes significantly more side effects, which could negatively impact compliance. Endocrine treatments administered over a period of many years show waning compliance, which tends to be only around 50 % after five years. Inadequate compliance compromises efficacy and increases the risk of mortality. For

  18. Administration of Reconstituted Polyphenol Oil Bodies Efficiently Suppresses Dendritic Cell Inflammatory Pathways and Acute Intestinal Inflammation

    PubMed Central

    Cavalcanti, Elisabetta; Vadrucci, Elisa; Delvecchio, Francesca Romana; Addabbo, Francesco; Bettini, Simona; Liou, Rachel; Monsurrò, Vladia; Huang, Alex Yee-Chen; Pizarro, Theresa Torres

    2014-01-01

    Polyphenols are natural compounds capable of interfering with the inflammatory pathways of several in vitro model systems. In this study, we developed a stable and effective strategy to administer polyphenols to treat in vivo models of acute intestinal inflammation. The in vitro suppressive properties of several polyphenols were first tested and compared for dendritic cells (DCs) production of inflammatory cytokines. A combination of the polyphenols, quercetin and piperine, were then encapsulated into reconstituted oil bodies (OBs) in order to increase their stability. Our results showed that administration of low dose reconstituted polyphenol OBs inhibited LPS-mediated inflammatory cytokine secretion, including IL-6, IL-23, and IL-12, while increasing IL-10 and IL-1Rα production. Mice treated with the polyphenol-containing reconstituted OBs (ROBs) were partially protected from dextran sodium sulfate (DSS)-induced colitis and associated weight loss, while mortality and inflammatory scores revealed an overall anti-inflammatory effect that was likely mediated by impaired DC immune responses. Our study indicates that the administration of reconstituted quercetin and piperine-containing OBs may represent an effective and potent anti-inflammatory strategy to treat acute intestinal inflammation. PMID:24558444

  19. Enhanced nicotine self-administration and suppressed dopaminergic systems in a rat model of diabetes

    PubMed Central

    O'Dell, Laura E.; Natividad, Luis A.; Pipkin, Joseph A.; Roman, Francisco; Torres, Ivan; Jurado, Jesus; Torres, Oscar V.; Friedman, Theodore C.; Tenayuca, John M.; Nazarian, Arbi

    2013-01-01

    Patients with diabetes display a heightened propensity to use tobacco; however, it is unclear whether they experience enhanced rewarding effects of nicotine. Thus, this study examined the reinforcing effects of nicotine in a rodent model of diabetes involving administration of streptozotocin (STZ), a drug that is toxic to pancreatic insulin-producing cells. The first study compared STZ- and vehicle-treated rats that had 23-hour access to intravenous self-administration (IVSA) of nicotine or saline and concomitant access to food and water. In order to examine the contribution of dopamine to our behavioral effects, dopamine transporter (DAT), D1 and D2 receptor levels were compared in the nucleus accumbens (NAc) following 10 days of nicotine or saline IVSA. Dopamine levels in the NAc were also compared following nicotine administration. Lastly, nicotine metabolism and dose-dependent effects of nicotine IVSA were assessed. The results revealed that STZ-treated rats displayed enhanced nicotine intake and a robust increase in food and water intake relative to controls. Protein analysis revealed an increase in DAT and a decrease in D1 receptor levels in the NAc of STZ- versus vehicle-treated rats regardless of IVSA condition. STZ-treated rats also displayed suppressed NAc dopamine levels during baseline and in response to nicotine. STZ treatment did not alter our assessment of nicotine metabolism. Furthermore, STZ treatment increased nicotine IVSA in a dose-dependent manner. Our findings suggest that STZ-treatment increased the rewarding effects of nicotine. This suggests that strong reinforcing effects of nicotine may contribute to greater tobacco use in patients with diabetes. PMID:23834715

  20. Active suppression of diabetes after oral administration of insulin is determined by antigen dosage.

    PubMed

    Bergerot, I; Fabien, N; Mayer, A; Thivolet, C

    1996-02-13

    We have previously demonstrated that feeding six-week-old female mice with 20 units of human insulin every 2 - 3 days for 15 or 30 days induced an active mechanism of suppression through the generation of regulatory T cells that reduced the number of successful diabetic transfers in irradiated NOD recipients. In the present study, we analyzed the effects of antigen dosage and the critical period of cell injection to obtain protection. The effects of the dose of insulin feeding were therefore compared during cotransfer experiments of 5 x 10(6) T cells from diabetic mice and 5 x 10(6) T cells from the spleen of mice receiving 10 units, 20 units, or 40 units of insulin or saline every 2 - 3 days for 15 days. Only T lymphocytes from mice fed with 20 units conferred active cellular protection during adoptive transfer with a significant delay in diabetes onset (p = 0.002). No significant difference was noticed during histological analysis of pancreatic glands, indicating tha insulitis was not prevented. However, mice receiving T lymphocytes from the 20 units of insulin-fed animals had a milder form of inflammation, with a significantly lower percentage of severely infiltrated islets. Injecting regulatory T cells 7 days and 14 days after iv injection of diabetogenic T cells did not modify the incidence curves of diabetes in the recipients, suggesting that cellular interactions and delay in cell trafficking were determinants. These results may have important clinical implications in humans. In conclusion, this study indicates the importance but also the limits of antigen therapy in type I diabetes. Antigen dosage is a critical element for active suppression. Such analysis is important to perform in humans before the initiation of a large-scale prevention trial in prediabetic individuals. PMID:8610991

  1. The Type of Responder T-Cell Has a Significant Impact in a Human In Vitro Suppression Assay

    PubMed Central

    Jana, Srikanta; Campbell, Hope; Woodliff, Jeffrey; Waukau, Jill; Jailwala, Parthav; Ghorai, Jugal; Ghosh, Soumitra; Glisic, Sanja

    2010-01-01

    Background In type 1 diabetes (T1D), a prototypic autoimmune disease, effector T cells destroy beta cells. Normally, CD4+CD25+high, or natural regulatory T cells (Tregs), counter this assault. In autoimmunity, the failure to suppress CD4+CD25low T cells is important for disease development. However, both Treg dysfunction and hyperactive responder T-cell proliferation contribute to disease. Methods/Principal Findings We investigated human CD4+CD25low T cells and compared them to CD4+CD25- T cells in otherwise equivalent in vitro proliferative conditions. We then asked whether these differences in suppression are exacerbated in T1D. In both single and co-culture with Tregs, the CD4+CD25low T cells divided more rapidly than CD4+CD25- T cells, which manifests as increased proliferation/reduced suppression. Time-course experiments showed that this difference could be explained by higher IL-2 production from CD4+CD25low compared to CD4+CD25- T cells. There was also a significant increase in CD4+CD25low T-cell proliferation compared to CD4+CD25- T cells during suppression assays from RO T1D and at-risk subjects (n = 28, p = 0.015 and p = 0.024 respectively). Conclusions/Significance The in vitro dual suppression assays proposed here could highlight the impaired sensitivity of certain responder T cells to the suppressive effect of Tregs in human autoimmune diseases. PMID:21151941

  2. Method of Administration of PROMIS Scales Did Not Significantly Impact Score Level, Reliability or Validity

    PubMed Central

    Bjorner, Jakob B.; Rose, Matthias; Gandek, Barbara; Stone, Arthur A.; Junghaenel, Doerte U.; Ware, John E.

    2014-01-01

    Objective To test the impact of method of administration (MOA) on score level, reliability, and validity of scales developed in the Patient Reported Outcomes Measurement Information System (PROMIS). Study Design and Setting Two non-overlapping parallel forms each containing 8 items from each of three PROMIS item banks (Physical Function, Fatigue and Depression) were completed by 923 adults with COPD, depression, or rheumatoid arthritis. In a randomized cross-over design, subjects answered one form by interactive voice response (IVR) technology, paper questionnaire (PQ), personal digital assistant (PDA), or personal computer (PC) and a second form by PC, in the same administration. Method equivalence was evaluated through analyses of difference scores, intraclass correlations (ICC), and convergent/discriminant validity. Results In difference score analyses, no significant mode differences were found and all confidence intervals were within the pre-specified MID of 0.2 SD. Parallel forms reliabilities were very high (ICC=0.85-0.93). Only one across mode ICC was significantly lower than the same mode ICC. Tests of validity showed no differential effect by MOA. Participants preferred screen interface over PQ and IVR. Conclusion We found no statistically or clinically significant differences in score levels or psychometric properties of IVR, PQ or PDA administration as compared to PC. PMID:24262772

  3. Limited significance of asymmetric adrenal visualization on dexamethasone-suppression scintigraphy

    SciTech Connect

    Gross, M.D.; Shapiro, B.; Freitas, J.E.

    1985-01-01

    To access whether a single measurement of the adrenal uptake of 6..beta..-(/sup 131/I)-iodomethylnorocholesterol (NP-59) on constant dexamethasone suppression would allow discrimination of adenoma from normal and bilateral hyperplasia, the adrenal uptake of 6..beta..-(/sup 131/I)-iodomethylnorocholesterol (NP-59) was determined in 50 patients with primary aldosteronism (30 adenoma, 20 hyperplasia) and in 13 with hyperandrogenism (six adenoma, seven hyperplasia). Bilateral adrenal NP-59 activity at 5 days was seen in 14 of 36 patients with adenoma whereas marked asymmetric uptake of NP-59 was seen in six of 27 patients with hyperplasia. Thus the level of adrenal NP-59 uptake does not alone serve to distinguish either adenoma from the normal, contralateral adrenal or the adrenal glands in bilateral hyperplasia in all cases. It appears that the pattern of adrenal imaging best serves to separate adrenal adenoma from bilateral hyperplasia.

  4. Bystander suppression to unrelated allergen sensitization through intranasal administration of tolerogenic exosomes in mouse.

    PubMed

    Prado, Noela; Cañamero, Marta; Villalba, Mayte; Rodríguez, Rosalía; Batanero, Eva

    2010-07-01

    Exosomes represent a new family of bioactive nanovesicles (30-100 nm in diameter) secreted by different cell types whose appealing features can be exploited for designing vaccines in the context of several human diseases. We previously reported the potential of bronchoalveolar lavage fluid (BALF)-derived tolerogenic exosomes (Exo(Tol)) to be used as a nasal allergy vaccine in a mouse model of sensitization to Ole e 1, the main allergen of olive pollen. The aim of the study was to investigate whether such nanovesicles specific to Ole e 1 can also prevent the sensitization to other unrelated allergen, as Bet v 1 from birch pollen. Exo(Tol) were isolated from BALF of mice tolerized against Ole e 1 and used in a prophylactic approach. BALB/c mice were intranasally pretreated with Exo(Tol) one week before sensitization/challenge with Bet v 1, and the magnitude of allergen-specific response was analyzed. Intranasal pretreatment with Exo(Tol) resulted in significant inhibition of both specific IgE and IgG1 antibodies levels. Moreover, T cells from mice pretreated with Exo(Tol) showed a reduction in IL-5 and IL-13 (Th2 cytokines) production. Lung inflammatory response triggered by unrelated allergen-challenge was also significantly reduced after pretreatment: perivascular/peribronchial inflammatory cell infiltration, eosinophilia and mucus secretion. In conclusion, Exo(Tol) specific to Ole e 1, in addition to inhibit specific immune response to this allergen, blocked the allergic response to a second unrelated allergen such as Bet v 1. The in vivo "bystander suppression" that we herein describe for Exo(Tol) may have implications for the treatment of allergy based on mucosal tolerance induction. PMID:20478618

  5. Annual committee reports on significant legislative, judicial, and administrative developments in 1981: Water-Quality committee

    SciTech Connect

    Not Available

    1982-01-01

    This review of 1981 developments is divided into four basic parts. The first covers legislative, judicial, and administrative developments under the Clean Water Act (CWA); the second covers judicial and administrative developments under the Safe Drinking Water Act (SDWA); the third covers judicial developments respecting private rights of action and the federal common law of nuisance. 109 references.

  6. Potentiated suppression of Dickkopf-1 in breast cancer by combined administration of the mevalonate pathway inhibitors zoledronic acid and statins.

    PubMed

    Göbel, Andy; Browne, Andrew J; Thiele, Stefanie; Rauner, Martina; Hofbauer, Lorenz C; Rachner, Tilman D

    2015-12-01

    The Wnt-inhibitor dickkopf-1 (DKK-1) promotes cancer-induced osteolytic bone lesions by direct inhibition of osteoblast differentiation and indirect activation of osteoclasts. DKK-1 is highly expressed in human breast cancer cells and can be suppressed by inhibitors of the mevalonate pathway such as statins and amino-bisphosphonates. However, supraphysiological concentrations are required to suppress DKK-1. We show that a sequential mevalonate pathway blockade using statins and amino-bisphosphonates suppresses DKK-1 more significantly than the individual agents alone. Thus, the reduction of the DKK-1 expression and secretion in the human osteotropic tumor cell lines MDA-MB-231, MDA-MET, and MDA-BONE by zoledronic acid was potentiated by the combination with low concentrations of statins (atorvastatin, simvastatin, and rosuvastatin) by up to 75% (p < 0.05). The specific rescue of prenylation using farnesyl pyrophosphate or geranylgeranyl pyrophosphate revealed that these effects were mediated by suppressed geranylgeranylation rather than by suppressed farnesylation. Moreover, combining low concentrations of statins (1 µM atorvastatin or 0.25 µM simvastatin) and zoledronic acid at low concentrations resulted in an at least 50% reversal of breast cancer-derived DKK-1-mediated inhibition of osteogenic markers in C2C12 cells (p < 0.05). Finally, the intratumoral injection of atorvastatin and zoledronic acid in as subcutaneous MDA-MB-231 mouse model reduced the serum level of human DKK-1 by 25% compared to untreated mice. Hence our study reveals that a sequential mevalonate pathway blockade allows for the combined use of low concentration of statins and amino-bisphosphonates. This combination still significantly suppresses breast cancer-derived DKK-1 to levels where it can no longer inhibit Wnt-mediated osteoblast differentiation. PMID:26515701

  7. Annual committee report on significant legislative, judicial, and administrative developments in 1980: Water Quality Committee

    SciTech Connect

    Not Available

    1981-01-01

    This review of 1980 developments is divided into three parts. The first covers judicial and administrative developments under the Clean Water Act (CWA) such as industrial guidelines and standards; the second covers judicial administrative and legislative developments under the Safe Drinking Water Act (SDWA); and the third covers judicial developments in the areas of private rights of action and the federal common law of nuisance. 320 references.

  8. Acute hypothalamic suppression significantly affects trabecular bone but not cortical bone following recovery and ovariectomy surgery in a rat model

    PubMed Central

    Mitchell, Kathryn A.; Lunny, Megan

    2016-01-01

    RH-a group compared to C, a similar deficit in BV/TV was also measured following recovery and post-OVX. The trabecular number and thickness were lower in the GnRH-a group compared to control. Conclusion. These data suggest that following a transient delay in pubertal onset, trabecular bone volume was significantly lower and no restoration of bone volume occurred following recovery or post-OVX surgery. However, cortical bone strength was maintained through architectural adaptations in the cortical bone envelope. An increase in the polar moment of inertia offset increased bone resorption. The current data are the first to suppress trabecular bone during growth, and then add an OVX protocol at maturity. Trabecular bone and cortical bone differed in their response to hypothalamic suppression during development; trabecular bone was more sensitive to the negative effects of hypothalamic suppression. PMID:26793427

  9. Acute hypothalamic suppression significantly affects trabecular bone but not cortical bone following recovery and ovariectomy surgery in a rat model.

    PubMed

    Yingling, Vanessa R; Mitchell, Kathryn A; Lunny, Megan

    2016-01-01

    RH-a group compared to C, a similar deficit in BV/TV was also measured following recovery and post-OVX. The trabecular number and thickness were lower in the GnRH-a group compared to control. Conclusion. These data suggest that following a transient delay in pubertal onset, trabecular bone volume was significantly lower and no restoration of bone volume occurred following recovery or post-OVX surgery. However, cortical bone strength was maintained through architectural adaptations in the cortical bone envelope. An increase in the polar moment of inertia offset increased bone resorption. The current data are the first to suppress trabecular bone during growth, and then add an OVX protocol at maturity. Trabecular bone and cortical bone differed in their response to hypothalamic suppression during development; trabecular bone was more sensitive to the negative effects of hypothalamic suppression. PMID:26793427

  10. Systemic high-mobility group box 1 administration suppresses skin inflammation by inducing an accumulation of PDGFRα+ mesenchymal cells from bone marrow

    PubMed Central

    Aikawa, Eriko; Fujita, Ryo; Kikuchi, Yasushi; Kaneda, Yasufumi; Tamai, Katsuto

    2015-01-01

    High-mobility group box 1 (HMGB1) mobilizes platelet-derived growth factor receptor alpha-positive (PDGFRα+) mesenchymal cells from bone marrow (BM) into circulation. However, whether HMGB1-induced endogenous PDGFRα+ mesenchymal cells stimulate skin regeneration has been unclear. Here, we investigated the functions of the HMGB1/BM-PDGFRα+ mesenchymal cell axis in the regeneration of mouse skin grafts. We found that intravenous HMGB1 administration induced an accumulation of endogenous BM-PDGFRα+ mesenchymal cells followed by significant inflammatory suppression in the grafts. In contrast, mice with reduced BM-PDGFRα+ mesenchymal cells showed massive inflammation of the grafts compared to mice that had normal levels of these cells even after HMGB1 administration, suggesting that BM-PDGFRα+ mesenchymal cells contribute to the HMGB1-induced anti-inflammatory effect. We also found that intravenously administered HMGB1 augmented the local migration of BM-PDGFRα+ mesenchymal cells from circulation to skin graft by inducing the expression of CXCR4, an SDF-1 receptor, on these cells. Finally, we showed the therapeutic activity of the HMGB1/BM-PDGFRα+ mesenchymal cell axis in an allergic contact dermatitis model. The results illustrated the contribution of the HMGB1/BM-PDGFRα+ mesenchymal cell axis in suppressing the inflammation of injured/inflamed skin. These findings may provide future perspectives on the use of HMGB1-based medicines for intractable diseases. PMID:26046579

  11. The dopamine β-hydroxylase inhibitor, nepicastat, suppresses chocolate self-administration and reinstatement of chocolate seeking in rats.

    PubMed

    Zaru, Alessandro; Maccioni, Paola; Colombo, Giancarlo; Gessa, Gian Luigi

    2013-10-01

    Craving for chocolate is a common phenomenon, which may evolve to an addictive-like behaviour and contribute to obesity. Nepicastat is a selective dopamine β-hydroxylase (DBH) inhibitor that suppresses cocaine-primed reinstatement of cocaine seeking in rats. We verified whether nepicastat was able to modify the reinforcing and motivational properties of a chocolate solution and to prevent the reinstatement of chocolate seeking in rats. Nepicastat (25, 50 and 100 mg/kg, intraperitoneal) produced a dose-related inhibition of operant self-administration of the chocolate solution in rats under fixed-ratio 10 (FR10) and progressive-ratio schedules of reinforcement, measures of the reinforcing and motivational properties of the chocolate solution, respectively. The effect of nepicastat on the reinstatement of chocolate seeking was studied in rats in which lever-responding had been extinguished by removing the chocolate solution for approximately 8 d. Nepicastat dose-dependently suppressed the reinstatement of lever-responding triggered by a 'priming' of the chocolate solution together with cues previously associated with the availability of the reward. In a separate group of food-restricted rats trained to lever-respond for regular food pellets, nepicastat reduced FR10 lever-responding with the same potency as for the chocolate solution. Spontaneous locomotor activity was not modified by nepicastat doses that reduced self-administration of the chocolate solution and regular food pellets and suppressed the reinstatement of chocolate seeking. The results indicate that nepicastat reduces motivation to food consumption sustained by appetite or palatability. Moreover, the results suggest that DBH inhibitors may be a new class of pharmacological agents potentially useful in the prevention of relapse to food seeking in human dieters. PMID:23561307

  12. Annual committee reports on significant legislative, judicial, and administrative developments in 1982: Environmental Quality Committee

    SciTech Connect

    Not Available

    1983-01-01

    Judicial developments during 1982 dominated activities involving the National Environmental Policy Act (NEPA), the Federal Insecticide, Fungicide and Rotenticide Act, and Marine Sanctuaries, with some changes in administrative procedures and no legislative developments. The Endangered Species Act was amended to expedite changes to the lists and to alter exemption and international trade requirements. Several lawsuits challenged review standards and litigation claims. 231 references. (DCK)

  13. Local administration of siRNA through Microneedle: Optimization, Bio-distribution, Tumor Suppression and Toxicity

    PubMed Central

    Tang, Tao; Deng, Yan; Chen, Jiao; Zhao, Yi; Yue, Ruifeng; Choy, Kwong Wai; Wang, Chi Chiu; Du, Quan; Xu, Yan; Han, Linxiao; Chung, Tony Kwok Hung

    2016-01-01

    Although RNA interference may become a novel therapeutic approach for cancer treatment, target-site accumulation of siRNA to achieve therapeutic dosage will be a major problem. Microneedle represents a better way to deliver siRNAs and we have evaluated for the first time the capability of a silicon microneedle array for delivery of Gapdh siRNA to the skin in vivo and the results showed that the microneedle arrays could effectively deliver siRNA to relevant regions of the skin noninvasively. For the further study in this field, we evaluated the efficacy of the injectable microneedle device for local delivery of siRNA to the mouse xenograft. The results presented here indicate that local administration of siRNA through injectable microneedle could effectively deliver siRNA into the tumor region, and inhibit tumor progression without major adverse effects. PMID:27457182

  14. Local administration of siRNA through Microneedle: Optimization, Bio-distribution, Tumor Suppression and Toxicity

    NASA Astrophysics Data System (ADS)

    Tang, Tao; Deng, Yan; Chen, Jiao; Zhao, Yi; Yue, Ruifeng; Choy, Kwong Wai; Wang, Chi Chiu; Du, Quan; Xu, Yan; Han, Linxiao; Chung, Tony Kwok Hung

    2016-07-01

    Although RNA interference may become a novel therapeutic approach for cancer treatment, target-site accumulation of siRNA to achieve therapeutic dosage will be a major problem. Microneedle represents a better way to deliver siRNAs and we have evaluated for the first time the capability of a silicon microneedle array for delivery of Gapdh siRNA to the skin in vivo and the results showed that the microneedle arrays could effectively deliver siRNA to relevant regions of the skin noninvasively. For the further study in this field, we evaluated the efficacy of the injectable microneedle device for local delivery of siRNA to the mouse xenograft. The results presented here indicate that local administration of siRNA through injectable microneedle could effectively deliver siRNA into the tumor region, and inhibit tumor progression without major adverse effects.

  15. Local administration of siRNA through Microneedle: Optimization, Bio-distribution, Tumor Suppression and Toxicity.

    PubMed

    Tang, Tao; Deng, Yan; Chen, Jiao; Zhao, Yi; Yue, Ruifeng; Choy, Kwong Wai; Wang, Chi Chiu; Du, Quan; Xu, Yan; Han, Linxiao; Chung, Tony Kwok Hung

    2016-01-01

    Although RNA interference may become a novel therapeutic approach for cancer treatment, target-site accumulation of siRNA to achieve therapeutic dosage will be a major problem. Microneedle represents a better way to deliver siRNAs and we have evaluated for the first time the capability of a silicon microneedle array for delivery of Gapdh siRNA to the skin in vivo and the results showed that the microneedle arrays could effectively deliver siRNA to relevant regions of the skin noninvasively. For the further study in this field, we evaluated the efficacy of the injectable microneedle device for local delivery of siRNA to the mouse xenograft. The results presented here indicate that local administration of siRNA through injectable microneedle could effectively deliver siRNA into the tumor region, and inhibit tumor progression without major adverse effects. PMID:27457182

  16. Brain-derived neurotrophic factor mediates the suppression of alcohol self-administration by memantine.

    PubMed

    Jeanblanc, Jérôme; Coune, Fabien; Botia, Béatrice; Naassila, Mickaël

    2014-09-01

    Brain-derived neurotrophic factor (BDNF) within the striatum is part of a homeostatic pathway regulating alcohol consumption. Memantine, a non-competitive antagonist of N-methyl-D-aspartate receptors, induces expression of BDNF in several brain regions including the striatum. We hypothesized that memantine could decrease ethanol (EtOH) consumption via activation of the BNDF signalling pathway. Effects of memantine were evaluated in Long-Evans rats self-administering moderate or high amounts of EtOH 6, 30 and 54 hours after an acute injection (12.5 and 25 mg/kg). Motivation to consume alcohol was investigated through a progressive ratio paradigm. The possible role for BDNF in the memantine effect was tested by blockade of the TrkB receptor using the pharmacological agent K252a and by the BDNF scavenger TrkB-Fc. Candidate genes expression was also assessed by polymerase chain reaction array 4 and 28 hours after memantine injection. We found that memantine decreased EtOH self-administration and motivation to consume EtOH 6 and 30 hours post-injection. In addition, we found that inhibition or blockade of the BDNF signalling pathway prevented the early, but not the delayed decrease in EtOH consumption induced by memantine. Finally, Bdnf expression was differentially regulated between the early and delayed timepoints. These results demonstrate that an acute injection of memantine specifically reduces EtOH self-administration and motivation to consume EtOH for at least 30 hours. Moreover, we showed that BDNF was responsible for the early effect, but that the delayed effect was BDNF-independent. PMID:23414063

  17. Oral administration of IL-12 suppresses anaphylactic reactions in a murine model of peanut hypersensitivity.

    PubMed

    Lee, S Y; Huang, C K; Zhang, T F; Schofield, B H; Burks, A W; Bannon, G A; Sampson, H A; Li, X M

    2001-11-01

    There is no satisfactory therapeutic intervention for peanut allergy, which accounts for most life-threatening food allergic reactions. Since IL-12 has been found to inhibit allergic airway responses in a mouse model of asthma and to cure Th2 cytokine-mediated murine schistosomiasis, we hypothesized that IL-12 treatment might also inhibit peanut allergic reactions. Consequently, we investigated the effects of oral IL-12 treatment in a murine model of peanut allergy and found that oral administration of liposome encapsulated rIL-12 could both prevent and reverse peanut hypersensitivity and could reduce histamine release, peanut-specific serum IgE and IgG1, and fecal IgA levels. Oral IL-12 treatment also increased IFN-gamma but did not decrease IL-4 or IL-5 levels. We conclude that oral rIL-12 treatment has therapeutic as well as preventive effects on peanut allergy, which are associated with increased IFN-gamma production. PMID:11683581

  18. Plasma concentration-dependent suppression of endogenous hydrocortisone in the horse after intramuscular administration of dexamethasone-21-isonicotinate.

    PubMed

    Ekstrand, C; Bondesson, U; Gabrielsson, J; Hedeland, M; Kallings, P; Olsén, L; Ingvast-Larsson, C

    2015-06-01

    Detection times and screening limits (SL) are methods used to ensure that the performance of horses in equestrian sports is not altered by drugs. Drug concentration-response relationship and knowledge of concentration-time profiles in both plasma and urine are required. In this study, dexamethasone plasma and urine concentration-time profiles were investigated. Endogenous hydrocortisone plasma concentrations and their relationship to dexamethasone plasma concentrations were also explored. A single dose of dexamethasone-21-isonicotinate suspension (0.03 mg/kg) was administered intramuscularly to six horses. Plasma was analysed for dexamethasone and hydrocortisone and urine for dexamethasone, using UPLC-MS/MS. Dexamethasone was quantifiable in plasma for 8.3 ± 2.9 days (LLOQ: 0.025 μg/L) and in urine for 9.8 ± 3.1 days (LLOQ: 0.15 μg/L). Maximum observed dexamethasone concentration in plasma was 0.61 ± 0.12 μg/L and in urine 4.2 ± 0.9 μg/L. Terminal plasma half-life was 38.7 ± 19 h. Hydrocortisone was significantly suppressed for 140 h. The plasma half-life of hydrocortisone was 2.7 ± 1.3 h. Dexamethasone potency, efficacy and sigmoidicity factor for hydrocortisone suppression were 0.06 ± 0.04 μg/L, 0.95 ± 0.04 and 6.2 ± 4.6, respectively. Hydrocortisone suppression relates to the plasma concentration of dexamethasone. Thus, determination of irrelevant plasma concentrations and SL is possible. Future research will determine whether hydrocortisone suppression can be used as a biomarker of the clinical effect of dexamethasone. PMID:25366540

  19. Suppression of Inflammation and Arthritis by Orally Administrated Cardiotoxin from Naja naja atra

    PubMed Central

    Chen, Cao-Xin; Chen, Jie-Yu; Kou, Jian-Qun; Xu, Yin-Li; Wang, Shu-Zhi; Zhu, Qi; Yang, Lu; Qin, Zheng-Hong

    2015-01-01

    Cardiotoxin (CTX) from Naja naja atra venom (NNAV) reportedly had analgesic effect in animal models but its role in inflammation and arthritis was unknown. In this study, we investigated the analgesic, anti-inflammatory, and antiarthritic actions of orally administered CTX-IV isolated from NNAV on rodent models of inflammation and adjuvant arthritis. CTX had significant anti-inflammatory effects in models of egg white induced nonspecific inflammation, filter paper induced rat granuloma formation, and capillary osmosis tests. CTX significantly reduced the swelling of paw induced by egg white, the inflammatory exudation, and the formation of granulomas. CTX reduced the swelling of paw, the AA clinical scores, and pathological alterations of joint. CTX significantly decreased the number of the CD4 T cells and inhibited the expression of relevant proinflammatory cytokines IL-17 and IL-6. CTX significantly inhibited the secretion of proinflammatory cytokine IL-6 and reduced the level of p-STAT3 in FLS. These results suggest that CTX inhibits inflammation and inflammatory pain and adjuvant-induced arthritis. CTX may be a novel therapeutic drug for treatment of arthritis. PMID:25767552

  20. Suppression of Inflammation and Arthritis by Orally Administrated Cardiotoxin from Naja naja atra.

    PubMed

    Chen, Cao-Xin; Chen, Jie-Yu; Kou, Jian-Qun; Xu, Yin-Li; Wang, Shu-Zhi; Zhu, Qi; Yang, Lu; Qin, Zheng-Hong

    2015-01-01

    Cardiotoxin (CTX) from Naja naja atra venom (NNAV) reportedly had analgesic effect in animal models but its role in inflammation and arthritis was unknown. In this study, we investigated the analgesic, anti-inflammatory, and antiarthritic actions of orally administered CTX-IV isolated from NNAV on rodent models of inflammation and adjuvant arthritis. CTX had significant anti-inflammatory effects in models of egg white induced nonspecific inflammation, filter paper induced rat granuloma formation, and capillary osmosis tests. CTX significantly reduced the swelling of paw induced by egg white, the inflammatory exudation, and the formation of granulomas. CTX reduced the swelling of paw, the AA clinical scores, and pathological alterations of joint. CTX significantly decreased the number of the CD4 T cells and inhibited the expression of relevant proinflammatory cytokines IL-17 and IL-6. CTX significantly inhibited the secretion of proinflammatory cytokine IL-6 and reduced the level of p-STAT3 in FLS. These results suggest that CTX inhibits inflammation and inflammatory pain and adjuvant-induced arthritis. CTX may be a novel therapeutic drug for treatment of arthritis. PMID:25767552

  1. Cycles of Transient High-Dose Cyclophosphamide Administration and Oncolytic Adenovirus Vector Intratumoral Injection for Long Term Tumor Suppression in Syrian Hamsters

    PubMed Central

    Dhar, Debanjan; Toth, Karoly; Wold, William S.M.

    2014-01-01

    Immune responses against oncolytic adenovirus (Ad) vectors are thought to limit vector anti-tumor efficacy. In Syrian hamsters, which are immunocompetent and whose tumors and normal tissues are permissive for replication of Ad5-based oncolytic Ad vectors, treating with high-dose cyclophosphamide to suppress the immune system and exert chemotherapeutic effects enhances Ad vector anti-tumor efficacy. However, long term cyclophosphamide treatment and immunosuppression can lead to anemia and vector spread to normal tissues. Here we employed three cycles of transient high-dose cyclophosphamide administration plus intratumoral injection of the oncolytic Ad vector VRX-007 followed by withdrawal from cyclophosphamide. Each cycle lasted 4-6 weeks. This protocol allowed the hamsters to remain healthy so the study could be continued for ~100 days. The tumors were very well suppressed throughout the study. With immunocompetent hamsters, the vector retarded tumor growth initially, but after 3-4 weeks the tumors resumed rapid growth and further injections of vector were ineffective. Preimmunization of the hamsters with Ad5 prevented vector spillover from the tumor to the liver yet still allowed for effective long term anti-tumor efficacy. Our results suggest that a clinical protocol might be developed with cycles of transient chemotherapy plus intratumoral vector injection to achieve significant anti-tumor efficacy while minimizing the side effects of cytostatic treatment. PMID:24722357

  2. Oral administration of poly-γ-glutamate ameliorates atopic dermatitis in Nc/Nga mice by suppressing Th2-biased immune response and production of IL-17A.

    PubMed

    Lee, Tae-Young; Kim, Doo-Jin; Won, Ji-Na; Lee, Il-Han; Sung, Moon-Hee; Poo, Haryoung

    2014-03-01

    Atopic dermatitis (AD) is a chronic inflammatory skin disease that is closely related to dysregulation of the T helper type 1 and 2 (Th1)/Th2 balance. A previous study showed that high molecular mass poly-γ-glutamate (γ-PGA) isolated from Bacillus subtilis sp. Chungkookjang induces the production of IL-12 from dendritic cells (DCs). Here, we investigated the effect of γ-PGA on AD-like skin disease using an Nc/Nga mouse model. In vitro, γ-PGA activated DCs and induced IL-12 production in mice. In vivo, oral administration of γ-PGA markedly reduced the AD symptoms, similar to the response seen in the dexamethasone (Dex)-treated group. Treatment with γ-PGA also decreased the serum levels of IgG1, the skin levels of Th2 cytokines, the extent of skin inflammation, and the accumulation of mast cells. Furthermore, γ-PGA was effective against established AD, significantly decreasing serum IgE and Th2 cytokines in the inflamed tissue. Interestingly, the production of IL-17A in splenocytes was also suppressed by γ-PGA, indicating that it inhibits both Th2 and Th17 immune responses. Collectively, these results suggest that oral administration of γ-PGA could be a therapeutic strategy for treating AD via the modulation of Th2-biased immune responses in an Nc/Nga mouse model. PMID:24025551

  3. 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

  4. Maternal intravenous administration of azithromycin results in significant fetal uptake in a sheep model of second trimester pregnancy.

    PubMed

    Kemp, Matthew W; 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

    2014-11-01

    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

  5. Intranasal administration of glial-derived neurotrophic factor (GDNF) rapidly and significantly increases whole-brain GDNF level in rats.

    PubMed

    Bender, T S; Migliore, M M; Campbell, R B; John Gatley, S; Waszczak, B L

    2015-09-10

    Previous studies have shown that glial cell line-derived neurotrophic factor (GDNF) exerts significant neuroprotective effects on substantia nigra (SN) neurons in the rat 6-hydroxydopamine (6-OHDA) model of Parkinson's disease (PD). In this study we used enzyme-linked immunosorbent assay (ELISA) to determine GDNF brain levels and distribution to target regions (i.e. striatum and SN) following intranasal administration of GDNF at different time points after administration. Brain levels increased significantly within 1h following a single 50-μg dose of GDNF in a liposomal formulation, returning to baseline by 24h. In a second study, different doses of GDNF (10-150 μg) in phosphate-buffered saline (PBS) were studied at the 1-h time point. Dose-dependent increases in brain GDNF levels were observed with apparent saturation of uptake at doses above 100 μg. Liposomes delivered 10-fold more GDNF to brain than PBS despite yielding similar neuroprotective efficacy in the 6-OHDA model, suggesting incomplete release of GDNF from liposomes in tissue. In a third study, autoradiography was performed on brain sections taken 1h after intranasal (125)I-labeled GDNF. Radioactivity was detected throughout the brain along the rostral-to-caudal axis, indicating that nasally administered GDNF can reach target areas. Collectively, these results demonstrate that intranasal administration of GDNF in liposomes or PBS achieves significant increases in GDNF in target brain areas, supporting use of intranasal administration as a non-invasive means of delivering GDNF to the brain to protect dopamine neurons and arrest disease progression in PD. PMID:26166725

  6. Transperitoneal administration of dissolved hydrogen for peritoneal dialysis patients: a novel approach to suppress oxidative stress in the peritoneal cavity

    PubMed Central

    2013-01-01

    Background Oxidative stress (OS) related to glucose degradation products such as methylglyoxal is reportedly associated with peritoneal deterioration in patients treated with peritoneal dialysis (PD). However, the use of general antioxidant agents is limited due to their harmful effects. This study aimed to clarify the influence of the novel antioxidant molecular hydrogen (H2) on peritoneal OS using albumin redox state as a marker. Methods Effluent and blood samples of 6 regular PD patients were obtained during the peritoneal equilibrium test using standard dialysate and hydrogen-enriched dialysate. The redox state of albumin in effluent and blood was determined using high-performance liquid chromatography. Results Mean proportion of reduced albumin (ƒ(HMA)) in effluent was significantly higher in H2-enriched dialysate (62.31 ± 11.10%) than in standard dialysate (54.70 ± 13.08%). Likewise, serum ƒ(HMA) after administration of hydrogen-enriched dialysate (65.75 ± 7.52%) was significantly higher than that after standard dialysate (62.44 ± 7.66%). Conclusions Trans-peritoneal administration of H2 reduces peritoneal and systemic OS. PMID:23816239

  7. Oral administration of Aloe vera gel powder prevents UVB-induced decrease in skin elasticity via suppression of overexpression of MMPs in hairless mice.

    PubMed

    Saito, Marie; Tanaka, Miyuki; Misawa, Eriko; Yao, Ruiquing; Nabeshima, Kazumi; Yamauchi, Kouji; Abe, Fumiaki; Yamamoto, Yuki; Furukawa, Fukumi

    2016-07-01

    This study reports the effects of oral Aloe vera gel powder (AVGP) containing Aloe sterols on skin elasticity and the extracellular matrix in ultraviolet B (UVB)-irradiated hairless mice. Ten-week-old hairless mice were fed diets containing 0.3% AVGP for 8 weeks and irradiated UVB for 6 weeks. Mice treated with AVGP showed significant prevention of the UVB-induced decrease in skin elasticity. To investigate the mechanism underlying this suppression of skin elasticity loss, we measured the expression of matrix metalloproteinase (MMP)-2, -9, and -13. AVGP prevented both the UVB-induced increases in MMPs expressions. Moreover, we investigated hyaluronic acid (HA) content of mice dorsal skin and gene expression of HA synthase-2 (Has2). In the results, AVGP oral administration prevented UVB-induced decreasing in skin HA content and Has2 expression and attenuates the UVB-induced decrease in serum adiponectin, which promotes Has2 expression. These results suggested that AVGP has the ability to prevent the skin photoaging. PMID:27045316

  8. Peripheral administration of a μ-opioid receptor agonist DAMGO suppresses the anxiolytic and stimulatory effects of caffeine.

    PubMed

    Sudakov, S K; Nazarova, G A; Alekseeva, E V; Kolpakov, A A

    2015-01-01

    We studied the possibility of modulation of the stimulatory and anxiolytic effects of caffeine by activation of μ-opioid receptors in the gastrointestinal tract. Caffeine in a dose of 10 mg/kg (but not in a dose of 100 mg/kg) had a strong anxiolytic and psychostimulant effect. This effect was manifested in a significant increase in the time spent in the open arms of the elevated plus-maze, elevation of locomotor activity, and stimulation of metabolism. Administration of DAMGO to animals receiving caffeine in a dose of 10 mg/kg abolished the anxiolytic and psychostimulant effects of caffeine. By contrast, administration of DAMGO to rats receiving caffeine in a dose of 100 mg/kg had the anxiolytic effect. Activation of peripheral μ-opioid receptors is followed by the inhibition of the central μ-opioid system. We observed a decrease in the number of μ-opioid receptors in the midbrain and cerebral cortex and inhibition of β-endorphin release from nerve ending of the cingulate cortex in rats. These changes are probably followed by activation of the adenosine system in the brain. Caffeine dose should be increased to achieve the effect. Therefore, the anxiolytic and stimulatory effects of caffeine in a dose of 10 mg/kg are abolished under these conditions. By contrast, the anxiolytic effect of caffeine in a dose of 100 mg/kg (not observed under normal conditions) develops after this treatment. PMID:25573353

  9. Dexamethasone Suppression FDG PET/CT for Differentiating between True- and False-Positive Pulmonary and Mediastinal Lymph Node Metastases in Non-Small Cell Lung Cancer: A Pilot Study of FDG PET/CT after Oral Administration of Dexamethasone.

    PubMed

    Nakajo, Masatoyo; Nakajo, Masayuki; Nakayama, Hirofumi; Jinguji, Megumi; Nakabeppu, Yoshiaki; Higashi, Michiyo; Nakamura, Yoshihiro; Sato, Masami; Yoshiura, Takashi

    2016-04-01

    Purpose To examine whether dexamethasone suppression can reduce fluorine 18 fluorodeoxyglucose (FDG) uptake in false-positive (FP) findings in pulmonary and mediastinal lymph nodes in non-small cell lung cancer (NSCLC). Materials and Methods Institutional ethics review board approved this prospective study with written informed consent. The study population was composed of 17 patients with NSCLC who underwent both baseline and dexamethasone suppression (24 hours after oral administration of 8 mg dexamethasone) FDG positron emission tomography/computed tomography and surgery. FDG uptake was evaluated by using a five-point visual scoring system (negative findings, score of 0-1; positive findings, score of 2-4) and maximum standardized uptake value (SUVmax). The Mann-Whitney U, Wilcoxon signed-rank, Kruskal-Wallis, or Spearman rank correlation tests were used as necessary for statistical evaluations. Results In 17 primary lesions, no significant difference was noted in visual score between baseline (mean, 3.4 ± 1.2) and dexamethasone suppression scans (mean, 3.3 ± 1.2; P = .16), although SUVmax was significantly lower on dexamethasone suppression scans (mean, 7.1 ± 5.2) than on baseline scans (mean, 8.6 ± 6.6; P = .005). In eight nodes with true-positive (TP) findings, there were no significant differences in visual score (mean for both, 3.8 ± 0.5) and SUVmax (mean, 5.3 ± 2.3 vs 5.5 ± 2.5, respectively; P = .81) between baseline and dexamethasone suppression scans. In 19 nodes with FP findings at baseline, dexamethasone suppression resulted in significantly lowered visual score (mean, 3.4 ± 0.6 vs 2.4 ± 0.8, respectively; P < .001) and SUVmax (mean, 3.5 ± 0.8 vs 2.7 ± 0.7, respectively; P < .001), and four nodes with FP findings were rated as true-negative findings on dexamethasone suppression scans, which resulted in a significant difference in SUVmax between nodal lesions with TP and FP findings (P = .014). Conclusion Oral dexamethasone has the potential

  10. Effect of Suberoylanilide Hydroxamic Acid (SAHA) Administration on the Residual Virus Pool in a Model of Combination Antiretroviral Therapy-Mediated Suppression in SIVmac239-Infected Indian Rhesus Macaques

    PubMed Central

    Del Prete, Gregory Q.; Shoemaker, Rebecca; Oswald, Kelli; Lara, Abigail; Trubey, Charles M.; Fast, Randy; Schneider, Douglas K.; Kiser, Rebecca; Coalter, Vicky; Wiles, Adam; Wiles, Rodney; Freemire, Brandi; Keele, Brandon F.; Estes, Jacob D.; Quiñones, Octavio A.; Smedley, Jeremy; Macallister, Rhonda; Sanchez, Rosa I.; Wai, John S.; Tan, Christopher M.; Alvord, W. Gregory; Hazuda, Daria J.; Piatak, Michael

    2014-01-01

    Nonhuman primate models are needed for evaluations of proposed strategies targeting residual virus that persists in HIV-1-infected individuals receiving suppressive combination antiretroviral therapy (cART). However, relevant nonhuman primate (NHP) models of cART-mediated suppression have proven challenging to develop. We used a novel three-class, six-drug cART regimen to achieve durable 4.0- to 5.5-log reductions in plasma viremia levels and declines in cell-associated viral RNA and DNA in blood and tissues of simian immunodeficiency virus SIVmac239-infected Indian-origin rhesus macaques, then evaluated the impact of treatment with the histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA; Vorinostat) on the residual virus pool. Ex vivo SAHA treatment of CD4+ T cells obtained from cART-suppressed animals increased histone acetylation and viral RNA levels in culture supernatants. cART-suppressed animals each received 84 total doses of oral SAHA. We observed SAHA dose-dependent increases in acetylated histones with evidence for sustained modulation as well as refractoriness following prolonged administration. In vivo virologic activity was demonstrated based on the ratio of viral RNA to viral DNA in peripheral blood mononuclear cells, a presumptive measure of viral transcription, which significantly increased in SAHA-treated animals. However, residual virus was readily detected at the end of treatment, suggesting that SAHA alone may be insufficient for viral eradication in the setting of suppressive cART. The effects observed were similar to emerging data for repeat-dose SAHA treatment of HIV-infected individuals on cART, demonstrating the feasibility, utility, and relevance of NHP models of cART-mediated suppression for in vivo assessments of AIDS virus functional cure/eradication approaches. PMID:25182644

  11. Chronic oral administration of minocycline to sheep with ovine CLN6 neuronal ceroid lipofuscinosis maintains pharmacological concentrations in the brain but does not suppress neuroinflammation or disease progression

    PubMed Central

    2013-01-01

    Background The neuronal ceroid lipofuscinoses (NCLs; or Batten disease) are fatal inherited human neurodegenerative diseases affecting an estimated 1:12,500 live births worldwide. They are caused by mutations in at least 11 different genes. Currently, there are no effective treatments. Progress into understanding pathogenesis and possible therapies depends on studying animal models. The most studied animals are the CLN6 South Hampshire sheep, in which the course of neuropathology closely follows that in affected children. Neurodegeneration, a hallmark of the disease, has been linked to neuroinflammation and is consequent to it. Activation of astrocytes and microglia begins prenatally, starting from specific foci associated with the later development of progressive cortical atrophy and the development of clinical symptoms, including the occipital cortex and blindness. Both neurodegeneration and neuroinflammation generalize and become more severe with increasing age and increasing clinical severity. The purpose of this study was to determine if chronic administration of an anti-inflammatory drug, minocycline, from an early age would halt or reverse the development of disease. Method Minocycline, a tetracycline family antibiotic with activity against neuroinflammation, was tested by chronic oral administration of 25 mg minocycline/kg/day to presymptomatic lambs affected with CLN6 NCL at 3 months of age to 14 months of age, when clinical symptoms are obvious, to determine if this would suppress neuroinflammation or disease progression. Results Minocycline was absorbed without significant rumen biotransformation to maintain pharmacological concentrations of 1 μM in plasma and 400 nM in cerebrospinal fluid, but these did not result in inhibition of microglial activation or astrocytosis and did not change the neuronal loss or clinical course of the disease. Conclusion Oral administration is an effective route for drug delivery to the central nervous system in large

  12. Intratumoral administration of anti-KITENIN shRNA-loaded PEI-alt-PEG nanoparticles suppressed colon carcinoma established subcutaneously in mice.

    PubMed

    Park, In-Kyu; Kim, Kyung Keun; Cho, Sang-Hee; Bae, Woo-Kyun; Jere, Dhananjay; Cho, Chong-Su; Chung, Ik-Joo

    2010-05-01

    Biodegradable gene carrier, termed as PEI-alt-PEG, has been synthesized based on Michael addition reaction between lower Mw PEI and poly(ethylene glycol) (PEG) diacrylate and tested its potential of anti-metastatic cancer gene therapy by using anti-KITENIN short hairpin RNA. KITENIN is known to promote invasion of mouse colon adenocarcinoma in vivo. Intratumoral administration of anti-KITENIN shRNA-loaded PEI-alt-PEG nanoparticles has shown suppressed proliferlation and enhanced apoptosis signal in tumor compared to commercial available liposome, leading to delayed tumor growth. PMID:20358939

  13. Reversal of high dietary fructose-induced PPARalpha suppression by oral administration of lipoxygenase/cyclooxygenase inhibitors.

    PubMed

    Kelley, Glen L; Azhar, Salman

    2005-08-01

    High fructose feeding causes diet-induced alterations of lipid metabolism and decreased insulin sensitivity, hallmark of which is a rapid and profound hypertriglyceridemia. One of the mechanisms that contribute to serum hypertriglyceridemia in this model is suppression of hepatic PPARalpha. HMG-CoA inhibitors, which reduce serum triglycerides in these animals, also elevate/restore hepatic PPARalpha. Previously we demonstrated that two known lipoxygenase/cyclooxygenase inhibitors reversed diet-induced hypertriglyceridemia in this model and that reversal of certain inflammatory markers in the liver correlated with the metabolic benefit. In this paper we extended these studies by examining the impact of these compounds on expression of PPARalpha, both at the level of transcription and expression. Our data show that diet-induced suppression of hepaic PPARalpha is reversed upon treatment with lipoxygenase/cyclooxygenase compounds. We then tested one of these compounds, BW-755c, over a range of doses from 10 mg/kg to 100 mg/kg to establish a dose-response relationship with the reduction of serum hypertriglyceridemia in this model. These experiments support the concept of using anti-inflammatory medications as one method to correct metabolic dysfunction. PMID:16091142

  14. First Use of a New Device for Administration of Buspirone and Acetaminophen to Suppress Shivering During Therapeutic Hypothermia.

    PubMed

    Honasoge, Akilesh; Parker, Braden; Wesselhoff, Kelly; Lyons, Neal; Kulstad, Erik

    2016-03-01

    Therapeutic hypothermia or targeted temperature management has been used after cardiac arrest to improve neurological outcomes and mortality. However, a side effect of temperature modulation is a centrally mediated shivering response. The Columbia Anti-Shivering Protocol sets up a systematic method of intravenous (IV) and oral medication escalation to suppress this response and preserve the benefits of this therapy. We present the case of a 59-year-old male who began shivering after therapeutic hypothermia for cardiac arrest, leading to a persistent rise in core temperature despite adequate sedation. He was also found to have gastric contents similar to coffee grounds through nasogastric tube suction. The shivering was effectively suppressed and the rising core temperature plateaued using rectal acetaminophen and buspirone administered by means of a novel device, the Macy Catheter. Also, when used in conjunction with other protocol-driven medications, the patient was able to achieve a core temperature of 33°C. The Macy Catheter appears to be a useful approach to rectally administer buspirone and acetaminophen, using an easy-to-place, nonsterile atraumatic device that requires no radiographic confirmation of placement. PMID:26807775

  15. First Use of a New Device for Administration of Buspirone and Acetaminophen to Suppress Shivering During Therapeutic Hypothermia

    PubMed Central

    Parker, Braden; Wesselhoff, Kelly; Lyons, Neal; Kulstad, Erik

    2016-01-01

    Therapeutic hypothermia or targeted temperature management has been used after cardiac arrest to improve neurological outcomes and mortality. However, a side effect of temperature modulation is a centrally mediated shivering response. The Columbia Anti-Shivering Protocol sets up a systematic method of intravenous (IV) and oral medication escalation to suppress this response and preserve the benefits of this therapy. We present the case of a 59-year-old male who began shivering after therapeutic hypothermia for cardiac arrest, leading to a persistent rise in core temperature despite adequate sedation. He was also found to have gastric contents similar to coffee grounds through nasogastric tube suction. The shivering was effectively suppressed and the rising core temperature plateaued using rectal acetaminophen and buspirone administered by means of a novel device, the Macy Catheter. Also, when used in conjunction with other protocol-driven medications, the patient was able to achieve a core temperature of 33°C. The Macy Catheter appears to be a useful approach to rectally administer buspirone and acetaminophen, using an easy-to-place, nonsterile atraumatic device that requires no radiographic confirmation of placement. PMID:26807775

  16. Glial cell line-derived neurotrophic factor-conjugated nanoparticles suppress acquisition of cocaine self-administration in rats.

    PubMed

    Green-Sadan, T; Kuttner, Y; Lublin-Tennenbaum, T; Kinor, N; Boguslavsky, Y; Margel, S; Yadid, G

    2005-07-01

    The neurotrophic factor glial cell line-derived neurotrophic factor (GDNF) may have therapeutic potential for preventing and treating cocaine addiction. Previously, we found that transplantation of a GDNF-expressing astrocyte cell line into the striatum and nucleus accumbens attenuates cocaine-seeking behavior in Sprague-Dawley rats. However, as a potential treatment for humans, cell transplantation presents several technical and ethical complications. Nanoparticulate systems are a safe and effective method for introducing exogenous compounds into the brain. Therefore, we examined the effect of GDNF-conjugated nanoparticles microinjected into the striatum and nucleus accumbens on cocaine self-administration in rats. GDNF-conjugated nanoparticles blocked the acquisition of cocaine self-administration compared to control treatments. Furthermore, a cocaine dose response demonstrated that decreased lever response in rats that received GDNF-conjugated nanoparticles persisted after substitution with different cocaine doses. This effect is not due to a non-specific disruption of locomotor or operant behavior, as seen following a water operant task. The current study is one of the first demonstrations that drug-conjugated nanoparticles may be effective in treating brain disorders. These findings suggest that GDNF-conjugated nanoparticles may serve as a novel potential treatment for drug addiction. PMID:15899247

  17. Administration of a Toll-like receptor 9 agonist decreases the proviral reservoir in virologically suppressed HIV-infected patients.

    PubMed

    Winckelmann, Anni A; Munk-Petersen, Lærke V; Rasmussen, Thomas A; Melchjorsen, Jesper; Hjelholt, Thomas J; Montefiori, David; Østergaard, Lars; Søgaard, Ole S; Tolstrup, Martin

    2013-01-01

    Toll-like receptor (TLR) agonists can reactivate HIV from latently infected cells in vitro. We aimed to investigate the TLR-9 agonist, CPG 7909's in vivo effect on the proviral HIV reservoir and HIV-specific immunity. This was a post-hoc analysis of a double-blind randomized controlled vaccine trial. HIV-infected adults were randomized 1:1 to receive pneumococcal vaccines with or without 1 mg CPG 7909 as adjuvant at 0, 3 and 9 months. In patients on suppressive antiretroviral therapy we quantified proviral DNA at 0, 3, 4, 9, and 10 months (31 subjects in the CPG group and 37 in the placebo-adjuvant group). Furthermore, we measured HIV-specific antibodies, characterized T cell phenotypes and HIV-specific T cell immunity. We observed a mean reduction in proviral DNA in the CPG group of 12.6% (95% CI: -23.6-0.0) following each immunization whereas proviral DNA in the placebo-adjuvant group remained largely unchanged (6.7% increase; 95% CI: -4.2-19.0 after each immunization, p = 0.02). Among participants with additional cryo-preserved PBMCs, HIV-specific CD8+ T cell immunity as indicated by increased expression of degranulation marker CD107a and macrophage inflammatory protein 1β (MIP1β) tended to be up-regulated following immunization with CPG 7909 compared with placebo as adjuvant. Further, increasing proportion of HIV-specific CD107a and MIP1β-expressing CD8+ T cells were strongly correlated with decreasing proviral load. No changes were observed in T cell phenotype distribution, HIV-specific CD4+ T cell immunity, or HIV-specific antibodies. TLR9-adjuvanted pneumococcal vaccination decreased proviral load. Reductions in proviral load correlated with increasing levels of HIV specific CD8+ T cells. Further investigation into the potential effect of TLR9 agonists on HIV latency is warranted. PMID:23637967

  18. Oral Administration of Royal Jelly Restores Tear Secretion Capacity in Rat Blink-Suppressed Dry Eye Model by Modulating Lacrimal Gland Function

    PubMed Central

    Imada, Toshihiro; Nakamura, Shigeru; Kitamura, Naoki; Shibuya, Izumi; Tsubota, Kazuo

    2014-01-01

    Tears are secreted from the lacrimal gland (LG), a dysfunction in which induces dry eye, resulting in ocular discomfort and visual impairment. Honey bee products are used as a nutritional source in daily life and medicine; however, little is known about their effects on dry eye. The aim of the present study was to investigate the effects of honey bee products on tear secretion capacity in dry eye. We selected raw honey, propolis, royal jelly (RJ), pollen, or larva from commercially available honey bee products. Tear secretion capacity was evaluated following the oral administration of each honey bee product in a rat blink-suppressed dry eye model. Changes in tear secretion, LG ATP content, and LG mitochondrial levels were measured. RJ restored the tear secretion capacity and decrease in LG ATP content and mitochondrial levels to the largest extent. Royal jelly can be used as a preventative intervention for dry eye by managing tear secretion capacity in the LG. PMID:25243778

  19. Intratracheal Administration of Mesenchymal Stem Cells Modulates Tachykinin System, Suppresses Airway Remodeling and Reduces Airway Hyperresponsiveness in an Animal Model

    PubMed Central

    Spaziano, Giuseppe; Piegari, Elena; Matteis, Maria; Cappetta, Donato; Esposito, Grazia; Russo, Rosa; Tartaglione, Gioia; De Palma, Raffaele; Rossi, Francesco; D’Agostino, Bruno

    2016-01-01

    Background The need for new options for chronic lung diseases promotes the research on stem cells for lung repair. Bone marrow-derived mesenchymal stem cells (MSCs) can modulate lung inflammation, but the data on cellular processes involved in early airway remodeling and the potential involvement of neuropeptides are scarce. Objectives To elucidate the mechanisms by which local administration of MSCs interferes with pathophysiological features of airway hyperresponsiveness in an animal model. Methods GFP-tagged mouse MSCs were intratracheally delivered in the ovalbumin mouse model with subsequent functional tests, the analysis of cytokine levels, neuropeptide expression and histological evaluation of MSCs fate and airway pathology. Additionally, MSCs were exposed to pro-inflammatory factors in vitro. Results Functional improvement was observed after MSC administration. Although MSCs did not adopt lung cell phenotypes, cell therapy positively affected airway remodeling reducing the hyperplastic phase of the gain in bronchial smooth muscle mass, decreasing the proliferation of epithelium in which mucus metaplasia was also lowered. Decrease of interleukin-4, interleukin-5, interleukin-13 and increase of interleukin-10 in bronchoalveolar lavage was also observed. Exposed to pro-inflammatory cytokines, MSCs upregulated indoleamine 2,3-dioxygenase. Moreover, asthma-related in vivo upregulation of pro-inflammatory neurokinin 1 and neurokinin 2 receptors was counteracted by MSCs that also determined a partial restoration of VIP, a neuropeptide with anti-inflammatory properties. Conclusion Intratracheally administered MSCs positively modulate airway remodeling, reduce inflammation and improve function, demonstrating their ability to promote tissue homeostasis in the course of experimental allergic asthma. Because of a limited tissue retention, the functional impact of MSCs may be attributed to their immunomodulatory response combined with the interference of neuropeptide

  20. 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.

  1. The intra-nasal administration of insulin induces significant hypoglycaemia and classical counterregulatory hormonal responses in normal man.

    PubMed

    Paquot, N; Scheen, A J; Franchimont, P; Lefebvre, P J

    1988-01-01

    The present study aimed at investigating the metabolic and hormonal consequences of intra-nasal administration of insulin in normal man. Lyophylisated regular porcine insulin (Insuline Ordinaire Organon) diluted with a non ionic detergent (Laureth-9 0,25%) was administered intra-nasally in 8 overnight fasted healthy volunteers using a calibrated aerosol delivery device (90 microliters = 9 U of insulin/spray) up to a total insulin dose close to 1 U/kg body weight. After intra-nasal insulin administration, plasma insulin levels rose from 5 +/- 1 to 38 +/- 10 mU/l (2p less than 0.01) at min 15, blood glucose concentrations decreased from 4.4 +/- 0.2 to 3.2 +/- 0.3 mmol/l (2p less than 0.01) at min 45, plasma C-peptide levels diminished from 327 +/- 31 to 174 +/- 28 mumol/l (2p less than 0.01) at min 60 and plasma free fatty acids concentrations fell from 336 +/- 109 to 130 +/- 31 mumol/l (2p less than 0.05) at min 30. The fall in blood glucose resulted in a prompt increase in plasma glucagon levels (from 78 +/- 28 to 150 +/- 24 ng/l at min 45; 2p less than 0.05) and in later rises in plasma growth hormone and cortisol concentrations. There was a close relationship between the individual maximal decreases in blood glucose levels and the individual maximal increases in plasma insulin (r = 0.81), glucagon (r = 0.88), cortisol (r = 0.87) and growth hormone (r = 0.76) concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3292305

  2. Silibinin and Paclitaxel Cotreatment Significantly Suppress the Activity and Lung Metastasis of Triple Negative 4T1 Mammary Tumor Cell in Mice

    PubMed Central

    Ho, Bing-Ying; Lin, Chun-Hung; Apaya, Maria Karmella; Chao, Wen-Wan; Shyur, Lie-Fen

    2012-01-01

    The in vitro and in vivo bioactivities of silibinin (SB), paclitaxel (PTX) and SB and PTX in combination (SB+PTX) against murine metastatic mammary 4T1 cancer cell line were investigated. Isobologram and combination index (CI) analyses showed that SB and PTX can function synergistically in the inhibition of 4T1 cell proliferation with a CI value < 1. Both SB and PTX alone or SB+PTX treatment inhibited 4T1 cell migration and motility possibly through downregulation of the serpin protease nexin-1 (PN-1) and N-cadherin expression, inhibition of matrix metalloprotease (MMP)-9 activity, and upregulation of E-cadherin. Flow cytometry and Western blot analyses demonstrated that both drugs deregulated cell-cycle mediators and induced apoptosis in 4T1 cells. A real-time in vivo bioluminescence imaging system to monitor the breast cancer cell metastasis in syngeneic BALB/c mice was established using a stable 4T1pGL-COX-2/Luc cell clone carrying a COX-2 promoter driven-luciferase reporter gene. In vivo study using the allograft 4T1pGL-COX-2/Luc metastatic mouse model indicated that SB co-treated with PTX can significantly suppress lung metastasis of 4T1 cells likely through inhibiting cell proliferation and angiogenesis. Together, this study demonstrates that SB could act synergistically with PTX in 4T1 cells, providing a therapeutic option for highly metastatic triple negative breast cancer. PMID:24716145

  3. Administrators' Perceptions of Factors Related to Student Retention at Colleges with a Significant Black Student Enrollment Affiliated with the Association for Biblical Higher Education

    ERIC Educational Resources Information Center

    Wilson, Wesley B.

    2013-01-01

    This study described and explored the factors perceived as relevant to student retention by administrators at colleges and universities with significant Black student populations. The sample was 31 institutions affiliated with the Association for Biblical Higher Education (ABHE) that had Black student enrollment of 20% or more. The study sought to…

  4. From 9/11 to Recession: Historically Significant Events in America and Their Impact on Research Administration

    ERIC Educational Resources Information Center

    Minnema, Linnea

    2011-01-01

    Federally sponsored research funding sources are not stagnant programs. Many things influence the nature of research, not all of them purely scientific. Historically significant events draw public attention to causes, and in the age of immediate information those events can have a powerful and lasting impact on research funding. September 11, 2001…

  5. Pigment epithelial-derived factor gene loaded novel COOH-PEG-PLGA-COOH nanoparticles promoted tumor suppression by systemic administration

    PubMed Central

    Yu, Ting; Xu, Bei; He, Lili; Xia, Shan; Chen, Yan; Zeng, Jun; Liu, Yongmei; Li, Shuangzhi; Tan, Xiaoyue; Ren, Ke; Yao, Shaohua; Song, Xiangrong

    2016-01-01

    Anti-angiogenesis has been proposed as an effective therapeutic strategy for cancer treatment. Pigment epithelium-derived factor (PEDF) is one of the most powerful endogenous anti-angiogenic reagents discovered to date and PEDF gene therapy has been recognized as a promising treatment option for various tumors. There is an urgent need to develop a safe and valid vector for its systemic delivery. Herein, a novel gene delivery system based on the newly synthesized copolymer COOH-PEG-PLGA-COOH (CPPC) was developed in this study, which was probably capable of overcoming the disadvantages of viral vectors and cationic lipids/polymers-based nonviral carriers. PEDF gene loaded CPPC nanoparticles (D-NPs) were fabricated by a modified double-emulsion water-in-oil-in-water (W/O/W) solvent evaporation method. D-NPs with uniform spherical shape had relatively high drug loading (~1.6%), probably because the introduced carboxyl group in poly (D,L-lactide-co-glycolide) terminal enhanced the interaction of copolymer with the PEDF gene complexes. An excellent in vitro antitumor effect was found in both C26 and A549 cells treated by D-NPs, in which PEDF levels were dramatically elevated due to the successful transfection of PEDF gene. D-NPs also showed a strong inhibitory effect on proliferation of human umbilical vein endothelial cells in vitro and inhibited the tumor-induced angiogenesis in vivo by an alginate-encapsulated tumor cell assay. Further in vivo antitumor investigation, carried out in a C26 subcutaneous tumor model by intravenous injection, demonstrated that D-NPs could achieve a significant antitumor activity with sharply reduced microvessel density and significantly promoted tumor cell apoptosis. Additionally, the in vitro hemolysis analysis and in vivo serological and biochemical analysis revealed that D-NPs had no obvious toxicity. All the data indicated that the novel CPPC nanoparticles were ideal vectors for the systemic delivery of PEDF gene and might be widely

  6. Reoxygenation of Asphyxiated Newborn Piglets: Administration of 100% Oxygen Causes Significantly Higher Apoptosis in Cortical Neurons, as Compared to 21%

    PubMed Central

    Faa, G.; Fanos, V.; Fanni, D.; Gerosa, C.; Faa, A.; Fraschini, M.; Pais, M. E.; Di Felice, E.; Papalois, A.; Varsami, M.; Xanthos, T.; Iacovidou, N.

    2014-01-01

    Objective. Evaluation of neuronal changes in an animal experimental model of normocapnic hypoxia- reoxygenation. Materials and Methods. Fifty male piglets were the study subjects; normocapnic hypoxia was induced in 40 piglets and ten were sham-operated (controls). When bradycardia and/or severe hypotension occurred, reoxygenation was initiated. Animals were allocated in 4 groups according to the oxygen concentration, they were resuscitated with 18%, 21%, 40%, and 100% O2. Persisting asystole despite 10 minutes of cardiopulmonary resuscitation and return of spontaneous circulation were the endpoints of the experiment. Surviving animals were euthanized and brain cortex samples were collected, hematoxylin and eosin-stained, and examined for apoptotic bodies observing 10 consecutive high power fields. Results. Histological examination of the control group did not show any pathological change. On the contrary, apoptosis of neurons was found in 87.5% of treated animals. When specimens were examined according to the oxygen concentration used for resuscitation, we found marked intergroup variability; a higher percentage of apoptotic neurons was observed in piglets of group 4 (100% oxygen) compared to the others (P = 0.001). Conclusions. This preliminary data shows that normocapnic hypoxia and reoxygenation in Landrace/Large White piglets resulted in significant histological changes in the brain cortex. The degree of pathological changes in cortical neurons was significantly associated with the oxygen concentration used for reoxygenation, with a higher percentage of apoptotic neurons being observed in piglets reoxygenated with 100% compared to 18% O2 and to 21% O2. PMID:24783208

  7. Delayed Administration of Bone Marrow Mesenchymal Stem Cell Conditioned Medium Significantly Improves Outcome After Retinal Ischemia in Rats

    PubMed Central

    Dreixler, John C.; Poston, Jacqueline N.; Balyasnikova, Irina; Shaikh, Afzhal R.; Tupper, Kelsey Y.; Conway, Sineadh; Boddapati, Venkat; Marcet, Marcus M.; Lesniak, Maciej S.; Roth, Steven

    2014-01-01

    Purpose. Delayed treatment after ischemia is often unsatisfactory. We hypothesized that injection of bone marrow stem cell (BMSC) conditioned medium after ischemia could rescue ischemic retina, and in this study we characterized the functional and histological outcomes and mechanisms of this neuroprotection. Methods. Retinal ischemia was produced in adult Wistar rats by increasing intraocular pressure for 55 minutes. Conditioned medium (CM) from rat BMSCs or unconditioned medium (uCM) was injected into the vitreous 24 hours after the end of ischemia. Recovery was assessed 7 days after ischemia using electroretinography, at which time we euthanized the animals and then prepared 4-μm-thick paraffin-embedded retinal sections. TUNEL and Western blot were used to identify apoptotic cells and apoptosis-related gene expression 24 hours after injections; that is, 48 hours after ischemia. Protein content in CM versus uCM was studied using tandem mass spectrometry, and bioinformatics methods were used to model protein interactions. Results. Intravitreal injection of CM 24 hours after ischemia significantly improved retinal function and attenuated cell loss in the retinal ganglion cell layer. CM attenuated postischemic apoptosis and apoptosis-related gene expression. By spectral counting, 19 proteins that met stringent identification criteria were increased in the CM compared to uCM; the majority were extracellular matrix proteins that mapped into an interactional network together with other proteins involved in cell growth and adhesion. Conclusions. By restoring retinal function, attenuating apoptosis, and preventing retinal cell loss after ischemia, CM is a robust means of delayed postischemic intervention. We identified some potential candidate proteins for this effect. PMID:24699381

  8. The incidence and significance of acute kidney injury following emergent contrast administration in patients with STEMI and stroke.

    PubMed

    Marchick, Michael Robert; Allen, Brandon Russell; Weeks, Emily Cassin; Shuster, Jonathan Jacob; Elie, Marie-Carmelle

    2016-09-01

    The authors have investigated the incidence of acute kidney injury (AKI) and short-term mortality following an activated STEMI and stroke alert at a tertiary referral and academic center. A single center, retrospective chart review of STEMI and stroke activation patients from January 2010 to March 2012. Data was collected and reviewed from an institutional database following IRB-approval. Inclusion criteria were STEMI patients taken for cardiac catheterization, excluding patients receiving hemodialysis due to end-stage renal disease (ESRD). Primary outcome measures were the incidence of AKI using the RIFLE criteria and short-term mortality. 745 patients were included (488 stroke, 257 STEMI). The median age was 65, and 39 % were female. Overall inpatient mortality was 7.0 %. 5.4 % (40/745) of patients experienced some degree of AKI (8.6 % of STEMI, 3.7 % of stroke patients). Overall, 30 % of patients with AKI died during their hospitalization. AKI was associated with a 7.1-fold (95 % CI 3.4-15.1) increase in mortality in the entire cohort. Among STEMI patients, AKI was associated with a 66.6-fold (95 % CI 12.9-343.4) increase in mortality. These findings follow similar trends published among critically ill patients with AKI. The risk of death with concomitant AKI in this hospital population is significant and deserves future study. Early recognition and awareness in the emergency department is paramount to the patient's survival. Future studies should focus on modalities to improve early recognition and preventative therapies. PMID:26910240

  9. Administration of Pigment Epithelium-Derived Factor Inhibits Airway Inflammation and Remodeling in Chronic OVA-Induced Mice via VEGF Suppression

    PubMed Central

    Zha, Wangjian; Su, Mei; Huang, Mao; Cai, Jiankang

    2016-01-01

    Purpose Pigment epithelium-derived factor (PEDF) is a recently discovered antiangiogenesis protein. PEDF possesses powerful anti-inflammatory, antioxidative, antiangiogenic, and antifibrosis properties. It has been reported that PEDF can regulate vascular endothelial growth factor (VEGF) expression. This study aimed to evaluate whether recombinant PEDF protein could attenuate allergic airway inflammation and airway remodeling via the negative regulation of VEGF using a murine model of chronic ovalbumin (OVA)-induced asthma and BEAS-2B human bronchial epithelial cells. Methods In an in vivo experiment, mice sensitized with OVA were chronically airway challenged with aerosolized 1% OVA solution for 8 weeks. Treated mice were given injections of recombinant PEDF protein (50 or 100 µg/kg body weight) via the tail vein. In an in vitro experiment, we investigated the effects of recombinant PEDF protein on VEGF release levels in BEAS-2B cells stimulated with IL-1β. Results Recombinant PEDF protein significantly inhibited eosinophilic airway inflammation, airway hyperresponsiveness, and airway remodeling, including goblet cell hyperplasia, subepithelial collagen deposition, and airway smooth muscle hypertrophy. In addition, recombinant PEDF protein suppressed the enhanced expression of VEGF protein in lung tissue and bronchoalveolar lavage fluid (BALF) in OVA-challenged chronically allergic mice. In the in vitro experiment, VEGF expression was increased after IL-1β stimulation. Pretreatment with 50 and 100 ng/mL of recombinant PEDF protein significantly attenuated the increase in VEGF release levels in a concentration-dependent manner in BEAS-2B cells stimulated by IL-1β. Conclusions These results suggest that recombinant PEDF protein may abolish the development of characteristic features of chronic allergic asthma via VEGF suppression, providing a potential treatment option for chronic airway inflammation diseases such as asthma. PMID:26739410

  10. Oral administration of curcumin suppresses production of matrix metalloproteinase (MMP)-1 and MMP-3 to ameliorate collagen-induced arthritis: inhibition of the PKCdelta/JNK/c-Jun pathway.

    PubMed

    Mun, Se Hwan; Kim, Hyuk Soon; Kim, Jie Wan; Ko, Na Young; Kim, Do Kyun; Lee, Beob Yi; Kim, Bokyung; Won, Hyung Sik; Shin, Hwa-Sup; Han, Jeung-Whan; Lee, Hoi Young; Kim, Young Mi; Choi, Wahn Soo

    2009-09-01

    We investigated whether oral administration of curcumin suppressed type II collagen-induced arthritis (CIA) in mice and its effect and mechanism on matrix metalloproteinase (MMP)-1 and MMP-3 production in CIA mice, RA fibroblast-like synoviocytes (FLS), and chondrocytes. CIA in mice was suppressed by oral administration of curcumin in a dose-dependent manner. Macroscopic observations were confirmed by histological examinations. Histological changes including infiltration of immune cells, synovial hyperplasia, cartilage destruction, and bone erosion in the hind paw sections were extensively suppressed by curcumin. The histological scores were consistent with clinical arthritis indexes. Production of MMP-1 and MMP-3 were inhibited by curcumin in CIA hind paw sections and tumor necrosis factor (TNF)-alpha-stimulated FLS and chondrocytes in a dose-dependent manner. As for the mechanism, curcumin inhibited activating phosphorylation of protein kinase Cdelta (PKCdelta) in CIA, FLS, and chondrocytes. Curcumin also suppressed the JNK and c-Jun activation in those cells. This study suggests that the suppression of MMP-1 and MMP-3 production by curcumin in CIA is mediated through the inhibition of PKCdelta and the JNK/c-Jun signaling pathway. PMID:19763044

  11. Difference in method of administration did not significantly impact item response: an IRT-based analysis from the Patient-Reported Outcomes Measurement Information System (PROMIS) initiative

    PubMed Central

    Rose, Matthias; Gandek, Barbara; Stone, Arthur A.; Junghaenel, Doerte U.; Ware, John E.

    2013-01-01

    Purpose To test the impact of method of administration (MOA) on the measurement characteristics of items developed in the Patient-Reported Outcomes Measurement Information System (PROMIS). Methods Two non-overlapping parallel 8-item forms from each of three PROMIS domains (physical function, fatigue, and depression) were completed by 923 adults (age 18–89) with chronic obstructive pulmonary disease, depression, or rheumatoid arthritis. In a randomized crossover design, subjects answered one form by interactive voice response (IVR) technology, paper questionnaire (PQ), personal digital assistant (PDA), or personal computer (PC) on the Internet, and a second form by PC, in the same administration. Structural invariance, equivalence of item responses, and measurement precision were evaluated using confirmatory factor analysis and item response theory methods. Results Multigroup confirmatory factor analysis supported equivalence of factor structure across MOA. Analyses by item response theory found no differences in item location parameters and strongly supported the equivalence of scores across MOA. Conclusions We found no statistically or clinically significant differences in score levels in IVR, PQ, or PDA administration as compared to PC. Availability of large item response theory-calibrated PROMIS item banks allowed for innovations in study design and analysis. PMID:23877585

  12. Suppression of acute proinflammatory cytokine and chemokine upregulation by post-injury administration of a novel small molecule improves long-term neurologic outcome in a mouse model of traumatic brain injury

    PubMed Central

    Lloyd, Eric; Somera-Molina, Kathleen; Van Eldik, Linda J; Watterson, D Martin; Wainwright, Mark S

    2008-01-01

    Background Traumatic brain injury (TBI) with its associated morbidity is a major area of unmet medical need that lacks effective therapies. TBI initiates a neuroinflammatory cascade characterized by activation of astrocytes and microglia, and increased production of immune mediators including proinflammatory cytokines and chemokines. This inflammatory response contributes both to the acute pathologic processes following TBI including cerebral edema, in addition to longer-term neuronal damage and cognitive impairment. However, activated glia also play a neuroprotective and reparative role in recovery from injury. Thus, potential therapeutic strategies targeting the neuroinflammatory cascade must use careful dosing considerations, such as amount of drug and timing of administration post injury, in order not to interfere with the reparative contribution of activated glia. Methods We tested the hypothesis that attenuation of the acute increase in proinflammatory cytokines and chemokines following TBI would decrease neurologic injury and improve functional neurologic outcome. We used the small molecule experimental therapeutic, Minozac (Mzc), to suppress TBI-induced up-regulation of glial activation and proinflammatory cytokines back towards basal levels. Mzc was administered in a clinically relevant time window post-injury in a murine closed-skull, cortical impact model of TBI. Mzc effects on the acute increase in brain cytokine and chemokine levels were measured as well as the effect on neuronal injury and neurobehavioral function. Results Administration of Mzc (5 mg/kg) at 3 h and 9 h post-TBI attenuates the acute increase in proinflammatory cytokine and chemokine levels, reduces astrocyte activation, and the longer term neurologic injury, and neurobehavioral deficits measured by Y maze performance over a 28-day recovery period. Mzc-treated animals also have no significant increase in brain water content (edema), a major cause of the neurologic morbidity associated

  13. Bacteriophage administration significantly reduces Shigella colonization and shedding by Shigella-challenged mice without deleterious side effects and distortions in the gut microbiota

    PubMed Central

    Mai, Volker; Ukhanova, Maria; Reinhard, Mary K; Li, Manrong; Sulakvelidze, Alexander

    2015-01-01

    We used a mouse model to establish safety and efficacy of a bacteriophage cocktail, ShigActive™, in reducing fecal Shigella counts after oral challenge with a susceptible strain. Groups of inbred C57BL/6J mice challenged with Shigella sonnei strain S43-NalAcR were treated with a phage cocktail (ShigActive™) composed of 5 lytic Shigella bacteriophages and ampicillin. The treatments were administered (i) 1 h after, (ii) 3 h after, (iii) 1 h before and after, and (iv) 1 h before bacterial challenge. The treatment regimens elicited a 10- to 100-fold reduction in the CFU's of the challenge strain in fecal and cecum specimens compared to untreated control mice, (P < 0.05). ShigActiveTM treatment was at least as effective as treatment with ampicillin but had a significantly less impact on the gut microbiota. Long-term safety studies did not identify any side effects or distortions in overall gut microbiota associated with bacteriophage administration. Shigella phages may be therapeutically effective in a “classical phage therapy” approach, at least during the early stages after Shigella ingestion. Oral prophylactic “phagebiotic” administration of lytic bacteriophages may help to maintain a healthy gut microbiota by killing specifically targeted bacterial pathogens in the GI tract, without deleterious side effects and without altering the normal gut microbiota. PMID:26909243

  14. The selective dopamine uptake inhibitor, D-84, suppresses cocaine self-administration, but does not occasion cocaine-like levels of generalization.

    PubMed

    Batman, Angela M; Dutta, Aloke K; Reith, Maarten E A; Beardsley, Patrick M

    2010-12-01

    A successful replacement pharmacotherapy for treating cocaine dependency would likely reduce cocaine's abuse, support a low abuse liability, overlap cocaine's subjective effects, and have a long duration of action. Inhibitors with varying selectivity at the dopamine transporter (DAT) have approximated these properties. The objective of the present study was to characterize the behavioural effects of an extremely selective DAT inhibitor, (+) trans-4-(2-Benzhydryloxyethyl)-1-(4-fluorobenzyl) piperadin-3-ol (D-84), a 3-hydroxy substituted piperidine derivative of GBR-12935, for its cocaine-like discriminative stimulus effects, its effects on cocaine self-administration, and for its own self-administration. During cocaine discrimination tests, cocaine occasioned the 10 mg/kg cocaine training stimulus with an ED(50) value of 3.13 (1.54-6.34) mg/kg, and reduced response rates with an ED(50) value of 20.39 (7.24-57.44) mg/kg. D-84 incompletely generalized to the cocaine stimulus occasioning a maximal 76% cocaine-lever responding, while reducing response rates with lower potency than cocaine (ED(50)=30.94 (12.34-77.60) mg/kg). Pretreatment with D-84 (9.6-30.4 mg/kg) significantly (P<0.05) reduced cocaine intake at 17.1 mg/kg D-84 when cocaine was self-administered at 0.5 mg/kg/infusion, and at 30.4 mg/kg D-84 when cocaine was self-administered at 0.1, 0.5 .and 1.0 mg/kg/infusion. During self-administration tests with D-84 (0.1-1 mg/kg/infusion), numbers of infusions significantly exceeded vehicle levels at 0.3 mg/kg/infusion. These results show that D-84 pretreatment can decrease cocaine intake especially when high doses of cocaine are being self-administered. This observation, combined with its incomplete generalization to the cocaine discriminative stimulus and its reported long duration of action, provides a profile consistent with a potential replacement therapy for treating cocaine-abusing patients. PMID:20840845

  15. 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. PMID:26525505

  16. Metformin combined with aspirin significantly inhibit pancreatic cancer cell growth in vitro and in vivo by suppressing anti-apoptotic proteins Mcl-1 and Bcl-2

    PubMed Central

    Yue, Wen; Zheng, Xi; Lin, Yong; Yang, Chung S.; Xu, Qing; Carpizo, Darren; Huang, Huarong; DiPaola, Robert S.; Tan, Xiang-Lin

    2015-01-01

    Metformin and aspirin have been studied extensively as cancer preventive or therapeutic agents. However, the effects of their combination on pancreatic cancer cells have not been investigated. Herein, we evaluated the effects of metformin and aspirin, alone or in combination, on cell viability, migration, and apoptosis as well as the molecular changes in mTOR, STAT3 and apoptotic signaling pathways in PANC-1 and BxPC3 cells. Metformin and aspirin, at relatively low concentrations, demonstrated synergistically inhibitory effects on cell viability. Compared to the untreated control or individual drug, the combination of metformin and aspirin significantly inhibited cell migration and colony formation of both PANC-1 and BxPC-3 cells. Metformin combined with aspirin significantly inhibited the phosphorylation of mTOR and STAT3, and induced apoptosis as measured by caspase-3 and PARP cleavage. Remarkably, metformin combined with aspirin significantly downregulated the anti-apoptotic proteins Mcl-1 and Bcl-2, and upregulated the pro-apoptotic proteins Bim and Puma, as well as interrupted their interactions. The downregulation of Mcl-1 and Bcl-2 was independent of AMPK or STAT3 pathway but partially through mTOR signaling and proteasome degradation. In a PANC-1 xenograft mouse model, we demonstrated that the combination of metformin and aspirin significantly inhibited tumor growth and downregulated the protein expression of Mcl-1 and Bcl-2 in tumors. Taken together, the combination of metformin and aspirin significantly inhibited pancreatic cancer cell growth in vitro and in vivo by regulating the pro- and anti-apoptotic Bcl-2 family members, supporting the continued investigation of this two drug combination as chemopreventive or chemotherapeutic agents for pancreatic cancer. PMID:26056043

  17. 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

  18. Sunitinib significantly suppresses the proliferation, migration, apoptosis resistance, tumor angiogenesis and growth of triple-negative breast cancers but increases breast cancer stem cells.

    PubMed

    Chinchar, Edmund; Makey, Kristina L; Gibson, John; Chen, Fang; Cole, Shelby A; Megason, Gail C; Vijayakumar, Srinivassan; Miele, Lucio; Gu, Jian-Wei

    2014-01-01

    The majority of triple-negative breast cancers (TNBCs) are basal-like breast cancers. However there is no reported study on anti-tumor effects of sunitinib in xenografts of basal-like TNBC (MDA-MB-468) cells. In the present study, MDA-MB-231, MDA-MB-468, MCF-7 cells were cultured using RPMI 1640 media with 10% FBS. Vascular endothelia growth factor (VEGF) protein levels were detected using ELISA (R & D Systams). MDA-MB-468 cells were exposed to sunitinib for 18 hours for measuring proliferation (3H-thymidine incorporation), migration (BD Invasion Chamber), and apoptosis (ApopTag and ApoScreen Anuexin V Kit). The effect of sunitinib on Notch-1 expression was determined by Western blot in cultured MDA-MB-468 cells. 10(6) MDA-MB-468 cells were inoculated into the left fourth mammary gland fat pad in athymic nude-foxn1 mice. When the tumor volume reached 100 mm(3), sunitinib was given by gavage at 80 mg/kg/2 days for 4 weeks. Tumor angiogenesis was determined by CD31 immunohistochemistry. Breast cancer stem cells (CSCs) isolated from the tumors were determined by flow cytometry analysis using CD44(+)/CD24(-) or low. ELISA indicated that VEGF was much more highly expressed in MDA-MB-468 cells than MDA-MB-231 and MCF-7 cells. Sunitinib significantly inhibited the proliferation, invasion, and apoptosis resistance in cultured basal like breast cancer cells. Sunitinib significantly increased the expression of Notch-1 protein in cultured MDA-MB-468 or MDA-MB-231 cells. The xenograft models showed that oral sunitinib significantly reduced the tumor volume of TNBCs in association with the inhibition of tumor angiogeneisis, but increased breast CSCs. These findings support the hypothesis that the possibility should be considered of sunitinib increasing breast CSCs though it inhibits TNBC tumor angiogenesis and growth/progression, and that effects of sunitinib on Notch expression and hypoxia may increase breast cancer stem cells. This work provides the groundwork for an

  19. Sunitinib significantly suppresses the proliferation, migration, apoptosis resistance, tumor angiogenesis and growth of triple-negative breast cancers but increases breast cancer stem cells

    PubMed Central

    2014-01-01

    The majority of triple-negative breast cancers (TNBCs) are basal-like breast cancers. However there is no reported study on anti-tumor effects of sunitinib in xenografts of basal-like TNBC (MDA-MB-468) cells. In the present study, MDA-MB-231, MDA-MB-468, MCF-7 cells were cultured using RPMI 1640 media with 10% FBS. Vascular endothelia growth factor (VEGF) protein levels were detected using ELISA (R & D Systams). MDA-MB-468 cells were exposed to sunitinib for 18 hours for measuring proliferation (3H-thymidine incorporation), migration (BD Invasion Chamber), and apoptosis (ApopTag and ApoScreen Anuexin V Kit). The effect of sunitinib on Notch-1 expression was determined by Western blot in cultured MDA-MB-468 cells. 106 MDA-MB-468 cells were inoculated into the left fourth mammary gland fat pad in athymic nude-foxn1 mice. When the tumor volume reached 100 mm3, sunitinib was given by gavage at 80 mg/kg/2 days for 4 weeks. Tumor angiogenesis was determined by CD31 immunohistochemistry. Breast cancer stem cells (CSCs) isolated from the tumors were determined by flow cytometry analysis using CD44+/CD24- or low. ELISA indicated that VEGF was much more highly expressed in MDA-MB-468 cells than MDA-MB-231 and MCF-7 cells. Sunitinib significantly inhibited the proliferation, invasion, and apoptosis resistance in cultured basal like breast cancer cells. Sunitinib significantly increased the expression of Notch-1 protein in cultured MDA-MB-468 or MDA-MB-231 cells. The xenograft models showed that oral sunitinib significantly reduced the tumor volume of TNBCs in association with the inhibition of tumor angiogeneisis, but increased breast CSCs. These findings support the hypothesis that the possibility should be considered of sunitinib increasing breast CSCs though it inhibits TNBC tumor angiogenesis and growth/progression, and that effects of sunitinib on Notch expression and hypoxia may increase breast cancer stem cells. This work provides the groundwork for an innovative

  20. Chimeric HBcAg virus-like particles presenting a HPV 16 E7 epitope significantly suppressed tumor progression through preventive or therapeutic immunization in a TC-1-grafted mouse model

    PubMed Central

    Chu, Xiaojie; Li, Yang; Long, Qiong; Xia, Ye; Yao, Yufeng; Sun, Wenjia; Huang, Weiwei; Yang, Xu; Liu, Cunbao; Ma, Yanbing

    2016-01-01

    Background Therapeutic human papillomavirus (HPV) vaccines are currently being developed. However, no therapeutic efficacy has been achieved in clinical trials for the treatment of cervical intraepithelial neoplasia or cancer. One of the important issues in increasing vaccine efficacy is determining the best way to enhance tumor antigen-specific cellular immune responses. This study aimed to explore the virus-like particles (VLPs) of hepatitis B core antigen (HBcAg) as potential therapeutic vaccine carriers and to assess its immunological characteristics. Methods Chimeric VLPs presenting a HPV 16 cytotoxic T lymphocytes epitope E749–57 (amino acid 49–57 of the E7 protein) were prepared using recombinant genes. C57BL/6 mice were immunized with VLPs and grafted with tumor cells TC-1 which is an E7-expressing tumorigenic cell line. The dynamic tumor growth was monitored and anti-tumor immune responses were investigated. Results Using a preventive strategy, immunization with VLPs resulted in nearly complete suppression of tumor growth. In treatment studies, VLP immunization significantly suppressed the tumor progression in mice carrying 2–3 mm tumors and in those bearing even larger tumors with diameters up to 8–9 mm. The VLP structure was shown to be important to induce vigorous antitumor immunity and effects. In immunized mice, enhanced E749–57-specific cellular immune responses were evidenced by increased interferon (IFN)-γ expression and decreased interleukin (IL)-4 expression in splenic lymphocytes, as well as an elevated number of effector cells expressing IFN-γ in response to the in vitro stimulation of the specific peptide E749–57. In addition, effective immune memory after VLP immunization was maintained for at least 16 weeks, preventing significant tumor growth after subsequent TC-1 challenge. Conclusion While VLPs were highly immunogenic in stimulating humoral immunity, our results strongly indicated that VLPs, such as HBcAg particles, might

  1. Significant School Law Cases Pending Before the U.S. Supreme Court. What Do They Portend for the Governance and Administration of the Public Schools?

    ERIC Educational Resources Information Center

    Shannon, Thomas A.

    Civil rights is the central theme of the cases affecting public school governance that the U.S. Supreme Court has agreed to hear this term. This paper discusses those cases in detail. It also notes that the cases the court refuses to hear have as significant an impact on school district governance as those cases it actually hears. School law cases…

  2. Oral administration of live exopolysaccharide-producing Pediococcus parvulus, but not purified exopolysaccharide, suppressed Enterobacteriaceae without affecting bacterial diversity in ceca of mice.

    PubMed

    Lindström, Cecilia; Xu, Jie; Oste, Rickard; Holst, Olle; Molin, Göran

    2013-08-01

    Growing evidence indicates that the gut microbiota could have an important role in the development of diet- and lifestyle-induced diseases. It has been shown that modulation of the gut microbiota by means of probiotics and prebiotics could improve host health. An oat-based product fermented by the exopolysaccharide (EPS)-producing organism Pediococcus parvulus 2.6 has been reported to have a bifidogenic effect. To find out whether the effect could be attributed to the EPS or the bacterium, mice were fed a diet supplemented with 2% purified EPS or 10(8) CFU/g of live P. parvulus 2.6 for 6 weeks. Both supplementations altered the gut microbiota composition but in different directions. Purified EPS not only significantly lowered the microbial diversity (P < 0.001) but decreased the bifidobacterial population (P = 0.01). In contrast, the live EPS-producing bacterium P. parvulus 2.6 antagonized Enterobacteriaceae without disturbing the homeostasis of the cecal microbiota. PMID:23770909

  3. Inhibition of titanium-particle-induced inflammatory osteolysis after local administration of dopamine and suppression of osteoclastogenesis via D2-like receptor signaling pathway.

    PubMed

    Yang, Huilin; Xu, Yaozeng; Zhu, Mo; Gu, Ye; Zhang, Wen; Shao, Hongguo; Wang, Yijun; Ping, Zichuan; Hu, Xuanyang; Wang, Liangliang; Geng, Dechun

    2016-02-01

    Chronic inflammation and extensive osteoclast formation play critical roles in wear-debris-induced peri-implant osteolysis. We investigated the potential impact of dopamine on titanium-particle-induced inflammatory osteolysis in vivo and in vitro. Twenty-eight C57BL/6J mice were randomly assigned to four groups: sham control (PBS treatment), titanium (titanium/PBS treatment), low- (titanium/2 μg kg(-1) day(-1) dopamine) and high-dopamine (titanium/10 μg kg(-1) day(-1) dopamine). After 2 weeks, mouse calvariae were collected for micro-computed tomography (micro-CT) and histomorphometry analysis. Bone-marrow-derived macrophages (BMMs) were isolated to assess osteoclast differentiation. Dopamine significantly reduced titanium-particle-induced osteolysis compared with the titanium group as confirmed by micro-CT and histomorphometric data. Osteoclast numbers were 34.9% and 59.7% (both p < 0.01) lower in the low- and high-dopamine-treatment groups, respectively, than in the titanium group. Additionally, low RANKL, tumor necrosis factor-α, interleukin-1β and interleukin-6 immunochemistry staining were noted in dopamine-treatment groups. Dopamine markedly inhibited osteoclast formation, osteoclastogenesis-related gene expression and pro-inflammatory cytokine expression in BMMs in a dose-dependent manner. Moreover, the resorption area was decreased with 10(-9) M and 10(-8) M dopamine to 40.0% and 14.5% (both p < 0.01), respectively. Furthermore, the inhibitory effect of dopamine was reversed by the D2-like-receptor antagonist haloperidol but not by the D1-like-receptor antagonist SCH23390. These results suggest that dopamine therapy could be developed into an effective and safe method for osteolysis-related disease caused by chronic inflammation and excessive osteoclast formation. PMID:26695376

  4. The Dexamethasone Suppression Test as an Indication of Depression in Patients with Mental Retardation.

    ERIC Educational Resources Information Center

    Mattes, Jeffrey A.; Amsell, Loren

    1993-01-01

    Administration of the Dexamethasone Suppression Test (DST) for three groups of institutionalized patients with severe/profound mental retardation found that the 12 depressed patients more frequently (though not significantly) had positive DSTs and significantly higher cortisol levels compared with nondepressed patients with and without other…

  5. Oral administration of transforming growth factor-β1 (TGF-β1) protects the immature gut from injury via Smad protein-dependent suppression of epithelial nuclear factor κB (NF-κB) signaling and proinflammatory cytokine production.

    PubMed

    Shiou, Sheng-Ru; Yu, Yueyue; Guo, Yuee; Westerhoff, Maria; Lu, Lei; Petrof, Elaine O; Sun, Jun; Claud, Erika C

    2013-11-29

    Inflammatory immune responses play an important role in mucosal homeostasis and gut diseases. Nuclear factor κB (NF-κB), central to the proinflammatory cascade, is activated in necrotizing enterocolitis (NEC), a devastating condition of intestinal injury with extensive inflammation in premature infants. TGF-β is a strong immune suppressor and a factor in breast milk, which has been shown to be protective against NEC. In an NEC animal model, oral administration of the isoform TGF-β1 activated the downstream effector Smad2 in intestine and significantly reduced NEC incidence. In addition, TGF-β1 suppressed NF-κB activation, maintained levels of the NF-κB inhibitor IκBα in the intestinal epithelium, and systemically decreased serum levels of IL-6 and IFN-γ. The immature human fetal intestinal epithelial cell line H4 was used as a reductionistic model of the immature enterocyte to investigate mechanism. TGF-β1 pretreatment inhibited the TNF-α-induced IκBα phosphorylation that targets the IκBα protein for degradation and inhibited NF-κB activation. Chromatin immunoprecipitation (ChIP) assays demonstrated decreased NF-κB binding to the promoters of IL-6, IL-8, and IκBα in response to TNF-α with TGF-β1 pretreatment. These TGF-β1 effects appear to be mediated through the canonical Smad pathway as silencing of the TGF-β central mediator Smad4 resulted in loss of the TGF-β1 effects. Thus, TGF-β1 is capable of eliciting anti-inflammatory effects by inhibiting NF-κB specifically in the intestinal epithelium as well as by decreasing systemic IL-6 and IFN-γ levels. Oral administration of TGF-β1 therefore can potentially be used to protect against gastrointestinal diseases. PMID:24129565

  6. Suppression of experimental allergic encephalomyelitis by 15-deoxyspergualin.

    PubMed

    Yamamura, T; Da-Lin, Y; Satoh, J; Tabira, T

    1987-12-01

    15-Deoxyspergualin (DSG), a novel antitumor antibiotic, was tested for treatment of acute experimental allergic encephalomyelitis (EAE) in Lewis rats. Clinical and histologic signs of EAE by active sensitization with myelin basic protein were profoundly inhibited by prophylactic administration of DSG in a dose-dependent manner. By the treatment during the inductive phase, the onset of EAE was significantly delayed. Antigen-specific proliferation of lymph node cells and the ability of spleen cells to transfer EAE were suppressed but concanavalin A-induced lymphocyte proliferation was not altered. Passive EAE induced with an encephalitogenic T cell line was also prevented by DSG-treatment, although DSG did not suppress but rather augmented the activation of T cells in vitro. Taken together, DSG is not a non-specific lymphocyte toxin but a unique immunomodulator that can suppress both inductive and effector phases of EAE. PMID:3502003

  7. Hyaluronic acid reagent suppressed endometriotic lesion formation in a mouse model.

    PubMed

    Hasegawa, Akiko; Yoshino, Osamu; Osuga, Yutaka; Kodama, Ako; Takamura, Masashi; Nishii, Osamu; Taketani, Yuji

    2010-05-15

    In an animal endometriosis model, the administration of hyaluronic acid (HA) reagent significantly suppressed the formation of endometriotic lesions in both number and weight. This effect was found when HA treatment was conducted at the time of endometrial fragment inoculation. PMID:20356589

  8. Significant Treasures.

    ERIC Educational Resources Information Center

    Andrews, Ian A.

    1999-01-01

    Provides a crossword puzzle with an answer key corresponding to the book entitled "Significant Treasures/Tresors Parlants" that is filled with color and black-and-white prints of paintings and artifacts from 131 museums and art galleries as a sampling of the 2,200 such Canadian institutions. (CMK)

  9. Galeterone and VNPT55 induce proteasomal degradation of AR/AR-V7, induce significant apoptosis via cytochrome c release and suppress growth of castration resistant prostate cancer xenografts in vivo

    PubMed Central

    Kwegyir-Afful, Andrew K.; Ramalingam, Senthilmurugan; Purushottamachar, Puranik; Ramamurthy, Vidya P.; Njar, Vincent C.O.

    2015-01-01

    Galeterone (Gal) is a first-in-class multi-target oral small molecule that will soon enter pivotal phase III clinical trials in castration resistant prostate cancer (CRPC) patients. Gal disrupts androgen receptor (AR) signaling via inhibition of CYP17, AR antagonism and AR degradation. Resistance to current therapy is attributed to up-regulation of full-length AR (fAR), splice variants AR (AR-Vs) and AR mutations. The effects of gal and VNPT55 were analyzed on f-AR and AR-Vs (AR-V7/ARv567es) in LNCaP, CWR22Rv1 and DU145 (transfected with AR-Vs) human PC cells in vitro and CRPC tumor xenografts. Galeterone/VNPT55 decreased fAR/AR-V7 mRNA levels and implicates Mdm2/CHIP enhanced ubiquitination of posttranslational modified receptors, targeting them for proteasomal degradation. Gal and VNPT55 also induced significant apoptosis in PC cells via increased Bax/Bcl2 ratio, cytochrome-c release with concomitant cleavage of caspase 3 and PARP. More importantly, gal and VNPT55 exhibited strong in vivo anti-CRPC activities, with no apparent host toxicities. This study demonstrate that gal and VNPT55 utilize cell-based mechanisms to deplete both fAR and AR-Vs. Importantly, the preclinical activity profiles, including profound apoptotic induction and inhibition of CRPC xenografts suggest that these agents offer considerable promise as new therapeutics for patients with CRPC and those resistant to current therapy. PMID:26196320

  10. Equol suppresses inflammatory response and bone erosion due to rheumatoid arthritis in mice.

    PubMed

    Lin, I-Chian; Yamashita, Shuya; Murata, Motoki; Kumazoe, Motofumi; Tachibana, Hirofumi

    2016-06-01

    Rheumatoid arthritis (RA) is a chronic and systemic autoimmune inflammatory disease. Typical pathological findings of RA include persistent synovitis and bone degradation in the peripheral joints. Equol, a metabolite of the major soybean isoflavone daidzein, shows superior bioactivity than other isoflavones. We investigated the effects of equol administration on inflammatory response and bone erosion in mice with collagen-induced arthritis (CIA). The severity of arthritis symptoms was significantly low in the equol-administered CIA mice. In addition, equol administration improved the CIA-induced bone mineral density decline. In the inflamed area of CIA mice, equol administration suppressed the expression of interleukin-6 and its receptor. Furthermore, equol reduced the expression of genes associated with bone formation inhibition, osteoclast and immature osteoblast specificity and cartilage destruction. These results suggest that equol suppresses RA development and RA-induced bone erosion by regulating inflammation and bone metabolism. PMID:27142742

  11. The Significance of National Association for the Education of Young Children Accreditation in Elevating Quality of Early Childhood Education: Administrators', Teachers', and Parents' Beliefs about Accreditation and Its Process

    ERIC Educational Resources Information Center

    Vardanyan, Kristine

    2013-01-01

    The following is a doctoral dissertation that studied administrators', teachers', and parents' perceptions and attitudes related to an early childhood center/preschool accreditation experience. A qualitative case study of one preschool center focused on the influence that the decision to pursue accreditation and implement the National Association…

  12. Growth hormone suppression test

    MedlinePlus

    The growth hormone suppression test determines whether growth hormone production is being suppressed by high blood sugar. ... away. The lab measures the glucose and growth hormone (GH) levels in each sample.

  13. Dexamethasone suppression test

    MedlinePlus

    Dexamethasone suppression test measures whether adrenocorticotrophic hormone ( ACTH ) secretion by the pituitary can be suppressed. ... During this test, you will receive dexamethasone. This is a strong ... your blood is drawn so that the cortisol level in your blood ...

  14. Dexamethasone suppression test

    MedlinePlus

    DST; ACTH suppression test; Cortisol suppression test ... During this test, you will receive dexamethasone. This is a strong man-made (synthetic) glucocorticoid medication. Afterward, your blood is drawn ...

  15. Growth hormone suppression test

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/003376.htm Growth hormone suppression test To use the sharing features on this page, please enable JavaScript. The growth hormone suppression test determines whether growth hormone production is ...

  16. Suppressive effects of ketamine on macrophage functions

    SciTech Connect

    Chang Yi; Chen, T.-L.; Sheu, J.-R.; Chen, R.-M. . E-mail: rmchen@tmu.edu.tw

    2005-04-01

    Ketamine is an intravenous anesthetic agent. Clinically, induction of anesthesia with ketamine can cause immunosuppression. Macrophages play important roles in host defense. In this study, we attempted to evaluate the effects of ketamine on macrophage functions and its possible mechanism using mouse macrophage-like Raw 264.7 cells as the experimental model. Exposure of macrophages to 10 and 100 {mu}M ketamine, which correspond to 0.1 and 1 times the clinically relevant concentration, for 1, 6, and 24 h had no effect on cell viability or lactate dehydrogenase release. When the administered concentration reached 1000 {mu}M, ketamine caused a release of lactate dehydrogenase and cell death. Ketamine, at 10 and 100 {mu}M, did not affect the chemotactic activity of macrophages. Administration of 1000 {mu}M ketamine in macrophages resulted in a decrease in cell migration. Treatment of macrophages with ketamine reduced phagocytic activities. The oxidative ability of macrophages was suppressed by ketamine. Treatment with lipopolysaccharide induced TNF-{alpha}, IL-1{beta}, and IL-6 mRNA in macrophages. Administration of ketamine alone did not influence TNF-{alpha}, IL-1{beta}, or IL-6 mRNA production. Meanwhile, cotreatment with ketamine and lipopolysaccharide significantly inhibited lipopolysaccharide-induced TNF-{alpha}, IL-1{beta}, and IL-6 mRNA levels. Exposure to ketamine led to a decrease in the mitochondrial membrane potential. However, the activity of mitochondrial complex I NADH dehydrogenase was not affected by ketamine. This study shows that a clinically relevant concentration of ketamine (100 {mu}M) can suppress macrophage function of phagocytosis, its oxidative ability, and inflammatory cytokine production possibly via reduction of the mitochondrial membrane potential instead of direct cellular toxicity.

  17. 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…

  18. Repeated administration of phytocannabinoid Δ(9)-THC or synthetic cannabinoids JWH-018 and JWH-073 induces tolerance to hypothermia but not locomotor suppression in mice, and reduces CB1 receptor expression and function in a brain region-specific manner.

    PubMed

    Tai, S; Hyatt, W S; Gu, C; Franks, L N; Vasiljevik, T; Brents, L K; Prather, P L; Fantegrossi, W E

    2015-12-01

    These studies probed the relationship between intrinsic efficacy and tolerance/cross-tolerance between ∆(9)-THC and synthetic cannabinoid drugs of abuse (SCBs) by examining in vivo effects and cellular changes concomitant with their repeated administration in mice. Dose-effect relationships for hypothermic effects were determined in order to confirm that SCBs JWH-018 and JWH-073 are higher efficacy agonists than ∆(9)-THC in mice. Separate groups of mice were treated with saline, sub-maximal hypothermic doses of JWH-018 or JWH-073 (3.0mg/kg or 10.0mg/kg, respectively) or a maximally hypothermic dose of 30.0mg/kg ∆(9)-THC once per day for 5 consecutive days while core temperature and locomotor activity were monitored via biotelemetry. Repeated administration of all drugs resulted in tolerance to hypothermic effects, but not locomotor effects, and this tolerance was still evident 14 days after the last drug administration. Further studies treated mice with 30.0mg/kg ∆(9)-THC once per day for 4 days, then tested with SCBs on day 5. Mice with a ∆(9)-THC history were cross-tolerant to both SCBs, and this cross-tolerance also persisted 14 days after testing. Select brain regions from chronically treated mice were examined for changes in CB1 receptor expression and function. Expression and function of hypothalamic CB1Rs were reduced in mice receiving chronic drugs, but cortical CB1R expression and function were not altered. Collectively, these data demonstrate that repeated ∆(9)-THC, JWH-018 and JWH-073 can induce long-lasting tolerance to some in vivo effects, which is likely mediated by region-specific downregulation and desensitization of CB1Rs. PMID:26361728

  19. Fire suppression and detection equipment

    SciTech Connect

    E.E. Bates

    2006-01-15

    Inspection and testing guidelines go beyond the 'Code of Federal Regulation'. Title 30 of the US Code of Federal Regulations (30 CFR) contains requirements and references to national standards for inspection, testing and maintenance of fire suppression and detection equipment for mine operators. However, federal requirements have not kept pace with national standards and best practices. The article lists National Fire Protection (NFPA) standards that are referenced by the US Mine Safety and Health Administration (MSHA) in 30 CFR. It then discusses other NFPA Standards excluded from 30 CFR and explains the NFPA standard development process. 2 refs., 3 tabs., 5 photos.

  20. The dipeptidyl peptidase-4 inhibitor sitagliptin suppresses mouse colon tumorigenesis in type 2 diabetic mice.

    PubMed

    Yorifuji, Naoki; Inoue, Takuya; Iguchi, Munetaka; Fujiwara, Kaori; Kakimoto, Kazuki; Nouda, Sadaharu; Okada, Toshihiko; Kawakami, Ken; Abe, Yosuke; Takeuchi, Toshihisa; Higuchi, Kazuhide

    2016-02-01

    Patients with type 2 diabetes mellitus are known to have an increased risk of colorectal neoplasia. Dipeptidyl peptidase-4 (DPP-4) inhibitors have been used as a new therapeutic tool for type 2 diabetes. Since the substrates for DPP-4 include intestinotrophic hormones and chemokines such as GLP-2 and stromal cell-derived factor-1 (SDF-1), which are associated with tumor progression, DPP-4 inhibitors may increase the risk of colorectal tumors. However, the influence of DPP-4 inhibitors on colorectal neoplasia in patients with type 2 diabetes remains unknown. In the present study, we show that long-term administration of a DPP-4 inhibitor, sitagliptin (STG), suppressed colon carcinogenesis in leptin-deficient (ob/ob) C57BL/6J mice. Colonic mucosal concentrations of glucagon‑like peptide-1 (GLP-1) and GLP-2 were significantly elevated in the ob/ob mice. However, mucosal GLP concentrations and the plasma level of SDF-1 were not affected by the administration of STG. Real‑time PCR analysis revealed that colonic mucosal IL-6 mRNA expression, which was significantly upregulated in the ob/ob mice, was significantly suppressed by the long-term administration of STG. These results suggest that a DPP-4 inhibitor may suppress colon carcinogenesis in mice with type 2 diabetes in a GLP-independent manner. Since DPP-4 has multiple biological functions, further studies analyzing other factors related to colon carcinogenesis are needed. PMID:26573958

  1. Sulindac suppresses beta-catenin expression in human cancer cells.

    PubMed

    Han, Anjia; Song, Zibo; Tong, Chang; Hu, Dong; Bi, Xiuli; Augenlicht, Leonard H; Yang, Wancai

    2008-03-31

    Sulindac has been reported to be effective in suppressing tumor growth through the induction of p21WAF1/cip1 in human, animal models of colon cancer and colon cancer cells. In this study, we treated human breast cancer cell line MCF-7 and lung cancer cell line A549 as well as colon cancer cell line SW620 with sulindac to observe the effects of sulindac in other tissue sites. In all cell lines, proliferation was significantly inhibited by sulindac after 24 and 72 h of treatment. Apoptosis was induced by sulindac in both lung cancer cells and colon cancer cells but was not induced in breast cancer cells. Western blots showed that p21 protein level were induced by sulindac in lung cancer cells and colon cancer cells, but not in breast cancer cells. However, the suppression of beta-catenin, a key mediator of Wnt signaling pathway, was seen in all three cell lines with sulindac administration. Further studies revealed that transcriptional activities of beta-catenin were significantly inhibited by sulindac and that the inhibition was sulindac dosage-dependent. The transcriptional targets of beta-catenin, c-myc, cyclin D1 and cdk 4 were also dramatically downregulated. In conclusion, our data demonstrated that the efficacy of sulindac in the inhibition of cell proliferation (rather than the induction of apoptosis) might be through the suppression of beta-catenin pathway in human cancer cells. PMID:18291362

  2. Modernizing Administration.

    ERIC Educational Resources Information Center

    Lombardi, Vincent L.; Hildebrand, Verna

    1981-01-01

    Suggests assignment of research duties and rotation of teaching and management roles for college administrators, to increase their effectiveness and diminish the negative effects of declining enrollments. (JD)

  3. Fire Suppression and Response

    NASA Technical Reports Server (NTRS)

    Ruff, Gary A.

    2004-01-01

    This report is concerned with the following topics regarding fire suppression:What is the relative effectiveness of candidate suppressants to extinguish a representative fire in reduced gravity, including high-O2 mole fraction, low -pressure environments? What are the relative advantages and disadvantages of physically acting and chemically-acting agents in spacecraft fire suppression? What are the O2 mole fraction and absolute pressure below which a fire cannot exist? What effect does gas-phase radiation play in the overall fire and post-fire environments? Are the candidate suppressants effective to extinguish fires on practical solid fuels? What is required to suppress non-flaming fires (smoldering and deep seated fires) in reduced gravity? How can idealized space experiment results be applied to a practical fire scenario? What is the optimal agent deployment strategy for space fire suppression?

  4. Administrative Support.

    ERIC Educational Resources Information Center

    Doran, Dorothy; And Others

    This guide is intended to assist business education teachers in administrative support courses. The materials presented are based on the Arizona validated occupational competencies and tasks for the occupations of receptionist, secretary, and administrative assistant. Word processing skills have been infused into each of the three sections. The…

  5. 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…

  6. Burst suppression probability algorithms: state-space methods for tracking EEG burst suppression

    NASA Astrophysics Data System (ADS)

    Chemali, Jessica; Ching, ShiNung; Purdon, Patrick L.; Solt, Ken; Brown, Emery N.

    2013-10-01

    Objective. Burst suppression is an electroencephalogram pattern in which bursts of electrical activity alternate with an isoelectric state. This pattern is commonly seen in states of severely reduced brain activity such as profound general anesthesia, anoxic brain injuries, hypothermia and certain developmental disorders. Devising accurate, reliable ways to quantify burst suppression is an important clinical and research problem. Although thresholding and segmentation algorithms readily identify burst suppression periods, analysis algorithms require long intervals of data to characterize burst suppression at a given time and provide no framework for statistical inference. Approach. We introduce the concept of the burst suppression probability (BSP) to define the brain's instantaneous propensity of being in the suppressed state. To conduct dynamic analyses of burst suppression we propose a state-space model in which the observation process is a binomial model and the state equation is a Gaussian random walk. We estimate the model using an approximate expectation maximization algorithm and illustrate its application in the analysis of rodent burst suppression recordings under general anesthesia and a patient during induction of controlled hypothermia. Main result. The BSP algorithms track burst suppression on a second-to-second time scale, and make possible formal statistical comparisons of burst suppression at different times. Significance. The state-space approach suggests a principled and informative way to analyze burst suppression that can be used to monitor, and eventually to control, the brain states of patients in the operating room and in the intensive care unit.

  7. Suppression of experimental allergic encephalomyelitis in rats by suppressor factor from a permanent T cell line.

    PubMed

    Stĕdra, J; Holán, V; Lodin, Z

    1986-01-01

    An antigen non-specific suppressor factor (SF4) produced by a permanent mouse T cell line inhibits the mitogen- and antigen-induced proliferation of cells in vitro. The suppression of immune response is not restricted by interspecies barrier. Administration of the SF4 factor in vivo had a significant suppressive effect on the induction and manifestation of experimental allergic encephalomyelitis (EAE) in rats. Rats treated with SF4 factor, the first dose being injected on the day of EAE induction, had no clinical manifestations or developed only mild clinical signs of EAE. Administration of the SF4 starting on day 4 after EAE induction, when the immune system had been activated, depressed the course of EAE. The results obtained in this model autoimmune disease indicate that the described suppressor factor is active in vivo and that it may be used to depress the autoaggressive immune reactions. PMID:3488925

  8. Intravenous lidocaine as a suppressant of coughing during tracheal intubation in elderly patients.

    PubMed

    Yukioka, H; Hayashi, M; Terai, T; Fujimori, M

    1993-08-01

    The effects of intravenously administered lidocaine on cough suppression in elderly patients over the age of 60 yr during tracheal intubation under general anesthesia were evaluated in two studies. In the first study, 100 patients received a placebo of either 0.5, 1.0, 1.5, or 2.0 mg/kg lidocaine intravenously 1 min before tracheal intubation. All visible coughs were classified as coughing. The incidence of coughing decreased as the dose of lidocaine increased. A dose of 1.5 mg/kg or more of intravenous lidocaine suppressed the cough reflex significantly (P < 0.01). In the second study, 108 patients received 2 mg/kg lidocaine intravenously or a placebo 1, 3, 5, 7, 10, or 15 min before intubation. The same criteria for determining whether a patient did or did not cough during tracheal intubation were used as in Study 1. The incidence of coughing decreased significantly (P < 0.01) when 2 mg/kg lidocaine was injected intravenously between 1 min and 3 min before attempting intubation. The cough reflex was almost entirely suppressed by plasma concentrations of lidocaine in excess of 4 micrograms/mL. The results suggest that intravenous administration of lidocaine is effective in suppressing the cough reflex during tracheal intubation in elderly patients under general anesthesia, but that relatively high plasma concentrations of lidocaine may be required for suppression of coughing. PMID:8346830

  9. AAVshRNA-Mediated Suppression of PTEN in Adult Rats in Combination with Salmon Fibrin Administration Enables Regenerative Growth of Corticospinal Axons and Enhances Recovery of Voluntary Motor Function after Cervical Spinal Cord Injury

    PubMed Central

    2014-01-01

    Conditional genetic deletion of phosphatase and tensin homolog (PTEN) in the sensorimotor cortex of neonatal mice enables regeneration of corticospinal tract (CST) axons after spinal cord injury (SCI). The present study addresses three questions: (1) whether PTEN knockdown in adult rats by nongenetic techniques enables CST regeneration, (2) whether interventions to enable CST regeneration enhance recovery of voluntary motor function, and (3) whether delivery of salmon fibrin into the injury site further enhances CST regeneration and motor recovery. Adult rats were trained in a staircase-reaching task and then received either intracortical injections of AAVshPTEN to delete PTEN or a control vector expressing shRNA for luciferase (AAVshLuc). Rats then received cervical dorsal hemisection injuries and salmon fibrin was injected into the injury site in half the rats, yielding four groups (AAVshPTEN, AAVshLuc, AAVshPTEN + fibrin, and AAVshLuc + fibrin). Forepaw function was assessed for 10 weeks after injury and CST axons were traced by injecting biotin-conjugated dextran amine into the sensorimotor cortex. Rats that received AAVshPTEN alone did not exhibit improved motor function, whereas rats that received AAVshPTEN and salmon fibrin had significantly higher forelimb-reaching scores. Tract tracing revealed that CST axons extended farther caudally in the group that received AAVshPTEN and salmon fibrin versus other groups. There were no significant differences in lesion size between the groups. Together, these data suggest that the combination of PTEN deletion and salmon fibrin injection into the lesion can significantly improve voluntary motor function after SCI by enabling regenerative growth of CST axons. PMID:25057197

  10. Bone suppression technique for chest radiographs

    NASA Astrophysics Data System (ADS)

    Huo, Zhimin; Xu, Fan; Zhang, Jane; Zhao, Hui; Hobbs, Susan K.; Wandtke, John C.; Sykes, Anne-Marie; Paul, Narinder; Foos, David

    2014-03-01

    High-contrast bone structures are a major noise contributor in chest radiographic images. A signal of interest in a chest radiograph could be either partially or completely obscured or "overshadowed" by the highly contrasted bone structures in its surrounding. Thus, removing the bone structures, especially the posterior rib and clavicle structures, is highly desirable to increase the visibility of soft tissue density. We developed an innovative technology that offers a solution to suppress bone structures, including posterior ribs and clavicles, on conventional and portable chest X-ray images. The bone-suppression image processing technology includes five major steps: 1) lung segmentation, 2) rib and clavicle structure detection, 3) rib and clavicle edge detection, 4) rib and clavicle profile estimation, and 5) suppression based on the estimated profiles. The bone-suppression software outputs an image with both the rib and clavicle structures suppressed. The rib suppression performance was evaluated on 491 images. On average, 83.06% (±6.59%) of the rib structures on a standard chest image were suppressed based on the comparison of computer-identified rib areas against hand-drawn rib areas, which is equivalent to about an average of one rib that is still visible on a rib-suppressed image based on a visual assessment. Reader studies were performed to evaluate reader performance in detecting lung nodules and pneumothoraces with and without a bone-suppression companion view. Results from reader studies indicated that the bone-suppression technology significantly improved radiologists' performance in the detection of CT-confirmed possible nodules and pneumothoraces on chest radiographs. The results also showed that radiologists were more confident in making diagnoses regarding the presence or absence of an abnormality after rib-suppressed companion views were presented

  11. 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.

  12. Daidzin suppresses ethanol consumption by Syrian golden hamsters without blocking acetaldehyde metabolism.

    PubMed Central

    Keung, W M; Lazo, O; Kunze, L; Vallee, B L

    1995-01-01

    Daidzin is a potent, selective, and reversible inhibitor of human mitochondrial aldehyde dehydrogenase (ALDH) that suppresses free-choice ethanol intake by Syrian golden hamsters. Other ALDH inhibitors, such as disulfiram (Antabuse) and calcium citrate carbimide (Temposil), have also been shown to suppress ethanol intake of laboratory animals and are thought to act by inhibiting the metabolism of acetaldehyde produced from ingested ethanol. To determine whether or not daidzin inhibits acetaldehyde metabolism in vivo, plasma acetaldehyde in daidzin-treated hamsters was measured after the administration of a test dose of ethanol. Daidzin treatment (150 mg/kg per day i.p. for 6 days) significantly suppresses (> 70%) hamster ethanol intake but does not affect overall acetaldehyde metabolism. In contrast, after administration of the same ethanol dose, plasma acetaldehyde concentration in disulfiram-treated hamsters reaches 0.9 mM, 70 times higher than that of the control. In vitro, daidzin suppresses hamster liver mitochondria-catalyzed acetaldehyde oxidation very potently with an IC50 value of 0.4 microM, which is substantially lower than the daidzin concentration (70 microM) found in the liver mitochondria of daidzin-treated hamsters. These results indicate that (i) the action of daidzin differs from that proposed for the classic, broad-acting ALDH inhibitors (e.g., disulfiram), and (ii) the daidzin-sensitive mitochondrial ALDH is not the one and only enzyme that is essential for acetaldehyde metabolism in golden hamsters. PMID:7568058

  13. Selenite suppression of cadmium-induced testicular apoptosis.

    PubMed

    Jones, M M; Xu, C; Ladd, P A

    1997-01-15

    The characteristic apoptotic ladder-like patterns of rat testicular DNA on agarose gel electrophoresis which results from treatment with CdCl2 are suppressed by the administration of Na2SeO3. The examination of testicular tissue using an ELISA programmed cell death detection procedure confirmed this selenite suppression of cadmium-induced apoptosis. The administration of the Na2SeO3 at either 0.5, 1, 2 h prior to or 0.5, 1, 2 h after the administration of the CdCl2 appear to be almost equally effective at suppressing the apoptotic response. These results are in accord with previous studies on the Na2SeO3 suppression of cadmium induced necrotic changes in tissues and suggest that Na2SeO3 interferes with both necrosis and apoptosis. PMID:9020518

  14. Cough suppression disorders spectrum.

    PubMed

    Reich, Jerome M

    2014-02-01

    Volitional cough suppression, identified exclusively in females, is an unusual causal mechanism for instances of lobar atalectasis and bronchiectasis. It is a postulated mechanism for the genesis of Lady Windermere Syndrome. PMID:24462261

  15. 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,…

  16. 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…

  17. ADMINISTRATIVE CLIMATE.

    ERIC Educational Resources Information Center

    BRUCE, ROBERT L.; CARTER, G.L., JR.

    IN THE COOPERATIVE EXTENSION SERVICE, STYLES OF LEADERSHIP PROFOUNDLY AFFECT THE QUALITY OF THE SERVICE RENDERED. ACCORDINGLY, MAJOR INFLUENCES ON ADMINISTRATIVE CLIMATE AND EMPLOYEE PRODUCTIVITY ARE EXAMINED IN ESSAYS ON (1) SOURCES OF JOB SATISFACTION AND DISSATISFACTION, (2) MOTIVATIONAL THEORIES BASED ON JOB-RELATED SATISFACTIONS AND NEEDS,…

  18. 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…

  19. Jet Noise Suppression

    NASA Technical Reports Server (NTRS)

    Gliebe, P. R.; Brausch, J. F.; Majjigi, R. K.; Lee, R.

    1991-01-01

    The objectives of this chapter are to review and summarize the jet noise suppression technology, to provide a physical and theoretical model to explain the measured jet noise suppression characteristics of different concepts, and to provide a set of guidelines for evolving jet noise suppression designs. The underlying principle for all jet noise suppression devices is to enhance rapid mixing (i.e., diffusion) of the jet plume by geometric and aerothermodynamic means. In the case of supersonic jets, the shock-cell broadband noise reduction is effectively accomplished by the elimination or mitigation of the shock-cell structure. So far, the diffusion concepts have predominantly concentrated on jet momentum and energy (kinetic and thermal) diffusion, in that order, and have yielded better noise reduction than the simple conical nozzles. A critical technology issue that needs resolution is the effect of flight on the noise suppression potential of mechanical suppressor nozzles. A more thorough investigation of this mechanism is necessary for the successful development and design of an acceptable noise suppression device for future high-speed civil transports.

  20. Rice (Oryza sativa japonica) Albumin Suppresses the Elevation of Blood Glucose and Plasma Insulin Levels after Oral Glucose Loading.

    PubMed

    Ina, Shigenobu; Ninomiya, Kazumi; Mogi, Takashi; Hase, Ayumu; Ando, Toshiki; Matsukaze, Narumi; Ogihara, Jun; Akao, Makoto; Kumagai, Hitoshi; Kumagai, Hitomi

    2016-06-22

    The suppressive effect of rice albumin (RA) of 16 kDa on elevation of blood glucose level after oral loading of starch or glucose and its possible mechanism were examined. RA suppressed the increase in blood glucose levels in both the oral starch tolerance test and the oral glucose tolerance test. The blood glucose concentrations 15 min after the oral administration of starch were 144 ± 6 mg/dL for control group and 127 ± 4 mg/dL for RA 200 mg/kg BW group, while those after the oral administration of glucose were 157 ± 7 mg/dL for control group and 137 ± 4 mg/dL for RA 200 mg/kg BW group. However, in the intraperitoneal glucose tolerance test, no significant differences in blood glucose level were observed between RA and the control groups, indicating that RA suppresses the glucose absorption from the small intestine. However, RA did not inhibit the activity of mammalian α-amylase. RA was hydrolyzed to an indigestible high-molecular-weight peptide (HMP) of 14 kDa and low-molecular-weight peptides by pepsin and pancreatin. Furthermore, RA suppressed the glucose diffusion rate through a semipermeable membrane like dietary fibers in vitro. Therefore, the indigestible HMP may adsorb glucose and suppress its absorption from the small intestine. PMID:27228466

  1. Suppression of the Primordial Gravitational Waves

    NASA Astrophysics Data System (ADS)

    Tumurtushaa, Gansukh; Koh, Seoktae; Lee, Bum-Hoon

    2016-07-01

    We study the primordial gravitational waves induced by space-space condensate inflation model. For modes that cross the comoving horizon during matter dominated era, we calculate the energy spectrum of gravitational waves. The energy spectrum of gravitational waves for our model has significantly suppressed in the low frequency range. The suppression occurs due to the phase transition during the early evolution of the Universe and depends on model parameter.

  2. Effects of suppression and appraisals on thought frequency and distress.

    PubMed

    Corcoran, Kathleen M; Woody, Sheila R

    2009-12-01

    Cognitive theories of obsessions highlight appraisals of personal significance and thought suppression in the development and maintenance of intrusive thoughts. The current study examined the role of personal significance within the context of a thought suppression paradigm. The primary aim was to examine whether suppression would have differential effects for target thoughts appraised as personally meaningful versus relatively unimportant. A blasphemous thought served as the target thought, and highly religious and nonreligious participants were recruited. Participants completed a two-interval thought suppression task; during interval 1 they were randomly assigned to suppress or not suppress the target thought and during interval 2, all participants were given "do not suppress" instructions. Suppression resulted in sustained frequency of thoughts in contrast to the decline in thought frequency observed for non-suppression. Differential effects of suppression were found across the two groups. Moreover, suppression was associated with increased negative mood and anxiety. Results suggest that suppression of personally meaningful thoughts is a counterproductive strategy. PMID:19765684

  3. Suppression of exercise-induced angina by magnesium sulfate in patients with variant angina

    SciTech Connect

    Kugiyama, K.; Yasue, H.; Okumura, K.; Goto, K.; Minoda, K.; Miyagi, H.; Matsuyama, K.; Kojima, A.; Koga, Y.; Takahashi, M.

    1988-11-01

    The effects of intravenous magnesium on exercise-induced angina were examined in 15 patients with variant angina and in 13 patients with stable effort angina and were compared with those of placebo. Symptom-limited bicycle exercise and thallium-201 myocardial scintigraphy were performed after intravenous administration of 0.27 mmol/kg body weight of magnesium sulfate and after placebo on different days. In all patients, serum magnesium levels after administration of magnesium sulfate were about twofold higher than levels after placebo. Exercise-induced angina associated with transient ST segment elevation occurred in 11 patients with variant angina receiving placebo and in only 2 of these patients receiving magnesium (p less than 0.005). On the other hand, exercise-induced angina was not suppressed by magnesium in any patient with stable effort angina. In these patients there was no significant difference in exercise duration after administration of placebo versus after administration of magnesium. The size of the perfusion defect as measured by thallium-201 scintigraphy was significantly less in patients with variant angina receiving magnesium than that in those receiving placebo (p less than 0.001), whereas it was not significantly different in patients with stable effort angina receiving placebo versus magnesium. In conclusion, exercise-induced angina is suppressed by intravenous magnesium in patients with variant angina but not in patients with stable effort angina. This beneficial effect of magnesium in patients with variant angina is most likely due to improvement of regional myocardial blood flow by suppression of coronary artery spasm.

  4. 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…

  5. Acetic acid suppresses the increase in disaccharidase activity that occurs during culture of caco-2 cells.

    PubMed

    Ogawa, N; Satsu, H; Watanabe, H; Fukaya, M; Tsukamoto, Y; Miyamoto, Y; Shimizu, M

    2000-03-01

    To understand how blood glucose level is lowered by oral administration of vinegar, we examined effects of acetic acid on glucose transport and disaccharidase activity in Caco-2 cells. Cells were cultured for 15 d in a medium containing 5 mmol/L of acetic acid. This chronic treatment did not affect cell growth or viability, and furthermore, apoptotic cell death was not observed. Glucose transport, evaluated with a nonmetabolizable substrate, 3-O-methyl glucose, also was not affected. However, the increase of sucrase activity observed in control cells (no acetic acid) was significantly suppressed by acetic acid (P < 0.01). Acetic acid suppressed sucrase activity in concentration- and time-dependent manners. Similar treatments (5 mmol/L and 15 d) with other organic acids such as citric, succinic, L-maric, L-lactic, L-tartaric and itaconic acids, did not suppress the increase in sucrase activity. Acetic acid treatment (5 mmol/L and 15 d) significantly decreased the activities of disaccharidases (sucrase, maltase, trehalase and lactase) and angiotensin-I-converting enzyme, whereas the activities of other hydrolases (alkaline phosphatase, aminopeptidase-N, dipeptidylpeptidase-IV and gamma-glutamyltranspeptidase) were not affected. To understand mechanisms underlying the suppression of disaccharidase activity by acetic acid, Northern and Western analyses of the sucrase-isomaltase complex were performed. Acetic acid did not affect the de novo synthesis of this complex at either the transcriptional or translational levels. The antihyperglycemic effect of acetic acid may be partially due to the suppression of disaccharidase activity. This suppression seems to occur during the post-translational processing. PMID:10702577

  6. Explosion suppression system

    DOEpatents

    Sapko, Michael J.; Cortese, Robert A.

    1992-01-01

    An explosion suppression system and triggering apparatus therefor are provided for quenching gas and dust explosions. An electrically actuated suppression mechanism which dispenses an extinguishing agent into the path ahead of the propagating flame is actuated by a triggering device which is light powered. This triggering device is located upstream of the propagating flame and converts light from the flame to an electrical actuation signal. A pressure arming device electrically connects the triggering device to the suppression device only when the explosion is sensed by a further characteristic thereof beside the flame such as the pioneer pressure wave. The light powered triggering device includes a solar panel which is disposed in the path of the explosion and oriented between horizontally downward and vertical. Testing mechanisms are also preferably provided to test the operation of the solar panel and detonator as well as the pressure arming mechanism.

  7. Noise suppression in surface microseismic data

    USGS Publications Warehouse

    Forghani-Arani, Farnoush; Batzle, Mike; Behura, Jyoti; Willis, Mark; Haines, Seth S.; Davidson, Michael

    2012-01-01

    We introduce a passive noise suppression technique, based on the τ − p transform. In the τ − p domain, one can separate microseismic events from surface noise based on distinct characteristics that are not visible in the time-offset domain. By applying the inverse τ − p transform to the separated microseismic event, we suppress the surface noise in the data. Our technique significantly improves the signal-to-noise ratios of the microseismic events and is superior to existing techniques for passive noise suppression in the sense that it preserves the waveform. We introduce a passive noise suppression technique, based on the τ − p transform. In the τ − p domain, one can separate microseismic events from surface noise based on distinct characteristics that are not visible in the time-offset domain. By applying the inverse τ − p transform to the separated microseismic event, we suppress the surface noise in the data. Our technique significantly improves the signal-to-noise ratios of the microseismic events and is superior to existing techniques for passive noise suppression in the sense that it preserves the waveform.

  8. Minocycline suppresses morphine-induced respiratory depression, suppresses morphine-induced reward, and enhances systemic morphine-induced analgesia

    PubMed Central

    Hutchinson, Mark R.; Northcutt, Alexis L.; Chao, Lindsey W.; Kearney, Jeffrey J.; Zhang, Yingning; Berkelhammer, Debra L.; Loram, Lisa C.; Rozeske, Robert R.; Bland, Sondra T.; Maier, Steven F.; Gleeson, Todd T.; Watkins, Linda R.

    2008-01-01

    Recent data suggest that opioids can activate immune-like cells of the central nervous system (glia). This opioid-induced glial activation is associated with decreased analgesia, owing to the release of proinflammatory mediators. Here we examine in rats whether the putative microglial inhibitor, minocycline, may affect morphine-induced respiratory depression and/or morphine-induced reward (conditioned place preference). Systemic co-administration of minocycline significantly attenuated morphine-induced reductions in tidal volume, minute volume, inspiratory force and expiratory force, but did not affect morphine-induced reductions in respiratory rate. Minocycline attenuation of respiratory depression was also paralleled with significant attenuation by minocycline of morphine-induced reductions in blood oxygen saturation. Minocycline also attenuated morphine conditioned place preference. Minocycline did not simply reduce all actions of morphine, as morphine analgesia was significantly potentiated by minocycline co-administration. Lastly, morphine dose-dependently increased cyclooxygenase-1 gene expression in a rat microglial cell line, an effect that was dose-dependently blocked by minocycline. Together, these data support that morphine can directly activate microglia in a minocycline-suppressible manner and suggest a pivotal role for minocycline-sensitive processes in the mechanisms of morphine-induced respiration depression, reward, and pain modulation. PMID:18706994

  9. Photoimmune suppression and photocarcinogenesis.

    PubMed

    Ullrich, Stephen E

    2002-03-01

    The primary cause of non-melanoma skin cancer, the most prevalent form of human neoplasia, is the ultraviolet (UV) radiation found in sunlight. Exposing mice to UV radiation induces skin cancers that are highly antigenic. Upon transfer of an UV-induced skin cancer to a normal syngeneic mouse, the tumor cells are recognized and rapidly destroyed by the immune system of the recipient. This raises the question of how these cancers avoided immune destruction during their development in the UV-irradiated host. This question was answered when it was discovered that in addition to being carcinogenic, UV radiation was also immunosuppressive. Studies with immune suppressed transplantation recipients, and biopsy proven skin cancer patients have confirmed that UV-induced immune suppression is a risk factor for skin cancer development in humans. It is of great importance, therefore, to understand the mechanisms underlying UV-induced immune suppression. The focus of this manuscript will be to use some examples from the more recent scientific literature to review the mechanisms by which UV radiation suppresses the immune response and allows for the progressive outgrowth of antigenic skin tumors. PMID:11861222

  10. Parasitic suppressing circuit

    NASA Technical Reports Server (NTRS)

    Fowler, J. T.; Raposa, F. L. (Inventor)

    1973-01-01

    A circuit for suppressing parasitic oscillations across an inductor operating in a resonant mode is described. The circuit includes a switch means and resistive means connected serially across the inductor. A unidirectional resistive-capacitive network is also connected across the inductor and to the switch means to automatically render the switch means conducting when inductive current through the inductor ceases to flow.

  11. Effect of Glutathione Administration on Serum Levels of Reactive Oxygen Metabolites in Patients with Paraquat Intoxication: A Pilot Study

    PubMed Central

    Kim, Jung-Hoon; Gil, Hyo-Wook; Yang, Jong-Oh; Lee, Eun-Young

    2010-01-01

    Background/Aims Based on preliminary in vitro data from a previous study, we proposed that 50 mg/kg glutathione (GSH) would be adequate for suppressing reactive oxygen species in patients with acute paraquat (PQ) intoxication. Methods Serum levels of reactive oxygen metabolites (ROM) were measured before and after the administration of 50 mg/kg GSH to each of five patients with acute PQ intoxication. Results In one patient, extremely high pretreatment ROM levels began to decrease prior to GSH administration. However, in the remaining four cases, ROM levels did not change significantly prior to GSH administration. ROM levels decreased significantly after GSH administration in all cases. In two cases, ROM levels decreased below that observed in the general population; one of these patients died after a cardiac arrest at 3 hours after PQ ingestion, while the other represented the sole survivor of PQ intoxication observed in this study. In the survivor, ROM levels decreased during the first 8 hours of GSH treatment, and finally dropped below the mean ROM level observed in the general population. Conclusions Treatment with 50 mg/kg GSH significantly suppressed serum ROM levels in PQ-intoxicated patients. However, this dose was not sufficient to suppress ROM levels when the PQ concentration was extremely high. PMID:20830225

  12. Buprenorphine alters ethanol self-administration in rats: dose-response and time-dependent effects.

    PubMed

    June, H L; Cason, C R; Chen, S H; Lewis, M J

    1998-11-01

    Buprenorphine is a partial opioid agonist derived from thebaine and has high affinity for mu and kappa opioid receptors. The present study investigated dose-response (0.03, 0.15, 0.3, 3 mg/kg) and time-dependent effects of buprenorphine (1.5 or 4 h post-treatment) on EtOH self-administration in outbred Sprague-Dawley rats. Freely feeding and drinking rats were trained to initiate EtOH self-administration for 1 h daily using the ascending concentration procedure, wherein they were provided with increasing concentrations of EtOH at 2, 5, 7, 9 and 11% (v/v), respectively. Water was concurrently available with each concentration. Animals were maintained on a given concentration of EtOH for 5 days. By day 21, animals began their stabilization on the 11% regimen and remained on this concentration throughout the remainder of the study. EtOH and water consumption were recorded daily at both 10- and 60-min intervals. At 1.5 h post-buprenorphine, all test doses greatly suppressed both EtOH and water intake at the 10-min interval. At the 60-min interval, all but the lowest dose (0.03 mg/kg) significantly suppressed EtOH intake, while only the highest dose (3 mg/kg) suppressed water intake. In contrast to the suppressant profile observed at 1.5 h post-buprenorphine, at 4 h post-buprenorphine the lower doses (0.03 and 0.15 mg/kg) significantly increased EtOH intake while the higher doses (0.3 and 3 mg/kg) continued to suppress intake. None of the doses of buprenorphine altered water intake 4 h post-buprenorphine. The results support previous research demonstrating the utility of low doses of buprenorphine in suppressing behavior rewarded by a non-opioid drug. PMID:9862399

  13. Cytokines inhibit sexual behavior in female rats: II. Prostaglandins mediate the suppressive effects of interleukin-1beta.

    PubMed

    Avitsur, R; Weidenfeld, J; Yirmiya, R

    1999-03-01

    The proinflammatory cytokine interleukin-1 (IL-1) induces several behavioral alterations that are characteristic of illness, such as anorexia and reduced locomotor and social activity. We have recently demonstrated that IL-1 inhibits sexual activity, motivation and attractivity in female, but not in male rats following either central or peripheral administration. In the present study we examined the involvement of prostaglandin (PG) synthesis in mediating IL-1-induced suppression of female sexual behavior. Administration of the cyclooxygenase blockers indomethacin or ibuprofen completely prevented IL-1-induced suppression of female sexual behavior, including the reduction in proceptive behavior, the lordosis response to a male's mounts, and the preference for a sexually active partner. In a subsequent study, ex-vivo release of hypothalamic PGE2 and the secretion of corticosterone (CS) were measured in males and estrous females following IL-1 administration. At the same time and dose of IL-1 administration that significantly reduced sexual behavior in female but not male rats, IL-1 produced a significant increase in PGE2 release in female, but not in male rats. In contrast, IL-1 induced a significant elevation of serum CS levels in males but not in females. These findings suggest that PG synthesis is involved in mediating the effects of IL-1 on female sexual behavior. Furthermore, differential secretion of PGs and CS may underlie the gender difference in the effects of IL-1 on sexual behavior. PMID:10371676

  14. Ribose Accelerates Gut Motility and Suppresses Mouse Body Weight Gaining

    PubMed Central

    Liu, Yan; Li, Tong-Ruei R; Xu, Cong; Xu, Tian

    2016-01-01

    The increasing prevalence of obesity is closely related to excessive energy consumption. Clinical intervention of energy intake is an attractive strategy to fight obesity. However, the current FDA-approved weight-loss drugs all have significant side effects. Here we show that ribose upregulates gut motility and suppresses mice body weight gain. Ribokinase, which is encoded by Rbks gene, is the first enzyme for ribose metabolism in vivo. Rbks mutation resulted in ribose accumulation in the small intestine, which accelerated gut movement. Ribose oral treatment in wild type mice also enhanced bowel motility and rendered mice resistance to high fat diets. The suppressed weight gain was resulted from enhanced ingested food excretion. In addition, the effective dose of ribose didn't cause any known side effects (i.e. diarrhea and hypoglycemia). Overall, our results show that ribose can regulate gut motility and energy homeostasis in mice, and suggest that administration of ribose and its analogs could regulate gastrointestinal motility, providing a novel therapeutic approach for gastrointestinal dysfunction and weight control. PMID:27194947

  15. Suppression of ongoing experimental myasthenia by oral treatment with an acetylcholine receptor recombinant fragment

    PubMed Central

    Im, Sin-Hyeog; Barchan, Dora; Fuchs, Sara; Souroujon, Miriam C.

    1999-01-01

    Myasthenia gravis (MG) is an autoimmune disorder in which the nicotinic acetylcholine receptor (AChR) is the major autoantigen. In an attempt to develop an antigen-specific therapy for MG, we administered a nonmyasthenogenic recombinant fragment of AChR orally to rats. This fragment, corresponding to the extracellular domain of the human AChR α-subunit (Hα1-205), protected rats from subsequently induced experimental autoimmune myasthenia gravis (EAMG) and suppressed ongoing EAMG when treatment was initiated during either the acute or chronic phases of disease. Prevention and suppression of EAMG were accompanied by a significant decrease in AChR-specific humoral and cellular responses. The underlying mechanism for the Hα1-205–induced oral tolerance seems to be active suppression, mediated by a shift from a T-helper 1 (Th1) to a Th2/Th3 response. This shift was assessed by changes in the cytokine profile, a deviation of anti-AChR IgG isotypes from IgG2 to IgG1, and a suppressed AChR-specific delayed-type hypersensitivity response. Our results in experimental myasthenia suggest that oral administration of AChR-specific recombinant fragments may be considered for antigen-specific immunotherapy of myasthenia gravis. J. Clin. Invest. 104:1723–1730 (1999). PMID:10606626

  16. Suppression of ongoing experimental myasthenia by oral treatment with an acetylcholine receptor recombinant fragment.

    PubMed

    Im, S H; Barchan, D; Fuchs, S; Souroujon, M C

    1999-12-01

    Myasthenia gravis (MG) is an autoimmune disorder in which the nicotinic acetylcholine receptor (AChR) is the major autoantigen. In an attempt to develop an antigen-specific therapy for MG, we administered a nonmyasthenogenic recombinant fragment of AChR orally to rats. This fragment, corresponding to the extracellular domain of the human AChR alpha-subunit (Halpha1-205), protected rats from subsequently induced experimental autoimmune myasthenia gravis (EAMG) and suppressed ongoing EAMG when treatment was initiated during either the acute or chronic phases of disease. Prevention and suppression of EAMG were accompanied by a significant decrease in AChR-specific humoral and cellular responses. The underlying mechanism for the Halpha1-205-induced oral tolerance seems to be active suppression, mediated by a shift from a T-helper 1 (Th1) to a Th2/Th3 response. This shift was assessed by changes in the cytokine profile, a deviation of anti-AChR IgG isotypes from IgG2 to IgG1, and a suppressed AChR-specific delayed-type hypersensitivity response. Our results in experimental myasthenia suggest that oral administration of AChR-specific recombinant fragments may be considered for antigen-specific immunotherapy of myasthenia gravis. PMID:10606626

  17. BMP4/Thrombospondin-1 loop paracrinically inhibits tumor angiogenesis and suppresses the growth of solid tumors.

    PubMed

    Tsuchida, R; Osawa, T; Wang, F; Nishii, R; Das, B; Tsuchida, S; Muramatsu, M; Takahashi, T; Inoue, T; Wada, Y; Minami, T; Yuasa, Y; Shibuya, M

    2014-07-17

    Bone morphogenetic protein 4 (BMP4) has potential as an anticancer agent. Recent studies have suggested that BMP4 inhibits the survival of cancer stem cells (CSCs) of neural and colon cancers. Here, we showed that BMP4 paracrinically inhibited tumor angiogenesis via the induction of Thrombospondin-1 (TSP1), and consequently suppressed tumor growth in vivo. Although HeLa (human cervical cancer), HCI-H460-LNM35 (highly metastatic human lung cancer) and B16 (murine melanoma) cells did not respond to the BMP4 treatment in vitro, the growth of xeno- and allografts of these cells was suppressed via reductions in tumor angiogenesis after intraperitoneal treatment with BMP4. When we assessed the mRNA expression of major angiogenesis-related factors in grafted tumors, we found that the expression of TSP1 was significantly upregulated by BMP4 administration. We then confirmed that BMP4 was less effective in suppressing the tumor growth of TSP1-knockdown cancer cells. Furthermore, we found that BMP4 reduced vascular endothelial growth factor (VEGF) expression in vivo in a TSP1-dependent manner, which indicates that BMP4 interfered with the stabilization of tumor angiogenesis. In conclusion, the BMP4/TSP1 loop paracrinically suppressed tumor angiogenesis in the tumor microenvironment, which subsequently reduced the growth of tumors. BMP4 may become an antitumor agent and open a new field of antiangiogenic therapy. PMID:24013228

  18. Broad-spectrum therapeutic suppression of metastatic melanoma through nuclear hormone receptor activation.

    PubMed

    Pencheva, Nora; Buss, Colin G; Posada, Jessica; Merghoub, Taha; Tavazoie, Sohail F

    2014-02-27

    Melanoma metastasis is a devastating outcome lacking an effective preventative therapeutic. We provide pharmacologic, molecular, and genetic evidence establishing the liver-X nuclear hormone receptor (LXR) as a therapeutic target in melanoma. Oral administration of multiple LXR agonists suppressed melanoma invasion, angiogenesis, tumor progression, and metastasis. Molecular and genetic experiments revealed these effects to be mediated by LXRβ, which elicits these outcomes through transcriptional induction of tumoral and stromal apolipoprotein-E (ApoE). LXRβ agonism robustly suppressed tumor growth and metastasis across a diverse mutational spectrum of melanoma lines. LXRβ targeting significantly prolonged animal survival, suppressed the progression of established metastases, and inhibited brain metastatic colonization. Importantly, LXRβ activation displayed melanoma-suppressive cooperativity with the frontline regimens dacarbazine, B-Raf inhibition, and the anti-CTLA-4 antibody and robustly inhibited melanomas that had acquired resistance to B-Raf inhibition or dacarbazine. We present a promising therapeutic approach that uniquely acts by transcriptionally activating a metastasis suppressor gene. PMID:24581497

  19. Pressure suppression containment system

    DOEpatents

    Gluntz, Douglas M.; Townsend, Harold E.

    1994-03-15

    A pressure suppression containment system includes a containment vessel surrounding a reactor pressure vessel and defining a drywell therein containing a non-condensable gas. An enclosed wetwell pool is disposed inside the containment vessel, and a gravity driven cooling system (GDCS) pool is disposed above the wetwell pool in the containment vessel. The wetwell pool includes a plenum for receiving the non-condensable gas carried with steam from the drywell following a loss-of coolant-accident (LOCA). The wetwell plenum is vented to a plenum above the GDCS pool following the LOCA for suppressing pressure rise within the containment vessel. A method of operation includes channeling steam released into the drywell following the LOCA into the wetwell pool for cooling along with the non-condensable gas carried therewith. The GDCS pool is then drained by gravity, and the wetwell plenum is vented into the GDCS plenum for channeling the non-condensable gas thereto.

  20. Pressure suppression containment system

    DOEpatents

    Gluntz, D.M.; Townsend, H.E.

    1994-03-15

    A pressure suppression containment system includes a containment vessel surrounding a reactor pressure vessel and defining a drywell therein containing a non-condensable gas. An enclosed wetwell pool is disposed inside the containment vessel, and a gravity driven cooling system (GDCS) pool is disposed above the wetwell pool in the containment vessel. The wetwell pool includes a plenum for receiving the non-condensable gas carried with steam from the drywell following a loss-of-coolant-accident (LOCA). The wetwell plenum is vented to a plenum above the GDCS pool following the LOCA for suppressing pressure rise within the containment vessel. A method of operation includes channeling steam released into the drywell following the LOCA into the wetwell pool for cooling along with the non-condensable gas carried therewith. The GDCS pool is then drained by gravity, and the wetwell plenum is vented into the GDCS plenum for channeling the non-condensable gas thereto. 6 figures.

  1. Efficacy of Mesenchymal Stem Cells in Suppression of Hepatocarcinorigenesis in Rats: Possible Role of Wnt Signaling

    PubMed Central

    2011-01-01

    Background The present study was conducted to evaluate the tumor suppressive effects of bone marrow derived mesenchymal stem cells (MSCs) in an experimental hepatocellular carcinoma (HCC) model in rats and to investigate the possible role of Wnt signaling in hepato-carcinogenesis. Methods Ninety rats were included in the study and were divided equally into: Control group, rats which received MSCs only, rats which received MSCs vehicle only, HCC group induced by diethylnitroseamine (DENA) and CCl4, rats which received MSCs after HCC induction, rats which received MSCs before HCC induction. Histopathological examination and gene expression of Wnt signaling target genes by real time, reverse transcription-polymerase chain reaction (RT-PCR) in rat liver tissue, in addition to serum levels of ALT, AST and alpha fetoprotein were performed in all groups. Results Histopathological examination of liver tissue from animals which received DENA-CCl4 only, revealed the presence of anaplastic carcinoma cells and macro-regenerative nodules type II with foci of large and small cell dysplasia. Administration of MSCs into rats after induction of experimental HCC improved the histopathological picture which showed minimal liver cell damage, reversible changes, areas of cell drop out filled with stem cells. Gene expression in rat liver tissue demonstrated that MSCs downregulated β-catenin, proliferating cell nuclear antigen (PCNA), cyclin D and survivin genes expression in liver tissues after HCC induction. Amelioration of the liver status after administration of MSCs has been inferred by the significant decrease of ALT, AST and Alpha fetoprotein serum levels. Administration of MSCs before HCC induction did not show any tumor suppressive or protective effect. Conclusions Administration of MSCs in chemically induced HCC has tumor suppressive effects as evidenced by down regulation of Wnt signaling target genes concerned with antiapoptosis, mitogenesis, cell proliferation and cell

  2. Menstrual suppression: current perspectives

    PubMed Central

    Hillard, Paula Adams

    2014-01-01

    Menstrual suppression to provide relief of menstrual-related symptoms or to manage medical conditions associated with menstrual morbidity or menstrual exacerbation has been used clinically since the development of steroid hormonal therapies. Options range from the extended or continuous use of combined hormonal oral contraceptives, to the use of combined hormonal patches and rings, progestins given in a variety of formulations from intramuscular injection to oral therapies to intrauterine devices, and other agents such as gonadotropin-releasing hormone (GnRH) antagonists. The agents used for menstrual suppression have variable rates of success in inducing amenorrhea, but typically have increasing rates of amenorrhea over time. Therapy may be limited by side effects, most commonly irregular, unscheduled bleeding. These therapies can benefit women’s quality of life, and by stabilizing the hormonal milieu, potentially improve the course of underlying medical conditions such as diabetes or a seizure disorder. This review addresses situations in which menstrual suppression may be of benefit, and lists options which have been successful in inducing medical amenorrhea. PMID:25018654

  3. Vibrotactile suppression of tinnitus

    NASA Astrophysics Data System (ADS)

    Lenhardt, Martin L.

    2002-05-01

    At the Society's 142nd meeting, the efficacy of high frequency bone conducted stimulation in suppressing tinnitus was presented. The hypothesized mechanism was the reprogramming of frequency tuning of auditory neurons in the central nervous system, secondarily to peripheral hearing loss. This mechanism is unlikely in cases of tinnitus in the presence of normal audiometric sensitivity. There is the possibility that hearing loss above 10 kHz can play a role in tinnitus, an association not thoroughly explored. Somatomotor stimulation influencing the quality of tinnitus has been reported, as have interconnections of the auditory and somatosensory systems. There would appear to be an evolutionary advantage of linking the sensorimotor organization of the external ear and the auditory function of the brainstem in sound localization. Thus, stimulation of the pinna and post auricular area may be a means of suppressing tinnitus. To that end a thin aluminum ceramic bimorph was constructed to fit on the inner surface of the pinna. When driven by low (<100 Hz) and high (>10 kHz) frequencies multiplied by MHz carriers, demodulation in the skin resulted in vibrotactile stimulation. Tactile stimulation was an adjunct to the high frequencies resulting in a multimodal suppressive effect in a small pilot study.

  4. Significant prolongation of segmental pancreatic allograft survival in two species

    SciTech Connect

    Du Toit, D.F.; Heydenrych, J.J.

    1988-06-01

    A study was conducted to assess the suppression of segmental pancreatic allograft rejection by cyclosporine (CSA) alone in baboons and dogs, and subtotal marrow irradiation (TL1) alone and TL 1 in combination with CSA in baboons. Total pancreatectomy in the dog and primate provided a reliable diabetic model, induced an absolute deficiency of insulin and was uniformly lethal if not treated. Continuous administration of CSA in baboons resulted in modest allograft survival. As in baboons, dogs receiving CSA 25 mg/kg/d rendered moderate graft prolongation but a dose of 40 mg/kg/d resulted in significant graft survival (greater than 100 days) in 5 of 8 allograft recipients. Irradiation alone resulted in minimal baboon pancreatic allograft survival of 20 baboons receiving TL1 1,000 rad and CSA, 3 had graft survival greater than of 100 days. Of 15 baboons receiving TL1 800 rad and CSA, 6 had graft survival of greater than 100 days. In conclusion, CSA administration in dogs and TL1 in combination with CSA in baboons resulted in highly significant segmental pancreatic allograft survival.

  5. Peripheral and central mediators of lipopolysaccharide induced suppression of defensive rage behavior in the cat.

    PubMed

    Bhatt, S; Bhatt, R S; Zalcman, S S; Siegel, A

    2009-11-10

    Based upon recent findings in our laboratory that cytokines microinjected into the medial hypothalamus or periaqueductal gray (PAG) powerfully modulate defensive rage behavior in cat, the present study determined the effects of peripherally released cytokines following lipopolysaccharide (LPS) challenge upon defensive rage. The study involved initial identification of the effects of peripheral administration of LPS upon defensive rage by electrical stimulation from PAG and subsequent determination of the peripheral and central mechanisms governing this process. The results revealed significant elevation in response latencies for defensive rage from 60 to 300 min, post LPS injection, with no detectable signs of sickness behavior present at 60 min. In contrast, head turning behavior elicited by stimulation of adjoining midbrain sites was not affected by LPS administration, suggesting a specificity of the effects of LPS upon defensive rage. Direct administration of LPS into the medial hypothalamus had no effect on defensive rage, suggesting that the effects of LPS were mediated by peripheral cytokines rather than by any direct actions upon hypothalamic neurons. Complete blockade of the suppressive effects of LPS by peripheral pretreatment with an Anti-tumor necrosis factor-alpha (TNFalpha) antibody but not with an anti- interleukin-1 (IL-1) antibody demonstrated that the effects of LPS were mediated through TNF-alpha rather than through an IL-1 mechanism. A determination of the central mechanisms governing LPS suppression revealed that pretreatment of the medial hypothalamus with PGE(2) or 5-HT(1A) receptor antagonists each completely blocked the suppressive effects of LPS, while microinjections of a TNF-alpha antibody into the medial hypothalamus were ineffective. Microinjections of -Iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) benzamide monohydrochloride (p-MPPI) into lateral hypothalamus (to test for anatomical specificity) had no effect upon

  6. Suppressed Charmed B Decay

    SciTech Connect

    Snoek, Hella Leonie

    2009-06-02

    This thesis describes the measurement of the branching fractions of the suppressed charmed B0 → D*- a0+ decays and the non-resonant B0 → D*- ηπ+ decays in approximately 230 million Υ(4S) → B$\\bar{B}$ events. The data have been collected with the BABAR detector at the PEP-II B factory at the Stanford Linear Accelerator Center in California. Theoretical predictions of the branching fraction of the B0 → D*- a{sub 0}+ decays show large QCD model dependent uncertainties. Non-factorizing terms, in the naive factorization model, that can be calculated by QCD factorizing models have a large impact on the branching fraction of these decay modes. The predictions of the branching fractions are of the order of 10-6. The measurement of the branching fraction gives more insight into the theoretical models. In general a better understanding of QCD models will be necessary to conduct weak interaction physics at the next level. The presence of CP violation in electroweak interactions allows the differentiation between matter and antimatter in the laws of physics. In the Standard Model, CP violation is incorporated in the CKM matrix that describes the weak interaction between quarks. Relations amongst the CKM matrix elements are used to present the two relevant parameters as the apex of a triangle (Unitarity Triangle) in a complex plane. The over-constraining of the CKM triangle by experimental measurements is an important test of the Standard Model. At this moment no stringent direct measurements of the CKM angle γ, one of the interior angles of the Unitarity Triangle, are available. The measurement of the angle γ can be performed using the decays of neutral B mesons. The B0 → D*- a0+ decay is sensitive to the angle γ and, in comparison to the current decays that are being employed, could significantly

  7. The Library Administrator's Automation Handbook.

    ERIC Educational Resources Information Center

    Boss, Richard W.

    One of the most significant decisions in a library administrator's career is the decision to automate one or more of a library's operations. This book describes the present state of local library automation; the planning, selection, and implementation process; and the library administrator's role in the process. The bulk of the text provides a…

  8. Redox nanoparticle increases the chemotherapeutic efficiency of pioglitazone and suppresses its toxic side effects.

    PubMed

    Thangavel, Sindhu; Yoshitomi, Toru; Sakharkar, Meena Kishore; Nagasaki, Yukio

    2016-08-01

    Pioglitazone is a widely used anti-diabetic drug that induces cytotoxicity in cancer cells; however, its clinical use is questioned due to its associated liver toxicity caused by increased oxidative stress. We therefore employed nitroxide-radical containing nanoparticle, termed redox nanoparticle (RNP(N)) which is an effective scavenger of reactive oxygen species (ROS) as a drug carrier. RNP(N) encapsulation increased pioglitazone solubility, thus increasing cellular uptake of encapsulated pioglitazone which reduced the dose required to induce toxicity in prostate cancer cell lines. Investigation of in vitro molecular mechanism of pioglitazone revealed that both apoptosis and cell cycle arrest were involved in tumor cell death. In addition, intravenously administered pioglitazone-loaded RNP(N) produced significant tumor volume reduction in vivo due to enhanced permeation and retention effect. Most importantly, oxidative damage caused by pioglitazone in the liver was significantly suppressed by pioglitazone-loaded RNP(N) due to the presence of nitroxide radicals. It is interesting to note that oral administration of encapsulated pioglitazone, and co-administration of RNP(N) and pioglitazone, i.e., no encapsulation of pioglitazone in RNP(N) also significantly contributed to suppression of the liver injury. Therefore, use of RNP(N) either as an adjuvant or as a carrier for drugs with severe side effects is a promising chemotherapeutic strategy. PMID:27235996

  9. Next generation fire suppressants

    NASA Technical Reports Server (NTRS)

    Brown, Jerry A.

    1995-01-01

    Spectrex, Inc., located in Cedar Grove, NJ is a manufacturer of fire detection and suppression equipment. Spectrex is one of the original pioneers in high speed fire detection and suppression systems for combat vehicles. Spectrex has installed fire suppressions systems in thousands of combat vehicles and ships throughout the world. Additionally, they manufacture flame explosion detectors, ship damage control systems, and optical gas and vapor detectors. The culmination of several years of research and development has recently produced an innovative electro-optical continuous monitoring systems called SharpEye 20/20I IR(sup 3) and SAFEYE that provide fast and reliable gas, vapor, aerosol, flame, and explosion detection. SharpEye 20/20I IR(sup 3) is a self-contained triple spectrum flame detector which scans for oscillating IR radiation (1 to 10 Hz) in the spectral bands ranging from 4.0 to 5.0 microns and uses programmed algorithms to check the ratio and correlation of data received by the three sensors to make the system highly immune to false alarms. It is extremely sensitive as it can detect a 1 x 1 square foot gasoline pan fire at 200 feet in less than 3 seconds. The sensitivity is user programmable, offering 4 ranges of detection. SAFEYE is comprised of a selected number of multispectral ban microprocessors controlled detectors which are in communication with one or more radiation sources that is projected along a 600 feet optical path. The signals from the selected narrow bands are processed and analyzed by highly sophisticated algorithms. It is ideal for high risk, remote, large areas such as petroleum and chemical manufacturing sites, waste dumps, aircraft cargo bays, and ship compartments. The SAFEYE will perform direct readings of the presence or rate of rise of concentrations of gases, vapors, or aerosols at the range of parts per million and provide alarms at various set points at different levels of concentrations.

  10. Next generation fire suppressants

    SciTech Connect

    Brown, J.A.

    1995-03-01

    Spectrex, Inc., located in Cedar Grove, NJ is a manufacturer of fire detection and suppression equipment. Spectrex is one of the original pioneers in high speed fire detection and suppression systems for combat vehicles. Spectrex has installed fire suppressions systems in thousands of combat vehicles and ships throughout the world. Additionally, they manufacture flame explosion detectors, ship damage control systems, and optical gas and vapor detectors. The culmination of several years of research and development has recently produced an innovative electro-optical continuous monitoring systems called SharpEye 20/20I IR(sup 3) and SAFEYE that provide fast and reliable gas, vapor, aerosol, flame, and explosion detection. SharpEye 20/20I IR(sup 3) is a self-contained triple spectrum flame detector which scans for oscillating IR radiation (1 to 10 Hz) in the spectral bands ranging from 4.0 to 5.0 microns and uses programmed algorithms to check the ratio and correlation of data received by the three sensors to make the system highly immune to false alarms. It is extremely sensitive as it can detect a 1 x 1 square foot gasoline pan fire at 200 feet in less than 3 seconds. The sensitivity is user programmable, offering 4 ranges of detection. SAFEYE is comprised of a selected number of multispectral band microprocessor controlled detectors which are in communication with one or more radiation sources that is projected along a 600 feet optical path. The signals from the selected narrow bands are processed and analyzed by highly sophisticated algorithms. It is ideal for high risk, remote, large areas such as petroleum and chemical manufacturing sites, waste dumps, aircraft cargo bays, and ship compartments. The SAFEYE will perform direct readings of the presence or rate of rise of concentrations of gases, vapors, or aerosols at the range of parts per million and provide alarms at various set points at different levels of concentrations.

  11. Suppression of flutter

    NASA Technical Reports Server (NTRS)

    Nissim, E. (Inventor)

    1973-01-01

    An active aerodynamic control system to control flutter over a large range of oscillatory frequencies is described. The system is not affected by mass, stiffness, elastic axis, or center of gravity location of the system, mode of vibration, or Mach number. The system consists of one or more pairs of leading edge and trailing edge hinged or deformable control surfaces, each pair operated in concert by a stability augmentation system. Torsion and bending motions are sensed and converted by the stability augmentation system into leading and trailing edge control surface deflections which produce lift forces and pitching moments to suppress flutter.

  12. Wing rock suppression using forebody vortex control

    NASA Technical Reports Server (NTRS)

    Ng, T. T.; Ong, L. Y.; Suarez, C. J.; Malcolm, G. N.

    1991-01-01

    Static and free-to-roll tests were conducted in a water tunnel with a configuration that consisted of a highly-slender forebody and 78-deg sweep delta wings. Flow visualization was performed and the roll angle histories were obtained. The fluid mechanisms governing the wing rock of this configuration were identified. Different means of suppressing wing rock by controlling the forebody vortices using small blowing jets were also explored. Steady blowing was found to be capable of suppressing wing rock, but significant vortex asymmetries had to be induced at the same time. On the other hand, alternating pulsed blowing on the left and right sides of the forebody was demonstrated to be potentially an effective means of suppressing wing rock and eliminating large asymmetric moments at high angles of attack.

  13. Planck-suppressed operators

    SciTech Connect

    Assassi, Valentin; Baumann, Daniel; Green, Daniel; McAllister, Liam E-mail: dbaumann@damtp.cam.ac.uk E-mail: mcallister@cornell.edu

    2014-01-01

    We show that the recent Planck limits on primordial non-Gaussianity impose strong constraints on light hidden sector fields coupled to the inflaton via operators suppressed by a high mass scale Λ. We study a simple effective field theory in which a hidden sector field is coupled to a shift-symmetric inflaton via arbitrary operators up to dimension five. Self-interactions in the hidden sector lead to non-Gaussianity in the curvature perturbations. To be consistent with the Planck limit on local non-Gaussianity, the coupling to any hidden sector with light fields and natural cubic couplings must be suppressed by a very high scale Λ > 10{sup 5}H. Even if the hidden sector has Gaussian correlations, nonlinearities in the mixing with the inflaton still lead to non-Gaussian curvature perturbations. In this case, the non-Gaussianity is of the equilateral or orthogonal type, and the Planck data requires Λ > 10{sup 2}H.

  14. Active manipulation of native soil microbial community structure and function to suppress soilborne diseases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The reality of naturally occurring biologically-induced disease suppressive soils suggests opportunity for managing resident soil microbial communities as a disease control method. Disease suppressive soils have yielded a significant body of knowledge concerning operative mechanisms leading to t...

  15. Suppression of bovine lymphocyte function by treatment with physiologic concentrations of cortisone

    SciTech Connect

    Ojo-Amaize, E.A.; Paape, M.J.; Guidry, A.J.; Mayer, H.K.

    1986-03-01

    The blastogenic response of peripheral blood lymphocytes (PBL) (8 cows) to capsular antigen extract of Staphylococcus aureus, PHA and LPS was measured in vitro using /sup 5/H-thymidine pulse labelling. isolated PBL were treated in vitro for 6-8 days with 10, 25 and 45 ng/ml cortisone. These concentrations simulate serum corticosteroid levels during environmental stress, acute clinical mastitis and ACTH therapy, respectively. To determine the minimal concentration of cortisone that would induce suppression, PBL were also incubated with increasing concentrations of cortisone starting at 10 pg/ml. All concentrations of cortisone caused a significant (P<0.01) depression of lymphocyte blastogenic response to S. aureus, PHA and LPS. Macrophage depletion experiments showed no macrophage suppressor effects. Both the blastogenic response of untreated peripheral blood lymphocytes to S. aureus, PHA and LPS and the degree to which that response was suppressed by cortisone differed significantly among cows. Results indicate that cortisone levels found during physiological stress and after therapeutic administration of ACTH can suppress lymphocyte function.

  16. CCN1 suppresses pulmonary vascular smooth muscle contraction in response to hypoxia

    PubMed Central

    Lee, Seon-jin; Zhang, Meng; Hu, Kebin; Lin, Ling; Zhang, Duo

    2015-01-01

    Abstract Pulmonary vasoconstriction and increased vascular resistance are common features in pulmonary hypertension (PH). One of the contributing factors in the development of pulmonary vasoconstriction is increased pulmonary artery smooth muscle cell (PASMC) contraction. Here we report that CCN1, an extracellular matrix molecule, suppressed PASMC contraction in response to hypoxia. CCN1 (Cyr61), discovered in past decade, belongs to the Cyr61-CTGF-Nov (CCN) family. It carries a variety of cellular functions, including angiogenesis and cell adhesion, death, and proliferation. Hypoxia robustly upregulated the expression of CCN1 in the pulmonary vessels and lung parenchyma. Given that CCN1 is a secreted protein and functions in a paracine manner, we examined the potential effects of CCN1 on the adjacent smooth muscle cells. Interestingly, bioactive recombinant CCN1 significantly suppressed hypoxia-induced contraction in human PASMCs in vitro. Consistently, in the in vivo functional studies, administration of bioactive CCN1 protein significantly decreased right ventricular pressure in three different PH animal models. Mechanistically, protein kinase A–pathway inhibitors abolished the effects of CCN1 in suppressing PASMC contraction. Furthermore, CCN1-inhibited smooth muscle contraction was independent of the known vasodilators, such as nitric oxide. Taken together, our studies indicated a novel cellular function of CCN1, potentially regulating the pathogenesis of PH. PMID:26697179

  17. Clostridium difficile suppresses colonic vasoactive intestinal peptide associated with altered motility.

    PubMed

    Nassif, A; Longo, W E; Sexe, R; Stratton, M; Standeven, J; Vernava, A M; Kaminski, D L

    1995-01-01

    We investigated whether Clostridium difficile toxin alters colonic tissue levels of vasoactive intestinal peptide (VIP) at the expense of changes in colonic motility in the isolated perfused rabbit left colon. Colonic inflammation was induced by the intracolonic administration of 10(-8) M C. difflcile toxin. Strain gauge transducers were sewn onto the serosal surface of the colon to evaluate colonic motility. C. difflcile administration produced histologic changes consistent with epithelial damage. This was associated with an increased production of prostaglandin E(2) and thromboxane B(2). Tissue levels of VIP but not substance P were significantly reduced. This was associated with an increased number of contractions per minute and an average force of each colonic contraction. These results suggest that tissue levels of VIP are suppressed by C. difflcile and may participate in colonic dysmotility during active inflammation. PMID:18475679

  18. OX40 agonist therapy enhances CD8 infiltration and decreases immune suppression in the tumor.

    PubMed

    Gough, Michael J; Ruby, Carl E; Redmond, William L; Dhungel, Birat; Brown, Alexis; Weinberg, Andrew D

    2008-07-01

    Acquisition of full T-cell effector function and memory differentiation requires appropriate costimulatory signals, including ligation of the costimulatory molecule OX40 (TNFRSF4, CD134). Tumors often grow despite the presence of tumor-specific T cells and establish an environment with weak costimulation and immune suppression. Administration of OX40 agonists has been shown to significantly increase the survival of tumor-bearing mice and was dependent on the presence of both CD4 and CD8 T cells during tumor-specific priming. To understand how OX40 agonists work in mice with established tumors, we developed a model to study changes in immune cell populations within the tumor environment. We show here that systemic administration of OX40 agonist antibodies increased the proportion of CD8 T cells at the tumor site in three different tumor models. The function of the CD8 T cells at the tumor site was also increased by administration of OX40 agonist antibody, and we observed an increase in the proportion of antigen-specific CD8 T cells within the tumor. Despite decreases in the proportion of T regulatory cells at the tumor site, T regulatory cell function in the spleen was unaffected by OX40 agonist antibody therapy. Interestingly, administration of OX40 agonist antibody caused significant changes in the tumor stroma, including decreased macrophages, myeloid-derived suppressor cells, and decreased expression of transforming growth factor-beta. Thus, therapies targeting OX40 dramatically changed the tumor environment by enhancing the infiltration and function of CD8 T cells combined with diminished suppressive influences within the tumor. PMID:18593921

  19. Delta modulation. [overshoot suppression algorithm for video data transmission

    NASA Technical Reports Server (NTRS)

    Schilling, D. L.

    1973-01-01

    The overshoot suppression algorithm has been more extensively studied. Computer generated test-pictures show a radical improvement due to the overshoot suppression algorithm. Considering the delta modulator link as a nonlinear digital filter, a formula that relates the minimum rise time that can be handled for given filter parameters and voltage swings has been developed. The settling time has been calculated for the case of overshoot suppression as well as when no suppression is employed. The results indicate a significant decrease in settling time when overshoot suppression is used. An algorithm for correcting channel errors has been developed. It is shown that pulse stuffing PCM words in the DM bit stream results in a significant reduction in error length.

  20. Platelet interaction with lymphatics aggravates intestinal inflammation by suppressing lymphangiogenesis.

    PubMed

    Sato, Hirokazu; Higashiyama, Masaaki; Hozumi, Hideaki; Sato, Shingo; Furuhashi, Hirotaka; Takajo, Takeshi; Maruta, Koji; Yasutake, Yuichi; Narimatsu, Kazuyuki; Yoshikawa, Kenichi; Kurihara, Chie; Okada, Yoshikiyo; Watanabe, Chikako; Komoto, Shunsuke; Tomita, Kengo; Nagao, Shigeaki; Miura, Soichiro; Hokari, Ryota

    2016-08-01

    Lymphatic failure is a histopathological feature of inflammatory bowel disease (IBD). Recent studies show that interaction between platelets and podoplanin on lymphatic endothelial cells (LECs) suppresses lymphangiogenesis. We aimed to investigate the role of platelets in the inflammatory process of colitis, which is likely to be through modulation of lymphangiogenesis. Lymphangiogenesis in colonic mucosal specimens from patients with IBD was investigated by studying mRNA expression of lymphangiogenic factors and histologically by examining lymphatic vessel (LV) densities. Involvement of lymphangiogenesis in intestinal inflammation was studied by administering VEGF-receptor 3 (VEGF-R3) inhibitors to the mouse model of colitis using dextran sulfate sodium and evaluating platelet migration to LVs. The inhibitory effect of platelets on lymphangiogenesis was investigated in vivo by administering antiplatelet antibody to the colitis mouse model and in vitro by coculturing platelets with lymphatic endothelial cells. Although mRNA expressions of lymphangiogenic factors such as VEGF-R3 and podoplanin were significantly increased in the inflamed mucosa of patients with IBD compared with those with quiescent mucosa, there was no difference in LV density between them. In the colitis model, VEGF-R3 inhibition resulted in aggravated colitis, decreased lymphatic density, and increased platelet migration to LVs. Administration of an antiplatelet antibody increased LV densities and significantly ameliorated colitis. Coculture with platelets inhibited proliferation of LECs in vitro. Our data suggest that despite elevated lymphangiogenic factors during colonic inflammation, platelet migration to LVs resulted in suppressed lymphangiogenesis, leading to aggravation of colitis by blocking the clearance of inflammatory cells. Modulating the interaction between platelets and LVs could be a new therapeutic means for treating IBD. PMID:27313177

  1. Antitumor activity of 2-hydroxycinnamaldehyde for human colon cancer cells through suppression of β-catenin signaling.

    PubMed

    Lee, Min Ai; Park, Hyen Joo; Chung, Hwa-Jin; Kim, Won Kyung; Lee, Sang Kook

    2013-07-26

    The antiproliferative and antitumor activities of 2-hydroxycinnamaldehyde (1), a phenylpropanoid isolated from the bark of Cinnamomum cassia, were investigated using human colorectal cancer cells. Compound 1 exhibited antiproliferative effects in HCT116 colon cancer cells, accompanied by modulation of the Wnt/β-catenin cell signaling pathway. This substance was found also to inhibit β-catenin/T-cell factor (TCF) transcriptional activity in HEK293 cells and HCT116 colon cancer cells. Further mechanistic investigations in human colon cancer cells with aberrantly activated Wnt/β-catenin signaling showed that 1 significantly suppressed the binding of β-catenin/TCF complexes to their specific genomic targets in the nucleus and led to the down-regulation of Wnt target genes such as c-myc and cyclin D1. In an in vivo xenograft model, the intraperitoneal administration of 1 (10 or 20 mg/kg body weight, three times/week) for four weeks suppressed tumor growth in athymic nude mice implanted with HCT116 colon cancer cells significantly, without any apparent toxicity. In an ex vivo biochemical analysis of the tumors, compound 1 was also found to suppress Wnt target genes associated with tumor growth including β-catenin, c-myc, cyclin D1, and survivin. The suppression of the Wnt/β-catenin signaling pathway is a plausible mechanism of action underlying the antiproliferative and antitumor activity of 1 in human colorectal cancer cells. PMID:23855266

  2. Factors influencing dust suppressant effectiveness

    SciTech Connect

    Copeland, C.R.; Eisele, T.C.; Chesney, D.J.; Kawatra, S.K.

    2008-11-15

    Water sprays are a common method used to reduce particulate matter (PM) emissions. Various factors such as wettability, surface area coverage, fine particle engulfment rates, interparticle adhesion forces, suppressant penetration and suppressant longevity have all been suggested as critical factors in achieving effective PM control. However, it has not been established which of these factors are the most important. Experimental work indicated that suppressant penetration is the most critical of these factors. The length of time after application that suppressants were effective was also improved by using hygroscopic reagents that retained moisture to prevent evaporation. Maximizing suppressant penetration and improving suppressant longevity led to an average 86% reduction in PM10 concentrations in laboratory dust tower tests.

  3. ZERO SUPPRESSION FOR RECORDERS

    DOEpatents

    Fort, W.G.S.

    1958-12-30

    A zero-suppression circuit for self-balancing recorder instruments is presented. The essential elements of the circuit include a converter-amplifier having two inputs, one for a reference voltage and the other for the signal voltage under analysis, and a servomotor with two control windings, one coupled to the a-c output of the converter-amplifier and the other receiving a reference input. Each input circuit to the converter-amplifier has a variable potentiometer and the sliders of the potentiometer are ganged together for movement by the servoinotor. The particular noveity of the circuit resides in the selection of resistance values for the potentiometer and a resistor in series with the potentiometer of the signal circuit to ensure the full value of signal voltage variation is impressed on a recorder mechanism driven by servomotor.

  4. Pressure suppression system

    DOEpatents

    Gluntz, D.M.

    1994-10-04

    A pressure suppression system includes a containment vessel surrounding a reactor pressure vessel and defining a drywell therein containing a non-condensable gas. An enclosed wetwell pool is disposed inside the containment vessel, and an enclosed gravity driven cooling system (GDCS) pool is disposed above the wetwell pool in the containment vessel. The GDCS pool includes a plenum for receiving through an inlet the non-condensable gas carried with steam from the drywell following a loss-of-coolant accident (LOCA). A condenser is disposed in the GDCS plenum for condensing the steam channeled therein and to trap the non-condensable gas therein. A method of operation includes draining the GDCS pool following the LOCA and channeling steam released into the drywell following the LOCA into the GDCS plenum for cooling along with the non-condensable gas carried therewith for trapping the gas therein. 3 figs.

  5. Interference suppression of SRS

    SciTech Connect

    Kochanov, V P

    2011-01-24

    The theory of three-wave SRS is developed, which takes into account nonlinear dispersion of a medium for arbitrary phases of the pump waves at the input to the medium. The effect of interference suppression of SRS is predicted for values of the total phase of the three-wave pump (2n+1){pi} (n=0, {+-}1, {+-}2...), the effect being caused by the destructive interference of polarisations of the nonresonant dipole-allowed transitions. The relation between the contributions of the linear and nonlinear dispersions to the SRS is found. It is shown that at a sufficiently large wave detuning, the anti-Stokes wave amplitude experiences spatial oscillations. (nonlinear-optics phenomena)

  6. Pressure suppression system

    DOEpatents

    Gluntz, Douglas M.

    1994-01-01

    A pressure suppression system includes a containment vessel surrounding a reactor pressure vessel and defining a drywell therein containing a non-condensable gas. An enclosed wetwell pool is disposed inside the containment vessel, and an enclosed gravity driven cooling system (GDCS) pool is disposed above the wetwell pool in the containment vessel. The GDCS pool includes a plenum for receiving through an inlet the non-condensable gas carried with steam from the drywell following a loss-of-coolant accident (LOCA). A condenser is disposed in the GDCS plenum for condensing the steam channeled therein and to trap the non-condensable gas therein. A method of operation includes draining the GDCS pool following the LOCA and channeling steam released into the drywell following the LOCA into the GDCS plenum for cooling along with the non-condensable gas carried therewith for trapping the gas therein.

  7. 30 CFR 75.1107-15 - Fire suppression devices; hazards; training of miners.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Fire suppression devices; hazards; training of miners. 75.1107-15 Section 75.1107-15 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Fire Protection Fire Suppression Devices...

  8. 30 CFR 75.1107-15 - Fire suppression devices; hazards; training of miners.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Fire suppression devices; hazards; training of miners. 75.1107-15 Section 75.1107-15 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Fire Protection Fire Suppression Devices...

  9. 30 CFR 75.1107-15 - Fire suppression devices; hazards; training of miners.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Fire suppression devices; hazards; training of miners. 75.1107-15 Section 75.1107-15 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Fire Protection Fire Suppression Devices...

  10. 30 CFR 75.1103-10 - Fire suppression systems; additional requirements.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Fire suppression systems; additional requirements. 75.1103-10 Section 75.1103-10 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT... Protection § 75.1103-10 Fire suppression systems; additional requirements. For each conveyor belt...

  11. 30 CFR 75.1103-10 - Fire suppression systems; additional requirements.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Fire suppression systems; additional requirements. 75.1103-10 Section 75.1103-10 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT... Protection § 75.1103-10 Fire suppression systems; additional requirements. For each conveyor belt...

  12. 30 CFR 75.1107-13 - Approval of other fire suppression devices.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Approval of other fire suppression devices. 75.1107-13 Section 75.1107-13 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Fire Protection Fire Suppression Devices and...

  13. 30 CFR 75.1107-8 - Fire suppression devices; extinguishant supply systems.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Fire suppression devices; extinguishant supply systems. 75.1107-8 Section 75.1107-8 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Fire Protection Fire Suppression Devices...

  14. 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)

  15. Oral administration of inosine produces antidepressant-like effects in mice

    PubMed Central

    Muto, Junko; Lee, Hosung; Lee, Hyunjin; Uwaya, Akemi; Park, Jonghyuk; Nakajima, Sanae; Nagata, Kazufumi; Ohno, Makoto; Ohsawa, Ikuroh; Mikami, Toshio

    2014-01-01

    Inosine, a breakdown product of adenosine, has recently been shown to exert immunomodulatory and neuroprotective effects. We show here that the oral administration of inosine has antidepressant-like effects in two animal models. Inosine significantly enhanced neurite outgrowth and viability of primary cultured neocortical neurons, which was suppressed by adenosine A1 and A2A receptor agonists. Oral administration of inosine to mice transiently increased its concentration in the brain and enhanced neuronal proliferation in the dentate gyrus, accompanied by phosphorylation of mitogen-activated protein kinase and increase in transcript level of brain-derived neurotrophic factor. In stress models, oral inosine prevented an increase in immobility time in forced swim test after chronically unexpected stress and mitigated a reduction in sucrose preference after chronic social defeat stress. These results indicate that oral administration of inosine has the potential to prevent depressive disorder via adenosine receptors. PMID:24569499

  16. An experimental evaluation of tic suppression and the tic rebound effect.

    PubMed

    Himle, Michael B; Woods, Douglas W

    2005-11-01

    Tourette's syndrome (TS) is a neurobiological disorder consisting of motor and vocal tics that are thought to be temporarily suppressible. Many professionals, however, believe that a paradoxical increase in tic frequency (above baseline levels) occurs when efforts to suppress have ceased (i.e., a rebound effect). To date, little research has investigated tic suppression or its effects. This study examined tic frequency during baseline, suppression, and post-suppression conditions using an experimental preparation reported to reliably produce tic suppression in children. Six children with TS and one with chronic tic disorder (CTD) were recorded during baseline and repeated suppression and post-suppression conditions. Tic frequency was significantly lower during suppression as compared to baseline. Although tic frequency during post-suppression was higher than during suppression, it was lower than baseline levels, arguing against a "rebound" effect of tic suppression. Exploratory analyses revealed that scores on the attention problems subscale of the Child Behavior Checklist significantly predicted tic suppressibility. The relationships between age, tic severity, and tic suppressibility were also explored. PMID:16159587

  17. Novice Administrators: Personality and Administrative Style Changes.

    ERIC Educational Resources Information Center

    Schmidt, Linda J.; Kosmoski, Georgia J.; Pollack, Dennis R.

    Since the advent of effective-schools research findings, educational administration experts have advocated a democratic and collegial leadership style for school administrators. This paper provides the findings of a study that examined 43 beginning administrators (25 females, 32 Caucasians, 9 African-Americans, 2 Hispanics) to determine what…

  18. COMPLETE RESPONSE OF CTNNB1-MUTATED TUMORS TO β-CATENIN SUPPRESSION BY LOCKED NUCLEIC ANTISENSE IN MOUSE HEPATOCARCINOGENESIS MODEL

    PubMed Central

    Delgado, Evan; Okabe, Hirohisa; Preziosi, Morgan; Russell, Jacquelyn Olivia; Alvarado, Tamara Feliciano; Oertel, Michael; Nejak-Bowen, Kari Nichole; Zhang, Yixian; Monga, Satdarshan P

    2014-01-01

    Background and Aims Hepatocellular cancer (HCC) remains a disease of poor prognosis highlighting the relevance of elucidating key molecular aberrations that may be targeted for novel therapies. Wnt signaling activation chiefly due to mutations in CTNNB1 have been identified in a major subset of HCC patients. While several in vitro proof-of-concept studies show the relevance of suppressing Wnt/β-catenin signaling in HCC cells or tumor xenograft models, no study has addressed the impact of β-catenin inhibition in a relevant murine HCC model driven by CTNNB1 mutations. Methods We studied the in vivo impact of β-catenin suppression by locked nucleic acid (LNA) antisense treatment after establishing CTNNB1 mutations-driven HCC by Diethylnitrosamine and Phenobarbital (DEN/PB) administration. Results The efficacy of LNA-directed against β-catenin versus scrambled sequence on Wnt signaling was demonstrated in vitro in HCC cells and in vivo in normal mice. DEN/PB model led to HCC with CTNNB1 mutations. A complete therapeutic response in the form of abrogation of HCC was observed after ten treatments of tumor-bearing mice with β-catenin LNA every 48 hours as compared to the scrambled control. A decrease in β-catenin activity, cell proliferation and increased cell death was evident after β-catenin suppression. No effect of β-catenin suppression was evident in non-CTNNB1 mutated HCC observed after DEN only administration. Conclusions Thus, we provide in vivo proof-of-concept that β-catenin suppression in HCC will be of significant therapeutic benefit provided the tumors display Wnt activation via mechanisms like CTNNB1 mutations. PMID:25457204

  19. An Alternative to Thought Suppression?

    ERIC Educational Resources Information Center

    Boice, Robert

    2012-01-01

    Comments on the original article, "Setting free the bears: Escape from thought suppression," by D. M. Wegner (see record 2011-25622-008). While Wegner supposed that we might have to learn to live with bad thoughts, the present author discusses the use of imagination and guided imagery as an alternative to forced thought suppression.

  20. STRV Cryocooler Tip Motion Suppression

    NASA Technical Reports Server (NTRS)

    Glaser, R.; Ross, R. G., Jr.; Johnson, D. L.

    1994-01-01

    The Space Technology Research Vehicle (STRV-1b) scheduled to fly at the beginning of June 1994, has a cryocooler vibration suppression experiment aboard doing motion suppression of the tip of the coldfinger. STRV-1b is a bread box sized satellite to be launched on the next flight of the Ariane-4.

  1. HIV-1 Reservoirs During Suppressive Therapy.

    PubMed

    Barton, Kirston; Winckelmann, Anni; Palmer, Sarah

    2016-05-01

    The introduction of antiretroviral therapy (ART) 20 years ago has dramatically reduced morbidity and mortality associated with HIV-1. Initially there was hope that ART would be curative, but it quickly became clear that even though ART was able to restore CD4(+) T cell counts and suppress viral loads below levels of detection, discontinuation of treatment resulted in a rapid rebound of infection. This is due to persistence of a small reservoir of latently infected cells with a long half-life, which necessitates life-long ART. Over the past few years, significant progress has been made in defining and characterizing the latent reservoir of HIV-1, and here we review how understanding the latent reservoir during suppressive therapy will lead to significant advances in curative approaches for HIV-1. PMID:26875617

  2. Thought Suppression in Patients With Bipolar Disorder

    PubMed Central

    Miklowitz, David J.; Alatiq, Yousra; Geddes, John R.; Goodwin, Guy M.; Williams, J. Mark G.

    2010-01-01

    Suppression of negative thoughts has been observed under experimental conditions among patients with major depressive disorder (MDD) but has never been examined among patients with bipolar disorder (BD). Patients with BD (n = 36), patients with MDD (n = 20), and healthy controls (n = 20) completed a task that required unscrambling 6-word strings into 5-word sentences, leaving out 1 word. The extra word allowed the sentences to be completed in a negative, neutral, or “hyperpositive” (manic/goal-oriented) way. Participants completed the sentences under conditions of cognitive load (rehearsing a 6-digit number), reward (a bell tone), load and reward, or neither load nor reward. We hypothesized that patients with BD would engage in more active suppression of negative and hyperpositive thoughts than would controls, as revealed by their unscrambling more word strings into negative or hyperpositive sentences. Under conditions of load or reward and in the absence of either load or reward, patients with BD unscrambled more negative sentences than did controls. Under conditions of reward, patients with BD unscrambled more negative sentences than did patients with MDD. Patients with BD also reported more use of negative thought suppression than did controls. These group differences in negative biases were no longer significant when current mood states were controlled. Finally, the groups did not differ in the proportion of hyperpositive sentence completions in any condition. Thought suppression may provide a critical locus for psychological interventions in BD. PMID:20455608

  3. Nonanesthetics can suppress learning.

    PubMed

    Kandel, L; Chortkoff, B S; Sonner, J; Laster, M J; Eger, E I

    1996-02-01

    Nonanesthetic gases or vapors do not abolish movement in response to noxious stimuli despite partial pressures and affinities for lipids that would, according to the Meyer-Overton hypothesis, predict such abolition. We investigated whether nonanesthetics depress learning and memory (i.e., provide amnesia). To define learning, we used a "fear-potentiated startle paradigm": rats trained to associate light with a noxious stimulus (footshock) will startle more, as measured by an accelerometer, when a startle-eliciting stimulus (e.g., a noise) is paired with light than when the startle-eliciting stimulus is presented alone. We imposed light-shock pairings on 98 rats under three conditions: no anesthesia (control); 0.20, 0.29, and 0.38 times the minimum alveolar anesthetic concentration (MAC) of desflurane; or two nonanesthetics (1,2-dichloroperfluorocyclobutane and perfluoropentane) at partial pressures predicted from their lipid solubilities to be between 0.2 and 1 MAC. Desflurane produced a dose-related depression of learning with abolition of learning at 0.28 MAC. Perfluoropentane at 0.2-predicted MAC had the same effect as 0.28 MAC desflurane. 1,2-Dichloroperfluorocyclobutane at 0.5- to 1-predicted MAC abolished learning. Because nonanesthetics suppress learning but not movement (the two critical components of anesthesia), they may prove useful in discriminating between mechanisms and sites of action of anesthetics. PMID:8561335

  4. Inducing amnesia through systemic suppression

    PubMed Central

    Hulbert, Justin C.; Henson, Richard N.; Anderson, Michael C.

    2016-01-01

    Hippocampal damage profoundly disrupts the ability to store new memories of life events. Amnesic windows might also occur in healthy people due to disturbed hippocampal function arising during mental processes that systemically reduce hippocampal activity. Intentionally suppressing memory retrieval (retrieval stopping) reduces hippocampal activity via control mechanisms mediated by the lateral prefrontal cortex. Here we show that when people suppress retrieval given a reminder of an unwanted memory, they are considerably more likely to forget unrelated experiences from periods surrounding suppression. This amnesic shadow follows a dose-response function, becomes more pronounced after practice suppressing retrieval, exhibits characteristics indicating disturbed hippocampal function, and is predicted by reduced hippocampal activity. These findings indicate that stopping retrieval engages a suppression mechanism that broadly compromises hippocampal processes and that hippocampal stabilization processes can be interrupted strategically. Cognitively triggered amnesia constitutes an unrecognized forgetting process that may account for otherwise unexplained memory lapses following trauma. PMID:26977589

  5. Inducing amnesia through systemic suppression.

    PubMed

    Hulbert, Justin C; Henson, Richard N; Anderson, Michael C

    2016-01-01

    Hippocampal damage profoundly disrupts the ability to store new memories of life events. Amnesic windows might also occur in healthy people due to disturbed hippocampal function arising during mental processes that systemically reduce hippocampal activity. Intentionally suppressing memory retrieval (retrieval stopping) reduces hippocampal activity via control mechanisms mediated by the lateral prefrontal cortex. Here we show that when people suppress retrieval given a reminder of an unwanted memory, they are considerably more likely to forget unrelated experiences from periods surrounding suppression. This amnesic shadow follows a dose-response function, becomes more pronounced after practice suppressing retrieval, exhibits characteristics indicating disturbed hippocampal function, and is predicted by reduced hippocampal activity. These findings indicate that stopping retrieval engages a suppression mechanism that broadly compromises hippocampal processes and that hippocampal stabilization processes can be interrupted strategically. Cognitively triggered amnesia constitutes an unrecognized forgetting process that may account for otherwise unexplained memory lapses following trauma. PMID:26977589

  6. Sound can suppress visual perception.

    PubMed

    Hidaka, Souta; Ide, Masakazu

    2015-01-01

    In a single modality, the percept of an input (e.g., voices of neighbors) is often suppressed by another (e.g., the sound of a car horn nearby) due to close interactions of neural responses to these inputs. Recent studies have also suggested that close interactions of neural responses could occur even across sensory modalities, especially for audio-visual interactions. However, direct behavioral evidence regarding the audio-visual perceptual suppression effect has not been reported in a study with humans. Here, we investigated whether sound could have a suppressive effect on visual perception. We found that white noise bursts presented through headphones degraded visual orientation discrimination performance. This auditory suppression effect on visual perception frequently occurred when these inputs were presented in a spatially and temporally consistent manner. These results indicate that the perceptual suppression effect could occur across auditory and visual modalities based on close and direct neural interactions among those sensory inputs. PMID:26023877

  7. Protective effect of carnosine after chronic cerebral hypoperfusion possibly through suppressing astrocyte activation

    PubMed Central

    Ma, Jing; Chen, Jihui; Bo, Shuhong; Lu, Xiaotong; Zhang, Jian

    2015-01-01

    Aim: Subcortical ischemic vascular dementia (SIVD) induced by chronic hypoperfusion is a common cause of vascular dementia. The aim of this study was to determine whether the protective effect of carnosine on white matter lesion after chronic cerebral hypoperfusion through suppressing astrocyte activation. Methods: Adult male mice (C57BL/6 strain) were subjected to permanent occlusion of the right unilateral common carotid arteries (rUCCAO) and treated with carnosine or histidine. Open field test, freezing test, Klüver-Barrera staining, immunohistochemical analyses and western blot were performed after rUCCAO. Results: We found that carnosine ameliorated white matter lesion and cognitive impairment after rUCCAO. Carnosine suppressed the activation of astrocyte in both wide type mice and histidine decarboxylase knockout mice. However, administration of histidine did not show the same effect. We found that there were no differences between rUCCAO group and sham group for the expression of glutamate transporter-1 (GLT-1) and glutamate/aspartate transporter (GLAST). Furthermore, carnosine significantly attenuated the increase of inflammatory cytokine interferon gama. Conclusion: These data suggest carnosine induced neuroprotection during SIVD in mice is not dependent on the histaminergic pathway or the regulation of the expression of GLT-1 and GLAST, but may be due to a suppression of astrocyte activation and inflammatory cytokine release. PMID:26885268

  8. Active flutter suppression - Control system design and experimental validation

    NASA Technical Reports Server (NTRS)

    Waszak, Martin R.; Srinathkumar, S.

    1991-01-01

    The synthesis and experimental validation of an active flutter suppression controller for the Active Flexible Wing wind-tunnel model is presented. The design is accomplished with traditional root locus and Nyquist methods using interactive computer graphics tools and with extensive use of simulation-based analysis. The design approach uses a fundamental understanding of the flutter mechanism to formulate a simple controller structure to meet stringent design specifications. Experimentally, the flutter suppression controller succeeded in simultaneous suppression of two flutter modes, significantly increasing the flutter dynamic pressure despite errors in flutter dynamic pressure and flutter frequency in the mathematical model. The flutter suppression controller was also successfully operated in combination with a roll maneuver controller to perform flutter suppression during rapid rolling maneuvers.

  9. Albizia lebbeck suppresses histamine signaling by the inhibition of histamine H1 receptor and histidine decarboxylase gene transcriptions.

    PubMed

    Nurul, Islam Mohammed; Mizuguchi, Hiroyuki; Shahriar, Masum; Venkatesh, Pichairajan; Maeyama, Kazutaka; Mukherjee, Pulok K; Hattori, Masashi; Choudhuri, Mohamed Sahabuddin Kabir; Takeda, Noriaki; Fukui, Hiroyuki

    2011-11-01

    Histamine plays major roles in allergic diseases and its action is mediated mainly by histamine H(1) receptor (H1R). We have demonstrated that histamine signaling-related H1R and histidine decarboxylase (HDC) genes are allergic diseases sensitive genes and their expression level affects severity of the allergic symptoms. Therefore, compounds that suppress histamine signaling should be promising candidates as anti-allergic drugs. Here, we investigated the effect of the extract from the bark of Albizia lebbeck (AL), one of the ingredients of Ayruvedic medicines, on H1R and HDC gene expression using toluene-2,4-diisocyanate (TDI) sensitized allergy model rats and HeLa cells expressing endogenous H1R. Administration of the AL extract significantly decreased the numbers of sneezing and nasal rubbing. Pretreatment with the AL extract suppressed TDI-induced H1R and HDC mRNA elevations as well as [(3)H]mepyramine binding, HDC activity, and histamine content in the nasal mucosa. AL extract also suppressed TDI-induced up-regulation of IL-4, IL-5, and IL-13 mRNA. In HeLa cells, AL extract suppressed phorbol-12-myristate-13-acetate- or histamine-induced up-regulation of H1R mRNA. Our data suggest that AL alleviated nasal symptoms by inhibiting histamine signaling in TDI-sensitized rats through suppression of H1R and HDC gene transcriptions. Suppression of Th2-cytokine signaling by AL also suggests that it could affect the histamine-cytokine network. PMID:21782040

  10. Glucose infusion does not suppress increased lipolysis after abdominal surgery.

    PubMed

    Schricker, T; Carli, F; Lattermann, R; Wachter, U; Georgieff, M

    2001-02-01

    The purpose of this study was to investigate the effect of glucose infusion on lipid metabolism after abdominal surgery. Patients (n = 6) with non-metastasized colorectal carcinoma were investigated on the second day after surgery and healthy volunteers were studied after an overnight fast. The rates of glycerol appearance (R(a) glycerol), i.e., lipolysis rates, were assessed by primed continuous infusion of [1,1,2,3,3,-5H2]glycerol before and after 3 h of glucose infusion (4 mg x kg(-1) x min(-1)). Plasma concentrations of glycerol, free fatty acids, glucose, lactate, insulin, and glucagon were determined. Fasting R(a) glycerol was higher in patients than in volunteers (7.7 +/- 1.8 versus 1.9 +/- 0.3 micromol x kg(-1) x min(-1), P < 0.05). Glucose infusion suppressed the R(a) glycerol in volunteers to 1.0 +/- 0.2 micromol x kg(-1) x min(-1) (P < 0.05), whereas lipolysis was not affected in patients. Plasma concentrations of glycerol and free fatty acids similarly decreased during glucose administration by 50% in both groups (P < 0.05). In contrast to the patients, a significant correlation (r = 0.78, P < 0.05) between the R(a) glycerol and plasma glycerol concentration was observed in normal subjects. The hyperglycemic response to glucose infusion was significantly more pronounced (P < 0.05) in patients (10.7 +/- 0.7 mmol/L) than in volunteers (7.1 +/- 0.4 mmol/L), whereas the plasma insulin increased to the same extent in the two groups (P < 0.001). In conclusion, lipolysis rates are increased after abdominal surgery and glucose administration, most likely due to insulin resistance, and fail to inhibit stimulated whole-body lipolysis. PMID:11240333

  11. Photodynamic therapy with simultaneous suppression of multiple treatment escape pathways (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Spring, Bryan Q.; Sears, R. Bryan; Zheng, Lei Z.; Mai, Zhiming; Watanabe, Reika; Sherwood, Margaret E.; Schoenfeld, David A.; Pogue, Brian W.; Pereira, Stephen P.; Villa, Elizabeth; Hasan, Tayyaba

    2016-03-01

    We introduce photoactivatable multi-inhibitor nanoliposomes (PMILs) for photodynamic tumor cell and microvessel damage in synchrony with photo-initiation of tumor-confined, multikinase inhibitor release. The PMIL is a biodegradable delivery system comprised of a nanoliposome carrying a photoactivable chromophore (benzoporphyrin derivative monoacid A, BPD) in its bilayer. A multikinase inhibitor-loaded PEG-PLGA nanoparticle is encapsulated within the liposome, which acts a barrier to nanoparticle erosion and drug release. Following intravenous PMIL administration, near infrared irradiation of tumors triggers photodynamic therapy and initiates tumor-confined drug release from the nanoparticle. This talk presents promising preclinical data in mouse models of pancreatic cancer utilizing this concept to suppress the VEGF and MET signaling pathways—both critical to cancer progression, metastasis and treatment escape. A single PMIL treatment using low doses of a multikanse inhibitor (cabozantinib, XL184) achieves sustained tumor reduction and suppresses metastatic escape, whereas combination therapy by co-administration of the individual agents has significantly reduced efficacy. The PMIL concept is amenable to a number of molecular inhibitors and offers new prospects for spatiotemporal synchronization of combination therapies whilst reducing systemic drug exposure and associated toxicities.

  12. Suppression of Acid Sphingomyelinase Protects the Retina from Ischemic Injury

    PubMed Central

    Fan, Jie; Wu, Bill X.; Crosson, Craig E.

    2016-01-01

    Purpose Acid sphingomyelinase (ASMase) catalyzes the hydrolysis of sphingomyelin to ceramide and mediates multiple responses involved in inflammatory and apoptotic signaling. However, the role ASMase plays in ischemic retinal injury has not been investigated. The purpose of this study was to investigate how reduced ASMase expression impacts retinal ischemic injury. Methods Changes in ceramide levels and ASMase activity were determined by high performance liquid chromatography-tandem mass spectrometry analysis and ASMase activity. Retinal function and morphology were assessed by electroretinography (ERG) and morphometric analyses. Levels of TNF-α were determined by ELISA. Activation of p38 MAP kinase was assessed by Western blot analysis. Results In wild-type mice, ischemia produced a significant increase in retinal ASMase activity and ceramide levels. These increases were associated with functional deficits as measured by ERG analysis and significant structural degeneration in most retinal layers. In ASMase+/− mice, retinal ischemia did not significantly alter ASMase activity, and the rise in ceramide levels were significantly reduced compared to levels in retinas from wild-type mice. In ASMase+/− mice, functional and morphometric analyses of ischemic eyes revealed significantly less retinal degeneration than in injured retinas from wild-type mice. The ischemia-induced increase in retinal TNF-α levels was suppressed by the administration of the ASMase inhibitor desipramine, or by reducing ASMase expression. Conclusions Our results demonstrate that reducing ASMase expression provides partial protection from ischemic injury. Hence, the production of ceramide and subsequent mediators plays a role in the development of ischemic retinal injury. Modulating ASMase may present new opportunities for adjunctive therapies when treating retinal ischemic disorders. PMID:27571014

  13. Immune Suppression and Immune Activation in Depression

    PubMed Central

    Blume, Joshua; Douglas, Steven D.; Evans, Dwight L.

    2010-01-01

    Depression has been characterized as a disorder of both immune suppression and immune activation. Markers of impaired cellular immunity (decreased natural killer cell cytotoxicity) and inflammation (elevated IL-6, TNFα, CRP) have been associated with depression. These immunological markers have been associated with other medical illnesses, suggesting that immune dysregulation may be a central feature common to both depression and to its frequent medical comorbidities. Yet the significant associations of findings of both immune suppression and immune activation with depression raise questions concerning the relationship between these two classes of immunological observations. Depressed populations are heterogeneous groups, and there may be differences in the immune profiles of populations that are more narrowly defined in terms of symptom profile and/or demographic features. There have been few reports concurrently investigating markers of immune suppression and immune activation in the same depressed individuals. An emerging preclinical literature suggests that chronic inflammation may directly contribute to the pathophysiology of immune suppression in the context of illnesses such as cancer and rheumatoid arthritis. This literature provides us with specific immunoregulatory mechanisms mediating these relationships that could also explain differences in immune disturbances between subsets of depressed individuals We propose a research agenda emphasizing the assessment of these immunoregulatory mechanisms in large samples of depressed subjects as a means to define the relationships among immune findings (suppression and/or activation) within the same depressed individuals and to characterize subsets of depressed subjects based on shared immune profiles. Such a program of research, building on and integrating our knowledge of the psychoneuroimmunology of depression, could lead to innovation in the assessment and treatment of depression and its medical comorbidities

  14. An iminosugar-based heparanase inhibitor heparastatin (SF4) suppresses infiltration of neutrophils and monocytes into inflamed dorsal air pouches.

    PubMed

    Sue, Mayumi; Higashi, Nobuaki; Shida, Hiroaki; Kogane, Yusuke; Nishimura, Yoshio; Adachi, Hayamitsu; Kolaczkowska, Elzbieta; Kepka, Magdalena; Nakajima, Motowo; Irimura, Tatsuro

    2016-06-01

    Local infiltration of inflammatory cells is regulated by a number of biological steps during which the cells likely penetrate through subendothelial basement membranes that contain heparan sulfate proteoglycans. In the present study, we examined whether administration of heparastatin (SF4), an iminosugar-based inhibitor of heparanase, could suppress local inflammation and degradation of heparan sulfate proteoglycans in basement membranes. In a carrageenan- or formyl peptide-induced dorsal air pouch inflammation model, the number of infiltrated neutrophils and monocytes was significantly lower in mice after topical administration of heparastatin (SF4). The concentration of chemokines MIP-2 and KC in pouch exudates of drug-treated mice was similar to control. In a zymosan-induced peritonitis model, the number of infiltrated cells was not altered in drug-treated mice. To further test how heparastatin (SF4) influences transmigration of inflammatory neutrophils, its suppressive effect on migration and matrix degradation was examined in vitro. In the presence of heparastatin (SF4), the number of neutrophils that infiltrated across a Matrigel-coated polycarbonate membrane was significantly lower, while the number of neutrophils passing through an uncoated membrane was not altered. Lysate of bone marrow-derived neutrophils released sulfate-radiolabeled macromolecules from basement membrane-like extracellular matrix, which was suppressed by heparastatin (SF4). Heparan sulfate degradation activity was almost completely abolished after incubation of lysate with protein G-conjugated anti-heparanase monoclonal antibody, strongly suggesting that the activity was due to heparanase-mediated degradation. Taken together, in a dorsal air pouch inflammation model heparastatin (SF4) potentially suppresses extravasation of inflammatory cells by impairing the degradation of basement membrane heparan sulfate. PMID:27015605

  15. Pharmacokinetic and therapeutic efficacy of intrapulmonary administration of zoledronate for the prevention of bone destruction in rheumatoid arthritis.

    PubMed

    Katsumi, Hidemasa; Mozume, Takunori; Yanagi, Shin-Ichiro; Hasei, Tomohiro; Watanabe, Tetsushi; Sakane, Toshiyasu; Yamamoto, Akira

    2016-07-01

    Zoledronate, a third-generation nitrogen-containing bisphosphonate, is a new therapeutic agent for the prevention of joint destruction in rheumatoid arthritis (RA). Due to the poor oral absorption of zoledronate, the intravenous route has been the preferred method of administration. To evaluate whether the lung is a promising alternative route of zoledronate administration for the prevention of joint destruction in RA, we examined the pharmacokinetics, safety and therapeutic potential of zoledronate after intrapulmonary administration. The bioavailability of zoledronate was 55% after intrapulmonary administration in rats. In a collagen-induced RA mouse model, an intrapulmonary administration of zoledronate given 7 d before the 2nd collagen immunization effectively suppressed bone loss and joint destruction to a level similar to that achieved with intravenous injection at 21 d after the 2nd collagen immunization. Zoledronate only slightly affected lactate dehydrogenase activity in bronchoalveolar lavage fluid 4 h after intrapulmonary administration of the therapeutic dose in rats. Moreover, zoledronate only slightly changed the plasma level of creatinine after intrapulmonary administration while creatinine significantly increased after intravenous injection of zoledronate in mice. These results indicate that the lung is a promising alternative route of zoledronate administration for the treatment and prevention of joint destruction in RA. PMID:26508267

  16. Mesenchymal stem cell-conditioned media suppresses inflammation-associated overproliferation of pulmonary artery smooth muscle cells in a rat model of pulmonary hypertension

    PubMed Central

    LIU, JUNFENG; HAN, ZHIBO; HAN, ZHONGCHAO; HE, ZHIXU

    2016-01-01

    Inflammation-associated overproliferation of pulmonary artery smooth muscle cells (PASMCs) is considered to be involved in the pathogenesis of pulmonary hypertension (PH). The administration of mesenchymal stem cell-conditioned media (MSC-CM) has displayed benefits in the treatment of PH, however, the exact mechanism has yet to be elucidated. The present study aimed to determine whether MSC-CM is able to suppress overproliferation of PASMCs in PH via immunoregulation. By the administration of MSC-CM to monocrotaline (MCT)-induced PH rats, and the development of an in vitro co-culture system comprised of PASMCs and activated T cells, the therapeutic effects of MSC-CM on PH, and the changes in the expression of correlated factors, including TNF-α, calcineurin (CaN) and nuclear factor of activated T cells (NFAT), were assessed. Immunohistochemical staining results indicated that MSC-CM was able to significantly suppress the production of TNF-α in MCT-induced PH and co-culture systems; and reverse transcription-quantitative polymerase chain reaction results showed significant downregulation of the expression of CaN and NFATc2 in PASMCs (P<0.01). Furthermore, MSC-CM was able to significantly suppress CaN activity and NFATc2 activation (P<0.01), thus inhibiting the overproliferation of PASMCs. Finally, MSC-CM improved abnormalities in hemodynamics and pulmonary histology in MCT-induced PH. In conclusion, the findings of the current study suggest that administration of MSC-CM has the potential to suppress inflammation-associated overproliferation of PASMCs due to its immunosuppressive effects in PH and, thus, may serve as a beneficial therapeutic strategy. PMID:26893632

  17. Characterization of scratching behavior induced by intradermal administration of morphine and fentanyl in mice.

    PubMed

    Yamamoto, Atsuki; Kuyama, Shoji; Kamei, Chiaki; Sugimoto, Yukio

    2010-02-10

    Itching is known as a commonly side effect of opioid administration. However, the relationship of opioid receptors to itching is unclear. In this study, we examined the effect of intradermal injection of morphine and fentanyl on the itching sensation. When injected intradermally into the rostral back of mice, morphine and fentanyl elicited scratching behavior. In addition, an opioid receptor antagonist, naloxone, and a peripherally restricted opioid receptor antagonist, naloxone methiodide, significantly suppressed morphine- and fentanyl-induced scratching behavior. Moreover, the morphine-induced scratching behavior was suppressed by histamine H(1) receptor antagonists, such as diphenhydramine, chlorpheniramine, epinastine and cetirizine. On the other hand, fentanyl-induced scratching behavior was not suppressed by histamine H(1) receptor antagonists. Additionally, scratching behavior induced by morphine and fentanyl were not suppressed by glucocorticoids (predonisolone and dexamethasone). In conclusion, opioid-induced itching may involve in peripheral opioid receptors. Moreover, histamine and arachidonic acid metabolites played no main role in opioid-induced scratching behavior. PMID:19900440

  18. Donor-derived, tolerogenic dendritic cells suppress immune rejection in the indirect allosensitization-dominant setting of corneal transplantation

    PubMed Central

    Hattori, Takaaki; Saban, Daniel R.; Emami-naeini, Parisa; Chauhan, Sunil K.; Funaki, Toshinari; Ueno, Hiroki; Dana, Reza

    2012-01-01

    Significant interest has been focused on the use of ex vivo-manipulated DCs to optimally induce transplant tolerance and promote allograft survival. Although it is understood that donor-derived, tolerogenic DCs suppress the direct pathway of allosensitization, whether such DCs can similarly suppress the indirect pathway remains unclear. We therefore used the murine model of corneal transplantation to address this, as these allografts are rejected in an indirect pathway-dominant manner. Interestingly, recipients administered with donor bone marrow-derived DCregs, generated via culturing with GM-CSF, IL-10, and TGF-β1, significantly prolonged survival of corneal allografts. Correspondingly, these recipients demonstrated a potent reduction in the frequency of indirectly allosensitized T cells, as determined by ELISPOT. Examination of DCregs relative to mDCs or iDCs showed a resistance to up-regulation of MHC-II and costimulatory molecules, as well as an impaired capacity to stimulate MLRs. In vivo, DCreg administration in corneal-allografted recipients led to inhibition of CD4+IFN-γ+ T cell frequencies and an associated increase in Foxp3 expression in the Treg compartment. We conclude that donor-derived, tolerogenic DCs significantly suppress the indirect pathway, thereby identifying a novel regulatory mechanism for these cells in transplantation. PMID:22291211

  19. Organization/Administration.

    ERIC Educational Resources Information Center

    Chaffee, Ellen Earle

    Patterns that emerged from reviewing 26 syllabi for courses on organization and administration in higher education are discussed, and six sample syllabi are presented. The syllabi focused more on organization than administration. Of the 26 syllabi, 19 dealt with organization and administration generally; 5 with administration in a specific…

  20. Prolactin regulation of kisspeptin neurones in the mouse brain and its role in the lactation-induced suppression of kisspeptin expression.

    PubMed

    Brown, R S E; Herbison, A E; Grattan, D R

    2014-12-01

    Hyperprolactinaemia is a major cause of infertility in both males and females, although the mechanism by which prolactin inhibits the reproductive axis is not clear. The aim of the present study was to test the hypothesis that elevated prolactin causes suppression of kisspeptin expression in the hypothalamus, resulting in reduced release of gonadotrophin-releasing hormone (GnRH) and consequent infertility. In oestrogen-treated ovariectomised mice, chronic prolactin-treatment prevented the rise in luteinising hormone (LH) seen in vehicle-treated mice. Kiss1 mRNA was significantly suppressed in both the rostral periventricular region of the third ventricle (RP3V) and arcuate nucleus after prolactin treatment. Exogenous prolactin treatment induced phosphorylated signal transducer and activator of transcription 5 (pSTAT5) in kisspeptin neurones, and suppression of endogenous prolactin using bromocriptine reduced levels of pSTAT5 in kisspeptin neurones, suggesting that prolactin acts directly on kisspeptin neurones. By contrast, fewer than 1% of GnRH neurones expressed pSTAT5 in either dioestrous or lactating mice. As reported previously, there was significant suppression of kisspeptin mRNA and protein in the RP3V on day 7 of lactation, although not in the arcuate nucleus. Bromocriptine treatment significantly increased Kiss1 mRNA expression in the RP3V, although not to dioestrous levels. Unilateral thelectomy, aiming to eliminate sensory inputs from nipples on one side of the body, failed to alter the reduction in the number of kisspeptin neurones observed in the RP3V. These data demonstrate that chronic prolactin administration suppressed serum LH, and reduced Kiss1 mRNA levels in both the RP3V and arcuate nucleus, consistent with the hypothesis that prolactin-induced suppression of kisspeptin secretion might mediate the inhibitory effects of prolactin on GnRH secretion. During lactation, however, the suppression of Kiss1 mRNA in the RP3V was only partially reversed

  1. Suppression of ERK phosphorylation through oxidative stress is involved in the mechanism underlying sevoflurane-induced toxicity in the developing brain

    PubMed Central

    Yufune, Shinya; Satoh, Yasushi; Akai, Ryosuke; Yoshinaga, Yosuke; Kobayashi, Yasushi; Endo, Shogo; Kazama, Tomiei

    2016-01-01

    In animal models, neonatal exposure to general anesthetics significantly increased neuronal apoptosis with subsequent behavioral deficits in adulthood. Although the underlying mechanism is largely unknown, involvement of extracellular signal-regulated kinases (ERKs) is speculated since ERK phosphorylation is decreased by neonatal anesthetic exposure. Importance of ERK phosphorylation for neuronal development is underscored by our recent finding that transient suppression of ERK phosphorylation during the neonatal period significantly increased neuronal apoptosis and induced behavioral deficits. However, it is still unknown as to what extent decreased ERK phosphorylation contributes to the mechanism underlying anesthetic-induced toxicity. Here we investigated the causal relationship of decreased ERK phosphorylation and anesthetic-induced toxicity in the developing brain. At postnatal day 6 (P6), mice were exposed to sevoflurane (2%) or the blood-brain barrier-penetrating MEK inhibitor, α-[amino[(4-aminophenyl)thio]methylene]-2-(trifluoromethyl)benzeneacetonitrile (SL327) (50 mg/kg). Transient suppression of ERK phosphorylation by an intraperitoneal injection of SL327 at P6 significantly increased apoptosis similar to sevoflurane-induced apoptosis. Conversely, SL327 administration at P14 or P21 did not induce apoptosis, even though ERK phosphorylation was inhibited. Restoring ERK phosphorylation by administration of molecular hydrogen ameliorated sevoflurane-induced apoptosis. Together, our results strongly suggests that suppressed ERK phosphorylation is critically involved in the mechanism underlying anesthetic-induced toxicity in the developing brain. PMID:26905012

  2. 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. PMID:27075430

  3. Immersion diuresis without expected suppression of vasopressin

    NASA Technical Reports Server (NTRS)

    Keil, L. C.; Silver, J. E.; Wong, N.; Spaul, W. A.; Greenleaf, J. E.; Kravik, S. E.

    1984-01-01

    There is a shift of blood from the lower parts of the body to the thoracic circulation during bed rest, water immersion, and presumably during weightlessness. On earth, this central fluid shift is associated with a profound diuresis. However, the mechanism involved is not yet well understood. The present investigation is concerned with measurements regarding the plasma vasopressin, fluid, electrolyte, and plasma renin activity (PRA) responses in subjects with normal preimmersion plasma vasopressin (PVP) concentration. In the conducted experiments, PRA was suppressed significantly at 30 min of immersion and had declined by 74 percent by the end of the experiment. On the basis of previously obtained results, it appears that sodium excretion during immersion may be independent of aldosterone action. Experimental results indicate that PVP is not suppressed by water immersion in normally hydrated subjects and that other factors may be responsible for the diuresis.

  4. Adaptive Suppression of Noise in Voice Communications

    NASA Technical Reports Server (NTRS)

    Kozel, David; DeVault, James A.; Birr, Richard B.

    2003-01-01

    A subsystem for the adaptive suppression of noise in a voice communication system effects a high level of reduction of noise that enters the system through microphones. The subsystem includes a digital signal processor (DSP) plus circuitry that implements voice-recognition and spectral- manipulation techniques. The development of the adaptive noise-suppression subsystem was prompted by the following considerations: During processing of the space shuttle at Kennedy Space Center, voice communications among test team members have been significantly impaired in several instances because some test participants have had to communicate from locations with high ambient noise levels. Ear protection for the personnel involved is commercially available and is used in such situations. However, commercially available noise-canceling microphones do not provide sufficient reduction of noise that enters through microphones and thus becomes transmitted on outbound communication links.

  5. Suppressive drug interactions between antifungals.

    PubMed

    de Vos, Marjon G J; Bollenbach, Tobias

    2014-04-24

    In this issue of Chemistry & Biology, Cokol and colleagues report a systematic study of drug interactions between antifungal compounds. Suppressive drug interactions occur more frequently than previously realized and come in different flavors with interesting implications. PMID:24766845

  6. Spent coffee ground extract suppresses ultraviolet B-induced photoaging in hairless mice.

    PubMed

    Choi, Hyeon-Son; Park, Eu Ddeum; Park, Yooheon; Suh, Hyung Joo

    2015-12-01

    The aim of this study is to evaluate the effect of spent coffee ground (SCG) ethanol extract on UVB-induced skin aging in hairless mice. An ethanol extract of SCG (ESCG) was prepared using the residue remaining after extraction of oil from roasted SCG. High performance liquid chromatography (HPLC) analysis showed that the content of caffeine (41.58 ± 0.54 μg/mg) was higher than that of chlorogenic acid isomers (~9.17 μg/mg) in ESCG. ESCG significantly decreased the UVB-induced intracellular reactive oxygen species in HaCaT cells. UVB-induced wrinkle formation in mice dorsal skin was effectively reduced by ESCG administration; high dose of ESCG (5 g/L) caused the reduction of wrinkle area by 30% compared with UVB-treated control (UVBC). This result correlated with the ESCG-mediated decrease in epidermis thickness (25%). In addition, ESCG administration significantly reduced transdermal water loss (20%) and erythema formation (35%) derived from UVB exposure. Collagen type I (COL-1) level in dorsal skin was effectively recovered by ESCG administration. These results were supported by down-regulation of collagen-degrading matrix metalloproteinase 2 (MMP2) and 9 (MMP9) expressions. Our results indicate that ESCG protects mouse skin from UVB-induced photoaging by suppressing the expression of matrix metalloproteinases. Our study suggests that ESCG may be anti-photoaging agent. PMID:26410040

  7. Butorphanol suppresses fentanyl-induced cough during general anesthesia induction

    PubMed Central

    Cheng, Xiao-Yan; Lun, Xiao-Qin; Li, Hong-Bo; Zhang, Zhi-Jie

    2016-01-01

    Abstract Fentanyl-induced cough (FIC) is unwanted in the patients requiring stable induction of general anesthesia. This study was designed to evaluate the suppressive effects of butorphanol pretreatment on the incidence and severity of FIC during the induction of general anesthesia. A total of 315 patients of American Society of Anesthesiologists physical status I and II, scheduled for elective surgery under general anesthesia were randomized into 3 equally sized groups (n = 0105). Two minutes before fentanyl bolus, group I received intravenously 5 mL normal saline, groups II and III received butorphanol 0.015 and 0.03 mg/kg (diluted with saline to 5 mL), respectively. Patients were then administrated with fentanyl 2.5 μg/kg within 5 s. The incidence and severity of FIC was recorded for 2 minutes after fentanyl bolus. During experimental period, the mean arterial pressure, heart rate, and peripheral capillary oxygen saturation (SpO2) were recorded before the administration of butorphanol or normal saline (T0), 2 minutes (T1) after butorphanol injection, and 2 minutes (T2) after fentanyl injection. The incidence of FIC was 31.4% in group I, 11.4% in group II, and 3.8% in group III. Group III had a lowest incidence of FIC among 3 groups (P < 0.001, vs group I; P < 0.05, vs group II). The severe FIC was not observed in groups II and III, but was recoded from 6 patients in group I. At 2 minutes after fentanyl injection (T2), the mean arterial pressure was significantly higher in group I than that in groups II and III (P < 0.01, vs group II; P < 0.05, vs group III), but the values remained within safe limits. In conclusion, pretreatment with butorphanol could effectively and safely suppress FIC during anesthesia induction. PMID:27367987

  8. Structured triacylglycerol containing behenic and oleic acids suppresses triacylglycerol absorption and prevents obesity in rats

    PubMed Central

    2010-01-01

    Background Dietary 1(3)-behenoyl-2,3(1)-dioleoyl-rac-glycerol (BOO) has been reported to inhibit pancreatic lipase activity in vitro and suppress postprandial hypertriacylglycerolemia in humans. In the present study, the anti-obesity activities of BOO and its inhibitory effects on lymphatic triacylglycerol (TAG) absorption were investigated in rats. Methods In Experiment 1, rats were fed either BOO or soybean oil (SO) diet for 6 weeks. In the BOO diet, 20% of SO was replaced with an experimental oil rich in BOO. In Experiments 2 and 3, rats cannulated in the thoracic duct were administered an emulsions containing trioleoylglycerol (OOO) or an oil mixture (OOO:BOO, 9:1). Tri[1-14C]oleoylglycerol (14C-OOO) was added to the emulsions administered in Experiment 3. Results No observable differences were detected in food intake or body weight gain between the BOO and SO groups in Experiment 1. Plasma and liver TAG concentrations and visceral fat weights were significantly lower in the BOO group than in the SO group. The apparent absorption rate of fat was significantly lower in the BOO group than in the SO group. In Experiment 2, the lymphatic recovery of oleic and behenic acids was significantly lower at 5 and 6 h after BOO administration than after OOO administration. In Experiment 3, the lymphatic recovery of 14C-OOO was significantly lower at 5 and 6 h after BOO administration than after OOO administration. Conclusions These results suggest that BOO prevents deposition of visceral fat and hepatic TAG by lowering and delaying intestinal absorption of TAG. PMID:20653972

  9. Rhizosphere ecology and phytoprotection in soils naturally suppressive to Thielaviopsis black root rot of tobacco.

    PubMed

    Almario, Juliana; Muller, Daniel; Défago, Geneviève; Moënne-Loccoz, Yvan

    2014-07-01

    Soil suppressiveness to disease is an intriguing emerging property in agroecosystems, with important implications because it enables significant protection of susceptible plants from soil-borne pathogens. Unlike many soils where disease suppressiveness requires crop monoculture to establish, certain soils are naturally suppressive to disease, and this type of specific disease suppressiveness is maintained despite crop rotation. Soils naturally suppressive to Thielaviopsis basicola-mediated black root rot of tobacco and other crops occur in Morens region (Switzerland) and have been studied for over 30 years. In Morens, vermiculite-rich suppressive soils formed on morainic deposits while illite-rich conducive soils developed on sandstone, but suppressiveness is of microbial origin. Antagonistic pseudomonads play a role in black root rot suppressiveness, including Pseudomonas protegens (formerly P. fluorescens) CHA0, a major model strain for research. However, other types of rhizobacterial taxa may differ in prevalence between suppressive and conducive soils, suggesting that the microbial basis of black root rot suppressiveness could be far more complex than solely a Pseudomonas property. This first review on black root rot suppressive soils covers early findings on these soils, the significance of recent results, and compares them with other types of suppressive soils in terms of rhizosphere ecology and plant protection mechanisms. PMID:24650207

  10. Are Claims of Global Warming Being Suppressed?

    NASA Astrophysics Data System (ADS)

    Crowley, Thomas J.

    2006-02-01

    Over the last few years, I have heard many rumors that climate science relevant to the global warming discussion is being suppressed by the Bush Administration. One cannot do much about third-hand information. However, on 29 January, the New York Times published a front page article on NASA efforts to suppress statements about global warming by James Hansen, director of the NASA Goddard Institute for Space Studies. A claim by one government scientist, though, no matter how distinguished, still requires examples from other scientists before a general conclusion can be drawn about the overall scope of the problem. But if the charges are more widespread, then some government scientists might be reluctant to make such claims, because they might feel that their positions were jeopardized. Therefore, an alternate way may be needed to determine the scope of the issue, while still safeguarding government workers from possible retaliation. -On 30 January, Rep. Sherwood Boehlert (R-N.Y.), chairman of the U.S. House of Representatives Committee on Science, wrote a letter to NASA Administrator Michael Griffin addressing many of the concerns Crowley has raised. Boehlert wrote,``It ought to go without saying that government scientists must be free to describe their scientific conclusions and the implications of those conclusions to their fellow scientists, policymakers and the general public.'' He continued,``Good science cannot long persist in an atmosphere of intimidation. Political figures ought to be reviewing their public statements to make sure they are consistent with the best available science; scientists should not be reviewing their statements to make sure they are consistent with the current political orthodoxy.'' I commend Rep. Boehlert for his quick and clear statement of the importance of unfettered communication of science. -FRED SPILHAUS, Editor

  11. Significant lexical relationships

    SciTech Connect

    Pedersen, T.; Kayaalp, M.; Bruce, R.

    1996-12-31

    Statistical NLP inevitably deals with a large number of rare events. As a consequence, NLP data often violates the assumptions implicit in traditional statistical procedures such as significance testing. We describe a significance test, an exact conditional test, that is appropriate for NLP data and can be performed using freely available software. We apply this test to the study of lexical relationships and demonstrate that the results obtained using this test are both theoretically more reliable and different from the results obtained using previously applied tests.

  12. Modified Beamformers for Coherent Source Region Suppression

    PubMed Central

    Sekihara, Kensuke; Nagarajan, Srikantan S.

    2011-01-01

    Many tomographic source localization algorithms used in biomagnetic imaging assume, explicitly or sometimes implicitly, that the source activity at different brain locations are either independent or that the correlation structure between sources is known. Among these algorithms is a class of adaptive spatial filters known as beamformers, which have superior spatiotemporal resolution abilities. The performance of beamformers is robust to weakly coherent sources. However, these algorithms are extremely sensitive to the presence of strongly coherent sources. A frequent mode of failure in beamformers occurs with reconstruction of auditory evoked fields (AEFs), in which bilateral auditory cortices are highly coherent in their activation. Here, we present a novel beamformer that suppresses activation from regions with interfering coherent sources. First, a volume containing the interfering sources is defined. The lead field matrix for this volume is computed and reduced into a few significant columns using singular value decomposition (SVD). A vector beamformer is then constructed by rejecting the contribution of sources in the suppression region while allowing for source reconstruction at other specified regions. Performance of this algorithm was first validated with simulated data. Subsequent tests of this modified beamformer were performed on bilateral AEF data. An unmodified vector beamformer using whole head coverage misplaces the source medially. After defining a suppression region containing the temporal cortex on one side, the described method consistently results in clear focal activations at expected regions of the contralateral superior temporal plane. PMID:16830939

  13. Statistical Significance Testing.

    ERIC Educational Resources Information Center

    McLean, James E., Ed.; Kaufman, Alan S., Ed.

    1998-01-01

    The controversy about the use or misuse of statistical significance testing has become the major methodological issue in educational research. This special issue contains three articles that explore the controversy, three commentaries on these articles, an overall response, and three rejoinders by the first three authors. They are: (1)…

  14. Lack of Statistical Significance

    ERIC Educational Resources Information Center

    Kehle, Thomas J.; Bray, Melissa A.; Chafouleas, Sandra M.; Kawano, Takuji

    2007-01-01

    Criticism has been leveled against the use of statistical significance testing (SST) in many disciplines. However, the field of school psychology has been largely devoid of critiques of SST. Inspection of the primary journals in school psychology indicated numerous examples of SST with nonrandom samples and/or samples of convenience. In this…

  15. Immunologic effects of nickel. 1. Suppression of cellular and humoral immunity

    SciTech Connect

    Smialowicz, R.J.; Rogers, R.R.; Riddle, M.M.; Stott, G.A.

    1984-04-01

    The effects of nickel chloride on the cellular and humoral immune responses of mice were studied. A single intramuscular injection of nickel chloride (18.3 mg/kg) caused a significant involution of the thymus within 2 days following treatment. Significant reductions in the in vitro mitogen-stimulated response of lymphocytes from nickel chloride-treated mice (24 hr following a single injection of 18.3 or 36.6 mg/kg) were observed for the T-cell mitogens phytohemagglutinin (PHA) and concanavalin A (Con A), and the B- and T-cell mitogen pokeweed mitogen (PWM) but not the B-cell mitogen lipopolysaccharide (LPS). Theta-positive but not Ig-positive spleen cells were significantly reduced in nickel-treated mice compared with controls. Significant suppression of the primary antibody response to the T-cell dependent antigen sheep red blood cells was observed following a single injection of 18.3 mg/kg NiCl/sub 2/. Natural killer (NK) cell activity was significantly suppressed following a single injection of 18.3 mg/kg NiCl/sub 2/. The administration of NiCl/sub 2/ (18.3 mg/kg) also decreased the amount of endotoxin required to kill 50% of treated mice, although this was not statistically significant. In all cases the immunosuppressive effects of NiCl/sub 2/ were found to be transient with responses returning to normal within a few days. No alteration in the response of mice immunized with the T-cell independent antigen polyvinylpyrrolidone was observed following treatment with nickel. Furthermore, the phagocytic capacity of resident peritoneal macrophages from nickel-treated mice was not significantly different from saline-injected mice. The results indicate that NiCl/sub 2/ predominantly affects T-cell mediated immune responses and natural killer cells.

  16. 18β-glycyrrhetinic acid suppresses experimental autoimmune encephalomyelitis through inhibition of microglia activation and promotion of remyelination.

    PubMed

    Zhou, Jieru; Cai, Wei; Jin, Min; Xu, Jingwei; Wang, Yanan; Xiao, Yichuan; Hao, Li; Wang, Bei; Zhang, Yanyun; Han, Jie; Huang, Rui

    2015-01-01

    Microglia are intrinsic immune cells in the central nervous system (CNS). The under controlled microglia activation plays important roles in inflammatory demyelination diseases, such as multiple sclerosis (MS). However, the means to modulate microglia activation as a therapeutic modality and the underlying mechanisms remain elusive. Here we show that administration of 18β-glycyrrhetinic acid (GRA), by using both preventive and therapeutic treatment protocols, significantly suppresses disease severity of experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. The treatment effect of GRA on EAE is attributed to its regulatory effect on microglia. GRA-modulated microglia significantly decreased pro-inflammatory profile in the CNS through suppression of MAPK signal pathway. The ameliorated CNS pro-inflammatory profile prevented the recruitment of encephalitogenic T cells into the CNS, which alleviated inflammation-induced demyelination. In addition, GRA treatment promoted remyelination in the CNS of EAE mice. The induced remyelination can be mediated by the overcome of inflammation-induced blockade of brain-derived neurotrophic factor expression in microglia, as well as enhancing oligodendrocyte precursor cell proliferation. Collectively, our results demonstrate that GRA-modulated microglia suppresses EAE through inhibiting microglia activation-mediated CNS inflammation, and promoting neuroprotective effect of microglia, which represents a potential therapeutic strategy for MS and maybe other neuroinflammatory diseases associated with microglia activation. PMID:26329786

  17. Effects of central administration of oxytocin-saporin cytotoxin on chronic inflammation and feeding/drinking behaviors in adjuvant arthritic rats.

    PubMed

    Matsuura, Takanori; Kawasaki, Makoto; Hashimoto, Hirofumi; Yoshimura, Mitsuhiro; Motojima, Yasuhito; Saito, Reiko; Ueno, Hiromichi; Maruyama, Takashi; Sabanai, Ken; Mori, Toshiharu; Ohnishi, Hideo; Sakai, Akinori; Ueta, Yoichi

    2016-05-16

    An increase in the arthritis index as a marker of chronic inflammation and suppression of food intake are observed in adjuvant arthritic (AA) rats. Our previous study demonstrated that central oxytocin (OXT)-ergic pathways were activated potently in AA rats. In the present study, OXT-saporin (SAP) cytotoxin, which chemically disrupts OXT signaling was administered centrally to determine whether central OXT may be involved in the developments of chronic inflammation and alteration of feeding/drinking behavior in AA rats. The arthritis index was significantly enhanced in AA rats pretreated with OXT-SAP administered intrathecally (i.t.) but not intracerebroventricularly (i.c.v.). Suppression of food intake was significantly attenuated transiently in AA rats pretreated with OXT-SAP administered i.c.v. but not i.t. Suppression of drinking behavior was not affected by i.t. or i.c.v. administration of OXT-SAP in AA rats. In addition, intraperitoneal administration of an OXT receptor antagonist did not change the arthritis index or feeding/drinking behavior in AA rats. These results suggest that central OXT-ergic pathways may be involved in anti-inflammation at the spinal level and suppression of feeding behavior at the forebrain-brainstem level in AA rats. PMID:27060190

  18. Histidine Augments the Suppression of Hepatic Glucose Production by Central Insulin Action

    PubMed Central

    Kimura, Kumi; Nakamura, Yusuke; Inaba, Yuka; Matsumoto, Michihiro; Kido, Yoshiaki; Asahara, Shun-ichiro; Matsuda, Tomokazu; Watanabe, Hiroshi; Maeda, Akifumi; Inagaki, Fuyuhiko; Mukai, Chisato; Takeda, Kiyoshi; Akira, Shizuo; Ota, Tsuguhito; Nakabayashi, Hajime; Kaneko, Shuichi; Kasuga, Masato; Inoue, Hiroshi

    2013-01-01

    Glucose intolerance in type 2 diabetes is related to enhanced hepatic glucose production (HGP) due to the increased expression of hepatic gluconeogenic enzymes. Previously, we revealed that hepatic STAT3 decreases the expression of hepatic gluconeogenic enzymes and suppresses HGP. Here, we show that increased plasma histidine results in hepatic STAT3 activation. Intravenous and intracerebroventricular (ICV) administration of histidine-activated hepatic STAT3 reduced G6Pase protein and mRNA levels and augmented HGP suppression by insulin. This suppression of hepatic gluconeogenesis by histidine was abolished by hepatic STAT3 deficiency or hepatic Kupffer cell depletion. Inhibition of HGP by histidine was also blocked by ICV administration of a histamine H1 receptor antagonist. Therefore, histidine activates hepatic STAT3 and suppresses HGP via central histamine action. Hepatic STAT3 phosphorylation after histidine ICV administration was attenuated in histamine H1 receptor knockout (Hrh1KO) mice but not in neuron-specific insulin receptor knockout (NIRKO) mice. Conversely, hepatic STAT3 phosphorylation after insulin ICV administration was attenuated in NIRKO but not in Hrh1KO mice. These findings suggest that central histidine action is independent of central insulin action, while both have additive effects on HGP suppression. Our results indicate that central histidine/histamine-mediated suppression of HGP is a potential target for the treatment of type 2 diabetes. PMID:23474485

  19. Administration for Community Living

    MedlinePlus

    ... by Acting Assistant Secretary for Aging and ACL Administrator Edwin Walker at the HCBS Conference (08/29/ ... Remarks by Assistant Secretary on Aging and ACL Administrator Kathy Greenlee at the n4a Answers on Aging ...

  20. The New Administrative Computing.

    ERIC Educational Resources Information Center

    Green, Kenneth C.

    1988-01-01

    The past decade has seen dramatic changes in administrative computing, including more systems, more applications, a new group of computer users, and new opportunities for computer use in campus administration. (Author/MSE)

  1. Transportation Security Administration

    MedlinePlus

    ... content Official website of the Department of Homeland Security Transportation Security Administration When I fly can I bring my... ... to know if you could bring through the security checkpoint. Main menu Administrator Travel Security Screening Special ...

  2. Nanoassembly of probucol enables novel therapeutic efficacy in the suppression of lung metastasis of breast cancer.

    PubMed

    Zhang, Zhiwen; Cao, Haiqiang; Jiang, Shijun; Liu, Zeying; He, Xinyu; Yu, Haijun; Li, Yaping

    2014-11-01

    Metastasis is one of the major obstacles hindering the success of cancer therapy. The directed nanoassembly of probucol results in the "DNP" system, which greatly improves the oral delivery of probucol and subsequently leads to a novel therapeutic efficacy of probucol in the suppression of lung metastasis of breast cancer. DNP is formed by employing the intermolecular hydrophobic interactions between probucol and polyethylene glycol p-(1,1,3,3-tetramethylbutyl)-phenyl ether (also known as Triton X-100). After oral administration, the probucol concentration in the intestines is surprisingly about 200 times higher if it is applied as DNP rather than free probucol; it can be absorbed into intestinal enterocytes via clathrin-mediated endocytosis and transported into the systemic circulation through the lymphatic pathway. Moreover, the oral bioavailability of probucol is significantly higher-13.55 times higher-when applied as DNP in place of free probucol. The drug concentration in major organs is also significantly increased. The in vitro measurements show that the migration and invasion abilities of 4T1 cells are obviously inhibited by DNP. In particular, in an orthotopic metastatic breast cancer model, the notable suppression of lung metastasis from DNP is observed, but no effect is seen from the free-probucol suspension. As a result, the directed drug nanoassembly may open a new route for enhancing oral drug delivery and enable new therapeutic abilities for probucol against cancer metastasis. PMID:24930590

  3. Cannabinoids suppress inflammatory and neuropathic pain by targeting α3 glycine receptors

    PubMed Central

    Xiong, Wei; Cui, Tanxing; Cheng, Kejun; Yang, Fei; Chen, Shao-Rui; Willenbring, Dan; Guan, Yun; Pan, Hui-Lin; Ren, Ke; Xu, Yan

    2012-01-01

    Certain types of nonpsychoactive cannabinoids can potentiate glycine receptors (GlyRs), an important target for nociceptive regulation at the spinal level. However, little is known about the potential and mechanism of glycinergic cannabinoids for chronic pain treatment. We report that systemic and intrathecal administration of cannabidiol (CBD), a major nonpsychoactive component of marijuana, and its modified derivatives significantly suppress chronic inflammatory and neuropathic pain without causing apparent analgesic tolerance in rodents. The cannabinoids significantly potentiate glycine currents in dorsal horn neurons in rat spinal cord slices. The analgesic potency of 11 structurally similar cannabinoids is positively correlated with cannabinoid potentiation of the α3 GlyRs. In contrast, the cannabinoid analgesia is neither correlated with their binding affinity for CB1 and CB2 receptors nor with their psychoactive side effects. NMR analysis reveals a direct interaction between CBD and S296 in the third transmembrane domain of purified α3 GlyR. The cannabinoid-induced analgesic effect is absent in mice lacking the α3 GlyRs. Our findings suggest that the α3 GlyRs mediate glycinergic cannabinoid-induced suppression of chronic pain. These cannabinoids may represent a novel class of therapeutic agents for the treatment of chronic pain and other diseases involving GlyR dysfunction. PMID:22585736

  4. NASA, NOAA administrators nominated

    NASA Astrophysics Data System (ADS)

    Richman, Barbara T.

    President Ronald Reagan recently said he intended to nominate James Montgomery Beggs as NASA Administrator and John V. Byrne as NOAA Administrator. These two positions are key scientific posts that have been vacant since the start of the Reagan administration on January 20. The President also said he intends to nominate Hans Mark as NASA Deputy Administrator. At press time, Reagan had not designated his nominee for the director of the Office of Science and Technology Policy.

  5. Significant Tsunami Events

    NASA Astrophysics Data System (ADS)

    Dunbar, P. K.; Furtney, M.; McLean, S. J.; Sweeney, A. D.

    2014-12-01

    Tsunamis have inflicted death and destruction on the coastlines of the world throughout history. The occurrence of tsunamis and the resulting effects have been collected and studied as far back as the second millennium B.C. The knowledge gained from cataloging and examining these events has led to significant changes in our understanding of tsunamis, tsunami sources, and methods to mitigate the effects of tsunamis. The most significant, not surprisingly, are often the most devastating, such as the 2011 Tohoku, Japan earthquake and tsunami. The goal of this poster is to give a brief overview of the occurrence of tsunamis and then focus specifically on several significant tsunamis. There are various criteria to determine the most significant tsunamis: the number of deaths, amount of damage, maximum runup height, had a major impact on tsunami science or policy, etc. As a result, descriptions will include some of the most costly (2011 Tohoku, Japan), the most deadly (2004 Sumatra, 1883 Krakatau), and the highest runup ever observed (1958 Lituya Bay, Alaska). The discovery of the Cascadia subduction zone as the source of the 1700 Japanese "Orphan" tsunami and a future tsunami threat to the U.S. northwest coast, contributed to the decision to form the U.S. National Tsunami Hazard Mitigation Program. The great Lisbon earthquake of 1755 marked the beginning of the modern era of seismology. Knowledge gained from the 1964 Alaska earthquake and tsunami helped confirm the theory of plate tectonics. The 1946 Alaska, 1952 Kuril Islands, 1960 Chile, 1964 Alaska, and the 2004 Banda Aceh, tsunamis all resulted in warning centers or systems being established.The data descriptions on this poster were extracted from NOAA's National Geophysical Data Center (NGDC) global historical tsunami database. Additional information about these tsunamis, as well as water level data can be found by accessing the NGDC website www.ngdc.noaa.gov/hazard/

  6. A Philosophy of Administration.

    ERIC Educational Resources Information Center

    Bruening, William H.

    Justification is given for paying relatively large salaries to college administrators, specifically the president or chancellor and the chief academic officer. Three administrative task areas are discussed as criteria: management, administration per se, and leadership. It is contended that only leadership can be used as a criterion for…

  7. 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…

  8. Difference in the action mechanism of radon inhalation and radon hot spring water drinking in suppression of hyperuricemia in mice.

    PubMed

    Etani, Reo; Kataoka, Takahiro; Kanzaki, Norie; Sakoda, Akihiro; Tanaka, Hiroshi; Ishimori, Yuu; Mitsunobu, Fumihiro; Yamaoka, Kiyonori

    2016-06-01

    Although radon therapy is indicated for hyperuricemia, the underlying mechanisms of action have not yet been elucidated in detail. Therefore, we herein examined the inhibitory effects of radon inhalation and hot spring water drinking on potassium oxonate (PO)-induced hyperuricemia in mice. Mice inhaled radon at a concentration of 2000 Bq/m(3) for 24 h or were given hot spring water for 2 weeks. Mice were then administrated PO at a dose of 500 mg/kg. The results obtained showed that serum uric acid levels were significantly increased by the administration of PO. Radon inhalation or hot spring water drinking significantly inhibited elevations in serum uric acid levels through the suppression of xanthine oxidase activity in the liver. Radon inhalation activated anti-oxidative functions in the liver and kidney. These results suggest that radon inhalation inhibits PO-induced hyperuricemia by activating anti-oxidative functions, while hot spring water drinking may suppress PO-induced elevations in serum uric acid levels through the pharmacological effects of the chemical compositions dissolved in it. PMID:27021217

  9. Difference in the action mechanism of radon inhalation and radon hot spring water drinking in suppression of hyperuricemia in mice

    PubMed Central

    Etani, Reo; Kataoka, Takahiro; Kanzaki, Norie; Sakoda, Akihiro; Tanaka, Hiroshi; Ishimori, Yuu; Mitsunobu, Fumihiro; Yamaoka, Kiyonori

    2016-01-01

    Although radon therapy is indicated for hyperuricemia, the underlying mechanisms of action have not yet been elucidated in detail. Therefore, we herein examined the inhibitory effects of radon inhalation and hot spring water drinking on potassium oxonate (PO)–induced hyperuricemia in mice. Mice inhaled radon at a concentration of 2000 Bq/m3 for 24 h or were given hot spring water for 2 weeks. Mice were then administrated PO at a dose of 500 mg/kg. The results obtained showed that serum uric acid levels were significantly increased by the administration of PO. Radon inhalation or hot spring water drinking significantly inhibited elevations in serum uric acid levels through the suppression of xanthine oxidase activity in the liver. Radon inhalation activated anti-oxidative functions in the liver and kidney. These results suggest that radon inhalation inhibits PO-induced hyperuricemia by activating anti-oxidative functions, while hot spring water drinking may suppress PO-induced elevations in serum uric acid levels through the pharmacological effects of the chemical compositions dissolved in it. PMID:27021217

  10. Intravenous infusion of H2-saline suppresses oxidative stress and elevates antioxidant potential in Thoroughbred horses after racing exercise

    PubMed Central

    Yamazaki, Masahiko; Kusano, Kanichi; Ishibashi, Toru; Kiuchi, Masataka; Koyama, Katsuhiro

    2015-01-01

    Upon intensive, exhaustive exercise, exercise-induced reactive oxygen species may exceed the antioxidant defence threshold, consequently resulting in muscular damage or late-onset chronic inflammation. Recently, the therapeutic antioxidant and anti-inflammatory effects of molecular hydrogen (H2) for human rheumatoid arthritis have been demonstrated. However, it is also important to clarify the effects of administrating H2 in large animals other than humans, as H2 is thought to reach the target organ by passive diffusion upon delivery from the blood flow, indicating that the distance from the administration point to the target is critical. However, data on the effects of H2 on oxidative stress in real-life exhaustive exercise in large animals are currently lacking. We here investigated 13 Thoroughbred horses administered intravenous 2-L saline with or without 0.6-ppm H2 (placebo, N = 6; H2, N = 7) before participating in a high-intensity simulation race. Intravenous H2-saline significantly suppressed oxidative stress immediately, 3 h, and 24 h after the race, although the antioxidant capability was not affected throughout the study. The serum creatine kinase, lactate, and uric acid levels were increased in both groups. Taken together, these results indicate that intravenous H2-saline can significantly and specifically suppress oxidative stress induced after exhaustive racing in Thoroughbred horses. PMID:26493164

  11. Visual Surround Suppression in Schizophrenia

    PubMed Central

    Tibber, Marc S.; Anderson, Elaine J.; Bobin, Tracy; Antonova, Elena; Seabright, Alice; Wright, Bernice; Carlin, Patricia; Shergill, Sukhwinder S.; Dakin, Steven C.

    2013-01-01

    Compared to unaffected observers patients with schizophrenia (SZ) show characteristic differences in visual perception, including a reduced susceptibility to the influence of context on judgments of contrast – a manifestation of weaker surround suppression (SS). To examine the generality of this phenomenon we measured the ability of 24 individuals with SZ to judge the luminance, contrast, orientation, and size of targets embedded in contextual surrounds that would typically influence the target’s appearance. Individuals with SZ demonstrated weaker SS compared to matched controls for stimuli defined by contrast or size, but not for those defined by luminance or orientation. As perceived luminance is thought to be regulated at the earliest stages of visual processing our findings are consistent with a suppression deficit that is predominantly cortical in origin. In addition, we propose that preserved orientation SS in SZ may reflect the sparing of broadly tuned mechanisms of suppression. We attempt to reconcile these data with findings from previous studies. PMID:23450069

  12. The amphetamine appetite suppressant saga.

    PubMed

    2004-02-01

    (1) In 1999, all amphetamine derivatives still sold in France as appetite suppressants were withdrawn from the market because of serious cardiovascular adverse effects. Sibutramine, marketed in France since 2001, is closely related to this group of drugs. (2) The adverse effects shared by these drugs are mainly neuropsychiatric (due to a psychostimulant action) and cardiovascular (arterial hypertension and tachycardia). (3) More specific cardiovascular adverse effects, such as pulmonary hypertension and severe cardiac valve damage, emerged after several years of use. The first reports date back to the 1960s. (4) The pulmonary hypertension associated with appetite suppressants can be fatal or necessitate transplantation. (5) Cardiac valve damage due to appetite suppressants is generally irreversible and sometimes requires surgery. PMID:15055225

  13. Vibration suppression using smart structures

    NASA Technical Reports Server (NTRS)

    Garcia, Ephrahim; Inman, Daniel J.; Dosch, Jeffrey

    1991-01-01

    The control of structures for vibration suppression is discussed in the context of using smart materials and structures. Here the use of smart structures refers to using embedded piezoelectric devices as both control actuators and sensors. Using embedded sensors and actuators allows great improvements in performance over traditional structures (both passive and active) for vibration suppression. The application of smart structures to three experimental flexible structures is presented. The first is a flexible beam, the second is a flexible beam undergoing slewing motion, the third is a ribbed antenna. A simple model of a piezoelectric actuator/sensor is presented. The equations of motion for each structure is presented. The control issues considered as those associated with multi-input, multi-output control, PID control and LQR control implementation. A modern control analysis illustrates the usefulness of smart structures for vibration suppression.

  14. Background suppression in MAS NMR

    NASA Astrophysics Data System (ADS)

    White, Jeffery L.; Beck, Larry W.; Ferguson, David B.; Haw, James F.

    Pulse sequences for suppressing background signals from spinning modules used in magic-angle spinning NMR are described. These pulse sequences are based on spatially selective composite 90° pulses originally reported by Bax, which provide for no net excitation of spins outside the homogeneous region of the coil. We have achieved essentially complete suppression of background signals originating from our Vespel spinning module (which uses a free-standing coil) in both 1H and 13C spectra without notable loss in signal intensity. Successful modification of both Bloch decay and cross-polarization pulse sequences to include spatially selective pulses was essential to acquire background-free spectra for weak samples. Background suppression was also found to be particularly valuable for both T1 and T1 ϱ, relaxation measurements.

  15. Attention-dependent early cortical suppression contributes to crowding.

    PubMed

    Chen, Juan; He, Yingchen; Zhu, Ziyun; Zhou, Tiangang; Peng, Yujia; Zhang, Xilin; Fang, Fang

    2014-08-01

    Crowding, the identification difficulty for a target in the presence of nearby flankers, is ubiquitous in spatial vision and is considered a bottleneck of object recognition and visual awareness. Despite its significance, the neural mechanisms of crowding are still unclear. Here, we performed event-related potential and fMRI experiments to measure the cortical interaction between the target and flankers in human subjects. We found that the magnitude of the crowding effect was closely associated with an early suppressive cortical interaction. The cortical suppression was reflected in the earliest event-related potential component (C1), which originated in V1, and in the BOLD signal in V1, but not other higher cortical areas. Intriguingly, spatial attention played a critical role in the manifestation of the suppression. These findings provide direct and converging evidence that attention-dependent V1 suppression contributes to crowding at a very early stage of visual processing. PMID:25100582

  16. Aging and repeated thought suppression success.

    PubMed

    Lambert, Ann E; Smyth, Frederick L; Beadel, Jessica R; Teachman, Bethany A

    2013-01-01

    Intrusive thoughts and attempts to suppress them are common, but while suppression may be effective in the short-term, it can increase thought recurrence in the long-term. Because intentional suppression involves controlled processing, and many aspects of controlled processing decline with age, age differences in thought suppression outcomes may emerge, especially over repeated thought suppression attempts as cognitive resources are expended. Using multilevel modeling, we examined age differences in reactions to thought suppression attempts across four thought suppression sequences in 40 older and 42 younger adults. As expected, age differences were more prevalent during suppression than during free monitoring periods, with younger adults indicating longer, more frequent thought recurrences and greater suppression difficulty. Further, younger adults' thought suppression outcomes changed over time, while trajectories for older adults' were relatively stable. Results are discussed in terms of older adults' reduced thought recurrence, which was potentially afforded by age-related changes in reactive control and distractibility. PMID:23776442

  17. Chronic administration of nalmefene leads to increased food intake and body weight gain in mice.

    PubMed

    Chen, Richard Z; Huang, Ruey-Ruey C; Shen, Chun-Pyn; MacNeil, Douglas J; Fong, Tung M

    2004-07-01

    Nalmefene is an orally available opioid receptor antagonist that has been shown to suppress appetite in humans, but its effects on chronic food intake and body weight remain unclear. Here, we report that chronic (21-day) oral administration of nalmefene at 2 or 10 mg/kg/day in diet-induced obese (DIO) mice led to significant increases (9-11%) in cumulative food intake. Mice in the nalmefene-treated groups also gained body weight at a rate faster than the control. Body composition analysis showed that the extra body weight gains in the treated animals were mostly due to increased fat accumulation. Since acute nalmefene treatment showed a trend toward a decrease rather than an increase in food intake, it is possible that the orexigenic effect of chronic oral administration of nalmefene was caused by pharmacologically active metabolites rather than the drug itself. Our results argue against the potential use of nalmefene for treating human obesity. PMID:15219821

  18. Noise suppressing capillary separation system

    DOEpatents

    Yeung, Edward S.; Xue, Yongjun

    1996-07-30

    A noise-suppressing capillary separation system for detecting the real-time presence or concentration of an analyte in a sample is provided. The system contains a capillary separation means through which the analyte is moved, a coherent light source that generates a beam which is split into a reference beam and a sample beam that irradiate the capillary, and a detector for detecting the reference beam and the sample beam light that transmits through the capillary. The laser beam is of a wavelength effective to be absorbed by a chromophore in the capillary. The system includes a noise suppressing system to improve performance and accuracy without signal averaging or multiple scans.

  19. Expressive suppression and neural responsiveness to nonverbal affective cues.

    PubMed

    Petrican, Raluca; Rosenbaum, R Shayna; Grady, Cheryl

    2015-10-01

    Optimal social functioning occasionally requires concealment of one's emotions in order to meet one's immediate goals and environmental demands. However, because emotions serve an important communicative function, their habitual suppression disrupts the flow of social exchanges and, thus, incurs significant interpersonal costs. Evidence is accruing that the disruption in social interactions, linked to habitual expressive suppression use, stems not only from intrapersonal, but also from interpersonal causes, since the suppressors' restricted affective displays reportedly inhibit their interlocutors' emotionally expressive behaviors. However, expressive suppression use is not known to lead to clinically significant social impairments. One explanation may be that over the lifespan, individuals who habitually suppress their emotions come to compensate for their interlocutors' restrained expressive behaviors by developing an increased sensitivity to nonverbal affective cues. To probe this issue, the present study used functional magnetic resonance imaging (fMRI) to scan healthy older women while they viewed silent videos of a male social target displaying nonverbal emotional behavior, together with a brief verbal description of the accompanying context, and then judged the target's affect. As predicted, perceivers who reported greater habitual use of expressive suppression showed increased neural processing of nonverbal affective cues. This effect appeared to be coordinated in a top-down manner via cognitive control. Greater neural processing of nonverbal cues among perceivers who habitually suppress their emotions was linked to increased ventral striatum activity, suggestive of increased reward value/personal relevance ascribed to emotionally expressive nonverbal behaviors. These findings thus provide neural evidence broadly consistent with the hypothesized link between habitual use of expressive suppression and compensatory development of increased responsiveness to

  20. Chronic cortisol suppresses pituitary and hypothalamic peptide message expression in pigtailed macaques.

    PubMed

    Szot, P; Wilkinson, C W; White, S S; Leverenz, J B; Greenup, J L; Colasurdo, E A; Peskind, E R; Raskind, M A

    2004-01-01

    The effects of chronic elevations in circulating glucocorticoids on the expression of peptides and peptide receptors of the hypothalamic-pituitary-adrenal (HPA) axis have been studied extensively in rodents, but they have not been examined in primates. To determine the responses of the HPA axis in primates to elevated cortisol, hypothalamic and pituitary tissue from normal older pigtailed macaques (Macaca nemestrina) that had received daily oral administration of cortisol or placebo for 1 year were studied. Pro-opiomelanocortin in the anterior pituitary and corticotropin-releasing factor (CRF) mRNA expression in the hypothalamic paraventricular nucleus (PVN) were significantly reduced in cortisol-treated monkeys in comparison with controls. CRF receptor 1 (CRF-R1) expression in the anterior pituitary and arginine vasopressin mRNA expression in the PVN were unchanged by chronic cortisol administration. Sustained elevation of circulating glucocorticoids results in suppression of HPA peptide and peptide receptor expression in the PVN and anterior pituitary similar to those found in rodents. Chronic therapeutic administration of glucocorticoids in humans may have unintended consequences for hypothalamic and pituitary function. PMID:15145089

  1. Surfactant protein (SP)-A suppresses preterm delivery and inflammation via TLR2.

    PubMed

    Agrawal, Varkha; Smart, Keith; Jilling, Tamas; Hirsch, Emmet

    2013-01-01

    Toll like receptors (TLRs) are pattern-recognition molecules that initiate the innate immune response to pathogens. Pulmonary surfactant protein (SP)-A is an endogenously produced ligand for TLR2 and TLR4. SP-A has been proposed as a fetally produced signal for the onset of parturition in the mouse. We examined the effect of interactions between SP-A and the pathogenic TLR agonists lipopolysaccharide (LPS), peptidoglycan (PGN) and polyinosinic:cytidylic acid (poly(I:C)) (ligands for TLR4, TLR2 and TLR3, respectively) on the expression of inflammatory mediators and preterm delivery. Three types of mouse macrophages (the cell line RAW 264.7, and fresh amniotic fluid and peritoneal macrophages, including macrophages from TLR4 and TLR2 knockout mice) were treated for up to 7 hours with pathogenic TLR agonists with or without SP-A. SP-A alone had no effect upon inflammatory mediators in mouse macrophages and did not independently induce preterm labor. SP-A significantly suppressed TLR ligand-induced expression of inflammatory mediators (interleukin (IL)-1β, tumor necrosis factor (TNF)-α and the chemokine CCL5) via a TLR2 dependent mechanism. In a mouse inflammation-induced preterm delivery model, intrauterine administration of SP-A significantly inhibited preterm delivery, suppressed the expression of proinflammatory mediators and enhanced the expression of the CXCL1 and anti-inflammatory mediator IL-10. We conclude that SP-A acts via TLR2 to suppress TLR ligand-induced preterm delivery and inflammatory responses. PMID:23700442

  2. Suppression of thyroid radioiodine uptake by various doses of stable iodide

    SciTech Connect

    Sternthal, E.; Lipworth, L.; Stanley, B.; Abreau, C.; Fang, S.L.; Braverman, L.E.

    1980-11-06

    We studied the effect of various doses of sodium iodide on thyroid radioiodine uptake in euthyroid volunteers by giving single doses of 10, 30, 50, and 100 mg and then daily doses of 10, 15, 30, 50, or 100 mg for 12 days thereafter. All single doses above 10 mg suppressed 24h thyroid uptake of /sup 123/I to 0.7 to 1.5 per cent. Continued daily administration of 15 mg of iodide or more resulted in values consistently below 2 per cent. A small but statistically significant fall in serum thyroxine (T/sub 4/) and triiodothyronine (T/sub 3/) and a rise in serum thyrotropin (TSH) concentrations were observed after eight and 12 days of iodide treatment. This study provides guidelines for stable iodide prophylaxis in the event of exposure to radioactive iodine.

  3. 45 CFR 1351.1 - Significant terms.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, FAMILY AND YOUTH SERVICES BUREAU RUNAWAY AND HOMELESS YOUTH PROGRAM Definition of Terms § 1351.1 Significant terms. For the... homeless youth and their families, following the youth's return home or placement in alternative...

  4. 45 CFR 1351.1 - Significant terms.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ..., DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, FAMILY AND YOUTH SERVICES BUREAU RUNAWAY AND HOMELESS YOUTH PROGRAM Definition of Terms § 1351.1 Significant terms. For the... homeless youth and their families, following the youth's return home or placement in alternative...

  5. 45 CFR 1351.1 - Significant terms.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, FAMILY AND YOUTH SERVICES BUREAU RUNAWAY AND HOMELESS YOUTH PROGRAM Definition of Terms § 1351.1 Significant terms. For the... homeless youth and their families, following the youth's return home or placement in alternative...

  6. 45 CFR 1351.1 - Significant terms.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 45 Public Welfare 4 2013-10-01 2013-10-01 false Significant terms. 1351.1 Section 1351.1 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, FAMILY AND YOUTH SERVICES BUREAU RUNAWAY AND HOMELESS...

  7. Statistical or biological significance?

    PubMed

    Saxon, Emma

    2015-01-01

    Oat plants grown at an agricultural research facility produce higher yields in Field 1 than in Field 2, under well fertilised conditions and with similar weather exposure; all oat plants in both fields are healthy and show no sign of disease. In this study, the authors hypothesised that the soil microbial community might be different in each field, and these differences might explain the difference in oat plant growth. They carried out a metagenomic analysis of the 16 s ribosomal 'signature' sequences from bacteria in 50 randomly located soil samples in each field to determine the composition of the bacterial community. The study identified >1000 species, most of which were present in both fields. The authors identified two plant growth-promoting species that were significantly reduced in soil from Field 2 (Student's t-test P < 0.05), and concluded that these species might have contributed to reduced yield. PMID:26541972

  8. Anthropological significance of phenylketonuria.

    PubMed

    Saugstad, L F

    1975-01-01

    The highest incidence rates of phenylketonuria (PKU) have been observed in Ireland and Scotlant. Parents heterozygous for PKU in Norway differ significantly from the general population in the Rhesus, Kell and PGM systems. The parents investigated showed an excess of Rh negative, Kell plus and PGM type 1 individuals, which makes them similar to the present populations in Ireland and Scotlant. It is postulated that the heterozygotes for PKU in Norway are descended from a completely assimilated sub-population of Celtic origin, who came or were brought here, 1ooo years ago. Bronze objects of Western European (Scottish, Irish) origin, found in Viking graves widely distributed in Norway, have been taken as evidence of Vikings returning with loot (including a number of Celts) from Western Viking settlements. The continuity of residence since the Viking age in most habitable parts of Norway, and what seems to be a nearly complete regional relationship between the sites where Viking graves contain western imported objects and the birthplaces of grandparents of PKUs identified in Norway, lend further support to the hypothesis that the heterozygotes for PKU in Norway are descended from a completely assimilated subpopulation. The remarkable resemblance between Iceland and Ireland, in respect of several genetic markers (including the Rhesus, PGM and Kell systems), is considered to be an expression of a similar proportion of people of Celtic origin in each of the two countries. Their identical, high incidence rates of PKU are regarded as further evidence of this. The significant decline in the incidence of PKU when one passes from Ireland, Scotland and Iceland, to Denmark and on to Norway and Sweden, is therefore explained as being related to a reduction in the proportion of inhabitants of Celtic extraction in the respective populations. PMID:803884

  9. Intravenous Administration of Lycopene, a Tomato Extract, Protects against Myocardial Ischemia-Reperfusion Injury

    PubMed Central

    Tong, Chao; Peng, Chuan; Wang, Lianlian; Zhang, Li; Yang, Xiaotao; Xu, Ping; Li, Jinjin; Delplancke, Thibaut; Zhang, Hua; Qi, Hongbo

    2016-01-01

    Background: Oral uptake of lycopene has been shown to be beneficial for preventing myocardial ischemia-reperfusion (I/R) injury. However, the strong first-pass metabolism of lycopene influences its bioavailability and impedes its clinic application. In this study, we determined an intravenous (IV) administration dose of lycopene protects against myocardial infarction (MI) in a mouse model, and investigated the effects of acute lycopene administration on reactive oxygen species (ROS) production and related signaling pathways during myocardial I/R. Methods: In this study, we established both in vitro hypoxia/reoxygenation (H/R) cell model and in vivo regional myocardial I/R mouse model by ligating left anterior artery descending. TTC dual staining was used to assess I/R induced MI in the absence and presence of acute lycopene administration via tail vein injection. Results: Lycopene treatment (1 μM) before reoxygenation significantly reduced cardiomyocyte death induced by H/R. Intravenous administration of lycopene to achieve 1 μM concentration in circulating blood significantly suppressed MI, ROS production, and JNK phosphorylation in the cardiac tissue of mice during in vivo regional I/R. Conclusion: Elevating circulating lycopene to 1 μM via IV injection protects against myocardial I/R injury through inhibition of ROS accumulation and consequent inflammation in mice. PMID:26950150

  10. Stimulus Fractionation by Interocular Suppression

    PubMed Central

    Zadbood, Asieh; Lee, Sang-Hun; Blake, Randolph

    2011-01-01

    Can human observers distinguish physical removal of a visible stimulus from phenomenal suppression of that stimulus during binocular rivalry? As so often happens, simple questions produce complex answers, and that is the case in the study reported here. Using continuous flash suppression to produce binocular rivalry, we were able to identify stimulus conditions where most – but not all – people utterly fail to distinguish physical from phenomenal stimulus removal, although we can be certain that those two equivalent perceptual states are accompanied by distinct neural events. More interestingly, we find subtle variants of the task where distinguishing the two states is trivially easy, even for people who utterly fail under the original conditions. We found that stimulus features are differentially vulnerable to suppression. Observers are able to be aware of existence/removal of some stimulus attributes (flicker) but not others (orientation), implying that interocular suppression breaks down the unitary awareness of integrated features belonging to a visual object. These findings raise questions about the unitary nature of awareness and, also, place qualifications on the utility of binocular rivalry as a tool for studying the neural concomitants of conscious visual awareness. PMID:22102839

  11. Charmonium suppression in nuclear collisions

    SciTech Connect

    Gavin, S. |

    1996-11-01

    Measurements of {psi} and {psi}{prime} production from experiment NA50 at the CERN SPS are compared to calculations based on a hadronic model of charmonium suppression developed previously. Data on centrality dependence and total cross sections are in good accord with these predictions. Uncertainties in theoretical quantities such as NA50`s L parameter are discussed.

  12. Suppressing explosive synchronization by contrarians

    NASA Astrophysics Data System (ADS)

    Zhang, Xiyun; Guan, Shuguang; Zou, Yong; Chen, Xiaosong; Liu, Zonghua

    2016-01-01

    Explosive synchronization (ES) has recently received increasing attention and studies have mainly focused on the conditions of its onset so far. However, its inverse problem, i.e. the suppression of ES, has not been systematically studied so far. As ES is usually considered to be harmful in certain circumstances such as the cascading failure of power grids and epileptic seizure, etc., its suppression is definitely important and deserves to be studied. We here study this inverse problem by presenting an efficient approach to suppress ES from a first-order to second-order transition, without changing the intrinsic network structure. We find that ES can be suppressed by only changing a small fraction of oscillators into contrarians with negative couplings and the critical fraction for the transition from the first order to the second order increases with both the network size and the average degree. A brief theory is presented to explain the underlying mechanism. This finding underlines the importance of our method to improve the understanding of neural interactions underlying cognitive processes.

  13. Conditioned suppression, punishment, and aversion

    NASA Technical Reports Server (NTRS)

    Orme-Johnson, D. W.; Yarczower, M.

    1974-01-01

    The aversive action of visual stimuli was studied in two groups of pigeons which received response-contingent or noncontingent electric shocks in cages with translucent response keys. Presentation of grain for 3 sec, contingent on key pecking, was the visual stimulus associated with conditioned punishment or suppression. The responses of the pigeons in three different experiments are compared.

  14. DENDRITIC POLYMERS AS FIRE SUPPRESSANTS

    EPA Science Inventory

    This report describes an evaluation of the applicability of one of the latest advances in polymer technology (dendritic polymers) to suppressing fires, one of the greatest survivability threats to military personnel and vehicles. Certain types of alkali and transition metal compl...

  15. Multiple cilia suppress tumour formation.

    PubMed

    Eberhart, Charles

    2016-04-01

    Primary cilia are cellular structures that have important functions in development and disease. The suppression of multiciliate differentiation of choroid plexus precursors, and maintenance of a single primary cilium by Notch1, is now shown to be involved in choroid plexus tumour formation. PMID:27027488

  16. Leuprolide acetate suppresses pedophilic urges and arousability.

    PubMed

    Schober, Justine M; Kuhn, Phyllis J; Kovacs, Paul G; Earle, James H; Byrne, Peter M; Fries, Ruth A

    2005-12-01

    Cognitive-behavioral psychotherapy was compared with cognitive-behavioral psychotherapy augmented by leuprolide acetate (LA) for suppression of pedophilic behavior. Five male pedophiles (M age, 50 years; range, 36-58) were administered LA by Depo injection for 12 months, followed by saline placebo for 12 months. Testosterone levels, sexual interest preference by visual reaction time (Abel Assessment), penile tumescence (Monarch Penile Plethysmography, PPG), as well as strong sexual urges toward children and masturbatory frequency involving thoughts of children (polygraph), were measured every 3 months. On LA, testosterone decreased to castrate levels. Penile tumescence was significantly suppressed compared with baseline, but sufficient response remained to detect pedophilic interest. Pedophilic interest was also detected by visual reaction times. When asked about having pedophilic urges and masturbating to thoughts of children, all subjects self-reported a decrease. Polygraph responses indicated subjects were not deceptive. On placebo, testosterone and physiologic arousal eventually rose to baseline. As noted by polygraph, at baseline and on placebo, subjects were deceptive regarding increased pedophilic urges and masturbatory frequency. Interest preference, as measured by Abel Assessment and Monarch PPG, was generally unchanged throughout the study. Cognitive-behavioral psychotherapy augmented with LA significantly reduced pedophilic fantasies, urges, and masturbation; however, pedophilic interest did not change during 1 year of therapy. Deceptive responses by polygraph suggested that self-report was unreliable. Follow-up utilizing objective measures is essential for monitoring efficacy of treatment in pedophilia. Our study supports the premise that suppression of pedophilic behavior is possible. LA may augment cognitive-behavioral psychotherapy and help break the sequence leading to a re-offense. PMID:16362253

  17. [Meta-cognitive beliefs about thought suppression and associated paradoxical effects].

    PubMed

    Hattori, Yosuke; Honma, Yoshiko; Tanno, Yoshihiko

    2014-10-01

    The purpose of this study was to clarify the contents of meta-cognitive beliefs about thought suppression and to investigate the relationship between these beliefs and the paradoxical effects of thought suppression. In Study 1, we developed a scale measuring the endorsement of meta-cognitive beliefs about thought suppression. This measure, the Meta-cognitive Beliefs about Thought Suppression Questionnaire (BTQ, has four subscales: Distraction, Paradoxical Effect, Regret, and Promotion of Concentration. In Study 2 and Study 3, the BTQ showed sufficient criterion-related validity and test-retest reliability. In Study 4, we conducted an experiment to investigate the relationship between meta-cognitive beliefs about thought suppression and its paradoxical eftects. Results showed that the Paradoxical Effect subscale score significantly predicted the number of intrusive thoughts during thought suppression. The development process of meta-cognitive beliefs about thought suppression and implications for research about cognitive control are discussed. PMID:25486842

  18. [Meta-cognitive beliefs about thought suppression and associated paradoxical effects].

    PubMed

    Hattori, Yosuke; Honma, Yoshiko; Tanno, Yoshihiko

    2014-10-01

    The purpose of this study was to clarify the contents of meta-cognitive beliefs about thought suppression and to investigate the relationship between these beliefs and the paradoxical effects of thought suppression. In Study 1, we developed a scale measuring the endorsement of meta-cognitive beliefs about thought suppression. This measure, the Meta-cognitive Beliefs about Thought Suppression Questionnaire (BTQ, has four subscales: Distraction, Paradoxical Effect, Regret, and Promotion of Concentration. In Study 2 and Study 3, the BTQ showed sufficient criterion-related validity and test-retest reliability. In Study 4, we conducted an experiment to investigate the relationship between meta-cognitive beliefs about thought suppression and its paradoxical eftects. Results showed that the Paradoxical Effect subscale score significantly predicted the number of intrusive thoughts during thought suppression. The development process of meta-cognitive beliefs about thought suppression and implications for research about cognitive control are discussed. PMID:25508973

  19. High temperature suppression of dioxins.

    PubMed

    Zhan, Ming-Xiu; Chen, Tong; Fu, Jian-Ying; Lin, Xiao-Qing; Lu, Sheng-Yong; Li, Xiao-Dong; Yan, Jian-Hua; Buekens, Alfons

    2016-03-01

    Combined Sulphur-Nitrogen inhibitors, such as sewage sludge decomposition gases (SDG), thiourea and amidosulphonic acid have been observed to suppress the de novo synthesis of dioxins effectively. In this study, the inhibition of PCDD/Fs formation from model fly ash was investigated at unusually high temperatures (650 °C and 850 °C), well above the usual range of de novo tests (250-400 °C). At 650 °C it was found that SDG evolving from dried sewage sludge could suppress the formation of 2,3,7,8-substituted PCDD/Fs with high efficiency (90%), both in weight units and in I-TEQ units. Additionally, at 850 °C, three kinds of sulphur-amine or sulphur-ammonium compounds were tested to inhibit dioxins formation during laboratory-scale tests, simulating municipal solid waste incineration. The suppression efficiencies of PCDD/Fs formed through homogeneous gas phase reactions were all above 85% when 3 wt. % of thiourea (98.7%), aminosulphonic acid (96.0%) or ammonium thiosulphate (87.3%) was added. Differences in the ratio of PCDFs/PCDDs, in weight average chlorination level and in the congener distribution of the 17 toxic PCDD/Fs indicated that the three inhibitors tested followed distinct suppression pathways, possibly in relation to their different functional groups of nitrogen. Furthermore, thiourea reduced the (weight) average chlorinated level. In addition, the thermal decomposition of TUA was studied by means of thermogravimetry-fourier transform infrared spectroscopy (TG-FTIR) and the presence of SO2, SO3, NH3 and nitriles (N≡C bonds) was shown in the decomposition gases; these gaseous inhibitors might be the primary dioxins suppressants. PMID:26716881

  20. Significant Radionuclides Determination

    SciTech Connect

    Jo A. Ziegler

    2001-07-31

    The purpose of this calculation is to identify radionuclides that are significant to offsite doses from potential preclosure events for spent nuclear fuel (SNF) and high-level radioactive waste expected to be received at the potential Monitored Geologic Repository (MGR). In this calculation, high-level radioactive waste is included in references to DOE SNF. A previous document, ''DOE SNF DBE Offsite Dose Calculations'' (CRWMS M&O 1999b), calculated the source terms and offsite doses for Department of Energy (DOE) and Naval SNF for use in design basis event analyses. This calculation reproduces only DOE SNF work (i.e., no naval SNF work is included in this calculation) created in ''DOE SNF DBE Offsite Dose Calculations'' and expands the calculation to include DOE SNF expected to produce a high dose consequence (even though the quantity of the SNF is expected to be small) and SNF owned by commercial nuclear power producers. The calculation does not address any specific off-normal/DBE event scenarios for receiving, handling, or packaging of SNF. The results of this calculation are developed for comparative analysis to establish the important radionuclides and do not represent the final source terms to be used for license application. This calculation will be used as input to preclosure safety analyses and is performed in accordance with procedure AP-3.12Q, ''Calculations'', and is subject to the requirements of DOE/RW-0333P, ''Quality Assurance Requirements and Description'' (DOE 2000) as determined by the activity evaluation contained in ''Technical Work Plan for: Preclosure Safety Analysis, TWP-MGR-SE-000010'' (CRWMS M&O 2000b) in accordance with procedure AP-2.21Q, ''Quality Determinations and Planning for Scientific, Engineering, and Regulatory Compliance Activities''.

  1. Fungi producing significant mycotoxins.

    PubMed

    2012-01-01

    Mycotoxins are secondary metabolites of microfungi that are known to cause sickness or death in humans or animals. Although many such toxic metabolites are known, it is generally agreed that only a few are significant in causing disease: aflatoxins, fumonisins, ochratoxin A, deoxynivalenol, zearalenone, and ergot alkaloids. These toxins are produced by just a few species from the common genera Aspergillus, Penicillium, Fusarium, and Claviceps. All Aspergillus and Penicillium species either are commensals, growing in crops without obvious signs of pathogenicity, or invade crops after harvest and produce toxins during drying and storage. In contrast, the important Fusarium and Claviceps species infect crops before harvest. The most important Aspergillus species, occurring in warmer climates, are A. flavus and A. parasiticus, which produce aflatoxins in maize, groundnuts, tree nuts, and, less frequently, other commodities. The main ochratoxin A producers, A. ochraceus and A. carbonarius, commonly occur in grapes, dried vine fruits, wine, and coffee. Penicillium verrucosum also produces ochratoxin A but occurs only in cool temperate climates, where it infects small grains. F. verticillioides is ubiquitous in maize, with an endophytic nature, and produces fumonisins, which are generally more prevalent when crops are under drought stress or suffer excessive insect damage. It has recently been shown that Aspergillus niger also produces fumonisins, and several commodities may be affected. F. graminearum, which is the major producer of deoxynivalenol and zearalenone, is pathogenic on maize, wheat, and barley and produces these toxins whenever it infects these grains before harvest. Also included is a short section on Claviceps purpurea, which produces sclerotia among the seeds in grasses, including wheat, barley, and triticale. The main thrust of the chapter contains information on the identification of these fungi and their morphological characteristics, as well as factors

  2. Cilostazol suppresses angiotensin II-induced apoptosis in endothelial cells

    PubMed Central

    SHI, MIAO-QIAN; SU, FEI-FEI; XU, XUAN; LIU, XIONG-TAO; WANG, HONG-TAO; ZHANG, WEI; LI, XUE; LIAN, CHENG; ZHENG, QIANG-SUN; FENG, ZHI-CHUN

    2016-01-01

    Patients with essential hypertension undergo endothelial dysfunction, particularly in the conduit arteries. Cilostazol, a type III phosphodiesterase inhibitor, serves a role in the inhibition of platelet aggregation and it is widely used in the treatment of peripheral vascular diseases. Previous studies have suggested that cilostazol suppresses endothelial dysfunction; however, it remains unknown whether cilostazol protects the endothelial function in essential hypertension. The aim of the present study was to investigate whether, and how, cilostazol suppresses angiotensin II (angII)-induced endothelial dysfunction. Human umbilical vein endothelial cells (HUVECs) and Sprague Dawley rats were exposed to angII and treated with cilostazol. Endothelial cell apoptosis and function, nitric oxide and superoxide production, phosphorylation (p) of Akt, and caspase-3 protein expression levels were investigated. AngII exposure resulted in the apoptosis of endothelial cells in vitro and in vivo. In vitro, cilostazol significantly suppressed the angII-induced apoptosis of HUVECs; however, this effect was reduced in the presence of LY294002, a phosphoinositide 3 kinase (PI3K) inhibitor. Furthermore, cilostazol suppressed the angII-induced p-Akt downregulation and cleaved caspase-3 upregulation. These effects were also alleviated by LY294002. In vivo, cilostazol suppressed the angII-induced endothelial cell apoptosis and dysfunction. Cilostazol was also demonstrated to partially reduced the angII-induced increase in superoxide production. The results of the present study suggested that cilostazol suppresses endothelial apoptosis and dysfunction by modulating the PI3K/Akt pathway. PMID:26862035

  3. Induction of cytokine synthesis and fever suppresses REM sleep and improves mood in patients with major depression.

    PubMed

    Bauer, J; Hohagen, F; Gimmel, E; Bruns, F; Lis, S; Krieger, S; Ambach, W; Guthmann, A; Grunze, H; Fritsch-Montero, R

    1995-11-01

    Beneficial effects of inflammatory events on certain psychiatric disorders, including depression, were reported sporadically by ancient Greek physicians, but have been described also in our times by a few psychiatrists during the past decades. During febrile inflammatory events, mediators of the immune system such as interleukin-1 can be detected in the brain and may act on their respective receptors which have also been demonstrated in the brain. Since cytokines such as interleukin-1 have been shown in animal studies to exert sedative behavioral effects, to be somnogenic, and to induce slow-wave sleep (SWS), we performed a pilot study to evaluate scientifically the anecdotically reported beneficial effects of inflammatory states on depressive disorders. Mood and sleep parameters were monitored in seven drug-free, severely depressed patients before, during, and after the administration of a single dose of endotoxin. All patients responded with a short pulse of increased synthesis of the cytokines tumor necrosis factor, interleukin-1, and interleukin-6 and elevated body temperature for several hours. During the night following endotoxin administration, rapid eye movement (REM) sleep was significantly suppressed, while changes in slow wave sleep were not significant. During the next day, all patients were in a significantly improved mood; however a rebound of REM sleep was observed in the second night after endotoxin administration and mood worsened again during the next days, indicating an only transient beneficial effect of the treatment. PMID:8573663

  4. Saikosaponin-d: A potential chemotherapeutics in castration resistant prostate cancer by suppressing cancer metastases and cancer stem cell phenotypes.

    PubMed

    Zhong, Di; Zhang, Hui-Jian; Jiang, Yao-Dong; Wu, Peng; Qi, Huan; Cai, Chao; Zheng, Shao-Bin; Dang, Qiang

    2016-06-10

    Androgen deprivation therapy is the gold standard regimen for advanced Prostate cancer (PCa) patients, nevertheless, patients eventually develop into castration-resistant prostate cancer (CRPC). Currently only a few chemotherapeutics are available for CRPC. Therefore, it is critical for identifying a new drug. In this study, we will explore a new agent, Saikosaponin-d (SSd), for CRPC therapy based on its mechanism of action. DU145 and CWR22Rv1 cells representing CRPC were employed in this study. A series of cell, biochemical, and molecular biologic assays such as Immunofluorescence, Zymography, Sphere formation, Colony formation, and MTT were used. Finally, we find SSd can significantly inhibit the growth of PCa cells in both dose- and time-dependent and suppress the colony formation during a long-term drug administration, it also can inhibit their migration and invasion abilities, which was accompanied by reverse the epithelial-mesenchymal transition (EMT) and suppress MMP2/9 expression as well as activities. Furthermore, SSd can suppress cancer stem cell (CSC) phenotypes such as self-renewal ability. Mechanistically, SSd blocks Wnt/β-catenin signaling pathway by decreasing GSK3β phosphorylation to affect EMT and CSC. These findings demonstrate the mechanism of anti-cancer activity of SSd in targeting EMT and CSC, suggesting SSd can be a potent agent for CRPC therapy. PMID:27155154

  5. Zyflamend Suppresses Growth and Sensitizes Human Pancreatic Tumors to Gemcitabine in an Orthotopic Mouse Model Through Modulation of Multiple Targets

    PubMed Central

    Kunnumakkara, Ajaikumar B.; Sung, Bokyung; Ravindran, Jayaraj; Diagaradjane, Parmeswaran; Deorukhkar, Amit; Dey, Sanjit; Koca, Cemile; Tong, Zhimin; Gelovani, Juri G.; Guha, Sushovan; Krishnan, Sunil; Aggarwal, Bharat B.

    2011-01-01

    Agents that can potentiate the efficacy of standard chemotherapy against pancreatic cancer are of great interest. Because of their low cost and safety, patients commonly use a variety of dietary supplements, although evidence of their efficacy is often lacking. One such commonly used food supplement, Zyflamend, is a polyherbal preparation with potent anti-inflammatory activities, and preclinical efficacy against prostate and oral cancer. Whether Zyflamend has any efficacy against human pancreatic cancer alone or in combination with gemcitibine, a commonly used agent, was examined in cell cultures and in an orthotopic mouse model. In vitro, Zyflamend inhibited the proliferation of pancreatic cancer cell lines regardless of p53 status and also enhanced gemcitabine-induced apoptosis. This finding correlated with inhibition of NF-κB activation by Zyflamend and suppression of cyclin D1, c-myc, COX-2, Bcl-2, IAP, survivin, VEGF, ICAM-1, and CXCR4. In nude mice, oral administration of Zyflamend alone significantly inhibited the growth of orthotopically transplanted human pancreatic tumors, and when combined with gemcitabine, further enhanced the antitumor effects. Immunohistochemical and Western blot analyses of tumor tissue showed that the suppression of pancreatic cancer growth correlated with inhibition of proliferation index marker (Ki-67), COX-2, MMP-9, NF-κB, and VEGF. Overall, these results suggest that the concentrated multiherb product Zyflamend alone can inhibit the growth of human pancreatic tumors and, in addition, can sensitize pancreatic cancers to gemcitabine through the suppression of multiple targets linked to tumorigenesis. PMID:21935918

  6. Onionin A inhibits ovarian cancer progression by suppressing cancer cell proliferation and the protumour function of macrophages

    PubMed Central

    Tsuboki, Junko; Fujiwara, Yukio; Horlad, Hasita; Shiraishi, Daisuke; Nohara, Toshihiro; Tayama, Shingo; Motohara, Takeshi; Saito, Yoichi; Ikeda, Tsuyoshi; Takaishi, Kiyomi; Tashiro, Hironori; Yonemoto, Yukihiro; Katabuchi, Hidetaka; Takeya, Motohiro; Komohara, Yoshihiro

    2016-01-01

    It is well known that tumour-associated macrophages (TAMs) play an important role in tumour development by modulating the tumour microenvironment, and targeting of protumour activation or the M2 polarization of TAMs is expected to be an effective therapy for cancer patients. We previously demonstrated that onionin A (ONA), a natural low molecular weight compound isolated from onions, has an inhibitory effect on M2 macrophage polarization. In the present study, we investigated whether ONA had a therapeutic anti-ovarian cancer effect using in vitro and in vivo studies. We found that ONA reduced the extent of ovarian cancer cell proliferation induced by co-culture with human macrophages. In addition, we also found that ONA directly suppressed cancer cell proliferation. A combinatorial effect with ONA and anti-cancer drugs was also observed. The activation of signal transducer and activator of transcription 3 (STAT3), which is involved in cell proliferation and chemo-resistance, was significantly abrogated by ONA in ovarian cancer cells. Furthermore, the administration of ONA suppressed cancer progression and prolonged the survival time in a murine ovarian cancer model under single and combined treatment conditions. Thus, ONA is considered useful for the additional treatment of patients with ovarian cancer owing to its suppression of the protumour activation of TAMs and direct cytotoxicity against cancer cells. PMID:27404320

  7. Onionin A inhibits ovarian cancer progression by suppressing cancer cell proliferation and the protumour function of macrophages.

    PubMed

    Tsuboki, Junko; Fujiwara, Yukio; Horlad, Hasita; Shiraishi, Daisuke; Nohara, Toshihiro; Tayama, Shingo; Motohara, Takeshi; Saito, Yoichi; Ikeda, Tsuyoshi; Takaishi, Kiyomi; Tashiro, Hironori; Yonemoto, Yukihiro; Katabuchi, Hidetaka; Takeya, Motohiro; Komohara, Yoshihiro

    2016-01-01

    It is well known that tumour-associated macrophages (TAMs) play an important role in tumour development by modulating the tumour microenvironment, and targeting of protumour activation or the M2 polarization of TAMs is expected to be an effective therapy for cancer patients. We previously demonstrated that onionin A (ONA), a natural low molecular weight compound isolated from onions, has an inhibitory effect on M2 macrophage polarization. In the present study, we investigated whether ONA had a therapeutic anti-ovarian cancer effect using in vitro and in vivo studies. We found that ONA reduced the extent of ovarian cancer cell proliferation induced by co-culture with human macrophages. In addition, we also found that ONA directly suppressed cancer cell proliferation. A combinatorial effect with ONA and anti-cancer drugs was also observed. The activation of signal transducer and activator of transcription 3 (STAT3), which is involved in cell proliferation and chemo-resistance, was significantly abrogated by ONA in ovarian cancer cells. Furthermore, the administration of ONA suppressed cancer progression and prolonged the survival time in a murine ovarian cancer model under single and combined treatment conditions. Thus, ONA is considered useful for the additional treatment of patients with ovarian cancer owing to its suppression of the protumour activation of TAMs and direct cytotoxicity against cancer cells. PMID:27404320

  8. The effect of titrated fentanyl on suppressed cough reflex in healthy adult volunteers.

    PubMed

    Kelly, H E; Shaw, G M; Brett, C N; Greenwood, F M; Huckabee, M L

    2016-05-01

    Cough suppression is part of the pharmacodynamic profile of opioids. We investigated the impact of clinical doses of fentanyl on suppressing the cough reflex. Thirteen volunteers received 2 μg.kg(-1) of fentanyl in a divided administration protocol. Three minutes after each administration and at 10 min intervals during washout, suppressed cough reflex testing with nebulised citric acid was performed and compared with fentanyl effect-site concentration. Mean (SD) citric acid concentration provoking cough increased from 0.5 (0.28) mol.l(-1) at baseline to 1.2 (0.50) mol.l(-1) after 2 μg.kg(-1) of fentanyl (p = 0.01). Mean (SD) fentanyl effect-site concentration after the final dose of fentanyl was 1.89 (0.05) ng.ml(-1) . A strong positive correlation was found between suppressed cough reflex thresholds and fentanyl effect-site concentrations during both fentanyl administration and washout phases of the study (r(2) = 0.79, p = 0.01). The mean (SD) length of time for return of suppressed cough response was 44.6 (18.8) min. Clinically relevant doses of fentanyl produced cough reflex suppression in healthy volunteers. PMID:26919658

  9. Salmonella typhimurium Suppresses Tumor Growth via the Pro-Inflammatory Cytokine Interleukin-1β

    PubMed Central

    Kim, Jung-Eun; Phan, Thuy Xuan; Nguyen, Vu Hong; Dinh-Vu, Hong-Van; Zheng, Jin Hai; Yun, Misun; Park, Sung-Gyoo; Hong, Yeongjin; Choy, Hyon E.; Szardenings, Michael; Hwang, Won; Park, Jin-A; Park, SunHee; Im, Sin-Hyeog; Min, Jung-Joon

    2015-01-01

    Although strains of attenuated Salmonella typhimurium and wild-type Escherichia coli show similar tumor-targeting capacities, only S. typhimurium significantly suppresses tumor growth in mice. The aim of the present study was to examine bacteria-mediated immune responses by conducting comparative analyses of the cytokine profiles and immune cell populations within tumor tissues colonized by E. coli or attenuated Salmonellae. CT26 tumor-bearing mice were treated with two different bacterial strains: S. typhimurium defective in ppGpp synthesis (ΔppGpp Salmonellae) or wild-type E. coli MG1655. Cytokine profiles and immune cell populations in tumor tissue colonized by these two bacterial strains were examined at two time points based on the pattern of tumor growth after ΔppGpp Salmonellae treatment: 1) when tumor growth was suppressed ('suppression stage') and 2) when they began to re-grow ('re-growing stage'). The levels of IL-1β and TNF-α were markedly increased in tumors colonized by ΔppGpp Salmonellae. This increase was associated with tumor regression; the levels of both IL-1β and TNF-α returned to normal level when the tumors started to re-grow. To identify the immune cells primarily responsible for Salmonellae-mediated tumor suppression, we examined the major cell types that produce IL-1β and TNF-α. We found that macrophages and dendritic cells were the main producers of TNF-α and IL-1β. Inhibiting IL-1β production in Salmonellae-treated mice restored tumor growth, whereas tumor growth was suppressed for longer by local administration of recombinant IL-1β or TNF-α in conjunction with Salmonella therapy. These findings suggested that IL-1β and TNF-α play important roles in Salmonella-mediated cancer therapy. A better understanding of host immune responses in Salmonella therapy may increase the success of a given drug, particularly when various strategies are combined with bacteriotherapy. PMID:26516371

  10. 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.

  11. Enhancement or Suppression of ACE Inhibitory Activity by a Mixture of Tea and Foods for Specified Health Uses (FOSHU) That Are Marketed as "Support for Normal Blood Pressure".

    PubMed

    Murakami, Isao; Hosono, Hiroyuki; Suzuki, Shigeto; Kurihara, Junichi; Itagaki, Fumio; Watanabe, Machiko

    2011-01-01

    The ACE inhibitory activities of mixtures of FOSHUs (Healthya, Goma-Mugicha, Lapis Support and Ameal) were examined in order to identify any antihypertensive interactions. Among combinations of Healthya with other samples that contain active peptides, only that with Ameal was found to have no inhibitory activity. Enhanced activity was observed in 2 other mixtures. The activity of a mixture of tea polyphenols and the whey component extracted from an Ameal solution was significantly decreased, thus demonstrating that whey protein lowered the ACE inhibitory activity of Healthya. Although oral administration of tea polyphenols alone significantly decreased SBP in SHR at 2 and 4 hr, combined administration with Ameal failed to decrease SBP at the same time points. In conclusion, the simultaneous intake of tea and FOSHUs that contain active peptides might affect daily self-antihypertensive management via enhancement or suppression of ACE inhibitory activity. PMID:22389857

  12. The efficacy of the appetite suppressant, diethylpropion, is dependent on both when it is given (day vs. night) and under conditions of high fat dietary restriction.

    PubMed

    Kalyanasundar, B; Solorio, Jessica; Perez, Claudia I; Hoyo-Vadillo, Carlos; Simon, Sidney A; Gutierrez, Ranier

    2016-05-01

    Obesity is a public health problem caused by excessive consumption of high caloric diets and/or lack of physical activity. Although treatments for obesity include low caloric diets and exercise programs, these activities frequently are supplemented with appetite suppressants. For the short-term treatment of weight loss, diethylpropion (DEP) is a commonly used appetite suppressant. However, little is known with regard to how to improve its weight loss efficacy. We therefore evaluated, in rats, two administration protocols where the animals received daily injections of DEP. First, when these nocturnal animals were normally active (at night) and when they were normally inactive (daytime), and second, with or without high fat dietary restriction (HFDR). We observed that DEP induced a greater weight-loss administered when the animals were in their active phase than in their inactive phase. Moreover, DEP's administration during the inactive phase (and to a lesser degree in the active phase) promotes the consumption of food during normal sleeping time. In addition, we found that DEP-induced weight loss under ad libitum access to a HF diet, but its efficacy significantly improved under conditions of HFDR. In summary, the efficacy of DEP, and presumably other like appetite suppressants, is enhanced by carefully controlling the time it is administered and under dietary restriction of HF diets. PMID:26867698

  13. Brimonidine suppresses loss of retinal neurons and visual function in a murine model of optic neuritis.

    PubMed

    Guo, Xiaoli; Namekata, Kazuhiko; Kimura, Atsuko; Noro, Takahiko; Azuchi, Yuriko; Semba, Kentaro; Harada, Chikako; Yoshida, Hiroshi; Mitamura, Yoshinori; Harada, Takayuki

    2015-04-10

    Optic neuritis is inflammation of the optic nerve and is strongly associated with multiple sclerosis (MS), an inflammatory demyelinating syndrome of the central nervous system. It leads to retinal ganglion cell (RGC) death and can cause severe vision loss. Brimonidine (BMD) is a selective α2-adrenergic receptor agonist that is used clinically for the treatment of glaucoma. BMD lowers intraocular pressure, but recent evidence suggests that its therapeutic efficacy may also mediate through mechanisms independent of modulation of intraocular pressure. In this study, we examined the effects of topical administration of BMD on retinal degeneration during optic neuritis in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. EAE was induced with MOG35-55 in C57BL/6J mice and BMD eyedrops were applied daily. In the EAE retina, the number of RGCs was significantly decreased and this effect was suppressed with BMD treatment. Consistent with histological analyses, the visual impairment observed in EAE mice was inhibited with BMD treatment, indicating the functional significance of the neuroprotective effect of BMD. Furthermore, BMD increased the expression level of basic fibroblast growth factor in the EAE retina, particularly in Müller glial cells and RGCs. Our findings suggest that topical administration of BMD may be available for RGC protection during optic neuritis, as well as for glaucoma. PMID:25736951

  14. Irsogladine maleate, a gastric mucosal protectant, suppresses intestinal polyp development in Apc-mutant mice

    PubMed Central

    Onuma, Wakana; Tomono, Susumu; Miyamoto, Shinngo; Fujii, Gen; Hamoya, Takahiro; Fujimoto, Kyoko; Miyoshi, Noriyuki; Fukai, Fumio; Wakabayashi, Keiji; Mutoh, Michihiro

    2016-01-01

    This study aimed to identify gastric mucosal protectants that suppress intestinal tumorigenesis in a mouse model. We chose six gastric mucosal protectants (ecabet sodium hydrate, irsogladine maleate, rebamipide, sofalcone, teprenone and troxipide) and examined their effects on the activity of oxidative stress-related transcriptional factors, including AP-1, NF-jB, NRF2, p53 and STAT3, in Caco-2 cells using a luciferase reporter gene assay. Among the six protectants, irsogladine maleate clearly inhibited NF-jB and AP-1 transcriptional activity. Furthermore, the chemopreventive property of irsogladine maleate was examined in a Min mouse model of familial adenomatous polyposis. Treatment with irsogladine maleate at doses of 5 and 50 ppm significantly reduced the number of intestinal polyps to 69% and 66% of the untreated control value, respectively. In these polyps, mRNA levels of the downstream targets of NF-jB, such as IL-1β and IL-6, were decreased by irsogladine maleate treatment. Moreover, the levels of oxidative stress-related markers, reactive carbonyl species, in the livers of Min mice were clearly decreased following the administration of irsogladine maleate. This study demonstrated that irsogladine maleate suppresses intestinal polyp formation in Min mice partly through the NF-jB signaling pathway, thus reducing oxidative stress. PMID:26840084

  15. Quercetin Suppresses Twist to Induce Apoptosis in MCF-7 Breast Cancer Cells

    PubMed Central

    Ranganathan, Santhalakshmi; Halagowder, Devaraj; Sivasithambaram, Niranjali Devaraj

    2015-01-01

    Quercetin is a dietary flavonoid which exerts anti-oxidant, anti-inflammatory and anti-cancer properties. In this study, we investigated the anti-proliferative effect of quercetin in two breast cancer cell lines (MCF-7 and MDA-MB-231), which differed in hormone receptor. IC50 value (37μM) of quercetin showed significant cytotoxicity in MCF-7 cells, which was not observed in MDA-MB-231 cells even at 100μM of quercetin treatment. To study the response of cancer cells to quercetin, with respect to different hormone receptors, both the cell lines were treated with a fixed concentration (40μM) of quercetin. MCF-7 cells on quercetin treatment showed more apoptotic cells with G1 phase arrest. In addition, quercetin effectively suppressed the expression of CyclinD1, p21, Twist and phospho p38MAPK, which was not observed in MDA-MB-231 cells. To analyse the molecular mechanism of quercetin in exerting an apoptotic effect in MCF-7 cells, Twist was over-expressed and the molecular changes were observed after quercetin administration. Quercetin effectively regulated the expression of Twist, in turn p16 and p21 which induced apoptosis in MCF-7 cells. In conclusion, quercetin induces apoptosis in breast cancer cells through suppression of Twist via p38MAPK pathway. PMID:26491966

  16. Suppression of macrophage functions impairs skeletal muscle regeneration with severe fibrosis

    SciTech Connect

    Segawa, Masashi; Fukada, So-ichiro Yamamoto, Yukiko; Yahagi, Hiroshi; Kanematsu, Masanori; Sato, Masaki; Ito, Takahito; Uezumi, Akiyoshi; Hayashi, Shin'ichi; Miyagoe-Suzuki, Yuko; Takeda, Shin'ichi; Tsujikawa, Kazutake; Yamamoto, Hiroshi

    2008-10-15

    When damaged, skeletal muscle regenerates. In the early phases of regeneration, inflammatory cells such as neutrophils/granulocytes and macrophages infiltrate damaged muscle tissue. To reveal the roles of macrophages during skeletal muscle regeneration, we injected an antibody, AFS98 that blocks the binding of M-CSF to its receptor into normal mice that received muscle damages. Anti-M-CSF receptor administration suppressed macrophage but not neutrophil infiltration. Histological study indicated that suppression of macrophages function leads to the incomplete muscle regeneration. In addition FACS and immunohistochemical study showed that the acute lack of macrophages delayed proliferation and differentiation of muscle satellite cells in vivo. Furthermore, mice injected with the anti-M-CSF receptor antibody exhibited not only adipogenesis, but also significant collagen deposition, i.e., fibrosis and continuous high expression of connective tissue growth factor. Finally we indicate that these fibrosis markers were strongly enriched in CD90(+) cells that do not include myogenic cells. These results indicate that macrophages directly affect satellite cell proliferation and that a macrophage deficiency severely impairs skeletal muscle regeneration and causes fibrosis.

  17. Salidroside protects against kainic acid-induced status epilepticus via suppressing oxidative stress.

    PubMed

    Si, Pei-Pei; Zhen, Jun-Li; Cai, Yun-Lei; Wang, Wen-Jing; Wang, Wei-Ping

    2016-04-01

    There are numerous mechanisms by which the brain generates seizures. It is well known that oxidative stress plays a pivotal role in status epilepticus (SE). Salidroside (SDS) extracted from Rhodiola rosea L. shows multiple bioactive properties, such as neuroprotection and antioxidant activity in vitro and in vivo. This study explored the role of SDS in kainic acid (KA)-induced SE and investigated the underlying mechanism. Latency to SE increased in the SDS-pretreated mice compared to the KA group, while the percentage of incidence of SE was significantly reduced. These results suggested that pretreatment with SDS not only delayed SE, but it also decreased the incidence of SE induced by KA. KA increased MDA level and reduced the production of SOD and GSH at multiple timepoints after KA administration. SDS inhibited the change of MDA, SOD and GSH induced by KA prior to SE onset, indicating that SDS protects against KA-induced SE via suppressing oxidative stress. Based on these results, we investigated the possible molecular mechanism of SDS. Pretreatment with SDS reversed the KA-induced decrease in AMP-activated protein kinase (AMPK); increased the sirtuin 1 (SIRT1) deacetylase activity in KA-treated mice, which had no demonstrable effect on SIRT1 mRNA and protein; and suppressed the KA-induced increase in Ace-FoxO1. These results showed that AMPK/SIRT1/FoxO1 signaling is possibly the molecular mechanism of neuroprotection by SDS. PMID:26940236

  18. 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…

  19. Muscle mTORC1 suppression by IL-6 during cancer cachexia: a role for AMPK.

    PubMed

    White, James P; Puppa, Melissa J; Gao, Song; Sato, Shuichi; Welle, Stephen L; Carson, James A

    2013-05-15

    Although catabolic signaling has a well-established role in muscle wasting during cancer cachexia, the suppression of anabolic signaling also warrants further investigation. In cachectic tumor-bearing mice, circulating IL-6 levels are associated with suppressed muscle protein synthesis and mTORC1 signaling. We have found AMPK and IGF-I/insulin signaling, two well-known regulators of the mammalian target of rapamycin (mTOR), are altered with the progression of cachexia. How IL-6 can induce suppression of mTORC1 signaling remains to be established. The purpose of this study was to examine mTOR complex 1 (mTORC1) activation and regulation by IL-6 during cancer cachexia. IL-6 effects on mTOR activation were examined in Apc(Min/+) mouse skeletal muscle and C2C12 myotubes. Systemic IL-6 overexpression in Apc(Min/+) mice produced a dose-dependent suppression of mTOR signaling that corresponded to induction of STAT3 and AMPK phosphorylation. This result was also evident in IL-6-treated myotubes. Basal mTOR activation and mTOR responsiveness to glucose administration were suppressed in cachectic skeletal muscle. However, insulin induction of mTOR activity was maintained in IL-6-treated myotubes. Whereas IL-6 suppression of myotube mTOR activity was rescued by AMPK inhibition, inhibition of STAT3 signaling was not sufficient to rescue IL-6 suppression of mTOR activity. Last, treadmill exercise training was able to prevent IL-6-induced inhibition of mTOR signaling in Apc(Min/+) mice independently of activated STAT. In conclusion, we report dose-dependent suppression of mTOR activity by IL-6 and suppressed mTOR responsiveness to glucose administration in Apc(Min/+) mice. IL-6 suppression of mTOR activity was dependent on AMPK activation and independent of STAT signaling in myotubes. PMID:23531613

  20. Capsinoids suppress fat accumulation via lipid metabolism.

    PubMed

    Hong, Qin; Xia, Chen; Xiangying, Hu; Quan, Yuan

    2015-03-01

    Capsaicin, found in red peppers, has been reported to have anti‑obesity, anti‑hypertension, anti‑diabetes and anti‑inflammatory functions. In the present study, we determined the effect of non‑pungent capsinoids on the metabolism of adipocytes. We demonstrated that capsinoids suppressed fat accumulation in vivo and in vitro in mice. Liver, the main tissue of lipid metabolism, was treated by capsinoids, and HMG‑CoA reductase, CPT‑1, FAT/CD36 and GLUT4 were found to be increased significantly, which demonstrated promotion of the lipid metabolism in liver and adipose tissues. In addition, by adding capsinoids, the induced adipocytes also demonstrated significantly increased levels of HMG‑CoA reductase, CPT‑1, FAT/CD36 and GLUT4. Oil red O staining also demonstrated that capsinoids decreased fat accumulation in the adipocytes. In conclusion, these results indicate that capsinoids may be worth investigating as a potential cure for obesity. PMID:25421144

  1. Retinal Pigment Epithelial Cell Line Suppression of Phagolysosome Activation

    PubMed Central

    Taylor, AW; Dixit, S; Yu, J

    2015-01-01

    The eye is an immune privileged tissue with multiple mechanisms of immunosuppression to protect the light gathering tissues from the damage of inflammation. One of theses mechanisms involves retinal pigment epithelial cell suppression of phagosome activation in macrophages. The objective of this work is to determine if the human RPE cell line ARPE-19 is capable of suppressing the activation of the phagolysosome in macrophages in a manner similar to primary RPE. The conditioned media of RPE eyecups, sub-confluent, just confluent cultures, or established confluent cultures of human ARPE-19 cells were generated. These condition media were used to treat macrophages phagocytizing pHrodo bioparticles. After 24 hours incubation the macrophages were imaged by fluorescent microscopy, and fluorescence was measured. The fluorescent intensity is proportional to the amount of bioparticles phagocytized and are in an activated phagolysosome. The conditioned media of in situ mouse RPE eyecups significantly suppressed the activation of phagolysosome. The conditioned media from cultures of human ARPE-19 cells, grown to sub-confluence (50%) or grown to confluence had no effect on phagolysosome activation. In contrast, the conditioned media from established confluent cultures significantly suppressed phagolysosome activation. The neuropeptides alpha-MSH and NPY were depleted from the conditioned media of established confluent ARPE-19 cell cultures. This depleted conditioned media had diminished suppression of phagolysosome activation while promoting macrophage cell death. In addition, the condition media from cultures of ARPE-19 monolayers wounded with a bisecting scrape was diminished in suppressing phagolysosome activation. This technical report suggests that like primary RPE monolayers, established confluent cultures of ARPE-19 cells produce soluble factors that suppress the activation of macrophages, and can be used to study the molecular mechanisms of retinal immunobiology. In

  2. Suppression of Ischemia-Induced Hippocampal Pyramidal Neuron Death by Hyaluronan Tetrasaccharide through Inhibition of Toll-Like Receptor 2 Signaling Pathway.

    PubMed

    Sunabori, Takehiko; Koike, Masato; Asari, Akira; Oonuki, Yoji; Uchiyama, Yasuo

    2016-08-01

    Toll-like receptors (TLRs) are one of the main contributors that induce inflammation under tissue injury and infection. Because excessive inflammation can aggravate disease states, it is important to control inflammation at a moderate level. Herein, we show that hyaluronan (HA) oligomer, HA tetrasaccharide (HA4), could suppress the expression of proinflammatory cytokine IL-1β when stimulated with both TLR2- and TLR4-specific agonists in primary hippocampal neurons. To understand the effect of HA4 against ischemic insult, we performed hypoxic-ischemic (H/I) brain injury against neonatal mice. HA4 treatment significantly prevented hippocampal pyramidal cell death even 7 days after H/I injury, compared with the control mice. Although TLR2 and TLR4 are known as receptors for HA and also act as a receptor for inducing inflammation, only TLR2-deficient mice showed tolerance against H/I injury. Moreover, HA4 administration suppressed gliosis by inhibiting the activation of NF-κB, the downstream target of TLR2, which led to the suppression of IL-1β expression. Taken together, our data suggest that the neuroprotective effect of HA4 relies on antagonizing the TLR2/NF-κB pathway to reduce inflammation through suppressing the expression of proinflammatory cytokines after neonatal H/I brain injury. PMID:27301359

  3. Noise suppressing capillary separation system

    DOEpatents

    Yeung, E.S.; Xue, Y.

    1996-07-30

    A noise-suppressing capillary separation system for detecting the real-time presence or concentration of an analyte in a sample is provided. The system contains a capillary separation means through which the analyte is moved, a coherent light source that generates a beam which is split into a reference beam and a sample beam that irradiate the capillary, and a detector for detecting the reference beam and the sample beam light that transmits through the capillary. The laser beam is of a wavelength effective to be absorbed by a chromophore in the capillary. The system includes a noise suppressing system to improve performance and accuracy without signal averaging or multiple scans. 13 figs.

  4. PPemd26, an anthraquinone derivative, suppresses angiogenesis via inhibiting VEGFR2 signalling

    PubMed Central

    Huang, S W; Lien, J C; Kuo, S C; Huang, T F

    2014-01-01

    Background and Purpose Angiogenesis contributes to coronary heart disease, immune disorders and numerous malignancies. VEGF-A and its receptors (VEGFRs) play a pivotal role in regulating angiogenesis. In an effort to discover more effective inhibitors of tumour angiogenesis, we have analysed the actions of a novel anthraquinone derivative, PPemd26, and explored its anti-angiogenic mechanisms. Experimental Approach The effects of PPemd26 were evaluated in vitro using HUVEC cultures to assess proliferation, migration, invasion and tube formation. Immunoblotting was used to analyse phosphorylation of signalling kinases. Effects in vivo were assayed using Matrigel plug and xenograft mouse models. Key Results PPemd26 significantly inhibited VEGF-A-induced proliferation, migration, invasion and tube formation of HUVECs. PPemd26 also attenuated VEGF-A-induced microvessel sprouting from rat aortic rings ex vivo and suppressed formation of new blood vessels in implanted Matrigel plugs in models of angiogenesis in vivo. In addition, PPemd26 inhibited VEGF-A-induced phosphorylation of VEGFR2 and its downstream protein kinases including Akt, focal adhesion kinase, ERK and Src. Furthermore, systemic administration of PPemd26 suppressed the growth of s.c. xenografts of human colon carcinoma in vivo. Histochemical analysis of the xenografts revealed a marked reduction in stainingfor the vascular marker CD31 and proliferation marker Ki-67. Conclusions and Implications This study provides evidence that PPemd26 suppressed tumour angiogenesis through inhibiting VEGFR2 signalling pathways, suggesting that PPemd26 is a potential drug candidate for developing anti-angiogenic agents for the treatment of cancer and angiogenesis-related diseases. PMID:25091695

  5. Juggling reveals a decisional component to tactile suppression.

    PubMed

    Juravle, Georgiana; Spence, Charles

    2011-08-01

    Goal-directed movements are characterized by sensory suppression, that is, by decreased sensitivity to tactile stimuli. In the present study, we investigated tactile suppression during movement using a complex motor task: basic 3-ball juggling. It was hypothesized that a decrease in tactile sensitivity would be observed, together with a shift in participants' response bias while juggling. In a first experiment, participants had to detect a short gap in an otherwise continuous vibratory stimulus, which was delivered to their wrist under conditions of rest or else while juggling. In a second experiment, participants detected a short time gap in a continuous auditory signal, under the same conditions. In a final control experiment performed at rest, participants detected a short time gap in an auditory or tactile signal. In an additional condition, the detection of a gap in tactile stimulation was required under conditions of intramodal tactile interference. Participants were significantly less sensitive to detect a gap in tactile stimulation whilst juggling. Most importantly, these results were paired with a significant shift toward participants adopting a more conservative criterion when responding to the presence of the gap (i.e. they were more likely to say that a gap was not present). Taken together, these results demonstrate movement-related tactile sensory suppression and point to a decisional component in tactile suppression, thus suggesting that tactile suppression could already be triggered in the brain ahead of the motor command. PMID:21717097

  6. CDS - Database Administrator's Guide

    NASA Astrophysics Data System (ADS)

    Day, J. P.

    This guide aims to instruct the CDS database administrator in: o The CDS file system. o The CDS index files. o The procedure for assimilating a new CDS tape into the database. It is assumed that the administrator has read SUN/79.

  7. Vocational Education Administration Handbook.

    ERIC Educational Resources Information Center

    Ryals, Karen, Ed.; Doherty, Susan Sloan, Ed.

    This handbook for vocational administrators presents an overview of vocational education programs, services, and administrative structures in Alaska. The manual contains three parts. The first, brief section introduces secondary vocational education and lists its enabling legislation. The second part presents a detailed overview of vocational…

  8. Reframing Research Administration

    ERIC Educational Resources Information Center

    Cole, Sharon Stewart

    2010-01-01

    The purpose of this paper is to inform administrators and organizational leaders that a change in the support offered to faculty and the environment of research administration is desirable. This recommendation is supported by the results of a Delphi study that was undertaken to gather expert opinions and recommendations from research faculty…

  9. Justifying Educational Administration.

    ERIC Educational Resources Information Center

    Evers, Colin; Lakomski, Gabriele

    1993-01-01

    The traditional conceptions of science dominating educational administration are mistaken. Unacceptable epistemologies, like those implicit in logical positivism, justify knowledge solely in terms of empirical adequacy. An improved science of educational administration embraces a coherent global theory accounting for all the phenomena of human…

  10. 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…

  11. DIMENSIONS OF ADMINISTRATIVE PERFORMANCE.

    ERIC Educational Resources Information Center

    HEMPHILL, JOHN; AND OTHERS

    THE MAJOR OBJECTIVES WERE TO DEVELOP CRITERIA FOR THE EVALUATION OF SCHOOL ADMINISTRATION, TO DEFINE THE NATURE OF THE JOB, AND TO DEVELOP AN INSTRUMENT FOR THE SELECTION OF ADMINISTRATORS. THE ELEMENTARY SCHOOL PRINCIPAL WAS CHOSEN FOR THE STUDY BECAUSE OF THE HOST OF PROBLEMS RELATED TO THE CONDUCT OF AN EDUCATIONAL PROGRAM, INCLUDING THE…

  12. 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…

  13. Networked Administration Streamlines Operations.

    ERIC Educational Resources Information Center

    School Planning and Management, 1996

    1996-01-01

    An Iowa school district has retooled its computer systems for more standardized administration. In addition to administration, the district is doing inhouse databasing of financial accounting, and doing inhouse scheduling and grade reporting. A partnership with the Chamber of Commerce contributed $500,000 for the network system. (MLF)

  14. 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…

  15. 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…

  16. Administration for Student Development.

    ERIC Educational Resources Information Center

    Bergen, J. J., Ed.

    This collection of papers focuses on school administration and its relation to students. It is contended that toay's student matures earlier; has higher expectations; is more affluent; is more isolated from adults; is more critical and outspoken; and, therefore, must be heard by teachers and administrators. A related document is EA 001578.…

  17. Administration of Computer Resources.

    ERIC Educational Resources Information Center

    Franklin, Gene F.

    Computing at Stanford University has, until recently, been performed at one of five facilities. The Stanford hospital operates an IBM 370/135 mainly for administrative use. The university business office has an IBM 370/145 for its administrative needs and support of the medical clinic. Under the supervision of the Stanford Computation Center are…

  18. 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 rural…

  19. School Business Administration.

    ERIC Educational Resources Information Center

    Jordan, K. Forbis; Webb, L. Dean

    1986-01-01

    Reviews the societal and organizational changes affecting school business administration, describes major activities encompassed in the practice of school business administration, and reviews current literature specifically related to such activities as electronic data processing, fiscal planning and budgeting, purchasing and property management,…

  20. 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…

  1. Handbook for Alumni Administration.

    ERIC Educational Resources Information Center

    Webb, Charles H., Ed.

    A definitive look at the field of alumni administration is presented, noting that the subject has until now received little attention. The 34 chapters are divided into nine sections: an overview of alumni administration; alumni as an essential resource; people management; budget and records; programming; communications; alumni education programs…

  2. A Novel Ras Effector Pathway Found to Play Significant Role in Tumor Suppression | Poster

    Cancer.gov

    By Nancy Parrish, Staff Writer; photo by Richard Frederickson, Staff Photographer Normal cells have mechanisms to prevent the development of cancer. Among these is a type of tumor suppressor mechanism known as oncogene-induced senescence, or OIS, which halts the uncontrolled growth of cells caused by mutations in oncogenes. The oncogene Ras plays a crucial role in inducing OIS through a specific cascade of proteins, as reported in a recent article in Molecular and Cellular Biology by Jacqueline Salotti, Ph.D., and colleagues in the Eukaryotic Transcriptional Regulation Section of the Mouse Cancer Genetics Program, Center for Cancer Research (CCR).

  3. Mechanism and Physiologic Significance of the Suppression of Cholesterol Esterification in Human Interstitial Fluid.

    PubMed

    Miller, Norman E; Olszewski, Waldemar L; Miller, Irina P; Nanjee, Mahmud N

    2016-01-01

    Cholesterol esterification in high density lipoproteins (HDLs) by lecithin:cholesterol acyltransferase (LCAT) promotes unesterified cholesterol (UC) transfer from red cell membranes to plasma in vitro. However, it does not explain the transfer of UC from most peripheral cells to interstitial fluid in vivo, as HDLs in afferent peripheral lymph are enriched in UC. Having already reported that the endogenous cholesterol esterification rate (ECER) in lymph is only 5% of that in plasma, we have now explored the underlying mechanism. In peripheral lymph from 20 healthy men, LCAT concentration, LCAT activity (assayed using an optimized substrate), and LCAT specific activity averaged, respectively, 11.8, 10.3, and 84.9% of plasma values. When recombinant human LCAT was added to lymph, the increments in enzyme activity were similar to those when LCAT was added to plasma. Addition of apolipoprotein AI (apo AI), fatty acid-free albumin, Intralipid, or the d < 1.006 g/ml plasma fraction had no effect on ECER. During incubation of lymph plus plasma, the ECER was similar to that observed with buffer plus plasma. When lymph was added to heat-inactivated plasma, the ECER was 11-fold greater than with lymph plus buffer. Addition of discoidal proteoliposomes of apo AI and phosphatidycholine (PC) to lymph increased ECER 10-fold, while addition of apo AI/PC/UC disks did so by only six-fold. We conclude that the low ECER in lymph is due to a property of the HDLs, seemingly substrate inhibition of LCAT by excess cell-derived UC. This is reversed when lymph enters plasma, consequent upon redistribution of UC from lymph HDLs to plasma lipoproteins. PMID:27471469

  4. A Novel Ras Effector Pathway Found to Play Significant Role in Tumor Suppression | Poster

    Cancer.gov

    By Nancy Parrish, Staff Writer; photo by Richard Frederickson, Staff Photographer Normal cells have mechanisms to prevent the development of cancer. Among these is a type of tumor suppressor mechanism known as oncogene-induced senescence, or OIS, which halts the uncontrolled growth of cells caused by mutations in oncogenes. The oncogene Ras plays a crucial role in inducing OIS through a specific cascade of proteins, as reported in a recent article in Molecular and Cellular Biology by Jacqueline Salotti, Ph.D., and colleagues in the Eukaryotic Transcriptional Regulation Section of the Mouse Cancer Genetics Program, Center for Cancer Research (CCR).

  5. Mechanism and Physiologic Significance of the Suppression of Cholesterol Esterification in Human Interstitial Fluid

    PubMed Central

    Miller, Norman E.; Olszewski, Waldemar L.; Miller, Irina P.; Nanjee, Mahmud N.

    2016-01-01

    Cholesterol esterification in high density lipoproteins (HDLs) by lecithin:cholesterol acyltransferase (LCAT) promotes unesterified cholesterol (UC) transfer from red cell membranes to plasma in vitro. However, it does not explain the transfer of UC from most peripheral cells to interstitial fluid in vivo, as HDLs in afferent peripheral lymph are enriched in UC. Having already reported that the endogenous cholesterol esterification rate (ECER) in lymph is only 5% of that in plasma, we have now explored the underlying mechanism. In peripheral lymph from 20 healthy men, LCAT concentration, LCAT activity (assayed using an optimized substrate), and LCAT specific activity averaged, respectively, 11.8, 10.3, and 84.9% of plasma values. When recombinant human LCAT was added to lymph, the increments in enzyme activity were similar to those when LCAT was added to plasma. Addition of apolipoprotein AI (apo AI), fatty acid-free albumin, Intralipid, or the d < 1.006 g/ml plasma fraction had no effect on ECER. During incubation of lymph plus plasma, the ECER was similar to that observed with buffer plus plasma. When lymph was added to heat-inactivated plasma, the ECER was 11-fold greater than with lymph plus buffer. Addition of discoidal proteoliposomes of apo AI and phosphatidycholine (PC) to lymph increased ECER 10-fold, while addition of apo AI/PC/UC disks did so by only six-fold. We conclude that the low ECER in lymph is due to a property of the HDLs, seemingly substrate inhibition of LCAT by excess cell-derived UC. This is reversed when lymph enters plasma, consequent upon redistribution of UC from lymph HDLs to plasma lipoproteins. PMID:27471469

  6. Impact of Antimicrobial Lipopeptides from Bacillus sp. on Suppression of Fusarium Yellows of Tatsoi

    PubMed Central

    Yokota, Kenji; Hayakawa, Hiroshige

    2015-01-01

    Iturin A and surfactin are antimicrobial lipopeptides produced by antagonistic Bacillus spp. We herein demonstrated that both lipopeptides amended the soil-mediated suppression of the soil-borne disease, Fusarium yellows of tatsoi (Brassica rapa var. rosularis). Significant disease suppression was conferred by the amendments of purified iturin A or surfactin to soil. However, an excess amount of iturin A or surfactin to soil resulted in the loss of disease suppression activity. PMID:26118972

  7. Impact of Antimicrobial Lipopeptides from Bacillus sp. on Suppression of Fusarium Yellows of Tatsoi.

    PubMed

    Yokota, Kenji; Hayakawa, Hiroshige

    2015-01-01

    Iturin A and surfactin are antimicrobial lipopeptides produced by antagonistic Bacillus spp. We herein demonstrated that both lipopeptides amended the soil-mediated suppression of the soil-borne disease, Fusarium yellows of tatsoi (Brassica rapa var. rosularis). Significant disease suppression was conferred by the amendments of purified iturin A or surfactin to soil. However, an excess amount of iturin A or surfactin to soil resulted in the loss of disease suppression activity. PMID:26118972

  8. 47 CFR 54.715 - Administrative expenses of the Administrator.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 3 2011-10-01 2011-10-01 false Administrative expenses of the Administrator. 54.715 Section 54.715 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) UNIVERSAL SERVICE Administration § 54.715 Administrative expenses of the Administrator. (a) The annual administrative expenses...

  9. 47 CFR 54.715 - Administrative expenses of the Administrator.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Administrative expenses of the Administrator. 54.715 Section 54.715 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) UNIVERSAL SERVICE Administration § 54.715 Administrative expenses of the Administrator. (a) The annual administrative expenses...

  10. Head of Administration

    NASA Astrophysics Data System (ADS)

    2005-03-01

    Purpose and scope of the position: The main task is to provide efficient administrative services and advice to the Director General, Division Leaders and to staff members in the scientific and technical areas in the fields of financial planning and accounting, personnel management, purchasing, legal and contractual matters, information systems and building and site maintenance. As a member of the ESO Management the Head of Administration contributes essentially to the development of the overall policy, strategic planning, relations to the members of the personnel and maintains professional contacts at highest level outside the Organisation. ESO employs in total approximately 650 staff members and the Administration Division comprises the Administration at the Headquarters in Garching near Munich and the Administration in Santiago (Chile). The successful candidate will be supported by some 50 qualified staff members.

  11. Hematological and Immunological Changes Due to Short-term Oral Administration of Acephate.

    PubMed

    Sankhala, Laxmi N; Tripathi, Syamantak M; Bhavsar, S K; Thaker, Aswin M; Sharma, Pramod

    2012-05-01

    To evaluate immunotoxicological effects of environmental chemical, subacute toxicity of repeated (28 day) oral administration of acephate (Ace) in BALB/c mice was assessed. Thirty two (sixteen male and sixteen female) mice were divided into four different groups with each group containing eight (four male and four female) mice. Mice of Group C1 were administered normal saline only and served as control. Group T1 was given 1/40(th) of apparent LD(50) (ALD(50)) (8.78 mg/kg), and group T2 was put on 1/30(th) of ALD(50) [11.7 mg/kg], while group T3 received 1/20(th) of ALD(50) [17.55 mg/kg] of Ace suspended in normal saline. The blood samples were collected from mice after 28 days of oral administration and analyzed for hematological, biochemical, and immunological parameters. The study showed that hematological parameters (monocytes and granulocytes) remained unaffected except total leukocyte count and lymphocyte which were decreased highly significantly [P≤0.01] in mice of group T3 on the 28(th) day of experiment. Serum total protein (TP) and serum globulin decreased significantly in mice of treatment groups dose dependently; however, no significant change was seen in serum albumin. Progressive increase in live body weight of mice decreased significantly in extremely toxic group only while spleen:body weight ratio decreased significantly in dose-dependent manner. Furthermore, Ace produced suppressed humoral immune response and the delayed-type hypersensitivity response to Sheep red blood cells (SRBCs) was altered nonsignificantly. The results of this study describe the suppression of immune responses following exposure to Ace at low concentrations in experimental mice. PMID:22778515

  12. Suppression of splenic lymphocyte proliferation by Eucommia ulmoides and genipin.

    PubMed

    Yang, Gabsik; Kyoung Seo, Eun; Lee, Je-Hyun; Young Lee, Joo

    2015-04-01

    We investigated the modulation of innate and adaptive immune cell activation by Eucommia ulmoides Oliver extract (EUE) and its ingredient genipin. As an innate immunity indicator, the phagocytic activity of macrophages was determined by measuring engulfed, fluorescently labeled Escherichia coli. As a surrogate marker for the respective activation of cellular and humoral adaptive immunity, concanavalin A (Con A) and lipopolysaccharide (LPS) induction of primary splenocyte proliferation was assayed in in vitro and ex vivo systems. EUE and genipin suppressed the proliferation of primary splenic lymphocytes induced by Con A or LPS, but not macrophage phagocytosis. Oral administration of EUE and genipin to mice decreased splenic lymphocyte proliferation induced by Con A or LPS. These results revealed that E. ulmoides and genipin suppressed cellular and humoral adaptive immunity, and they suggest that E. ulmoides and genipin are promising candidates for immunosuppressive drugs that target diseases that involve excessive activation of adaptive immunity. PMID:25879499

  13. miR-340 suppresses glioblastoma multiforme.

    PubMed

    Huang, Daquan; Qiu, Shuwei; Ge, Ruiguang; He, Lei; Li, Mei; Li, Yi; Peng, Ying

    2015-04-20

    Deregulation of microRNAs (miRs) contributes to tumorigenesis. Down-regulation of miR-340 is observed in multiple types of cancers. However, the biological function of miR-340 in glioblastoma multiforme (GBM) remains largely unknown. In the present study, we demonstrated that expression of miR-340 was downregulated in both glioma cell lines and tissues. Survival of GBM patients with high levels of miR-340 was significantly extended in comparison to patients expressing low miR-340 levels. Biological functional experiments showed that the restoration of miR-340 dramatically inhibited glioma cell proliferation, induced cell-cycle arrest and apoptosis, suppressed cell motility and promoted autophagy and terminal differentiation. Mechanistic studies disclosed that, miR-340 over-expression suppressed several oncogenes including p-AKT, EZH2, EGFR, BMI1 and XIAP. Furthermore, ROCK1 was validated as a direct functional target miR-340 and silencing of ROCK1 phenocopied the anti-tumor effect of mR-340. Our findings indicate an important role of miR-340 as a glioma killer, and suggest a potential prognosis biomarker and therapeutic target for GBM. PMID:25831237

  14. Inhibition of SIRT2 suppresses hepatic fibrosis.

    PubMed

    Arteaga, Maribel; Shang, Na; Ding, Xianzhong; Yong, Sherri; Cotler, Scott J; Denning, Mitchell F; Shimamura, Takashi; Breslin, Peter; Lüscher, Bernhard; Qiu, Wei

    2016-06-01

    Liver fibrosis can progress to cirrhosis and result in serious complications of liver disease. The pathogenesis of liver fibrosis involves the activation of hepatic stellate cells (HSCs), the underlying mechanisms of which are not fully known. Emerging evidence suggests that the classic histone deacetylases play a role in liver fibrosis, but the role of another subfamily of histone deacetylases, the sirtuins, in the development of hepatic fibrosis remains unknown. In this study, we found that blocking the activity of sirtuin 2 (SIRT2) by using inhibitors or shRNAs significantly suppressed fibrogenic gene expression in HSCs. We further demonstrated that inhibition of SIRT2 results in the degradation of c-MYC, which is important for HSC activation. In addition, we discovered that inhibition of SIRT2 suppresses the phosphorylation of ERK, which is critical for the stabilization of c-MYC. Moreover, we found that Sirt2 deficiency attenuates the hepatic fibrosis induced by carbon tetrachloride (CCl4) and thioacetamide (TAA). Furthermore, we showed that SIRT2, p-ERK, and c-MYC proteins are all overexpressed in human hepatic fibrotic tissues. These data suggest a critical role for the SIRT2/ERK/c-MYC axis in promoting hepatic fibrogenesis. Inhibition of the SIRT2/ERK/c-MYC axis represents a novel strategy to prevent and to potentially treat liver fibrosis and cirrhosis. PMID:27125275

  15. A Testa Extract of Black Soybean (Glycine max (L.) Merr.) suppresses Adipogenic Activity of Adipose-derived Stem Cells.

    PubMed

    Jeon, Younmi; Lee, Myoungsook; Cheon, Yong-Pil

    2015-12-01

    Black soybean teata is helpful to preventing obesity through enhancing energy expenditure and suppressing accumulation in mesenteric adipose tissue. The ethanol testa-extract of Cheongja #3 black soybean (ETCBS) is also have similar effects on obesity. So far, it is not clear whether the ethanol testa extract of black soybean can have effect on the characters of subcutaneous adipose stem cells such as proliferation, activity, and adipogenicity. The doubling time was different between subcutaneous adipose-derived stem (ADS) and visceral ADS cells. By the in vitro culture and passage, the doubling time was increased both of them. The shape was not different between groups and their passages were not cause the change of shapes. In the case of visceral ADS cells, the doubling time was 62.3 h or 40.3 h in control or high fat diet administrated mice, respectively, but not modified in subcutaneous ADS cells. ETCBS administration caused of increased the doubling time from 62.3 h to 84.2 h. ETCBS had suppressive effects on the cellular activity of subcutaneous ADS cells. The intensity of Oil Red O staining was very faint in 100 and 200 μg/mL ETCBS treated groups. The amounts of accumulated triglyceride were also significantly low in 100 and 200 μg/mL treated groups. From these results we know that the doubling times and the effects of ETCBS are different by the anatomical origin of ADS cells. It also suggested that ETCBS may suppress the differentiation of subcutaneous ADS cells into the precursors and maturing of adipocytes. PMID:26973975

  16. Chronic binge alcohol consumption does not diminish effectiveness of continuous antiretroviral suppression of viral load in SIV-infected macaques

    PubMed Central

    Molina, Patricia E.; Amedee, Angela M.; Veazey, Ron; Dufour, Jason; Volaufova, Julia; Bagby, Gregory J.; Nelson, Steve

    2015-01-01

    Background Alcohol use disorders (AUD) are a frequent comorbidity in a large percentage of people living with HIV/AIDS (PLWHA). PLWHA with comorbid AUDs are consistently found to perform poorly at most levels of the HIV treatment cascade, resulting in a higher likelihood of virologic non-suppression. This has been partly attributed to lower rates of persistence with and adherence to antiretroviral therapies (ART). Focus groups of in-care PLWHA identify the need to suspend ART on drinking days because of the potential for toxicity and/or lack of therapeutic effectiveness. The aim of this study was to examine whether chronic binge alcohol (CBA) consumption decreases the effectiveness of uninterrupted ART, specifically that of nucleoside reverse transcriptase inhibitors (NRTI) tenofovir and emtricitabine in suppressing viral replication, or results in drug toxicity in simian immunodeficiency virus (SIV) infected rhesus macaques. Methods Daily CBA or isocaloric sucrose (SUC) administration was initiated three months prior to intrarectal SIVmac251 inoculation and continued throughout the study period. ART was initiated 2.5 months after SIV infection and continued through the study period. Results CBA administration did not prevent or delay the ART-mediated reduction in viral load. Following ART, circulating levels of total protein and creatinine were significantly higher than baseline values in both sucrose- and alcohol-treated animals, but still within a normal range. No evidence of ART toxicity was observed in either CBA- or SUC-administered macaques. Conclusions These findings indicate that CBA does not attenuate effectiveness of NRTI suppression of viral load, nor does it appear to interact with NRTI to produce toxicity during the initial 2 months of treatment. We conclude that while efforts to reduce AUD in PLWHA should be a priority, and that counseling on the importance of adherence to ART even on drinking days should also be promoted. PMID:25257285

  17. Diversity and Activity of Lysobacter Species from Disease Suppressive Soils

    PubMed Central

    Gómez Expósito, Ruth; Postma, Joeke; Raaijmakers, Jos M.; De Bruijn, Irene

    2015-01-01

    The genus Lysobacter includes several species that produce a range of extracellular enzymes and other metabolites with activity against bacteria, fungi, oomycetes, and nematodes. Lysobacter species were found to be more abundant in soil suppressive against the fungal root pathogen Rhizoctonia solani, but their actual role in disease suppression is still unclear. Here, the antifungal and plant growth-promoting activities of 18 Lysobacter strains, including 11 strains from Rhizoctonia-suppressive soils, were studied both in vitro and in vivo. Based on 16S rRNA sequencing, the Lysobacter strains from the Rhizoctonia-suppressive soil belonged to the four species Lysobacter antibioticus, Lysobacter capsici, Lysobacter enzymogenes, and Lysobacter gummosus. Most strains showed strong in vitro activity against R. solani and several other pathogens, including Pythium ultimum, Aspergillus niger, Fusarium oxysporum, and Xanthomonas campestris. When the Lysobacter strains were introduced into soil, however, no significant and consistent suppression of R. solani damping-off disease of sugar beet and cauliflower was observed. Subsequent bioassays further revealed that none of the Lysobacter strains was able to promote growth of sugar beet, cauliflower, onion, and Arabidopsis thaliana, either directly or via volatile compounds. The lack of in vivo activity is most likely attributed to poor colonization of the rhizosphere by the introduced Lysobacter strains. In conclusion, our results demonstrated that Lysobacter species have strong antagonistic activities against a range of pathogens, making them an important source for putative new enzymes and antimicrobial compounds. However, their potential role in R. solani disease suppressive soil could not be confirmed. In-depth omics'–based analyses will be needed to shed more light on the potential contribution of Lysobacter species to the collective activities of microbial consortia in disease suppressive soils. PMID:26635735

  18. Diversity and Activity of Lysobacter Species from Disease Suppressive Soils.

    PubMed

    Gómez Expósito, Ruth; Postma, Joeke; Raaijmakers, Jos M; De Bruijn, Irene

    2015-01-01

    The genus Lysobacter includes several species that produce a range of extracellular enzymes and other metabolites with activity against bacteria, fungi, oomycetes, and nematodes. Lysobacter species were found to be more abundant in soil suppressive against the fungal root pathogen Rhizoctonia solani, but their actual role in disease suppression is still unclear. Here, the antifungal and plant growth-promoting activities of 18 Lysobacter strains, including 11 strains from Rhizoctonia-suppressive soils, were studied both in vitro and in vivo. Based on 16S rRNA sequencing, the Lysobacter strains from the Rhizoctonia-suppressive soil belonged to the four species Lysobacter antibioticus, Lysobacter capsici, Lysobacter enzymogenes, and Lysobacter gummosus. Most strains showed strong in vitro activity against R. solani and several other pathogens, including Pythium ultimum, Aspergillus niger, Fusarium oxysporum, and Xanthomonas campestris. When the Lysobacter strains were introduced into soil, however, no significant and consistent suppression of R. solani damping-off disease of sugar beet and cauliflower was observed. Subsequent bioassays further revealed that none of the Lysobacter strains was able to promote growth of sugar beet, cauliflower, onion, and Arabidopsis thaliana, either directly or via volatile compounds. The lack of in vivo activity is most likely attributed to poor colonization of the rhizosphere by the introduced Lysobacter strains. In conclusion, our results demonstrated that Lysobacter species have strong antagonistic activities against a range of pathogens, making them an important source for putative new enzymes and antimicrobial compounds. However, their potential role in R. solani disease suppressive soil could not be confirmed. In-depth omics'-based analyses will be needed to shed more light on the potential contribution of Lysobacter species to the collective activities of microbial consortia in disease suppressive soils. PMID:26635735

  19. Central injection of CDP-choline suppresses serum ghrelin levels while increasing serum leptin levels in rats.

    PubMed

    Kiyici, Sinem; Basaran, Nesrin Filiz; Cavun, Sinan; Savci, Vahide

    2015-10-01

    In this study we aimed to test central administration of CDP-choline on serum ghrelin, leptin, glucose and corticosterone levels in rats. Intracerebroventricular (i.c.v.) 0.5, 1.0 and 2.0 µmol CDP-choline and saline were administered to male Wistar-Albino rats. For the measurement of serum leptin and ghrelin levels, blood samples were obtained baseline and at 5, 15, 30, 60 and 120 min following i.c.v. CDP-choline injection. Equimolar doses of i.c.v. choline (1.0 µmol) and cytidine (1.0 µmol) were administered and measurements were repeated throughout the second round of the experiment. Atropine (10 µg) and mecamylamine (50 µg) were injected intracerebroventricularly prior to CDP-choline and measurements repeated in the third round of the experiment. After 1 µmol CDP-choline injection, serum ghrelin levels were suppressed significantly at 60 min (P=0.025), whereas serum leptin levels were increased at 60 and 120 min (P=0.012 and P=0.017 respectively). CDP-choline injections also induced a dose- and time-dependent increase in serum glucose and corticosterone levels. The effect of choline on serum leptin and ghrelin levels was similar with CDP-choline while no effect was seen with cytidine. Suppression of serum ghrelin levels was eliminated through mecamylamine pretreatment while a rise in leptin was prevented by both atropine and mecamylamine pretreatments. In conclusion; centrally injected CDP-choline suppressed serum ghrelin levels while increasing serum leptin levels. The observed effects following receptor antagonist treatment suggest that nicotinic receptors play a role in suppression of serum ghrelin levels,whereas nicotinic and muscarinic receptors both play a part in the increase of serum leptin levels. PMID:26162700

  20. Zinc L-carnosine protects colonic mucosal injury through induction of heat shock protein 72 and suppression of NF-kappaB activation.

    PubMed

    Odashima, Masaru; Otaka, Michiro; Jin, Mario; Wada, Isao; Horikawa, Youhei; Matsuhashi, Tamotsu; Ohba, Reina; Hatakeyama, Natsumi; Oyake, Jinko; Watanabe, Sumio

    2006-11-10

    In this study, we investigated the effects of zinc L-carnosine, an anti-ulcer drug, on acetic acid-induced colonic mucosal injury and the correlation of these effects with expression of 72-kDa heat shock proteins (HSP72) and nuclear factor kappa B (NF-kappaB) activation in rat colonic mucosa in vivo. After intrarectal administration of zinc L-carnosine, the rats received intrarectal infusion of 5% acetic acid (1 ml). The colonic mucosal damage was evaluated by macroscopic assessments 24 h after the intrarectal infusion of acetic acid. Expression of HSP72 in rat colonic mucosa was evaluated by Western blot analysis before and after zinc L-carnosine administration. NF-kappaB activation was evaluated by electrophoretic mobility shift assays (EMSA). Zinc L-carnosine inhibited visible damage in rat colonic mucosa by acetic acid. Expression of HSP72 was significantly increased at 6 h after zinc L-carnosine administration. Furthermore, NF-kappaB activation in colonic mucosa was suppressed 6 h after zinc L-carnosine treatment. These results suggested that zinc L-carnosine protects the colonic mucosa against acetic acid by induction of HSP72 and suppression of NF-kappaB activation and zinc L-carnosine may be a novel therapeutic agent for the therapy of inflammatory bowel disease. PMID:16949620

  1. Withaferin-A suppress AKT induced tumor growth in colorectal cancer cells

    PubMed Central

    Suman, Suman; Das, Trinath P.; Sirimulla, Suman; Alatassi, Houda; Ankem, Murali K.; Damodaran, Chendil

    2016-01-01

    The oncogenic activation of AKT gene has emerged as a key determinant of the aggressiveness of colorectal cancer (CRC); hence, research has focused on targeting AKT signaling for the treatment of advanced stages of CRC. In this study, we explored the anti-tumorigenic effects of withaferin A (WA) on CRC cells overexpressing AKT in preclinical (in vitro and in vivo) models. Our results indicated that WA, a natural compound, resulted in significant inhibition of AKT activity and led to the inhibition of cell proliferation, migration and invasion by downregulating the epithelial to mesenchymal transition (EMT) markers in CRC cells overexpressing AKT. The oral administration of WA significantly suppressed AKT-induced aggressive tumor growth in a xenograft model. Molecular analysis revealed that the decreased expression of AKT and its downstream pro-survival signaling molecules may be responsible for tumor inhibition. Further, significant inhibition of some important EMT markers, i.e., Snail, Slug, β-catenin and vimentin, was observed in WA-treated human CRC cells overexpressing AKT. Significant inhibition of micro-vessel formation and the length of vessels were evident in WA-treated tumors, which correlated with a low expression of the angiogenic marker RETIC. In conclusion, the present study emphasizes the crucial role of AKT activation in inducing cell proliferation, angiogenesis and EMT in CRC cells and suggests that WA may overcome AKT-induced cell proliferation and tumor growth in CRC. PMID:26883103

  2. Withaferin-A suppress AKT induced tumor growth in colorectal cancer cells.

    PubMed

    Suman, Suman; Das, Trinath P; Sirimulla, Suman; Alatassi, Houda; Ankem, Murali K; Damodaran, Chendil

    2016-03-22

    The oncogenic activation of AKT gene has emerged as a key determinant of the aggressiveness of colorectal cancer (CRC); hence, research has focused on targeting AKT signaling for the treatment of advanced stages of CRC. In this study, we explored the anti-tumorigenic effects of withaferin A (WA) on CRC cells overexpressing AKT in preclinical (in vitro and in vivo) models. Our results indicated that WA, a natural compound, resulted in significant inhibition of AKT activity and led to the inhibition of cell proliferation, migration and invasion by downregulating the epithelial to mesenchymal transition (EMT) markers in CRC cells overexpressing AKT. The oral administration of WA significantly suppressed AKT-induced aggressive tumor growth in a xenograft model. Molecular analysis revealed that the decreased expression of AKT and its downstream pro-survival signaling molecules may be responsible for tumor inhibition. Further, significant inhibition of some important EMT markers, i.e., Snail, Slug, β-catenin and vimentin, was observed in WA-treated human CRC cells overexpressing AKT. Significant inhibition of micro-vessel formation and the length of vessels were evident in WA-treated tumors, which correlated with a low expression of the angiogenic marker RETIC. In conclusion, the present study emphasizes the crucial role of AKT activation in inducing cell proliferation, angiogenesis and EMT in CRC cells and suggests that WA may overcome AKT-induced cell proliferation and tumor growth in CRC. PMID:26883103

  3. Serving the Space Administration

    ERIC Educational Resources Information Center

    Campbell, Jack E.; Thompson, Arthur W.

    1974-01-01

    The purpose of the current program was to establish an upward mobility program that afforded employees an opportunity to improve their credibility in job opportunity selection under the directives of the National Aeronautics and Space Administration. (Author/RK)

  4. Copyright Implications for Administrators.

    ERIC Educational Resources Information Center

    Simpson, Carol Mann

    1994-01-01

    Discusses copyright compliance policies for school administrators and the librarian's role in policy implementation. Topics addressed include fines; court litigation; monitoring compliance; training sessions for teachers and staff; computer software audits; and sources for more information. (LRW)

  5. Goldstone (GDSCC) administrative computing

    NASA Technical Reports Server (NTRS)

    Martin, H.

    1981-01-01

    The GDSCC Data Processing Unit provides various administrative computing services for Goldstone. Those activities, including finance, manpower and station utilization, deep-space station scheduling and engineering change order (ECO) control are discussed.

  6. Confrontation and Administrative Response

    ERIC Educational Resources Information Center

    Auerbach, Arnold J.

    1969-01-01

    Describes some of the sociological and psychological effects of organizational conflict and offers 10 operational principles to guide public administrators of schools and social agencies in meeting the confrontation tactics of activist groups. (JH)

  7. One for the Administrators

    ERIC Educational Resources Information Center

    American School and University, 1978

    1978-01-01

    Earth berms, a heavily insulated roof, and a narrow band of thermal pane windows, save energy at the administrative headquarters of the Anoka Hennepin school district in Coon Rapids, a suburb of Minneapolis, Minnesota. (Author/MLF)

  8. The Purchasing Administrator.

    ERIC Educational Resources Information Center

    Ferguson, Joyce E.

    1985-01-01

    Discusses the professional purchasing administrator's most common areas of responsibility: (1) staffing the department, (2) maintaining professional objectivity in vendor relationships, (3) following bidding policies, (4) receiving user input and feedback, and (5) seeking local equipment service and maintenance. (MLF)

  9. Introducing Public Administration

    ERIC Educational Resources Information Center

    Stein, Jay W.

    1975-01-01

    The use of documents and the analysis of definitions are recommended as a means for adding zest to an introduction to public administration course to obtain student interest and motivation. (Author/ND)

  10. Distracted by cues for suppressed memories.

    PubMed

    Hertel, Paula T; Hayes, Jeffrey A

    2015-06-01

    We examined the potential cost of practicing suppression of negative thoughts on subsequent performance in an unrelated task. Cues for previously suppressed and unsuppressed (baseline) responses in a think/no-think procedure were displayed as irrelevant flankers for neutral words to be judged for emotional valence. These critical flankers were homographs with one negative meaning denoted by their paired response during learning. Responses to the targets were delayed when suppression cues (compared with baseline cues and new negative homographs) were used as flankers, but only following direct-suppression instructions and not when benign substitutes had been provided to aid suppression. On a final recall test, suppression-induced forgetting following direct suppression and the flanker task was positively correlated with the flanker effect. Experiment 2 replicated these findings. Finally, valence ratings of neutral targets were influenced by the valence of the flankers but not by the prior role of the negative flankers. PMID:25904596

  11. Suppression effects on musical and verbal memory.

    PubMed

    Schendel, Zachary A; Palmer, Caroline

    2007-06-01

    Three experiments contrasted the effects of articulatory suppression on recognition memory for musical and verbal sequences. In Experiment 1, a standard/comparison task was employed, with digit or note sequences presented visually or auditorily while participants remained silent or produced intermittent verbal suppression (saying "the") or musical suppression (singing "la"). Both suppression types decreased performance by equivalent amounts, as compared with no suppression. Recognition accuracy was lower during suppression for visually presented digits than during that for auditorily presented digits (consistent with phonological loop predictions), whereas accuracy was equivalent for visually presented notes and auditory tones. When visual interference filled the retention interval in Experiment 2, performance with visually presented notes but not digits was impaired. Experiment 3 forced participants to translate visually presented music sequences by presenting comparison sequences auditorily. Suppression effects for visually presented music resembled those for digits only when the recognition task required sensory translation of cues. PMID:17848022

  12. Experience with IBS-suppression lattice in RHIC

    SciTech Connect

    Litvinenko,V.N.; Luo, Y.; Ptitsyn, V.; Satogata, T.; Tepikian, S.; Bai, M.; Bruno, D.; Cameron, P.; Connolly, R.; Della Penna, A.; Drees, A.; Fedotov, A.; Ganetis, G.; Hoff, L.; Louie, W.; Malitsky, N.; Marr, G.; Marusic, A.; Montag, C.; Pilat, F.; Roser, T.; Trbojevic, D.; Tsoupas, N.

    2008-06-23

    An intra-beam scattering (IBS) is the limiting factor of the luminosity lifetime for RHIC operating with heavy ions. In order to suppress the IBS we designed and implemented new lattice with higher betatron tunes. This lattice had been developed during last three years and had been used for gold ions in yellow ring of the RHIC during d-Au part of the RHIC Run-8. The use of this lattice allowed both significant increases in the luminosity lifetime and the luminosity levels via reduction of beta-stars in the IPS. In this paper we report on the development, the tests and the performance of IBS-suppression lattice in RHIC, including the resulting increases in the peak and the average luminosity. We also report on our plans for future steps with the IBS suppression.

  13. Vibration suppression of composite laminated plate with nonlinear energy sink

    NASA Astrophysics Data System (ADS)

    Zhang, Ye-Wei; Zhang, Hao; Hou, Shuai; Xu, Ke-Fan; Chen, Li-Qun

    2016-06-01

    The composite laminated plate is widely used in supersonic aircraft. So, there are many researches about the vibration suppression of composite laminated plate. In this paper, nonlinear energy sink (NES) as an effective method to suppress vibration is studied. The coupled partial differential governing equations of the composite laminated plate with the nonlinear energy sink (NES) are established by using the Hamilton principle. The fourth-order Galerkin discrete method is used to truncate the partial differential equations, which are solved by numerical integration method. Meanwhile study about the precise effectiveness of the nonlinear energy sink (NES) by discussing the different installation location of the nonlinear energy sink (NES) at the same speed. The results indicate that the nonlinear energy sink (NES) can significantly suppress the severe vibration of the composite laminated plate with speed wind loadings in to protect the composite laminated plate from excessive vibration.

  14. Oral administration of FAK inhibitor TAE226 inhibits the progression of peritoneal dissemination of colorectal cancer

    SciTech Connect

    Hao, Hui-fang; Takaoka, Munenori; Bao, Xiao-hong; Wang, Zhi-gang; Tomono, Yasuko; Sakurama, Kazufumi; Ohara, Toshiaki; Fukazawa, Takuya; Yamatsuji, Tomoki; Fujiwara, Toshiyoshi; Naomoto, Yoshio

    2012-07-13

    Highlights: Black-Right-Pointing-Pointer A novel FAK inhibitor TAE226 suppressed FAK activity in HCT116 colon cancer cells. Black-Right-Pointing-Pointer TAE226 suppressed proliferation and migration, with a modest effect on adhesion. Black-Right-Pointing-Pointer Silencing of FAK by siRNA made no obvious difference on cancer cell attachment. Black-Right-Pointing-Pointer TAE226 treatment suppressed the progression of peritoneal dissemination. Black-Right-Pointing-Pointer Oral administration of TAE226 prolonged the survival of tumor-bearing mice. -- Abstract: Peritoneal dissemination is one of the most terrible types of colorectal cancer progression. Focal adhesion kinase (FAK) plays a crucial role in the biological processes of cancer, such as cell attachment, migration, proliferation and survival, all of which are essential for the progression of peritoneal dissemination. Since we and other groups have reported that the inhibition of FAK activity exhibited a potent anticancer effect in several cancer models, we hypothesized that TAE226, a novel ATP-competitive tyrosine kinase inhibitor designed to target FAK, can prevent the occurrence and progression of peritoneal dissemination. In vitro, TAE226 greatly inhibited the proliferation and migration of HCT116 colon cancer cells, while their adhesion on the matrix surface was minimally inhibited when FAK activity and expression was suppressed by TAE226 and siRNA. In vivo, when HCT116 cells were intraperitoneally inoculated in mice, the cells could attach to the peritoneum and begin to grow within 24 h regardless of the pretreatment of cells with TAE226 or FAK-siRNA, suggesting that FAK is not essential, at least for the initial integrin-matrix contact. Interestingly, the treatment of mice before and after inoculation significantly suppressed cell attachment to the peritoneum. Furthermore, oral administration of TAE226 greatly reduced the size of disseminated tumors and prolonged survival in tumor-bearing mice. Taken

  15. Hyperadrenergic borderline hypertension is characterized by suppressed aggression.

    PubMed

    Perini, C; Müller, F B; Rauchfleisch, U; Battegay, R; Bühler, F R

    1986-01-01

    The effect of suppressed aggression on the reactivity of the sympathetic nervous and cardiovascular systems has been investigated in two groups of 24 subjects each with either borderline hypertension or normal blood pressure and no family history of hypertension. Groups were matched for sex and age (18-24 years). Suppressed aggression was defined by the newly standardized Rosenzweig Picture-Frustration test, a projective method assessing the reaction to everyday stress. Responses of blood pressure, heart rate, and venous plasma catecholamines were measured before and during application of mental stressors, using the Stroop color-word conflict test and mental arithmetic. In an analysis of covariance for repeated measures, which eliminates the influence of anxiety, borderline hypertensive subjects with suppressed aggression had significantly higher heart rates and diastolic blood pressures and a greater noradrenaline reactivity than borderline hypertensive subjects without suppressed aggression or normotensive subjects. Suppressed aggression may lead to a hyperadrenergic form of early borderline hypertension and thereby contribute to higher blood pressure. PMID:2427886

  16. Organic and Inorganic Nitrogen Amendments to Soil as Nematode Suppressants

    PubMed Central

    Rodríguez-Kábana, R.

    1986-01-01

    Inorganic fertilizers containing ammoniacal nitrogen or formulations releasing this form of N in the soil are most effective for suppressing nematode populations. Anhydrous ammonia has been shown to reduce soil populations of Tylenchorhynchus claytoni, Helicotylenchus dihystera, and Heterodera glycines. The rates required to obtain significant suppression of nematode populations are generally in excess of 150 kg N/ha. Urea also suppresses several nematode species, including Meloidogyne spp., when applied at rates above 300 kg N/ha. Additional available carbon must be provided with urea to permit soil microorganisms to metabolize excess N and avoid phytotoxic effects. There is a direct relation between the amount of "protein" N in organic amendments and their effectiveness as nematode population suppressants. Most nematicidal amendments are oil cakes, or animal excrements containing 2-7% (w:w) N; these materials are effective at rates of 4-10 t/ha. Organic soil amendments containing mucopolysaccharides (e.g., mycelial wastes, chitinous matter) are also effective nematode suppressants. PMID:19294153

  17. Interaction between noise suppression and inhomogeneity correction in MRI

    NASA Astrophysics Data System (ADS)

    Montillo, Albert; Udupa, Jayaram K.; Axel, Leon; Metaxas, Dimitri N.

    2003-05-01

    While cardiovascular disease is the leading cause of death in most developed countries, SPAMM-MRI can reduce morbidity by facilitating patient diagnosis. An image analysis method with a high degree of automation is essential for clinical adoption of SPAMM-MRI. The degree of this automation is dependent on the amount of thermal noise and surface coil-induced intensity inhomogeneity that can be removed from the images. An ideal noise suppression algorithm removes thermal noise yet retains or enhances the strength of the edges of salient structures. In this paper, we quantitatively compare and rank several noise suppression algorithms in images from both normal and diseased subjects using measures of the residual noise and edge strength and the statistical significance levels and confidence intervals of these measures. We also investigate the interrelationship between inhomogeneity correction and noise suppression algorithms and compare the effect of the ordering of these algorithms. The variance of thermal noise does not tend to change with position, however, inhomogeneity correction increases noise variance in deep thoracic regions. We quantify the degree to which an inhomogeneity estimate can improve noise suppression and how well noise suppression can facilitate the identification of homogeneous tissue regions and thereby, assist in inhomogeneity correction.

  18. Attenuation of antigenic immunogenicity by kynurenine, a novel suppressive adjuvant.

    PubMed

    Duan, Zhiqing; Duan, Yunqing; Lei, Huangui; Hu, Ningzhu; Shi, Jiandong; Shen, Dong; Wang, Xi; Hu, Yunzhang

    2014-01-01

    A novel therapeutic strategy is required for autoimmune diseases characterized by the production of autoantibody, because current clinical strategies have limitations. Vaccination against autoimmune diseases is a feasible strategy because vaccines induce immune response memory and the antigen specificity. However, no suitable adjuvant is available to direct the immune response toward tolerance or suppression. In the current study, we evaluated whether kynurenine (Kyn) could serve as a novel suppressive adjuvant to decrease the humoral immune responses against hepatitis A virus (HAV) in the ICR mouse model in vivo and lipopolysaccharide (LPS) in B cells in vitro. The underlying mechanisms of Kyn-mediated suppression of LPS-induced IgM responses were explored. The results showed that Kyn significantly decreased HAV immunogenicity when co-administered with HAV, and that Kyn (100 μM/1000 μM) impaired IgM generation compared with that induced by LPS alone. We also demonstrated that microRNA30b (miR30b) played a critical role in the process of Kyn-mediated suppression of IgM responses induced by LPS, and that Bach2, a transcriptional repressor of B cell terminal differentiation, was a novel target of miR30b. These findings suggest that Kyn can serve as a novel and effective suppressive adjuvant for vaccines. PMID:24583631

  19. Attenuation of antigenic immunogenicity by kynurenine, a novel suppressive adjuvant

    PubMed Central

    Duan, Zhiqing; Duan, Yunqing; Lei, Huangui; Hu, Ningzhu; Shi, Jiandong; Shen, Dong; Wang, Xi; Hu, Yunzhang

    2014-01-01

    A novel therapeutic strategy is required for autoimmune diseases characterized by the production of autoantibody, because current clinical strategies have limitations. Vaccination against autoimmune diseases is a feasible strategy because vaccines induce immune response memory and the antigen specificity. However, no suitable adjuvant is available to direct the immune response toward tolerance or suppression. In the current study, we evaluated whether kynurenine (Kyn) could serve as a novel suppressive adjuvant to decrease the humoral immune responses against hepatitis A virus (HAV) in the ICR mouse model in vivo and lipopolysaccharide (LPS) in B cells in vitro. The underlying mechanisms of Kyn-mediated suppression of LPS-induced IgM responses were explored. The results showed that Kyn significantly decreased HAV immunogenicity when co-administered with HAV, and that Kyn (100 μM/1000 μM) impaired IgM generation compared with that induced by LPS alone. We also demonstrated that microRNA30b (miR30b) played a critical role in the process of Kyn-mediated suppression of IgM responses induced by LPS, and that Bach2, a transcriptional repressor of B cell terminal differentiation, was a novel target of miR30b. These findings suggest that Kyn can serve as a novel and effective suppressive adjuvant for vaccines. PMID:24583631

  20. Experience in the detection and suppression of torsional vibration from mud logging data

    SciTech Connect

    Fear, M.J.; Abbassian, F.

    1994-12-31

    Vibration detection from mud logging systems has revealed that torsional vibration is common in harsh drilling environments, and is a major cause of bit and drillstring failures. Suppressing this type of vibration with an automated vibration detection system, torque feedback, and rigsite vibration suppression guidelines has produced a significant improvement in drilling performance.

  1. The relationship between thought suppression and retrieval-induced forgetting: an analysis of witness memories.

    PubMed

    Pica, Gennaro; Pierro, Antonio; Giannini, Annamaria

    2015-02-01

    The aim of the present research was to examine the relationship between individual differences in thought suppression and retrieval-induced forgetting (RIF) in witness-like situations. We predicted that people who are more prone to suppress undesired thoughts and memories would demonstrate a stronger RIF effect. Consistent with findings obtained in a US sample (Blumberg in Personal Individ Differ 29:943-950, 2000), results of a preliminary study (Study 1) confirmed the three-factor structure of the white bear suppression inventory (WBSI): the tendency to rely on thought suppression (suppression dimension), the frequency of experiencing intrusive thoughts (intrusion dimension), and the frequency of using self-distraction to avoid undesired thoughts (self-distraction dimension). Consistent with our hypotheses, Study 2 found that only the suppression sub-dimension of the WBSI was positively and significantly related to RIF. Theoretical expectations of these findings and implications for witness research are discussed. PMID:25064740

  2. Food thought suppression: a matched comparison of obese individuals with and without binge eating disorder.

    PubMed

    Barnes, Rachel D; Masheb, Robin M; Grilo, Carlos M

    2011-12-01

    Preliminary studies of non-clinical samples suggest that purposely attempting to avoid thoughts of food, referred to as food thought suppression, is related to a number of unwanted eating- and weight-related consequences, particularly in obese individuals. Despite possible implications for the treatment of obesity and eating disorders, little research has examined food thought suppression in obese individuals with binge eating disorder (BED). This study compared food thought suppression in 60 obese patients with BED to an age-, gender-, and body mass index (BMI)-matched group of 59 obese persons who do not binge eat (NBO). In addition, this study examined the associations between food thought suppression and eating disorder psychopathology within the BED and NBO groups and separately by gender. Participants with BED and women endorsed the highest levels of food thought suppression. Food thought suppression was significantly and positively associated with many features of ED psychopathology in NBO women and with eating concerns in men with BED. Among women with BED, higher levels of food thought suppression were associated with higher frequency of binge eating, whereas among men with BED, higher levels of food thought suppression were associated with lower frequency of binge eating. Our findings suggest gender differences in the potential significance of food thought suppression in obese groups with and without co-existing binge eating problems. PMID:22051359

  3. The effect of omeprazole pre-treatment on rafts formed by reflux suppressant tablets containing alginate.

    PubMed

    Dettmar, P W; Little, S L; Baxter, T

    2005-01-01

    Alginate-based reflux suppressant preparations provide symptom relief by forming a physical barrier on top of the stomach contents in the form of a neutral floating gel or raft. This study investigated whether reduced acidity in the stomach brought about by omeprazole pre-treatment affected the formation and gastric residence time of alginate rafts. It was a balanced, cross-over study in 12 healthy non-patient volunteers following a single dose of two indium-111-labelled alginate tablets in the presence or absence of 3 days' pre-treatment with omeprazole. Raft formation and gastric residence, in the presence of a technetium-99m-labelled meal, were assessed by gamma scintigraphy for 3 h after alginate tablet administration. The relative raft-forming ability of alginate tablets after omeprazole compared with alginate tablets alone was 0.950 with 95% confidence intervals of 0.882 and 1.018. Pre-treatment and co-administration with omeprazole has no significant effect on the raft-forming ability of alginate tablets. PMID:15938591

  4. Comparison of Filters Dedicated to Speckle Suppression in SAR Images

    NASA Astrophysics Data System (ADS)

    Kupidura, P.

    2016-06-01

    This paper presents the results of research on the effectiveness of different filtering methods dedicated to speckle suppression in SAR images. The tests were performed on RadarSat-2 images and on an artificial image treated with simulated speckle noise. The research analysed the performance of particular filters related to the effectiveness of speckle suppression and to the ability to preserve image details and edges. Speckle is a phenomenon inherent to radar images - a deterministic noise connected with land cover type, but also causing significant changes in digital numbers of pixels. As a result, it may affect interpretation, classification and other processes concerning radar images. Speckle, resembling "salt and pepper" noise, has the form of a set of relatively small groups of pixels of values markedly different from values of other pixels representing the same type of land cover. Suppression of this noise may also cause suppression of small image details, therefore the ability to preserve the important parts of an image, was analysed as well. In the present study, selected filters were tested, and methods dedicated particularly to speckle noise suppression: Frost, Gamma-MAP, Lee, Lee-Sigma, Local Region, general filtering methods which might be effective in this respect: Mean, Median, in addition to morphological filters (alternate sequential filters with multiple structuring element and by reconstruction). The analysis presented in this paper compared the effectiveness of different filtering methods. It proved that some of the dedicated radar filters are efficient tools for speckle suppression, but also demonstrated a significant efficiency of the morphological approach, especially its ability to preserve image details.

  5. Eye gaze adaptation under interocular suppression.

    PubMed

    Stein, Timo; Peelen, Marius V; Sterzer, Philipp

    2012-01-01

    The perception of eye gaze is central to social interaction in that it provides information about another person's goals, intentions, and focus of attention. Direction of gaze has been found to reflexively shift the observer's attention in the corresponding direction, and prolonged exposure to averted eye gaze adapts the visual system, biasing perception of subsequent gaze in the direction opposite to the adapting face. Here, we tested the role of conscious awareness in coding eye gaze directions. To this end, we measured aftereffects induced by adapting faces with different eye gaze directions that were presented during continuous flash suppression, a potent interocular suppression technique. In some trials the adapting face was rendered fully invisible, whereas in others it became partially visible. In Experiment 1, the adapting and test faces were presented in identical sizes and to the same eye. Even fully invisible faces were capable of inducing significant eye gaze aftereffects, although these were smaller than aftereffects from partially visible faces. When the adapting and test faces were shown to different eyes in Experiment 2, significant eye gaze aftereffects were still observed for the fully invisible faces, thus showing interocular transfer. Experiment 3 disrupted the spatial correspondence between adapting and test faces by introducing a size change. Under these conditions, aftereffects were restricted to partially visible adapting faces. These results were replicated in Experiment 4 using a blocked adaptation design. Together, these findings indicate that size-dependent low-level components of eye gaze can be represented without awareness, whereas object-centered higher-level representations of eye gaze directions depend on visual awareness. PMID:22753441

  6. Water Mist fire suppression experiment

    NASA Technical Reports Server (NTRS)

    2001-01-01

    The Water Mist commercial research program is scheduled to fly an investigation on STS-107 in 2002. This investigation will be flown as an Experimental Mounting Structure (EMS) insert into the updated Combustion Module (CM-2), a sophisticated combustion chamber plus diagnostic equipment. (The investigation hardware is shown here mounted in a non-flight frame similar to the EMS.) Water Mist is a commercial research program by the Center for Commercial Applications of Combustion in Space (CCACS), a NASA Commercial Space Center located at the Colorado School of Mines, in Golden, CO and Industry Partner Environmental Engineering Concepts. The program is focused on developing water mist as a replacement for bromine-based chemical fire suppression agents (halons). By conducting the experiments in microgravity, interference from convection currents is minimized and fundamental knowledge can be gained. This knowledge is incorporated into models, which can be used to simulate a variety of physical environments. The immediate objective of the project is to study the effect of a fine water mist on a laminar propagating flame generated in a propane-air mixture at various equivalence ratios. The effects of droplet size and concentration on the speed of the flame front is used as a measure of the effectiveness of fire suppression in this highly controlled experimental environment.

  7. Suppressed epidemics in multirelational networks

    NASA Astrophysics Data System (ADS)

    Xu, Elvis H. W.; Wang, Wei; Xu, C.; Tang, Ming; Do, Younghae; Hui, P. M.

    2015-08-01

    A two-state epidemic model in networks with links mimicking two kinds of relationships between connected nodes is introduced. Links of weights w1 and w0 occur with probabilities p and 1 -p , respectively. The fraction of infected nodes ρ (p ) shows a nonmonotonic behavior, with ρ drops with p for small p and increases for large p . For small to moderate w1/w0 ratios, ρ (p ) exhibits a minimum that signifies an optimal suppression. For large w1/w0 ratios, the suppression leads to an absorbing phase consisting only of healthy nodes within a range pL≤p ≤pR , and an active phase with mixed infected and healthy nodes for p pR . A mean field theory that ignores spatial correlation is shown to give qualitative agreement and capture all the key features. A physical picture that emphasizes the intricate interplay between infections via w0 links and within clusters formed by nodes carrying the w1 links is presented. The absorbing state at large w1/w0 ratios results when the clusters are big enough to disrupt the spread via w0 links and yet small enough to avoid an epidemic within the clusters. A theory that uses the possible local environments of a node as variables is formulated. The theory gives results in good agreement with simulation results, thereby showing the necessity of including longer spatial correlations.

  8. Chaos suppression through asymmetric coupling

    NASA Astrophysics Data System (ADS)

    Bragard, J.; Vidal, G.; Mancini, H.; Mendoza, C.; Boccaletti, S.

    2007-12-01

    We study pairs of identical coupled chaotic oscillators. In particular, we have used Roessler (in the funnel and no funnel regimes), Lorenz, and four-dimensional chaotic Lotka-Volterra models. In all four of these cases, a pair of identical oscillators is asymmetrically coupled. The main result of the numerical simulations is that in all cases, specific values of coupling strength and asymmetry exist that render the two oscillators periodic and synchronized. The values of the coupling strength for which this phenomenon occurs is well below the previously known value for complete synchronization. We have found that this behavior exists for all the chaotic oscillators that we have used in the analysis. We postulate that this behavior is presumably generic to all chaotic oscillators. In order to complete the study, we have tested the robustness of this phenomenon of chaos suppression versus the addition of some Gaussian noise. We found that chaos suppression is robust for the addition of finite noise level. Finally, we propose some extension to this research.

  9. CDK2 and mTOR are direct molecular targets of isoangustone A in the suppression of human prostate cancer cell growth

    SciTech Connect

    Lee, Eunjung; Son, Joe Eun; Byun, Sanguine; Lee, Seung Joon; Kim, Yeong A; Liu, Kangdong; Kim, Jiyoung; Lim, Soon Sung; Park, Jung Han Yoon; Dong, Zigang; Lee, Ki Won; Lee, Hyong Joo

    2013-10-01

    Licorice extract which is used as a natural sweetener has been shown to possess inhibitory effects against prostate cancer, but the mechanisms responsible are poorly understood. Here, we report a compound, isoangustone A (IAA) in licorice that potently suppresses the growth of aggressive prostate cancer and sought to clarify its mechanism of action. We analyzed its inhibitory effects on the growth of PTEN-deleted human prostate cancer cells, in vitro and in vivo. Administration of IAA significantly attenuated the growth of prostate cancer cell cultures and xenograft tumors. These effects were found to be attributable to inhibition of the G1/S phase cell cycle transition and the accumulation of p27{sup kip1}. The elevated p27{sup kip1} expression levels were concurrent with the decrease of its phosphorylation at threonine 187 through suppression of CDK2 kinase activity and the reduced phosphorylation of Akt at Serine 473 by diminishing the kinase activity of the mammalian target of rapamycin (mTOR). Further analysis using recombinant proteins and immunoprecipitated cell lysates determined that IAA exerts suppressive effects against CDK2 and mTOR kinase activity by direct binding with both proteins. These findings suggested that the licorice compound IAA is a potent molecular inhibitor of CDK2 and mTOR, with strong implications for the treatment of prostate cancer. Thus, licorice-derived extracts with high IAA content warrant further clinical investigation for nutritional sources for prostate cancer patients. - Highlights: • Isoangustone A suppresses growth of PC3 and LNCaP prostate cancer cells. • Administration of isoangustone A inhibits tumor growth in mice. • Treatment of isoangustone A induces cell cycle arrest and accumulation of p27{sup kip1}. • Isoangustone A inhibits CDK2 and mTOR activity. • Isoangustone A directly binds with CDK2 and mTOR complex in prostate cancer cells.

  10. Wireless Inductive Power Device Suppresses Blade Vibrations

    NASA Technical Reports Server (NTRS)

    Morrison, Carlos R.; Provenza, Andrew J.; Choi, Benjamin B.; Bakhle, Milind A.; Min, James B.; Stefko, George L.; Duffy, Kirsten P.; Fougers, Alan J.

    2011-01-01

    possible to moderate vibration on or in turbomachinery blades by providing 100 W of wireless electrical power and actuation control to thin, lightweight vibration-suppressing piezoelectric patches (eight actuation and eight sensor patches in this prototype, for a total of 16 channels) positioned strategically on the surface of, or within, titanium fan blades, or embedded in composite fan blades. This approach moves significantly closer to the ultimate integration of "active" vibration suppression technology into jet engines and other turbomachinery devices such as turbine electrical generators used in the power industry. The novel feature of this device is in its utilization of wireless technology to simultaneously sense and actively control vibration in rotating or stationary turbomachinery blades using piezoelectric patches. In the past, wireless technology was used solely for sensing and diagnostics. This technology, however, will accomplish much more, in terms of simultaneously sensing, suppressing blade vibration, and making it possible for detailed study of vibration impact in turbomachinery blades.

  11. Apoptotic and proliferative activity of mouse gastric mucosa following oral administration of fumonisin B1

    PubMed Central

    Alizadeh, Ali Mohammad; Mohammadghasemi, Fahimeh; Zendehdel, Kazem; Kamyabi-moghaddam, Zahra; Tavassoli, Abbas; Amini-najafi, Fatemeh; Khosravi, Alireza

    2015-01-01

    Objective(s): Fumonisins are a group of toxic and carcinogenic mycotoxins, which contaminate the grains and their products. The aim of this study was to examine the apoptotic and proliferative activity of mouse gastric mucosa following administration of fumonisin B1 (FB1). Materials and Methods: Twenty-nine female mice divided into treatment (n=15) and control (n=14) groups. The treatment group received FB1 (150 mg/kg diet) for 16 weeks. The gastric atrophy was allocated using grading criteria modeled on the updated Sydney System. Immunohistochemistry studies were performed for evaluation of apoptosis and proliferative activity in gastric mucosa. Results: Mild to moderate gastric atrophy were observed in microscopic findings of the gastric mucosa in treated animals (P<0.05). Number of parietal cells significantly decreased in the treatment group in comparison with the control (P<0.05). Treatment with FB1 for 16 weeks significantly reduced both gastric mucosa height and mitotic index in the gastric glands (P<0.05). TUNEL- and Bax-labeled positive cell numbers significantly increased in the FB1-treated group compared to the control (P<0.05). In addition, proliferative activity of gastric glands in the treated group was significantly lower than the control (P<0.05). Conclusion: Oral administration of FB1 caused atrophy in gastric mucosa both via increasing of apoptosis and suppressing the mitotic activity of these cells. PMID:25810870

  12. Suppression of leaky expression of adenovirus genes by insertion of microRNA-targeted sequences in the replication-incompetent adenovirus vector genome.

    PubMed

    Shimizu, Kahori; Sakurai, Fuminori; Tomita, Kyoko; Nagamoto, Yasuhito; Nakamura, Shin-Ichiro; Katayama, Kazufumi; Tachibana, Masashi; Kawabata, Kenji; Mizuguchi, Hiroyuki

    2014-01-01

    Leaky expression of adenovirus (Ad) genes occurs following transduction with a conventional replication-incompetent Ad vector, leading to an induction of cellular immunity against Ad proteins and Ad protein-induced toxicity, especially in the late phase following administration. To suppress the leaky expression of Ad genes, we developed novel Ad vectors by incorporating four tandem copies of sequences with perfect complementarity to miR-122a or miR-142-3p into the 3'-untranslated region (UTR) of the E2A, E4, or pIX gene, which were mainly expressed from the Ad vector genome after transduction. These Ad vectors easily grew to high titers comparable to those of a conventional Ad vector in conventional 293 cells. The leaky expression of these Ad genes in mouse organs was significantly suppressed by 2- to 100-fold, compared with a conventional Ad vector, by insertion of the miRNA-targeted sequences. Notably, the Ad vector carrying the miR-122a-targeted sequences into the 3'-UTR of the E4 gene expressed higher and longer-term transgene expression and more than 20-fold lower levels of all the Ad early and late genes examined in the liver than a conventional Ad vector. miR-122a-mediated suppression of the E4 gene expression in the liver significantly reduced the hepatotoxicity which an Ad vector causes via both adaptive and non-adaptive immune responses. PMID:26015975

  13. 30 CFR 75.1107-15 - Fire suppression devices; hazards; training of miners.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Fire suppression devices; hazards; training of miners. 75.1107-15 Section 75.1107-15 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES...

  14. Tumor-suppressive effects of natural-type interferon-β through CXCL10 in melanoma

    SciTech Connect

    Kobayashi, Hikaru; Nobeyama, Yoshimasa Nakagawa, Hidemi

    2015-08-21

    Introduction: Type 1 interferon is in widespread use as adjuvant therapy to inhibit melanoma progression. Considering the tumor-suppressive effects of local administration of interferon-β (IFN-β) on lymphatic metastasis, the present study was conducted to identify melanoma-suppressive molecules that are up-regulated by IFN-β treatment of lymphatic endothelial cells. Materials and methods: Lymphatic endothelial cells, fibroblasts, and melanoma cells were treated with natural-type IFN-β, and melanoma cells were treated with CXCL10. Genome-wide oligonucleotide microarray analysis was performed using lymphatic endothelial cells with or without IFN-β treatment. Quantitative real-time reverse transcription-PCR and an enzyme-linked immunosorbent assay were performed to examine CXCL10 expression. A proliferation assay was performed to examine the effects of IFN-β and CXCL10 in melanoma cells. Results: Genome-wide microarray analyses detected CXCL10 as a gene encoding a secretory protein that was up-regulated by IFN-β in lymphatic endothelial cells. IFN-β treatment significantly induced CXCL10 in dermal lymphatic endothelial cells and melanoma cells that are highly sensitive to IFN-β. CXCL10 reduced melanoma cell proliferation in IFN-β-sensitive cells as well as resistant cells. Melanoma cells in which CXCL10 was knocked down were sensitive to IFN-β. CXCR3-B, which encodes the CXCL10 receptor, was up-regulated in melanoma cells with high sensitivity to IFN-β and down-regulated in melanoma cells with medium to low sensitivity. Conclusions: Our data suggest that IFN-β suppresses proliferation and metastasis from the local lymphatic system and melanoma cells via CXCL10. Down-regulation of CXCR3-B by IFN-β may be associated with resistance to IFN-β. - Highlights: • We search melanoma-suppressive molecules induced by IFN-β. • IFN-β induces a high amount of CXCL10 from lymphatic endothelial cells. • CXCL10 induction level in melanoma cells is correlated

  15. Permanent Suppression of Cortical Oscillations in Mice After Adolescent Exposure to Cannabinoids: Receptor Mechanisms

    PubMed Central

    Raver, Sylvina M.; Keller, Asaf

    2014-01-01

    Marijuana use in adolescence, but not adulthood, may permanently impair cognitive functioning and increase the risk of developing schizophrenia. Cortical oscillations are patterns of neural network activity implicated in cognitive processing, and are abnormal in patients with schizophrenia. We have recently reported that cortical oscillations are suppressed in adult mice that were treated, in adolescence but not adulthood, with the cannabinoids WIN55,212-2 (WIN) or Δ9tetrahydrocannabinol (THC). WIN and THC are cannabinoid types 1 and 2 receptor (CB1R & CB2R) agonists, and also have activity at non-cannabinoid receptor targets. However, as acute WIN and THC administration can suppress oscillations through CB1Rs, we hypothesize that a similar mechanism underlies the permanent suppression of oscillations by repeated cannabinoid exposure in adolescence. Here we test the prediction that cannabinoid exposure in adolescence permanently suppresses cortical oscillations by acting through CB1Rs, and that these suppressive effects can be antagonized by a CB1R antagonist. We treated adolescent mice with various cannabinoid compounds, and pharmacologically-evoked oscillations in vitro in adult mice. We find that WIN exposure for six days in early adolescence suppresses oscillations preferentially in adult medial prefrontal cortex (mPFC) via CB1Rs, and that a similar CB1R mechanism accounts for the suppressive effects of long-term (20 day) adolescent THC in adult somatosensory cortex (SCx). Unexpectedly, we also find that CB2Rs may be involved in the suppression of oscillations in both mPFC and SCx by long-term adolescent cannabinoid exposure, and that non-cannabinoid receptors may also contribute to oscillation suppression in adult mPFC. These findings represent a novel attempt to antagonize the effects of adolescent cannabinoid exposure on neural network activity, and reveal the contribution of non-CB1R targets to the suppression of cortical oscillations. PMID:25036610

  16. Permanent suppression of cortical oscillations in mice after adolescent exposure to cannabinoids: receptor mechanisms.

    PubMed

    Raver, Sylvina M; Keller, Asaf

    2014-11-01

    Marijuana use in adolescence, but not adulthood, may permanently impair cognitive functioning and increase the risk of developing schizophrenia. Cortical oscillations are patterns of neural network activity implicated in cognitive processing, and are abnormal in patients with schizophrenia. We have recently reported that cortical oscillations are suppressed in adult mice that were treated with the cannabinoids WIN55,212-2 (WIN) or Δ(9)tetrahydrocannabinol (THC) in adolescence, but not adulthood. WIN and THC are cannabinoid-1 (CB1R) and CB2R agonists, and also have activity at non-cannabinoid receptor targets. However, as acute WIN and THC administration can suppress oscillations through CB1Rs, we hypothesize that a similar mechanism underlies the permanent suppression of oscillations by repeated cannabinoid exposure in adolescence. Here we test the prediction that cannabinoid exposure in adolescence permanently suppresses cortical oscillations by acting through CB1Rs, and that these suppressive effects can be antagonized by a CB1R antagonist. We treated adolescent mice with various cannabinoid compounds, and pharmacologically-evoked oscillations in local field potentials (LFPs) in vitro in adults. We find that WIN exposure for six days in early adolescence suppresses oscillations preferentially in adult medial prefrontal cortex (mPFC) via CB1Rs, and that a similar CB1R mechanism accounts for the suppressive effects of long-term (20 day) adolescent THC in adult somatosensory cortex (SCx). Unexpectedly, we also find that CB2Rs may be involved in the suppression of oscillations in both mPFC and SCx by long-term adolescent cannabinoid exposure, and that non-cannabinoid receptors may also contribute to oscillation suppression in adult mPFC. These findings represent a novel attempt to antagonize the effects of adolescent cannabinoid exposure on neural network activity, and reveal the contribution of non-CB1R targets to the suppression of cortical oscillations. PMID

  17. Suppression of Angiogenesis and Tumor Growth by the Inhibitor K1-5 Generated by Plasmin-Mediated Proteolysis

    NASA Astrophysics Data System (ADS)

    Cao, Renhai; Wu, Hua-Lin; Veitonmaki, Niina; Linden, Philip; Farnebo, Jacob; Shi, Guey-Yueh; Cao, Yihai

    1999-05-01

    Proteolytic enzymes are involved in generation of a number of endogenous angiogenesis inhibitors. Previously, we reported that angiostatin, a potent angiogenesis inhibitor, is a protcolytic fragment containing the first four kringle modules of plasminogen. In this report, we demonstrate that urokinase-activated plasmin can process plasminogen to release an angiogenesis inhibitor, K1-5 (protease-activated kringles 1-5). K1-5 inhibits endothelial-cell proliferation with a half-maximal concentration of approximately 50 pM. This inhibitory effect is endothelial-cell-specific and appears to be at least approximately 50-fold greater than that of angiostatin. A synergistic efficacy of endothelial inhibition was observed when angiostatin and kringle 5 (K5) were coincubated with capillary endothelial cells. The synergistic effect is comparable to that produced by K1-5 alone. Systemic treatment of mice with K1-5 at a low dose significantly blocked the fibroblast growth factor-induced corneal neovascularization, whereas angiostatin had no effect at the same dose. K1-5 also suppressed angiogenesis in chicken embryos. Systemic administration of K1-5 at a low dose at which angiostatin was ineffective significantly suppressed the growth of a murine T241 fibrosarcoma in mice. The antitumor effect correlates with the reduced neovascularization. These findings suggest that the plasmin-mediated proteolysis may be involved in the negative switch of angiogenesis.

  18. 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. PMID:23419864

  19. An improved prototype ignition suppression device for underground electrical face cutting equipment

    SciTech Connect

    Luzik, S.J.

    1988-01-01

    An improved ignition suppression device was investigated by the Mine Safety and Health Administration. The device, developed by the Industrial Safety Division, is designed to be installed on the boom of a continuous mining machine and would function to suppress frictionally induced methane ignitions in the face areas of underground coal mines. It was anticipated that the basic device could be modified to accommodate other types of electrical face cutting equipment with minimal design changes. Ultraviolet (UV) detection is used to sense the developing fireball and suppression is achieved by explosively rupturing steel canisters filled with an extinguishing agent. Canisters are enclosed in specially designed baffled mufflers which serve to abate high impulse noise and afford protection against roof falls and other physical abuse. The devices proved successful in suppressing simulated frictional ignitions in a limited number of gallery tests incorporating a mock-up cutter head of a continuous mining machine.

  20. Morphine-induced suppression of conditioned stimulus intake: Effects of stimulus type and insular cortex lesions

    PubMed Central

    Lin, Jian-You; Roman, Christopher; Reilly, Steve

    2009-01-01

    Intake of an unconditionally preferred taste stimulus (e.g., saccharin) is reduced by contingent administration of a drug of abuse (e.g., morphine). We examined the influence of insular cortex (IC) lesions on morphine-induced suppression of an olfactory cue and two taste stimuli with different levels of perceived innate reward value. Two major findings emerged from this study. First, morphine suppressed intake of an aqueous odor as well as each taste stimulus in neurologically intact rats. Second, IC lesions disrupted morphine-induced suppression of the taste stimuli but not the aqueous odor cue. These results indicate that the perceived innate reward value of the CS is not a factor that governs drug-induced intake suppression. PMID:19631620

  1. 9. SITE MAP HIGHLIGHTING SIGNIFICANT BUILDINGS AND SHOWING LOCATION LOCATION ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    9. SITE MAP HIGHLIGHTING SIGNIFICANT BUILDINGS AND SHOWING LOCATION LOCATION OF OUTPATIENT CLINIC ADDITION - U.S. Veterans Administration Medical Center, 600 South Seventieth Street, Lincoln, Lancaster County, NE

  2. Astronaut Administrator Richard Truly

    NASA Technical Reports Server (NTRS)

    1979-01-01

    Astronaut Richard H. Truly, pilot of the Space Shuttle Columbia on mission STS-2 and Commander of Shuttle Challenger on mission STS-8, became NASA's eighth Administrator on July 1, 1989. One day earlier he concluded a 30 year Naval career retiring as a Vice Admiral. He was the first astronaut to head the nation's civilian space agency. Truly became Deputy Associate Administrator for Space Flight on February 20, 1986. In this position, he led the painstaking rebuilding of the Space Shuttle program less than one month after the Challenger disaster. This was highlighted by the much heralded 'Return to Flight' on September 29, 1988 with the launch of Shuttle Discovery, 32 months after Challenger's final flight. On February 12th, 1992 Richard Truly resigned as NASA Administrator at the request of President George Bush.

  3. Simvastatin sensitizes human gastric cancer xenograft in nude mice to capecitabine by suppressing nuclear factor-kappa B-regulated gene products.

    PubMed

    Manu, Kanjoormana A; Shanmugam, Muthu K; Li, Feng; Chen, Luxi; Siveen, Kodappully Sivaraman; Ahn, Kwang Seok; Kumar, Alan Prem; Sethi, Gautam

    2014-03-01

    Chemoresistance remains a major problem in the treatment of gastric cancer patients. Hence, novel pharmacological agents that can overcome drug resistance are urgently required. Whether simvastatin can sensitize the gastric cancer to the antitumor effects of capecitabine in vitro and in vivo was investigated. The effect of simvastatin on the proliferation of gastric cancer cells was examined by mitochondrial dye-uptake 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method, apoptosis by esterase staining, NF-κB activation by DNA binding assay, and protein expression by western blot analysis. The effect of simvastatin on the tumor growth in xenograft mouse model of human gastric cancer was also examined. Simvastatin suppressed the proliferation of gastric cancer cells, enhanced the apoptotic effects of capecitabine, suppressed the constitutive activation of NF-κB, and abrogated the expression of cyclooxygenase-2 (COX-2), cyclin D1, Bcl-2, survivin, CXC motif receptor 4, and MMP-9 proteins. In a xenograft mouse model, we observed that the administration of simvastatin alone (5 mg/kg body weight, intraperitoneal thrice/week) significantly suppressed the growth of the tumor and this effect was further potentiated by capecitabine treatment. As compared to the vehicle control, simvastatin also suppressed the expression of NF-κB-regulated gene products such as cyclin D1, COX-2, ICAM-1, MMP-9, survivin, Bcl-xL, and XIAP in tumor tissues. Overall, our results demonstrate that simvastatin can enhance the effects of capecitabine through suppression of NF-κB-regulated markers of proliferation, invasion, angiogenesis, and metastasis. PMID:24233024

  4. Chloroform fraction of Euphorbia maculata has antiplatelet activity via suppressing thromboxane B2 formation.

    PubMed

    Kwon, Se-Uk; Cha, Ji-Yoon; Lee, Hoon-Yeon; Xin, Mingjie; Ji, Su-Jeong; Kim, Dae-Ki; Park, Do-Sim; Pyo, Mi-Kyung; Lee, Young-Mi

    2015-06-01

    Euphorbia maculata (EM) is a traditionally used antidiarrheal, antibacterial, antifungal and antioxidant agent. However, the effects of EM on platelet activity remain to be elucidated. Therefore, the present study investigated the antiplatelet effect of various EM extract fractions on platelet aggregation in rats. The antiplatelet activity of the EM fractions on collagen or adenosine diphosphate (ADP)‑induced platelet aggregation was evaluated in vitro and ex vivo. Thromboxane B2 (TXB2) formation, rat‑tail bleeding time and coagulation time were also measured. Among the fractions, the chloroform fraction of EM (CFEM) significantly inhibited ADP‑induced platelet aggregation in vitro. Furthermore, oral administration of 50 mg/kg CFEM to rats significantly reduced ADP‑induced platelet aggregation without increasing the tail bleeding time or coagulation time. In addition, EM significantly inhibited the level of TXB2 formation in a dose‑dependent manner. These results suggest that CFEM exhibits antiplatelet activity, without causing bleeding, via the suppression of TXB2 formation. CFEM may be a type of food which has the potential for preventing cardiovascular disease. PMID:25672843

  5. Weight Suppression Predicts Maintenance and Onset of Bulimic Syndromes at 10-Year Follow-up

    PubMed Central

    Keel, Pamela K.; Heatherton, Todd F.

    2010-01-01

    Conflicting results have emerged regarding the prognostic significance of weight suppression for maintenance of bulimic symptoms. This study examined whether the magnitude of weight suppression would predict bulimic syndrome maintenance and onset in college-based samples of men (n=369) and women (n=968) at 10-year follow-up. Data come from a longitudinal study of body weight and disordered eating with high retention (80%). Among those with a bulimic syndrome at baseline, greater weight suppression significantly predicted maintenance of the syndrome, and, among those without a bulimic syndrome at baseline, greater weight suppression predicted onset of a bulimic syndrome at 10-year follow-up in multivariate models that included baseline body mass index, diet frequency, and weight perception. Future research should address mechanisms that could account for the effects of weight suppression over a long duration of follow-up. PMID:20455599

  6. Intravenous lidocaine as a suppressant of coughing during tracheal intubation.

    PubMed

    Yukioka, H; Yoshimoto, N; Nishimura, K; Fujimori, M

    1985-12-01

    Effects of intravenously administered lidocaine on cough suppression during tracheal intubation under general anesthesia were evaluated in two studies. In study 1, 100 patients received either a placebo or 0.5, 1.0, 1.5, or 2.0 mg/kg lidocaine intravenously 1 min before tracheal intubation. All visible coughs were classified as coughing. The incidence of coughing decreased as the dose of lidocaine increased. A dose of 1 mg/kg or more of intravenous lidocaine suppressed the cough reflex significantly (P less than 0.01). Coughing was suppressed completely by 2 mg/kg of intravenous lidocaine. In study 2, 108 patients received 2 mg/kg lidocaine intravenously or a placebo 1, 3, 5, 7, 10, or 15 min before intubation. The same criteria for determining whether a patient did or did not cough during tracheal intubation were used as in study 1. The incidence of coughing decreased significantly (P less than 0.01) when 2 mg/kg of lidocaine was injected intravenously between 1 and 5 min before our attempting intubation. Cough reflex was suppressed completely by plasma concentrations of lidocaine in excess of 3 micrograms/ml. PMID:4061901

  7. Rosmarinus officinalis Extract Suppresses Propionibacterium acnes–Induced Inflammatory Responses

    PubMed Central

    Tsai, Tsung-Hsien; Chuang, Lu-Te; Lien, Tsung-Jung; Liing, Yau-Rong; Chen, Wei-Yu

    2013-01-01

    Abstract Propionibacterium acnes is a key pathogen involved in the progression of acne inflammation. The development of a new agent possessing antimicrobial and anti-inflammatory activity against P. acnes is therefore of interest. In this study, we investigated the inhibitory effect of rosemary (Rosmarinus officinalis) extract on P. acnes–induced inflammation in vitro and in vivo. The results showed that ethanolic rosemary extract (ERE) significantly suppressed the secretion and mRNA expression of proinflammatory cytokines, including interleukin (IL)-8, IL-1β, and tumor necrosis factor-α in P. acnes–stimulated monocytic THP-1 cells. In an in vivo mouse model, concomitant intradermal injection of ERE attenuated the P. acnes–induced ear swelling and granulomatous inflammation. Since ERE suppressed the P. acnes–induced nuclear factor kappa-B (NF-κB) activation and mRNA expression of Toll-like receptor (TLR) 2, the suppressive effect of ERE might be due, at least partially, to diminished NF-κB activation and TLR2-mediated signaling pathways. Furthermore, three major constituents of ERE, carnosol, carnosic acid, and rosmarinic acid, exerted different immumodulatory activities in vitro. In brief, rosmarinic acid significantly suppressed IL-8 production, while the other two compounds inhibited IL-1β production. Further study is needed to explore the role of bioactive compounds of rosemary in mitigation of P. acnes–induced inflammation. PMID:23514231

  8. Suppression of Bean Defense Responses by Pseudomonas syringae.

    PubMed Central

    Jakobek, JL; Smith, JA; Lindgren, PB

    1993-01-01

    We have developed a model system to examine suppression of defense responses in bean by the compatible bacterium Pseudomonas syringae pv phaseolicola. Previously, we have shown that there is a general mechanism for the induction of the bean defense genes phenylalanine ammonia-lyase (PAL), chalcone synthase (CHS), chalcone isomerase (CHI), and chitinase (CHT) by incompatible, compatible, and nonpathogenic bacteria. Here, we show that bean plants infiltrated with isolates of P. s. phaseolicola failed to produce transcripts for PAL, CHS, or CHI up to 120 hr after infiltration and CHT transcript accumulation was significantly delayed when compared to the incompatible P. syringae strains. Infiltration of bean plants with 108 cells per mL of P. s. phaseolicola NPS3121 8 hr prior to infiltration with an equal concentration of incompatible P. s. pv tabaci Pt11528 significantly reduced the typical profile of defense transcript accumulation when compared to plants infiltrated with Pt11528 alone. A corresponding suppression of phytoalexin accumulation was also observed. NPS3121 also suppressed PAL, CHS, CHI, and CHT transcript accumulation and phytoalexin production induced by Escherichia coli DH5[alpha] or the elicitor glutathione. Heat-killed NPS3121 cells or cells treated with protein synthesis inhibitors lost the suppressor activity. Taken together, these experiments suggest that NPS3121 has an active mechanism to suppress the accumulation of defense transcripts and phytoalexin biosynthesis in bean. PMID:12271016

  9. Rosmarinus officinalis extract suppresses Propionibacterium acnes-induced inflammatory responses.

    PubMed

    Tsai, Tsung-Hsien; Chuang, Lu-Te; Lien, Tsung-Jung; Liing, Yau-Rong; Chen, Wei-Yu; Tsai, Po-Jung

    2013-04-01

    Propionibacterium acnes is a key pathogen involved in the progression of acne inflammation. The development of a new agent possessing antimicrobial and anti-inflammatory activity against P. acnes is therefore of interest. In this study, we investigated the inhibitory effect of rosemary (Rosmarinus officinalis) extract on P. acnes-induced inflammation in vitro and in vivo. The results showed that ethanolic rosemary extract (ERE) significantly suppressed the secretion and mRNA expression of proinflammatory cytokines, including interleukin (IL)-8, IL-1β, and tumor necrosis factor-α in P. acnes-stimulated monocytic THP-1 cells. In an in vivo mouse model, concomitant intradermal injection of ERE attenuated the P. acnes-induced ear swelling and granulomatous inflammation. Since ERE suppressed the P. acnes-induced nuclear factor kappa-B (NF-κB) activation and mRNA expression of Toll-like receptor (TLR) 2, the suppressive effect of ERE might be due, at least partially, to diminished NF-κB activation and TLR2-mediated signaling pathways. Furthermore, three major constituents of ERE, carnosol, carnosic acid, and rosmarinic acid, exerted different immumodulatory activities in vitro. In brief, rosmarinic acid significantly suppressed IL-8 production, while the other two compounds inhibited IL-1β production. Further study is needed to explore the role of bioactive compounds of rosemary in mitigation of P. acnes-induced inflammation. PMID:23514231

  10. Suppression of Th1-Mediated Autoimmunity by Embryonic Stem Cell-Derived Dendritic Cells

    PubMed Central

    Ikeda, Tokunori; Hirata, Shinya; Takamatsu, Koutaro; Haruta, Miwa; Tsukamoto, Hirotake; Ito, Takaaki; Uchino, Makoto; Ando, Yukio; Nagafuchi, Seiho; Nishimura, Yasuharu; Senju, Satoru

    2014-01-01

    We herein demonstrate the immune-regulatory effect of embryonic stem cell-derived dendritic cells (ES-DCs) using two models of autoimmune disease, namely non-obese diabetic (NOD) mice and experimental autoimmune encephalomyelitis (EAE). Treatment of pre-diabetic NOD mice with ES-DCs exerted almost complete suppression of diabetes development during the observation period for more than 40 weeks. The prevention of diabetes by ES-DCs was accompanied with significant reduction of insulitis and decreased number of Th1 and Th17 cells in the spleen. Development of EAE was also inhibited by the treatment with ES-DCs, and the therapeutic effect was obtained even if ES-DCs were administrated after the onset of clinical symptoms. Treatment of EAE-induced mice with ES-DCs reduced the infiltration of inflammatory cells into the spinal cord and suppressed the T cell response to the myelin antigen. Importantly, the ES-DC treatment did not affect T cell response to an exogenous antigen. As the mechanisms underlying the reduction of the number of infiltrating Th1 cells, we observed the inhibition of differentiation and proliferation of Th1 cells by ES-DCs. Furthermore, the expression of VLA-4α on Th1 cells was significantly inhibited by ES-DCs. Considering the recent advances in human induced pluripotent stem cell-related technologies, these results suggest a clinical application for pluripotent stem cell-derived dendritic cells as a therapy for T cell-mediated autoimmune diseases. PMID:25522369

  11. Stronger Pharmacological Cortisol Suppression and Anticipatory Cortisol Stress Response in Transient Global Amnesia

    PubMed Central

    Griebe, Martin; Nees, Frauke; Gerber, Benjamin; Ebert, Anne; Flor, Herta; Wolf, Oliver T.; Gass, Achim; Hennerici, Michael G.; Szabo, Kristina

    2015-01-01

    Transient global amnesia (TGA) is a disorder characterized by a sudden attack of severe anterograde memory disturbance that is frequently preceded by emotional or physical stress and resolves within 24 h. By using MRI following the acute episode in TGA patients, small lesions in the hippocampus have been observed. Hence, it has been hypothesized that the disorder is caused by a stress-related transient inhibition of memory formation in the hippocampus. To study the factors that may link stress and TGA, we measured the cortisol day-profile, the dexamethasone feedback inhibition and the effect of experimental exposure to stress on cortisol levels (using the socially evaluated cold pressor test and a control procedure) in 20 patients with a recent history of TGA and in 20 healthy controls. We used self-report scales of depression, anxiety and stress, and a detailed neuropsychological assessment to characterize our collective. We did not observe differences in mean cortisol levels in the cortisol day-profile between the two groups. After administration of low-dose dexamethasone, TGA patients showed significantly stronger cortisol suppression in the daytime profile compared to the control group (p = 0.027). The mean salivary cortisol level was significantly higher in the TGA group prior to and after the experimental stress exposure (p = 0.008 and 0.010 respectively), as well as prior to and after the control condition (p = 0.022 and 0.024, respectively). The TGA group had higher scores of depressive symptomatology (p = 0.021) and anxiety (p = 0.007), but the groups did not differ in the neuropsychological assessment. Our findings of a stronger pharmacological suppression and higher cortisol levels in anticipation of experimental stress in participants with a previous TGA indicate a hypersensitivity of the HPA axis. This suggests that an individual stress sensitivity might play a role in the pathophysiology of TGA. PMID:25805980

  12. Vinpocetine suppresses pathological vascular remodeling by inhibiting vascular smooth muscle cell proliferation and migration.

    PubMed

    Cai, Yujun; Knight, Walter E; Guo, Shujie; Li, Jian-Dong; Knight, Peter A; Yan, Chen

    2012-11-01

    Abnormal vascular smooth muscle cell (SMC) activation is associated with various vascular disorders such as atherosclerosis, in-stent restenosis, vein graft disease, and transplantation-associated vasculopathy. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. However, its role in pathological vascular remodeling remains unexplored. Herein, we show that systemic administration of vinpocetine significantly reduced neointimal formation in carotid arteries after ligation injury. Vinpocetine also markedly decreased spontaneous remodeling of human saphenous vein explants in ex vivo culture. In cultured SMCs, vinpocetine dose-dependently suppressed cell proliferation and caused G1-phase cell cycle arrest, which is associated with a decrease in cyclin D1 and an increase in p27Kip1 levels. In addition, vinpocetine dose-dependently inhibited platelet-derived growth factor (PDGF)-stimulated SMC migration as determined by the two-dimensional migration assays and three-dimensional aortic medial explant invasive assay. Moreover, vinpocetine significantly reduced PDGF-induced type I collagen and fibronectin expression. It is noteworthy that PDGF-stimulated phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2), but not protein kinase B, was specifically inhibited by vinpocetine. Vinpocetine powerfully attenuated intracellular reactive oxidative species (ROS) production, which largely mediates the inhibitory effects of vinpocetine on ERK1/2 activation and SMC growth. Taken together, our results reveal a novel function of vinpocetine in attenuating neointimal hyperplasia and pathological vascular remodeling, at least partially through suppressing ROS production and ERK1/2 activation in SMCs. Given the safety profile of vinpocetine, this study provides insight into the therapeutic potential of vinpocetine in proliferative vascular disorders. PMID:22915768

  13. Vinpocetine Suppresses Pathological Vascular Remodeling by Inhibiting Vascular Smooth Muscle Cell Proliferation and Migration

    PubMed Central

    Cai, Yujun; Knight, Walter E.; Guo, Shujie; Li, Jian-Dong; Knight, Peter A.

    2012-01-01

    Abnormal vascular smooth muscle cell (SMC) activation is associated with various vascular disorders such as atherosclerosis, in-stent restenosis, vein graft disease, and transplantation-associated vasculopathy. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. However, its role in pathological vascular remodeling remains unexplored. Herein, we show that systemic administration of vinpocetine significantly reduced neointimal formation in carotid arteries after ligation injury. Vinpocetine also markedly decreased spontaneous remodeling of human saphenous vein explants in ex vivo culture. In cultured SMCs, vinpocetine dose-dependently suppressed cell proliferation and caused G1-phase cell cycle arrest, which is associated with a decrease in cyclin D1 and an increase in p27Kip1 levels. In addition, vinpocetine dose-dependently inhibited platelet-derived growth factor (PDGF)-stimulated SMC migration as determined by the two-dimensional migration assays and three-dimensional aortic medial explant invasive assay. Moreover, vinpocetine significantly reduced PDGF-induced type I collagen and fibronectin expression. It is noteworthy that PDGF-stimulated phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2), but not protein kinase B, was specifically inhibited by vinpocetine. Vinpocetine powerfully attenuated intracellular reactive oxidative species (ROS) production, which largely mediates the inhibitory effects of vinpocetine on ERK1/2 activation and SMC growth. Taken together, our results reveal a novel function of vinpocetine in attenuating neointimal hyperplasia and pathological vascular remodeling, at least partially through suppressing ROS production and ERK1/2 activation in SMCs. Given the safety profile of vinpocetine, this study provides insight into the therapeutic potential of vinpocetine in proliferative vascular disorders. PMID:22915768

  14. Suppression of Th1-mediated autoimmunity by embryonic stem cell-derived dendritic cells.

    PubMed

    Ikeda, Tokunori; Hirata, Shinya; Takamatsu, Koutaro; Haruta, Miwa; Tsukamoto, Hirotake; Ito, Takaaki; Uchino, Makoto; Ando, Yukio; Nagafuchi, Seiho; Nishimura, Yasuharu; Senju, Satoru

    2014-01-01

    We herein demonstrate the immune-regulatory effect of embryonic stem cell-derived dendritic cells (ES-DCs) using two models of autoimmune disease, namely non-obese diabetic (NOD) mice and experimental autoimmune encephalomyelitis (EAE). Treatment of pre-diabetic NOD mice with ES-DCs exerted almost complete suppression of diabetes development during the observation period for more than 40 weeks. The prevention of diabetes by ES-DCs was accompanied with significant reduction of insulitis and decreased number of Th1 and Th17 cells in the spleen. Development of EAE was also inhibited by the treatment with ES-DCs, and the therapeutic effect was obtained even if ES-DCs were administrated after the onset of clinical symptoms. Treatment of EAE-induced mice with ES-DCs reduced the infiltration of inflammatory cells into the spinal cord and suppressed the T cell response to the myelin antigen. Importantly, the ES-DC treatment did not affect T cell response to an exogenous antigen. As the mechanisms underlying the reduction of the number of infiltrating Th1 cells, we observed the inhibition of differentiation and proliferation of Th1 cells by ES-DCs. Furthermore, the expression of VLA-4α on Th1 cells was significantly inhibited by ES-DCs. Considering the recent advances in human induced pluripotent stem cell-related technologies, these results suggest a clinical application for pluripotent stem cell-derived dendritic cells as a therapy for T cell-mediated autoimmune diseases. PMID:25522369

  15. Continuous flash suppression reduces negative afterimages.

    PubMed

    Tsuchiya, Naotsugu; Koch, Christof

    2005-08-01

    Illusions that produce perceptual suppression despite constant retinal input are used to manipulate visual consciousness. Here we report on a powerful variant of existing techniques, continuous flash suppression. Distinct images flashed successively at approximately 10 Hz into one eye reliably suppress an image presented to the other eye. The duration of perceptual suppression is at least ten times greater than that produced by binocular rivalry. Using this tool we show that the strength of the negative afterimage of an adaptor was reduced by half when it was perceptually suppressed by input from the other eye. The more completely the adaptor was suppressed, the more strongly the afterimage intensity was reduced. Paradoxically, trial-to-trial visibility of the adaptor did not correlate with the degree of reduction. Our results imply that formation of afterimages involves neuronal structures that access input from both eyes but that do not correspond directly to the neuronal correlates of perceptual awareness. PMID:15995700

  16. Engineered decoherence: Characterization and suppression

    NASA Astrophysics Data System (ADS)

    Hegde, Swathi S.; Mahesh, T. S.

    2014-06-01

    Due to omnipresent environmental interferences, quantum coherences inevitably undergo irreversible transformations over certain time scales, thus leading to the loss of encoded information. This process, known as decoherence, has been a major obstacle in realizing efficient quantum information processors. Understanding the mechanism of decoherence is crucial in developing tools to inhibit it. Here we utilize a method proposed by Teklemariam et al. [Phys. Rev. A 67, 062316 (2003), 10.1103/PhysRevA.67.062316] to engineer artificial decoherence in the system qubits by randomly perturbing their surrounding ancilla qubits. Using a two-qubit nuclear magnetic resonance quantum register, we characterize the artificial decoherence by noise spectroscopy and quantum process tomography. Further, we study the efficacy of dynamical decoupling sequences in suppressing the artificial decoherence. Here we describe the experimental results and their comparisons with theoretical simulations.

  17. Computer hardware fault administration

    DOEpatents

    Archer, Charles J.; Megerian, Mark G.; Ratterman, Joseph D.; Smith, Brian E.

    2010-09-14

    Computer hardware fault administration carried out in a parallel computer, where the parallel computer includes a plurality of compute nodes. The compute nodes are coupled for data communications by at least two independent data communications networks, where each data communications network includes data communications links connected to the compute nodes. Typical embodiments carry out hardware fault administration by identifying a location of a defective link in the first data communications network of the parallel computer and routing communications data around the defective link through the second data communications network of the parallel computer.

  18. MCS Systems Administration Toolkit

    2001-09-30

    This package contains a number of systems administration utilities to assist a team of system administrators in managing a computer environment by automating routine tasks and centralizing information. Included are utilities to help install software on a network of computers and programs to make an image of a disk drive, to manage and distribute configuration files for a number of systems, and to run self-testss on systems, as well as an example of using amore » database to manage host information and various utilities.« less

  19. MEK5 suppresses osteoblastic differentiation

    SciTech Connect

    Kaneshiro, Shoichi; Otsuki, Dai; Yoshida, Kiyoshi; Yoshikawa, Hideki; Higuchi, Chikahisa

    2015-07-31

    Extracellular signal-regulated kinase 5 (ERK5) is a member of the mitogen-activated protein kinase (MAPK) family and is activated by its upstream kinase, MAPK kinase 5 (MEK5), which is a member of the MEK family. Although the role of MEK5 has been investigated in several fields, little is known about its role in osteoblastic differentiation. In this study, we have demonstrated the role of MEK5 in osteoblastic differentiation in mouse preosteoblastic MC3T3-E1 cells and bone marrow stromal ST2 cells. We found that treatment with BIX02189, an inhibitor of MEK5, increased alkaline phosphatase (ALP) activity and the gene expression of ALP, osteocalcin (OCN) and osterix, as well as it enhanced the calcification of the extracellular matrix. Moreover, osteoblastic cell proliferation decreased at a concentration of greater than 0.5 μM. In addition, knockdown of MEK5 using siRNA induced an increase in ALP activity and in the gene expression of ALP, OCN, and osterix. In contrast, overexpression of wild-type MEK5 decreased ALP activity and attenuated osteoblastic differentiation markers including ALP, OCN and osterix, but promoted cell proliferation. In summary, our results indicated that MEK5 suppressed the osteoblastic differentiation, but promoted osteoblastic cell proliferation. These results implied that MEK5 may play a pivotal role in cell signaling to modulate the differentiation and proliferation of osteoblasts. Thus, inhibition of MEK5 signaling in osteoblasts may be of potential use in the treatment of osteoporosis. - Highlights: • MEK5 inhibitor BIX02189 suppresses proliferation of osteoblasts. • MEK5 knockdown and MEK5 inhibitor promote differentiation of osteoblasts. • MEK5 overexpression inhibits differentiation of osteoblasts.

  20. Genetics of barley hooded suppression.

    PubMed Central

    Roig, Cristina; Pozzi, Carlo; Santi, Luca; Müller, Judith; Wang, Yamei; Stile, Maria Rosaria; Rossini, Laura; Stanca, Michele; Salamini, Francesco

    2004-01-01

    The molecular basis of the barley dominant Hooded (K) mutant is a duplication of 305 bp in intron IV of the homeobox gene Bkn3. A chemical mutagenesis screen was carried out to identify genetical factors that participate in Bkn3 intron-mediated gene regulation. Plants from recurrently mutagenized KK seeds were examined for the suppression of the hooded awn phenotype induced by the K allele and, in total, 41 suK (suppressor of K) recessive mutants were identified. Complementation tests established the existence of five suK loci, and alleles suKB-4, suKC-33, suKD-25, suKE-74, and suKF-76 were studied in detail. All K-suppressed mutants showed a short-awn phenotype. The suK loci have been mapped by bulked segregant analysis nested in a standard mapping procedure based on AFLP markers. K suppressor loci suKB, B, E, and F all map in a short interval of chromosome 7H, while the locus suKD is assigned to chromosome 5H. A complementation test between the four suK mutants mapping on chromosome 7H and the short-awn mutant lks2, located nearby, excluded the allelism between suK loci and lks2. The last experiment made clear that the short-awn phenotype of suK mutants is due to a specific dominant function of the K allele, a function that is independent from the control on hood formation. The suK loci are discussed as candidate participants in the regulation of Bkn3 expression. PMID:15166167

  1. Optical suppression of drug-evoked phasic dopamine release

    PubMed Central

    McCutcheon, James E.; Cone, Jackson J.; Sinon, Christopher G.; Fortin, Samantha M.; Kantak, Pranish A.; Witten, Ilana B.; Deisseroth, Karl; Stuber, Garret D.; Roitman, Mitchell F.

    2014-01-01

    Brief fluctuations in dopamine concentration (dopamine transients) play a key role in behavior towards rewards, including drugs of abuse. Drug-evoked dopamine transients may result from actions at both dopamine cell bodies and dopamine terminals. Inhibitory opsins can be targeted to dopamine neurons permitting their firing activity to be suppressed. However, as dopamine transients can become uncoupled from firing, it is unknown whether optogenetic hyperpolarization at the level of the soma is able to suppress dopamine transients. Here, we used in vivo fast-scan cyclic voltammetry to record transients evoked by cocaine and raclopride in nucleus accumbens (NAc) of urethane-anesthetized rats. We targeted halorhodopsin (NpHR) specifically to dopamine cells by injecting Cre-inducible virus into ventral tegmental area (VTA) of transgenic rats that expressed Cre recombinase under control of the tyrosine hydroxylase promoter (TH-Cre+ rats). Consistent with previous work, co-administration of cocaine and raclopride led to the generation of dopamine transients in NAc shell. Illumination of VTA with laser strongly suppressed the frequency of transients in NpHR-expressing rats, but not in control rats. Laser did not have any effect on amplitude of transients. Thus, optogenetics can effectively reduce the occurrence of drug-evoked transients and is therefore a suitable approach for studying the functional role of such transients in drug-associated behavior. PMID:25278845

  2. Appetite suppression and weight reduction by a centrally active aminosterol.

    PubMed

    Ahima, Rexford S; Patel, Hiralben R; Takahashi, Nobuhiko; Qi, Yong; Hileman, Stanley M; Zasloff, Michael A

    2002-07-01

    The rise in obesity and its complications has generated enormous interest in the regulation of feeding and body weight. We show that a spermine metabolite of cholesterol (MSI-1436) decreases body weight, specifically fat, by suppressing feeding and preventing the reduction in energy expenditure, hormonal changes, and patterns of neuropeptide expression normally associated with weight loss. MSI-1436 enters the brain after peripheral injection and is more potent when injected into the cerebral ventricle (intracerebroventricular [ICV]). Systemic or ICV MSI-1436 administration induced similar patterns of Fos immunoreactivity in the brain, especially the paraventricular hypothalamic nucleus (PVN). This brain region integrates neural signals from hypothalamic and brain stem nuclei and regulates feeding behavior, autonomic function, and neuroendocrine function. Microinjection of MSI-1436 into the PVN potently suppressed feeding and reduced body weight for several days. Unlike caloric restriction, MSI-1436 decreased mRNA levels of agouti-related peptide and neuropeptide Y in the hypothalamus. These findings indicate that MSI-1436 acts in the brain to regulate food intake and energy expenditure, likely through suppression of orexigenic hypothalamic pathways. PMID:12086938

  3. The Effects of Chronic Ethanol Administration on Amygdala Neuronal Firing and Ethanol Withdrawal Seizures

    PubMed Central

    Feng, Hua-Jun; Faingold, Carl L.

    2008-01-01

    Summary Physical dependence on ethanol results in an ethanol withdrawal (ETX) syndrome including susceptibility to audiogenic seizures (AGS) in rodents after abrupt cessation of ethanol. Chronic ethanol administration and ETX induce functional changes of neurons in several brain regions, including the amygdala. Amygdala neurons are requisite elements of the neuronal network subserving AGS propagation during ETX induced by a subacute “binge” ethanol administration protocol. However, the effects of chronic ethanol administration on amygdala neuronal firing and ETX seizure behaviors are unknown. In the present study ethanol (5 g/kg) was administered intragastrically in Sprague-Dawley rats once daily for 28 days [chronic intermittent ethanol (CIE) protocol]. One week later the rats began receiving ethanol intragastrically 3 times daily for 4 days (binge protocol). Microwire electrodes were implanted prior to CIE or on the day after CIE ended day 29 to record extracellular action potentials in lateral amygdala (LAMG) neurons. The first dose of ethanol administered in the binge protocol following CIE treatment did not alter LAMG neuronal firing, which contrasts with firing suppression seen previously in the binge protocol alone. These data indicate that CIE induces neuroadaptive changes in the ETX network which reduce LAMG response to ethanol. LAMG neuronal responses to acoustic stimuli prior to AGS were significantly decreased during ETX as compared to those before ethanol treatment. LAMG neurons fired tonically throughout the tonic convulsions during AGS. CIE plus binge treatment resulted in a significantly greater mean seizure duration and a significantly elevated incidence of death than was seen previously with the binge protocol alone, indicating an elevated seizure severity following chronic ethanol administration. PMID:18614185

  4. Mechanisms of suppression in mixed allogeneic chimeras

    SciTech Connect

    Sykes, M.; Sachs, D.H.

    1988-08-01

    Cells with the ability to suppress cytotoxic T lymphocyte generation are found in the spleens of whole-body-irradiated (WBI) mixed allogeneic and syngeneic bone marrow transplant recipients in the early weeks after BMT. Previous studies have indicated that suppression is mediated by null cells similar to natural suppressor (NS) cells (1), and have ruled out several possible trivial explanations for the suppressive effect. We report here the results of additional experiments designed to assess possible mechanisms of suppression. We compared the cell populations after 5 days' incubation of cultures containing normal responding splenocytes plus irradiated allogeneic stimulator cells, with or without a cocultured suppressive chimeric splenocyte population. The data indicate that total viable cell yields are only slightly reduced, if at all, in suppressed cultures, but that the proportion of T cells is markedly reduced as measured at the end of the incubation period. Splenocytes from early BMT recipients do not appear to proliferate during the suppression of a mixed lymphocyte culture, and such populations represent only 15% of cells at the end of the 5-day incubation period. Suppression is strongest when the suppressive population is added at the initiation of MLC, and is lost if addition is delayed beyond day 3. Suppression can be overcome by T cell growth factor (TCGF)--and, to a lesser extent, by recombinant IL-2 (rIL-2), although resting suppressive populations do not consume appreciable amounts of these lymphokines. These results therefore suggest that suppression in MLC may occur primarily during the induction of helper T lymphocytes.

  5. Acoustic Suppression Systems and Related Methods

    NASA Technical Reports Server (NTRS)

    Kolaini, Ali R. (Inventor); Kern, Dennis L. (Inventor)

    2013-01-01

    An acoustic suppression system for absorbing and/or scattering acoustic energy comprising a plurality of acoustic targets in a containment is described, the acoustic targets configured to have resonance frequencies allowing the targets to be excited by incoming acoustic waves, the resonance frequencies being adjustable to suppress acoustic energy in a set frequency range. Methods for fabricating and implementing the acoustic suppression system are also provided.

  6. Noise Suppression for Dual-Energy CT Through Entropy Minimization.

    PubMed

    Petrongolo, Michael; Zhu, Lei

    2015-11-01

    In dual energy CT (DECT), noise amplification during signal decomposition significantly limits the utility of basis material images. Since clinically relevant objects typically contain a limited number of different materials, we propose an Image-domain Decomposition method through Entropy Minimization (IDEM) for noise suppression in DECT. Pixels of decomposed images are first linearly transformed into 2D clusters of data points, which are highly asymmetric due to strong signal correlation. An optimal axis is identified in the 2D space via numerical search such that the projection of data clusters onto the axis has minimum entropy. Noise suppression is performed on each image pixel by estimating the center-of-mass value of each data cluster along the direction perpendicular to the projection axis. The IDEM method is distinct from other noise suppression techniques in that it does not suppress pixel noise by reducing spatial variation between neighboring pixels. As supported by studies on Catphan©600 and anthropomorphic head phantoms, this feature endows our algorithm with a unique capability of reducing noise standard deviation on DECT decomposed images by approximately one order of magnitude while preserving spatial resolution and image noise power spectra (NPS). Compared with a filtering method and recently developed iterative method at the same level of noise suppression, the IDEM algorithm obtains high-resolution images with less artifacts. It also maintains accuracy of electron density measurements with less than 2% bias error. The IDEM method effectively suppresses noise of DECT for quantitative use, with appealing features on preservation of image spatial resolution and NPS. PMID:25955585

  7. SUPPRESSION OF STAR FORMATION IN NGC 1266

    SciTech Connect

    Alatalo, Katherine; Lanz, Lauranne; Bitsakis, Theodoros; Appleton, Philip N.; Ogle, Patrick M.; Lacy, Mark; Lonsdale, Carol J.; Nyland, Kristina; Meier, David S.; Cales, Sabrina L.; Chang, Philip; Davis, Timothy A.; De Zeeuw, P. T.; Martín, Sergio

    2015-01-01

    NGC 1266 is a nearby lenticular galaxy that harbors a massive outflow of molecular gas powered by the mechanical energy of an active galactic nucleus (AGN). It has been speculated that such outflows hinder star formation (SF) in their host galaxies, providing a form of feedback to the process of galaxy formation. Previous studies, however, indicated that only jets from extremely rare, high-power quasars or radio galaxies could impart significant feedback on their hosts. Here we present detailed observations of the gas and dust continuum of NGC 1266 at millimeter wavelengths. Our observations show that molecular gas is being driven out of the nuclear region at M-dot {sub out}≈110 M{sub ⊙} yr{sup –1}, of which the vast majority cannot escape the nucleus. Only 2 M {sub ☉} yr{sup –1} is actually capable of escaping the galaxy. Most of the molecular gas that remains is very inefficient at forming stars. The far-infrared emission is dominated by an ultra-compact (≲ 50 pc) source that could either be powered by an AGN or by an ultra-compact starburst. The ratio of the SF surface density (Σ{sub SFR}) to the gas surface density (Σ{sub H{sub 2}}) indicates that SF is suppressed by a factor of ≈50 compared to normal star-forming galaxies if all gas is forming stars, and ≈150 for the outskirt (98%) dense molecular gas if the central region is powered by an ultra-compact starburst. The AGN-driven bulk outflow could account for this extreme suppression by hindering the fragmentation and gravitational collapse necessary to form stars through a process of turbulent injection. This result suggests that even relatively common, low-power AGNs are able to alter the evolution of their host galaxies as their black holes grow onto the M-σ relation.

  8. Deconstructing Interocular Suppression: Attention and Divisive Normalization.

    PubMed

    Li, Hsin-Hung; Carrasco, Marisa; Heeger, David J

    2015-10-01

    In interocular suppression, a suprathreshold monocular target can be rendered invisible by a salient competitor stimulus presented in the other eye. Despite decades of research on interocular suppression and related phenomena (e.g., binocular rivalry, flash suppression, continuous flash suppression), the neural processing underlying interocular suppression is still unknown. We developed and tested a computational model of interocular suppression. The model included two processes that contributed to the strength of interocular suppression: divisive normalization and attentional modulation. According to the model, the salient competitor induced a stimulus-driven attentional modulation selective for the location and orientation of the competitor, thereby increasing the gain of neural responses to the competitor and reducing the gain of neural responses to the target. Additional suppression was induced by divisive normalization in the model, similar to other forms of visual masking. To test the model, we conducted psychophysics experiments in which both the size and the eye-of-origin of the competitor were manipulated. For small and medium competitors, behavioral performance was consonant with a change in the response gain of neurons that responded to the target. But large competitors induced a contrast-gain change, even when the competitor was split between the two eyes. The model correctly predicted these results and outperformed an alternative model in which the attentional modulation was eye specific. We conclude that both stimulus-driven attention (selective for location and feature) and divisive normalization contribute to interocular suppression. PMID:26517321

  9. Issues in Numerical Simulation of Fire Suppression

    SciTech Connect

    Tieszen, S.R.; Lopez, A.R.

    1999-04-12

    This paper outlines general physical and computational issues associated with performing numerical simulation of fire suppression. Fire suppression encompasses a broad range of chemistry and physics over a large range of time and length scales. The authors discuss the dominant physical/chemical processes important to fire suppression that must be captured by a fire suppression model to be of engineering usefulness. First-principles solutions are not possible due to computational limitations, even with the new generation of tera-flop computers. A basic strategy combining computational fluid dynamics (CFD) simulation techniques with sub-grid model approximations for processes that have length scales unresolvable by gridding is presented.

  10. ISS Update: Burning and Suppression of Solids

    NASA Video Gallery

    ISS Update Commentator Pat Ryan interviews Paul Ferkul, Principal Investigator for the Burning and Suppression of Solids (BASS) experiment, about performing combustion experiments in microgravity. ...

  11. Deconstructing Interocular Suppression: Attention and Divisive Normalization

    PubMed Central

    Li, Hsin-Hung; Carrasco, Marisa; Heeger, David J.

    2015-01-01

    In interocular suppression, a suprathreshold monocular target can be rendered invisible by a salient competitor stimulus presented in the other eye. Despite decades of research on interocular suppression and related phenomena (e.g., binocular rivalry, flash suppression, continuous flash suppression), the neural processing underlying interocular suppression is still unknown. We developed and tested a computational model of interocular suppression. The model included two processes that contributed to the strength of interocular suppression: divisive normalization and attentional modulation. According to the model, the salient competitor induced a stimulus-driven attentional modulation selective for the location and orientation of the competitor, thereby increasing the gain of neural responses to the competitor and reducing the gain of neural responses to the target. Additional suppression was induced by divisive normalization in the model, similar to other forms of visual masking. To test the model, we conducted psychophysics experiments in which both the size and the eye-of-origin of the competitor were manipulated. For small and medium competitors, behavioral performance was consonant with a change in the response gain of neurons that responded to the target. But large competitors induced a contrast-gain change, even when the competitor was split between the two eyes. The model correctly predicted these results and outperformed an alternative model in which the attentional modulation was eye specific. We conclude that both stimulus-driven attention (selective for location and feature) and divisive normalization contribute to interocular suppression. PMID:26517321

  12. Aurantiamide acetate suppresses the growth of malignant gliomas in vitro and in vivo by inhibiting autophagic flux

    PubMed Central

    Yang, Yi; Zhang, Li-hui; Yang, Bing-xian; Tian, Jin-kui; Zhang, Lin

    2015-01-01

    We aim to investigate the effect of aurantiamide acetate isolated from the aerial parts of Clematis terniflora DC against gliomas. Human malignant glioma U87 and U251 cells were incubated with different concentrations (0–100 μM) of aurantiamide acetate. Aurantiamide acetate greatly decreased the cell viability in a dose- and time-dependent manner. It induced moderate mitochondrial fragmentation and the loss of mitochondrial membrane potential. No significant difference was found in the alternation of other intracellular organelles, although F-actin structure was slightly disturbed. Apparent ultrastructure alternation with increased autophagosome and autolysosome accumulation was observed in aurantiamide acetate-treated cells. The expression of LC3-II was greatly up-regulated in cells exposed to aurantiamide acetate (P < 0.05 compared with control). The cytoplasmic accumulation of autophagosomes and autolysosomes induced by aurantiamide acetate treatment was confirmed by fluorescent reporter protein labelling. Administration of chloroquine (CQ), which inhibits the fusion step of autophagosomes, further increased the accumulation of autophagosomes in the cytoplasm of U87 cells. Autophagy inhibition by 3-methyladenine, Bafilomycin A1 or CQ had no influence on aurantiamide acetate-induced cytotoxicity, whereas autophagy stimulator rapamycin significantly suppressed aurantiamide acetate-induced cell death. The anti-tumour effects of aurantiamide acetate were further evaluated in tumour-bearing nude mice. Intratumoural injection of aurantiamide acetate obviously suppressed tumour growth, and increased number of autophagic vacuoles was observed in tumour tissues of animals receiving aurantiamide acetate. Our findings suggest that aurantiamide acetate may suppress the growth of malignant gliomas by blocking autophagic flux. PMID:25704599

  13. Aurantiamide acetate suppresses the growth of malignant gliomas in vitro and in vivo by inhibiting autophagic flux.

    PubMed

    Yang, Yi; Zhang, Li-hui; Yang, Bing-xian; Tian, Jin-kui; Zhang, Lin

    2015-05-01

    We aim to investigate the effect of aurantiamide acetate isolated from the aerial parts of Clematis terniflora DC against gliomas. Human malignant glioma U87 and U251 cells were incubated with different concentrations (0-100 μM) of aurantiamide acetate. Aurantiamide acetate greatly decreased the cell viability in a dose- and time-dependent manner. It induced moderate mitochondrial fragmentation and the loss of mitochondrial membrane potential. No significant difference was found in the alternation of other intracellular organelles, although F-actin structure was slightly disturbed. Apparent ultrastructure alternation with increased autophagosome and autolysosome accumulation was observed in aurantiamide acetate-treated cells. The expression of LC3-II was greatly up-regulated in cells exposed to aurantiamide acetate (P < 0.05 compared with control). The cytoplasmic accumulation of autophagosomes and autolysosomes induced by aurantiamide acetate treatment was confirmed by fluorescent reporter protein labelling. Administration of chloroquine (CQ), which inhibits the fusion step of autophagosomes, further increased the accumulation of autophagosomes in the cytoplasm of U87 cells. Autophagy inhibition by 3-methyladenine, Bafilomycin A1 or CQ had no influence on aurantiamide acetate-induced cytotoxicity, whereas autophagy stimulator rapamycin significantly suppressed aurantiamide acetate-induced cell death. The anti-tumour effects of aurantiamide acetate were further evaluated in tumour-bearing nude mice. Intratumoural injection of aurantiamide acetate obviously suppressed tumour growth, and increased number of autophagic vacuoles was observed in tumour tissues of animals receiving aurantiamide acetate. Our findings suggest that aurantiamide acetate may suppress the growth of malignant gliomas by blocking autophagic flux. PMID:25704599

  14. Valproic acid induces autophagy by suppressing the Akt/mTOR pathway in human prostate cancer cells

    PubMed Central

    Xia, Qinghua; Zheng, Yi; Jiang, Wei; Huang, Zhongxian; Wang, Muwen; Rodriguez, Ronald; Jin, Xunbo

    2016-01-01

    Previous studies have demonstrated that the chronic administration of valproic acid (VPA) suppresses angiogenesis in vivo; however, the mechanisms implicated in VPA-induced autophagy remain unclear. The current study aimed to assess VPA-induced autophagy in three prostate cancer cell lines (PC3, DU145 and LNCaP), in addition to analyzing the Akt/mammalian target of rapamycin (mTOR) signal pathway. Prostate cancer cell lines were cultured with various doses of VPA. Cell cycle was analyzed using flow cytometry, and autophagy markers [1A/1B-light chain 3 (LC3)-II and Beclin-1] were examined using transmission electron microscopy, fluorescent microscopy and western blotting. Activation of the Akt/mTOR signal pathway was also assessed by western blotting. The results demonstrated that VPA induced autophagosomes and suppressed the Akt/mTOR signal pathway. This was confirmed by detection of increased LC3-II and Beclin-1 in VPA-treated cells compared with untreated controls. Phosphorylated forms of Akt (PC3, P=0.048; DU145, P=0.045; LNCaP, P=0.039) and mTOR (PC3, P=0.012; DU145, P=0.41; LNCaP, P=0.35) were significantly reduced following VPA treatment. These results suggest that VPA may function as a histone deacetylase inhibitor, suppressing the growth of prostate cancer cells by modulating autophagy pathways, including inhibition of the Akt/mTOR pathway. Further experiments are required to determine the significance of all involved pathways regarding VPA-induced growth inhibition. PMID:27588130

  15. The antiallodynic action of pregabalin may depend on the suppression of spinal neuronal hyperexcitability in rats with spared nerve injury

    PubMed Central

    Ding, Lei; Cai, Jie; Guo, Xiang-Yang; Meng, Xiu-Li; Xing, Guo-Gang

    2014-01-01

    BACKGROUND: Pregabalin (PGB) is a novel antiepileptic drug and is also used as a first-line medication for the treatment of neuropathic pain. However, the mechanisms of its analgesic effects remain largely unknown. OBJECTIVES: To elucidate the mechanisms underlying the antiallodynic action of PGB in rats with neuropathic pain. METHODS: In a rat model of neuropathic pain induced by spared nerve injury, mechanical allodynia, as a behavioural sign of neuropathic pain, was assessed by measuring 50% paw withdrawal threshold with von Frey filaments. Activities of dorsal horn wide dynamic range (WDR) neurons were examined by extracellular electrophysiological recording in vivo. RESULTS: Spinal administration of PGB exerted a significant antiallodynic effect and a prominent inhibitory effect on the hypersensitivity of dorsal horn WDR neurons in rats with spared nerve injury. CONCLUSION: The antiallodynic action of PGB is likely dependent on the suppression of WDR neuron hyperexcitability in rats with neuropathic pain. PMID:24851240

  16. Simultaneous suppression of tone burst-evoked otoacoustic emissions: Two and three-tone burst combinations.

    PubMed

    Killan, Edward C; Lutman, Mark E; Thyer, Nicholas J

    2015-09-01

    Previous investigations have shown that components of a tone burst-evoked otoacoustic emission (TBOAE) evoked by a 1 kHz tone burst (TB1) can be suppressed by the simultaneous presence of a 2 kHz tone burst (TB2) or a pair of tone bursts at 2 and 3 kHz (TB2 and TB3 respectively). No previous study has measured this "simultaneous suppression of TBOAEs" for both TB2 alone and TB2 and TB3 from the same ears, so that the effect of the additional presence of TB3 on suppression caused by TB2 is not known. In simple terms, three outcomes are possible; suppression increases, suppression is reduced or suppression is not affected. Comparison of previously reported simultaneous suppression data suggests TB3 causes a reduction in suppression, though it is not clear if this is a genuine effect or simply reflects methodological and ear differences between studies. This issue has implications for previously proposed mechanisms of simultaneous suppression of TBOAEs and the interpretation of clinical data, and is clarified by the present study. Simultaneous suppression of TBOAEs was measured for TB1 and TB2 as well as TB1, TB2 and TB3 at 50, 60 and 70 dB p.e. SPL from nine normal human ears. Results showed no significant difference between mean suppression obtained for the two and three-tone burst combinations, indicating the reduction of suppression inferred from comparison of previous data is likely a result of methodological and ear differences rather than a genuine effect. PMID:25959270

  17. Disinfection practices in intravenous drug administration.

    PubMed

    Helder, Onno K; Kornelisse, René F; Reiss, Irwin K M; Ista, Erwin

    2016-06-01

    The aim of the study was to determine the effectiveness of a feedback intervention on adherence to disinfection procedures during intravenous medication preparation and administration. We found that full adherence to the protocols significantly improved from 7.3% to 21.5% (P < .001) regarding medication preparation and from 7.9% to 15.5% (P = .012) regarding medication administration. However, disinfection practices still need improvement. PMID:26899528

  18. Triacylglycerol kinetics in endotoxic rats with suppressed lipoprotein lipase activity

    SciTech Connect

    Bagby, G.J.; Corll, C.B.; Martinez, R.R.

    1987-07-01

    Hypertriglyceridemia observed in animals after bacterial endotoxin administration and some forms of sepsis can result from increased hepatic triacylglycerol (TG) output or decreased TG clearance by extrahepatic tissues. To differentiate between these two possibilities, TG and free fatty acid (FFA) kinetics were determined in control and endotoxin-injected rats 18 h after treatment. Plasma TG and FFA kinetics were assessed by a constant intravenous infusion with (9,10-/sup 3/H)palmitate-labeled very low-density lipoprotein and (1-/sup 14/C)palmitate bound to albumin, respectively. In addition, lipoprotein lipase (LPL) activity was determined in heart, skeletal muscle, and adipose tissue as well as in postheparin plasma of functionally hepatectomized, adrenalectomized, and gonadectomized rats. Plasma FFA acid concentrations were slightly increased in endotoxin-treated rats but their turnover did not differ from control. Endotoxin-treated rats had a threefold increase in plasma TG concentrations and decreased heart, skeletal muscle, and post-heparin plasma LPL activity. Plasma TG turnover was decreased, indicating that hypertriglyceridemia was not due to an increased TG output by the liver. Instead, the endotoxin-induced increase in plasma TG concentration was consequence of the 80% reduction in TG metabolic clearance rate. Thus, suppression of LPL activity in endotoxic animals impairs TG clearance resulting in hypertriglyceridemia. Furthermore, endotoxin administration reduced the delivery of TG-FFA to extrahepatic tissues because hepatic synthesis and secretion of TG from plasma FFA was decreased and LPL activity was suppressed.

  19. Telecommunications administration standard

    SciTech Connect

    Gustwiller, K.D.

    1996-05-01

    The administration of telecommunications is critical to proper maintenance and operation. The intent is to be able to properly support telecommunications for the distribution of all information within a building/campus. This standard will provide a uniform administration scheme that is independent of applications, and will establish guidelines for owners, installers, designers and contractors. This standard will accommodate existing building wiring, new building wiring and outside plant wiring. Existing buildings may not readily adapt to all applications of this standard, but the requirement for telecommunications administration is applicable to all buildings. Administration of the telecommunications infrastructure includes documentation (labels, records, drawings, reports, and work orders) of cables, termination hardware, patching and cross-connect facilities, telecommunications rooms, and other telecommunications spaces (conduits, grounding, and cable pathways are documented by Facilities Engineering). The investment in properly documenting telecommunications is a worthwhile effort. It is necessary to adhere to these standards to ensure quality and efficiency for the operation and maintenance of the telecommunications infrastructure for Sandia National Laboratories.

  20. Study Shows Administrative Shortage.

    ERIC Educational Resources Information Center

    Sullivan, John R., Jr.

    1989-01-01

    Summarizes "Administrative Shortage in New England: The Evidence, the Causes, the Recommendations." High pressure, long hours, low salaries, and high housing costs are among the reasons cited for the shortage. Recommendations are centered on role identity, staff support, training, and recruitment. (SI)

  1. Central Administration. Interim Report.

    ERIC Educational Resources Information Center

    Duke Univ., Durham, NC.

    Because the configuration of the central administration of Duke University has recently been modified, this report was prepared: (1) to describe the changes and rearrangements thus far introduced; (2) to propose desirable clarifications not yet provided; (3) to recommend certain additional changes where these may already appear to be needed; and…

  2. Guidebook for School Administrators.

    ERIC Educational Resources Information Center

    Hess, Fritz, Ed.

    To provide guidance and advice regarding day-to-day responsibilities of new and experienced school administrators and superintendents in New York State, this compendium of knowledge and advice submitted by practitioners is presented with emphasis on all major aspects of superintendency. The section on general aspects of superintendency includes…

  3. Redis database administration tool

    2013-02-13

    MyRedis is a product of the Lorenz subproject under the ASC Scirntific Data Management effort. MyRedis is a web based utility designed to allow easy administration of instances of Redis databases. It can be usedd to view and manipulate data as well as run commands directly against a variety of different Redis hosts.

  4. Female Administrator Acceptance.

    ERIC Educational Resources Information Center

    Pawlitschek, Elizabeth Ann

    The number of women in educational administration is declining, despite official efforts to end sex discrimination. Women are hampered on the way to obtaining an adequate education, finding roadblocks from sex bias in elementary readers to discrimination in graduate programs; are considered responsible for home and children even when working full…

  5. Hospital Library Administration.

    ERIC Educational Resources Information Center

    Cramer, Anne

    The objectives of a hospital are to improve patient care, while the objectives of a hospital library are to improve services to the staff which will support their efforts. This handbook dealing with hospital administration is designed to aid the librarian in either implementing a hospital library, or improving services in an existing medical…

  6. Discretionary Grants Administration Manual.

    ERIC Educational Resources Information Center

    Office of Human Development Services (DHHS), Washington, DC.

    This manual sets forth applicable administrative policies and procedures to recipients of discretionary project grants or cooperative agreements awarded by program offices in the Office of Human Development Services (HDS). It is intended to serve as a basic reference for project directors and business officers of recipient organizations who are…

  7. [Rural School Administrator's Resources.

    ERIC Educational Resources Information Center

    AEL, Inc., Charleston, WV.

    This packet contains resources on five topics relevant to rural school administrators. "Assessing Parent Involvement: A Checklist for Rural Schools": discusses educator beliefs that support successful parent engagement programs, challenges and advantages of rural schools attempting to involve parents and community, and aspects of successful…

  8. Information for School Administrators.

    ERIC Educational Resources Information Center

    Kowitz, Gerald T.; And Others

    Modern management theory, based on the reduction of uncertainties, demands the collection and manipulation of large amounts of information. School Administrators choke in the process of trying to digest a proliferation of data, only some of which are useful. The aims of the study were to explore the extent to which large amounts of data could be…

  9. Research Administration: Lessons Learned.

    ERIC Educational Resources Information Center

    Dummer, George H.

    1995-01-01

    The ways in which accountability issues have affected federal-university relationships, particularly in the area of academic research, are examined. Lessons university administrators have learned since issuance of Office of Management and Budget Circular A-21 in 1958, Congressional hearings on the operations of the National Institutes of Health…

  10. Administrators Confront Student "Sexting"

    ERIC Educational Resources Information Center

    Manzo, Kathleen Kennedy

    2009-01-01

    Cellphone-savvy students have created instructional and disciplinary challenges for educators for years. But the recent emergence of "sexting" by adolescents over their mobile phones caught many school administrators off guard, and the practice is prompting efforts around the country to craft policy responses. Students' sharing of nude or…

  11. Championing the Latino Administrator

    ERIC Educational Resources Information Center

    Garcia, Carlos A.

    2011-01-01

    When the author worked as a vice principal at a K-8 school in Watsonville, California, a school predominantly filled with migrant workers' children, he felt a lack of support as a Latino as he began moving up into school administration. He also continued to see what he had seen as a teacher--which was how underserved minority students were. These…

  12. Hispanic Administrators in Kentucky

    ERIC Educational Resources Information Center

    Ballestero, Victor; Wright, Sam

    2008-01-01

    The study was designed to provide information on Hispanic administrators in the Commonwealth of Kentucky. The data was obtained from Kentucky school Superintendents or their designees in 175 public school districts. The Hispanic survey contained six questions. The survey was mailed to Kentucky Superintendents on April 21, 2008. A follow-up survey…

  13. Educational Administration's Weber.

    ERIC Educational Resources Information Center

    Gronn, Peter

    1994-01-01

    Discusses Max Weber's importance in Greenfield's work, particularly in Greenfield and Ribbins'"Greenfield on Educational Administration" (1993). In concentrating on human actors' subjective understanding, Greenfield was a faithful Weberian. However, he deviated from Weber by disavowing structural explanations of social and organizational…

  14. "Complicating" Educational Administrators.

    ERIC Educational Resources Information Center

    Bell, Colleen S.

    Administrators desiring to lead organizations that will adapt and survive in a complex environment like today's public schools need to develop what Karl Weick calls "complicated" understanding of "requisite variety." The law of requisite variety states that a diverse and complicated environment demands similar diversity from its inhabitants if…

  15. A Treatise on Administration.

    ERIC Educational Resources Information Center

    Moore, Thomas R.

    1988-01-01

    Expands Henri Fayol's definition of the administrative process to include a humanistic approach involving planning, organizing, implementing, controlling, evaluating, and satisfying functions. This empirical definition differs from some theoretical approaches by looking beyond resource consumption to consider ecological effects on the environment…

  16. Administrative Uses of Microcomputers.

    ERIC Educational Resources Information Center

    Crawford, Chase

    1987-01-01

    This paper examines the administrative uses of the microcomputer, stating that high performance educational managers are likely to have microcomputers in their organizations. Four situations that would justify the use of a computer are: (1) when massive amounts of data are processed through well-defined operations; (2) when data processing is…

  17. Administrative Utility Analysis: Appendices.

    ERIC Educational Resources Information Center

    Peat, Marwick, Mitchell and Co., San Juan, Puerto Rico.

    Appendixes to a study on administrative utility analysis and vocational education programs for the Area of Vocational and Technical Education (AVTE) in the Puerto Rico Department of Education contain the planning and budgeting system elements, position descriptions, and information on the growth of vocational education in Puerto Rico. The elements…

  18. Educator Effectiveness Administrative Manual

    ERIC Educational Resources Information Center

    Pennsylvania Department of Education, 2014

    2014-01-01

    The goal of this manual is to provide guidance in the evaluation of educators, highlight critical components of effectiveness training, and offer opportunities for professional growth. The term "educator" includes teachers, all professional and temporary professional employees, education specialists, and school administrators/principals.…

  19. Standards and Administration.

    ERIC Educational Resources Information Center

    Gross, S. P.

    1978-01-01

    Presents a literature review of water quality standards and administration, covering publications of 1976-77. Consideration is given to municipal facilities, National Pollutant Discharge Elimination Systems, regional and international water quality management, and effluent standards. A list of 99 references is also presented. (HM)

  20. Migrant Education Administrative Handbook.

    ERIC Educational Resources Information Center

    Louisiana State Dept. of Education, Baton Rouge. Bureau of Migrant Education.

    Intended to provide information pertaining to the administration of migrant education projects in Louisiana, the handbook is divided into two sections: basic guidelines for program operations and support services--nursing. Section I covers the Federal and State migrant program, local migrant projects, project personnel and staff development, and…

  1. Using Administrative Data. Introduction.

    ERIC Educational Resources Information Center

    DiLeonardi, Joan W.; Yuan, Ying-Ying T.

    2000-01-01

    Discusses the value of administrative data to child welfare researchers. Considers issues in using client records--confidentiality, selection of data, historical data, sampling reliability, replication of findings, and access to data--that can be resolved in standardized ways. Notes other problematic issues, such as greater distance from subject,…

  2. Standards for Administrators.

    ERIC Educational Resources Information Center

    Lashway, Larry

    1998-01-01

    This newsletter reviews five reports that address the implications of standards for administrators. These texts include "Designing and Implementing Standards-Based Accountability System" (Education Commission of the States), which describes some of the policy implications of standards-driven accountability; "Why Principals Fail: Are National…

  3. Administrative Effectiveness in Higher Education.

    ERIC Educational Resources Information Center

    Whetten, David A.; Cameron, Kim S.

    1985-01-01

    Determinants of organizational and administrative effectiveness in higher education are discussed, and eight administrator characteristics associated with maintaining and enhancing institutional effectiveness are identified. (MSE)

  4. Leadership Behaviors of Vocational Education Administrators in the Midwest.

    ERIC Educational Resources Information Center

    Baugher, Shirley L.; And Others

    1985-01-01

    Leadership behaviors of vocational education administrators in 15 midwestern states were studied. The administrators, representing four institutional types, responded to Part LB of the Boss' Management Styles Survey and the Bem Sex Role Inventory. The MANOVA procedure revealed statistically significant differences among administrative roles with…

  5. Suppression by 1-β-d-Ribofuranosyl-1,2,4-Triazole-3-Carboxamide (Virazole, ICN 1229) of Influenza Virus-Induced Infections in Mice

    PubMed Central

    Khare, Gyaneshwar P.; Sidwell, Robert W.; Witkowski, J. T.; Simon, Lionel N.; Robins, Roland K.

    1973-01-01

    1-β-d-Ribofuranosyl-1,2,4-triazole-3-carboxamide (Virazole) was found to possess significant antiviral activity against aerosol-induced or intranasally induced influenza A0, A2, and B virus infections in mice. Significant protection was achieved by both oral and intraperitoneal routes of administration. Depending upon the level of virus infection, antiviral activity was best observed at the daily dose of 75 mg/kg. The efficacy of the compound was evidenced by an increase in survivor number, prolongation of mean survival time, suppression of lung consolidation, or decrease in hemagglutinin titer in the infected lung samples. The therapeutic value of this synthetic triazole nucleoside was evident as noted by a significant increase in survivor number even if the treatment was started as late as 24 h after infection with an aerosol of influenza A2 virus. PMID:4790606

  6. Aerosol administration of phospho-sulindac inhibits lung tumorigenesis.

    PubMed

    Cheng, Ka Wing; Wong, Chi C; Alston, Ninche; Mackenzie, Gerardo G; Huang, Liqun; Ouyang, Nengtai; Xie, Gang; Wiedmann, Timothy; Rigas, Basil

    2013-08-01

    Phospho-sulindac is a sulindac derivative with promising anticancer activity in lung cancer, but its limited metabolic stability presents a major challenge for systemic therapy. We reasoned that inhalation delivery of phospho-sulindac might overcome first-pass metabolism and produce high levels of intact drug in lung tumors. Here, we developed a system for aerosolization of phospho-sulindac and evaluated the antitumor efficacy of inhaled phospho-sulindac in an orthotopic model of human non-small cell lung cancer (A549 cells). We found that administration by inhalation delivered high levels of phospho-sulindac to the lungs and minimized its hydrolysis to less active metabolites. Consequently, inhaled phospho-sulindac (6.5 mg/kg) was highly effective in inhibiting lung tumorigenesis (75%; P < 0.01) and significantly improved the survival of mice bearing orthotopic A549 xenografts. Mechanistically, phospho-sulindac suppressed lung tumorigenesis by (i) inhibiting EGF receptor (EGFR) activation, leading to profound inhibition of Raf/MEK/ERK and PI3K/AKT/mTOR survival cascades; (ii) inducing oxidative stress, which provokes the collapse of mitochondrial membrane potential and mitochondria-dependent cell death; and (iii) inducing autophagic cell death. Our data establish that inhalation delivery of phospho-sulindac is an efficacious approach to the control of lung cancer, which merits further evaluation. PMID:23645590

  7. The effects of suppressing intrusive thoughts on dream content, dream distress and psychological parameters.

    PubMed

    Kröner-Borowik, Tana; Gosch, Stefanie; Hansen, Kathrin; Borowik, Benjamin; Schredl, Michael; Steil, Regina

    2013-10-01

    Suppressing unwanted thoughts can lead to an increased occurrence of the suppressed thought in dreams. This is explainable by the ironic control theory, which theorizes why the suppression of thoughts might make them more persistent. The present study examined the influence of thought suppression on dream rebound, dream distress, general psychiatric symptomatology, depression, sleep quality and perceived stress. Thirty healthy participants (good sleepers) were investigated over a period of 1 week. Half were instructed to suppress an unwanted thought 5 min prior to sleep, whereas the other half were allowed to think of anything at all. Dream content was assessed through a dream diary. Independent raters assessed whether or not the dreams were related to the suppressed target thought. The results demonstrated increased target-related dreams and a tendency to have more distressing dreams in the suppression condition. Moreover, the data imply that thought suppression may lead to significantly increased general psychiatric symptomatology. No significant effects were found for the other secondary outcomes. PMID:23679926

  8. Thought Suppression is Associated with Psychological Distress in Homebound Older Adults

    PubMed Central

    Petkus, Andrew J.; Gum, Amber; Wetherell, Julie Loebach

    2014-01-01

    Background Engaging in thought suppression as a coping mechanism has been associated with higher rates of anxiety and depressive disorders in younger adults. Homebound older adults are a population of elders experiencing poor health and high levels of depression and anxiety. It is unclear the extent to which psychological factors, such as thought suppression, are associated with distress, given that their health and disability status may be more salient. The aim of this study was to investigate thought suppression in relation to anxiety and depressive symptoms in homebound older adults. Methods Participants (N = 142) were clients of home-based case management services delivered by aging service agencies in Florida. Participants were administered a research interview that included the White Bear Suppression Inventory, Structured Clinical Interview for DSM-IV Diagnosis (SCID), Brief Symptom Inventory-18 (BSI-18), and Modified Mini-Mental Status Examination (3MS). Case managers provided standard assessments containing functional and health status of the participant. Results After controlling for physical health and cognitive functioning, thought suppression was significantly associated with higher likelihood of clinically significant somatic, depressive, and anxiety symptoms on the BSI-18. Thought suppression was also associated with meeting criteria for a SCID depressive or adjustment disorder. Engaging in thought suppression was associated with worse mental health in this sample of homebound older adults even after taking into account physical health, disability, and cognitive functioning. Conclusions These findings suggest the need to develop and test interventions that may address thought suppression as a coping mechanism. PMID:22170756

  9. Celastrol Ameliorates Ulcerative Colitis-Related Colorectal Cancer in Mice via Suppressing Inflammatory Responses and Epithelial-Mesenchymal Transition

    PubMed Central

    Lin, Lianjie; Sun, Yan; Wang, Dongxu; Zheng, Shihang; Zhang, Jing; Zheng, Changqing

    2016-01-01

    Celastrol, also named as tripterine, is a pharmacologically active ingredient extracted from the root of traditional Chinese herb Tripterygium wilfordii Hook F with potent anti-inflammatory and anti-tumor activities. In the present study, we investigated the effects of celastrol on ulcerative colitis-related colorectal cancer (UC-CRC) as well as CRC in vivo and in vitro and explored its underlying mechanisms. UC-CRC model was induced in C57BL/6 mice by administration of azoxymethane (AOM) and dextran sodium sulfate (DSS). Colonic tumor xenograft models were developed in BALB/c-nu mice by subcutaneous injection with HCT116 and HT-29 cells. Intragastric administration of celastrol (2 mg/kg/d) for 14 weeks significantly increased the survival ratio and reduced the multiplicity of colonic neoplasms compared with AOM/DSS model mice. Mechanically, celastrol treatment significantly prevented AOM/DSS-induced up-regulation of expression levels of oncologic markers including mutated p53 and phospho-p53, β-catenin and proliferating cell nuclear antigen (PCNA). In addition, treatment with celastrol inhibited inflammatory responses, as indicated by the decrease of serum tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6, down-regulation of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), and inactivation of nuclear factor κB (NF-κB). Moreover, celastrol obviously suppressed epithelial-mesenchymal transition (EMT) through up-regulating E-cadherin and down-regulating N-cadherin, Vimentin and Snail. Additionally, we also demonstrated that celastrol inhibited human CRC cell proliferation and attenuated colonic xenograft tumor growth via reversing EMT. Taken together, celastrol could effectively ameliorate UC-CRC by suppressing inflammatory responses and EMT, suggesting a potential drug candidate for UC-CRC therapy. PMID:26793111

  10. Naloxone administration following operant training of sucrose/water discrimination in the rat.

    PubMed

    O'Hare, E O; Cleary, J; Bartz, P J; Weldon, D T; Billington, C J; Levine, A S

    1997-02-01

    The suppression of food intake observed following naloxone administration has often been ascribed to palatability or taste. Unfortunately, many confounds become apparent when attempts are made to isolate such factors in the investigation of ingestive behaviors. In the present study, rats (two groups) were trained to discriminate either a 10% or 5% sucrose solution from water (0.1 ml). These mildly food deprived subjects (95% of free-feeding weight) were trained to press the appropriate lever in a two-lever operant chamber following sampling of sucrose or water; successful responding was reinforced by delivery of a 45 mg grain food pellet. Following random exposure to reduced sucrose concentrations tested under extinction, a sucrose concentration gradient (1.0, 0.5, 0.1, 0.05, 0.01 and 0.005% sucrose solution) was established for both training groups under i.p. saline administration. Data collected under i.p. saline were then compared to those collected following random i.pf1p4loxone administration (3.0, 1.0, 0.3 and 0.1 mg/kg). No significant differences were observed between the sucrose concentration gradients obtained under saline and those obtained under naloxone, suggesting that the anorectic effect of naloxone is not primarily determined by discrimination of sweet taste. PMID:9084069

  11. Effects of preoperative and intraoperative glucose administration on glucose use and fat catabolism during laparotomy under sevoflurane anesthesia in fasted rats.

    PubMed

    Mori, Yoshiteru; Kitamura, Takayuki; Kawamura, Gaku; Sato, Kanako; Sato, Rui; Araki, Yuko; Yamada, Yoshitsugu

    2015-11-01

    Preoperative fasting as well as surgical stress significantly modifies metabolisms. Recent studies reported the possible advantageous effects of glucose administration on perioperative metabolisms; however, the underlying mechanisms have not been fully elucidated. Rats were allocated to three groups. During the fasting period, groups A and B were administered water, but group C was administered glucose. During laparotomy and the insulin tolerance test (ITT) under sevoflurane anesthesia, group A was administered saline, but groups B and C were administered glucose. During laparotomy, group C showed higher glucose levels and lower β-hydroxybutyrate (β-OHB) levels than group A, and group B showed more decreases in β-OHB levels than group A without differences in changes in glucose levels. Insulin levels and insulin sensitivity during laparotomy were similar among the three groups. No significant difference in insulin sensitivity was also confirmed in ITT. In conclusion, perioperative glucose administration suppresses lipolysis without affecting insulin secretion and sensitivity. PMID:26280893

  12. Materials Science Research Rack-1 Fire Suppressant Distribution Test Report

    NASA Technical Reports Server (NTRS)

    Wieland, P. O.

    2002-01-01

    Fire suppressant distribution testing was performed on the Materials Science Research Rack-1 (MSRR-1), a furnace facility payload that will be installed in the U.S. Lab module of the International Space Station. Unlike racks that were tested previously, the MSRR-1 uses the Active Rack Isolation System (ARIS) to reduce vibration on experiments, so the effects of ARIS on fire suppressant distribution were unknown. Two tests were performed to map the distribution of CO2 fire suppressant throughout a mockup of the MSRR-1 designed to have the same component volumes and flowpath restrictions as the flight rack. For the first test, the average maximum CO2 concentration for the rack was 60 percent, achieved within 45 s of discharge initiation, meeting the requirement to reach 50 percent throughout the rack within 1 min. For the second test, one of the experiment mockups was removed to provide a worst-case configuration, and the average maximum CO2 concentration for the rack was 58 percent. Comparing the results of this testing with results from previous testing leads to several general conclusions that can be used to evaluate future racks. The MSRR-1 will meet the requirements for fire suppressant distribution. Primary factors that affect the ability to meet the CO2 distribution requirements are the free air volume in the rack and the total area and distribution of openings in the rack shell. The length of the suppressant flowpath and degree of tortuousness has little correlation with CO2 concentration. The total area of holes in the rack shell could be significantly increased. The free air volume could be significantly increased. To ensure the highest maximum CO2 concentration, the PFE nozzle should be inserted to the stop on the nozzle.

  13. Specific microbial attachment to root knot nematodes in suppressive soil.

    PubMed

    Adam, Mohamed; Westphal, Andreas; Hallmann, Johannes; Heuer, Holger

    2014-05-01

    Understanding the interactions of plant-parasitic nematodes with antagonistic soil microbes could provide opportunities for novel crop protection strategies. Three arable soils were investigated for their suppressiveness against the root knot nematode Meloidogyne hapla. For all three soils, M. hapla developed significantly fewer galls, egg masses, and eggs on tomato plants in unsterilized than in sterilized infested soil. Egg numbers were reduced by up to 93%. This suggested suppression by soil microbial communities. The soils significantly differed in the composition of microbial communities and in the suppressiveness to M. hapla. To identify microorganisms interacting with M. hapla in soil, second-stage juveniles (J2) baited in the test soil were cultivation independently analyzed for attached microbes. PCR-denaturing gradient gel electrophoresis of fungal ITS or 16S rRNA genes of bacteria and bacterial groups from nematode and soil samples was performed, and DNA sequences from J2-associated bands were determined. The fingerprints showed many species that were abundant on J2 but not in the surrounding soil, especially in fungal profiles. Fungi associated with J2 from all three soils were related to the genera Davidiella and Rhizophydium, while the genera Eurotium, Ganoderma, and Cylindrocarpon were specific for the most suppressive soil. Among the 20 highly abundant operational taxonomic units of bacteria specific for J2 in suppressive soil, six were closely related to infectious species such as Shigella spp., whereas the most abundant were Malikia spinosa and Rothia amarae, as determined by 16S rRNA amplicon pyrosequencing. In conclusion, a diverse microflora specifically adhered to J2 of M. hapla in soil and presumably affected female fecundity. PMID:24532076

  14. Specific Microbial Attachment to Root Knot Nematodes in Suppressive Soil

    PubMed Central

    Adam, Mohamed; Westphal, Andreas; Hallmann, Johannes

    2014-01-01

    Understanding the interactions of plant-parasitic nematodes with antagonistic soil microbes could provide opportunities for novel crop protection strategies. Three arable soils were investigated for their suppressiveness against the root knot nematode Meloidogyne hapla. For all three soils, M. hapla developed significantly fewer galls, egg masses, and eggs on tomato plants in unsterilized than in sterilized infested soil. Egg numbers were reduced by up to 93%. This suggested suppression by soil microbial communities. The soils significantly differed in the composition of microbial communities and in the suppressiveness to M. hapla. To identify microorganisms interacting with M. hapla in soil, second-stage juveniles (J2) baited in the test soil were cultivation independently analyzed for attached microbes. PCR-denaturing gradient gel electrophoresis of fungal ITS or 16S rRNA genes of bacteria and bacterial groups from nematode and soil samples was performed, and DNA sequences from J2-associated bands were determined. The fingerprints showed many species that were abundant on J2 but not in the surrounding soil, especially in fungal profiles. Fungi associated with J2 from all three soils were related to the genera Davidiella and Rhizophydium, while the genera Eurotium, Ganoderma, and Cylindrocarpon were specific for the most suppressive soil. Among the 20 highly abundant operational taxonomic units of bacteria specific for J2 in suppressive soil, six were closely related to infectious species such as Shigella spp., whereas the most abundant were Malikia spinosa and Rothia amarae, as determined by 16S rRNA amplicon pyrosequencing. In conclusion, a diverse microflora specifically adhered to J2 of M. hapla in soil and presumably affected female fecundity. PMID:24532076

  15. Compost suppressiveness against Phytophthora capsicion pepper in potting trials.

    PubMed

    Pugliese, M; Marenco, M; Gullino, M L; Garibaldi, A

    2013-01-01

    Suppression of soil-borne plant diseases with composts has been widely studied. Composts suppressive to soil-borne pathogens have been detected in various cropping systems. Vegetable plants are generally propagated in pots, allowing the use of suppressive substrates to control zoospore-producing pathogens, like Phytophthora sp. The objective of the present work was to assess compost suppressiveness against Phytophthora capsici on pepper (cv. Corno di Toro). A municipal compost showing a good suppressive activity in previous trials on vegetable crops was used. Compost was mixed at 10, 20, 40, 60, 80 and 100% (v/v) with a commercial peat substrate, used as control. Substrates have been inoculated at 0.25, 0.5 and 1 g/l with wheat and hemp kernels infested with P. capsici and after one week 10 plants were transplanted for each treatment in 4 trays of 10 liters volume capacity and placed in greenhouse at 20 degrees C. Diseased plants were assessed weekly after transplanting and above-ground biomass of plants was assessed at the end of the trials. Compost applied at 80% significantly controlled the disease at high inoculum density (1 g/l), while at lower inoculums density, 0.25 and 0.5 g/l, reduced compost applications, 40% and 60% respectively, were sufficient to significantly control the disease. The application of compost at 20%, in absence of the pathogen, increased the biomass of pepper plants compared to control. The use of compost based substrates can be a suitable strategy for controlling soil-borne diseases on pepper, but results depends on application rates. PMID:25151829

  16. Photoperiodic Suppression of Drug Reinstatement

    PubMed Central

    Sorg, Barbara A.; Stark, Gemaine; Sergeeva, Anna; Jansen, Heiko T.

    2011-01-01

    The rewarding influence of drugs of abuse varies with time of day and appears to involve interactions between the circadian and the mesocorticolimbic dopamine systems. The circadian system is also intimately involved in measuring daylength. Thus, the present study examined the impact of changing daylength (photoperiod) on cocaine-seeking behaviors. Male Sprague Dawley rats were trained and tested on a 12L:12D light:dark schedule for cocaine-induced reinstatement of conditioned place preference (CPP) at three times of day (Zeitgeber time (ZT): 4, 12, and 20) to determine a preference score. Rats were then shifted to either shorter (6L:18D) or longer (18L:6D) photoperiods and then to constant conditions, re-tested for cocaine-induced reinstatement under each different condition, and then returned to their original photoperiod (12L:12D) and tested once more. Rats exhibited a circadian profile of preference score in constant darkness with a peak at 12h after lights-off. At both ZT4 and ZT20, but not at ZT12, shorter photoperiods profoundly suppressed cocaine reinstatement, which did not recover even after switching back to 12L:12D. In contrast, longer photoperiods did not alter reinstatement. Separate studies showed that the suppression of cocaine reinstatement was not due to repeated testing. In an additional experiment, we examined the photoperiodic regulation of tyrosine hydroxylase (TH) and dopamine transporter (DAT) proteins in drug-naive rats. These results revealed photoperiodic modulation of proteins in the prefrontal cortex and dorsal striatum, but not in the nucleus accumbens or ventral tegmental area. Together, these findings add further support to the circadian genesis of cocaine-seeking behaviors and demonstrate that drug-induced reinstatement is modulated by photoperiod. Furthermore, the results suggest that photoperiod partly contributes to the seasonal expression of certain drug-related behaviors in humans living at different latitudes and thus our

  17. Intravenous Immunoglobulin (IVIG) Attenuates TNF-Induced Pathologic Bone Resorption and Suppresses Osteoclastogenesis by Inducing A20 Expression.

    PubMed

    Lee, Min Joon; Lim, Elisha; Mun, Se-Hwan; Bae, Seyeon; Murata, Koichi; Ivashkiv, Lionel B; Park-Min, Kyung-Hyun

    2016-02-01

    Investigations on the therapeutic effects of intravenous immunoglobulin (IVIG) have focused on the suppression of autoantibody and immune complex-mediated inflammatory pathogenesis. Inflammatory diseases such as rheumatoid arthritis are often accompanied by excessive bone erosion but the effect of IVIG on osteoclasts, bone-resorbing cells, has not been studied. Here, we investigate whether IVIG directly regulates osteoclast differentiation and has therapeutic potential for suppressing osteoclast-mediated pathologic bone resorption. IVIG or cross-linking of Fcγ receptors with plate-bound IgG suppressed receptor activator of nuclear factor-κ B ligand (RANKL)-induced osteoclastogenesis and expression of osteoclast-related genes such as integrin β3 and cathepsin K in a dose-dependent manner. Mechanistically, IVIG or plate-bound IgG suppressed osteoclastogenesis by downregulating RANKL-induced expression of NFATC1, the master regulator of osteoclastogenesis. IVIG suppressed NFATC1 expression by attenuating RANKL-induced NF-κB signaling, explained in part by induction of the inflammatory signaling inhibitor A20. IVIG administration attenuated in vivo osteoclastogenesis and suppressed bone resorption in the tumor necrosis factor (TNF)-induced calvarial osteolysis model. Our findings show that, in addition to suppressing inflammation, IVIG directly inhibits osteoclastogenesis through a mechanism involving suppression of RANK signaling. Direct suppression of osteoclast differentiation may provide beneficial effects on preserving bone mass when IVIG is used to treat rheumatic disorders. PMID:26189496

  18. Oral administration of royal jelly inhibits the development of atopic dermatitis-like skin lesions in NC/Nga mice.

    PubMed

    Taniguchi, Yoshifumi; Kohno, Keizo; Inoue, Shin-ichiro; Koya-Miyata, Satomi; Okamoto, Iwao; Arai, Norie; Iwaki, Kanso; Ikeda, Masao; Kurimoto, Masashi

    2003-09-01

    We have shown previously that in addition to IL-4, IL-5 and IL-10, antigen-specific interferon-gamma (IFN-gamma) production by spleen cells from ovalbumin (OVA)/Alum-immunized mice is inhibited by the administration of royal jelly (RJ). Since it has been shown that both Th1 and Th2 cytokines play pathogenic roles in the generation of atopic dermatitis (AD), we have examined whether RJ suppresses the development of AD-like skin lesions in NC/Nga mice induced by repeated application of picryl chloride (PiCl) under specific pathogen-free (SPF) conditions. Oral administration of RJ to the PiCl-treated NC/Nga mice inhibited the development of AD-like skin lesions in these mice as exemplified by the significant decrease in the total skin severity scores and the decrease in hypertrophy, hyperkeratosis, and infiltration of the epidermis and corium by inflammatory cells. IFN-gamma production by spleen cells from PiCl-treated NC/Nga mice in response to TNP-KLH was partially but significantly inhibited by the oral administration of RJ, while IFN-gamma production by Con A-stimulated spleen cells was not affected. Since inducible nitric oxide (NO) synthase (iNOS)-derived NO has been suggested as an important immunoregulatory mediator in inflammatory autoimmune diseases, we have also examined the expression of iNOS in the dorsal skin lesions of PiCl-treated NC/Nga mice. Interestingly, the expression of iNOS was significantly increased in the skin lesions of RJ-administered mice compared with those of control PBS-administered mice. Thus, our results suggest that RJ suppresses the development of AD-like skin lesions in PiCl-treated NC/Nga mice, possibly by a combination of down-regulating TNP-specific IFN-gamma production and up-regulating iNOS expression. PMID:12890429

  19. Perilla frutescens extract ameliorates DSS-induced colitis by suppressing proinflammatory cytokines and inducing anti-inflammatory cytokines.

    PubMed

    Urushima, Hayato; Nishimura, Junichi; Mizushima, Tsunekazu; Hayashi, Noriyuki; Maeda, Kazuhisa; Ito, Toshinori

    2015-01-01

    Anti-inflammatory effects have been reported in Perilla frutescens leaf extract (PE), which is a plant of the genus belonging to the Lamiaceae family. We examined the effect of PE on dextran sulfate sodium (DSS)-induced colitis. Preliminarily, PE was safely administered for 7 wk without any adverse effects. In the preventive protocol, mice were fed 1.5% DSS solution dissolved in distilled water (control group) or 0.54% PE solution (PE group) ad libitum for 7 days. In the therapeutic protocol, distilled water or 0.54% PE solution was given for 10 days just after administration of 1.5% DSS for 5 days. PE intake significantly improved body weight loss. The serum cytokine profile demonstrated that TNF-α, IL-17A, and IL-10 were significantly lower in the PE group than in the control group. In the therapeutic protocol, mice in the PE group showed significantly higher body weight and lower histological colitis scores compared with mice in the control group on day 15. The serum cytokine profile demonstrated that TGF-β was significantly higher in the PE group than in the control group. In distal colon mRNA expression, TNF-α, and IL-17A were significantly downregulated. In vitro analyses of biologically active ingredients, such as luteolin, apigenin, and rosmarinic acid, in PE were performed. Luteolin suppressed production of proinflammatory cytokines, such as TNF-α, IL-1β, IL-6, and IL-17A. Apigenin also suppressed secretion of IL-17A and increased the anti-inflammatory cytokine IL-10. Rosmarinic acid increased the regulatory T cell population. We conclude that PE might be useful in treatment and prevention of DSS-induced colitis. PMID:25359539

  20. Suppression of NF-κB Activation By Gentian Violet Promotes Osteoblastogenesis and Suppresses Osteoclastogenesis

    PubMed Central

    Yamaguchi, M.; Vikulina, T.; Arbiser, J.L.; Weitzmann, M.N.

    2015-01-01

    Skeletal mass is regulated by the coordinated action of bone forming osteoblasts and bone resorbing osteoclasts. Accelerated rates of bone resorption relative to bone formation lead to net bone loss and the development of osteoporosis, a devastating disease that predisposes the skeleton to fractures. Bone fractures are associated with significant morbidity and in the case of hip fractures, high mortality. Gentian violet (GV), a cationic triphenylmethane dye, has long been used as an antifungal and antibacterial agent and is presently under investigation as a potential chemotherapeutic and antiangiogenic agent. However, effects on bone cells have not been previously reported and the mechanisms of action of GV, are poorly understood. In this study we show that GV suppresses receptor activator of NF-κB ligand (RANKL)-induced differentiation of RAW264.7 osteoclast precursors into mature osteoclasts, but paradoxically stimulates the differentiation of MC3T3 cells into mineralizing osteoblasts. These actions stem from the capacity of GV to suppress activation of the nuclear factor kappa B (NF-κB) signal transduction pathway that is required for osteoclastogenesis, but inhibitory to osteoblast differentiation and activity. Our data reveal that GV is an inhibitor of NF-κB activation and may hold promise for modulation of bone turnover to promote a balance between bone formation and bone resorption, favorable to gain of bone mass. PMID:25056540

  1. 7 CFR 2902.32 - Dust suppressants.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Dust suppressants. 2902.32 Section 2902.32... Items § 2902.32 Dust suppressants. (a) Definition. Products formulated to reduce or eliminate the spread of dust associated with gravel roads, dirt parking lots, or similar sources of dust,...

  2. Suppressing Irrelevant Information: Knowledge Activation or Inhibition?

    ERIC Educational Resources Information Center

    McNamara, Danielle S.; McDaniel, Mark A.

    2004-01-01

    In 3 experiments, the authors examined the role of knowledge activation in the suppression of contextually irrelevant meanings for ambiguous homographs. In Experiments 1 and 2, participants with greater baseball knowledge, regardless of reading skill, more quickly suppressed the irrelevant meaning of ambiguous words in baseball-related, but not…

  3. Ferromagnetic resonance probe liftoff suppression apparatus

    DOEpatents

    Davis, Thomas J.; Tomeraasen, Paul L.

    1985-01-01

    A liftoff suppression apparatus utilizing a liftoff sensing coil to sense the amount a ferromagnetic resonance probe lifts off the test surface during flaw detection and utilizing the liftoff signal to modulate the probe's field modulating coil to suppress the liftoff effects.

  4. Identifying separate components of surround suppression

    PubMed Central

    Schallmo, Michael-Paul; Murray, Scott O.

    2016-01-01

    Surround suppression is a well-known phenomenon in which the response to a visual stimulus is diminished by the presence of neighboring stimuli. This effect is observed in neural responses in areas such as primary visual cortex, and also manifests in visual contrast perception. Studies in animal models have identified at least two separate mechanisms that may contribute to surround suppression: one that is monocular and resistant to contrast adaptation, and another that is binocular and strongly diminished by adaptation. The current study was designed to investigate whether these two mechanisms exist in humans and if they can be identified psychophysically using eye-of-origin and contrast adaptation manipulations. In addition, we examined the prediction that the monocular suppression component is broadly tuned for orientation, while suppression between eyes is narrowly tuned. Our results confirmed that when center and surrounding stimuli were presented dichoptically (in opposite eyes), suppression was orientation-tuned. Following adaptation in the surrounding region, no dichoptic suppression was observed, and monoptic suppression no longer showed orientation selectivity. These results are consistent with a model of surround suppression that depends on both low-level and higher level components. This work provides a method to assess the separate contributions of these components during spatial context processing in human vision. PMID:26756172

  5. Acute Morphine Administration Reduces Cell-Mediated Immunity and Induces Reactivation of Latent Herpes Simplex Virus Type 1 in BALB/c Mice

    PubMed Central

    Mojadadi, Shafi; Jamali, Abbas; Khansarinejad, Behzad; Soleimanjahi, Hoorieh; Bamdad, Taravat

    2009-01-01

    Acute morphine administration is known to alter the course of herpes simplex virus infection. In this study, the effect of acute morphine administration on the reactivation of latent herpes was investigated in a mouse model. Because of the important role of cytolytic T lymphocyte (CTL) activity in the inhibition of herpes simplex virus type 1 (HSV-1) reactivation, the effect of acute morphine administration on CTL responses was also evaluated. Furthermore, lymphocyte proliferation and IFN-γ production were evaluated for their roles in the induction of the CTL response. The findings showed that acute morphine administration significantly reduced CTL responses, lymphocyte proliferation, and IFN-γ production. Furthermore, acute morphine administration has been shown to reactivate latent HSV-1. Previous studies have shown that cellular immune responses have important roles in the inhibition of HSV reactivation. These findings suggest that suppression of a portion of the cellular immune response after acute morphine administration may constitute one part of the mechanism that induces HSV reactivation. PMID:19403060

  6. First Observation of the Greisen-Zatsepin-Kuzmin Suppression

    NASA Astrophysics Data System (ADS)

    Abbasi, R. U.; Abu-Zayyad, T.; Allen, M.; Amman, J. F.; Archbold, G.; Belov, K.; Belz, J. W.; Ben Zvi, S. Y.; Bergman, D. R.; Blake, S. A.; Brusova, O. A.; Burt, G. W.; Cannon, C.; Cao, Z.; Connolly, B. C.; Deng, W.; Fedorova, Y.; Finley, C. B.; Gray, R. C.; Hanlon, W. F.; Hoffman, C. M.; Holzscheiter, M. H.; Hughes, G.; Hüntemeyer, P.; Jones, B. F.; Jui, C. C. H.; Kim, K.; Kirn, M. A.; Loh, E. C.; Maestas, M. M.; Manago, N.; Marek, L. J.; Martens, K.; Matthews, J. A. J.; Matthews, J. N.; Moore, S. A.; O'Neill, A.; Painter, C. A.; Perera, L.; Reil, K.; Riehle, R.; Roberts, M.; Rodriguez, D.; Sasaki, N.; Schnetzer, S. R.; Scott, L. M.; Sinnis, G.; Smith, J. D.; Sokolsky, P.; Song, C.; Springer, R. W.; Stokes, B. T.; Thomas, S. B.; Thomas, J. R.; Thomson, G. B.; Tupa, D.; Westerhoff, S.; Wiencke, L. R.; Zhang, X.; Zech, A.

    2008-03-01

    The High Resolution Fly’s Eye (HiRes) experiment has observed the Greisen-Zatsepin-Kuzmin suppression (called the GZK cutoff) with a statistical significance of five standard deviations. HiRes’ measurement of the flux of ultrahigh energy cosmic rays shows a sharp suppression at an energy of 6×1019eV, consistent with the expected cutoff energy. We observe the ankle of the cosmic-ray energy spectrum as well, at an energy of 4×1018eV. We describe the experiment, data collection, and analysis and estimate the systematic uncertainties. The results are presented and the calculation of the statistical significance of our observation is described.

  7. Expectation Suppression in Early Visual Cortex Depends on Task Set

    PubMed Central

    St. John-Saaltink, Elexa; Utzerath, Christian; Kok, Peter; Lau, Hakwan C.; de Lange, Floris P.

    2015-01-01

    Stimulus expectation can modulate neural responses in early sensory cortical regions, with expected stimuli often leading to a reduced neural response. However, it is unclear whether this expectation suppression is an automatic phenomenon or is instead dependent on the type of task a subject is engaged in. To investigate this, human subjects were presented with visual grating stimuli in the periphery that were either predictable or non-predictable while they performed three tasks that differently engaged cognitive resources. In two of the tasks, the predictable stimulus was task-irrelevant and spatial attention was engaged at fixation, with a high load on either perceptual or working memory resources. In the third task, the predictable stimulus was task-relevant, and therefore spatially attended. We observed that expectation suppression is dependent on the cognitive resources engaged by a subjects’ current task. When the grating was task-irrelevant, expectation suppression for predictable items was visible in retinotopically specific areas of early visual cortex (V1-V3) during the perceptual task, but it was abolished when working memory was loaded. When the grating was task-relevant and spatially attended, there was no significant effect of expectation in early visual cortex. These results suggest that expectation suppression is not an automatic phenomenon, but dependent on attentional state and type of available cognitive resources. PMID:26098331

  8. Hemodilution, vasopressin suppression, and diuresis during water immersion in man

    NASA Technical Reports Server (NTRS)

    Greenleaf, J. E.; Keil, L. C.; Shvartz, E.

    1981-01-01

    The possible role of hemodilution in the early stages of water immersion in the suppression of antidiuretic hormone (vasopressin) and subsequent diuresis in man is investigated. Parameters characterizing hemodilution as well as water balance and intercompartmental fluid levels were measured before, during and after the immersion of ten subjects in a semireclining position in tap water up to their necks at 34.6 C for 8 hr. Results indicate that hemodilution and the suppression of vasopressin and plasma renin activity were present by the second hour of immersion, with the early hemodilution due to a slight increase in plasma volume with no change in plasma sodium or osmotic contents, even though urine volume and osmotic excretion rates increased significantly. Hyponatremia, hyposmotemia and plasma renin activity suppression are observed to continue to the end of immersion, resulting in final decreases of 15.6% in plasma volume, 18.8% in extracellular volume, 19.6% in interstitial volume and 10.7% in red cell volume. Findings suggest the transfer of hypotonic fluid into the vascular system, which contributes to vasopressin suppression observed during immersion.

  9. SUPPRESSION OF DIELECTRONIC RECOMBINATION DUE TO FINITE DENSITY EFFECTS

    SciTech Connect

    Nikolic, D.; Gorczyca, T. W.; Korista, K. T.; Ferland, G. J.; Badnell, N. R.

    2013-05-01

    We have developed a general model for determining density-dependent effective dielectronic recombination (DR) rate coefficients in order to explore finite-density effects on the ionization balance of plasmas. Our model consists of multiplying by a suppression factor those highly-accurate total zero-density DR rate coefficients which have been produced from state-of-the-art theoretical calculations and which have been benchmarked by experiment. The suppression factor is based upon earlier detailed collision-radiative calculations which were made for a wide range of ions at various densities and temperatures, but used a simplified treatment of DR. A general suppression formula is then developed as a function of isoelectronic sequence, charge, density, and temperature. These density-dependent effective DR rate coefficients are then used in the plasma simulation code Cloudy to compute ionization balance curves for both collisionally ionized and photoionized plasmas at very low (n{sub e} = 1 cm{sup -3}) and finite (n{sub e} = 10{sup 10} cm{sup -3}) densities. We find that the denser case is significantly more ionized due to suppression of DR, warranting further studies of density effects on DR by detailed collisional-radiative calculations which utilize state-of-the-art partial DR rate coefficients. This is expected to impact the predictions of the ionization balance in denser cosmic gases such as those found in nova and supernova shells, accretion disks, and the broad emission line regions in active galactic nuclei.

  10. Chinese medicinal herbs reverse macrophage suppression induced by urological tumors.

    PubMed

    Rittenhouse, J R; Lui, P D; Lau, B H

    1991-08-01

    Tumors are known to produce factors suppressing macrophage function. In this study we demonstrated in vitro suppression of macrophage chemiluminescent oxidative burst associated with viable cells and cell-free extracts of two urological neoplasms--murine renal cell carcinoma (Renca) and murine bladder tumor (MBT). Suppression was reversed by extracts of two Chinese medicinal herbs, Astragalus membranaceus (AM) and Ligustrum lucidum (LL). Murine macrophage cell line J774 was incubated with either the viable tumor cells or the cell-free tumor extract for 18 hours at 37C and 5% CO2. Chemiluminescent oxidative burst as an indicator of macrophage function was triggered by adding zymosan A suspension containing luminol and assayed in an automated luminometer. Photon emission over time was counted and the results were expressed as integrated photon emission. Significant dose-related depression of oxidative burst occurred with either the viable tumor cells or the cell-free tumor extracts. Depression was partially or completely reversed by the presence of 50-100 micrograms./ml. of either the AM or the LL extract. AM and LL have previously been shown to modulate immune response. Data from this study suggest that they may also exert their antitumor activity via abolition of tumor-associated macrophage suppression. PMID:1856958

  11. Suppression of developmental anomalies by maternal macrophages in mice

    SciTech Connect

    Nomura, T.; Hata, S.; Kusafuka, T. )

    1990-11-01

    We tested whether nonspecific tumoricidal immune cells can suppress congenital malformations by killing precursor cells destined to cause such defects. Pretreatment of pregnant ICR mice with synthetic (Pyran copolymer) and biological (Bacillus Calmette-Guerin) agents significantly suppressed radiation- and chemical-induced congenital malformations (cleft palate, digit anomalies, tail anomalies, etc.). Such suppressive effects were associated with the activation of maternal macrophages by these agents, but were lost either after the disruption of activated macrophages by supersonic waves or by inhibition of their lysosomal enzyme activity with trypan blue. These results indicate that a live activated macrophage with active lysosomal enzymes can be an effector cell to suppress maldevelopment. A similar reduction by activated macrophages was observed in strain CL/Fr, which has a high spontaneous frequency of cleft lips and palates. Furthermore, Pyran-activated maternal macrophages could pass through the placenta, and enhanced urethane-induced cell killing (but not somatic mutation) in the embryo. It is likely that a maternal immunosurveillance system eliminating preteratogenic cells allows for the replacement with normal totipotent blast cells during the pregnancy to protect abnormal development.

  12. Kinetic modeling of spectra of flames with suppressants

    SciTech Connect

    Green, A.E.S.; Xue, Hui

    1995-12-31

    The phase out of halons in response to the Montreal Protocol and the quest for alternative fire suppressants has focused attention on the current lack of understanding of mechanisms of flame extinction. Challenges to the free-radical scavenging mechanism in which chemical chains in combustion are interrupted have raised serious questions as to why the halons are effective. Low-resolution ultraviolet computer spectroscopy can be used to observe the OH radical and other simple molecules when acted upon by halon or alternative suppressants. However, the physical and chemical interpretation of such observations requires reaction rates leading to the OH radical and other observable molecules in 3-6 eV electronic states. Using a simple kinetics model, the authors illustrate where major reaction rates to excited states would be helpful to the interpretation of the interaction of suppressants with flames. Quantum chemists could provide a valuable service by providing such rates and helping to assess whether or not flame suppression by free-radical scavenging is a significant mechanism. 29 refs., 5 figs.

  13. Impacts of suppressing guide on information spreading

    NASA Astrophysics Data System (ADS)

    Xu, Jinghong; Zhang, Lin; Ma, Baojun; Wu, Ye

    2016-02-01

    It is quite common that guides are introduced to suppress the information spreading in modern society for different purposes. In this paper, an agent-based model is established to quantitatively analyze the impacts of suppressing guides on information spreading. We find that the spreading threshold depends on the attractiveness of the information and the topology of the social network with no suppressing guides at all. Usually, one would expect that the existence of suppressing guides in the spreading procedure may result in less diffusion of information within the overall network. However, we find that sometimes the opposite is true: the manipulating nodes of suppressing guides may lead to more extensive information spreading when there are audiences with the reversal mind. These results can provide valuable theoretical references to public opinion guidance on various information, e.g., rumor or news spreading.

  14. 31 CFR 561.328 - Reduce significantly, significantly reduced, and significant reduction.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Reduce significantly, significantly reduced, and significant reduction. 561.328 Section 561.328 Money and Finance: Treasury Regulations... IRANIAN FINANCIAL SANCTIONS REGULATIONS General Definitions § 561.328 Reduce significantly,...

  15. 31 CFR 561.328 - Reduce significantly, significantly reduced, and significant reduction.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Reduce significantly, significantly reduced, and significant reduction. 561.328 Section 561.328 Money and Finance: Treasury Regulations... IRANIAN FINANCIAL SANCTIONS REGULATIONS General Definitions § 561.328 Reduce significantly,...

  16. "Clinical" Significance: "Clinical" Significance and "Practical" Significance are NOT the Same Things

    ERIC Educational Resources Information Center

    Peterson, Lisa S.

    2008-01-01

    Clinical significance is an important concept in research, particularly in education and the social sciences. The present article first compares clinical significance to other measures of "significance" in statistics. The major methods used to determine clinical significance are explained and the strengths and weaknesses of clinical significance…

  17. 7. Administrative structures.

    PubMed

    2014-05-01

    The basic systems of any society rarely can operate independently. Instead, they are dependent and often interdependent upon other entities. Such entities control the resources within their respective systems. Thus, coordination and control agencies require contracts or memoranda of understanding with these entities in order to assure access to the resources required during a crisis. These administrative structures include: (1) governmental institutions and agencies, including the military; (2) intergovernmental organisations; (3) nongovernmental organisations; (4) commercial private sector organisations; and (5) academic institutions. These dependencies create potential barriers to the provision of coordination and control including: (1) the complexity of the administrative structures with which coordination and control must interact; (2) the location of resources; (3) finding responsible person(s); (4) the competence and compatibility; (5) methods of access; (6) payment; (7) contracts and memoranda of understanding; (8) inventories of accessible resources; (9) competition for the mandate, power, and resources; and (10) jealousy. The need for potential interactions between administrative structures requires that agreements for the sharing of resources during crises be reached as part of planning and preparedness. Gaining an understanding of these relationships is an important area for research. PMID:24785804

  18. Multichannel photonic mixing based on cascade carrier suppression

    NASA Astrophysics Data System (ADS)

    Xu, Fangxing

    2015-10-01

    Designed a multi-channel photonic mixing system based on cascade carrier suppression, which can achieve frequency conversions simultaneously for multi-channels, effectively inhibit the generation of third-order intermodulation, and significantly reduce the insertion loss in the conversion process. Meanwhile, a simulation with the software Optisystem has been done, indicating excellent frequency-conversion characteristics and good scalability of this scheme, that shows the microwave photonic frequency conversion can be a potential application for microwave signal parallel processing.

  19. Proanthocyanidins from grape seeds inhibit UV-radiation-induced immune suppression in mice: detection and analysis of molecular and cellular targets.

    PubMed

    Katiyar, Santosh K

    2015-01-01

    Ultraviolet (UV)-radiation-induced immunosuppression has been linked with the risk of skin carcinogenesis. Approximately, 2 million new cases of skin cancers, including melanoma and nonmelanoma, diagnosed each year in the USA and therefore have a tremendous bad impact on public health. Dietary phytochemicals are promising options for the development of effective strategy for the prevention of photodamaging effects of UV radiation including the risk of skin cancer. Grape seed proanthocyanidins (GSPs) are such phytochemicals. Dietary administration of GSPs with AIN76A control diet significantly inhibits UV-induced skin tumor development as well as suppression of immune system. UV-induced suppression of immune system is commonly determined using contact hypersensitivity (CHS) model which is a prototype of T-cell-mediated immune response. We present evidence that inhibition of UV-induced suppression of immune system by GSPs is mediated through: (i) the alterations in immunoregulatory cytokines, interleukin (IL)-10 and IL-12, (ii) DNA repair, (iii) stimulation of effector T cells and (iv) DNA repair-dependent functional activation of dendritic cells in mouse model. These information have important implications for the use of GSPs as a dietary supplement in chemoprevention of UV-induced immunosuppression as well as photocarcinogenesis. PMID:25112437

  20. 3-bromopyruvate and sodium citrate target glycolysis, suppress survivin, and induce mitochondrial-mediated apoptosis in gastric cancer cells and inhibit gastric orthotopic transplantation tumor growth.

    PubMed

    Wang, Ting-An; Zhang, Xiao-Dong; Guo, Xing-Yu; Xian, Shu-Lin; Lu, Yun-Fei

    2016-03-01

    Glycolysis is the primary method utilized by cancer cells to produce the energy (adenosine triphosphate, ATP) required for cell proliferation. Therefore, inhibition of glycolysis may inhibit tumor growth. We previously found that both 3-bromopyruvate (3-BrPA) and sodium citrate (SCT) can inhibit glycolysis in vitro; however, the underlying inhibitory mechanisms remain unclear. In the present study, we used a human gastric cancer cell line (SGC-7901) and an orthotopic transplantation tumor model in nude mice to explore the specific mechanisms of 3-BrPA and SCT. We found that both 3-BrPA and SCT effectively suppressed cancer cell proliferation, arrested the cell cycle, induced apoptosis, and decreased the production of lactate and ATP. 3-BrPA significantly reduced the glycolytic enzyme hexokinase activity, while SCT selectively inhibited phosphofructokinase-1 activity. Furthermore, 3-BrPA and SCT upregulated the expression of pro-apoptotic proteins (Bax, cytochrome c, and cleaved caspase-3) and downregulated the expression of anti-apoptotic proteins (Bcl-2 and survivin). Finally, our animal model of gastric cancer indicated that intraperitoneal injection of 3-BrPA and SCT suppressed orthotopic transplantation tumor growth and induced tumor apoptosis. Taken together, these results suggest that 3-BrPA and SCT selectively suppress glycolytic enzymes, decrease ATP production, induce mitochondrial-mediated apoptosis, downregulate survivin, and inhibit tumor growth. Moreover, an intraperitoneal injection is an effective form of administration of 3-BrPA and SCT. PMID:26708213

  1. 3-Bromopyruvate and sodium citrate target glycolysis, suppress survivin, and induce mitochondrial-mediated apoptosis in gastric cancer cells and inhibit gastric orthotopic transplantation tumor growth

    PubMed Central

    WANG, TING-AN; ZHANG, XIAO-DONG; GUO, XING-YU; XIAN, SHU-LIN; LU, YUN-FEI

    2016-01-01

    Glycolysis is the primary method utilized by cancer cells to produce the energy (adenosine triphosphate, ATP) required for cell proliferation. Therefore, inhibition of glycolysis may inhibit tumor growth. We previously found that both 3-bromopyruvate (3-BrPA) and sodium citrate (SCT) can inhibit glycolysis in vitro; however, the underlying inhibitory mechanisms remain unclear. In the present study, we used a human gastric cancer cell line (SGC-7901) and an orthotopic transplantation tumor model in nude mice to explore the specific mechanisms of 3-BrPA and SCT. We found that both 3-BrPA and SCT effectively suppressed cancer cell proliferation, arrested the cell cycle, induced apoptosis, and decreased the production of lactate and ATP. 3-BrPA significantly reduced the glycolytic enzyme hexokinase activity, while SCT selectively inhibited phosphofructokinase-1 activity. Furthermore, 3-BrPA and SCT upregulated the expression of pro-apoptotic proteins (Bax, cytochrome c, and cleaved caspase-3) and downregulated the expression of anti-apoptotic proteins (Bcl-2 and survivin). Finally, our animal model of gastric cancer indicated that intraperitoneal injection of 3-BrPA and SCT suppressed orthotopic transplantation tumor growth and induced tumor apoptosis. Taken together, these results suggest that 3-BrPA and SCT selectively suppress glycolytic enzymes, decrease ATP production, induce mitochondrial-mediated apoptosis, downregulate survivin, and inhibit tumor growth. Moreover, an intraperitoneal injection is an effective form of administration of 3-BrPA and SCT. PMID:26708213

  2. CDK2 and mTOR are direct molecular targets of isoangustone A in the suppression of human prostate cancer cell growth.

    PubMed

    Lee, Eunjung; Son, Joe Eun; Byun, Sanguine; Lee, Seung Joon; Kim, Yeong A; Liu, Kangdong; Kim, Jiyoung; Lim, Soon Sung; Park, Jung Han Yoon; Dong, Zigang; Lee, Ki Won; Lee, Hyong Joo

    2013-10-01

    Licorice extract which is used as a natural sweetener has been shown to possess inhibitory effects against prostate cancer, but the mechanisms responsible are poorly understood. Here, we report a compound, isoangustone A (IAA) in licorice that potently suppresses the growth of aggressive prostate cancer and sought to clarify its mechanism of action. We analyzed its inhibitory effects on the growth of PTEN-deleted human prostate cancer cells, in vitro and in vivo. Administration of IAA significantly attenuated the growth of prostate cancer cell cultures and xenograft tumors. These effects were found to be attributable to inhibition of the G1/S phase cell cycle transition and the accumulation of p27(kip1). The elevated p27(kip1) expression levels were concurrent with the decrease of its phosphorylation at threonine 187 through suppression of CDK2 kinase activity and the reduced phosphorylation of Akt at Serine 473 by diminishing the kinase activity of the mammalian target of rapamycin (mTOR). Further analysis using recombinant proteins and immunoprecipitated cell lysates determined that IAA exerts suppressive effects against CDK2 and mTOR kinase activity by direct binding with both proteins. These findings suggested that the licorice compound IAA is a potent molecular inhibitor of CDK2 and mTOR, with strong implications for the treatment of prostate cancer. Thus, licorice-derived extracts with high IAA content warrant further clinical investigation for nutritional sources for prostate cancer patients. PMID:23707764

  3. Bromoenol Lactone, an Inhibitor of Calcium-Independent Phospholipase A2, Suppresses Carrageenan-Induced Prostaglandin Production and Hyperalgesia in Rat Hind Paw

    PubMed Central

    Tsuchida, Keiichiro; Ibuki, Takae; Matsumura, Kiyoshi

    2015-01-01

    Prostaglandin (PG) E2 and PGI2 are essential to hyperalgesia in inflammatory tissues. These prostaglandins are produced from arachidonic acid, which is cleaved from membrane phospholipids by the action of phospholipase A2 (PLA2). Which isozyme of PLA2 is responsible for the cleavage of arachidonic acid and the production of prostaglandins essential to inflammation-induced hyperalgesia is not clear. In this study, we examined the effects of two PLA2 isozyme-specific inhibitors on carrageenan-induced production of PGE2 and PGI2 in rat hind paw and behavioral nociceptive response to radiant heat. Local administration of bromoenol lactone (BEL), an inhibitor of calcium-independent PLA2 (iPLA2), significantly reduced carrageenan-induced elevation of prostaglandins in the inflamed foot pad 3 h after injection. It also ameliorated the hyperalgesic response between 1 h and 3 h after carrageenan injection. On the other hand, AACOCF3, an inhibitor of cytosolic PLA2, suppressed neither prostaglandin production nor the hyperalgesic response. BEL did not suppress the mRNA levels of iPLA2β, iPLA2γ, cyclooxygenase-2, microsomal prostaglandin E synthase, prostaglandin I synthase, or proinflammatory cytokines in the inflamed foot pad, indicating that BEL did not suppress inflammation itself. These results suggest that iPLA2 is involved in the production of prostaglandins and hyperalgesia at the inflammatory loci. PMID:26063975

  4. Nonerythropoietic Erythropoietin-Derived Peptide Suppresses Adipogenesis, Inflammation, Obesity and Insulin Resistance

    PubMed Central

    Liu, Yuqi; Luo, Bangwei; Shi, Rongchen; Wang, Jinsong; Liu, Zongwei; Liu, Wei; Wang, Shufeng; Zhang, Zhiren

    2015-01-01

    Erythropoietin (EPO) has been identified as being crucial for obesity modulation; however, its erythropoietic activity may limit its clinical application. EPO-derived Helix B-surface peptide (pHBSP) is nonerythrogenic but has been reported to retain other functions of EPO. The current study aimed to evaluate the effects and potential mechanisms of pHBSP in obesity modulation. We found that pHBSP suppressed adipogenesis, adipokine expression and peroxisome proliferator-activated receptor γ (PPARγ) levels during 3T3-L1 preadipocyte maturation through the EPO receptor (EPOR). In addition, also through EPOR, pHBSP attenuated macrophage inflammatory activation and promoted PPARγ expression. Furthermore, PPARγ deficiency partly ablated the anti-inflammatory activity of pHBSP in macrophages. Correspondingly, pHBSP administration to high-fat diet (HFD)-fed mice significantly improved obesity, insulin resistance (IR) and adipose tissue inflammation without stimulating hematopoiesis. Therefore, pHBSP can significantly protect against obesity and IR partly by inhibiting adipogenesis and inflammation. These findings have therapeutic implications for metabolic disorders, such as obesity and diabetes. PMID:26459940

  5. Pituitary suppression before frozen embryo transfer is beneficial for patients suffering from idiopathic repeated implantation failure.

    PubMed

    Yang, Xing; Huang, Rui; Wang, Yan-fang; Liang, Xiao-yan

    2016-02-01

    Long-term gonadotropin-releasing hormone agonist (GnRHa) administration before in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) in infertile women with endometriosis or adenomyosis significantly enhanced the chances of pregnancy in both fresh and frozen embryo transfer cycles. We hypothesized that long-term GnRHa treatment might also be beneficial for the idiopathic repeated implantation failure (RIF) patients. In the 21 patients receiving GnRHa and hormone replacement therapy (G-HRT) protocols for frozen embryo transfer, their data were compared with those of the 56 of frozen/fresh cycles they had previously undergone (previous protocols). Comparison showed that the finial results were significantly better with G-HRT protocols than with their previous protocols, with pregnancy rate, clinical pregnancy rate, implantation rate and on-going pregnancy rate being 70%, 60%, 40% and 38% respectively with G-HRT protocols, against 17%, 11%, 6.3% and 5% with previous protocols. The results showed that hormonally controlled endometrial preparation with prior GnRHa suppression could be used for patients who had experienced repeated failures of IVF treatment despite having morphologically optimal embryos, and the treatment may help increase the receptivity of the endometrium in these patients. PMID:26838753

  6. Decoy Receptor 3 Improves Survival in Experimental Sepsis by Suppressing the Inflammatory Response and Lymphocyte Apoptosis

    PubMed Central

    Liang, DongYu; Hou, YanQiang; Lou, XiaoLi; Chen, HongWei

    2015-01-01

    Purpose Unbalanced inflammatory response and lymphocyte apoptosis is associated with high mortality in septic patients. Decoy receptor 3 (DcR3), a member of the tumor necrosis factor receptor superfamily, is an anti-inflammatory and anti-apoptotic factor. Recently, DcR3 expression was found to be increased in septic patients. This study evaluated the therapeutic effect and mechanisms of DcR3 on cecal ligation and puncture (CLP)-induced sepsis in mice. Methods C57BL/6 mice were subjected to CLP-induced polymicrobial sepsis. DcR3 Fc was intravenously injected 30 min before and 6 h after CLP. Bacterial clearance, cytokine production, histology, lymphocyte apoptosis and survival were evaluated. Furthermore, we investigated the systemic effects of DcR3 in in vitro lymphocyte apoptosis regulation. Results Our results demonstrated that DcR3 protein treatments significantly improved survival in septic mice (p <0.05). Treatment with DcR3 protein significantly reduced the inflammatory response and decreased lymphocyte apoptosis in the thymus and spleen. Histopathological findings of the lung and liver showed milder impairment after DcR3 administration. In vitro experiments showed that DcR3 Fc inhibited Fas-FasL mediated lymphocyte apoptosis. Conclusions Treatment with the DcR3 protein protects mice from sepsis by suppressing the inflammatory response and lymphocyte apoptosis. DcR3 protein may be useful in treatment of sepsis. PMID:26121476

  7. Progranulin suppresses titanium particle induced inflammatory osteolysis by targeting TNFα signaling.

    PubMed

    Zhao, Yun-peng; Wei, Jian-lu; Tian, Qing-yun; Liu, Alexander Tianxing; Yi, Young-su; Einhorn, Thomas A; Liu, Chuan-ju

    2016-01-01

    Aseptic loosening is a major complication of prosthetic joint surgery, characterized by chronic inflammation, pain, and osteolysis surrounding the bone-implant interface. Progranulin (PGRN) is known to have anti-inflammatory action by binding to Tumor Necrosis Factor (TNF) receptors and antagonizing TNFα. Here we report that titanium particles significantly induced PGRN expression in RAW264.7 cells and also in a mouse air-pouch model of inflammation. PGRN-deficiency enhanced, whereas administration of recombinant PGRN effectively inhibited, titanium particle-induced inflammation in an air pouch model. In addition, PGRN also significantly inhibited titanium particle-induced osteoclastogenesis and calvarial osteolysis in vitro, ex vivo and in vivo. Mechanistic studies demonstrated that the inhibition of PGRN on titanium particle induced-inflammation is primarily via neutralizing the titanium particle-activated TNFα/NF-κB signaling pathway and this is evidenced by the suppression of particle-induced IκB phosphorylation, NF-κB p65 nuclear translocation, and activity of the NF-κB-specific reporter gene. Collectively, these findings not only demonstrate that PGRN plays an important role in inhibiting titanium particle-induced inflammation, but also provide a potential therapeutic agent for the prevention of wear debris-induced inflammation and osteolysis. PMID:26864916

  8. Nimbidin suppresses functions of macrophages and neutrophils: relevance to its antiinflammatory mechanisms.

    PubMed

    Kaur, Gurpreet; Sarwar Alam, M; Athar, M

    2004-05-01

    Nimbidin is a mixture of tetranortriterpenes and is the major active principle of the seed oil of Azadirachta indica A. Juss (Meliaceae) possessing potent antiinflammatory and antiarthritic activities. The present study revealed that nimbidin significantly inhibited some of the functions of macrophages and neutrophils relevant to the inflammatory response following both in vivo and in vitro exposure. Oral administration of 5-25 mg/kg nimbidin to rats for 3 consecutive days significantly inhibited the migration of macrophages to their peritoneal cavities in response to inflammatory stimuli and also inhibited phagocytosis and phorbol-12-myristate-13-acetate (PMA) stimulated respiratory burst in these cells. In vitro exposure of rat peritoneal macrophages to nimbidin also inhibited phagocytosis and PMA stimulated respiratory burst in these cells. Nimbidin also inhibited nitric oxide (NO) and prostaglandin E2 (PGE2) production in lipopolysaccharide (LPS) stimulated macrophages following in vitro exposure, whereas interleukin 1 (IL-1) was only weakly inhibited. Probing the mechanism of NO inhibition revealed that nimbidin ameliorated the induction of inducible NO synthase (iNOS) without any inhibition in its catalytic activity. In addition, nimbidin also attenuated degranulation in neutrophils assessed in terms of release of beta-glucuronidase, myeloperoxidase and lysozyme. The results suggest that nimbidin suppresses the functions of macrophages and neutrophils relevant to inflammation. Thus nimbidin can be valuable in treating inflammation/inflammatory diseases. PMID:15174005

  9. Progranulin suppresses titanium particle induced inflammatory osteolysis by targeting TNFα signaling

    PubMed Central

    Zhao, Yun-peng; Wei, Jian-lu; Tian, Qing-yun; Liu, Alexander Tianxing; Yi, Young-Su; Einhorn, Thomas A.; Liu, Chuan-ju

    2016-01-01

    Aseptic loosening is a major complication of prosthetic joint surgery, characterized by chronic inflammation, pain, and osteolysis surrounding the bone-implant interface. Progranulin (PGRN) is known to have anti-inflammatory action by binding to Tumor Necrosis Factor (TNF) receptors and antagonizing TNFα. Here we report that titanium particles significantly induced PGRN expression in RAW264.7 cells and also in a mouse air-pouch model of inflammation. PGRN-deficiency enhanced, whereas administration of recombinant PGRN effectively inhibited, titanium particle-induced inflammation in an air pouch model. In addition, PGRN also significantly inhibited titanium particle-induced osteoclastogenesis and calvarial osteolysis in vitro, ex vivo and in vivo. Mechanistic studies demonstrated that the inhibition of PGRN on titanium particle induced-inflammation is primarily via neutralizing the titanium particle-activated TNFα/NF-κB signaling pathway and this is evidenced by the suppression of particle-induced IκB phosphorylation, NF-κB p65 nuclear translocation, and activity of the NF-κB-specific reporter gene. Collectively, these findings not only demonstrate that PGRN plays an important role in inhibiting titanium particle-induced inflammation, but also provide a potential therapeutic agent for the prevention of wear debris-induced inflammation and osteolysis. PMID:26864916

  10. Evaluation of tibolone administration in bone architectural by MicroCT

    SciTech Connect

    Carvalho, A. C. B.; Henriques, H. N.; Granjeiro, J. M.; Guzman-Silva, M. A.; Lopes, R. T.; Lima, I.

    2011-07-01

    Elderly women are at higher risk for hip fracture because of additional and relatively rapid bone loss due to estrogen deficiency by loss of the ovarian function and a longer average life span than men. The early application of agents that suppress the increase in bone turnover due to estrogen deficiency is essential to prevent bone loss and reduce the risk of osteoporosis. Some advanced imaging techniques may be required to investigate osteoporosis. X-ray micro-computed tomography has been used to generate high-resolution 3D images of cancellous and cortical bone morphology from normal and pathologic human and animal specimens. The aim of this study is to verify the effects of tibolone administration by evaluating the trabecular bone region. The experiment was performed on two groups of rats previously ovariectomized in which one received tibolone while the other did not. Tibolone administration (1 mg/day) began thirty days after the ovariectomy and the treatment remained for five months. At last, the animals were euthanized and femurs were collected. The scan was obtained using a Hamamatsu 10 Mp camera with a pixel size of 11.59 {mu}m and trabecular region in the right femoral head were quantified. All results were statistically evaluated with significance set at P<0.05%. Tibolone administration was shown to be beneficial in some analysis of the femoral head, performing higher bone volume and reducing the porosity when compared to ovariectomized. It can be concluded that tibolone administered to ovariectomized rats significantly preserved bone mass in the femoral head and microtomography was an efficient method to identify bone loss process and to evaluate potential therapies, as tibolone administration. (authors)

  11. Effect of intraperitoneal and intravenous administration of cholecystokinin-8 and apolipoprotein AIV on intestinal lymphatic CCK-8 and apo AIV concentration

    PubMed Central

    Lo, Chun-Min; Xu, Min; Yang, Qing; Zheng, Shuqin; Carey, Katherine M.; Tubb, Matthew R.; Davidson, W. Sean; Liu, Min; Woods, Stephen C.; Tso, Patrick

    2009-01-01

    CCK and apolipoprotein AIV (apo AIV) are gastrointestinal satiety signals whose synthesis and secretion by the gut are stimulated by fat absorption. Intraperitoneally administered CCK-8 is more potent in suppressing food intake than a similar dose administered intravenously, but the reason for this disparity is unclear. In contrast, both intravenous and intraperitoneally administered apo AIV are equally as potent in inhibiting food intake. When we compared the lymphatic concentration of CCK-8 and apo AIV, we found that neither intraperitoneally nor intravenously administered CCK-8 or apo AIV altered lymphatic flow rate. Interestingly, intraperitoneal administration of CCK-8 produced a significantly higher lymphatic concentration at 15 min than did intravenous administration. Intraperitoneal injection of apo AIV also yielded a higher lymphatic concentration at 30 min than did intravenous administration. Intraperitoneal administration of CCK-8 and apo AIV also resulted in a much longer period of elevated CCK-8 and apo AIV peptide concentration in lymph than intravenous administration. Furthermore, enzymatic activity of dipeptidyl peptidase IV (DPPIV) and aminopeptidase was higher in plasma than in lymph during fasting, and so, satiation peptides, such as CCK-8 and apo AIV in the lymph, are protected from degradation by the significantly lower DPPIV and aminopeptidase activity levels in lymph than in plasma. Therefore, the higher potency of intraperitoneally administered CCK-8 compared with intravenously administered CCK-8 in inhibiting food intake may be explained by both its higher concentration in lymph and the prolonged duration of its presence in the lamina propria. PMID:19020287

  12. Prazosin, an alpha 1-adrenergic receptor antagonist, suppresses experimental autoimmune encephalomyelitis in the Lewis rat.

    PubMed Central

    Brosnan, C F; Goldmuntz, E A; Cammer, W; Factor, S M; Bloom, B R; Norton, W T

    1985-01-01

    Prazosin, an antagonist of alpha 1-adrenergic receptors, has been found to suppress the clinical and histological expression of experimental autoimmune encephalomyelitis (EAE) in the Lewis rat. Suppression was more significant in females than in males and was a dose-dependent phenomenon. Analysis of the effect of other adrenergic receptor antagonists supports the conclusion that the suppressive effect of prazosin is a consequence of blockade of the alpha 1-receptor since treatment with either the alpha 2-antagonist yohimbine or the beta-antagonist propranolol exacerbated the disease, whereas treatment with the long-acting mixed alpha 1/alpha 2-antagonist phenoxybenzamine had some suppressive activity. Treatment with prazosin was also able to suppress clinical and histological signs of EAE in animals sensitized by adoptive transfer with activated spleen or lymph node cells. Whether prazosin acts through altering vascular permeability or the immune response, or both, remains to be determined. Images PMID:2994053

  13. Design and experimental validation of a flutter suppression controller for the active flexible wing

    NASA Technical Reports Server (NTRS)

    Waszak, Martin R.; Srinathkumar, S.

    1992-01-01

    The synthesis and experimental validation of an active flutter suppression controller for the Active Flexible Wing wind tunnel model is presented. The design is accomplished with traditional root locus and Nyquist methods using interactive computer graphics tools and extensive simulation based analysis. The design approach uses a fundamental understanding of the flutter mechanism to formulate a simple controller structure to meet stringent design specifications. Experimentally, the flutter suppression controller succeeded in simultaneous suppression of two flutter modes, significantly increasing the flutter dynamic pressure despite modeling errors in predicted flutter dynamic pressure and flutter frequency. The flutter suppression controller was also successfully operated in combination with another controller to perform flutter suppression during rapid rolling maneuvers.

  14. Flutter suppression for the Active Flexible Wing - Control system design and experimental validation

    NASA Technical Reports Server (NTRS)

    Waszak, M. R.; Srinathkumar, S.

    1992-01-01

    The synthesis and experimental validation of a control law for an active flutter suppression system for the Active Flexible Wing wind-tunnel model is presented. The design was accomplished with traditional root locus and Nyquist methods using interactive computer graphics tools and with extensive use of simulation-based analysis. The design approach relied on a fundamental understanding of the flutter mechanism to formulate understanding of the flutter mechanism to formulate a simple control law structure. Experimentally, the flutter suppression controller succeeded in simultaneous suppression of two flutter modes, significantly increasing the flutter dynamic pressure despite errors in the design model. The flutter suppression controller was also successfully operated in combination with a rolling maneuver controller to perform flutter suppression during rapid rolling maneuvers.

  15. Differences in self- and other-induced Mu suppression are correlated with empathic abilities.

    PubMed

    Woodruff, C Chad; Martin, Tim; Bilyk, Nick

    2011-08-01

    Recent research suggests a role of the human mirror neuron system in empathic processing. Electroencephalographic (EEG) mu suppression in the 8-13Hz band-range has been proposed to reflect mirror-like activation of sensorimotor cortices. We therefore investigated the relationship between suppression in the 8-13Hz range and empathic abilities as measured by the Interpersonal Reactivity Index (IRI). Based on previous work showing significant differences between execution- and observation-related mu suppression and on theories of empathy pointing to the importance of discriminating self from other, we predicted that the size of this difference within individuals would correlate with participants' perspective-taking abilities. Larger differences in execution- and observation-induced mu suppression were associated with greater scores on the perspective-taking subscale of the IRI. The current data are therefore consistent with the claim that neural activity reflected in mu suppression is related to empathic abilities. PMID:21741034

  16. Local administration of resveratrol inhibits excitability of nociceptive wide-dynamic range neurons in rat trigeminal spinal nucleus caudalis.

    PubMed

    Shimazu, Yoshihito; Shibuya, Eri; Takehana, Shiori; Sekiguchi, Kenta; Oshima, Katsuo; Kamata, Hiroaki; Karibe, Hiroyuki; Takeda, Mamoru

    2016-06-01

    Although we recently reported that intravenous administration of resveratrol suppresses trigeminal nociception, the precise peripheral effect of resveratrol on nociceptive and non-nociceptive mechanical stimulation-induced trigeminal neuron activity in vivo remains to be determined. The aim of the present study was to investigate whether local subcutaneous administration of resveratrol attenuates mechanical stimulation-induced excitability of trigeminal spinal nucleus caudalis (SpVc) neuron activity in rats, in vivo. Extracellular single-unit recordings were made of SpVc wide-dynamic range (WDR) neuron activity in response to orofacial mechanical stimulation in pentobarbital-anesthetized rats. Neurons responded to non-noxious and noxious mechanical stimulation applied to the orofacial skin. Local subcutaneous administration of resveratrol (1-10mM) into the orofacial skin dose dependently and significantly reduced the mean number of SpVc WDR neurons firing in response to both non-noxious and noxious mechanical stimuli, with the maximal inhibition of discharge frequency in response to both stimuli being seen within 5min. These inhibitory effects were no longer evident after approximately 20min. The mean magnitude of inhibition by resveratrol (10mM) of SpVc neuron discharge frequency was almost equal to that of the local anesthetic 1% lidocaine (37mM). These results suggest that local injection of resveratrol into the peripheral receptive field suppresses the excitability of SpVc neurons, possibly via inhibition of Na(+) channels in the nociceptive nerve terminals of trigeminal ganglion neurons. Therefore, local subcutaneous administration of resveratrol may provide relief of trigeminal nociceptive pain, without side effects, thus contributing to the suite of complementary and alternative medicines used as local anesthetic agents. PMID:27288246

  17. Administration of 3,5-diiodothyronine (3,5-T2) causes central hypothyroidism and stimulates thyroid-sensitive tissues

    PubMed Central

    Padron, Alvaro Souto; Neto, Ruy Andrade Louzada; Pantaleão, Thiago Urgal; de Souza dos Santos, Maria Carolina; Araujo, Renata Lopes; de Andrade, Bruno Moulin; da Silva Leandro, Monique; de Castro, João Pedro Saar Werneck; Ferreira, Andrea Claudia Freitas; de Carvalho, Denise Pires

    2014-01-01

    In general, 3,5-diiodothyronine (3,5-T2) increases the resting metabolic rate and oxygen consumption, exerting short-term beneficial metabolic effects on rats subjected to a high-fat diet. Our aim was to evaluate the effects of chronic 3,5-T2 administration on the hypothalamus–pituitary–thyroid axis, body mass gain, adipose tissue mass, and body oxygen consumption in Wistar rats from 3 to 6 months of age. The rats were treated daily with 3,5-T2 (25, 50, or 75 μg/100 g body weight, s.c.) for 90 days between the ages of 3 and 6 months. The administration of 3,5-T2 suppressed thyroid function, reducing not only thyroid iodide uptake but also thyroperoxidase, NADPH oxidase 4 (NOX4), and thyroid type 1 iodothyronine deiodinase (D1 (DIO1)) activities and expression levels, whereas the expression of the TSH receptor and dual oxidase (DUOX) were increased. Serum TSH, 3,3′,5-triiodothyronine, and thyroxine were reduced in a 3,5-T2 dose-dependent manner, whereas oxygen consumption increased in these animals, indicating the direct action of 3,5-T2 on this physiological variable. Type 2 deiodinase activity increased in both the hypothalamus and the pituitary, and D1 activities in the liver and kidney were also increased in groups treated with 3,5-T2. Moreover, after 3 months of 3,5-T2 administration, body mass and retroperitoneal fat pad mass were significantly reduced, whereas the heart rate and mass were unchanged. Thus, 3,5-T2 acts as a direct stimulator of energy expenditure and reduces body mass gain; however, TSH suppression may develop secondary to 3,5-T2 administration. PMID:24692290

  18. 42 CFR 137.22 - May the Secretary consider uncorrected significant and material audit exceptions identified...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... financial and administrative functions, such as personnel, payroll, property management, etc., the Secretary... and material audit exceptions identified regarding centralized financial and administrative functions... uncorrected significant and material audit exceptions identified regarding centralized financial...

  19. 42 CFR 137.22 - May the Secretary consider uncorrected significant and material audit exceptions identified...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... financial and administrative functions, such as personnel, payroll, property management, etc., the Secretary... and material audit exceptions identified regarding centralized financial and administrative functions... uncorrected significant and material audit exceptions identified regarding centralized financial...

  20. 42 CFR 137.22 - May the Secretary consider uncorrected significant and material audit exceptions identified...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... financial and administrative functions, such as personnel, payroll, property management, etc., the Secretary... and material audit exceptions identified regarding centralized financial and administrative functions... uncorrected significant and material audit exceptions identified regarding centralized financial...

  1. 42 CFR 137.22 - May the Secretary consider uncorrected significant and material audit exceptions identified...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... financial and administrative functions, such as personnel, payroll, property management, etc., the Secretary... and material audit exceptions identified regarding centralized financial and administrative functions... uncorrected significant and material audit exceptions identified regarding centralized financial...

  2. 42 CFR 137.22 - May the Secretary consider uncorrected significant and material audit exceptions identified...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... financial and administrative functions, such as personnel, payroll, property management, etc., the Secretary... and material audit exceptions identified regarding centralized financial and administrative functions... uncorrected significant and material audit exceptions identified regarding centralized financial...

  3. Enhancement or Suppression of ACE Inhibitory Activity by a Mixture of Tea and Foods for Specified Health Uses (FOSHU) That Are Marketed as “Support for Normal Blood Pressure”

    PubMed Central

    Murakami, Isao; Hosono, Hiroyuki; Suzuki, Shigeto; Kurihara, Junichi; Itagaki, Fumio; Watanabe, Machiko

    2011-01-01

    The ACE inhibitory activities of mixtures of FOSHUs (Healthya, Goma-Mugicha, Lapis Support and Ameal) were examined in order to identify any antihypertensive interactions. Among combinations of Healthya with other samples that contain active peptides, only that with Ameal was found to have no inhibitory activity. Enhanced activity was observed in 2 other mixtures. The activity of a mixture of tea polyphenols and the whey component extracted from an Ameal solution was significantly decreased, thus demonstrating that whey protein lowered the ACE inhibitory activity of Healthya. Although oral administration of tea polyphenols alone significantly decreased SBP in SHR at 2 and 4 hr, combined administration with Ameal failed to decrease SBP at the same time points. In conclusion, the simultaneous intake of tea and FOSHUs that contain active peptides might affect daily self-antihypertensive management via enhancement or suppression of ACE inhibitory activity. PMID:22389857

  4. Seed-colonizing microbes from municipal biosolids compost suppress Pythium ultimum damping-off on different plant species.

    PubMed

    Chen, M-H; Nelson, E B

    2008-09-01

    Composts are known for their suppressive properties toward many different seed- and root-infecting pathogens and diseases. Although disease and pathogen suppression induced by composts is believed to be mediated by microbial activities, the nature of the microbial species and processes responsible for suppressiveness remain unknown. We demonstrated previously that seed-colonizing microbial consortia from leaf compost could explain the observed levels of Pythium ultimum-induced damping-off suppression on cotton. The aim of the present work was to determine whether seed-colonizing microbial consortia could explain Pythium damping-off suppression in municipal biosolids compost on three different plant species. Significant levels of disease suppression were observed on cucumber, wheat, and pea at water potentials of -2 kPa. The suppression of damping-off on cucumber and wheat could be eliminated by autoclaving the compost prior to sowing. High levels of suppressiveness were expressed both on cucumber and on wheat seed surfaces within 8 h of sowing. However, the expression of damping-off suppression on the surface of pea seeds was inconsistent and highly variable. Our results demonstrate that compost-induced suppression of P. ultimum damping-off of cucumber and wheat can be explained by the microbial consortia colonizing seeds within 8 h of sowing. These results further suggest that disease suppression in composts is related to microbial species that interact with the pathogen in its infection court and not in the bulk compost. PMID:18943739

  5. Suppression of spermatogenesis by testosterone undecanoate-loaded injectable in situ-forming implants in adult male rats.

    PubMed

    Zhang, Xiao-Wei; Zhang, Chong; Zhang, Wei; Yang, Dan; Meng, Shu; Wang, Ping; Guo, Jing; Liu, Dan-Hua

    2016-01-01

    We have investigated the feasibility of administration of testosterone undecanoate (TU)-loaded injectable in situ-forming implant (ISFI) for contraception in adult male Sprague-Dawley rats. Male rats were treated with vehicle, TU-loaded ISFIs (540, 270 and 135 mg TU kg-1 ) or TU injections (45 mg TU kg-1 every 30 days) for 120 days. Fertility tests served for determining infertility or restoration of fertility in treated rats. Serum testosterone concentration, epididymal sperm count, motility, morphology, and histology of the testis were monitored. The TU-loaded ISFIs increased serum testosterone levels in rats steadily without fluctuation over 3 months. One month after TU administration, the epididymal sperm count decreased significantly in all experimental groups. After 3 months, the animals treated with 270 and 135 mg kg-1 TU-loaded ISFIs were 100% infertile, and no implantation sites were produced in the mated females. However, some of males treated with 540 mg kg-1 ISFI or TU injections were still fertile but numbers of implantation sites were also significantly lower than control values. TU-loaded ISFI at an appropriate dose has potential as a long-acting male contraceptive drug that suppresses spermatogenesis consistently over a period of 3 months. PMID:26459781

  6. Vitamin D inhibits the occurrence of experimental cerebral malaria in mice by suppressing the host inflammatory response

    PubMed Central

    He, Xiyue; Yan, Juan; Zhu, Xiaotong; Wang, Qinghui; Pang, Wei; Qi, Zanmei; Wang, Meilian; Luo, Enjie; Parker, Daniel M.; Cantorna, Margherita T.; Cui, Liwang; Cao, Yaming

    2014-01-01

    In animal models of experimental cerebral malaria (ECM), neuropathology is associated with an overwhelming inflammatory response and sequestration of leucocytes and parasite-infected red blood cells in the brain. Here we explored the effect of vitamin D (VD, cholecalciferol) treatment on host immunity and outcome of ECM in C57BL/6 mice during Plasmodium berghei ANKA (PbA) infection. We observed that oral administration of VD both before and after PbA infection completely protected mice from ECM. VD administration significantly dampened the inducible systemic inflammatory responses with reduced circulating cytokines IFN-γ and TNF and decreased expression of these cytokines by the spleen cells. Meanwhile, VD also resulted in decreased expression of the chemokines CXCL9 and CXCL10 and cytoadhesion molecules (ICAM-1, VCAM-1 and CD36) in the brain, leading to reduced accumulation of pathogenic T cells in the brain and ultimately substantial improvement of the blood-brain barriers of PbA-infected mice. In addition, VD inhibited the differentiation, activation and maturation of splenic dendritic cells. Meanwhile, regulatory T cells and IL-10 expression levels were upregulated upon VD treatment. These data collectively demonstrated the suppressive function of VD on host inflammatory responses, which provides significant survival benefits in the murine ECM model. PMID:24965778

  7. Caffeic acid phenethyl ester suppresses the proliferation of human prostate cancer cells through inhibition of AMPK and Akt signaling networks

    PubMed Central

    Chuu, Chih-Pin; Lin, Hui-Ping; Ciaccio, Mark F.; Kokontis, John M.; Hause, Ronald J.; Hiipakka, Richard A.; Liao, Shutsung; Jones, Richard Baker

    2016-01-01

    Caffeic acid phenethyl ester (CAPE) is a bioactive component derived from honeybee hive propolis. CAPE has been shown to have anti-mitogenic, anti-carcinogenic, and other beneficial medicinal properties. Many of its effects have been shown to be mediated through its inhibition of NF-κB signaling pathways. We took a systematic approach to uncover CAPE’s effects from hours to days on the signaling networks in human prostate cancer cells. We observed that CAPE dosage-dependently suppressed the proliferation of LNCaP, DU-145, and PC-3 human prostate cancer cells. Administration of CAPE by gavage significantly inhibited the tumor growth of LNCaP xenografts in nude mice. Using LNCaP cells as a model system, we examined CAPE’s effect on gene expression, protein signaling, and transcriptional regulatory networks using Micro-Western Arrays and PCR arrays. We built a model of CAPE’s impact on cell signaling which suggested that it acted through inhibition of Akt-related protein signaling networks. Over-expression of Akt1 or cMyc, a downstream target of Akt signaling, significantly blocked the anti-proliferative effects of CAPE. In summary, our results suggest that CAPE administration may be useful as an adjuvant therapy for prostate and potentially other types of cancers that are driven by the AMPK and Akt signaling networks. PMID:22562408

  8. Suppression of spermatogenesis by testosterone undecanoate-loaded injectable in situ-forming implants in adult male rats

    PubMed Central

    Zhang, Xiao-Wei; Zhang, Chong; Zhang, Wei; Yang, Dan; Meng, Shu; Wang, Ping; Guo, Jing; Liu, Dan-Hua

    2016-01-01

    We have investigated the feasibility of administration of testosterone undecanoate (TU)-loaded injectable in situ-forming implant (ISFI) for contraception in adult male Sprague–Dawley rats. Male rats were treated with vehicle, TU-loaded ISFIs (540, 270 and 135 mg TU kg−1) or TU injections (45 mg TU kg−1 every 30 days) for 120 days. Fertility tests served for determining infertility or restoration of fertility in treated rats. Serum testosterone concentration, epididymal sperm count, motility, morphology, and histology of the testis were monitored. The TU-loaded ISFIs increased serum testosterone levels in rats steadily without fluctuation over 3 months. One month after TU administration, the epididymal sperm count decreased significantly in all experimental groups. After 3 months, the animals treated with 270 and 135 mg kg−1 TU-loaded ISFIs were 100% infertile, and no implantation sites were produced in the mated females. However, some of males treated with 540 mg kg−1 ISFI or TU injections were still fertile but numbers of implantation sites were also significantly lower than control values. TU-loaded ISFI at an appropriate dose has potential as a long-acting male contraceptive drug that suppresses spermatogenesis consistently over a period of 3 months. PMID:26459781

  9. Suppression of aversive memories associates with changes in early and late stages of neurocognitive processing.

    PubMed

    Chen, Chunping; Liu, Chao; Huang, Ruiwang; Cheng, Dazhi; Wu, Haiyan; Xu, Pengfei; Mai, Xiaoqin; Luo, Yue-Jia

    2012-10-01

    Unwanted memories, such as emotionally negative, can be intentionally suppressed through voluntary control in humans. Memory suppression is thought to be mediated by the interplay of a chain of neurocognitive processes. However, empirical data in support of this notion is lacking. Using high-temporal resolution event-related potential (ERP) technique, we investigated the time course of ERPs associated with suppression of negative and neutral memories in a Think/No-Think paradigm in young, healthy participants. Results showed that participants had greater difficulty in suppressing emotionally negative memories than neutral ones. ERPs and source analyses demonstrated that memory suppression processing for negative and neutral memories were generally associated with changes during early components of a time window of 70-260 ms, such as P1 and N2, mainly at the right inferior frontal gyrus and occipital lobe; suppression of aversive memories was associated with two major late ERP components between 380 and 800 ms, with significantly smaller later negativity (LN) but larger late parietal positivity (LPP), primarily at the right medial and superior frontal gyri. These results suggest that differences in early components may reflect early stages of suppression processing including visual awareness, attention reallocation, and executive processing. Differences in late components between suppression of aversive and neutral memories may reflect a process of down-regulating conscious recollection of memory representations supported by prefrontal and parietal networks. A less effective control of this process, as evidenced by smaller LN and larger LPP, may explain the fact that emotionally negative memories were harder to be suppressed. Altogether, these findings suggest that suppression of aversive memories requires down-regulation of late conscious recollection, which can be dissociated from early visual and attention processing in memory suppression. PMID:22917568

  10. A specific aptamer-cell penetrating peptides complex delivered siRNA efficiently and suppressed prostate tumor growth in vivo.

    PubMed

    Diao, Yanjun; Liu, Jiayun; Ma, Yueyun; Su, Mingquan; Zhang, Hongyi; Hao, Xiaoke

    2016-05-01

    Specific and efficient delivery of siRNA into intended tumor cells remains as a challenge, even though RNAi has been exploited as a new strategy for prostate cancer therapy. This work aims to address both specificity and efficiency of SURVIVIN-siRNA delivery by constructing a therapeutic complex using combinatorial strategies. A fusion protein STD was first expressed to serve as a backbone, consisting of streptavidin, a cell-penetrating peptide called Trans-Activator of Transcription (TAT) and a double-stranded RNA binding domain. A biotinylated Prostate Specific Membrane Antigen (PSMA) specific aptamer A10 and SURVIVIN-siRNA were then linked to STD protein to form the therapeutic complex. This complex could specifically targeted PSMA(+) tumor cells. Compared to lipofectamine and A10-siRNA chimera, it demonstrated higher efficiency in delivering siRNA into target cells by 19.2% and 59.9%, and increased apoptosis by 16.8% and 26.1% respectively. Upon systemic administration, this complex also showed significant efficacy in suppressing tumor growth in athymic mice (p <0.001). We conclude that this therapeutic complex could specifically and efficiently deliver SURVIVIN-siRNA to target cells and suppressed tumor growth in vivo, which indicates its potential to be used as a new strategy in prostate cancer therapy. PMID:26954374

  11. Zoledronic acid suppresses transforming growth factor-β-induced fibrogenesis by human gingival fibroblasts

    PubMed Central

    KOMATSU, YUKO; IBI, MIHO; CHOSA, NAOYUKI; KYAKUMOTO, SEIKO; KAMO, MASAHARU; SHIBATA, TOSHIYUKI; SUGIYAMA, YOSHIKI; ISHISAKI, AKIRA

    2016-01-01

    Bisphosphonates (BPs) are analogues of pyro-phosphate that are known to prevent bone resorption by inhibiting osteoclast activity. Nitrogen-containing BPs, such as zoledronic acid (ZA), are widely used in the treatment of osteoporosis and bone metastasis. However, despite having benefits, ZA has been reported to induce BP-related osteonecrosis of the jaw (BRONJ) in cancer patients. The molecular pathological mechanisms responsible for the development of BRONJ, including necrotic bone exposure after tooth extraction, remain to be elucidated. In this study, we examined the effects of ZA on the transforming growth factor-β (TGF-β)-induced myofibroblast (MF) differentiation of human gingival fibroblasts (hGFs) and the migratory activity of hGFs, which are important for wound closure by fibrous tissue formation. The ZA maximum concentration in serum (Cmax) was found to be approximately 1.47 µM, which clinically, is found after the intravenous administration of 4 mg ZA, and ZA at this dose is considered appropriate for the treatment of cancer bone metastasis or bone diseases, such as Erdheim-Chester disease. At Cmax, ZA significantly suppressed i) the TGF-β-induced promotion of cell viability, ii) the TGF-β-induced expression of MF markers such as α-smooth muscle actin (α-SMA) and type I collagen, iii) the TGF-β-induced migratory activity of hGFs and iv) the expression level of TGF-β type I receptor on the surfaces of hGFs, as well as the TGF-β-induced phosphorylation of Smad2/3. Thus, ZA suppresses TGF-β-induced fibrous tissue formation by hGFs, possibly through the inhibition of Smad-dependent signal transduction. Our findings partly elucidate the molecular mechanisms underlying BRONJ and may prove to be beneficial to the identification of drug targets for the treatment of this symptom at the molecular level. PMID:27176567

  12. Ginsenoside Rd Is Efficacious Against Acute Ischemic Stroke by Suppressing Microglial Proteasome-Mediated Inflammation.

    PubMed

    Zhang, Guangyun; Xia, Feng; Zhang, Yunxia; Zhang, Xiao; Cao, Yuhong; Wang, Ling; Liu, Xuedong; Zhao, Gang; Shi, Ming

    2016-05-01

    A great deal of attention has been paid to neuroprotective therapies for cerebral ischemic stroke. Our two recent clinical trials showed that ginsenoside Rd (Rd), a kind of monomeric compound extracted from Chinese herbs, Panax ginseng and Panax notoginseng, was safe and efficacious for the treatment of ischemic stroke. In this study, we conducted a pooled analysis of the data from 199 patients with acute ischemic stroke in the first trial and 390 in the second to reanalyze the efficacy and safety of Rd. Moreover, animal stroke models were carried out to explore the possible molecular mechanisms underlying Rd neuroprotection. The pooled analysis showed that compared with placebo group, Rd could improve patients' disability as assessed by modified Rankin Scale (mRS) score on day 90 post-stroke and reduce neurologic deficits on day 15 or day 90 post-stroke as assessed by NIH Stroke Scale (NIHSS) and Barthel Index (BI) scores. For neuroprotective mechanisms, administration of Rd 4 h after stroke could inhibit ischemia-induced microglial activation, decrease the expression levels of various proinflammatory cytokines, and suppress nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha (IκBα) phosphorylation and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) nuclear translocation. An in vitro proteasome activity assay revealed a significant inhibitory effect of Rd on proteasome activity in microglia. Interestingly, Rd was showed to have less side effects than glucocorticoid. Therefore, our study demonstrated that Rd could safely improve the outcome of patients with ischemic stroke, and this therapeutic effect may result from its capability of suppressing microglial proteasome activity and sequential inflammation. PMID:26081140

  13. Suppressive effect of formononetin on platelet-derived growth factor-BB-stimulated proliferation and migration of vascular smooth muscle cells

    PubMed Central

    Chen, Zhuo; Liu, Suixin; Cai, Ying; Xie, Kangling; Zhang, Wenliang; Dong, Lei; Liu, Yuan; Zheng, Fan; Dun, Yaoshan; Li, Ning

    2016-01-01

    Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) has been implicated in intimal hyperplasia, atherosclerosis and restenosis following percutaneous coronary intervention. Formononetin, a phytoestrogen extracted from the root of Astragalus membranaceus, has been widely used in Chinese tradition medicine due to its protective effects against certain symptoms of cancer, hypertension, inflammation, hypoxia-induced cytotoxicity and ovariectomy-induced bone loss. However, the effect of formononetin on platelet-derived growth factor (PDGF)-BB-induced proliferation and migration of VSMCs, as well as the underlying molecular mechanism, remains largely unclear. In the present study, treatment with formononetin significantly inhibited PDGF-BB-induced proliferation and migration of human VSMCs. Investigation into the underlying molecular mechanism revealed that the administration of formononetin suppressed PDGF-BB-stimulated switch of VSMCs to a proliferative phenotype. Furthermore, treatment with formononetin inhibited the PDGF-BB-induced upregulation of cell cycle-related proteins, matrix metalloproteinase (MMP2) and MMP9. In addition, the that administration of formononetin inhibited the phosphorylation of AKT induced by PDGF-BB in VSMCs. The present results suggest that formononetin has a suppressive effect on PDGF-BB-stimulated VSMCs proliferation and migration, which may occur partly via the inhibition of AKT signaling pathway. Therefore, formononetin may be useful for the treatment of intimal hyperplasia, atherosclerosis and restenosis. PMID:27588108

  14. Hydrogen suppresses UO 2 corrosion

    NASA Astrophysics Data System (ADS)

    Carbol, Paul; Fors, Patrik; Gouder, Thomas; Spahiu, Kastriot

    2009-08-01

    Release of long-lived radionuclides such as plutonium and caesium from spent nuclear fuel in deep geological repositories will depend mainly on the dissolution rate of the UO 2 fuel matrix. This dissolution rate will, in turn, depend on the redox conditions at the fuel surface. Under oxidative conditions UO 2 will be oxidised to the 1000 times more soluble UO 2.67. This may occur in a repository as the reducing deep groundwater becomes locally oxidative at the fuel surface under the effect of α-radiolysis, the process by which α-particles emitted from the fuel split water molecules. On the other hand, the groundwater corrodes canister iron generating large amounts of hydrogen. The role of molecular hydrogen as reductant in a deep bedrock repository is questioned. Here we show evidence of a surface-catalysed reaction, taking place in the H 2-UO 2-H 2O system where molecular hydrogen is able to reduce oxidants originating from α-radiolysis. In our experiment the UO 2 surface remained stoichiometric proving that the expected oxidation of UO 2.00 to UO 2.67 due to radiolytic oxidants was absent. As a consequence, the dissolution of UO 2 stopped when equilibrium was reached between the solid phase and U 4+ species in the aqueous phase. The steady-state concentration of uranium in solution was determined to be 9 × 10 -12 M, about 30 times lower than previously reported for reducing conditions. Our findings show that fuel dissolution is suppressed by H 2. Consequently, radiotoxic nuclides in spent nuclear fuel will remain immobilised in the UO 2 matrix. A mechanism for the surface-catalysed reaction between molecular hydrogen and radiolytic oxidants is proposed.

  15. MEK5 suppresses osteoblastic differentiation.

    PubMed

    Kaneshiro, Shoichi; Otsuki, Dai; Yoshida, Kiyoshi; Yoshikawa, Hideki; Higuchi, Chikahisa

    2015-07-31

    Extracellular signal-regulated kinase 5 (ERK5) is a member of the mitogen-activated protein kinase (MAPK) family and is activated by its upstream kinase, MAPK kinase 5 (MEK5), which is a member of the MEK family. Although the role of MEK5 has been investigated in several fields, little is known about its role in osteoblastic differentiation. In this study, we have demonstrated the role of MEK5 in osteoblastic differentiation in mouse preosteoblastic MC3T3-E1 cells and bone marrow stromal ST2 cells. We found that treatment with BIX02189, an inhibitor of MEK5, increased alkaline phosphatase (ALP) activity and the gene expression of ALP, osteocalcin (OCN) and osterix, as well as it enhanced the calcification of the extracellular matrix. Moreover, osteoblastic cell proliferation decreased at a concentration of greater than 0.5 μM. In addition, knockdown of MEK5 using siRNA induced an increase in ALP activity and in the gene expression of ALP, OCN, and osterix. In contrast, overexpression of wild-type MEK5 decreased ALP activity and attenuated osteoblastic differentiation markers including ALP, OCN and osterix, but promoted cell proliferation. In summary, our results indicated that MEK5 suppressed the osteoblastic differentiation, but promoted osteoblastic cell proliferation. These results implied that MEK5 may play a pivotal role in cell signaling to modulate the differentiation and proliferation of osteoblasts. Thus, inhibition of MEK5 signaling in osteoblasts may be of potential use in the treatment of osteoporosis. PMID:25998381

  16. Mutual Suppression: Comment on Paulhus et Al. (2004)

    ERIC Educational Resources Information Center

    Nickerson, Carol

    2008-01-01

    Paulhus, Robins, Trzesniewski, and Tracy ("Multivariate Behavioral Research," 2004, 39, 305-328) suggested that the three types of two-predictor suppression situations--classical suppression, cooperative suppression, and net suppression--can all be considered special cases of mutual suppression, in that the magnitude of each of the two…

  17. Training of binocular rivalry suppression suggests stimulus-specific plasticity in monocular and binocular visual areas

    PubMed Central

    Vergeer, Mark; Wagemans, Johan; van Ee, Raymond

    2016-01-01

    The plasticity of the human brain, as shown in perceptual learning, is generally reflected by improved task performance after training. Here, we show that perceptual suppression can be increased through training. In the first experiment, binocular rivalry suppression of a specific orientation was trained, leading to a relative reduction in sensitivity to the trained orientation. In a second experiment, two orthogonal orientations were suppressed in alternating training blocks, in the left and right eye, respectively. This double-training procedure lead to reduced sensitivity for the orientation that was suppression-trained in each specific eye, implying that training of feature suppression is specific for the eye in which the oriented grating was presented during training. Results of a control experiment indicate that the obtained effects are indeed due to suppression during training, instead of being merely due to the repetitive presentation of the oriented gratings. Visual plasticity is essential for a person’s visual development. The finding that plasticity can result in increased perceptual suppression reported here may prove to be significant in understanding human visual development. It emphasizes that for stable vision, not only the enhancement of relevant signals is crucial, but also the reliable and stable suppression of (task) irrelevant signals. PMID:27160838

  18. Role of activation in alveolar macrophage-mediated suppression of the plaque-forming cell response.

    PubMed Central

    Mbawuike, I N; Herscowitz, H B

    1988-01-01

    Alveolar macrophages (AM) are highly suppressive of the in vitro plaque-forming cell (PFC) response of spleen cells obtained from mice primed with sheep erythrocytes. Comparison of macrophage populations obtained from disparate anatomical sites revealed that although in both cases there was a cell-concentration-dependent suppression of the PFC response, resident AM or AM activated as a result of intravenous injection of Mycobacterium bovis BCG were equally suppressive at the doses examined. Although there was a similar dose-dependent suppression with peritoneal macrophages, BCG-activated cells were more suppressive of the PFC response than were resident cells. In contrast, splenic macrophages at comparable concentrations were not at all suppressive. Resident AM exhibited significantly lower levels of 5'-nucleotidase activity than did resident peritoneal macrophages. Macrophage-mediated suppression of the in vitro PFC response could not be attributed to the release of toxic oxygen metabolites (H2O2, O2- ,and .OH) or prostaglandins, since the addition of catalase, superoxide dismutase, 2-mercaptoethanol, or indomethacin did not completely reverse suppression. These results suggest that the lung microenvironment may maintain AM in an activated state which contributes to their potential immunoregulatory functions. PMID:2830191

  19. Training of binocular rivalry suppression suggests stimulus-specific plasticity in monocular and binocular visual areas.

    PubMed

    Vergeer, Mark; Wagemans, Johan; van Ee, Raymond

    2016-01-01

    The plasticity of the human brain, as shown in perceptual learning, is generally reflected by improved task performance after training. Here, we show that perceptual suppression can be increased through training. In the first experiment, binocular rivalry suppression of a specific orientation was trained, leading to a relative reduction in sensitivity to the trained orientation. In a second experiment, two orthogonal orientations were suppressed in alternating training blocks, in the left and right eye, respectively. This double-training procedure lead to reduced sensitivity for the orientation that was suppression-trained in each specific eye, implying that training of feature suppression is specific for the eye in which the oriented grating was presented during training. Results of a control experiment indicate that the obtained effects are indeed due to suppression during training, instead of being merely due to the repetitive presentation of the oriented gratings. Visual plasticity is essential for a person's visual development. The finding that plasticity can result in increased perceptual suppression reported here may prove to be significant in understanding human visual development. It emphasizes that for stable vision, not only the enhancement of relevant signals is crucial, but also the reliable and stable suppression of (task) irrelevant signals. PMID:27160838

  20. Mesenchymal stem cells suppress CaN/NFAT expression in the pulmonary arteries of rats with pulmonary hypertension

    PubMed Central

    LIU, JUNFENG; HAN, ZHIBO; HAN, ZHONGCHAO; HE, ZHIXU

    2015-01-01

    Inflammation and hyperproliferation of pulmonary artery smooth muscle cells (PASMCs) is considered the primary pathological feature of pulmonary hypertension (PH). The present study determined that mesenchymal stem cells (MSCs) suppress the expression of calcineurin (CaN) and nuclear factor of activated T-cells (NFAT) in the pulmonary arteries of rats, and this may exert a therapeutic effect on PH. The potential therapeutic effects of MSCs on PH were assessed via the transplantation of human umbilical cord-derived MSCs, which were cultured in serum-free medium, into a monocrotaline (MCT)-induced PH rat model. Subsequently, the expression levels of tumor necrosis factor (TNF)-α in lung tissue and plasma, and of CaN and NFATc2 in pulmonary arteries were assessed. In the rat model of MCT-induced PH, investigated in the present study, TNF-α expression levels were detected in the lung tissue, and the levels of TNF-α in the plasma were increased. Furthermore, in addition to hemodynamic changes and the evident medial hypertrophy of the pulmonary muscular arterioles, CaN and NFATc2 expression levels were significantly upregulated in the pulmonary arteries. In the present study, the transplantation of MSCs, cultured in serum-free medium, decreased the levels of TNF-α in the lung tissue and plasma of rats, and downregulated CaN and NFATc2 expression in the pulmonary arteries. Furthermore, hemodynamic abnormalities and medial hypertrophy of the pulmonary muscular arterioles were notably improved. Therefore, the results of the present study may suggest that the administration of MSCs in PH may suppress the production of TNF-α, and downregulate the expression of CaN and NFATc2 in pulmonary arteries, which may provide an effective treatment for PH by suppressing the pathological proliferation of PASMCs. PMID:26640533