Sample records for acute stimulatory effect

  1. Self-stimulatory behavior and perceptual reinforcement.

    PubMed Central

    Lovaas, I; Newsom, C; Hickman, C

    1987-01-01

    Self-stimulatory behavior is repetitive, stereotyped, functionally autonomous behavior seen in both normal and developmentally disabled populations, yet no satisfactory theory of its development and major characteristics has previously been offered. We present here a detailed hypothesis of the acquisition and maintenance of self-stimulatory behavior, proposing that the behaviors are operant responses whose reinforcers are automatically produced interoceptive and exteroceptive perceptual consequences. The concept of perceptual stimuli and reinforcers, the durability of self-stimulatory behaviors, the sensory extinction effect, the inverse relationship between self-stimulatory and other behaviors, the blocking effect of self-stimulatory behavior on new learning, and response substitution effects are discussed in terms of the hypothesis. Support for the hypothesis from the areas of sensory reinforcement and sensory deprivation is also reviewed. Limitations of major alternative theories are discussed, along with implications of the perceptual reinforcement hypothesis for the treatment of excessive self-stimulatory behavior and for theoretical conceptualizations of functionally related normal and pathological behaviors. PMID:3583964

  2. Interferon beta 2/B-cell stimulatory factor type 2 shares identity with monocyte-derived hepatocyte-stimulating factor and regulates the major acute phase protein response in liver cells.

    PubMed Central

    Gauldie, J; Richards, C; Harnish, D; Lansdorp, P; Baumann, H

    1987-01-01

    One of the oldest and most preserved of the homeostatic responses of the body to injury is the acute phase protein response associated with inflammation. The liver responds to hormone-like mediators by the increased synthesis of a series of plasma proteins called acute phase reactants. In these studies, we examined the relationship of hepatocyte-stimulating factor derived from peripheral blood monocytes to interferon beta 2 (IFN-beta 2), which has been cloned. Antibodies raised against fibroblast-derived IFN-beta having neutralizing activity against both IFN-beta 1 and -beta 2 inhibited the major hepatocyte-stimulating activity derived from monocytes. Fibroblast-derived mediator elicited the identical stimulated response in human HepG2 cells and primary rat hepatocytes as the monocyte cytokine. Finally, recombinant-derived human B-cell stimulatory factor type 2 (IFN-beta 2) from Escherichia coli induced the synthesis of all major acute phase proteins studied in human hepatoma HepG2 and primary rat hepatocyte cultures. These data demonstrate that monocyte-derived hepatocyte-stimulating factor and IFN-beta 2 share immunological and functional identity and that IFN-beta 2, also known as B-cell stimulatory factor and hybridoma plasmacytoma growth factor, has the hepatocyte as a major physiologic target and thereby is essential in controlling the hepatic acute phase response. Images PMID:2444978

  3. Effects of a weighted vest on attention to task and self-stimulatory behaviors in preschoolers with pervasive developmental disorders.

    PubMed

    Fertel-Daly, D; Bedell, G; Hinojosa, J

    2001-01-01

    This study examined the effectiveness of using a weighted vest for increasing attention to a fine motor task and decreasing self-stimulatory behaviors in preschool children with pervasive developmental disorders (PDD). Using an ABA single-subject design, the duration of attention to task and self-stimulatory behaviors and the number of distractions were measured in five preschool children with PDD over a period of 6 weeks. During the intervention phase, all participants displayed a decrease in the number of distractions and an increase in the duration of focused attention while wearing the weighted vest. All but 1 participant demonstrated a decrease in the duration of self-stimulatory behaviors while wearing a weighted vest; however, the type of self-stimulatory behaviors changed and became less self-abusive for this child while she wore the vest. During the intervention withdrawal phase, 3 participants experienced an increase in the duration of self-stimulatory behaviors, and all participants experienced an increase in the number of distractions and a decrease in the duration of focused attention. The increase or decrease, however, never returned to baseline levels for these behaviors. The findings suggest that for these 5 children with PDD, the use of a weighted vest resulted in an increase in attention to task and decrease in self-stimulatory behaviors. The most consistent improvement observed was the decreased number of distractions. Additional research is necessary to build consensus about the effectiveness of wearing a weighted vest to increase attention to task and decrease self-stimulatory behaviors for children with PDD.

  4. Effects of Punishment Procedures on the Self-Stimulatory Behavior of an Autistic Child.

    ERIC Educational Resources Information Center

    Friman, Patrick C.; And Others

    1984-01-01

    Three punishment procedures--contingent applications of water mist, lemon juice, and vinegar--were evaluated as aversive treatment methods for a self-stimulatory behavior exhibited by a severely retarded 11-year-old male. The water mist procedure was as effective as lemon juice or vinegar, presented less physical threat to the client, and was…

  5. Propranolol blocks the stimulatory effects of naloxone on ventilation and oxygen consumption in hamsters.

    PubMed

    Schlenker, E H; Eikanger, J

    1997-06-01

    The purposes of these studies were: 1) to determine the effects of various doses of propranolol, a nonspecific beta-adrenergic antagonist, on ventilation, oxygen consumption, and body temperature in hamsters, and 2) to test the hypothesis that in hamsters the stimulatory effects of naloxone, an opioid receptor antagonist, on ventilation and oxygen consumption occur, at least in part, through the release of catecholamines that act via beta-adrenergic receptors. Propranolol, a non-specific beta adrenergic receptor antagonist, at a 20 mg/kg depressed body temperature, oxygen consumption, tidal volume, and ventilation relative to saline. The lower dose of 10 mg/kg had only transitory effects on tidal volume at 60 min and ventilation at 30 min post-injection-Naloxone (1 mg/kg) relative to saline stimulated ventilation and oxygen consumption. These effects were blocked by propranolol pretreatment. The results of these experiments demonstrate that in the hamster, 1) body temperature, oxygen consumption, and ventilation appear to be modulated by beta-adrenergic receptors, and 2) the stimulatory effects of naloxone on oxygen consumption and ventilation may occur through the interaction of endogenous opioids and beta-adrenergic receptor systems.

  6. Stimulatory and inhibitory effects of PKC isozymes are mediated by serine/threonine PKC sites of the Cav2.3α1 subunits.

    PubMed

    Rajagopal, Senthilkumar; Burton, Brittney K; Fields, Blanche L; El, India O; Kamatchi, Ganesan L

    2017-05-01

    Protein kinase C (PKC) isozymes modulate voltage-gated calcium (Ca v ) currents through Ca v 2.2 and Ca v 2.3 channels by targeting serine/threonine (Ser/Thr) phosphorylation sites of Ca v α 1 subunits. Stimulatory (Thr-422, Ser-2108 and Ser-2132) and inhibitory (Ser-425) sites were identified in the Ca v 2.2α 1 subunits to PKCs βII and ε. In the current study, we investigated if the homologous sites of Ca v 2.3α 1 subunits (stimulatory: Thr-365, Ser-1995 and Ser-2011; inhibitory: Ser-369) behaved in similar manner. Several Ala and Asp mutants were constructed in Ca v 2.3α 1 subunits in such a way that the Ser/Thr sites can be examined in isolation. These mutants or WT Ca v 2.3α 1 along with auxiliary β 1b and α 2 /δ subunits were expressed in Xenopus oocytes and the effects of PKCs βII and ε studied on the barium current (I Ba ). Among these sites, stimulatory Thr-365 and Ser-1995 and inhibitory Ser-369 behaved similar to their homologs in Ca v 2.2α 1 subunits. Furthermore PKCs produced neither stimulation nor inhibition when stimulatory Thr-365 or Ser-1995 and inhibitory Ser-369 were present together. However, the PKCs potentiated the I Ba when two stimulatory sites, Thr-365 and Ser-1995 were present together, thus overcoming the inhibitory effect of Ser-369. Taken together net PKC effect may be the difference between the responses of the stimulatory and inhibitory sites. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Effects of aluminum trichloride on the cartilage stimulatory growth factors in rats.

    PubMed

    Zhang, Fan; Sun, Xudong; Yu, Hongyan; Yang, Xu; Song, Miao; Han, Yanfei; Li, Yanfei; Zhu, Yanzhu

    2017-02-01

    Aluminum (Al) is considered to be a potentially toxic metal and inhibits cartilage formation. Transforming growth factor β1 (TGF-β1) and bone morphogenetic protein 2 (BMP-2) are cartilage stimulatory growth factors, which play important roles in regulating the cartilage formation. To investigate the effects of aluminum trichloride (AlCl 3 ) on the regulation of cartilage formation. Eighty Wistar rats were orally exposed to 0 (control group), 0.4 g/L (low-dose group), 0.8 g/L (mid-dose group) and 1.6 g/L (high-dose group) AlCl 3 for 120 days, respectively. The rats body weight were decreased, the cartilage histological structure were disrupted, the cartilage and serum contents of Al and the serum level of C-telopeptide of type II collagen were all increased, the serum level of type II collagen (Col II) and alkaline phosphatase (ALP), and the mRNA expressions of TGF-β1, BMP-2, ALP and Col II were all decreased in the AlCl 3 -treated groups compared with those in control group. These results indicate that AlCl 3 inhibits the cartilage formation through inhibition of the cartilage stimulatory growth factors expressions.

  8. Immune-Stimulatory Effects of Althaea rosea Flower Extracts through the MAPK Signaling Pathway in RAW264.7 Cells.

    PubMed

    Kim, Yon-Suk; Kim, Eun-Kyung; Nawarathna, Weligala Pahalagedara Amila Srilal; Dong, Xin; Shin, Woen-Bin; Park, Jin-Su; Moon, Sang-Ho; Park, Pyo-Jam

    2017-04-25

    Althaea rosea (Linn.) is a medicinal plant from China and Korea that has been traditionally used to control inflammation, to stop bedwetting and as a mouthwash in cases of bleeding gums. Its flowers are employed medicinally for their emollient, demulcent and diuretic properties, which make them useful in chest complaints. Furthermore, a flower extract decoction is used to improve blood circulation, for the treatment of constipation, dysmenorrhoea, haemorrhages, etc. However, the possible mechanisms of the immune-stimulatory effect remains to be elucidated. Therefore, we investigated the role of Althaea rosea flower (ARF) extracts in the immune-stimulatory effect of macrophages and the underlying mechanisms of action. ARF water extract (ARFW) could dose-dependently increase NO production and cytokines (IL-6 and TNF-α). We also found that ARFW significantly increased the expression of iNOS and COX-2 proteins in RAW264.7 cells. Consistent with these results, MAPK protein (JNK, ERK, p38) expression levels were induced after treatment with ARFW. Additionally, ARFW showed a marked increase in the phosphorylation level of IκBα and subsequent IκBα degradation allowing NF-κB nuclear translocation. These results suggest that the immune-stimulatory effect of A. rosea flower extracts is mediated through the translocation of NF-κB p65 subunit into the nucleus from the cytoplasm and subsequent activation of pro-inflammatory cytokines (IL-6 and TNF-α) and other mediators (iNOS and COX-2), which occurs mainly through MAPK signalling pathway. Thus, we suggest that ARFW could be considered as a potential therapeutic agent useful in the development of immune-stimulatory compounds.

  9. Stimulatory effects of bombesin on plasma trypsin release and exocrine pancreatic secretion in dogs.

    PubMed

    Kiriyama, S; Hayakawa, T; Kondo, T; Shibata, T; Kitagawa, M; Sakai, Y; Sobajima, H; Ikei, N; Kodaira, T; Hamaoka, T

    1990-01-01

    We examined the effect of bombesin on plasma trypsin release and exocrine pancreatic secretion in dogs. Bombesin significantly increased plasma immunoreactive trypsin (IRT). Atropine significantly inhibited the response of plasma IRT to bombesin. Pancreatic trypsin secretion was also increased by bombesin, as well as bicarbonate and protein outputs. Atropine failed to inhibit pancreatic trypsin secretion. In conclusion, bombesin has a stimulatory effect on plasma trypsin release mediated by a cholinergic mechanism and different from pancreatic secretion.

  10. Treatment of Shwachman syndrome by Japanese herbal medicine (Juzen-taiho-to): stimulatory effects of its fatty acids on hemopoiesis in patients.

    PubMed

    Hisha, Hiroko; Kohdera, Urara; Hirayama, Masahiro; Yamada, Haruki; Iguchi-Uehira, Tomoko; Fan, Tian-Xue; Cui, Yun-Ze; Yang, Guo-Xiang; Li, Yongan; Sugiura, Kikuya; Inaba, Muneo; Kobayashi, Yohnosuke; Ikehara, Susumu

    2002-01-01

    Juzen-taiho-to (a Japanese herbal medicine) has been traditionally administered to patients with anemia, neutropenia, or wasting syndrome. We previously attempted to isolate and purify the hemopoiesis-stimulatory components in Juzen-taiho-to extracts using an in vitro hemopoietic stem cell (HSC) assay method in which mouse HSCs can proliferate on a stromal cell line (MS-5). We have found that fatty acids (particularly oleic acid and linolenic acid) actively promote the proliferation of HSCs, and that the effect is mediated by stromal cells, rather than by any direct action on the HSCs. In the present study, we show, using human normal bone marrow cells (BMCs) and umbilical cord blood cells, that similar stimulatory effects are due to the presence of oleic acid and linolenic acid, which stimulate the proliferation of HSCs in stroma-based culture systems. Furthermore, a marked stimulatory effect was noted on BMCs from patients with Shwachman syndrome, which shows pancreatic and bone marrow dysfunctions. We also show the data on hemopoietic recovery after the administration of Juzen-taiho-to to a patient with Shwachman syndrome. These findings suggest that decreased fatty acid levels in the blood, caused by exocrine pancreatic insufficiency, induce bone marrow dysfunction in Shwachman syndrome.

  11. 'Fingerprints' of central stimulatory drug effects by means of quantitative radioelectroencephalography in the rat (tele-stereo-EEG).

    PubMed

    Dimpfel, W; Spüler, M; Nickel, B; Tibes, U

    1986-01-01

    The new electrophysiological model earlier described as stereo-EEG is extended now to allow recording from the freely moving rat by means of a telemetric device. Chronic implantation of 4 electrodes into the brain allows simultaneous transmission of field potentials from frontal cortex, hippocampus, striatum and reticular formation. Frequency analysis of these potentials results in a drug-specific 'fingerprint' which cannot only be used to compare different chemicals with each other but also to detect onset and time dependence of drug actions. Application of the model to the question if fenetylline has its own intrinsic mode of action or merely develops its stimulatory effect after metabolic separation into its molecular moieties amphetamine and theophylline (prodrug hypothesis) revealed that fenetylline indeed displays its own stimulatory effect to the same extent and at a similar time course as amphetamine and theophylline. The 'fingerprint' as obtained by the analysis of the action of fenetylline in the rat resembles closely that obtained after the application of theophylline with respect to decreased alpha activity, but resembles amphetamine with respect to beta 1 activity. Thus the applied method allows studying structure function relationships as the action of fenetylline seems to reflect both its molecular moieties.

  12. Stimulatory effects of calcium on respiration and NAD(P)H synthesis in intact rat heart mitochondria utilizing physiological substrates cannot explain respiratory control in vivo.

    PubMed

    Vinnakota, Kalyan C; Dash, Ranjan K; Beard, Daniel A

    2011-09-02

    Mitochondrial TCA cycle dehydrogenase enzymes have been shown to be stimulated by Ca(2+) under various substrate and ADP incubation conditions in an attempt to determine and understand the role of Ca(2+) in maintaining energy homeostasis in working hearts. In this study, we tested the hypothesis that, at physiological temperature and 1 mM extramitochondrial free magnesium, Ca(2+) can stimulate the overall mitochondrial NAD(P)H generation flux in rat heart mitochondria utilizing pyruvate and malate as substrates at both subsaturating and saturating concentrations. In both cases, we found that, in the physiological regime of mitochondrial oxygen consumption observed in the intact animal and in the physiological range of cytosolic Ca(2+) concentration averaged per beat, Ca(2+) had no observable stimulatory effect. A modest apparent stimulatory effect (22-27%) was observable at supraphysiological maximal ADP-stimulated respiration at 2.5 mM initial phosphate. The stimulatory effects observed over the physiological Ca(2+) range are not sufficient to make a significant contribution to the control of oxidative phosphorylation in the heart in vivo.

  13. Stimulatory Effects of Calcium on Respiration and NAD(P)H Synthesis in Intact Rat Heart Mitochondria Utilizing Physiological Substrates Cannot Explain Respiratory Control in Vivo*

    PubMed Central

    Vinnakota, Kalyan C.; Dash, Ranjan K.; Beard, Daniel A.

    2011-01-01

    Mitochondrial TCA cycle dehydrogenase enzymes have been shown to be stimulated by Ca2+ under various substrate and ADP incubation conditions in an attempt to determine and understand the role of Ca2+ in maintaining energy homeostasis in working hearts. In this study, we tested the hypothesis that, at physiological temperature and 1 mm extramitochondrial free magnesium, Ca2+ can stimulate the overall mitochondrial NAD(P)H generation flux in rat heart mitochondria utilizing pyruvate and malate as substrates at both subsaturating and saturating concentrations. In both cases, we found that, in the physiological regime of mitochondrial oxygen consumption observed in the intact animal and in the physiological range of cytosolic Ca2+ concentration averaged per beat, Ca2+ had no observable stimulatory effect. A modest apparent stimulatory effect (22–27%) was observable at supraphysiological maximal ADP-stimulated respiration at 2.5 mm initial phosphate. The stimulatory effects observed over the physiological Ca2+ range are not sufficient to make a significant contribution to the control of oxidative phosphorylation in the heart in vivo. PMID:21757763

  14. Stimulatory effect of cooling tower biocides on amoebae.

    PubMed

    Srikanth, S; Berk, S G

    1993-10-01

    Two species of amoebae were isolated from the cooling tower of an air-conditioning system and examined for effects of exposure to four cooling tower biocides, a thiocarbamate compound, tributyltin neodecanoate mixed with quaternary ammonium compounds, another quaternary ammonium compound alone, and an isothiazolin derivative. The amoebae isolated were Acanthamoeba hatchetti and a Cochliopodium species. Two other amoeba cultures, an A. hatchetti culture and Cochliopodium bilimbosum, were obtained from the American Type Culture Collection (ATCC) and were also tested. The cooling tower isolates were more resistant to most of the biocides than the ATCC isolates were. The isothiazolin derivative was the least inhibitory to all four amoeba isolates, and tributyltin neodecanoate mixed with quaternary ammonium compounds was the most inhibitory to three of the four isolates. After exposure to lower concentrations of the biocides, including for one strain the manufacturer's recommended concentration of one biocide, the cooling tower amoeba populations increased significantly compared with unexposed controls, whereas the ATCC isolates were not stimulated at any of the concentrations tested. In some cases, concentrations which stimulated cooling tower amoebae inhibited the growth of the ATCC isolates. These results suggest that cooling tower amoebae may adapt to biocides, underscoring the need to use freshly isolated cooling tower organisms rather than organisms from culture collections for testing the efficacy of such biocides. The stimulatory effect of biocides on amoeba populations is an alarming observation, since these organisms may be reservoirs for legionellae. Biocides used to control microbial growth may actually enhance populations of host organisms for pathogenic bacteria.

  15. Stimulatory effects of histamine on migration of nasal fibroblasts.

    PubMed

    Hong, Sung-Moon; Park, Il-Ho; Um, Ji-Young; Shin, Jae-Min; Lee, Heung-Man

    2015-10-01

    Fibroblast migration is crucial for normal wound repair after sinonasal surgery. Histamine is known to be involved in wound healing by its effects on cell proliferation and migration. This study aimed to determine whether histamine affects the migration of nasal fibroblasts and to investigate the mechanism of action of histamine on nasal fibroblasts. Primary cultures of nasal fibroblasts were established from inferior turbinate samples. Fibroblast migration was evaluated with scratch assays. Cells were treated with histamine and/or histamine receptor-selective antagonists. U-73122 and pertussis toxin, which are selective inhibitors of the lower signaling pathway of H1R and H4R, were used to confirm the modulation of nasal fibroblast migration by histamine. Fibroblast cytoskeletal structures were visualized with immunocytochemistry. Histamine significantly stimulated the migration of nasal fibroblasts. Antagonists selective for HR1 and HR4 significantly reduced nasal fibroblast migration. In immunocytochemical staining, histamine treatment increased membrane ruffling and pyrilamine, diphenhydramine, fexofenadine, and JNJ7777120 decreased histamine-induced membrane ruffling. U-73122 and pertussis toxin also decreased histamine-induced migration of fibroblasts. Histamine maintains its stimulatory effects on fibroblast migration in the presence of mitomycin C, which blocks proliferation of cells. We showed that histamine stimulates fibroblast migration in nasal fibroblasts. This effect appeared to be mediated by HR1 and HR4. However, because fibroblast migration also can be involved in scaring and fibrosis, more research is necessary to determine the effects of antihistamine on wound healing after sinus surgery. © 2015 ARS-AAOA, LLC.

  16. GPER is involved in the stimulatory effects of aldosterone in breast cancer cells and breast tumor-derived endothelial cells.

    PubMed

    Rigiracciolo, Damiano Cosimo; Scarpelli, Andrea; Lappano, Rosamaria; Pisano, Assunta; Santolla, Maria Francesca; Avino, Silvia; De Marco, Paola; Bussolati, Benedetta; Maggiolini, Marcello; De Francesco, Ernestina Marianna

    2016-01-05

    Aldosterone induces relevant effects binding to the mineralcorticoid receptor (MR), which acts as a ligand-gated transcription factor. Alternate mechanisms can mediate the action of aldosterone such as the activation of epidermal growth factor receptor (EGFR), MAPK/ERK, transcription factors and ion channels. The G-protein estrogen receptor (GPER) has been involved in the stimulatory effects of estrogenic signalling in breast cancer. GPER has been also shown to contribute to certain responses to aldosterone, however the role played by GPER and the molecular mechanisms implicated remain to be fully understood. Here, we evaluated the involvement of GPER in the stimulatory action exerted by aldosterone in breast cancer cells and breast tumor derived endothelial cells (B-TEC). Competition assays, gene expression and silencing studies, immunoblotting and immunofluorescence experiments, cell proliferation and migration were performed in order to provide novel insights into the role of GPER in the aldosterone-activated signalling. Our results demonstrate that aldosterone triggers the EGFR/ERK transduction pathway in a MR- and GPER-dependent manner. Aldosterone does not bind to GPER, it however induces the direct interaction between MR and GPER as well as between GPER and EGFR. Next, we ascertain that the up-regulation of the Na+/H+ exchanger-1 (NHE-1) induced by aldosterone involves MR and GPER. Biologically, both MR and GPER contribute to the proliferation and migration of breast and endothelial cancer cells mediated by NHE-1 upon aldosterone exposure. Our data further extend the current knowledge on the molecular mechanisms through which GPER may contribute to the stimulatory action elicited by aldosterone in breast cancer.

  17. Isolation and Characterization of Lactoferrin Peptides with Stimulatory Effect on Osteoblast Proliferation.

    PubMed

    Fan, Fengjiao; Tu, Maolin; Liu, Meng; Shi, Pujie; Wang, Yun; Wu, Di; Du, Ming

    2017-08-23

    Lactoferrin is reported to be a potential food protein with osteogenic activity. However, the activity of lactoferrin peptides is questionable. In the present study, we isolated and characterized peptides from lactoferrin with stimulatory effect on osteoblast proliferation. Peptides from the lactoferrin pepsin hydrolysate were purified using cation-exchange and gel-filtration chromatography. Effects of different hydrolysates and peptides on the proliferation of osteoblast MC3T3-E1 cells were compared by MTT assay. Results showed that fraction P5-a from Superdex Peptide 10/300 GL gel chromatography showed better activity. Tricine-sodium dodecyl sulfate polyacrylamide gel electrophoresis and high-performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry confirmed that two peptides components of P5-a corresponded to fractions of 20-78 and 191-277 amino acids in Bos taurus lactoferrin molecule (GI: 221706349). These results will provide some theoretical and practical data for the preparation and application of osteogenic peptides in functional food industry.

  18. GPER is involved in the stimulatory effects of aldosterone in breast cancer cells and breast tumor-derived endothelial cells

    PubMed Central

    Rigiracciolo, Damiano Cosimo; Scarpelli, Andrea; Lappano, Rosamaria; Pisano, Assunta; Santolla, Maria Francesca; Avino, Silvia; De Marco, Paola; Bussolati, Benedetta; Maggiolini, Marcello; De Francesco, Ernestina Marianna

    2016-01-01

    Aldosterone induces relevant effects binding to the mineralcorticoid receptor (MR), which acts as a ligand-gated transcription factor. Alternate mechanisms can mediate the action of aldosterone such as the activation of epidermal growth factor receptor (EGFR), MAPK/ERK, transcription factors and ion channels. The G-protein estrogen receptor (GPER) has been involved in the stimulatory effects of estrogenic signalling in breast cancer. GPER has been also shown to contribute to certain responses to aldosterone, however the role played by GPER and the molecular mechanisms implicated remain to be fully understood. Here, we evaluated the involvement of GPER in the stimulatory action exerted by aldosterone in breast cancer cells and breast tumor derived endothelial cells (B-TEC). Competition assays, gene expression and silencing studies, immunoblotting and immunofluorescence experiments, cell proliferation and migration were performed in order to provide novel insights into the role of GPER in the aldosterone-activated signalling. Our results demonstrate that aldosterone triggers the EGFR/ERK transduction pathway in a MR- and GPER-dependent manner. Aldosterone does not bind to GPER, it however induces the direct interaction between MR and GPER as well as between GPER and EGFR. Next, we ascertain that the up-regulation of the Na+/H+ exchanger-1 (NHE-1) induced by aldosterone involves MR and GPER. Biologically, both MR and GPER contribute to the proliferation and migration of breast and endothelial cancer cells mediated by NHE-1 upon aldosterone exposure. Our data further extend the current knowledge on the molecular mechanisms through which GPER may contribute to the stimulatory action elicited by aldosterone in breast cancer. PMID:26646587

  19. Stimulatory effect of vascular endothelial growth factor on progesterone production and survivability of cultured bubaline luteal cells.

    PubMed

    Chouhan, V S; Dangi, S S; Gupta, M; Babitha, V; Khan, F A; Panda, R P; Yadav, V P; Singh, G; Sarkar, M

    2014-08-01

    The objectives of the present study were to investigate the effects of vascular endothelial growth factor (VEGF) on progesterone (P4) synthesis in cultured luteal cells from different stages of the estrous cycle and on expression of steroidogenic acute regulatory protein (STARD1), cytochrome P450 cholesterol side chain cleavage (CYP11A1) and 3β-hydroxysteroid dehydrogenase (HSD3B), antiapoptotic gene PCNA, and proapoptotic gene BAX in luteal cells obtained from mid-luteal phase (MLP) of estrous cycle in buffalo. Corpus luteum samples from the early luteal phase (ELP; day 1st-4th; n=4), MLP (day 5th-10th; n=4), and the late luteal phase (LLP; day 11th-16th; n=4) of oestrous cycle were obtained from a slaughterhouse. Luteal cell cultures were treated with VEGF (0, 1, 10 and 100 ng/ml) for 24, 48 and 72h. Progesterone was assessed by RIA, while mRNA expression was determined by quantitative real-time PCR (qRT-PCR). Results indicated a dose- and time-dependent stimulatory effect of VEGF on P4 synthesis and expression of steroidogenic enzymes. Moreover, VEGF treatment led to an increase in PCNA expression and decrease in BAX expression. In summary, these findings suggest that VEGF acts locally in the bubaline CL to modulate steroid hormone synthesis and cell survivability, which indicates that this factor has an important role as a regulator of CL development and function in buffalo. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Human milk 90K (Mac-2 BP): possible protective effects against acute respiratory infections.

    PubMed

    Fornarini, B; Iacobelli, S; Tinari, N; Natoli, C; De Martino, M; Sabatino, G

    1999-01-01

    Eighty-six children fed human milk were followed prospectively from birth to 12 months of age to assess the effect of milk 90K, a secreted glycoprotein with immune-stimulatory properties, on development of acute respiratory infections (ARI). The level of human milk 90K was inversely related to episodes of ARI (r = - 0.34; P = 0.001). The average 90K level in human milk fed to children who did not develop ARI was significantly higher than in milk fed to children in whom infection occurred on multiple occasions (156.6 +/- 144.8 microg/ml versus 70.9 +/- 92.3 microg/ml; P = 0.001). These data suggest that the protective effects of human milk against ARI may be due in part to immune maturation effects by secreted 90K.

  1. New Horizons in Enhancing the Proliferation and Differentiation of Neural Stem Cells Using Stimulatory Effects of the Short Time Exposure to Radiofrequency Radiation

    PubMed Central

    Eghlidospour, M.; Mortazavi, S. M. J.; Yousefi, F.; Mortazavi, S. A. R.

    2015-01-01

    Mobile phone use and wireless communication technology have grown explosively over the past decades. This rapid growth has caused widespread global concern about the potential detrimental effects of this technology on human health. Stem cells generate specialized cell types of the tissue in which they reside through normal differentiation pathways. Considering the undeniable importance of stem cells in modern medicine, numerous studies have been performed on the effects of ionizing and non-ionizing radiation on cellular processes such as: proliferation, differentiation, cell cycle and DNA repair processes. We have conducted extensive studies on beneficial (stimulatory) or detrimental biological effects of exposure to different sources of electromagnetic fields such as mobile phones, mobile phone base stations, mobile phone jammers, radar systems, magnetic resonance imaging (MRI) systems and dentistry cavitrons over the past years. In this article, recent studies on the biological effects of non-ionizing electromagnetic radiation in the range of radiofrequency (RF) on some important features of stem cells such as their proliferation and differentiation are reviewed. Studies reviewed in this paper indicate that the stimulatory or inhibitory effects of RF radiation on the proliferation and differentiation of stem cells depend on various factors such as the biological systems, experiment conditions, the frequency and intensity of RF and the duration of exposure. PMID:26396965

  2. New Horizons in Enhancing the Proliferation and Differentiation of Neural Stem Cells Using Stimulatory Effects of the Short Time Exposure to Radiofrequency Radiation.

    PubMed

    Eghlidospour, M; Mortazavi, S M J; Yousefi, F; Mortazavi, S A R

    2015-09-01

    Mobile phone use and wireless communication technology have grown explosively over the past decades. This rapid growth has caused widespread global concern about the potential detrimental effects of this technology on human health. Stem cells generate specialized cell types of the tissue in which they reside through normal differentiation pathways. Considering the undeniable importance of stem cells in modern medicine, numerous studies have been performed on the effects of ionizing and non-ionizing radiation on cellular processes such as: proliferation, differentiation, cell cycle and DNA repair processes. We have conducted extensive studies on beneficial (stimulatory) or detrimental biological effects of exposure to different sources of electromagnetic fields such as mobile phones, mobile phone base stations, mobile phone jammers, radar systems, magnetic resonance imaging (MRI) systems and dentistry cavitrons over the past years. In this article, recent studies on the biological effects of non-ionizing electromagnetic radiation in the range of radiofrequency (RF) on some important features of stem cells such as their proliferation and differentiation are reviewed. Studies reviewed in this paper indicate that the stimulatory or inhibitory effects of RF radiation on the proliferation and differentiation of stem cells depend on various factors such as the biological systems, experiment conditions, the frequency and intensity of RF and the duration of exposure.

  3. Stimulatory Effects of Arsenic-Tolerant Soil Fungi on Plant Growth Promotion and Soil Properties

    PubMed Central

    Srivastava, Pankaj Kumar; Shenoy, Belle Damodara; Gupta, Manjul; Vaish, Aradhana; Mannan, Shivee; Singh, Nandita; Tewari, Shri Krishna; Tripathi, Rudra Deo

    2012-01-01

    Fifteen fungi were obtained from arsenic-contaminated agricultural fields in West Bengal, India and examined for their arsenic tolerance and removal ability in our previous study. Of these, the four best arsenic-remediating isolates were tested for plant growth promotion effects on rice and pea in the present study. A greenhouse-based pot experiment was conducted using soil inocula of individual fungi. The results indicated a significant (P<0.05) increase in plant growth and improvement of soil properties in inoculated soils compared to the control. A significant increase in plant growth was recorded in treated soils and varied from 16–293%. Soil chemical and enzymatic properties varied from 20–222% and 34–760%, respectively, in inoculated soil. Plants inoculated with inocula of Westerdykella and Trichoderma showed better stimulatory effects on plant growth and soil nutrient availability than Rhizopus and Lasiodiplodia. These fungi improved soil nutrient content and enhanced plant growth. These fungi may be used as bioinoculants for plant growth promotion and improved soil properties in arsenic-contaminated agricultural soils. PMID:23047145

  4. Stimulatory effects of arsenic-tolerant soil fungi on plant growth promotion and soil properties.

    PubMed

    Srivastava, Pankaj Kumar; Shenoy, Belle Damodara; Gupta, Manjul; Vaish, Aradhana; Mannan, Shivee; Singh, Nandita; Tewari, Shri Krishna; Tripathi, Rudra Deo

    2012-01-01

    Fifteen fungi were obtained from arsenic-contaminated agricultural fields in West Bengal, India and examined for their arsenic tolerance and removal ability in our previous study. Of these, the four best arsenic-remediating isolates were tested for plant growth promotion effects on rice and pea in the present study. A greenhouse-based pot experiment was conducted using soil inocula of individual fungi. The results indicated a significant (P<0.05) increase in plant growth and improvement of soil properties in inoculated soils compared to the control. A significant increase in plant growth was recorded in treated soils and varied from 16-293%. Soil chemical and enzymatic properties varied from 20-222% and 34-760%, respectively, in inoculated soil. Plants inoculated with inocula of Westerdykella and Trichoderma showed better stimulatory effects on plant growth and soil nutrient availability than Rhizopus and Lasiodiplodia. These fungi improved soil nutrient content and enhanced plant growth. These fungi may be used as bioinoculants for plant growth promotion and improved soil properties in arsenic-contaminated agricultural soils.

  5. Stimulatory versus suppressive effects of GM-CSF on tumor progression in multiple cancer types

    PubMed Central

    Hong, In-Sun

    2016-01-01

    Granulocyte-macrophage colony-stimulating factor (GM-CSF, also called CSF-2) is best known for its critical role in immune modulation and hematopoiesis. A large body of experimental evidence indicates that GM-CSF, which is frequently upregulated in multiple types of human cancers, effectively marks cancer cells with a ‘danger flag' for the immune system. In this context, most studies have focused on its function as an immunomodulator, namely its ability to stimulate dendritic cell (DC) maturation and monocyte/macrophage activity. However, recent studies have suggested that GM-CSF also promotes immune-independent tumor progression by supporting tumor microenvironments and stimulating tumor growth and metastasis. Although some studies have suggested that GM-CSF has inhibitory effects on tumor growth and metastasis, an even greater number of studies show that GM-CSF exerts stimulatory effects on tumor progression. In this review, we summarize a number of findings to provide the currently available information regarding the anticancer immune response of GM-CSG. We then discuss the potential roles of GM-CSF in the progression of multiple types of cancer to provide insights into some of the complexities of its clinical applications. PMID:27364892

  6. Dendritic cell co-stimulatory and co-inhibitory markers in chronic HCV: An Egyptian study

    PubMed Central

    Fouad, Hanan; Raziky, Maissa Saeed El; Aziz, Rasha Ahmed Abdel; Sabry, Dina; Aziz, Ghada Mahmoud Abdel; Ewais, Manal; Sayed, Ahmed Reda

    2013-01-01

    AIM: To assess co-stimulatory and co-inhibitory markers of dendritic cells (DCs) in hepatitis C virus (HCV) infected subjects with and without uremia. METHODS: Three subject groups were included in the study: group 1 involved 50 control subjects, group 2 involved 50 patients with chronic HCV infection and group 3 involved 50 HCV uremic subjects undergoing hemodialysis. CD83, CD86 and CD40 as co-stimulatory markers and PD-L1 as a co-inhibitory marker were assessed in peripheral blood mononuclear cells by real-time polymerase chain reaction. Interleukin-10 (IL-10) and hyaluronic acid (HA) levels were also assessed. All findings were correlated with disease activity, viral load and fibrogenesis. RESULTS: There was a significant decrease in co-stimulatory markers; CD83, CD86 and CD40 in groups 2 and 3 vs the control group. Co-stimulatory markers were significantly higher in group 3 vs group 2. There was a significant elevation in PD-L1 in both HCV groups vs the control group. PD-L1 was significantly lower in group 3 vs group 2. There was a significant elevation in IL-10 and HA levels in groups 2 and 3, where IL-10 was higher in group 3 and HA was lower in group 3 vs group 2. HA level was significantly correlated with disease activity and fibrosis grade in group 2. IL-10 was significantly correlated with fibrosis grade in group 2. There were significant negative correlations between co-stimulatory markers and viral load in groups 2 and 3, except CD83 in dialysis patients. There was a significant positive correlation between PD-L1 and viral load in both HCV groups. CONCLUSION: A significant decrease in DC co-stimulatory markers and a significant increase in a DC co-inhibitory marker were observed in HCV subjects and to a lesser extent in dialysis patients. PMID:24282359

  7. Characterization of a Dopaminergic Stimulatory Factor Derived from Monoclonal Cell Lines of Striatal Origin

    DTIC Science & Technology

    2006-12-01

    other substrates for its biosynthesis would be effective in raising MN9D dopamine content. The pyrimidine, cytidine triphosphate (CTP) reacts with...phosphatidylethanolamine or phosphatidylcholine. MN9D cells were treated for 48 hrs with 2 mM CTP, cytidine diphosphate (CDP) or cytidine monophosphate (CMP), in the...presence or absence of 25 µM ethanolamine or 25 µM phosphoethanolamine. Cytidine alone did not alter the dopaminergic stimulatory effect of

  8. The Initial Immune Reaction to a New Tumor Antigen Is Always Stimulatory and Probably Necessary for the Tumor's Growth

    PubMed Central

    Prehn, Richmond T.

    2010-01-01

    All nascent neoplasms probably elicit at least a weak immune reaction. However, the initial effect of the weak immune reaction on a nascent tumor is always stimulatory rather than inhibitory to tumor growth, assuming only that exposure to the tumor antigens did not antedate the initiation of the neoplasm (as may occur in some virally induced tumors). This conclusion derives from the observation that the relationship between the magnitude of an adaptive immune reaction and tumor growth is not linear but varies such that while large quantities of antitumor immune reactants tend to inhibit tumor growth, smaller quantities of the same reactants are, for unknown reasons, stimulatory. Any immune reaction must presumably be small before it can become large; hence the initial reaction to the first presentation of a tumor antigen must always be small and in the stimulatory portion of this nonlinear relationship. In mouse-skin carcinogenesis experiments it was found that premalignant papillomas were variously immunogenic, but that the carcinomas that arose in them were, presumably because of induced immune tolerance, nonimmunogenic in the animal of origin. PMID:20811480

  9. The initial immune reaction to a new tumor antigen is always stimulatory and probably necessary for the tumor's growth.

    PubMed

    Prehn, Richmond T

    2010-01-01

    All nascent neoplasms probably elicit at least a weak immune reaction. However, the initial effect of the weak immune reaction on a nascent tumor is always stimulatory rather than inhibitory to tumor growth, assuming only that exposure to the tumor antigens did not antedate the initiation of the neoplasm (as may occur in some virally induced tumors). This conclusion derives from the observation that the relationship between the magnitude of an adaptive immune reaction and tumor growth is not linear but varies such that while large quantities of antitumor immune reactants tend to inhibit tumor growth, smaller quantities of the same reactants are, for unknown reasons, stimulatory. Any immune reaction must presumably be small before it can become large; hence the initial reaction to the first presentation of a tumor antigen must always be small and in the stimulatory portion of this nonlinear relationship. In mouse-skin carcinogenesis experiments it was found that premalignant papillomas were variously immunogenic, but that the carcinomas that arose in them were, presumably because of induced immune tolerance, nonimmunogenic in the animal of origin.

  10. GPER, IGF-IR, and EGFR transduction signaling are involved in stimulatory effects of zinc in breast cancer cells and cancer-associated fibroblasts.

    PubMed

    Pisano, Assunta; Santolla, Maria Francesca; De Francesco, Ernestina Marianna; De Marco, Paola; Rigiracciolo, Damiano Cosimo; Perri, Maria Grazia; Vivacqua, Adele; Abonante, Sergio; Cappello, Anna Rita; Dolce, Vincenza; Belfiore, Antonino; Maggiolini, Marcello; Lappano, Rosamaria

    2017-02-01

    Zinc (Zn) is an essential trace mineral that contributes to the regulation of several cellular functions; however, it may be also implicated in the progression of breast cancer through different mechanisms. It has been largely reported that the classical estrogen receptor (ER), as well as the G protein estrogen receptor (GPER, previously known as GPR30) can exert a main role in the development of breast tumors. In the present study, we demonstrate that zinc chloride (ZnCl 2 ) involves GPER in the activation of insulin-like growth factor receptor I (IGF-IR)/epidermal growth factor receptor (EGFR)-mediated signaling, which in turn triggers downstream pathways like ERK and AKT in breast cancer cells, and main components of the tumor microenvironment namely cancer-associated fibroblasts (CAFs). Further corroborating these findings, ZnCl 2 stimulates a functional crosstalk of GPER with IGF-IR and EGFR toward the transcription of diverse GPER target genes. Then, we show that GPER contributes to the stimulatory effects induced by ZnCl 2 on cell-cycle progression, proliferation, and migration of breast cancer cells as well as migration of CAFs. Together, our data provide novel insights into the molecular mechanisms through which zinc may exert stimulatory effects in breast cancer cells and CAFs toward tumor progression. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. Tim-3 directly enhances CD8 T cell responses to acute Listeria monocytogenes infection

    PubMed Central

    Gorman, Jacob V.; Starbeck-Miller, Gabriel; Pham, Nhat-Long L.; Traver, Geri L.; Rothman, Paul B.; Harty, John T.; Colgan, John D.

    2014-01-01

    Tim-3 is a surface molecule expressed throughout the immune system that can mediate both stimulatory and inhibitory effects. Previous studies have provided evidence that Tim-3 functions to enforce CD8 T cell exhaustion, a dysfunctional state associated with chronic stimulation. In contrast, the role of Tim-3 in the regulation of CD8 T cell responses to acute and transient stimulation remains undefined. To address this knowledge gap, we examined how Tim-3 affects CD8 T cell responses to acute Listeria monocytogenes (LM) infection. Analysis of wild-type (WT) mice infected with LM revealed that Tim-3 was transiently expressed by activated CD8 T cells and was associated primarily with acquisition of an effector phenotype. Comparison of responses to LM by WT and Tim-3 KO mice showed that the absence of Tim-3 significantly reduced the magnitudes of both primary and secondary CD8 T cell responses, which correlated with decreased IFN-γ production and degranulation by Tim-3 KO cells stimulated with peptide antigen ex vivo. To address the T cell-intrinsic role of Tim-3, we analyzed responses to LM infection by WT and Tim-3 KO TCR-transgenic CD8 T cells following adoptive transfer into a shared WT host. In this setting, the accumulation of CD8 T cells and the generation of cytokine-producing cells were significantly reduced by the lack of Tim-3, demonstrating that this molecule has a direct effect on CD8 T cell function. Combined, our results suggest that Tim-3 can mediate a stimulatory effect on CD8 T cell responses to an acute infection. PMID:24567532

  12. Stimulatory actions of bioflavenoids on tyrosine uptake into cultured bovine adrenal chromaffin cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Morita, K.; Hamano, S.; Oka, M.

    1990-09-28

    The effects of flavenoids on L-({sup 14}C)tyrosine uptake into cultured adrenal chromaffin cells were examined. Flavone markedly stimulated tyrosine uptake into these cells in a manner dependent on its concentration. Apigenin also caused a moderate stimulatory action, but quercetin had no significant effect on the uptake. Flavone also stimulated the uptake of histidine, but did not affect the uptake of serine, lysine, or glutamic acid. These results are considered to propose the possibility that flavonoids may be able to stimulate the precursor uptake into the cells, resulting in an enhancement of the biogenic amine production.

  13. Peptide-Conjugated Nanoparticles Reduce Positive Co-stimulatory Expression and T Cell Activity to Induce Tolerance.

    PubMed

    Kuo, Robert; Saito, Eiji; Miller, Stephen D; Shea, Lonnie D

    2017-07-05

    Targeted approaches to treat autoimmune diseases would improve upon current therapies that broadly suppress the immune system and lead to detrimental side effects. Antigen-specific tolerance was induced using poly(lactide-co-glycolide) nanoparticles conjugated with disease-relevant antigen to treat a model of multiple sclerosis. Increasing the nanoparticle dose and amount of conjugated antigen both resulted in more durable immune tolerance. To identify active tolerance mechanisms, we investigated downstream cellular and molecular events following nanoparticle internalization by antigen-presenting cells. The initial cell response to nanoparticles indicated suppression of inflammatory signaling pathways. Direct and functional measurement of surface MHC-restricted antigen showed positive correlation with both increasing particle dose from 1 to 100 μg/mL and increasing peptide conjugation by 2-fold. Co-stimulatory analysis of cells expressing MHC-restricted antigen revealed most significant decreases in positive co-stimulatory molecules (CD86, CD80, and CD40) following high doses of nanoparticles with higher peptide conjugation, whereas expression of a negative co-stimulatory molecule (PD-L1) remained high. T cells isolated from mice immunized against myelin proteolipid protein (PLP 139-151 ) were co-cultured with antigen-presenting cells administered PLP 139-151 -conjugated nanoparticles, which resulted in reduced T cell proliferation, increased T cell apoptosis, and a stronger anti-inflammatory response. These findings indicate several potential mechanisms used by peptide-conjugated nanoparticles to induce antigen-specific tolerance. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  14. Neurite outgrowth stimulatory effects of culinary-medicinal mushrooms and their toxicity assessment using differentiating Neuro-2a and embryonic fibroblast BALB/3T3.

    PubMed

    Phan, Chia-Wei; David, Pamela; Naidu, Murali; Wong, Kah-Hui; Sabaratnam, Vikineswary

    2013-10-11

    Mushrooms are not only regarded as gourmet cuisine but also as therapeutic agent to promote cognition health. However, little toxicological information is available regarding their safety. Therefore, the aim of this study was to screen selected ethno-pharmacologically important mushrooms for stimulatory effects on neurite outgrowth and to test for any cytotoxicity. The stimulatory effect of mushrooms on neurite outgrowth was assessed in differentiating mouse neuroblastoma (N2a) cells. Neurite length was measured using Image-Pro Insight processor system. Neuritogenesis activity was further validated by fluorescence immunocytochemical staining of neurofilaments. In vitro cytotoxicity was investigated by using mouse embryonic fibroblast (BALB/3T3) and N2a cells for any embryo- and neuro-toxic effects; respectively. Aqueous extracts of Ganoderma lucidum, Lignosus rhinocerotis, Pleurotus giganteus and Grifola frondosa; as well as an ethanol extract of Cordyceps militaris significantly (p < 0.05) promoted the neurite outgrowth in N2a cells by 38.4 ± 4.2%, 38.1 ± 2.6%, 33.4 ± 4.6%, 33.7 ± 1.5%, and 35.8 ± 3.4%; respectively. The IC50 values obtained from tetrazolium (MTT), neutral red uptake (NRU) and lactate dehydrogenase (LDH) release assays showed no toxic effects following 24 h exposure of N2a and 3T3 cells to mushroom extracts. Our results indicate that G. lucidum, L. rhinocerotis, P. giganteus, G. frondosa and C. militaris may be developed as safe and healthy dietary supplements for brain and cognitive health.

  15. A stimulatory effect of Artemisia leaf extract on the proliferation of cultured endothelial cells.

    PubMed

    Kaji, T; Kaga, K; Miezi, N; Ejiri, N; Sakuragawa, N

    1990-02-01

    To investigate the effect of the hot water extract from Artemisia leaf (Artemisia princeps Panpanini) (AFE) on the proliferation of endothelial cells, the cells from bovine aorta were cultured for up to 96 h in the presence of 1, 5, 10 or 50 micrograms/ml AFE in RPMI1640 medium supplemented with 10% fetal bovine serum. After a 72 h culture, the cell number was significantly increased by AFE at 1, 5 and 10 micrograms/ml. An increase in the cell number by 5 micrograms/ml AFE observed after a 72 or 96 h treatment. The incorporations of both [3H]thymidine and [14C]leucine by the growing cells were significantly increased by 5 micrograms/ml AFE after a 72 h treatment. In addition, the incorporation of [3H]thymidine by either growing or confluent cells was significantly increased by 50 micrograms/ml AFE after a 72 h treatment. The stimulatory activity of AFE was recognized in the low-molecular-weight fraction (molecular weight less than or equal to 10000 dalton). These results clearly indicated that AFE contained some low-molecular-weight component(s) which stimulates the proliferation of vascular endothelial cells in vitro.

  16. Mephedrone (4-Methylmethcathinone): Acute Behavioral Effects, Hyperthermic, and Pharmacokinetic Profile in Rats

    PubMed Central

    Šíchová, Klára; Pinterová, Nikola; Židková, Monika; Horsley, Rachel R.; Lhotková, Eva; Štefková, Kristýna; Vejmola, Čestmír; Uttl, Libor; Balíková, Marie; Kuchař, Martin; Páleníček, Tomáš

    2018-01-01

    Mephedrone (MEPH) is a synthetic cathinone derivative with effects that mimic MDMA and/or cocaine. Our study in male Wistar rats provides detailed investigations of MEPH’s and its primary metabolite nor-mephedrone’s (nor-MEPH) pharmacokinetics and bio-distribution to four different substrates (serum, brain, lungs, and liver), as well as comparative analysis of their effects on locomotion [open field test (OFT)] and sensorimotor gating [prepulse inhibition of acoustic startle reaction (PPI ASR)]. Furthermore, in order to mimic the crowded condition where MEPH is typically taken (e.g., clubs), the acute effect of MEPH on thermoregulation in singly- and group-housed rats was evaluated. Pharmacokinetics of MEPH and nor-MEPH after MEPH (5 mg/kg, sc.) were analyzed over 8 h using liquid chromatography with mass spectrometry. MEPH (2.5, 5, or 20 mg/kg, sc.) and nor-MEPH (5 mg/kg, sc.) were administered 5 or 40 min before the behavioral testing in the OFT and PPI ASR; locomotion and its spatial distribution, ASR, habituation and PPI itself were quantified. The effect of MEPH on rectal temperature was measured after 5 and 20 mg/kg, sc. Both MEPH and nor-MEPH were detected in all substrates, with the highest levels detected in lungs. Mean brain: serum ratios were 1:1.19 (MEPH) and 1:1.91 (nor-MEPH), maximum concentrations were observed at 30 min; at 2 and 4 h after administration, nor-MEPH concentrations were higher compared to the parent drug. While neither of the drugs disrupted PPI, both increased locomotion and affected its spatial distribution. The effects of MEPH were dose dependent, rapid, and short-lasting, and the intensity of locomotor stimulant effects was comparable between MEPH and nor-MEPH. Despite the disappearance of behavioral effects within 40 min after administration, MEPH induced rectal temperature elevations that persisted for 3 h even in singly housed rats. To conclude, we observed a robust, short-lasting, and most likely

  17. Stimulatory effects of Euphorbia cheiradenia on cell mediated immunity and humoral antibody synthesis.

    PubMed

    Amirghofran, Zahra; Azadmehr, Abbas; Bahmani, Masoud; Javidnia, Katayoun

    2008-06-01

    Studies have demonstrated that plant extracts possess various biological characteristics including immunomodulatory activity. Euphorbia cheiradenia Boiss et Hohen (Euphorbiaceae), a medicinal herb native to Iran was investigated for its immunomodulatory effects. The methanolic extract of the plant was prepared and added to mitogen-induced human peripheral blood lymphocyte cultures at different concentrations. Effect of E. cheiradenia on in vivo cell-mediated immunity was measured by delayed type hypersensitivity (DTH) reaction. The effect of the extract on humoral antibody synthesis was also measured in immunized mice treated with different extract concentrations. The stimulation index (SI) for cultures treated with 0.01 to 200 microg/ml of the extract ranged from 1.3+/-0.04 to 2.4+/-0.06, (p<0.01) showing a significant stimulatory effect of E. cheiradenia on the lymphocytes. IL-2 secreted from lymphocytes treated with the extract was significantly higher than that from the non-treated cells (p<0.001). Cell cycle analysis on mitogen-treated lymphocytes exposed to different concentrations of the extract showed an increase in the percentage of cells at G2M phase with increases in the concentration of the extract, but the results was not significant. In DTH skin test, the mean footpad thickness of all mice groups treated with 1, 50 and 100 mg/kg of the extract at 24 hours after immunization with antigen was 3.5+/-0.6 mm compared to 2.5+/-0.5 mm for the non-treated group (p=0.005). Moreover, an increase in production of specific antibody in mice immunized with different extract concentrations was also demonstrated. Results of this study showed the ability of the E. cheiradenia extract to induce proliferation of lymphocytes and enhance both cellular and humoral specific immune responses.

  18. Comparison of the effects of acute fluvoxamine and desipramine administration on melatonin and cortisol production in humans.

    PubMed Central

    Skene, D J; Bojkowski, C J; Arendt, J

    1994-01-01

    1. Acute administration of the specific serotonin uptake inhibitor, fluvoxamine (100 mg at 16.00 h), markedly increased nocturnal plasma melatonin concentrations, with high levels extending into the morning hours. 2. Acute administration of the noradrenaline uptake inhibitor, desipramine (DMI) (100 mg at 16.00 h), increased evening plasma melatonin concentrations. 3. Both drug treatments increased the duration of melatonin secretion, fluvoxamine significantly delaying the offset time and DMI significantly advancing the onset time. 4. The stimulatory effect of DMI on plasma melatonin was mirrored by increased urinary 6-sulphatoxymelatonin (aMT6s) excretion. 5. On the contrary, there was no correlation between plasma melatonin and urinary aMT6s concentrations following fluvoxamine treatment, suggesting that fluvoxamine may inhibit the metabolism of melatonin. 6. Treatment with DMI increased plasma cortisol concentrations in the evening and early morning, treatment with fluvoxamine increased plasma cortisol at 03.00 h, 10.00 h and 11.00 h. 7. The drug treatments affected different aspects of the nocturnal plasma melatonin profile suggesting that the amplitude of the melatonin rhythm may depend upon serotonin availability and/or melatonin metabolism whilst the onset of melatonin production depends upon noradrenaline availability. PMID:8186063

  19. Neurite outgrowth stimulatory effects of culinary-medicinal mushrooms and their toxicity assessment using differentiating Neuro-2a and embryonic fibroblast BALB/3T3

    PubMed Central

    2013-01-01

    Background Mushrooms are not only regarded as gourmet cuisine but also as therapeutic agent to promote cognition health. However, little toxicological information is available regarding their safety. Therefore, the aim of this study was to screen selected ethno-pharmacologically important mushrooms for stimulatory effects on neurite outgrowth and to test for any cytotoxicity. Methods The stimulatory effect of mushrooms on neurite outgrowth was assessed in differentiating mouse neuroblastoma (N2a) cells. Neurite length was measured using Image-Pro Insight processor system. Neuritogenesis activity was further validated by fluorescence immunocytochemical staining of neurofilaments. In vitro cytotoxicity was investigated by using mouse embryonic fibroblast (BALB/3T3) and N2a cells for any embryo- and neuro-toxic effects; respectively. Results Aqueous extracts of Ganoderma lucidum, Lignosus rhinocerotis, Pleurotus giganteus and Grifola frondosa; as well as an ethanol extract of Cordyceps militaris significantly (p < 0.05) promoted the neurite outgrowth in N2a cells by 38.4 ± 4.2%, 38.1 ± 2.6%, 33.4 ± 4.6%, 33.7 ± 1.5%, and 35.8 ± 3.4%; respectively. The IC50 values obtained from tetrazolium (MTT), neutral red uptake (NRU) and lactate dehydrogenase (LDH) release assays showed no toxic effects following 24 h exposure of N2a and 3T3 cells to mushroom extracts. Conclusion Our results indicate that G. lucidum, L. rhinocerotis, P. giganteus, G. frondosa and C. militaris may be developed as safe and healthy dietary supplements for brain and cognitive health. PMID:24119256

  20. OX62+OX6+OX35+ rat dendritic cells are unable to prime CD4+ T cells for an effective immune response following acute burn injury.

    PubMed

    Fazal, Nadeem

    2013-01-01

    Co-stimulatory molecules expressed on Dendritic Cells (DCs) function to coordinate an efficient immune response by T cells in the peripheral lymph nodes. We hypothesized that CD4+ T cell-mediated immune suppression following burn injury may be related to dysfunctional DCs residing in gut associated lymphoid tissues (GALT), such as Mesenteric Lymph Nodes (MLN). Therefore, we studied co-stimulatory molecules expressed on burn rat MLN DCs as an index of functional DCs that would mount an effective normal CD4+ T cell immune response. In a rat model of 30% Total Body Surface Area (TBSA) scald burn, OX62+OX6+OX35+ DCs and CD4+ T cells were isolated from MLN of day 3 post-burn and sham control rats. DCs were tested for their expression of co-stimulatory molecules, and prime CD4+ T cell (DC:CD4+T cell co-culture assays) to determine an effector immune response such as CD4+ T cell proliferation. The surface receptor expressions of MLN DCs co-stimulatory molecules, i.e., MHC-II, CD40, CD80 (B7-1), and CD86 (B7-2) were determined by Flow cytometry (quantitatively) and confocal microscopy (qualitatively). Tritiated thymidine and CFDA-SE determined CD4+ T cell proliferation following co-incubation with DCs. Cytokine milieu of MLN (IL-12 and IL-10) was assessed by mRNA determination by RT-PCR. The results showed down-regulated expressions of co-stimulatory markers (CD80, CD86, CD40 and MHC-II) of MLN DCs obtained from burn-injured rats, as well as lack of ability of these burn-induced DCs to stimulate CD4+ T cell proliferation in co-culture assays, as compared to the sham rats. Moreover, anti-CD40 stimulation of affected burn MLN DCs did not reverse this alteration. Furthermore, a marked up-regulation of mRNA IL-10 and down-regulation of mRNA IL-12 in burn MLN as compared to sham animals was also observed. To surmise, the data indicated that dysfunctional OX62+OX6+OX35+ rat MLN DCs may contribute to CD4+ T-cell-mediated immune suppression observed following acute burn injury.

  1. OX62+OX6+OX35+ rat dendritic cells are unable to prime CD4+ T cells for an effective immune response following acute burn injury☆

    PubMed Central

    Fazal, Nadeem

    2013-01-01

    Co-stimulatory molecules expressed on Dendritic Cells (DCs) function to coordinate an efficient immune response by T cells in the peripheral lymph nodes. We hypothesized that CD4+ T cell-mediated immune suppression following burn injury may be related to dysfunctional DCs residing in gut associated lymphoid tissues (GALT), such as Mesenteric Lymph Nodes (MLN). Therefore, we studied co-stimulatory molecules expressed on burn rat MLN DCs as an index of functional DCs that would mount an effective normal CD4+ T cell immune response. In a rat model of 30% Total Body Surface Area (TBSA) scald burn, OX62+OX6+OX35+ DCs and CD4+ T cells were isolated from MLN of day 3 post-burn and sham control rats. DCs were tested for their expression of co-stimulatory molecules, and prime CD4+ T cell (DC:CD4+T cell co-culture assays) to determine an effector immune response such as CD4+ T cell proliferation. The surface receptor expressions of MLN DCs co-stimulatory molecules, i.e., MHC-II, CD40, CD80 (B7-1), and CD86 (B7-2) were determined by Flow cytometry (quantitatively) and confocal microscopy (qualitatively). Tritiated thymidine and CFDA-SE determined CD4+ T cell proliferation following co-incubation with DCs. Cytokine milieu of MLN (IL-12 and IL-10) was assessed by mRNA determination by RT-PCR. The results showed down-regulated expressions of co-stimulatory markers (CD80, CD86, CD40 and MHC-II) of MLN DCs obtained from burn-injured rats, as well as lack of ability of these burn-induced DCs to stimulate CD4+ T cell proliferation in co-culture assays, as compared to the sham rats. Moreover, anti-CD40 stimulation of affected burn MLN DCs did not reverse this alteration. Furthermore, a marked up-regulation of mRNA IL-10 and down-regulation of mRNA IL-12 in burn MLN as compared to sham animals was also observed. To surmise, the data indicated that dysfunctional OX62+OX6+OX35+ rat MLN DCs may contribute to CD4+ T-cell-mediated immune suppression observed following acute burn injury

  2. Effect of olive mill wastewaters on the oxygen consumption by activated sludge microorganisms: an acute toxicity test method.

    PubMed

    Paixão, S M; Anselmo, A M

    2002-01-01

    The test for inhibition of oxygen consumption by activated sludge (ISO 8192-1986 (E)) was evaluated as a tool for assessing, the acute toxicity of olive mill wastewaters (OMW). According to the ISO test, information generated by this method may be helpful in estimating the effect of a test material on bacterial communities in the aquatic environment, especially in aerobic biological treatment systems. However, the lack of standardized bioassay methodology for effluents imposed that the test conditions were modified and adapted. The experiments were conducted in the presence or absence of an easily biodegradable carbon source (glucose) with different contact times (20 min and 24 h). The results obtained showed a remarkable stimulatory effect of this effluent to the activated sludge microorganisms. In fact, the oxygen uptake rate values increase with increasing effluent concentrations and contact times up to 0.98 microl O(2) h(-1) mg(-1) dry weight for a 100% OMW sample, 24 h contact time, with blanks exhibiting an oxygen uptake rate of ca. 1/10 of this value (0.07-0.10). It seems that the application of the ISO test as an acute toxicity test for effluents should be reconsidered, with convenient adaptation for its utilization as a method of estimating the effect on bacterial communities present in aerobic biological treatment systems. Copyright 2002 John Wiley & Sons, Ltd.

  3. Heparin affin regulatory peptide/pleiotrophin mediates fibroblast growth factor 2 stimulatory effects on human prostate cancer cells.

    PubMed

    Hatziapostolou, Maria; Polytarchou, Christos; Katsoris, Panagiotis; Courty, Jose; Papadimitriou, Evangelia

    2006-10-27

    Fibroblast growth factor 2 (FGF2) is a pleiotropic growth factor that has been implicated in prostate cancer formation and progression. In the present study we found that exogenous FGF2 significantly increased human prostate cancer LNCaP cell proliferation and migration. Heparin affin regulatory peptide (HARP) or pleiotrophin seems to be an important mediator of FGF2 stimulatory effects, since the latter had no effect on stably transfected LNCaP cells that did not express HARP. Moreover, FGF2, through FGF receptors (FGFRs), significantly induced HARP expression and secretion by LNCaP cells and increased luciferase activity of a reporter gene vector carrying the full-length promoter of HARP gene. Using a combination of Western blot analyses, as well as genetic and pharmacological inhibitors, we found that activation of FGFR by FGF2 in LNCaP cells leads to NAD(P)H oxidase-dependent hydrogen peroxide production, phosphorylation of ERK1/2 and p38, activation of AP-1, increased expression and secretion of HARP, and, finally, increased cell proliferation and migration. These results establish the role and the mode of activity of FGF2 in LNCaP cells and support an interventional role of HARP in FGF2 effects, providing new insights on the interplay among growth factor pathways within prostate cancer cells.

  4. Prostate Cancer Cell Growth: Stimulatory Role of Neurotensin and Mechanism of Inhibition by Flavonoids as Related to Protein Kinase C

    DTIC Science & Technology

    2009-01-01

    Stimulatory Role of Neurotensin and Mechanism of Inhibition by Flavonoids as Related to Protein Kinase C PRINCIPAL INVESTIGATOR: Robert E. Carraway...CONTRACT NUMBER Prostate Cancer Cell Growth: Stimulatory Role of Neurotensin and Mechanism of Inhibition by Flavonoids as Related to Protein Kinase C...relationship between neurotensin (NT) and protein kinases and to investigate the mechanism by which flavonoids (FLAV) inhibit NT growth signaling in PC3

  5. The stimulatory effect of neuropeptide Y on growth hormone expression, food intake, and growth in olive flounder (Paralichthys olivaceus).

    PubMed

    Li, Meijie; Tan, Xungang; Sui, Yulei; Jiao, Shuang; Wu, Zhihao; Wang, Lijuan; You, Feng

    2017-02-01

    Neuropeptide Y (NPY) is a 36-amino acid peptide known to be a strong orexigenic (appetite-stimulating) factor in many species. In this study, we investigated the effect of NPY on food intake and growth in the olive flounder (Paralichthys olivaceus). Recombinant full-length NPY was injected intraperitoneally into olive flounder at the dose of 1 μg/g body weight; phosphate buffered saline was used as the negative control. In a long-term experiment, NPY and control groups were injected every fifth day over a period of 30 days. In a short-term experiment, NPY and control groups were given intraperitoneal injections and maintained for 24 h. Food intake and growth rates were significantly higher in fish injected with recombinant NPY than in the control fish (P < 0.05). Higher growth hormone (GH) and NPY mRNA transcript levels were observed in both experiments, indicating a stimulatory effect of NPY on GH release. These findings demonstrate that NPY is an effective appetite-stimulating factor in olive flounder with the potential to improve the growth of domestic fish species and enhance efficiency in aquaculture.

  6. The STAT3 inhibitor pyrimethamine displays anti-cancer and immune stimulatory effects in murine models of breast cancer.

    PubMed

    Khan, Mohammad W; Saadalla, Abdulrahman; Ewida, Ahmed H; Al-Katranji, Khalid; Al-Saoudi, Ghadier; Giaccone, Zachary T; Gounari, Fotini; Zhang, Ming; Frank, David A; Khazaie, Khashayarsha

    2018-01-01

    The transcription factor signal activator and transducer or transcription (STAT3), which regulates genes controlling proliferation, survival, and invasion, is activated inappropriately in many human cancers, including breast cancer. Activation of STAT3 can lead to both malignant cellular behavior and suppression of immune cell function in the tumor microenvironment. Through a chemical-biology screen, pyrimethamine (PYR), an FDA approved anti-microbial drug, was identified as an inhibitor of STAT3 function at concentrations known to be achieved safely in humans. We report that PYR shows therapeutic activity in two independent mouse models of breast cancer, with both direct tumor inhibitory and immune stimulatory effects. PYR-inhibited STAT3 activity in TUBO and TM40D-MB metastatic breast cancer cells in vitro and inhibited tumor cell proliferation and invasion into Matrigel basement membrane matrix. In tumor-transplanted mice, PYR had both direct and indirect tumor inhibitory effects. Tumor-bearing mice treated with PYR showed reduced STAT3 activation in tumor cells, attenuated tumor growth, and reduced tumor-associated inflammation. In addition, expression of Lamp1 by tumor infiltrating CD8 + T cells was elevated, indicating enhanced release of cytotoxic granules. These findings suggest that PYR may have beneficial effects in the treatment of breast cancer.

  7. Prostate Cancer Cell Growth: Stimulatory Role of Neurotensin And Mechanism of Inhibition by Flavonoids as Related to Protein Kinase C

    DTIC Science & Technology

    2008-01-31

    Stimulatory Role of Neurotensin And Mechanism of Inhibition by Flavonoids as Related to Protein Kinase C. PRINCIPAL INVESTIGATOR: Robert E...SUBTITLE Prostate Cancer Cell Growth: Stimulatory Role of Neurotensin and 5a. CONTRACT NUMBER Mechanism of Inhibition by Flavonoids as Related to...isotypes and to investigate the mechanism by which flavonoids (FLAV) inhibit NT growth signaling in PC3 cells. The long-range scope is to determine the

  8. Antibacterial and osteo-stimulatory effects of a borate-based glass series doped with strontium ions.

    PubMed

    Li, Yiming; Stone, Wendy; Schemitsch, Emil H; Zalzal, Paul; Papini, Marcello; Waldman, Stephen D; Towler, Mark R

    2016-11-01

    This work considered the effect of both increasing additions of Strontium (Sr 2+ ) and incubation time on solubility and both antibacterial and osteo-stimulatory effects of a series of glasses based on the B 2 O 3 -P 2 O 5 -CaCO 3 -Na 2 CO 3 -TiO 2 -SrCO 3 series. The amorphous nature of all the glasses was confirmed by X-ray diffraction. Discs of each glass were immersed in de-ionized water for 1, 7 and 30 days, and the water extracts were used for ion release profiles, pH measurements and cytotoxicity testing. Atomic absorption spectroscopy was employed to detect the release of Na + , Ca 2+ and Sr 2+ ions from the glasses with respect to maturation, which indicated that the addition of Sr 2+ retarded solubility of the glass series. This effect was also confirmed by weight loss analysis through comparing the initial weight of glass discs before and after periods of incubation. The incorporation of Sr 2+ in the glasses did not influence the pH of the water extracts when the glasses were stored for up to 30 days. Cytotoxicity testing with an osteoblastic cell line (MC3T3-E1) indicated that glasses with the higher (20 mol% and 25 mol%) Sr 2+ incorporation promoted proliferation of osteoblast cells, while the glasses with lower Sr 2+ contents inhibited cell growth. The glass series, except for Ly-B5 (which contained the highest Sr 2+ incorporation; 25 mol%), were bacteriostatic against S. aureus in the short term (1-7 days) as a result of the dissolution products released. © The Author(s) 2016.

  9. Effects of copper, hypoxia and acute temperature shifts on mitochondrial oxidation in rainbow trout (Oncorhynchus mykiss) acclimated to warm temperature.

    PubMed

    Sappal, Ravinder; Fast, Mark; Stevens, Don; Kibenge, Fred; Siah, Ahmed; Kamunde, Collins

    2015-12-01

    Temperature fluctuations, hypoxia and metals pollution frequently occur simultaneously or sequentially in aquatic systems and their interactions may confound interpretation of their biological impacts. With a focus on energy homeostasis, the present study examined how warm acclimation influences the responses and interactions of acute temperature shift, hypoxia and copper (Cu) exposure in fish. Rainbow trout (Oncorhynchus mykiss) were acclimated to cold (11°C; control) and warm (20°C) temperature for 3 weeks followed by exposure to environmentally realistic levels of Cu and hypoxia for 24h. Subsequently, mitochondrial electron transport system (ETS) respiratory activity supported by complexes I-IV (CI-IV), plasma metabolites and condition indices were measured. Warm acclimation reduced fish condition, induced aerobic metabolism and altered the responses of fish to acute temperature shift, hypoxia and Cu. Whereas warm acclimation decelerated the ETS and increased the sensitivity of maximal oxidation rates of the proximal (CI and II) complexes to acute temperature shift, it reduced the thermal sensitivity of state 4 (proton leak). Effects of Cu with and without hypoxia were variable depending on the acclimation status and functional index. Notably, Cu stimulated respiratory activity in the proximal ETS segments, while hypoxia was mostly inhibitory and minimized the stimulatory effect of Cu. The effects of Cu and hypoxia were modified by temperature and showed reciprocal antagonistic interaction on the ETS and plasma metabolites, with modest additive actions limited to CII and IV state 4. Overall, our results indicate that warm acclimation came at a cost of reduced ETS efficiency and increased sensitivity to added stressors. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Co-stimulatory molecules in and beyond co-stimulation - tipping the balance in atherosclerosis?

    PubMed

    Gerdes, N; Zirlik, A

    2011-11-01

    A plethora of basic laboratory and clinical studies has uncovered the chronic inflammatory nature of atherosclerosis. The adaptive immune system with its front-runner, the T cell, drives the atherogenic process at all stages. T cell function is dependent on and controlled by a variety of either co-stimulatory or co-inhibitory signals. In addition, many of these proteins enfold T cell-independent pro-atherogenic functions on a variety of cell types. Accordingly they represent potential targets for immune-modulatory and/or anti-inflammatory therapy of atherosclerosis. This review focuses on the diverse role of co-stimulatory molecules of the B7 and tumour necrosis factor (TNF)-superfamily and their downstream signalling effectors in atherosclerosis. In particular, the contribution of CD28/CD80/CD86/CTLA4, ICOS/ICOSL, PD-1/PDL-1/2, TRAF, CD40/CD154, OX40/OX40L, CD137/CD137L, CD70/CD27, GITR/GITRL, and LIGHT to arterial disease is reviewed. Finally, the potential for a therapeutic exploitation of these molecules in the treatment of atherosclerosis is discussed.

  11. A swinging seesaw as a novel model mechanism for time-dependent hormesis under dose-dependent stimulatory and inhibitory effects: A case study on the toxicity of antibacterial chemicals to Aliivibrio fischeri.

    PubMed

    Sun, Haoyu; Calabrese, Edward J; Zheng, Min; Wang, Dali; Pan, Yongzheng; Lin, Zhifen; Liu, Ying

    2018-08-01

    Hormesis occurs frequently in broadly ranging biological areas (e.g. plant biology, microbiology, biogerontology), toxicology, pharmacology and medicine. While numerous mechanisms (e.g. receptor and pathway mediated pathway responses) account for stimulatory and inhibitory features of hormetic dose responses, the vast majority emphasizes the inclusion of many doses but only one timepoint or use of a single optimized dose that is assessed over a broad range of timepoints. In this paper, a toxicity study was designed using a large number of properly spaced doses with responses determined over a large number of timepoints, which could help us reveal the underlying mechanism of hormesis. We present the results of a dose-time-response study on hormesis using five antibacterial chemicals on the bioluminescence of Aliivibrio fischeri, measuring expression of protein mRNA based on quorum sensing, simulating bioluminescent reaction and analyzing toxic actions of test chemicals. The findings show dose-time-dependent responses conforming to the hormetic dose-response model, while revealing unique response dynamics between agent induced stimulatory and inhibitory effects within bacterial growth phase dynamics. These dynamic dose-time features reveal a type of biological seesaw model that integrates stimulatory and inhibitory responses within unique growth phase, dose and time features, which has faultlessly explained the time-dependent hormetic phenomenon induced by five antibacterial chemicals (characterized by low-dose stimulation and high-dose inhibition). This study offers advances in understanding cellular dynamics, the biological integration of diverse and opposing responses and their role in evolutionary adaptive strategies to chemicals, which can provide new insight into the mechanistic investigation of hormesis. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Effects of snake venom from Saudi cobras and vipers on hormonal levels in peripheral blood.

    PubMed

    Abdel-Galil, Khidir A; Al-Hazimi, Awdah M

    2004-08-01

    Knowledge about the effects of snake venoms on endocrine glands in the Kingdom of Saudi Arabia (KSA) is meager. The aim of the present study is to investigate the acute and chronic envenomation from 4 snakes out of 8 species of Saudi Cobras and Vipers on the tissues of endocrine glands and peripheral hormonal levels in male rats. The peripheral blood levels of 4 hormones mainly testosterone, cortisol, insulin and thyroxin were investigated in male Wistar rats following acute and chronic treatment of the rats with poisonous snake venoms at the Department of Physiology, Faculty of Medicine, King Abdul-Aziz University, Jeddah, Kingdom of Saudi Arabia between September 2000 to May 2001. Using radio immunoassay for hormonal analysis, a rise in testosterone levels in peripheral blood was obtained following acute treatment, which is due to the effect of the venoms on vascular permeability and increased blood flow. In contrast, the chronic treatment with venoms resulted in a delayed effect on vascular permeability and testicular degeneration resulting in a decreased blood flow and a significant drop in testosterone concentration. Cortisol levels were no different from the controls during acute treatment but it demonstrates gradual rise following chronic treatment to withstand the stress imposed on the animals. Similar results were obtained for insulin, which showed normal values with acute treatment but decreased levels of chronic treatment suggesting insulin insufficiently. Likewise, the thyroxin levels were decreased with chronic treatment suggesting a toxic effect of the poison on the rich blood supply of the thyroid follicles with a subsequent decrease in blood flow to the tissues and therefore, decreased thyroid hormone levels. The effects of venom toxicity on testosterone levels were either normal or stimulatory with acute treatment or inhibitory with chronic treatment depending on the vascular blood flow and testicular degeneration. Cortisol levels were normal at

  13. Signals generating anorexia during acute illness.

    PubMed

    Langhans, Wolfgang

    2007-08-01

    Anorexia is part of the body's acute-phase response to illness. Microbial products such as lipopolysaccharides (LPS), which are also commonly used to model acute illness, trigger the acute-phase response and cause anorexia mainly through pro-inflammatory cytokines. LPS stimulate cytokine production through the cell-surface structural molecule CD14 and toll-like receptor-4. Cytokines ultimately change neural activity in brain areas controlling food intake and energy balance. The blood-brain barrier endothelial cells (BBB EC) are an important site of cytokine action in this context. BBB EC and perivascular cells (microglia and macrophages) form a complex regulatory interface that modulates neuronal activity by the release of messengers (e.g. PG, NO) in response to peripheral challenges. Serotonergic neurons originating in the raphe nuclei and glucagon-like peptide-1-expressing neurons in the hindbrain may be among the targets of these messengers, because serotonin (5-HT), acting through the 5-HT2C receptor, and glucagon-like peptide-1 have recently emerged as neurochemical mediators of LPS anorexia. The central melanocortin system, which is a downstream target of serotonergic neurons, also appears to be involved in mediation of LPS anorexia. Interestingly, LPS also reduce orexin expression and the activity of orexin neurons in the lateral hypothalamic area of fasted mice. As the eating-stimulatory properties of orexin are apparently related to arousal, the inhibitory effect of LPS on orexin neurons might be involved in LPS-induced inactivity and anorexia. In summary, the immune signalling pathways of LPS-induced, and presumably acute illness-induced, anorexia converge on central neural signalling systems that control food intake and energy balance in healthy individuals.

  14. Mesenchymal Stromal Cell Secreted Sphingosine 1-Phosphate (S1P) Exerts a Stimulatory Effect on Skeletal Myoblast Proliferation

    PubMed Central

    Tani, Alessia; Anderloni, Giulia; Pierucci, Federica; Matteini, Francesca; Chellini, Flaminia; Zecchi Orlandini, Sandra; Meacci, Elisabetta

    2014-01-01

    Bone-marrow-derived mesenchymal stromal cells (MSCs) have the potential to significantly contribute to skeletal muscle healing through the secretion of paracrine factors that support proliferation and enhance participation of the endogenous muscle stem cells in the process of repair/regeneration. However, MSC-derived trophic molecules have been poorly characterized. The aim of this study was to investigate paracrine signaling effects of MSCs on skeletal myoblasts. It was found, using a biochemical and morphological approach that sphingosine 1-phosphate (S1P), a natural bioactive lipid exerting a broad range of muscle cell responses, is secreted by MSCs and represents an important factor by which these cells exert their stimulatory effects on C2C12 myoblast and satellite cell proliferation. Indeed, exposure to conditioned medium obtained from MSCs cultured in the presence of the selective sphingosine kinase inhibitor (iSK), blocked increased cell proliferation caused by the conditioned medium from untreated MSCs, and the addition of exogenous S1P in the conditioned medium from MSCs pre-treated with iSK further increased myoblast proliferation. Finally, we also demonstrated that the myoblast response to MSC-secreted vascular endothelial growth factor (VEGF) involves the release of S1P from C2C12 cells. Our data may have important implications in the optimization of cell-based strategies to promote skeletal muscle regeneration. PMID:25264785

  15. Evaluation of scopadulciol-related molecules for their stimulatory effect on the cytotoxicity of acyclovir and ganciclovir against Herpes simplex virus type 1 thymidine kinase gene-transfected HeLa cells.

    PubMed

    Hayashi, Kyoko; Rahman, S M Abdur; Ohno, Hiroaki; Tanaka, Tetsuaki; Toyooka, Naoki; Nemoto, Hideo; Hayashi, Toshimitsu

    2004-08-01

    Herpes simplex virus type 1 thymidine kinase (HSV TK) is involved in both antiherpetic therapy and cancer gene therapy with acyclovir (ACV) and ganciclovir (GCV). Enhanced sensitivity to these drugs is advantageous in their clinical use. In the present study, scopadulciol (SDC) and its related compounds were evaluated for their stimulatory effect on the cytotoxicity of ACV and GCV by determination of selective toxicities against HSV TK-expressing HeLa cells. Although SDC remarkably potenciated the cytotoxicity of ACV and GCV, the other tested compounds showed only weak selectivity, except for compound 34.

  16. Co-stimulatory signaling determines tumor antigen sensitivity and persistence of CAR T cells targeting PSCA+ metastatic prostate cancer

    PubMed Central

    Priceman, Saul J.; Gerdts, Ethan A.; Tilakawardane, Dileshni; Kennewick, Kelly T.; Murad, John P.; Park, Anthony K.; Jeang, Brook; Yamaguchi, Yukiko; Urak, Ryan; Weng, Lihong; Chang, Wen-Chung; Wright, Sarah; Pal, Sumanta; Reiter, Robert E.; Brown, Christine E.; Forman, Stephen J.

    2018-01-01

    ABSTRACT Advancing chimeric antigen receptor (CAR)-engineered adoptive T cells for the treatment of solid cancers is a major focus in the field of immunotherapy, given impressive recent clinical responses in hematological malignancies. Prostate cancer may be amenable to T cell-based immunotherapy since several tumor antigens, including prostate stem-cell antigen (PSCA), are widely over-expressed in metastatic disease. While antigen selectivity of CARs for solid cancers is crucial, it is problematic due to the absence of truly restricted tumor antigen expression and potential safety concerns with “on-target off-tumor” activity. Here, we show that the intracellular co-stimulatory signaling domain can determine a CAR's sensitivity for tumor antigen expression. A 4-1BB intracellular co-stimulatory signaling domain in PSCA-CARs confers improved selectivity for higher tumor antigen density, reduced T cell exhaustion phenotype, and equivalent tumor killing ability compared to PSCA-CARs containing the CD28 co-stimulatory signaling domain. PSCA-CARs exhibit robust in vivo anti-tumor activity in patient-derived bone-metastatic prostate cancer xenograft models, and 4-1BB-containing CARs show superior T cell persistence and control of disease compared with CD28-containing CARs. Our study demonstrates the importance of co-stimulation in defining an optimal CAR T cell, and also highlights the significance of clinically relevant models in developing solid cancer CAR T cell therapies. PMID:29308300

  17. Effect of siRNA silencing of inducible co-stimulatory molecule on myocardial cell hypertrophy after cardiac infarction in rats.

    PubMed

    Wang, W M; Liu, Z; Chen, G

    2016-05-20

    As the most common cardiac disease, myocardial infarction is followed by hypertrophy of cardiac myocytes and reconstruction of ventricular structure. The up-regulation of a series of factors including metalloproteinases, inflammatory factors, and growth factors after primary infarction lead to the hypertrophy, apoptosis, necrosis, and fibroblast proliferation in cardiac muscle tissues. Recent studies have reported on the potency of small interfering RNA (siRNA) in treating cardiac diseases. We thus investigated the efficacy of inducible co-stimulatory molecule (ICOS)-specific siRNA silencing in myocardial hypertrophy in a cardiac infarction rat model. This cardiac infarction model was prepared by ligating the left anterior descending coronary artery. ICOS-siRNA treatment was administered in parallel with non-sense siRNA. After 18 days, the cross-sectional area of cardiac muscle tissues and the left ventricle weight index were measured, along with ICOS mRNA and protein expression levels, and pathological staining. Compared to those in the control groups, in myocardial infarcted rats, the application of ICOS-siRNA effectively decreased the left ventricle weight index, as well as the surface area of cardiac myocytes. Both mRNA and protein levels of ICOS were also significantly decreased. HE staining was consistent with these results. In conclusion, ICOS-targeted siRNA can effectively silence gene expression of ICOS, and provided satisfactory treatment efficacy for myocardial cell hypertrophy after infarction.

  18. Effect of purified fractions from cell culture supernate of high-density pre-B acute lymphoblastic leukemia cells (ALL3) on the growth of ALL3 cells at low density.

    PubMed

    Patel, Sapan J; Darie, Costel C; Clarkson, Bayard D

    2017-02-01

    The mechanisms underlying the aberrant growth and interactions between cells are not understood very well. The pre-B acute lymphoblastic leukemia cells directly obtained from an adult patient grow very poorly or do not grow at all at low density (LD), but grow better at high starting cell density (HD). We found that the LD ALL3 cells can be stimulated to grow in the presence of diffusible, soluble factors secreted by ALL3 cells themselves growing at high starting cell density. We then developed a biochemical purification procedure that allowed us to purify the factor(s) with stimulatory activity and analyzed them by nanoliquid chromatography-tandem mass spectrometry (nanoLC-MS/MS). Using nanoLC-MS/MS we have identified several proteins which were further processed using various bioinformatics tools. This resulted in eight protein candidates which might be responsible for the growth activity on non-growing LD ALL3 cells and their involvement in the stimulatory activity are discussed. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. The evolving clinical profile of abatacept (CTLA4–Ig): a novel co-stimulatory modulator for the treatment of rheumatoid arthritis

    PubMed Central

    2005-01-01

    Abatacept (CTLA4–Ig) is a novel fusion protein designed to modulate the T cell co-stimulatory signal mediated through the CD28–CD80/86 pathway. Clinical trials have provided preliminary evidence of the efficacy of this compound in the treatment of rheumatoid arthritis. This review describes the molecular and biologic bases for the use of abatacept in rheumatoid arthritis and summarizes the current clinical data on its safety and effectiveness in this disease. PMID:15833145

  20. Evidence for Alterations in Stimulatory G proteins and Oxytocin Levels in Children with Autism

    PubMed Central

    Jacobson, Jill D.; Ellerbeck, Kathryn A.; Kelly, Kelsie A.; Fleming, Kandace K.; Jamison, T. Rene; Coffey, Charles W.; Smith, Catherine M.; Reese, R. Matthew; Sands, Scott A.

    2014-01-01

    The neurotransmitter oxytocin plays an important role in social affiliation. Low oxytocin levels and defects in the oxytocin receptor have been reported in childhood autism. However, little is known about oxytocin’s post-receptor signaling pathways in autism. Oxytocin signals via stimulatory and inhibitory G proteins. c-fos mRNA expression has been used as a marker of OT signaling as well as of G protein signaling. Herein, we hypothesized that oxytocin and its signaling pathways would be altered in children with autism. We measured plasma oxytocin levels by ELISA, G-protein and c-fos mRNA by PCR, and G proteins by immunoblot in cultured peripheral blood mononuclear cells (PBMCs) in children with autism and in age-matched controls. Males with autism displayed elevated oxytocin levels compared to controls (p<0.05). Children with autism displayed significantly higher mRNA for stimulatory G proteins compared to controls (p<0.05). Oxytocin levels correlated strongly positively with c-fos mRNA levels, but only in control participants (p<0.01). Oxytocin, G-protein, and c-fos mRNA levels correlated inversely with measures of social and emotional behaviors, but only in control participants. These data suggest that children with autism may exhibit a dysregulation in oxytocin and/or its signaling pathways. PMID:24485488

  1. First report of Nitzschia navis-varingica in the Mediterranean Sea and growth stimulatory effects of Nitzschia navis-varingica, Chrysochromulina alifera and Heterocapsa pygmaea on different mammalian cell types.

    PubMed

    Ayaz, Furkan; Eker-Develi, Elif; Sahin, Merve

    2018-05-28

    A benthic diatom, Nitzschia navis-varingica was found for the first time in the Mediterranean Sea. Effects of this diatom species together with the haptophyte Chrysochromulina alifera and the dinoflagellate Heterocapsa pygmaea isolated from the northeastern Mediterranean Sea coast on prostate, breast cancer and fibroblast cell lines were investigated. Algal extracts did not exert any toxic effect on these cell lines and it had growth stimulatory impact on the cells without discrimination of cell type. Our results suggest potential use of these algal extracts in tissue repair and cell growth boosting additive in the diet of humans as well as animals. Moreover, these algal extracts have potential to be used as natural resource in the skin vitalizing creams of cosmetics industry and as wound healing agents in the atopic drugs.

  2. [THE CHANGES OF NOCICEPTIVE THRESHOLD AND ACTIVITY OF THE ADENYLYL CYCLASE SYSTEM IN THE SKELETAL MUSCLES OF RATS WITH ACUTE AND MILD TYPE 1 DIABETES MELLITUS ].

    PubMed

    Shipilov, V N; Trost, A M; Chistyakova, O V; Derkach, K V; Shpakov, A O

    2016-02-01

    Diabetic peripheral neuropathy (DPN) is one of the most common complications of the type 1 diabetes mellitus (DM1). The aim of the work was to study the dynamics of a painful DPN and functional state of the hormone-sensitive ACSS in the skeletal muscles of rats with the models of acute and mild DM1, as well as the study of impact on them of insulin therapy with different ways of hormone delivery - intranasal and peripheral. In both models of DM1, the level of nociceptive threshold in rats decreased and the stimulatory effects of guanine nucleotides (GppNHp) and adrenergic agonists (isoproterenol, BRL-37344) on adenylyl cyclase (AC) activity were attenuated. The AC stimulating effect of relaxin decreased in animals with acute DM1, but in mild DM1, the decrease was insignificant. Peripheral administration of insulin in rats with acute DM1 increased the nociceptive threshold and partially restored the AC effect of ß 3-agonist BRL-37344. Intranasal administration of insulin in rats with DM1 also increased the nociceptive threshold and partially restored the basal and BRL-37344-stimulated AC activity in the skeletal muscles of diabetic animals. Thus, in the skeletal muscles of rats with acute and mild DM1 the nociceptive sensitivity and the functions of ACSS were disturbed, and they were partially restored by the treatment with peripheral (acute DM1) or intranasal (mild DM1) insulin.

  3. Differential effects of acute and chronic estrogen treatment on thermogenic and metabolic pathways in ovariectomized sheep.

    PubMed

    Clarke, Scott D; Clarke, Iain J; Rao, Alexandra; Evans, Roger G; Henry, Belinda A

    2013-01-01

    Estrogen is protective against weight gain, but the underlying mechanisms are not fully elucidated. We sought to characterize the effects of estrogen on energy expenditure in skeletal muscle and adipose tissue in ovariectomized sheep. Temperature probes were implanted into sc (gluteal) and visceral (retroperitoneal) fat depots and skeletal muscle of the hind limb (vastus lateralis). Food was available from 1100-1600 h to entrain postprandial thermogenesis. We characterized the effects of single (50 μg estradiol benzoate, im) and repeated (25 μg estradiol-17β, iv) injections as well as chronic (3 × 3 cm estradiol-17β implants for 7 d) treatment on heat production. A single injection of estrogen increased heat production in visceral fat and skeletal muscle, without an effect on food intake. Increased heat production in skeletal muscle was sustained by repeated estradiol-17β injections. On the other hand, continuous treatment reduced food intake but had no effect on thermogenesis. To determine possible mechanisms that underpin estradiol-17β-induced heat production, we measured femoral artery blood flow, the expression of uncoupling protein (UCP) mRNA and the phosphorylation of AMP-activated protein kinase and Akt in fat and muscle. There was little effect of either single or repeated injections of estradiol-17β on the expression of UCP1, -2, or -3 mRNA in visceral fat or skeletal muscle. Acute injection of estradiol-17β increased the phosphorylation of AMP-activated protein kinase and Akt in muscle only. Estradiol-17β treatment did not alter femoral artery blood flow. Thus, the stimulatory effect of estradiol-17β on thermogenesis in female sheep is dependent upon a pulsatile pattern of treatment and not constant continuous exposure.

  4. Mediation by prostaglandins of the stimulatory effect of substance P on cyclic AMP production in dog iris sphincter smooth muscle.

    PubMed

    Marathe, G K; Yousufzai, S Y; Abdel-Latif, A A

    1996-10-25

    The purpose of the present study was to examine the mechanism of the stimulatory effect of substance P (SP) on cyclic AMP (cAMP) accumulation in dog iris sphincter. We found that: (1) SP increased cAMP accumulation in a time- and concentration-dependent manner, the T1/2 and EC50 values being 1.2 min and 44 nM, respectively. SP has no effect on inositol trisphosphate and muscle contraction in this tissue. (2) SP-stimulated cAMP formation was inhibited by quinacrine, a non-specific phospholipase A2 inhibitor (IC50 = 9.5 microM), and by indomethacin (Indo), a cyclooxygenase inhibitor (IC50 = 3.5 nM), in a concentration-dependent manner, suggesting that SP induces cAMP accumulation via an Indo-sensitive pathway. (3) SP-induced arachidonic acid release and SP-induced prostaglandin E2 (PGE2) release were inhibited concentration dependently by quinacrine and Indo, with IC50 values of 11 microM and 0.8 nM, respectively. (4) PGE2 (1 microM) increased cAMP formation in the sphincter muscle by 94%, and, furthermore, the PG, but not SP, stimulated the activity of adenylyl cyclase in membrane fractions isolated from this tissue. (5) Indo (1 microM) blocked the relaxing effect of SP (1 microM) in iris sphincter precontracted with carbachol (1 microM). (6) The inhibitory effect of Indo on SP-induced cAMP accumulation was species specific. Increases in cAMP represent a mechanism by which extracellular SP can regulate smooth muscle function. Thus, we conclude from these studies that in dog iris sphincter SP-induced cAMP accumulation is mediated through PGs, and that in this cholinergically innervated muscle SP via cAMP could function, in part, to modulate the physiological responses to muscarinic receptor stimulation.

  5. Stimulatory action of itopride hydrochloride on colonic motor activity in vitro and in vivo.

    PubMed

    Tsubouchi, Tadashi; Saito, Takaharu; Mizutani, Fujie; Yamauchi, Toshie; Iwanaga, Yuji

    2003-08-01

    We investigated the effects of itopride hydrochloride (itopride, N-[4-[2-(dimethylamino)ethoxy]benzyl]-3,4-dimethoxybenzamide hydrochloride), a gastroprokinetic agent, on the colonic motor activity in vitro and in vivo, in comparison with benzamides, cisapride hydrate (cisapride), and mosapride citrate (mosapride). Itopride stimulated both peristaltic and segmental motility induced by applying intraluminal pressure to the isolated guinea pig colon. Although cisapride and mosapride enhanced the segmental motility, they markedly reduced the peristaltic motility. In conscious dogs with implanted strain gauge force transducers, itopride stimulated contractile activity in the gastrointestinal tract from the stomach to the colon. Cisapride stimulated contractile activity in the gastric antrum, ileum, and ascending colon. Mosapride stimulated contractile activity only in the gastric antrum and ileum. In guinea pigs and rats, itopride accelerated colonic luminal transit. On the other hand, cisapride and mosapride failed to enhance colonic transit. These results demonstrate that itopride has a stimulatory action on colonic peristalsis, propelling colonic luminal contents, different from that of cisapride and mosapride. Therefore, itopride may be a useful drug for the treatment of functional bowel disorders such as functional constipation.

  6. Monocytes/macrophages infected with Toxoplasma gondii do not increase co-stimulatory molecules while maintaining their migratory ability.

    PubMed

    Seipel, Daniele; Ribeiro-Gomes, Flavia Lima; Barcelos, Michelle Willmen; Ramalho, André Villaça; Kanashiro, Milton M; Kipnis, Thereza Liberman; Arnholdt, Andrea Cristina Veto

    2009-09-01

    Toxoplasma gondii is an obligate intracellular parasite that is able to disseminate into deep tissues and cross biological barriers, reaching immunoprivileged sites such as the brain and retina. The parasite is able to infect macrophages and dendritic cells and use them for dispersal throughout the body, but the activation state of those cells is unknown. We investigated the ability of human and murine cells from monocytic/macrophage lineages that had not previously been exposed to inflammatory cytokines to up-regulate co-stimulatory and adhesion molecules upon infection. Toxoplasma gondii-infected human monocytes (freshly isolated and THP1 lineage) were unable to up-regulate CD86, CD83, CD40 or CD1a. CD80 expression increased in infected cells but expression of l-selectin and beta2 integrin was unaltered. We evaluated the ability of infected macrophages from wild type C57/BL/6 or CD14(-/-) mice to migrate in 8 mum transwells. Infected cells from CD14(-/-) mice were more likely to de-adhere than infected cells from wild type mice but they did not show any increase in migratory ability. The non-stimulatory profile of these infected cells may contribute to parasite spread throughout the lymphatic circulation in the initial phases of infection.

  7. Triterpene glycosides with stimulatory activity on melanogenesis from the aerial parts of Weigela subsessilis.

    PubMed

    Won, Yu-Mi; Seong, Zuh-Kyung; Kim, Jae-Lim; Kim, Hui-Seong; Song, Hyuk-Hwan; Kim, Doo-Young; Kim, Jung-Hee; Oh, Sei-Ryang; Cho, Hyun-Woo; Cho, Jung-Hee; Lee, Hyeong-Kyu

    2015-08-01

    Three new triterpene glycosides (Lonicerosides K, L and M) and 11 known compounds were isolated from the aerial parts of Weigela subsessilis. Among the known isolated compounds, loniceroside A, sweroside, kaempferol-3-O-glucopyranoside 6″-(3-hydroxy-3-methylglutarate), kaempferol-3-O-acetylglucoside and grandifloroside were reported for the first time in a Weigela genus plant. Their chemical structures were identified using extensive spectroscopic analysis including two-dimensional (2D)-NMR experiments, HR-ESI-QTOF-MS and comparison with reported data. Among these compounds, lonicerosides A and L had potent melanogenesis stimulatory activity in murine B16F0 melanoma cells. The structural relationship of active compounds was discussed.

  8. Stimulatory Effect of Food Restriction on the Steroidogenesis of Aldosterone in Ovariectomized Rats.

    PubMed

    Kau, Mei-Mei; Yu, Ching-Han; Tsai, Shiow-Chwen; Wang, Jiing-Rong; Wang, Paulus S.

    2017-04-30

    Food or calorie restriction (FR or CR) induces several physiological changes including weight loss, metabolic adaptations, mineral and hormonal changes. However, the effects of FR on aldosterone steroidogenesis in zona glomerulosa (ZG) cells have not been elucidated. Therefore, the present study was designed to investigate the effects of FR on aldosterone secretion and the involved mechanisms in ovariectomized (Ovx) rats. Ovx rats were divided into ad libitum fed (control) and FR groups. The FR rats exhibited decreased body weight, water intake, urine flow, sodium excretion and increased plasma aldosterone in comparison with control rats. FR elevated the basal and angiotensin II-stimulated aldosterone secretion from ZG cells. The conversions of 25-hydroxy-cholesterol to pregnenolone or corticosterone to aldosterone in ZG cells of FR group were greater than that in control group. FR group had a higher protein expression of steroidogenic acute regulatory (StAR) protein in ZG cells. However, there was no different protein expression of cytochrome P450 sidechain cleavage enzyme (P450scc) in ZG cells between control and FR groups. In summary, the increased activities of P450scc and aldosterone synthase as well as the protein expression of StAR protein in ZG cells are involved in the effects of FR on aldosterone steroidogenesis in Ovx rats. We also suggest that the increase of aldosterone might be associated with anti-diuresis and antinatriuresis in FR group. These results are helpful for understanding the role of aldosterone in physiological adaptation and renal sodium conservation during FR.

  9. 5'-Triphosphate siRNA targeting MDR1 reverses multi-drug resistance and activates RIG-I-induced immune-stimulatory and apoptotic effects against human myeloid leukaemia cells.

    PubMed

    Li, Dengzhe; Gale, Robert Peter; Liu, Yanfeng; Lei, Baoxia; Wang, Yuan; Diao, Dongmei; Zhang, Mei

    2017-07-01

    Multi-drug resistance (MDR), immune suppression and decreased apoptosis are important causes of therapy-failure in leukaemia. Short interfering RNAs (siRNAs) down-regulate gene transcription, have sequence-independent immune-stimulatory effects and synergize with other anti-cancer therapies in some experimental models. We designed a siRNA targeting MDR1 with 5'-triphosphate ends (3p-siRNA-MDR1). Treatment of leukaemia cells with 3p-siRNA-MDR1 down-regulated MDR1 expression, reduced-drug resistance and induced immune and pro-apoptotic effects in drug-resistant HL-60/Adr and K562/Adr human leukaemia cell lines. We show mechanisms-of-action of these effects involve alterations in the anti-viral cytosolic retinoic acid-inducible protein-I (RIG-I; encoded by RIG-I or DDX58) mediated type-I interferon signal induction, interferon-gamma-inducible protein 10 (IP-10; encoded by IP10 or CXCL10) secretion, major histocompatibility complex-I expression (MHC-I) and caspase-mediated cell apoptosis. 3p-siRNA-MDR1 transfection also enhanced the anti-leukaemia efficacy of doxorubicin. These data suggest a possible synergistic role for 3p-siRNA-MDR1 in anti-leukaemia therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Pro-stimulatory role of methemoglobin in inflammation through hemin oxidation and polymerization.

    PubMed

    Deshmukh, Rohitas; Trivedi, Vishal

    2013-02-01

    Inflammation or vascular occlusion by parasitized red blood cell contributes to the pathogenesis of cerebral malaria. The current study aimed to characterize the role of major pro-oxidant factor methemoglobin present in the malaria culture supernatant contributing in inflammation during malaria. Heme and heme polymer stimulate macrophage to secrete large amount of reactive oxygen species into the external micro-environment. The addition of methemoglobin along with heme or heme polymer amplifies production of ROS from macrophages several folds. Methemoglobin mediated stimulatory effect is not due to release of iron, enhanced production of H2O2 or mutual interaction of reaction components. Spectroscopic studies show that methemoglobin accepts heme as a substrate and oxidizes it through a single electron transfer mechanism. Heme oxidation product is a heme polymer with similar chemical and structural properties to synthetic β-hematin. Phenyl N-t-butylnitrone inhibits heme polymerization (IC50=30 nM) and indicates the absolute necessity of heme oxidation and heme free radical generation for heme polymerization. Methemoglobin produced heme polymer is a potent pro-inflammatory factor to release ROS into external microenvironment. Interestingly, methemoglobin not only produces pro-inflammatory heme polymer, but it also amplifies the potential of heme or preformed heme polymer (haemozoin or β-hematin) to produce several folds high ROS production from macrophages. This study illustrates the pro-inflammatory effect of methemoglobin, the underlying novel mechanism by which this occurs and a possible clinical intervention. Based on the results, we recommend methemoglobin directed peroxidase inhibitors as an adjuvant therapy during malaria.

  11. The thyroid endocrine disruptor perchlorate affects reproduction, growth, and survival of mosquitofish.

    PubMed

    Park, June-Woo; Rinchard, Jacques; Liu, Fujun; Anderson, Todd A; Kendall, Ronald J; Theodorakis, Christopher W

    2006-03-01

    The perchlorate anion--an oxidizer found in rockets, missiles, some ammunition, flares, airbags, and fireworks--occurs as a contaminant in ground and surface water in many parts of the United States. Its toxic effects include inhibition of thyroid hormone synthesis. To investigate its chronic toxicity, mosquitofish (Gambusia holbrooki) adults and fry were exposed to aqueous sodium perchlorate at 1, 10, and 100mg/L, and growth and reproductive performance (fecundity, eggs/embryos mass, and gonadosomatic index [GSI]) were determined. Five-day acute toxicity tests were also performed. Perchlorate had a stimulatory effect on fecundity, GSI, and egg/embryo mass, at least for some treatments. The LC50 of sodium perchlorate was 404 mg/L. Growth was enhanced at 1mg/L but inhibited at 10mg/L. These results suggest that, at environmentally relevant concentrations, perchlorate does not induce acutely toxic effects but may have mild stimulatory or hormetic effects on fitness parameters in this species.

  12. Acute and Developmental Behavioral Effects of Flame ...

    EPA Pesticide Factsheets

    As polybrominated diphenyl ethers are phased out, numerous compounds are emerging as potential replacement flame retardants for use in consumer and electronic products. Little is known, however, about the neurobehavioral toxicity of these replacements. This study evaluated the neurobehavioral effects of acute or developmental exposure to t-butylphenyl diphenyl phosphate (BPDP), 2-ethylhexyl diphenyl phosphate (EHDP), isodecyl diphenyl phosphate (IDDP), isopropylated phenyl phosphate (IPP), tricresyl phosphate (TMPP; also abbreviated TCP), triphenyl phosphate (TPHP; also abbreviated TPP), tetrabromobisphenol A (TBBPA), tris (2-chloroethyl) phosphate (TCEP), tris (1,3-dichloroisopropyl) phosphate (TDCIPP; also abbreviated TDCPP), tri-o-cresyl phosphate (TOCP), and 2,2-,4,4’-tetrabromodiphenyl ether (BDE-47) in zebrafish (Danio rerio) larvae. Larvae (n≈24 per dose per compound) were exposed to test compounds (0.4 - 120 µM) at sub-teratogenic concentrations either developmentally or acutely, and locomotor activity was assessed at 6 days post fertilization. When given developmentally, all chemicals except BPDP, IDDP and TBBPA produced behavioral effects. When given acutely, all chemicals produced behavioral effects, with TPHP, TBBPA, EHDP, IPP, and BPDP eliciting the most effects at the most concentrations. The results indicate that these replacement flame retardants may have developmental or pharmacological effects on the vertebrate nervous system. This study

  13. Inhalation of diethylamine--acute nasal effects and subjective response

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lundqvist, G.R.; Yamagiwa, M.; Pedersen, O.F.

    1992-03-01

    Adult volunteers were exposed to 25 ppm (75 mg/m3) diethylamine in a climate chamber for 15 min in order to study the acute nasal reactions to an exposure equivalent to the present threshold limit value-short-term exposure limit. Changes in nasal volume and nasal resistance were measured by acoustic rhinometry and by rhinomanometry. Acute change in nasal volume, usually seen as acute nasal mucosa response to thermal stimuli, was not observed, nor was an acute change in nasal airway resistance. In a subsequent experiment, the aim was to measure acute sensory effects. Exposure to a concentration increasing from 0 to 12more » ppm took place for 60 min, equal to an average concentration of 10 ppm (30 mg/m3). A moderate to strong olfactory response and distinct nasal and eye irritation were observed. In spite of considerable individual variation, the results were in agreement with sensory effect estimates obtained from animal studies.« less

  14. Effect of saposins on acid sphingomyelinase.

    PubMed Central

    Tayama, M; Soeda, S; Kishimoto, Y; Martin, B M; Callahan, J W; Hiraiwa, M; O'Brien, J S

    1993-01-01

    The effect of saposins (A, B, C and D) on acid sphingomyelinase activity was determined using a crude human kidney sphingomyelinase preparation and a purified sphingomyelinase preparation from human placenta. Saposin D stimulated the activity of the crude enzyme by increasing its apparent Km and Vmax. values for sphingomyelin hydrolysis. Unlike the crude enzyme, the activity of the purified enzyme was strongly inhibited by saposin D as well as other saposins. Saposin D decreased the apparent Km and Vmax values of purified sphingomyelinase activity. The effects of saposin D on the activity of different sphingomyelinase preparations appear to depend on Triton X-100, which is present in the crude enzyme but not in the purified enzyme. When the detergent was removed from the crude preparation, the effect of saposin D changed from being stimulatory to inhibitory. Conversely, when the detergent is added to the purified enzyme, the effect of saposin D on sphingomyelinase activity changed from being inhibitory to stimulatory. While other saposins were inhibitory or had no effect on sphingomyelinase activity in the above assay system, not only saposin D but also saposins A and C exhibited a stimulatory effect upon purified sphingomyelinase activity when the substrate, sphingomyelin, was added in the form of liposomes without detergent. Saposin B was not only inhibitory in the liposome system, but also reduced the stimulatory effect of saposins A, C and D. These observations indicate that the stimulatory effect of saposins A, C and D on acid sphingomyelinase activity is greatly influenced by the physical environment of the enzyme and suggest that similar effects by saposins may be exerted in lysosomal membranes. PMID:8452527

  15. Effects of granulocyte-macrophage colony-stimulating factor and interleukin 6 on the growth of leukemic blasts in suspension culture.

    PubMed

    Tsao, C J; Cheng, T Y; Chang, S L; Su, W J; Tseng, J Y

    1992-05-01

    We examined the stimulatory effects of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 6 (IL)-6 on the in vitro proliferation of leukemic blast cells from patients with acute leukemia. Bone marrow or peripheral blood leukemic blast cells were obtained from 21 patients, including 14 cases of acute myeloblastic leukemia (AML), four cases of acute lymphoblastic leukemia (ALL), two cases of acute undifferentiated leukemia, and one case of acute mixed-lineage leukemia. The proliferation of leukemic blast cells was evaluated by measuring the incorporation of 3H-thymidine into cells incubated with various concentrations of cytokines for 3 days. GM-CSF stimulated the DNA synthesis (with greater than 2.0 stimulation index) of blast cells in 9 of 14 (64%) AML cases, two cases of acute undifferentiated leukemia and one case of acute mixed-lineage leukemia. Only two cases of AML blasts responded to IL-6 to grow in the short-term suspension cultures. GM-CSF and IL-6 did not display a synergistic effect on the growth of leukemic cells. Moreover, GM-CSF and IL-6 did not stimulate the proliferation of ALL blast cells. Binding study also revealed the specific binding of GM-CSF on the blast cells of acute undifferentiated leukemia and acute mixed-lineage leukemia. Our results indicated that leukemic blast cells of acute undifferentiated leukemia and acute mixed-lineage leukemia possessed functional GM-CSF receptors.

  16. Immunosuppressive Myeloid Cells' Blockade in the Glioma Microenvironment Enhances the Efficacy of Immune-Stimulatory Gene Therapy.

    PubMed

    Kamran, Neha; Kadiyala, Padma; Saxena, Meghna; Candolfi, Marianela; Li, Youping; Moreno-Ayala, Mariela A; Raja, Nicholas; Shah, Diana; Lowenstein, Pedro R; Castro, Maria G

    2017-01-04

    Survival of glioma (GBM) patients treated with the current standard of care remains dismal. Immunotherapeutic approaches that harness the cytotoxic and memory potential of the host immune system have shown great benefit in other cancers. GBMs have developed multiple strategies, including the accumulation of myeloid-derived suppressor cells (MDSCs) to induce immunosuppression. It is therefore imperative to develop multipronged approaches when aiming to generate a robust anti-tumor immune response. Herein, we tested whether combining MDSC depletion or checkpoint blockade would augment the efficacy of immune-stimulatory herpes simplex type-I thymidine kinase (TK) plus Fms-like tyrosine kinase ligand (Flt3L)-mediated immune stimulatory gene therapy. Our results show that MDSCs constitute >40% of the tumor-infiltrating immune cells. These cells express IL-4Rα, inducible nitric oxide synthase (iNOS), arginase, programmed death ligand 1 (PDL1), and CD80, molecules that are critically involved in antigen-specific T cell suppression. Depletion of MDSCs strongly enhanced the TK/Flt3L gene therapy-induced tumor-specific CD8 T cell response, which lead to increased median survival and percentage of long-term survivors. Also, combining PDL1 or CTLA-4 immune checkpoint blockade greatly improved the efficacy of TK/Flt3L gene therapy. Our results, therefore, indicate that blocking MDSC-mediated immunosuppression holds great promise for increasing the efficacy of gene therapy-mediated immunotherapies for GBM. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  17. Immune-stimulatory and anti-inflammatory activities of Curcuma longa extract and its polysaccharide fraction

    PubMed Central

    Chandrasekaran, Chinampudur V.; Sundarajan, Kannan; Edwin, Jothie R.; Gururaja, Giligar M.; Mundkinajeddu, Deepak; Agarwal, Amit

    2013-01-01

    Background: While curcuminoids have been reported to possess diverse biological activities, the anti-inflammatory activity of polar extracts (devoid of curcuminoids) of Curcuma longa (C. longa) has seldom been studied. In this study, we have investigated immune-stimulatory and anti-inflammatory activities of an aqueous based extract of C. longa (NR-INF-02) and its fractions in presence and absence of mitogens. Materials and Methods: Effects of NR-INF-02 (Turmacin™, Natural Remedies Pvt. Ltd., Bangalore, India) on proliferation, nitric oxide (NO), monocyte chemotactic protein-1 (MCP-1), interleukins (ILs) and prostaglandin (PGE2) levels of mouse splenocytes and mouse macrophage (RAW264.7) cells were determined. Results: NR-INF-02 increased splenocytes number in presence and absence of lipopolysaccharide (LPS) or concanavalin A. Treatment of NR-INF-02 showed a significant increase of NO, IL-2, IL-6, IL-10, IL-12, interferon (IFN) gamma, tumor necrosis factor (TNF) alpha and MCP-1 production in unstimulated mouse splenocytes and mouse macrophages. Interestingly, NR-INF-02 showed potent inhibitory effect towards release of PGE2 and IL-12 levels in LPS stimulated mouse splenocytes. Further, NR-INF-02 was fractionated into polysaccharide fraction (F1) and mother liquor (F2) to study their immune-modulatory effects. F1 was found to be more potent than F2 toward inhibiting PGE2 and IL-12 in LPS stimulated splenocytes. Conclusion: Present findings revealed the novel anti-inflammatory property of NR-INF-02 and its polysaccharide fraction by inhibiting the secretion of IL-12 and PGE2 in vitro. PMID:23798880

  18. Frameshifting in alphaviruses: a diversity of 3' stimulatory structures.

    PubMed

    Chung, Betty Y-W; Firth, Andrew E; Atkins, John F

    2010-03-26

    Programmed ribosomal frameshifting allows the synthesis of alternative, N-terminally coincident, C-terminally distinct proteins from the same RNA. Many viruses utilize frameshifting to optimize the coding potential of compact genomes, to circumvent the host cell's canonical rule of one functional protein per mRNA, or to express alternative proteins in a fixed ratio. Programmed frameshifting is also used in the decoding of a small number of cellular genes. Recently, specific ribosomal -1 frameshifting was discovered at a conserved U_UUU_UUA motif within the sequence encoding the alphavirus 6K protein. In this case, frameshifting results in the synthesis of an additional protein, termed TF (TransFrame). This new case of frameshifting is unusual in that the -1 frame ORF is very short and completely embedded within the sequence encoding the overlapping polyprotein. The present work shows that there is remarkable diversity in the 3' sequences that are functionally important for efficient frameshifting at the U_UUU_UUA motif. While many alphavirus species utilize a 3' RNA structure such as a hairpin or pseudoknot, some species (such as Semliki Forest virus) apparently lack any intra-mRNA stimulatory structure, yet just 20 nt 3'-adjacent to the shift site stimulates up to 10% frameshifting. The analysis, both experimental and bioinformatic, significantly expands the known repertoire of -1 frameshifting stimulators in mammalian and insect systems.

  19. Cytosolic sensing of immuno-stimulatory DNA, the enemy within.

    PubMed

    Dhanwani, Rekha; Takahashi, Mariko; Sharma, Sonia

    2018-02-01

    In the cytoplasm, DNA is sensed as a universal danger signal by the innate immune system. Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor/enzyme that catalyzes formation of 2'-5'-cGAMP, an atypical cyclic di-nucleotide second messenger that binds and activates the Stimulator of Interferon Genes (STING), resulting in recruitment of Tank Binding Kinase 1 (TBK1), activation of the transcription factor Interferon Regulatory Factor 3 (IRF3), and trans-activation of innate immune response genes, including type I Interferon cytokines (IFN-I). Activation of the pro-inflammatory cGAS-STING-IRF3 response is triggered by direct recognition of the DNA genomes of bacteria and viruses, but also during RNA virus infection, neoplastic transformation, tumor immunotherapy and systemic auto-inflammatory diseases. In these circumstances, the source of immuno-stimulatory DNA has often represented a fundamental yet poorly understood aspect of the response. This review focuses on recent findings related to cGAS activation by an array of self-derived DNA substrates, including endogenous retroviral elements, mitochondrial DNA (mtDNA) and micronuclei generated as a result of genotoxic stress and DNA damage. These findings emphasize the role of the cGAS axis as a cell-intrinsic innate immune response to a wide variety of genomic insults. Copyright © 2017. Published by Elsevier Ltd.

  20. Acute and chronic sensitivity to copper of a promising ecotoxicological model species, the annual killifish Nothobranchius furzeri.

    PubMed

    Philippe, Charlotte; Grégoir, Arnout F; Janssens, Lizanne; Pinceel, Tom; De Boeck, Gudrun; Brendonck, Luc

    2017-10-01

    Nothobranchius furzeri is a promising model for ecotoxicological research due to the species' short life cycle and the production of drought-resistant eggs. Although the species is an emerging vertebrate fish model for several fundamental as well as applied research domains, its potential for ecotoxicological research has not yet been tested. The aim of this study was to characterise the acute and chronic sensitivity of this species to copper as compared to other model organisms. Effects of both acute and chronic copper exposure were tested on survival, life history and physiological traits. We report a 24h-LC 50 of 53.93µg Cu/L, which is situated within the sensitivity range of other model species such as Brook Trout, Fathead Minnow and Rainbow Trout. Moreover, in the full life cycle exposure, we show that an exposure concentration of 10.27µg/L did not cause acute adverse effects (96h), but did cause mortality after prolonged exposure (3-4 weeks). Also chronic, sublethal effects were observed, such as a reduction in growth rate, delayed maturation and postponed reproduction. Based on our results, we define the NOEC at 6.68µg Cu/L, making N. furzeri more sensitive to copper as compared to Brook Trout and Fathead Minnow. We found stimulatory effects on peak fecundity at subinhibitory levels of copper concentrations (hormesis). Finally, we found indications for detoxifying and copper-excreting mechanisms, demonstrating the ability of the fish to cope with this essential metal, even when exposed to stressful amounts. The successful application of current ecotoxicological protocols on N. furzeri and its sensitivity range comparable to that of other model organisms forms the basis to exploit this species in further ecotoxicological practices. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. The effects of acute stress on Pavlovian-instrumental transfer in rats.

    PubMed

    Pielock, Steffi M; Braun, Stephanie; Hauber, Wolfgang

    2013-03-01

    Pavlovian stimuli invigorate ongoing instrumental action, a phenomenon termed the Pavlovian-instrumental transfer (PIT) effect. Acute stressors can markedly enhance the release of corticotropin-releasing factor (CRF), and CRF injection into the nucleus accumbens increases the PIT effect. However, it is unknown whether acute stressors by themselves would amplify the PIT effect. Here, we examined the effects of acute stressors on PIT. Rats first received Pavlovian and instrumental training, and then the impact of the Pavlovian stimuli on instrumental responding was analyzed in the subsequent PIT test. Acute stressors were applied prior to the PIT test. Because the effects of acute stressors critically depend on stressor type and time of day, we used two acute stressors that involved one or several distinct stressors (denoted here as "single" vs. "multiple" stressors) applied either in the light or the dark period of the light:dark cycle. The results revealed that single and multiple stressors applied in the light period did not alter the PIT effect--that is, the ability of an appetitive Pavlovian stimulus to enhance leverpressing--or the basal leverpress rate. When applied in the dark period, single and multiple stressors also did not alter the PIT effect, but they did markedly reduce the basal leverpress rate. Diazepam pretreatment did not counteract the declines in basal instrumental responding in the PIT test that were induced by either a single or multiple stressors. Our findings suggest that acute stressors were unable to amplify the incentive salience of reward-predictive Pavlovian stimuli to activate instrumental responding, but, depending on the time of day of stressor exposure, they did reduce basal instrumental responding.

  2. A dual challenge of corticotropin releasing hormone and vasopressin alters immune cell profiles in beef heifers

    USDA-ARS?s Scientific Manuscript database

    The duration and magnitude of cortisol release can have different effects on the immune response. Over the last decade, studies have suggested that acute stress, when cortisol is elevated for a short duration of time, can be immuno-stimulatory rather than immuno-suppressive. This study was designed ...

  3. Tetherin/BST-2 promotes dendritic cell activation and function during acute retrovirus infection

    PubMed Central

    Li, Sam X.; Barrett, Bradley S.; Guo, Kejun; Kassiotis, George; Hasenkrug, Kim J.; Dittmer, Ulf; Gibbert, Kathrin; Santiago, Mario L.

    2016-01-01

    Tetherin/BST-2 is a host restriction factor that inhibits retrovirus release from infected cells in vitro by tethering nascent virions to the plasma membrane. However, contradictory data exists on whether Tetherin inhibits acute retrovirus infection in vivo. Previously, we reported that Tetherin-mediated inhibition of Friend retrovirus (FV) replication at 2 weeks post-infection correlated with stronger natural killer, CD4+ T and CD8+ T cell responses. Here, we further investigated the role of Tetherin in counteracting retrovirus replication in vivo. FV infection levels were similar between wild-type (WT) and Tetherin KO mice at 3 to 7 days post-infection despite removal of a potent restriction factor, Apobec3/Rfv3. However, during this phase of acute infection, Tetherin enhanced myeloid dendritic cell (DC) function. DCs from infected, but not uninfected, WT mice expressed significantly higher MHC class II and the co-stimulatory molecule CD80 compared to Tetherin KO DCs. Tetherin-associated DC activation during acute FV infection correlated with stronger NK cell responses. Furthermore, Tetherin+ DCs from FV-infected mice more strongly stimulated FV-specific CD4+ T cells ex vivo compared to Tetherin KO DCs. The results link the antiretroviral and immunomodulatory activity of Tetherin in vivo to improved DC activation and MHC class II antigen presentation. PMID:26846717

  4. Tetherin/BST-2 promotes dendritic cell activation and function during acute retrovirus infection.

    PubMed

    Li, Sam X; Barrett, Bradley S; Guo, Kejun; Kassiotis, George; Hasenkrug, Kim J; Dittmer, Ulf; Gibbert, Kathrin; Santiago, Mario L

    2016-02-05

    Tetherin/BST-2 is a host restriction factor that inhibits retrovirus release from infected cells in vitro by tethering nascent virions to the plasma membrane. However, contradictory data exists on whether Tetherin inhibits acute retrovirus infection in vivo. Previously, we reported that Tetherin-mediated inhibition of Friend retrovirus (FV) replication at 2 weeks post-infection correlated with stronger natural killer, CD4+ T and CD8+ T cell responses. Here, we further investigated the role of Tetherin in counteracting retrovirus replication in vivo. FV infection levels were similar between wild-type (WT) and Tetherin KO mice at 3 to 7 days post-infection despite removal of a potent restriction factor, Apobec3/Rfv3. However, during this phase of acute infection, Tetherin enhanced myeloid dendritic cell (DC) function. DCs from infected, but not uninfected, WT mice expressed significantly higher MHC class II and the co-stimulatory molecule CD80 compared to Tetherin KO DCs. Tetherin-associated DC activation during acute FV infection correlated with stronger NK cell responses. Furthermore, Tetherin+ DCs from FV-infected mice more strongly stimulated FV-specific CD4+ T cells ex vivo compared to Tetherin KO DCs. The results link the antiretroviral and immunomodulatory activity of Tetherin in vivo to improved DC activation and MHC class II antigen presentation.

  5. Co-stimulatory function in primary germinal center responses: CD40 and B7 are required on distinct antigen-presenting cells.

    PubMed

    Watanabe, Masashi; Fujihara, Chiharu; Radtke, Andrea J; Chiang, Y Jeffrey; Bhatia, Sumeena; Germain, Ronald N; Hodes, Richard J

    2017-09-04

    T cell-dependent germinal center (GC) responses require coordinated interactions of T cells with two antigen-presenting cell (APC) populations, B cells and dendritic cells (DCs), in the presence of B7- and CD40-dependent co-stimulatory pathways. Contrary to the prevailing paradigm, we found unique cellular requirements for B7 and CD40 expression in primary GC responses to vaccine immunization with protein antigen and adjuvant: B7 was required on DCs but was not required on B cells, whereas CD40 was required on B cells but not on DCs in the generation of antigen-specific follicular helper T cells, antigen-specific GC B cells, and high-affinity class-switched antibody production. There was, in fact, no requirement for coexpression of B7 and CD40 on the same cell in these responses. Our findings support a substantially revised model for co-stimulatory function in the primary GC response, with crucial and distinct contributions of B7- and CD40-dependent pathways expressed by different APC populations and with important implications for understanding how to optimize vaccine responses or limit autoimmunity. This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.

  6. RNAi-mediated silencing of hepatic Alas1 effectively prevents and treats the induced acute attacks in acute intermittent porphyria mice.

    PubMed

    Yasuda, Makiko; Gan, Lin; Chen, Brenden; Kadirvel, Senkottuvelan; Yu, Chunli; Phillips, John D; New, Maria I; Liebow, Abigail; Fitzgerald, Kevin; Querbes, William; Desnick, Robert J

    2014-05-27

    The acute hepatic porphyrias are inherited disorders of heme biosynthesis characterized by life-threatening acute neurovisceral attacks. Factors that induce the expression of hepatic 5-aminolevulinic acid synthase 1 (ALAS1) result in the accumulation of the neurotoxic porphyrin precursors 5-aminolevulinic acid (ALA) and porphobilinogen (PBG), which recent studies indicate are primarily responsible for the acute attacks. Current treatment of these attacks involves i.v. administration of hemin, but a faster-acting, more effective, and safer therapy is needed. Here, we describe preclinical studies of liver-directed small interfering RNAs (siRNAs) targeting Alas1 (Alas1-siRNAs) in a mouse model of acute intermittent porphyria, the most common acute hepatic porphyria. A single i.v. dose of Alas1-siRNA prevented the phenobarbital-induced biochemical acute attacks for approximately 2 wk. Injection of Alas1-siRNA during an induced acute attack significantly decreased plasma ALA and PBG levels within 8 h, more rapidly and effectively than a single hemin infusion. Alas1-siRNA was well tolerated and a therapeutic dose did not cause hepatic heme deficiency. These studies provide proof-of-concept for the clinical development of RNA interference therapy for the prevention and treatment of the acute attacks of the acute hepatic porphyrias.

  7. Piezoelectric materials as stimulatory biomedical materials and scaffolds for bone repair.

    PubMed

    Tandon, Biranche; Blaker, Jonny J; Cartmell, Sarah H

    2018-04-16

    The process of bone repair and regeneration requires multiple physiological cues including biochemical, electrical and mechanical - that act together to ensure functional recovery. Myriad materials have been explored as bioactive scaffolds to deliver these cues locally to the damage site, amongst these piezoelectric materials have demonstrated significant potential for tissue engineering and regeneration, especially for bone repair. Piezoelectric materials have been widely explored for power generation and harvesting, structural health monitoring, and use in biomedical devices. They have the ability to deform with physiological movements and consequently deliver electrical stimulation to cells or damaged tissue without the need of an external power source. Bone itself is piezoelectric and the charges/potentials it generates in response to mechanical activity are capable of enhancing bone growth. Piezoelectric materials are capable of stimulating the physiological electrical microenvironment, and can play a vital role to stimulate regeneration and repair. This review gives an overview of the association of piezoelectric effect with bone repair, and focuses on state-of-the-art piezoelectric materials (polymers, ceramics and their composites), the fabrication routes to produce piezoelectric scaffolds, and their application in bone repair. Important characteristics of these materials from the perspective of bone tissue engineering are highlighted. Promising upcoming strategies and new piezoelectric materials for this application are presented. Electrical stimulation/electrical microenvironment are known effect the process of bone regeneration by altering the cellular response and are crucial in maintaining tissue functionality. Piezoelectric materials, owing to their capability of generating charges/potentials in response to mechanical deformations, have displayed great potential for fabricating smart stimulatory scaffolds for bone tissue engineering. The growing

  8. Acute toxicity and effects analysis of endosulfan sulfate to freshwater fish species.

    PubMed

    Carriger, John F; Hoang, Tham C; Rand, Gary M; Gardinali, Piero R; Castro, Joffre

    2011-02-01

    Endosulfan sulfate is a persistent environmental metabolite of endosulfan, an organochlorine insecticide-acaricide presently registered by the United States Environmental Protection Agency. There is, however, limited acute fish toxicity data for endosulfan sulfate. This study determines the acute toxicity (LC₅₀s and LC₁₀s) of endosulfan sulfate to three inland Florida native fish species (mosquitofish [Gambusia affinis]; least killifish [Heterandria formosa]; and sailfin mollies [Poecilia latipinna]) as well as fathead minnows (Pimephales promelas). Ninety-six-h acute toxicity tests were conducted with each fish species under flow-through conditions. For all of the above-mentioned fish species, 96-h LC₅₀ estimates ranged from 2.1 to 3.5 μg/L endosulfan sulfate. The 96-h LC₁₀ estimates ranged from 0.8 to 2.1 μg/L endosulfan sulfate. Of all of the fish tested, the least killifish appeared to be the most sensitive to endosulfan sulfate exposure. The above-mentioned data were combined with previous acute toxicity data for endosulfan sulfate and freshwater fish for an effects analysis. The effects analysis estimated hazardous concentrations expected to exceed 5, 10, and 50% of the fish species' acute LC₅₀ or LC₁₀ values (HC₅, HC₁₀, and HC₅₀). The endosulfan sulfate freshwater-fish acute tests were also compared with the available freshwater-fish acute toxicity data for technical endosulfan. Technical endosulfan is a mixture of α- and β-endosulfan. The LC₅₀s had a wider range for technical endosulfan, and their distribution produced a lower HC₁₀ than for endosulfan sulfate. The number of freshwater-fish LC₅₀s for endosulfan sulfate is much smaller than the number available for technical endosulfan, reflecting priorities in examining the toxicity of the parent compounds of pesticides. The toxicity test results and effects analyses provided acute effect values for endosulfan sulfate and freshwater fish that might be applied

  9. A novel 3-dimensional culture system uncovers growth stimulatory actions by TGFβ in pancreatic cancer cells.

    PubMed

    Sempere, Lorenzo F; Gunn, Jason R; Korc, Murray

    2011-08-01

    Transforming Growth Factor-β (TGF-β) exerts cell type-specific and context-dependent effects. Understanding the intrinsic effects of TGF-β on cancer cells in pancreatic ductal adenocarcinoma (PDAC) is a prerequisite for rationalized clinical implementation of TGF-β targeting therapies. Since the tumor microenvironment can affect how cancer cell respond to TGF-β, we employed a novel three-dimensional (3D) culturing system to recapitulate stromal and extracellular matrix interactions. We show here that TGF-β stimulates growth of human and murine pancreatic cancer cell lines (PCCs) when embedded in a 3% collagen IV/laminin-rich gelatinous medium (Matrigel™) over a solidified layer of soft agar. Moreover, in this novel 3D model, concomitant treatment with TGF-β1 and epidermal growth factor (EGF) enhanced PCC growth to a greater extent than either growth factor alone, and conferred increased chemoresistance to cytotoxic compounds. These cooperative growth-stimulatory effects were blocked by pharmacological inhibition of TGF-β type I receptor with SB431542 or the EGF receptor with erlotinib. Co-incubation with SB431542 and erlotinib enhanced the efficacy of gemcitabine and cisplatin in PCCs and in primary cell cultures established from pancreata of genetically-engineered mouse models of PDAC. These findings suggest that concomitant inhibition of TGF-β and EGF signaling may represent an effective therapeutic strategy in PDAC, and that this 3D culturing system could be utilized to test ex vivo the therapeutic response of pancreatic tumor biopsies from PDAC patients, thereby providing a functional assay to facilitate personalized targeted therapies.

  10. Repeated handling, restraint, or chronic crowding impair the hypothalamic-pituitary-adrenocortical response to acute restraint stress.

    PubMed

    Gadek-Michalska, A; Bugajski, J

    2003-09-01

    The purpose of the present study was to assess whether, and to what extent prior handling, restraint or social crowding stress during 3-10 days affects the hypothalamic-pituitary-adrenocortical (HPA) response to an acute short-lasting restraint stress. Also the effect of a feedback inhibitory mechanism of corticosterone in the impairment of HPA axis by these stressors was investigated. Male Wistar rats were pretreated with handling 1 min/day for 3-10 days, restraint 2 times daily for 3-7 days and crowding stress for 7 days before exposure to acute restraint stress in metal tubes for 10 min. Some group of rats received exogenous s.c. corticosterone either once 25 mg/kg or 2 times daily 10 mg/kg for 3-10 days before restraint stress. After the last restraint the rats were decapitated and their trunk blood was collected for the measurement of plasma ACTH and serum corticosterone levels. Handling for 3-7 days, restraint for 3-7 days, and crowding for 7 days and a single pretreatment with corticosterone--all significantly and to a similar extent inhibited the restraint stress-induced increase in ACTH and corticosterone secretion. Chronic pretreatment with corticosterone blunted the restraint stress-induced increase in HPA axis activity. These results indicate that repeated short-lasting stress induced by handling, restraint, or crowding potently attenuates the acute restraint stress-induced stimulatory action of the HPA axis. They also indicate adaptive action of moderate stress on the HPA axis response to acute stress. The results also suggest that a short-lasting hypersecretion of corticosterone during psychological stress may induce a prolonged feedback inhibition of the HPA axis activity. The attenuation of HPA axis response by prior handling has also obvious methodological implications.

  11. Experimental Effects of Acute Exercise on Prospective Memory and False Memory.

    PubMed

    Green, David; Loprinzi, Paul D

    2018-01-01

    Research demonstrates that acute exercise can enhance retrospective episodic memory performance. However, limited research has examined the effects of acute exercise on prospective memory, and no studies have examined the effects of exercise on false memory performance. This study examined the potential effects of acute exercise on prospective memory and false memory performance. A between-group randomized controlled trial was employed, with participants (college students; M age  = 20 years) randomized into an exercise group (15-minute acute bout of treadmill walking; N = 25) or a control group (15 minutes of sitting; N = 26). Prospective memory was assessed from two laboratory and two naturalistic assessments outside the lab. False memory was assessed using a word-list trial. There were no statistically significant differences in prospective memory based on group allocation (F Group×Time  = 1.17; P = 0.32; η 2  = 0.06). However, the control group recalled more false words and had a higher rate of false memory recognition (F Group×Time  = 3.15; P = 0.01; η 2  = 0.26). These findings indicate that acute moderate-intensity aerobic exercise is not associated with prospective memory performance but provides some suggestive evidence that acute exercise may reduce the rate of false memories.

  12. Spaceflight Sensorimotor Analogs: Simulating Acute and Adaptive Effects

    NASA Technical Reports Server (NTRS)

    Taylor, Laura C.; Harm, Deborah L.; Kozlovskaya, Inessa; Reschke, Millard F.; Wood, Scott J.

    2009-01-01

    Adaptive changes in sensorimotor function during spaceflight are reflected by spatial disorientation, motion sickness, gaze destabilization and decrements in balance, locomotion and eye-hand coordination that occur during and following transitions between different gravitational states. The purpose of this study was to conduct a meta-synthesis of data from spaceflight analogs to evaluate their effectiveness in simulating adaptive changes in sensorimotor function. METHODS. The analogs under review were categorized as either acute analogs used to simulate performance decrements accompanied with transient changes, or adaptive analogs used to drive sensorimotor learning to altered sensory feedback. The effectiveness of each analog was evaluated in terms of mechanisms of action, magnitude and time course of observed deficits compared to spaceflight data, and the effects of amplitude and exposure duration. RESULTS. Parabolic flight has been used extensively to examine effects of acute variation in gravitational loads, ranging from hypergravity to microgravity. More recently, galvanic vestibular stimulation has been used to elicit acute postural, locomotor and gaze dysfunction by disrupting vestibular afferents. Patient populations, e.g., with bilateral vestibular loss or cerebellar dysfunction, have been proposed to model acute sensorimotor dysfunction. Early research sponsored by NASA involved living onboard rotating rooms, which appeared to approximate the time course of adaptation and post-exposure recovery observed in astronauts following spaceflight. Exposure to different bed-rest paradigms (6 deg head down, dry immersion) result in similar motor deficits to that observed following spaceflight. Shorter adaptive analogs have incorporated virtual reality environments, visual distortion paradigms, exposure to conflicting tilt-translation cues, and exposure to 3Gx centrifugation. As with spaceflight, there is considerable variability in responses to most of the analogs

  13. Effectiveness and safety of Saccharomyces boulardii for acute infectious diarrhea.

    PubMed

    Dinleyici, Ener Cagri; Eren, Makbule; Ozen, Metehan; Yargic, Zeynel Abidin; Vandenplas, Yvan

    2012-04-01

    Acute diarrhea continues to be a leading cause of morbidity, hospitalization and mortality worldwide and probiotics have been proposed as a complementary therapy in the treatment of acute diarrhea. Regarding the treatment of acute diarrhea, a few probiotics including Saccharomyces boulardii seem to be promising therapeutic agents. We performed a systematic review and meta-analysis regarding the use of S. boulardii in the treatment of acute infectious diarrhea with relevant studies that searched with the PubMed, Embase, Scopus, Google Scholar, the Cochrane Controlled Trials Library, and the Cochrane Database of Systematic Reviews through October 2011. This review describes the effects of S. boulardii on the duration of diarrhea, the risk of diarrhea during the treatment (especially at the third day) and duration of hospitalization in patients with acute infectious diarrhea. This review also focused on the potential effects of S. boulardii for acute infectious diarrhea due to different etiological causes. S. boulardii significantly reduced the duration of diarrhea approximately 24 h and that of hospitalization approximately 20 h. S. boulardii shortened the initial phase of watery stools; mean number of stools started to decrease at day 2; moreover, a significant reduction was reported at days 3 and 4. This systematic review and meta-analysis of the efficacy of S. boulardii in the treatment of acute infectious diarrhea show that there is strong evidence that this probiotic has a clinically significant benefit, whatever the cause, including in developing countries. Therefore, with S. boulardii, the shortened duration of diarrhea and the reduction in hospital stay result in social and economic benefits.

  14. Induced desensitization of the insulinotropic effects of antidiabetic drugs, BTS 67 582 and tolbutamide.

    PubMed

    McClenaghan, N H; Ball, A J; Flatt, P R

    2000-05-01

    Acute and chronic mechanisms of action of novel insulinotropic antidiabetic drug, BTS 67 582 (1, 1-dimethyl-2-(2-morpholinophenyl)guanidine fumarate), were examined in the stable cultured BRIN-BD11 cell line. BTS 67 582 (100 - 400 microM) stimulated a concentration-dependent increase (P<0.01) in insulin release at both non-stimulatory (1.1 mM) and stimulatory (8. 4 mM) glucose. Long-term exposure (3 - 18 h) to 100 microM BTS 67 582 in culture time-dependently decreased subsequent responsiveness to acute challenge with 200 microM BTS 67 582 or 200 microM tolbutamide at 12 - 18 h (P<0.001). Similarly 3 - 18 h culture with the sulphonylurea, tolbutamide (100 microM), also effectively suppressed subsequent insulinotropic responses to both BTS 67 582 and tolbutamide. Culture with 100 microM BTS 67 582 or 100 microM tolbutamide did not affect basal insulin secretion, cellular insulin content, or cell viability and exerted no influence on the secretory responsiveness to 200 microM of the imidazoline, efaroxan. While 18 h BTS 67 582 culture did not affect the insulin-releasing actions (P<0.001) of 16.7 mM glucose, 10 mM arginine, 30 mM KCl, 25 microM forskolin or 10 nM phorbol-12-myristate 13-acetate (PMA), significant inhibition (P<0.001) of the insulinotropic effects of 10 mM 2-ketoisocaproic acid (KIC) and 10 mM alanine were observed. These data suggest that BTS 67 582 shares a common signalling pathway to sulphonylurea but not imidazoline drugs. Desensitization of drug action may provide an important approach to dissect sites of action of novel and established insulinotropic antidiabetic agents.

  15. Cardiovascular effects of linalyl acetate in acute nicotine exposure.

    PubMed

    Kim, Ju Ri; Kang, Purum; Lee, Hui Su; Kim, Ka Young; Seol, Geun Hee

    2017-04-24

    Smoking is a risk factor for cardiovascular diseases as well as pulmonary dysfunction. In particular, adolescent smoking has been reported to have a higher latent risk for cardiovascular disease. Despite the risk to and vulnerability of adolescents to smoking, the mechanisms underlying the effects of acute nicotine exposure on adolescents remain unknown. This study therefore evaluated the mechanism underlying the effects of linalyl acetate on cardiovascular changes in adolescent rats with acute nicotine exposure. Parameters analyzed included heart rate (HR), systolic blood pressure, lactate dehydrogenase (LDH) activity, vascular contractility, and nitric oxide levels. Compared with nicotine alone, those treated with nicotine plus 10 mg/kg (p = 0.036) and 100 mg/kg (p = 0.023) linalyl acetate showed significant reductions in HR. Moreover, the addition of 1 mg/kg (p = 0.011), 10 mg/kg (p = 0.010), and 100 mg/kg (p = 0.011) linalyl acetate to nicotine resulted in significantly lower LDH activity. Nicotine also showed a slight relaxation effect, followed by a sustained recontraction phase, whereas nicotine plus linalyl acetate or nifedipine showed a constant relaxation effect on contraction of mouse aorta (p < 0.001). Furthermore, nicotine-induced increases in nitrite levels were decreased by treatment with linalyl acetate (p < 0.001). Taken together, our findings suggest that linalyl acetate treatment resulted in recovery of cell damage and cardiovascular changes caused by acute nicotine-induced cardiovascular disruption. Our evaluation of the influence of acute nicotine provides potential insights into the effects of environmental tobacco smoke and suggests linalyl acetate as an available mitigating agent.

  16. Metformin alleviated endotoxemia-induced acute lung injury via restoring AMPK-dependent suppression of mTOR.

    PubMed

    Wu, Kejia; Tian, Rui; Huang, Jing; Yang, Yongqiang; Dai, Jie; Jiang, Rong; Zhang, Li

    2018-05-31

    Inflammation requires intensive metabolic support and modulation of the metabolic pathways might become a novel strategy to limit inflammatory injury. Recent studies have revealed the anti-inflammatory effects of the anti-diabetic reagent metformin, but the underlying mechanisms remain unclear. In the present study, the potential effects of metformin on endotoxemia-induced acute lung injury (ALI) and their relationship with the representative metabolic regulator, including AMPK, sirtuin 1 and mTOR, were investigated. The results indicated that treatment with metformin suppressed LPS-induced upregulation of IL-6 and TNF-α, alleviated pulmonary histological abnormalities, improved the survival rate of LPS-challenged mice. Treatment with metformin reversed LPS-induced decline of AMPK phosphorylation. Co-administration of the AMPK inhibitor compound C abolished the stimulatory effects of metformin on AMPK phosphorylation, the suppressive effects of metformin on IL-6 induction and pulmonary lesions. In addition, co-administration of the mTOR activator 3BDO but not the sirtuin 1 inhibitor EX-527 abolished the effects of metformin on IL-6 induction and pulmonary lesions. Finally, treatment with metformin suppressed LPS-induced p70S6K1 phosphorylation, which was abolished by the AMPK inhibitor. These data suggest that metformin might provide anti-inflammatory benefits in endotoxemia-induced inflammatory lung injury via restoring AMPK-dependent suppression of mTOR. Copyright © 2018. Published by Elsevier B.V.

  17. Effects of Payment Changes on Trends in Post-Acute Care

    PubMed Central

    Buntin, Melinda Beeuwkes; Colla, Carrie Hoverman; Escarce, José J

    2009-01-01

    Objective To test how the implementation of new Medicare post-acute payment systems affected the use of inpatient rehabilitation facilities (IRFs), skilled nursing facilities (SNFs), and home health agencies. Data Sources Medicare acute hospital, IRF, and SNF claims; provider of services file; enrollment file; and Area Resource File data. Study Design We used multinomial logit models to measure realized access to post-acute care and to predict how access to alternative sites of care changed in response to prospective payment systems. Data Extraction Methods A file was constructed linking data for elderly Medicare patients discharged from acute care facilities between 1996 and 2003 with a diagnosis of hip fracture, stroke, or lower extremity joint replacement. Principal Findings Although the effects of the payment systems on the use of post-acute care varied, most reduced the use of the site of care they directly affected and boosted the use of alternative sites of care. Payment system changes do not appear to have differentially affected the severely ill. Conclusions Payment system incentives play a significant role in determining where Medicare beneficiaries receive their post-acute care. Changing these incentives results in shifting of patients between post-acute sites. PMID:19490159

  18. Effects of payment changes on trends in post-acute care.

    PubMed

    Buntin, Melinda Beeuwkes; Colla, Carrie Hoverman; Escarce, José J

    2009-08-01

    To test how the implementation of new Medicare post-acute payment systems affected the use of inpatient rehabilitation facilities (IRFs), skilled nursing facilities (SNFs), and home health agencies. Medicare acute hospital, IRF, and SNF claims; provider of services file; enrollment file; and Area Resource File data. We used multinomial logit models to measure realized access to post-acute care and to predict how access to alternative sites of care changed in response to prospective payment systems. A file was constructed linking data for elderly Medicare patients discharged from acute care facilities between 1996 and 2003 with a diagnosis of hip fracture, stroke, or lower extremity joint replacement. Although the effects of the payment systems on the use of post-acute care varied, most reduced the use of the site of care they directly affected and boosted the use of alternative sites of care. Payment system changes do not appear to have differentially affected the severely ill. Payment system incentives play a significant role in determining where Medicare beneficiaries receive their post-acute care. Changing these incentives results in shifting of patients between post-acute sites.

  19. Effects of Saccharomyces boulardii in children with acute diarrhoea.

    PubMed

    Kurugöl, Z; Koturoğlu, G

    2005-01-01

    Certain probiotic agents, e.g. Lactobacillus GG, have shown efficacy in clinical trials for the treatment of acute childhood diarrhoea, but few studies have examined the effect of Saccharomyces boulardii. We evaluated the effect of S. boulardii in children with acute diarrhoea. Two hundred children were randomized to receive S. boulardii in a granulated form in a daily dose of 250 mg (S. boulardii group) or placebo (placebo group) for 5 d. Clinical and demographic characteristics on admission were similar between the study groups. The medians of the average stool frequency after the second day of the treatment were significantly lower in the S. boulardii group than in the placebo group (p = 0.003). The duration of diarrhoea significantly reduced in the S. boulardii group compared with the placebo group (4.7 vs 5.5 d, p = 0.03). The effect of S. boulardii on watery diarrhoea became apparent after the second day of the treatment. The duration of hospital stay was shorter in the S. boulardii group than in the placebo group (2.9 vs 3.9 d, p < 0.001). Four children from the placebo group versus only one child from the S. boulardii group had persisting diarrhoea. The placebo-controlled study suggested that S. boulardii significantly reduced the duration of acute diarrhoea and the duration of hospital stay. S. boulardii seems to be a promising agent for the amelioration of the course of acute diarrhoea in children when used therapeutically.

  20. Histopathological and genotoxic effects of chlorpyrifos in rats.

    PubMed

    Ezzi, Lobna; Belhadj Salah, Imen; Haouas, Zohra; Sakly, Amina; Grissa, Intissar; Chakroun, Sana; Kerkeni, Emna; Hassine, Mohsen; Mehdi, Meriem; Ben Cheikh, Hassen

    2016-03-01

    This study aims to investigate the effects of chlorpyrifos's sub-acute exposure on male rats. Two groups with six animals each were orally treated, respectively, with 3.1 mg/kg b w and 6.2 mg/kg b w of chlorpyrifos during 4 weeks. The genotoxic effect of chlopyrifos was investigated using the comet assay and the micronucleus test. Some hematological and liver's histopathological changes were also evaluated. Results revealed that chlorpyrifos induced histopathological alterations in liver parenchyma. The lymphoid infiltration observed in liver sections and the increase in white blood cells parameter are signs of inflammation. A significant increase in the platelet' count and in polychromatic erythrocytes/normochromatic erythrocytes (PCE/NCE) ratio was observed in chlorpyrifos-treated groups which could be due to the stimulatory effect of chlorpyrifos on cell formation in the bone marrow at lower doses. In addition, the increase of bone marrow micronucleus percentage and the comet tail length revealed a genotoxic potential of chlorpyrifos in vivo.

  1. Investigation of intracellular signalling cascades mediating stimulatory effect of a Gymnema sylvestre extract on insulin secretion from isolated mouse and human islets of Langerhans.

    PubMed

    Al-Romaiyan, A; Liu, B; Docherty, R; Huang, G-C; Amiel, S; Persaud, S J; Jones, P M

    2012-12-01

    Traditional plant-based remedies such as Gymnema sylvestre (GS) extracts have been used to treat diabetes mellitus for many centuries. We have shown previously that a novel GS extract, OSA®, has a direct effect on insulin secretion but its mode of action has not been studied in detail Thus this study investigated the possible underlying mechanism(s) by which OSA® exerts its action. The effects of OSA® on [Ca(2+)]i and K(+) conductances were assessed by Ca(2+) microfluorimetry and electrophysiology in dispersed mouse islets and MIN6 β-cells, respectively. Isolated mouse (from 20 to 25 mice) and human (from 3 donors) islets, and MIN6 β-cells, were used to investigate whether the stimulatory effect of OSA® on insulin secretion was dependent on the presence of extracellular calcium and protein kinase activation. OSA ®-induced insulin secretion from mouse islets and MIN6 β-cells was inhibited by nifedipine, a voltage-gated Ca(2+) channel blocker, and by the removal of extracellular Ca(2+), respectively. OSA® did not affect the activities of KATP channels or voltage-dependent K(+) channels in MIN6 β-cells but it caused an increase in intracellular Ca(2+) ([Ca(2+)]i) concentrations in Fura-2-loaded mouse islet cells. The insulin secretagogue effect of OSA® was dependent, in part, on protein kinase activation since incubating mouse or human islets with staurosporine, a general protein kinase inhibitor, resulted in partial inhibition of OSA®-induced insulin secretion. Experiments using permeabilized, Ca(2+)-clamped MIN6 β-cells revealed a Ca(2+)-independent component action of OSA® at a late stage in the stimulus-response coupling pathway. OSA®-induced insulin secretion was unexpectedly associated with a decrease in intracellular cAMP levels. These data indicate that the GS isolate OSA® stimulates insulin secretion from mouse and human islets in vitro, at least in part as a consequence of Ca(2+) influx and protein kinase activation. © 2012 Blackwell

  2. Acute anticonvulsant effects of capric acid in seizure tests in mice.

    PubMed

    Wlaź, Piotr; Socała, Katarzyna; Nieoczym, Dorota; Żarnowski, Tomasz; Żarnowska, Iwona; Czuczwar, Stanisław J; Gasior, Maciej

    2015-03-03

    Capric acid (CA10) is a 10-carbon medium-chain fatty acid abundant in the medium-chain triglyceride ketogenic diet (MCT KD). The purpose of this study was to characterize acute anticonvulsant effects of CA10 across several seizure tests in mice. Anticonvulsant effects of orally (p.o.) administered CA10 were assessed in the maximal electroshock seizure threshold (MEST), 6-Hz seizure threshold, and intravenous pentylenetetrazole (i.v. PTZ) seizure tests in mice. Acute effects of CA10 on motor coordination were assessed in the grip and chimney tests. Plasma and brain concentrations of CA10 were measured. Co-administration studies with CA10 and another abundant medium-chain fatty acid, caprylic acid (CA8) were performed. CA10 showed significant and dose-dependent anticonvulsant properties by increasing seizure thresholds in the 6-Hz and MEST seizure tests; it was ineffective in the i.v. PTZ seizure test. At higher doses than those effective in the 6-Hz and MEST seizure tests, CA10 impaired motor performance in the grip and chimney tests. An enhanced anticonvulsant response in the 6-Hz seizure test was produced when CA8 and CA10 were co-administered. An acute p.o. administration of CA10 resulted in dose-proportional increases in its plasma and brain concentrations. CA10 exerted acute anticonvulsant effects at doses that produce plasma exposures comparable to those reported in epileptic patients on the MCT KD. An enhanced anticonvulsant effect is observed when CA10 and the other main constituent of the MCT KD, CA8, were co-administered. Thus, acute anticonvulsant properties of CA10 and CA8 may influence the overall clinical efficacy of the MCT KD. Copyright © 2014. Published by Elsevier Inc.

  3. Effects of a psychiatric intensive care unit in an acute psychiatric department.

    PubMed

    Vaaler, A E; Morken, G; Fløvig, J C; Iversen, V C; Linaker, O M

    2006-01-01

    Psychiatric acute units use different levels of segregation to satisfy needs for containment and decrease in sensory input for behaviourally disturbed patients. Controlled studies evaluating the effects of the procedure are lacking. The aim of the present study was to compare effects in acutely admitted patients with the use of a psychiatric intensive care unit (PICU) and not in a psychiatric acute department. In a naturalistic study, one group of consecutively referred patients had access only to the PICU, the other group to the whole acute unit. Data were obtained for 56 and 62 patients using several scales. There were significant differences in reduction of behaviour associated with imminent, threatening incidents (Broset Violence Checklist), and actual number of such incidents (Staff Observation Aggression Scale-Revised) in favour of the group that was treated in a PICU. The principles of patient segregation in PICUs have favourable effects on behaviours associated with and the actual numbers of violent and threatening incidents.

  4. Effect of bromocriptine on acute ethanol tolerance in UChB rats.

    PubMed

    Tampier, L; Prado, C; Quintanilla, M E; Mardones, J

    1999-07-01

    It has been suggested that a higher capacity to develop acute tolerance during a single dose of ethanol may promote higher ethanol consumption in alcohol-preferring rodents. Several studies have shown that the dopaminergic system may be involved in voluntary ethanol consumption. In the present paper we studied the effect of bromocriptine, a dopaminergic agonist drug, that is known to reduce voluntary consumption of ethanol, on acute tolerance in high (UChB) ethanol consumer rats. Acute tolerance was evaluated in bromocriptine and saline-treated rats by motor impairment induced by a subnarcotic dose of ethanol of 2.3 g/kg IP using a modified tilting plane test. Results showed a highly significant positive correlation between acute tolerance and the voluntary ethanol consumption by the rat. Bromocriptine treatment decreased ethanol consumption and also decreased acute tolerance development. This adds further support to the postulate that the acquisition of acute tolerance to ethanol may promote increased alcohol consumption. Moreover, these results also suggest that dopaminergic receptors involved in ethanol voluntary consumption may also be in acute tolerance development.

  5. Effects of Acute Withdrawal on Ethanol-Induced Conditioned Place Preference in DBA/2J mice

    PubMed Central

    Dreumont, Sarah E.; Cunningham, Christopher L.

    2013-01-01

    Rationale Re-exposure to ethanol during acute withdrawal might facilitate the transition to alcoholism by enhancing the rewarding effect of ethanol. Objective The conditioned place preference (CPP) procedure was used to test whether ethanol reward is enhanced during acute withdrawal. Methods DBA/2J mice were exposed to an unbiased one-compartment CPP procedure. Ethanol (0.75, 1.0 or 1.5 g/kg IP) was paired with a distinctive floor cue (CS+), whereas saline was paired with a different floor cue (CS−). The Withdrawal (W) group received CS+ trials during acute withdrawal produced by a large dose of ethanol (4 g/kg) given 8 h before each trial. The No Withdrawal (NW) group did not experience acute withdrawal during conditioning trials, but was matched for acute withdrawal experience. Floor preference was tested in the absence of ethanol or acute withdrawal. Results All groups eventually showed a dose-dependent preference for the ethanol-paired cue, but development of CPP was generally more rapid and stable in the W groups than in the NW groups. Acute withdrawal suppressed the normal activating effect of ethanol during CS+ trials, but there were no group differences in test activity. Conclusions Acute withdrawal enhanced ethanol’s rewarding effect as indexed by CPP. Since this effect depended on ethanol exposure during acute withdrawal, the enhancement of ethanol reward was likely mediated by the alleviation of acute withdrawal, i.e., negative reinforcement. Enhancement of ethanol reward during acute withdrawal may be a key component in the shift from episodic to chronic ethanol consumption that characterizes alcoholism. PMID:24096534

  6. Acute and Chronic Effects of Cocaine on the Spontaneous Behavior of Pigeons

    ERIC Educational Resources Information Center

    Pinkston, Jonathan W.; Branch, Marc N.

    2010-01-01

    The present experiment examined the effects of acute and daily cocaine on spontaneous behavior patterns of pigeons. After determining the acute effects of a range of doses, 9 pigeons were divided into three groups that received one of three doses of cocaine daily, either 1.0, 3.0, or 10.0 mg/kg cocaine. Measures were taken of spontaneous…

  7. Acute and chronic effects of the insecticide endrin on renal function and renal hemodynamics.

    DOT National Transportation Integrated Search

    1963-10-01

    Chronic and acute effects of the insecticide endrin on renal function were studied in dogs. Animals were exposed to endrin chronically by intramuscular injection and acutely by intravenous infusion. In acute studies dogs developed systemic hypertensi...

  8. Acute alerting effects of light: A systematic literature review.

    PubMed

    Souman, Jan L; Tinga, Angelica M; Te Pas, Susan F; van Ee, Raymond; Vlaskamp, Björn N S

    2018-01-30

    Periodic, well timed exposure to light is important for our health and wellbeing. Light, in particular in the blue part of the spectrum, is thought to affect alertness both indirectly, by modifying circadian rhythms, and directly, giving rise to acute effects. We performed a systematic review of empirical studies on direct, acute effects of light on alertness to evaluate the reliability of these effects. In total, we identified 68 studies in which either light intensity, spectral distribution, or both were manipulated, and evaluated the effects on behavioral measures of alertness, either subjectively or measured in reaction time performance tasks. The results show that increasing the intensity of polychromatic white light has been found to increase subjective ratings of alertness in a majority of studies, though a substantial proportion of studies failed to find significant effects, possibly due to small sample sizes or high baseline light intensities. The effect of the color temperature of white light on subjective alertness is less clear. Some studies found increased alertness with higher color temperatures, but other studies reported no detrimental effects of filtering out the short wavelengths from the spectrum. Similarly, studies that used monochromatic light exposure showed no systematic pattern for the effects of blue light compared to longer wavelengths. Far fewer studies investigated the effects of light intensity or spectrum on alertness as measured with reaction time tasks and of those, very few reported significant effects. In general, the small sample sizes used in studies on acute alerting effects of light make it difficult to draw definitive conclusions and better powered studies are needed, especially studies that allow for the construction of dose-response curves. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Acute psychological benefits of exercise: reconsideration of the placebo effect.

    PubMed

    Szabo, Attila

    2013-10-01

    The psychological benefits of exercise are repeatedly and consistently reported in the literature. Various forms of exercise, varying in duration and intensity, yield comparably positive changes in affect, which sheds doubt on the significance of exercise characteristics in the acute mental health benefits resulting from physical activity. Based on research evidence, it is argued that the placebo effect may play a key role in the subjective exercise experience. This report is aimed at highlighting those aspects of the extant literature that call for the reconsideration of the placebo effect in the understanding of the acute mental benefits of physical activity. This narrative review focuses on research evidence demonstrating that the duration and intensity of physical activity are not mediatory factors in the mental health benefits of acute exercise. Current research evidence pointing to the roles of expectancy and conditioning in the affective benefits of exercise calls for the reconsideration of the placebo effect. The present evaluation concludes that new research effort ought to be invested in the placebo-driven affective beneficence of exercise.

  10. Acute effects of tea consumption on attention and mood.

    PubMed

    Einöther, Suzanne J; Martens, Vanessa E

    2013-12-01

    Tea has historically been associated with mood and performance benefits, such as relaxation and concentration. This review summarizes the research on the acute effects of tea, and its ingredients theanine and caffeine, on attention and mood. Consistent with abundant research on the benefits of caffeine, the performance benefits of tea were identified in a number of studies, with particularly consistent evidence for improved attention. Tea consumption also consistently improved self-reported alertness and arousal, whereas effects on pleasure or relaxation were less consistent. In addition to the research on caffeine in real-life performance, 2 recent studies have provided a broader perspective on tea's effects on psychological function in that they showed beneficial effects in related areas such as work performance and creativity. These studies showed the validity of laboratory findings by supporting the idea that tea consumption has acute benefits on both mood and performance in real-life situations.

  11. The effect of olanzapine pretreatment on acute cocaine toxicity in mice.

    PubMed

    Heard, Kennon J; Cleveland, Nathan R; Krier, Shay

    2009-07-01

    Acute cocaine poisoning causes neuroexcitation and can be fatal. The toxic effects of cocaine can be attenuated by antagonists of serotonin, muscarinic cholinergic, and dopamine receptors. Olanzapine, an atypical antipsychotic medication, is an antagonist of these receptors. The objective of this study is to evaluate the efficacy of olanzapine pretreatment for attenuation of acute cocaine toxicity using a mouse model. Eighty male CF-1 mice were randomly assigned to olanzapine (1 mg/kg) or placebo pretreatment. Fifteen minutes later, all animals received 103 mg/kg intraperitoneal cocaine. Overall mortality was 11% for olanzapine-treated animals and 45% for placebo. Olanzapine also appeared to alter the characteristics of seizures due to cocaine. In this model of acute cocaine toxicity, olanzapine pretreatment attenuated acute cocaine toxicity. Olanzapine should be evaluated further as a potential treatment for acute cocaine poisoning.

  12. Neuroprotective effect of ethanol in acute carbon monoxide intoxication: A retrospective study.

    PubMed

    Kim, Hyuk-Hoon; Choi, Sang Chun; Chae, Minjung Kathy; Min, Young-Gi

    2018-01-01

    In acute carbon monoxide (CO) intoxication, treatment of neurologic injury and prevention of neurological sequelae are primary concerns. Ethanol is the one of the frequent substances which is co-ingested in intentional CO poisoning. Neuroprotective effect of ethanol was highlighted and demonstrated in isolated brain injury recently. We assessed the neuroprotective effect of ethanol in acute CO intoxication using magnetic resonance imaging (MRI).We retrospectively reviewed medical records for patients who visited an emergency medical center of a university-affiliated hospital during a period of 73 months, from March 2009 to April 2015. Enrolled patients were divided into 2 groups, patients with or without abnormal brain lesion in brain MRI. Multivariate logistic regression analysis was performed to assess the factors associated with brain injury in MRI.A total of 109 patients with acute CO intoxication were evaluated of which 66 (60.55%) tested positive in brain MRI. MRI lesion-positive patients were more likely to have electrocardiogram change, elevation of serum troponin I and s100 protein level and lower serum ethanol level. Serum ethanol positivity was an independent factor for prevalence of brain injury in MRI in acute CO poisoning.This study revealed that ethanol which is co-ingested in acute CO intoxication may work the neuroprotective effect and could consequence more favorable neurological outcome in acute CO intoxication. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  13. Acute pulmonary and innate immunity health effects in mice inhaling cookstove emissions

    EPA Science Inventory

    Background: Burning of solid-fuels in rudimentary stoves generates harmful emissions that contribute to poor indoor air quality and have detrimental impacts on human health. Acute health effects include respiratory and eye irritation, cough, acute lower respiratory infection and ...

  14. REINFORCEMENT ENHANCING EFFECTS OF ACUTE NICOTINE VIA ELECTRONIC CIGARETTES

    PubMed Central

    Perkins, Kenneth A.; Karelitz, Joshua L.; Michael, Valerie C.

    2015-01-01

    Background Recent human studies confirm animal research showing that nicotine enhances reinforcement from rewards unrelated to nicotine. These effects of acute nicotine via tobacco smoking may also occur when consumed from non-tobacco products. Methods We assessed acute effects of nicotine via electronic cigarettes (“e-cigarettes”) on responding reinforced by music, video, or monetary rewards, or for no reward (control). In a fully within-subjects design, adult dependent smokers (N=28) participated in three similar experimental sessions, each following overnight abstinence (verified by CO≤10 ppm). Varying only in e-cigarette condition, sessions involved controlled exposure to a nicotine (labeled “36 mg/ml”) or placebo (“0”) e-cigarette, or no e-cigarette use. A fourth session involved smoking one’s own tobacco cigarette brand after no abstinence, specifically to compare responses under typical nicotine satiation with these acute e-cigarette conditions after abstinence. Results Reinforced responding for video reward, but not the other rewards, was greater due to use of the nicotine versus placebo e-cigarette (i.e., nicotine per se), while no differences were found between the placebo e-cigarette and no e-cigarette conditions (i.e., e-cigarette use per se). For nicotine via tobacco smoking, responding compared to the nicotine e-cigarette was similar for video but greater for music, while both video and music reward were enhanced relative to the non-nicotine conditions (placebo and no e-cigarette). Conclusions Acute nicotine from a non-tobacco product has some reinforcement enhancing effects in humans, in a manner partly consistent with nicotine via tobacco smoking and perhaps contributing to the rising popularity of nicotine e-cigarette use. PMID:26070455

  15. Reinforcement enhancing effects of acute nicotine via electronic cigarettes.

    PubMed

    Perkins, Kenneth A; Karelitz, Joshua L; Michael, Valerie C

    2015-08-01

    Recent human studies confirm animal research showing that nicotine enhances reinforcement from rewards unrelated to nicotine. These effects of acute nicotine via tobacco smoking may also occur when consumed from non-tobacco products. We assessed acute effects of nicotine via electronic cigarettes ("e-cigarettes") on responding reinforced by music, video, or monetary rewards, or for no reward (control). In a fully within-subjects design, adult dependent smokers (N=28) participated in three similar experimental sessions, each following overnight abstinence (verified by CO≤10ppm). Varying only in e-cigarette condition, sessions involved controlled exposure to a nicotine (labeled "36mg/ml") or placebo ("0″) e-cigarette, or no e-cigarette use. A fourth session involved smoking one's own tobacco cigarette brand after no abstinence, specifically to compare responses under typical nicotine satiation with these acute e-cigarette conditions after abstinence. Reinforced responding for video reward, but not the other rewards, was greater due to use of the nicotine versus placebo e-cigarette (i.e., nicotine per se), while no differences were found between the placebo e-cigarette and no e-cigarette conditions (i.e., e-cigarette use per se). For nicotine via tobacco smoking, responding compared to the nicotine e-cigarette was similar for video but greater for music, while both video and music reward were enhanced relative to the non-nicotine conditions (placebo and no e-cigarette). Acute nicotine from a non-tobacco product has some reinforcement enhancing effects in humans, in a manner partly consistent with nicotine via tobacco smoking and perhaps contributing to the rising popularity of nicotine e-cigarette use. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Effects of acute and chronic cilazapril treatment in spontaneously hypertensive rats

    PubMed Central

    Fischli, W.; Hefti, F.; Clozel, J.-P.

    1989-01-01

    1 The effects of acute and chronic treatment with cilazapril, a new ACE inhibitor, on peripheral vasculature and renal excretory function were assessed in spontaneously hypertensive rats. Regional blood flow and cardiac output were measured by the radio-active microspheres technique. 2 Acute treatment (3 mg kg-1 intravenously) reduced mean arterial blood pressure from 171 ± 7 to 140 241 ± 7 mm Hg (P < 0.001), chronic treatment (1 × 10 mg kg-1 day-1 orally for 9 weeks) from 191 ± 5 to 122 ± 3 mm Hg P < 0.001). With both kinds of treatments cardiac output was unchanged. Heart rate was slightly decreased (-9%, P < 0.05) with chronic treatment. Acutely, the main effect of cilazapril was a decrease of the renal vascular resistance (-41%, P < 0.001) associated with an increase of the fraction of the cardiac output distributed to the kidney (+46%, P < 0.001). Chronically, cilazapril decreased regional vascular resistance in most of the peripheral vascular beds except the heart. 3 With a high dose of cilazapril (10 mg kg-1 orally) both acute and chronic treatment increased diuresis (+107% and +92%, P < 0.001) and natriuresis (+124% and +111%, P < 0.001) with a slight increase in kaliuresis. However, with a low dose (1 mg kg-1 orally) the kidneys responded only to chronic treatment. 4 It is concluded that chronic treatment with cilazapril decreases arterial blood pressure more than acute treatment. This effect seems to be due to a greater peripheral vasodilation. In addition, diuretic and natriuretic effects of cilazapril probably contribute to blood pressure reduction. PMID:2527529

  17. Effect of acarbose on acute acidosis.

    PubMed

    McLaughlin, C L; Thompson, A; Greenwood, K; Sherington, J; Bruce, C

    2009-06-01

    , acidosis was induced in 7 of 7 animals in the control, 1% sodium bicarbonate, and 12 mg of monensin/kg of dry matter intake groups and in 3 of 8 steers administered 1.07 mg of acarbose/kg of BW in the challenge. Increases in lactate concentrations and decreases in total VFA associated with acute acidosis were mitigated by acarbose. Thus, acarbose, an amylase and glucosidase inhibitor, prevented or reduced the incidence of acidosis in an acute challenge model in steers and was more effective than monensin or sodium bicarbonate.

  18. Frondoside A potentiates the effects of conventional therapeutic agents in acute leukemia.

    PubMed

    Sajwani, F H; Collin, P; Adrian, T E

    2017-12-01

    Acute leukemia is the major cause of mortality in hematological malignancies. Despite improvement of survival with current chemotherapies, patients die from the disease or side-effects of treatment. Thus, new therapeutic agents are needed. Frondoside A is a triterpenoid glycoside originally isolated from the sea cucumber, Cucumaria frondosa that has potent antitumor effects in various cancers. The current study investigated the effects of frondoside A in acute leukemia cell lines alone and in combination with drugs used for this malignancy. This study is the first comparing the efficacy of frondoside A to available conventional drugs. The acute leukemia cell lines used were CCRF-CEM, HL-60 and THP-1. Cells were cultured and treated with different concentrations of vincristine sulphate, asparaginase and prednisolone alone and in combination with frondoside A. The inhibitory concentration 50 (IC 50 ) for each compound was determined for the cell lines. CCRF-CEM cells were very sensitive to frondoside A treatment while HL-60 and THP1 were less sensitive. Frondoside A markedly enhanced the anticancer effects of all of the conventional drugs. Synergistic effects were seen with most of the combinations. Frondoside A may be valuable in the treatment of acute leukemia, particularly when used in combination with current therapeutic drugs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Stimulatory effect of insulin on 5alpha-reductase type 1 (SRD5A1) expression through an Akt-dependent pathway in ovarian granulosa cells.

    PubMed

    Kayampilly, Pradeep P; Wanamaker, Brett L; Stewart, James A; Wagner, Carrie L; Menon, K M J

    2010-10-01

    Elevated levels of 5α-reduced androgens have been shown to be associated with hyperandrogenism and hyperinsulinemia, the leading causes of ovulatory dysfunction in women. 5α-Dihydrotestosterone reduces ovarian granulosa cell proliferation by inhibiting FSH-mediated mitogenic signaling pathways. The present study examined the effect of insulin on 5α-reductase, the enzyme that catalyses the conversion of androgens to their 5α-derivatives. Granulosa cells isolated from immature rat ovaries were cultured in serum-free, phenol red-free DMEM-F12 media and treated with different doses of insulin (0, 0.1, 1.0, and 10.0 μg/ml) for different time intervals up to 12 h. The expression of 5α-reductase type 1 mRNA, the predominant isoform found in granulosa cells, showed a significant (P<0.05) increase in response to the insulin treatment up to 12 h compared with control. The catalytic activity of 5α-reductase enzyme was also stimulated in a dose-depended manner (P<0.05). Inhibiting the Akt-dependent signaling pathway abolished the insulin-mediated increase in 5α-reductase mRNA expression, whereas inhibition of the ERK-dependent pathway had no effect. The dose-dependent increase in 5α-reductase mRNA expression as well as catalytic activity seen in response to insulin treatment was also demonstrated in the human granulosa cell line (KGN). In addition to increased mRNA expression, a dose-dependent increase in 5α-reductase protein expression in response to insulin was also seen in KGN cells, which corroborated well with that of mRNA expression. These results suggest that elevated levels of 5α-reduced androgens seen in hyperinsulinemic conditions might be explained on the basis of a stimulatory effect of insulin on 5α-reductase in granulosa cells. The elevated levels of these metabolites, in turn, might adversely affect growth and proliferation of granulosa cells, thereby impairing follicle growth and ovulation.

  20. Stimulatory Effect of Insulin on 5α-Reductase Type 1 (SRD5A1) Expression through an Akt-Dependent Pathway in Ovarian Granulosa Cells

    PubMed Central

    Kayampilly, Pradeep P.; Wanamaker, Brett L.; Stewart, James A.; Wagner, Carrie L.; Menon, K. M. J.

    2010-01-01

    Elevated levels of 5α-reduced androgens have been shown to be associated with hyperandrogenism and hyperinsulinemia, the leading causes of ovulatory dysfunction in women. 5α-Dihydrotestosterone reduces ovarian granulosa cell proliferation by inhibiting FSH-mediated mitogenic signaling pathways. The present study examined the effect of insulin on 5α-reductase, the enzyme that catalyses the conversion of androgens to their 5α-derivatives. Granulosa cells isolated from immature rat ovaries were cultured in serum-free, phenol red-free DMEM-F12 media and treated with different doses of insulin (0, 0.1, 1.0, and 10.0 μg/ml) for different time intervals up to 12 h. The expression of 5α-reductase type 1 mRNA, the predominant isoform found in granulosa cells, showed a significant (P < 0.05) increase in response to the insulin treatment up to 12 h compared with control. The catalytic activity of 5α-reductase enzyme was also stimulated in a dose-depended manner (P < 0.05). Inhibiting the Akt-dependent signaling pathway abolished the insulin-mediated increase in 5α-reductase mRNA expression, whereas inhibition of the ERK-dependent pathway had no effect. The dose-dependent increase in 5α-reductase mRNA expression as well as catalytic activity seen in response to insulin treatment was also demonstrated in the human granulosa cell line (KGN). In addition to increased mRNA expression, a dose-dependent increase in 5α-reductase protein expression in response to insulin was also seen in KGN cells, which corroborated well with that of mRNA expression. These results suggest that elevated levels of 5α-reduced androgens seen in hyperinsulinemic conditions might be explained on the basis of a stimulatory effect of insulin on 5α-reductase in granulosa cells. The elevated levels of these metabolites, in turn, might adversely affect growth and proliferation of granulosa cells, thereby impairing follicle growth and ovulation. PMID:20810561

  1. Acute side effects of three commonly used gadolinium contrast agents in the paediatric population.

    PubMed

    Neeley, Chris; Moritz, Michael; Brown, Jeffrey J; Zhou, Yihua

    2016-07-01

    To determine the incidence of acute side effects of three commonly used gadolinium contrast agents in the paediatric population. A retrospective review of medical records was performed to determine the incidence of acute adverse side effects of i.v. gadolinium contrast agents [MultiHance(®) (Bracco Diagnostics Inc., Princeton, NJ), Magnevist(®) (Bayer Healthcare Pharmaceuticals, Wayne, NJ) or Gadavist(®) (Bayer HealthCare Pharmaceuticals)] in paediatric patients. 40 of the 2393 patients who received gadolinium contrast agents experienced acute side effects, representing an incidence of 1.7%. The majority of the acute side effects (in 30 patients) were nausea and vomiting. The incidence was significantly higher in non-sedated patients (2.37% vs 0.7%; p = 0.0018). Furthermore, without sedation, the incidence of both nausea and vomiting was significantly higher in children receiving MultiHance, with a 4.48% incidence of nausea when compared with Magnevist (0.33%, p < 0.0001) and Gadavist (0.28%, p < 0.0001) and a 2.36% incidence of vomiting compared with those for Magnevist (0.50%, p = 0.0054) and Gadavist (0.28%, p = 0.014), whereas no difference was observed between Magnevist and Gadavist within the power of the study. In addition, there was no apparent difference between any of the three contrast agents for the incidence of allergy or other acute side effects detected, given the sample size. The gadolinium contrast agents MultiHance, Magnevist and Gadavist have a low incidence of acute side effects in the paediatric population, a rate that is further reduced in moderately sedated patients. MultiHance demonstrated significantly increased incidence of gastrointestinal symptoms compared with Magnevist and Gadavist. The incidence of acute side effects of three commonly used gadolinium contrast agents was determined in the paediatric population, which can have clinical implications.

  2. Possible mechanism of the stimulatory effect of Artemisia leaf extract on the proliferation of cultured endothelial cells: involvement of basic fibroblast growth factor.

    PubMed

    Kaji, T; Kaga, K; Miezi, N; Hayashi, T; Ejiri, N; Sakuragawa, N

    1990-09-01

    To investigate the possible mechanism of the stimulatory effect of a hot water extract from Artemisia leaf (Artemisia princeps PANPANINI) (AFE) on the proliferation of endothelial cells, cells from bovine aorta were cultured for 72 h in RPMI1640 medium supplemented with 10% fetal calf serum in the presence of 5 micrograms/ml AFE. The AFE treatment significantly increased the cell number after culture, while in the presence of 10 micrograms/ml unfractionated heparin, AFE conversely decreased it. This implied that AFE enhanced the cell growth promotion by basic fibroblast growth factor (bFGF). The accumulation of bFGF was significantly increased in the culture medium, in the low-affinity (glycosaminoglycans-binding) fraction, and in the cell extract fraction, but was unchanged in the high-affinity (receptor-binding) fraction. The contents of [35S]sulfate-labeled glycosaminoglycans in both cell layer and the medium were not increased by AFE treatment. The proliferation of A10 cells, an established cell line of smooth muscle cells from murine aorta, was not stimulated by AFE. A10 cells did not produce a significant amount of bFGF in the presence or absence of AFE. Thus, the production of bFGF was considered to be involved in AFE stimulation of cell proliferation. In conclusion, it was suggested that AFE stimulated endothelial cell proliferation by increasing the production of bFGF rather than by an increase in the number of bFGF receptors and the content of glycosaminoglycans in the cell layer. The enhanced reserve of bFGF in the low-affinity fraction of cell layer and in the medium would cause the AFE-stimulated proliferation of endothelial cells.

  3. Effects of emotional exposure on state anxiety after acute exercise.

    PubMed

    Smith, J Carson

    2013-02-01

    Despite the well-known anxiolytic effect of acute exercise, it is unknown if anxiety reductions after acute exercise conditions survive in the face of a subsequently experienced arousing emotional exposure. The purpose of this study was to compare the effects of moderate-intensity cycle ergometer exercise to a seated rest control condition on state anxiety symptoms after exposure to a variety of highly arousing pleasant and unpleasant stimuli. Thirty-seven healthy and normally physically active young adults completed two conditions on separate days: 1) 30 min of seated rest and 2) 30 min of moderate-intensity cycle ergometer exercise (RPE = 13; "somewhat hard"). After each condition, participants viewed 90 arousing pleasant, unpleasant, and neutral pictures from the International Affective Picture System for 30 min. State anxiety was measured before and 15 min after each condition, and again after exposure to the affective pictures. State anxiety significantly decreased from baseline to after the exercise and seated rest conditions (P = 0.003). After the emotional picture-viewing period, state anxiety significantly increased to baseline values after the seated rest condition (P = 0.001) but remained reduced after the exercise condition. These findings suggest that the anxiolytic effects of acute exercise may be resistant to the potentially detrimental effects on mood after exposure to arousing emotional stimuli.

  4. Cost-effectiveness of optimizing acute stroke care services for thrombolysis.

    PubMed

    Penaloza-Ramos, Maria Cristina; Sheppard, James P; Jowett, Sue; Barton, Pelham; Mant, Jonathan; Quinn, Tom; Mellor, Ruth M; Sims, Don; Sandler, David; McManus, Richard J

    2014-02-01

    Thrombolysis in acute stroke is effective up to 4.5 hours after symptom onset but relies on early recognition, prompt arrival in hospital, and timely brain scanning. This study aimed to establish the cost-effectiveness of increasing thrombolysis rates through a series of hypothetical change strategies designed to optimize the acute care pathway for stroke. A decision-tree model was constructed, which relates the acute management of patients with suspected stroke from symptom onset to outcome. Current practice was modeled and compared with 7 change strategies designed to facilitate wider eligibility for thrombolysis. The model basecase consisted of data from consenting patients following the acute stroke pathway recruited in participating hospitals with data on effectiveness of treatment and costs from published sources. All change strategies were cost saving while increasing quality-adjusted life years gained. Using realistic estimates of effectiveness, the change strategy with the largest potential benefit was that of better recording of onset time, which resulted in 3.3 additional quality-adjusted life years and a cost saving of US $46,000 per 100,000 population. All strategies increased the number of thrombolysed patients and the number requiring urgent brain imaging (by 9% to 21% dependent on the scenario). Assuming a willingness-to-pay of US $30,000 per quality-adjusted life year gained, the potential budget available to deliver the interventions in each strategy ranged from US $50,000 to US $144,000. These results suggest that any strategy that increases thrombolysis rates will result in cost savings and improved patient quality of life. Healthcare commissioners could consider this model when planning improvements in stroke care.

  5. Acute and long-term effects of cannabis use: a review.

    PubMed

    Karila, Laurent; Roux, Perrine; Rolland, Benjamin; Benyamina, Amine; Reynaud, Michel; Aubin, Henri-Jean; Lançon, Christophe

    2014-01-01

    Cannabis remains the most commonly used and trafficked illicit drug in the world. Its use is largely concentrated among young people (15- to 34-year-olds). There is a variety of cannabis use patterns, ranging from experimental use to dependent use. Men are more likely than women to report both early initiation and frequent use of cannabis. Due to the high prevalence of cannabis use, the impact of cannabis on public health may be significant. A range of acute and chronic health problems associated with cannabis use has been identified. Cannabis can frequently have negative effects in its users, which may be amplified by certain demographic and/or psychosocial factors. Acute adverse effects include hyperemesis syndrome, impaired coordination and performance, anxiety, suicidal ideations/tendencies, and psychotic symptoms. Acute cannabis consumption is also associated with an increased risk of motor vehicle crashes, especially fatal collisions. Evidence indicates that frequent and prolonged use of cannabis can be detrimental to both mental and physical health. Chronic effects of cannabis use include mood disorders, exacerbation of psychotic disorders in vulnerable people, cannabis use disorders, withdrawal syndrome, neurocognitive impairments, cardiovascular and respiratory and other diseases.

  6. The effect of vitamin E on acute skin reaction caused by radiotherapy.

    PubMed

    Dirier, A; Akmansu, M; Bora, H; Gurer, M

    2007-09-01

    Ionizing radiation affects healthy organs and tissues as well as diseased tissues during radiation therapy. Skin reactions varying from acute erythema to necrosis can be seen. It has been found that vitamin E can prevent mutagenic and/or carcinogenic effects of ionizing radiation in both animals and cell cultures. This study investigated the preventative effect of antioxidant vitamin E on irradiation-induced acute skin reactions. No protective effect of vitamin E was demonstrated. It is possible that the vehicle induced free radical exposure in the irradiated skin.

  7. The in vivo regulation of heart rate in the murine sinoatrial node by stimulatory and inhibitory heterotrimeric G proteins

    PubMed Central

    Sebastian, Sonia; Ang, Richard; Abramowitz, Joel; Weinstein, Lee S.; Chen, Min; Ludwig, Andreas; Birnbaumer, Lutz

    2013-01-01

    Reciprocal physiological modulation of heart rate is controlled by the sympathetic and parasympathetic systems acting on the sinoatrial (SA) node. However, there is little direct in vivo work examining the role of stimulatory and inhibitory G protein signaling in the SA node. Thus, we designed a study to examine the role of the stimulatory (Gαs) and inhibitory G protein (Gαi2) in in vivo heart rate regulation in the SA node in the mouse. We studied mice with conditional deletion of Gαs and Gαi2 in the conduction system using cre-loxP technology. We crossed mice in which cre recombinase expression was driven by a tamoxifen-inducible conduction system-specific construct with “Gαs floxed” and “Gαi2 floxed” mice. We studied the heart rate responses of adult mice compared with littermate controls by using radiotelemetry before and after administration of tamoxifen. The mice with conditional deletion of Gαs and Gαi2 had a loss of diurnal variation and were bradycardic or tachycardic, respectively, in the daytime. In mice with conditional deletion of Gαs, there was a selective loss of low-frequency power, while with deletion of Gαi2, there was a loss of high-frequency power in power spectral analysis of heart rate variability. There was no evidence of pathological arrhythmia. Pharmacological modulation of heart rate by isoprenaline was impaired in the Gαs mice, but a muscarinic agonist was still able to slow the heart rate in Gαi2 mice. We conclude that Gαs- and Gαi2-mediated signaling in the sinoatrial node is important in the reciprocal regulation of heart rate through the autonomic nervous system. PMID:23697798

  8. The in vivo regulation of heart rate in the murine sinoatrial node by stimulatory and inhibitory heterotrimeric G proteins.

    PubMed

    Sebastian, Sonia; Ang, Richard; Abramowitz, Joel; Weinstein, Lee S; Chen, Min; Ludwig, Andreas; Birnbaumer, Lutz; Tinker, Andrew

    2013-08-15

    Reciprocal physiological modulation of heart rate is controlled by the sympathetic and parasympathetic systems acting on the sinoatrial (SA) node. However, there is little direct in vivo work examining the role of stimulatory and inhibitory G protein signaling in the SA node. Thus, we designed a study to examine the role of the stimulatory (Gαs) and inhibitory G protein (Gαi2) in in vivo heart rate regulation in the SA node in the mouse. We studied mice with conditional deletion of Gαs and Gαi2 in the conduction system using cre-loxP technology. We crossed mice in which cre recombinase expression was driven by a tamoxifen-inducible conduction system-specific construct with "Gαs floxed" and "Gαi2 floxed" mice. We studied the heart rate responses of adult mice compared with littermate controls by using radiotelemetry before and after administration of tamoxifen. The mice with conditional deletion of Gαs and Gαi2 had a loss of diurnal variation and were bradycardic or tachycardic, respectively, in the daytime. In mice with conditional deletion of Gαs, there was a selective loss of low-frequency power, while with deletion of Gαi2, there was a loss of high-frequency power in power spectral analysis of heart rate variability. There was no evidence of pathological arrhythmia. Pharmacological modulation of heart rate by isoprenaline was impaired in the Gαs mice, but a muscarinic agonist was still able to slow the heart rate in Gαi2 mice. We conclude that Gαs- and Gαi2-mediated signaling in the sinoatrial node is important in the reciprocal regulation of heart rate through the autonomic nervous system.

  9. Consensus definitions of 14 severe acute toxic effects for childhood lymphoblastic leukaemia treatment: a Delphi consensus.

    PubMed

    Schmiegelow, Kjeld; Attarbaschi, Andishe; Barzilai, Shlomit; Escherich, Gabriele; Frandsen, Thomas Leth; Halsey, Christina; Hough, Rachael; Jeha, Sima; Kato, Motohiro; Liang, Der-Cherng; Mikkelsen, Torben Stamm; Möricke, Anja; Niinimäki, Riitta; Piette, Caroline; Putti, Maria Caterina; Raetz, Elizabeth; Silverman, Lewis B; Skinner, Roderick; Tuckuviene, Ruta; van der Sluis, Inge; Zapotocka, Ester

    2016-06-01

    Although there are high survival rates for children with acute lymphoblastic leukaemia, their outcome is often counterbalanced by the burden of toxic effects. This is because reported frequencies vary widely across studies, partly because of diverse definitions of toxic effects. Using the Delphi method, 15 international childhood acute lymphoblastic leukaemia study groups assessed acute lymphoblastic leukaemia protocols to address toxic effects that were to be considered by the Ponte di Legno working group. 14 acute toxic effects (hypersensitivity to asparaginase, hyperlipidaemia, osteonecrosis, asparaginase-associated pancreatitis, arterial hypertension, posterior reversible encephalopathy syndrome, seizures, depressed level of consciousness, methotrexate-related stroke-like syndrome, peripheral neuropathy, high-dose methotrexate-related nephrotoxicity, sinusoidal obstructive syndrome, thromboembolism, and Pneumocystis jirovecii pneumonia) that are serious but too rare to be addressed comprehensively within any single group, or are deemed to need consensus definitions for reliable incidence comparisons, were selected for assessment. Our results showed that none of the protocols addressed all 14 toxic effects, that no two protocols shared identical definitions of all toxic effects, and that no toxic effect definition was shared by all protocols. Using the Delphi method over three face-to-face plenary meetings, consensus definitions were obtained for all 14 toxic effects. In the overall assessment of outcome of acute lymphoblastic leukaemia treatment, these expert opinion-based definitions will allow reliable comparisons of frequencies and severities of acute toxic effects across treatment protocols, and facilitate international research on cause, guidelines for treatment adaptation, preventive strategies, and development of consensus algorithms for reporting on acute lymphoblastic leukaemia treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Effect of acute acoustic stress on anorectal function sensation in healthy human.

    PubMed

    Gonlachanvit, S; Rhee, J; Sun, W M; Chey, W D

    2005-04-01

    Little is known about the effects of acute acoustic stress on anorectal function. To determine the effects of acute acoustic stress on anorectal function and sensation in healthy volunteers. Ten healthy volunteers (7 M, 3 F, mean age 34 +/- 3 years) underwent anorectal manometry, testing of rectal compliance and sensation using a barostat with and without acute noise stress on separate days. Rectal perception was assessed using an ascending method of limits protocol and a 5-point Likert scale. Arousal and anxiety status were evaluated using a visual analogue scale. Acoustic stress significantly increased anxiety score (P < 0.05). Rectal compliance was significantly decreased with acoustic stress compared with control P (P < 0.000001). In addition, less intraballoon volume was needed to induce the sensation of severe urgency with acoustic stress (P < 0.05). Acoustic stress had no effect on hemodynamic parameters, anal sphincter pressure, threshold for first sensation, sensation of stool, or pain. Acute acoustic stimulation increased anxiety scores, decreased rectal compliance, and enhanced perception of severe urgency to balloon distention but did not affect anal sphincter pressure in healthy volunteers. These results may offer insight into the pathogenesis of stress-in-induced diarrhoea and faecal urgency.

  11. 21 CFR 320.28 - Correlation of bioavailability with an acute pharmacological effect or clinical evidence.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... pharmacological effect or clinical evidence. 320.28 Section 320.28 Food and Drugs FOOD AND DRUG ADMINISTRATION... Correlation of bioavailability with an acute pharmacological effect or clinical evidence. Correlation of in vivo bioavailability data with an acute pharmacological effect or clinical evidence of safety and...

  12. Effect of aphasia on acute stroke outcomes

    PubMed Central

    Boehme, Amelia K.; Martin-Schild, Sheryl; Marshall, Randolph S.

    2016-01-01

    Objective: To determine the independent effects of aphasia on outcomes during acute stroke admission, controlling for total NIH Stroke Scale (NIHSS) scores and loss of consciousness. Methods: Data from the Tulane Stroke Registry were used from July 2008 to December 2014 for patient demographics, NIHSS scores, length of stay (LOS), complications (sepsis, deep vein thrombosis), and discharge modified Rankin Scale (mRS) score. Aphasia was defined as a score >1 on question 9 on the NIHSS on admission and hemiparesis as >1 on questions 5 or 6. Results: Among 1,847 patients, 866 (46%) had aphasia on admission. Adjusting for NIHSS score and inpatient complications, those with aphasia had a 1.22 day longer LOS than those without aphasia, whereas those with hemiparesis (n = 1,225) did not have any increased LOS compared to those without hemiparesis. Those with aphasia had greater odds of having a complication (odds ratio [OR] 1.44, confidence interval [CI] 1.07–1.93, p = 0.0174) than those without aphasia, which was equivalent to those having hemiparesis (OR 1.47, CI 1.09–1.99, p = 0.0137). Controlling for NIHSS scores, aphasia patients had higher odds of discharge mRS 3–6 (OR 1.42 vs 1.15). Conclusion: Aphasia is independently associated with increased LOS and complications during the acute stroke admission, adding $2.16 billion annually to US acute stroke care. The presence of aphasia was more likely to produce a poor functional outcome than hemiparesis. These data suggest that further research is necessary to determine whether establishing adaptive communication skills can mitigate its consequences in the acute stroke setting. PMID:27765864

  13. Effect of aphasia on acute stroke outcomes.

    PubMed

    Boehme, Amelia K; Martin-Schild, Sheryl; Marshall, Randolph S; Lazar, Ronald M

    2016-11-29

    To determine the independent effects of aphasia on outcomes during acute stroke admission, controlling for total NIH Stroke Scale (NIHSS) scores and loss of consciousness. Data from the Tulane Stroke Registry were used from July 2008 to December 2014 for patient demographics, NIHSS scores, length of stay (LOS), complications (sepsis, deep vein thrombosis), and discharge modified Rankin Scale (mRS) score. Aphasia was defined as a score >1 on question 9 on the NIHSS on admission and hemiparesis as >1 on questions 5 or 6. Among 1,847 patients, 866 (46%) had aphasia on admission. Adjusting for NIHSS score and inpatient complications, those with aphasia had a 1.22 day longer LOS than those without aphasia, whereas those with hemiparesis (n = 1,225) did not have any increased LOS compared to those without hemiparesis. Those with aphasia had greater odds of having a complication (odds ratio [OR] 1.44, confidence interval [CI] 1.07-1.93, p = 0.0174) than those without aphasia, which was equivalent to those having hemiparesis (OR 1.47, CI 1.09-1.99, p = 0.0137). Controlling for NIHSS scores, aphasia patients had higher odds of discharge mRS 3-6 (OR 1.42 vs 1.15). Aphasia is independently associated with increased LOS and complications during the acute stroke admission, adding $2.16 billion annually to US acute stroke care. The presence of aphasia was more likely to produce a poor functional outcome than hemiparesis. These data suggest that further research is necessary to determine whether establishing adaptive communication skills can mitigate its consequences in the acute stroke setting. © 2016 American Academy of Neurology.

  14. Effectiveness of Acute Geriatric Unit Care Using Acute Care for Elders Components: A Systematic Review and Meta-Analysis

    PubMed Central

    Fox, Mary T; Persaud, Malini; Maimets, Ilo; O'Brien, Kelly; Brooks, Dina; Tregunno, Deborah; Schraa, Ellen

    2012-01-01

    Objectives To compare the effectiveness of acute geriatric unit care, based on all or part of the Acute Care for Elders (ACE) model and introduced in the acute phase of illness or injury, with that of usual care. Design Systematic review and meta-analysis of 13 randomized controlled and quasi-experimental trials with parallel comparison groups retrieved from multiple sources. Setting Acute care geriatric and nongeriatric hospital units. Participants Acutely ill or injured adults (N = 6,839) with an average age of 81. Interventions Acute geriatric unit care characterized by one or more ACE components: patient-centered care, frequent medical review, early rehabilitation, early discharge planning, prepared environment. Measurements Falls, pressure ulcers, delirium, functional decline at discharge from baseline 2-week prehospital and hospital admission statuses, length of hospital stay, discharge destination (home or nursing home), mortality, costs, and hospital readmissions. Results Acute geriatric unit care was associated with fewer falls (risk ratio (RR) = 0.51, 95% confidence interval (CI) = 0.29–0.88), less delirium (RR = 0.73, 95% CI = 0.61–0.88), less functional decline at discharge from baseline 2-week prehospital admission status (RR = 0.87, 95% CI = 0.78–0.97), shorter length of hospital stay (weighted mean difference (WMD) = −0.61, 95% CI = −1.16 to −0.05), fewer discharges to a nursing home (RR = 0.82, 95% CI = 0.68–0.99), lower costs (WMD = −$245.80, 95% CI = −$446.23 to −$45.38), and more discharges to home (RR = 1.05, 95% CI = 1.01–1.10). A nonsignificant trend toward fewer pressure ulcers was observed. No differences were found in functional decline between baseline hospital admission status and discharge, mortality, or hospital readmissions. Conclusion Acute geriatric unit care, based on all or part of the ACE model and introduced during the acute phase of older adults' illness or injury, improves patient- and system

  15. Acute Ischemia Induced by High-Density Culture Increases Cytokine Expression and Diminishes the Function and Viability of Highly Purified Human Islets of Langerhans.

    PubMed

    Smith, Kate E; Kelly, Amy C; Min, Catherine G; Weber, Craig S; McCarthy, Fiona M; Steyn, Leah V; Badarinarayana, Vasudeo; Stanton, J Brett; Kitzmann, Jennifer P; Strop, Peter; Gruessner, Angelika C; Lynch, Ronald M; Limesand, Sean W; Papas, Klearchos K

    2017-11-01

    Encapsulation devices have the potential to enable cell-based insulin replacement therapies (such as human islet or stem cell-derived β cell transplantation) without immunosuppression. However, reasonably sized encapsulation devices promote ischemia due to high β cell densities creating prohibitively large diffusional distances for nutrients. It is hypothesized that even acute ischemic exposure will compromise the therapeutic potential of cell-based insulin replacement. In this study, the acute effects of high-density ischemia were investigated in human islets to develop a detailed profile of early ischemia induced changes and targets for intervention. Human islets were exposed in a pairwise model simulating high-density encapsulation to normoxic or ischemic culture for 12 hours, after which viability and function were measured. RNA sequencing was conducted to assess transcriptome-wide changes in gene expression. Islet viability after acute ischemic exposure was reduced compared to normoxic culture conditions (P < 0.01). Insulin secretion was also diminished, with ischemic β cells losing their insulin secretory response to stimulatory glucose levels (P < 0.01). RNA sequencing revealed 657 differentially expressed genes following ischemia, with many that are associated with increased inflammatory and hypoxia-response signaling and decreased nutrient transport and metabolism. In order for cell-based insulin replacement to be applied as a treatment for type 1 diabetes, oxygen and nutrient delivery to β cells will need to be maintained. We demonstrate that even brief ischemic exposure such as would be experienced in encapsulation devices damages islet viability and β cell function and leads to increased inflammatory signaling.

  16. Antibodies to B7.1 define the GFCC'C" face of the N-terminal domain as critical for co-stimulatory interactions.

    PubMed

    Wang, Suyue; Veldman, Geertruida M; Stahl, Mark; Xing, Yuzhe; Tobin, James F; Erbe, David V

    2002-09-02

    Antagonists of the B7 family of co-stimulatory molecules have the potential for altering immune responses therapeutically. To better define the requirements for such inhibitors, we have mapped the binding of an entire panel of blocking antibodies specific for human B7.1. By mutagenesis, each of the residues critical for blocking antibody binding appeared to fall entirely within the N-terminal V-set domain of B7.1. Thus, although antibody-antigen interacting surfaces can be quite large, these results indicate that a relatively small portion of the GFCC'C" face of this domain is crucial for further antagonist development.

  17. Acute Alcohol Intoxication: Differences in School Levels and Effects on Educational Performance

    ERIC Educational Resources Information Center

    Van Hoof, Joris J.; Klerk, Frouktje Ade; Van der Lely, Nicolaas

    2018-01-01

    This study examines the effects of acute alcohol intoxication on adolescents' school performance. In the 2007-2015 period, 3,317 adolescents (ages 12 to 17 years) were treated for acute alcohol intoxication, and 37 adolescents were admitted to the hospital twice. Alcohol intoxication has an overrepresentation in "low" school levels. The…

  18. Side effects induced by the acute levodopa challenge in Parkinson's Disease and atypical parkinsonisms.

    PubMed

    Vasta, Rosario; Nicoletti, Alessandra; Mostile, Giovanni; Dibilio, Valeria; Sciacca, Giorgia; Contrafatto, Donatella; Cicero, Calogero Edoardo; Raciti, Loredana; Luca, Antonina; Zappia, Mario

    2017-01-01

    Acute levodopa challenge may be performed to predict levodopa chronic responsiveness. The aim of the study was to investigate frequency of side effects during the acute levodopa challenge in PD and atypical parkinsonisms. We enrolled 34 de novo PD patients and 29 patients affected by atypical parkinsonisms (Multiple System Atrophy, MSA, n = 10; Progressive Supranuclear Palsy, PSP, n = 12 and Corticobasal Degeneration, CBD, n = 7) who underwent an acute levodopa challenge. Side effects occurring during test were recorded. Side effects were more frequent among atypical parkinsonisms as unique group when compared to PD patients (64.3% versus 23.5%; p-value 0.002) with an adjusted OR of 4.36 (95%CI 1.40-13.5). Each atypical parkinsonisms showed almost double occurrence of side effects (MSA 90%, PSP 41.7% and CBD 57%). Side effects during acute levodopa challenge may be frequent in atypical parkinsonisms. This information could be useful in order to better prepare the patient for the test. Furthermore, it could represent a useful cue in differential diagnosis with PD.

  19. An Investigation of the Interaction Effects of Acute Self-Esteem and Perceived Competence on Conformity.

    DTIC Science & Technology

    1978-12-22

    a demonstration of the interaction effects of acute self - esteem and perceived competence. Acute self - esteem manipulations (high, low or no) were...On the basis of previous research on conformity it was predicted that subjects who were subjected to acute self - esteem manipulations and perceived...role in conformity. The main effect of self - esteem and the interaction of self - esteem and perceived competence did not prove significant. Results were

  20. Simultaneous and Dose Dependent Melanoma Cytotoxic and Immune Stimulatory Activity of Betulin

    PubMed Central

    Arlt, Olga; Neske, Christina; Dehelean, Cristina; Pfeilschifter, Josef M.; Radeke, Heinfried H.

    2015-01-01

    Conventional cytostatic cancer treatments rarely result in the complete eradication of tumor cells. Therefore, new therapeutic strategies focus on antagonizing the immunosuppressive activity of established tumors. In particular, recent studies of antigen-loaded dendritic cells (DCs) eliciting a specific antitumor immune response has raised the hopes of achieving the complete elimination of tumor tissue. Genistein, fingolimod and betulin have already been described as active compounds in different types of cancer. Herein, we applied an integrated screening approach to characterize both their cytostatic and their immune-modulating properties side-by-side. As will be described in detail, our data confirmed that all three compounds exerted proapoptotic and antiproliferative activity in different B16 melanoma cell lines to a given extent, as revealed by an MTT assay, CFSE and DAPI staining. However, while genistein and fingolimod also affected the survival of primary bone marrow (BM) derived DCs of C57BL/6 mice, betulin exhibited a lower cytotoxicity for BMDCs in comparison to the melanoma cells. Moreover, we could show for the first time, that only betulin caused a simultaneous, highly specific immune-stimulating activity, as measured by the IL-12p70 release of Toll-like receptor 4-stimulated BMDCs by ELISA, which was due to increased IL-12p35 mRNA expression. Interestingly, the activation of DCs resulted in enhanced T lymphocyte stimulation, indicated by increased IL-2 and IFN-γ production of cytotoxic T cells in spleen cell co-culture assays which led to a decreased viability of B16 cells in an antigen specific model system. This may overcome the immunosuppressive environment of a tumor and destroy tumor cells more effectively in vivo if the immune response is specific targeted against the tumor tissue by antigen-loaded dendritic cells. In summary, cytostatic agents, such as betulin, that simultaneously exhibit immune stimulatory activity may serve as lead compounds

  1. Acute Effects of Cannabis on Breath-Holding Duration

    PubMed Central

    Farris, Samantha G.; Metrik, Jane

    2016-01-01

    Distress intolerance (an individual’s perceived or actual inability to tolerate distressing psychological or physiological states) is associated with cannabis use. It is unknown whether a bio-behavioral index of distress intolerance, breath-holding duration, is acutely influenced (increased or decreased) by cannabis. Such information may further inform understanding of the expression of psychological or physiological distress post-cannabis use. This within-subjects study examined whether smoked marijuana with 2.7–3.0 % delta-9-tetrahydrocannabinol (THC), relative to placebo, acutely changed duration of breath-holding. Participants (n = 88; 65.9% male) were non-treatment seeking frequent cannabis users who smoked placebo or active THC cigarette on two separate study days and completed breath-holding task. Controlling for baseline breath-holding duration and participant sex, THC produced significantly lower breath-holding durations relative to placebo. There was a significant interaction of drug administration x frequency of cannabis use, such that THC decreased breath-holding time among less frequent but not among more frequent users. Findings indicate that cannabis may be exacerbating distress intolerance (via breath-holding duration). As compared to less frequent cannabis users, frequent users display tolerance to cannabis’ acute effects including increased ability to tolerate respiratory distress when holding breath. Objective measures of distress intolerance are sensitive to contextual factors such as acute drug intoxication, and may inform the link between cannabis use and the expression of psychological distress. PMID:27454678

  2. Synergistic anticonvulsant effects of pregabalin and amlodipine on acute seizure model of epilepsy in mice.

    PubMed

    Qureshi, Itefaq Hussain; Riaz, Azra; Khan, Rafeeq Alam; Siddiqui, Afaq Ahmed

    2017-08-01

    Status epilepticus is a life threatening neurological medical emergency. It may cause serious damage to the brain and even death in many cases if not treated properly. There is limited choice of drugs for the short term and long term management of status epilepticus and the dugs recommended for status epilepticus possess various side effects. The present study was designed to investigate synergistic anticonvulsant effects of pregabalin with amlodipine on acute seizure model of epilepsy in mice. Pentylenetetrazole was used to induce acute seizures which mimic status epilepticus. Pregabalin and amlodipine were used in combination to evaluate synergistic anti-seizure effects on acute seizure model of epilepsy in mice. Diazepam and valproate were used as reference dugs. The acute anti-convulsive activity of pregabalin with amlodipine was evaluated in vivo by the chemical induced seizures and their anti-seizure effects were compared with pentylenetetrazole, reference drugs and to their individual effects. The anti-seizure effects of tested drugs were recorded in seconds on seizure characteristics such as latency of onset of threshold seizures, rearing and fallings and Hind limbs tonic extensions. The seizure protection and mortality to the animals exhibited by the drugs were recorded in percentage. Combination regimen of pregabalin with amlodipine exhibited dose dependent significant synergistic anticonvulsant effects on acute seizures which were superior to their individual effects and equivalent to reference drugs.

  3. Cocaine-induced renal disease.

    PubMed

    Gitman, Michael D; Singhal, Pravin C

    2004-09-01

    Cocaine has anaesthetic, vasoconstrictive and CNS stimulatory effects. Presently, it is used clinically as a local anaesthetic and abused as a recreational drug. It has been implicated in both acute and chronic renal failure and has been reported to affect every aspect of the nephron. This article will review the spectrum of cocaine-induced kidney disease and attempt to give insight into the pathophysiological mechanisms involved.

  4. [Acute tonsillopharyngitis: the effectiveness of topical therapy].

    PubMed

    Nosulya, E V; Kim, I A; Chernykh, N M; Karnoukhova, O A

    2015-01-01

    The objective of the present study was to evaluate the clinical effectiveness of a furasol sore throat gargle solution for the treatment of acute tonsillopharyngitis. Forty patients presenting with acute tonsillopharyngitis were allocated to two groups, 20 subjects in each, by means of independent sequential randomization. Prior to the onset of the treatment, all the patients were examined for determining the species composition of pharyngeal microflora with the use of an «AutoScan4 System» analyzer («Siemens», USA) and estimating the resistance to antibacterial preparations (by the disk diffusion method). All the participants of the study were prescribed antibacterial therapy. In the patients of group 1 (study group), the antibacterial treatment of acute tonsillopharyngitis was supplemented by a furasol sore throat gargle solution whereas those of group 2 (controls) were treated without topical therapy. The quantitative evaluation of the severity of manifestations of the disease before and after the treatment was based on a 5-point visual-analog scale. It was shown that systemic antibacterial therapy resulted in the consistent decrease of the frequency of occurrence of pathogenic and potentially pathogenic microflora in the patients comprising both groups. Treatment with a furasol sore throat gargle solution did not lead to the appearance of bacterial species alien to the oropharynx, nor was it accompanied by the impairment of resistance of its mucous membrane to the colonization by microorganisms. The results of the study give evidence of the well apparent regression of the subjective signs of tonsillopharyngitis and the inflammatory changes in the mucous membrane of the pharynx in the patients given the topical treatment in the form of a furasol sore throat gargle solution in addition to antibacterial therapy. It is concluded that a furasol sore throat gargle solution can be recommended for the introduction into the combined treatment of the patients

  5. Strain-dependent Effects of Acute, Chronic, and Withdrawal from Chronic Nicotine on Fear Conditioning

    PubMed Central

    Portugal, George S.; Wilkinson, Derek S.; Kenney, Justin W.; Sullivan, Colleen

    2013-01-01

    The effects of nicotine on cognitive processes such as learning and memory may play an important role in the addictive liability of tobacco. However, it remains unknown whether genetic variability modulates the effects of nicotine on learning and memory. The present study characterized the effects of acute, chronic, and withdrawal from chronic nicotine administration on fear conditioning, somatic signs, and the elevated plus maze in 8 strains of inbred mice. Strain-dependent effects of acute nicotine and nicotine withdrawal on contextual fear conditioning, somatic signs, and the elevated plus maze were observed, but no association between the effects of acute nicotine and nicotine withdrawal on contextual fear conditioning were observed, suggesting that different genetic substrates may mediate these effects. The identification of genetic factors that may alter the effects of nicotine on cognition may lead to more efficacious treatments for nicotine addiction. PMID:21822688

  6. Effects of Erdosteine on Experimental Acute Pancreatitis Model.

    PubMed

    Karapolat, Banu; Karapolat, Sami; Gurleyik, Emin; Yasar, Mehmet

    2017-10-01

    To create acute pancreatitis condition experimentally in rats using cerulein, and to reveal histopathological effects in pancreatic tissue with erdosteine. An experimental study. Department of General Surgery, Duzce University, Turkey, from June to October 2014. Thirty male Wistar albino rats were divided into three groups. No procedures were applied to Group 1. The rats in Group 2 and Group 3 were injected cerulein, to establish an experimental pancreatitis model and the blood amylase and lipase values were examined. The rats in Group 3 were given 10 mg/kg erdosteine. This treatment was continued for another 2 days and the rats were sacrificed. The pancreatic tissues were examined histopathologically for edema, inflammation, acinar necrosis, fat necrosis, and vacuolization. The lipase and amylase values and the histopathological examination of pancreatic tissues evidenced that the experimental acute pancreatitis model was established and edema, inflammation, acinar necrosis, fat necrosis, and vacuolization were observed in the pancreatic tissues. The statistical results suggest that erdosteine can decrease the edema, inflammation, acinar necrosis, fat necrosis and vacuolization scores in the tissues. The severity of acute pancreatitis, induced by cerulein in rats, is reduced with the use of erdosteine.

  7. Increased sensitivity to the acute effects of MDMA ("ecstasy") in female rats.

    PubMed

    Palenicek, T; Votava, M; Bubenikova, V; Horacek, J

    2005-11-15

    Behavioral effects of +/-3,4-methylenedioxymethamphetamine (MDMA, ecstasy) are relatively well described in humans as well as in animals. However, little is known about gender differences to the effects of MDMA. The aim of our study was to evaluate gender differences in stimulant effects of MDMA (2.5, 5.0, and 10.0 mg/kg subcutaneously (s.c.)) in male and female Wistar rats. We have used three behavioral methods (activity cage, open field, and elevated plus-maze) each describing a different pattern of spontaneous behavior. In the activity cage, 30 min after the MDMA administration, horizontal and vertical locomotor activities were registered for a period of 3 min. In the open field test rats were placed into an arena 15 min after drug treatment and locomotor activity was registered for a period of 30 min. Finally, in the elevated plus-maze test, rats were given MDMA 30 min prior to measurements and subsequently they were tested in the maze for a period of 5 min. In our experiments we observed a dose-dependent locomotion-enhancing effect of MDMA both in male and female rats in both locomotor tests. Female rats were more sensitive to the locomotor-stimulating effect than males in both tests, suggesting higher sensitivity to the stimulatory effect of MDMA. Further on, MDMA increased thigmotaxis in female rats in the open field test and decreased "anxious-like" behavior in the elevated plus-maze in both genders. In conclusion, we observed higher sensitivity of females to the locomotor-stimulant effect of MDMA. Increased sensitivity of females to the behavioral effects of MDMA can be explained by increased reactivity of serotonergic and dopaminergic systems.

  8. Prolonged Effects of Acute Stress on Decision-Making under Risk: A Human Psychophysiological Study

    PubMed Central

    Yamakawa, Kaori; Ohira, Hideki; Matsunaga, Masahiro; Isowa, Tokiko

    2016-01-01

    This study investigates the prolonged effects of physiological responses induced by acute stress on risk-taking in decision-making. Participants were divided into a Stress group (N = 14) and a Control group (N = 12). The Trier Social Stress Test was administered as an acute stressor, and reading was administered as a control task; thereafter, participants performed a decision-making task in which they needed to choose a sure option or a gamble option in Gain and Loss frame trials 2 h after (non-) exposure to the stressor. Increased cortisol, adrenaline, heart rate (HR), and subjective stress levels validated acute stress manipulation. Stressed participants made fewer risky choices only in the Gain domain, whereas no effect of stress was shown in the Loss domain. Deceleration of HR reflecting attention was greater for Gains compared with Losses only in the Stress group. Risk avoidance was determined by increased levels of cortisol caused by acute stress. These results suggest that processes regarding glucocorticoid might be involved in the prolonged effects of acute stress on the evaluation of risks and the monitoring of outcomes in decision-making. PMID:27679566

  9. Induced desensitization of the insulinotropic effects of antidiabetic drugs, BTS 67 582 and tolbutamide

    PubMed Central

    McClenaghan, Neville H; Ball, Andrew J; Flatt, Peter R

    2000-01-01

    Acute and chronic mechanisms of action of novel insulinotropic antidiabetic drug, BTS 67 582 (1,1-dimethyl-2-(2-morpholinophenyl)guanidine fumarate), were examined in the stable cultured BRIN-BD11 cell line. BTS 67 582 (100–400 μM) stimulated a concentration-dependent increase (P<0.01) in insulin release at both non-stimulatory (1.1 mM) and stimulatory (8.4 mM) glucose. Long-term exposure (3–18 h) to 100 μM BTS 67 582 in culture time-dependently decreased subsequent responsiveness to acute challenge with 200 μM BTS 67 582 or 200 μM tolbutamide at 12–18 h (P<0.001). Similarly 3–18 h culture with the sulphonylurea, tolbutamide (100 μM), also effectively suppressed subsequent insulinotropic responses to both BTS 67 582 and tolbutamide. Culture with 100 μM BTS 67 582 or 100 μM tolbutamide did not affect basal insulin secretion, cellular insulin content, or cell viability and exerted no influence on the secretory responsiveness to 200 μM of the imidazoline, efaroxan. While 18 h BTS 67 582 culture did not affect the insulin-releasing actions (P<0.001) of 16.7 mM glucose, 10 mM arginine, 30 mM KCl, 25 μM forskolin or 10 nM phorbol-12-myristate 13-acetate (PMA), significant inhibition (P<0.001) of the insulinotropic effects of 10 mM 2-ketoisocaproic acid (KIC) and 10 mM alanine were observed. These data suggest that BTS 67 582 shares a common signalling pathway to sulphonylurea but not imidazoline drugs. Desensitization of drug action may provide an important approach to dissect sites of action of novel and established insulinotropic antidiabetic agents. PMID:10807689

  10. Acute glucocorticoid effects on response inhibition in borderline personality disorder.

    PubMed

    Carvalho Fernando, Silvia; Beblo, Thomas; Schlosser, Nicole; Terfehr, Kirsten; Wolf, Oliver Tobias; Otte, Christian; Löwe, Bernd; Spitzer, Carsten; Driessen, Martin; Wingenfeld, Katja

    2013-11-01

    Growing evidence suggests inhibition dysfunctions in borderline personality disorder (BPD). Moreover, abnormalities in hypothalamic-pituitary-adrenal (HPA) axis functioning have also been found in BPD patients. In healthy individuals, response inhibition has been sensitive to acute stress, and previous research indicates that effects mediated by the HPA axis become particularly apparent when emotional stimuli are processed. This study aimed to explore the influence of acute hydrocortisone administration on response inhibition of emotional stimuli in BPD patients compared to healthy control participants. After a single administration of 10mg hydrocortisone or placebo, 32 female BPD patients and 32 healthy female participants performed an adapted emotional go/no-go paradigm to assess response inhibition for emotional face stimuli in a cross-over study. Acute cortisol elevations decreased the reaction times to target stimuli in both BPD patients and healthy controls. Patients and controls did not differ in task performance; however, BPD patients with comorbid posttraumatic stress disorder (PTSD) displayed longer reaction times than patients without PTSD. In contrast, the occurrence of comorbid eating disorder had no significant impact on go/no-go performance. No significant interaction effect between the treatment condition and the emotional valence of the face stimuli was found. Acute hydrocortisone administration enhances response inhibition of face stimuli in BPD patients and healthy controls, regardless of their emotional valence. Our results agree with the suggestion that moderate cortisol enhancement increases the inhibition of task-irrelevant distracters. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Effects of Acute Exercise on Long-Term Memory

    ERIC Educational Resources Information Center

    Labban, Jeffrey D.; Etnier, Jennifer L.

    2011-01-01

    In this study, we tested the effect of acute exercise on long-term memory, specifically the timing of exercise relative to the memory challenge. We assessed memory via paragraph recall, in which participants listened to two paragraphs (exposure) and recounted them following a 35-min delay. Participants (n = 48) were randomly assigned to one of…

  12. Effect of Antiepileptic Drugs for Acute and Chronic Seizures in Children with Encephalitis.

    PubMed

    Lin, Kuang-Lin; Lin, Jainn-Jim; Hsia, Shao-Hsuan; Chou, Min-Liang; Hung, Po-Cheng; Wang, Huei-Shyong

    2015-01-01

    Encephalitis presents with seizures in the acute phase and increases the risk of late unprovoked seizures and epilepsy. This study aimed to evaluate the effect of antiepileptic drugs in pediatric patients with acute seizures due to encephalitis and epilepsy. Cases of acute pediatric encephalitis between January 2000 and December 2010 were reviewed. Clinical data, including onset at age, seizure type, seizure frequency, effects of antiepileptic drugs, and prognosis were analyzed. During the study period, 1038 patients (450 girls, 588 boys) were enrolled. Among them, 44.6% (463) had seizures in the acute phase, 33% had status epilepticus, and 26% (251) developed postencephalitic epilepsy. At one year of follow-up, 205 of the 251 patients with postencephalitic epilepsy were receiving antiepileptic drugs while 18% were seizure free even after discontinuing the antiepileptic drugs. Among those with postencephalitic epilepsy, 67% had favorable outcomes and were using <2 anti-epileptic drugs while 15% had intractable seizures and were using ≥ 2 antiepileptic drugs. After benzodiazepines, intravenous phenobarbital was preferred over phenytoin as treatment of postencephalitic seizures in the acute phase. For refractory status epilepticus, high-dose topiramate combined with intravenous high-dose phenobarbital or high-dose lidocaine had less side effects. Children with encephalitis have a high rate of postencephalitic epilepsy. Phenobarbital and clonazepam are the most common drugs used, alone or in combination, for postencephalitic epilepsy.

  13. Acute Stressor Effects on Goal-Directed Action in Rats

    ERIC Educational Resources Information Center

    Braun, Stephanie; Hauber, Wolfgang

    2013-01-01

    Here we examined effects of acute stressors that involve either systemic coadministration of corticosterone/yohimbine (3 mg/kg each) to increase glucocorticoid/noradrenaline activity (denoted as "pharmacological" stressor) or one or several distinct restraint stressors (denoted as "single" vs. "multiple" stressor) on…

  14. Regulation of 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase expression and activity in the hypophysectomized rat ovary: Interactions between the stimulatory effect of human chorionic gonadotropin and the luteolytic effect of prolactin

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Martel, C.; Labrie, C.; Dupont, E.

    1990-12-01

    The enzyme 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD) catalyzes an obligatory step in the conversion of pregnenolone and other 5-ene-3 beta-hydroxysteroids into progesterone as well as precursors of all androgens and estrogens in the ovary. Since 3 beta-HSD is likely to be an important target for regulation by pituitary hormones, we have studied the effect of chronic treatment with LH (hCG), FSH, and PRL on ovarian 3 beta-HSD expression and activity in hypophysectomized adult female rats. Human CG (hCG) (10 IU, twice a day (bid)), ovine FSH (0.5 microgram, bid), and ovine PRL (1 mg, bid) were administered,more » singly or in combination, for a period of 10 days starting 15 days after hypophysectomy. In hypophysectomized rats, PRL exerted a potent inhibitory effect on all the parameters studied. In fact, PRL caused a 81% decrease in ovarian 3 beta-HSD mRNA content accompanied by a similar decrease in 3 beta-HSD activity and protein levels. In addition, ovarian weight decreased by 40% whereas serum progesterone fell dramatically from 1.92 nmol/liter to undetectable levels after treatment with PRL. Whereas hCG alone had only slight stimulatory effects on 3 beta-HSD mRNA, protein content and activity levels, treatment with the gonadotropin partially or completely reversed the potent inhibitory effects of oPRL on all the parameters measured. FSH, on the other hand, had no significant effect on 3 beta-HSD expression and activity. In situ hybridization experiments using the 35S-labeled rat ovary 3 beta-HSD cDNA probe show that the inhibitory effect of PRL is exerted primarily on luteal cell 3 beta-HSD expression and activity. On the other hand, it can be seen that hCG stimulates 3 beta-HSD mRNA accumulation in interstitial cells.« less

  15. Acute Effects of Ecstasy on Memory Are more Extensive than Chronic Effects

    PubMed Central

    Shariati, Mohamad Bakhtiar Hesam; Sohrabi, Maryam; Shahidi, Siamak; Nikkhah, Ali; Mirzaei, Fatemeh; Medizadeh, Mehdi; Asl, Sara Soleimani

    2014-01-01

    Introduction Exposure to 3, 4- methylenedioxymethamphetamine (MDMA) could lead to serotonergic system toxicity in the brain. This system is responsible for learning and memory functions. Studies show that MDMA causes memory impairment dose-dependently and acutely. The present study was designed to evaluate the chronic and acute effects of MDMD on spatial memory and acquisition of passive avoidance. Methods Adult male Wistar rats (200-250 g) were given single or multiple injections of MDMA (10 mg/kg, IP). Using passive avoidance and Morris Water Maze (MWM) tasks, learning and spatial memory functions were assessed. The data were analyzed by SPSS 16 software and one- way analysis of variance (ANOVA) test. Results Our results showed that there were significant differences in latency to enter the dark compartment (STL) between sham and MDMA- treated groups. Acute group significantly showed more STL in comparison with chronic group. Furthermore, MDMA groups spent more time in dark compartment (TDS) than the sham group. Administration of single dose of MDMA significantly caused an increase in TDS compared with the chronic group. In the MWM, MDMA treatment significantly increased the traveled distance and escaped latency compared to the sham group. Like to passive avoidance task, percentage of time spent in the target quadrant in MDMA- treated animals impaired in MWM compared with sham group. Discussion These data suggest that MDMA treatment impairs learning and memory functions that are more extensive in acute- treated rats. PMID:25337384

  16. Acute Effects of Ecstasy on Memory Are more Extensive than Chronic Effects.

    PubMed

    Shariati, Mohamad Bakhtiar Hesam; Sohrabi, Maryam; Shahidi, Siamak; Nikkhah, Ali; Mirzaei, Fatemeh; Medizadeh, Mehdi; Asl, Sara Soleimani

    2014-01-01

    Exposure to 3, 4- methylenedioxymethamphetamine (MDMA) could lead to serotonergic system toxicity in the brain. This system is responsible for learning and memory functions. Studies show that MDMA causes memory impairment dose-dependently and acutely. The present study was designed to evaluate the chronic and acute effects of MDMD on spatial memory and acquisition of passive avoidance. Adult male Wistar rats (200-250 g) were given single or multiple injections of MDMA (10 mg/kg, IP). Using passive avoidance and Morris Water Maze (MWM) tasks, learning and spatial memory functions were assessed. The data were analyzed by SPSS 16 software and one- way analysis of variance (ANOVA) test. Our results showed that there were significant differences in latency to enter the dark compartment (STL) between sham and MDMA- treated groups. Acute group significantly showed more STL in comparison with chronic group. Furthermore, MDMA groups spent more time in dark compartment (TDS) than the sham group. Administration of single dose of MDMA significantly caused an increase in TDS compared with the chronic group. In the MWM, MDMA treatment significantly increased the traveled distance and escaped latency compared to the sham group. Like to passive avoidance task, percentage of time spent in the target quadrant in MDMA- treated animals impaired in MWM compared with sham group. These data suggest that MDMA treatment impairs learning and memory functions that are more extensive in acute- treated rats.

  17. 21 CFR 320.28 - Correlation of bioavailability with an acute pharmacological effect or clinical evidence.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Correlation of bioavailability with an acute pharmacological effect or clinical evidence. 320.28 Section 320.28 Food and Drugs FOOD AND DRUG ADMINISTRATION... Correlation of bioavailability with an acute pharmacological effect or clinical evidence. Correlation of in...

  18. Effects of acute and chronic psychological stress on platelet aggregation in mice.

    PubMed

    Matsuhisa, Fumikazu; Kitamura, Nobuo; Satoh, Eiki

    2014-03-01

    Although psychological stress has long been known to alter cardiovascular function, there have been few studies on the effect of psychological stress on platelets, which play a pivotal role in cardiovascular disease. In the present study, we investigated the effects of acute and chronic psychological stress on the aggregation of platelets and platelet cytosolic free calcium concentration ([Ca(2+)]i). Mice were subjected to both transportation stress (exposure to novel environment, psychological stress) and restraint stress (psychological stress) for 2 h (acute stress) or 3 weeks (2 h/day) (chronic stress). In addition, adrenalectomized mice were subjected to similar chronic stress (both transportation and restraint stress for 3 weeks). The aggregation of platelets from mice and [Ca(2+)]i was determined by light transmission assay and fura-2 fluorescence assay, respectively. Although acute stress had no effect on agonist-induced platelet aggregation, chronic stress enhanced the ability of the platelet agonists thrombin and ADP to stimulate platelet aggregation. However, chronic stress failed to enhance agonist-induced increase in [Ca(2+)]i. Adrenalectomy blocked chronic stress-induced enhancement of platelet aggregation. These results suggest that chronic, but not acute, psychological stress enhances agonist-stimulated platelet aggregation independently of [Ca(2+)]i increase, and the enhancement may be mediated by stress hormones secreted from the adrenal glands.

  19. Acute and Chronic Effects of Cannabinoids on Human Cognition-A Systematic Review.

    PubMed

    Broyd, Samantha J; van Hell, Hendrika H; Beale, Camilla; Yücel, Murat; Solowij, Nadia

    2016-04-01

    Cannabis use has been associated with impaired cognition during acute intoxication as well as in the unintoxicated state in long-term users. However, the evidence has been mixed and contested, and no systematic reviews of the literature on neuropsychological task-based measures of cognition have been conducted in an attempt to synthesize the findings. We systematically review the empirical research published in the past decade (from January 2004 to February 2015) on acute and chronic effects of cannabis and cannabinoids and on persistence or recovery after abstinence. We summarize the findings into the major categories of the cognitive domains investigated, considering sample characteristics and associations with various cannabis use parameters. Verbal learning and memory and attention are most consistently impaired by acute and chronic exposure to cannabis. Psychomotor function is most affected during acute intoxication, with some evidence for persistence in chronic users and after cessation of use. Impaired verbal memory, attention, and some executive functions may persist after prolonged abstinence, but persistence or recovery across all cognitive domains remains underresearched. Associations between poorer performance and a range of cannabis use parameters, including a younger age of onset, are frequently reported. Little further evidence has emerged for the development of tolerance to the acutely impairing effects of cannabis. Evidence for potential protection from harmful effects by cannabidiol continues to increase but is not definitive. In light of increasing trends toward legalization of cannabis, the knowledge gained from this body of research needs to be incorporated into strategies to minimize harm. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  20. Effect of formoterol/budesonide combination on arterial blood gases in patients with acute exacerbation of COPD.

    PubMed

    Cazzola, M; Noschese, P; De Michele, F; D'Amato, G; Matera, M G

    2006-02-01

    Patients with severe chronic airway obstruction might suffer dangerous hypoxemia after administration of a beta-agonist despite bronchodilation. We first compared the acute effects on gas exchange of two doses of formoterol Turbuhaler (9 and 18 microg) in 10 patients with acute exacerbation of COPD. Afterwards, we compared the acute effects of formoterol Turbuhaler 9 microug with those of formoterol/budesonide combination in a single inhaler (Turbuhaler) 9/320 microg in 10 other patients with acute exacerbation of COPD. Finally, we compared the changes in PaO(2) induced by formoterol Turbuhaler 9 microg or formoterol/budesonide combination in a single inhaler (Turbuhaler) 9/320 microg with those in FEV(1) in 10 other patients with acute exacerbation of COPD. Each agent was given on separate days, and the patients' arterial blood gases were measured at baseline and at intervals of 120 min. Small but statistically significant declines in PaO(2) were found after administration of both formoterol 9 and 18 microg. In the second group of patients, formoterol 9 microg alone again induced a significant decrease in PaO(2). However, the simultaneous administration of budesonide 320 microg significantly reduced the acute effect of formoterol on PaO(2). In a third group of 10 patients we confirmed a small but significant decrease in PaO(2) after formoterol alone and the reduction of this effect when budesonide was administered simultaneously. Moreover, we also documented that addition of budesonide amplified the fast onset of action of formoterol. These results suggest that when treating patients suffering from acute exacerbation of COPD with formoterol, it is prudent to check their arterial blood gases. In any case, combined administration of formoterol and budesonide reduces the potential for acute effects of formoterol on blood-gas tensions.

  1. Effect of Antiepileptic Drugs for Acute and Chronic Seizures in Children with Encephalitis

    PubMed Central

    Lin, Kuang-Lin; Lin, Jainn-Jim; Hsia, Shao-Hsuan; Chou, Min-Liang; Hung, Po-Cheng; Wang, Huei-Shyong

    2015-01-01

    Background Encephalitis presents with seizures in the acute phase and increases the risk of late unprovoked seizures and epilepsy. This study aimed to evaluate the effect of antiepileptic drugs in pediatric patients with acute seizures due to encephalitis and epilepsy. Patients and Methods Cases of acute pediatric encephalitis between January 2000 and December 2010 were reviewed. Clinical data, including onset at age, seizure type, seizure frequency, effects of antiepileptic drugs, and prognosis were analyzed. Results During the study period, 1038 patients (450 girls, 588 boys) were enrolled. Among them, 44.6% (463) had seizures in the acute phase, 33% had status epilepticus, and 26% (251) developed postencephalitic epilepsy. At one year of follow-up, 205 of the 251 patients with postencephalitic epilepsy were receiving antiepileptic drugs while 18% were seizure free even after discontinuing the antiepileptic drugs. Among those with postencephalitic epilepsy, 67% had favorable outcomes and were using <2 anti-epileptic drugs while 15% had intractable seizures and were using ≥ 2 antiepileptic drugs. After benzodiazepines, intravenous phenobarbital was preferred over phenytoin as treatment of postencephalitic seizures in the acute phase. For refractory status epilepticus, high-dose topiramate combined with intravenous high-dose phenobarbital or high-dose lidocaine had less side effects. Conclusions Children with encephalitis have a high rate of postencephalitic epilepsy. Phenobarbital and clonazepam are the most common drugs used, alone or in combination, for postencephalitic epilepsy. PMID:26444013

  2. Effect of photoperiod and 6-methoxybenzoxazolinone (6-MBOA) on the reproduction of male Brandt's voles (Lasiopodomys brandtii).

    PubMed

    Dai, Xin; Shi, Jia; Han, Mei; Wang, Ai Qin; Wei, Wan Hong; Yang, Sheng Mei

    2017-05-15

    Plant secondary metabolite 6-methoxybenzoxazolinone (6-MBOA) has been suggested to stimulate animal reproduction. 6-MBOA is detected in Leymus chinensis, a main diet of Brandt's vole (Lasiopodomys brandtii). We have previously reported a stimulatory effect of 6-MBOA on reproduction of male Brandt's voles under a short-day photoperiod. The goal of this study was to investigate the effect of 6-MBOA on reproductive physiology of male Brandt's voles under a long-day photoperiod and examine if 6-MBOA under this photoperiodic regime altered the reproductive status of male Brandt's voles differently than the short-day photoperiod. Under the long-day photoperiod, a high dose of 6-MBOA decreased KiSS-1 mRNA in the arcuate nucleus (ARC), and we also saw a decrease in circulating levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone (T). Steroidogenic acute regulatory protein (StAR) and cytochrome P450 11a1 (CYP11a1) in the testes, and relative testis weight also decreased with 6-MBOA administration. Compared to the short-day photoperiod, animals under the long-day photoperiod exhibited increased body weight as well as all other reproductive parameters. Our results showed that 6-MBOA inhibited the reproduction of male Brandt's vole under a long-day photoperiod, a stark contrast from its stimulatory effects under a short-day photoperiod. The paradoxical effects of 6-MBOA suggest it may act as a partial agonist of melatonin. These results provide insight into the complex interactions between environmental factors such as photoperiod and diet in the control of Brandt's vole reproduction. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. [Protective effect of Uncaria rhynchophylla total alkaloids pretreatment on hippocampal neurons after acute hypoxia].

    PubMed

    Liu, Wei; Zhang, Zhao-qin; Zhao, Xiao-min; Gao, Yun-sheng

    2006-05-01

    To investigate the effect of Uncaria rhynchophylla total alkaloids (RTA) pretreatment on the voltage-gated sodium currents of the rat hippocampal neurons after acute hypoxia. Primary cultured hippocampal neurons were divided into RTA pre-treated and non-pretreated groups. Patch clamp whole-cell recording was used to compare the voltage-gated sodium current amplitude and threshold with those before hypoxia. After acute hypoxia, sodium current amplitude was significantly decreased and its threshold was upside. RTA pretreatment could inhibit the reduction of sodium current amplitude. RTA pretreatment alleviates the acute hypoxia-induced change of sodium currents, which may be one of the mechanisms for protective effect of RTA on cells.

  4. Effect of acute ethanol administration on zebrafish tail-beat motion.

    PubMed

    Bartolini, Tiziana; Mwaffo, Violet; Butail, Sachit; Porfiri, Maurizio

    2015-11-01

    Zebrafish is becoming a species of choice in neurobiological and behavioral studies of alcohol-related disorders. In these efforts, the activity of adult zebrafish is typically quantified using indirect activity measures that are either scored manually or identified automatically from the fish trajectory. The analysis of such activity measures has produced important insight into the effect of acute ethanol exposure on individual and social behavior of this vertebrate species. Here, we leverage a recently developed tracking algorithm that reconstructs fish body shape to investigate the effect of acute ethanol administration on zebrafish tail-beat motion in terms of amplitude and frequency. Our results demonstrate a significant effect of ethanol on the tail-beat amplitude as well as the tail-beat frequency, both of which were found to robustly decrease for high ethanol concentrations. Such a direct measurement of zebrafish motor functions is in agreement with evidence based on indirect activity measures, offering a complementary perspective in behavioral screening. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. WHY DO THE ACUTE BEHAVIORAL EFFECTS OT TOLUENE IN RATS DEPEND ON THE ROUTE OF EXPOSURE?

    EPA Science Inventory

    Despite evidence suggesting that the acute effects of organic solvents are related to their concentration in the brain, we have observed route-dependent differences in the acute behavioral effects of toluene. Whereas inhaled toluene disrupts the performance of rats on a visual si...

  6. Effect of acute moderate exercise on induced inflammation and arterial function in older adults.

    PubMed

    Ranadive, Sushant Mohan; Kappus, Rebecca Marie; Cook, Marc D; Yan, Huimin; Lane, Abbi Danielle; Woods, Jeffrey A; Wilund, Kenneth R; Iwamoto, Gary; Vanar, Vishwas; Tandon, Rudhir; Fernhall, Bo

    2014-04-01

    Acute inflammation reduces flow-mediated vasodilatation and increases arterial stiffness in young healthy individuals. However, this response has not been studied in older adults. The aim of this study, therefore, was to evaluate the effect of acute induced systemic inflammation on endothelial function and wave reflection in older adults. Furthermore, an acute bout of moderate-intensity aerobic exercise can be anti-inflammatory. Taken together, we tested the hypothesis that acute moderate-intensity endurance exercise, immediately preceding induced inflammation, would be protective against the negative effects of acute systemic inflammation on vascular function. Fifty-nine healthy volunteers between 55 and 75 years of age were randomized to an exercise or a control group. Both groups received a vaccine (induced inflammation) and sham (saline) injection in a counterbalanced crossover design. Inflammatory markers, endothelial function (flow-mediated vasodilatation) and measures of wave reflection and arterial stiffness were evaluated at baseline and at 24 and 48 h after injections. There were no significant differences in endothelial function and arterial stiffness between the exercise and control group after induced inflammation. The groups were then analysed together, and we found significant differences in the inflammatory markers 24 and 48 h after induction of acute inflammation compared with sham injection. However, flow-mediated vasodilatation, augmentation index normalized for heart rate (AIx75) and β-stiffness did not change significantly. Our results suggest that acute inflammation induced by influenza vaccination did not affect endothelial function in older adults.

  7. The effects of acute sleep deprivation during residency training.

    PubMed

    Bartle, E J; Sun, J H; Thompson, L; Light, A I; McCool, C; Heaton, S

    1988-08-01

    Verbal and symbol concentration, learning, problem solving, clear thinking, manual skills, and memory were tested in 42 surgical residents to assess the effects of acute sleep deprivation on specific neuropsychological parameters. A series of eight neuropsychological tests--digit symbols, digit vigilance, story memory, trail making, PASAT, Raven matrices, delayed story, and pegboard--and a questionnaire on mood states were completed by the residents both when fatigued (less than 4 hours of sleep: mean, 2.0 +/- 1.5 hours) and when rested (more than 4 hours of sleep: mean, 6.5 +/- 1.0 hours), with at least 7 days between tests. In order to eliminate the effects of learning from the first test series, randomization of residents was performed so that one half were first evaluated when rested and one half when fatigued. ANOVA, multiple regression analysis, and the Student t test were used to assess differences. In the acute sleep-deprived state, residents were less vigorous and more fatigued, depressed, tense, confused, and angry (p less than 0.05) than they were in rested state. Despite these changes in mood, however, the responses on all of the functional tests were no different statistically in those who were rested and those who were fatigued (even in those with less than 2 hours' sleep). We conclude that acute sleep deprivation of less than 4 hours alters mood state but does not change performance in test situations in which concentration, clear thinking, and problem solving are important.

  8. Targeting the T-cell co-stimulatory CD27/CD70 pathway in cancer immunotherapy: rationale and potential.

    PubMed

    van de Ven, Koen; Borst, Jannie

    2015-01-01

    In 2013, cancer immunotherapy was named 'breakthrough of the year' based on the outcome of clinical trials with blocking antibodies to the T-cell co-inhibitory receptors CTLA-4 and PD-1. This success has emphasized that cytotoxic T-cell responses to cancer can occur, but are limited by peripheral tolerance and by immunosuppression in the tumor microenvironment. Targeting of CTLA-4, PD-1 or its ligands partly overcomes these limitations and can now be applied in multiple immunogenic cancer types. Furthermore, an increased success rate is expected from combining CTLA-4 and/or PD-1 blocking with deliberate engagement of T-cell co-stimulatory receptors, particularly TNF receptor (R) family members. The TNFR family includes CD27 (Tnfrsf7), for which an agonistic antibody has recently entered clinical trials. In this review, we describe how CD27 co-stimulation impacts the T-cell response, with the purpose to illuminate how CD27 agonism can be exploited in cancer immunotherapy.

  9. Thyroid Receptor β Involvement in the Effects of Acute Nicotine on Hippocampus-Dependent Memory

    PubMed Central

    Leach, Prescott T.; Kenney, Justin W.; Connor, David; Gould, Thomas J.

    2015-01-01

    Cigarette smoking is common despite adverse health effects. Nicotine’s effects on learning may contribute to addiction by enhancing drug-context associations. Effects of nicotine on learning could be direct or could occur by altering systems that modulate cognition. Because thyroid signaling can alter cognition and nicotine/smoking may change thyroid function, nicotine could affect learning through changes in thyroid signaling. These studies investigate the functional contributions of thyroid receptor (TR) subtypes β and α1 to nicotine-enhanced learning and characterize the effects of acute nicotine and learning on thyroid hormone levels. We conducted a high throughput screen of transcription factor activity to identify novel targets that may contribute to the effects of nicotine on learning. Based on these results, which showed that combined nicotine and learning uniquely acted to increase TR activation, we identified TRs as potential targets of nicotine. Further analyses were conducted to determine the individual and combined effects of nicotine and learning on thyroid hormone levels, but no changes were seen. Next, to determine the role of TRβ and TRα1 in the effects of nicotine on learning, mice lacking the TRβ or TRα1 gene and wildtype littermates were administered acute nicotine prior to fear conditioning. Nicotine enhanced contextual fear conditioning in TRα1 knockout mice and wildtypes from both lines but TRβ knockout mice did not show nicotine-enhanced learning. This finding supports involvement of TRβ signaling in the effect of acute nicotine on hippocampus-dependent memory. Acute nicotine enhances learning and these effects may involve processes regulated by the transcription factor TRβ. PMID:25666034

  10. COMPARISON OF ACUTE NEUROBEHAVIORAL EFFECTS OF N-METHYL CARBAMATE INSECTICIDES.

    EPA Science Inventory

    The acute neurobehavioral and cholinesterase (ChE)-inhibiting effects of N-methyl carbamate insecticides have not been systematically compared. We evaluated five carbamates - carbaryl (CB), propoxur (PP), oxamyl (OM), methomyl (MM), and methiocarb (MC). Adult male Long-Evans ra...

  11. Effect of agmatine on acute and mononeuropathic pain.

    PubMed

    Aricioglu, Feyza; Korcegez, Eylem; Bozkurt, Ayhan; Ozyalcin, Suleyman

    2003-12-01

    Agmatine is a polycationic amine synthesized from L-arginine by arginine decarboxylase in brain and several tissues. It binds to N-methyl-D-aspartate (NMDA) subtype of glutamatergic, alpha(2)-adrenergic and imidazoline (I) receptors. The present study was designed to investigate effect of agmatine on acute and mononeuropathic pain after chronic constriction injury (CCI). CCI was created by four loose ligations around the right sciatic nerve. The analgesic threshold in rats was evaluated by using thermal hyperalgesia/allodynia (THA) at 4 degrees C. The evaluations were made preoperatively, on postoperative day 15, and after drug administration. Agmatine (10, 20, 40, 80, and 100 mg/kg) was administered intraperitoneally for 5 days beginning on postoperative day 15. Agmatine significantly reduced the hyperalgesia in all doses applied. When agmatine was injected intraperitoneally (10, 20, 40, 80, and 100 mg/kg), it increased the nociceptive threshold in the tail-immersion test in a dose-dependent manner, but it had no effect in the hot-plate test. This effect of agmatine in the tail-immersion test was blocked by both yohimbine (1 mg/kg) and idazoxan (0.5 mg/kg). When agmatine was administered intracerebroventricularly (25-200 microg/10 microL), it increased the nociceptive threshold in the hot-plate but not in the tail-immersion test. We conclude that agmatine, an endogenous substance derived from arginine, can modulate both acute and chronic pain.

  12. Long-Term Follow-up of the Delayed Effects of Acute Radiation Exposure in Primates

    DTIC Science & Technology

    2016-10-01

    MV, Katz BP, Smith CP, Jackson W 3rd, Cohen DM, et al. A nonhuman primate model of the hematopoietic acute radiation syndrome plus medical management...subsyndrome of the acute radiation syndrome : a rhesus macaque model. Health Phys 2012; 103:411–26. 32. Robbins ME, Bourland JD, Cline JM, Wheeler KT, Deadwyler...AD______________ AWARD NUMBER: W81XWH-15-1-0574 TITLE: Long-Term Follow-up of the Delayed Effects of Acute Radiation Exposure in Primates

  13. Protective effect of Flos puerariae extract following acute alcohol intoxication in mice.

    PubMed

    Chen, Xiao; Cai, Fei; Guo, Shuang; Ding, Fang; He, Yi; Wu, Jiliang; Liu, Chao

    2014-07-01

    The effect of Flos Puerariae extract (FPE) on alcohol metabolism, hepatic injury, and memory impairment was assessed following acute ethanol (EtOH) intoxication in mice. The model of acute EtOH intoxication was established by intragastric administration with 8 g/kg EtOH in mice. FPE was orally administrated (gavage) once a day for 7 consecutive days. Mice were randomly divided into 4 groups: control group, model group, and FPE groups (100, 200 mg/kg). Alcohol tolerance and intoxication time, blood alcohol concentration, the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in liver, aspartate amino transferase (AST) and alanine amino transferase (ALT) in serum, superoxide dismutase (SOD), glutathione peroxidase (GSH-px), catalase and the formation of malondialdehyde (MDA) in both liver and brain, as well as memory ability were determined after acute alcohol exposure. Compared with model group, pretreatment with FPE significantly prolonged alcohol tolerance time and shortened intoxication time, which is accompanied by decreased blood alcohol concentration and elevated activities of ADH and ALDH in liver. Moreover, the index of hepatic injury, ALT, and AST activities in serum was markedly decreased by pretreatment with FPE. Additionally, decreased MDA level, enhanced GSH-px and catalase activities in liver, as well as enhanced SOD and catalase activities in brain were found in FPE pretreated mice after acute exposure to EtOH. Furthermore, FPE pretreated mice showed markedly relieved memory disruption following acute EtOH intoxication. This study suggests that FPE pretreatment could enhance alcohol metabolism, prevent hepatic injury, and relieve memory impairment after acute alcohol intoxication and that this effect is likely related to its modulation on the alcohol metabolizing and antioxidant enzymes. Copyright © 2014 by the Research Society on Alcoholism.

  14. Cognitive and physiological effects of an acute physical activity intervention in elementary school children

    PubMed Central

    Jäger, Katja; Schmidt, Mirko; Conzelmann, Achim; Roebers, Claudia M.

    2014-01-01

    The aim of the present study was to investigate the effects of an acute physical activity intervention that included cognitive engagement on executive functions and on cortisol level in young elementary school children. Half of the 104 participating children (6–8 years old) attended a 20-min sport sequence, which included cognitively engaging and playful forms of physical activity. The other half was assigned to a resting control condition. Individual differences in children's updating, inhibition, and shifting performance as well as salivary cortisol were assessed before (pre-test), immediately after (post-test), and 40 min after (follow-up) the intervention or control condition, respectively. Results revealed a significantly stronger improvement in inhibition in the experimental group compared to the control group, while it appeared that acute physical activity had no specific effect on updating and shifting. The intervention effect on inhibition leveled out 40 min after physical activity. Salivary cortisol increased significantly more in the experimental compared to the control group between post-test and follow-up and results support partly the assumed inverted U-shaped relationship between cortisol level and cognitive performance. In conclusion, results indicate that acute physical activity that includes cognitive engagement may have immediate positive effects on inhibition, but not necessarily on updating and shifting in elementary school children. This positive effect may partly be explained through cortisol elevation after acute physical activity. PMID:25566148

  15. cap alpha. /sub i/-3 cDNA encodes the. cap alpha. subunit of G/sub k/, the stimulatory G protein of receptor-regulated K/sup +/ channels

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Codina, J.; Olate, J.; Abramowitz, J.

    1988-05-15

    cDNA cloning has identified the presence in the human genome of three genes encoding ..cap alpha.. subunits of pertussis toxin substrates, generically called G/sub i/. They are named ..cap alpha../sub i/-1, ..cap alpha../sub i/-2 and ..cap alpha../sub i/-3. However, none of these genes has been functionally identified with any of the ..cap alpha.. subunits of several possible G proteins, including pertussis toxin-sensitive G/sub p/'s, stimulatory to phospholipase C or A/sub 2/, G/sub i/, inhibitory to adenylyl cyclase, or G/sub k/, stimulatory to a type of K/sup +/ channels. The authors now report the nucleotide sequence and the complete predicted aminomore » acid sequence of human liver ..cap alpha../sub i/-3 and the partial amino acid sequence of proteolytic fragments of the ..cap alpha.. subunit of human erythrocyte G/sub k/. The amino acid sequence of the proteolytic fragment is uniquely encoded by the cDNA of ..cap alpha../sub i/-3, thus identifying it as ..cap alpha../sub k/. The probable identity of ..cap alpha../sub i/-1 with ..cap alpha../sub p/ and possible roles for ..cap alpha../sub i/-2, as well as additional roles for ..cap alpha../sub i/-1 and ..cap alpha../sub i/-3 (..cap alpha../sub k/) are discussed.« less

  16. Acute cognitive effects of high doses of dextromethorphan relative to triazolam in humans

    PubMed Central

    Carter, Lawrence P.; Reissig, Chad J.; Johnson, Matthew W.; Klinedinst, Margaret A.; Griffiths, Roland R.

    2012-01-01

    BACKGROUND Although concerns surrounding high-dose dextromethorphan (DXM) abuse have recently increased, few studies have examined the acute cognitive effects of high doses of DXM. The aim of this study was to compare the cognitive effects of DXM with those of triazolam and placebo. METHODS Single, acute, oral doses of DXM (100, 200, 300, 400, 500, 600, 700, 800 mg/70 kg), triazolam (0.25, 0.5 mg /70 kg), and placebo were administered p.o. to twelve healthy volunteers with histories of hallucinogen use, under double-blind conditions, using an ascending dose run-up design. Effects on cognitive performance were examined at baseline and after drug administration for up to 6 hours. RESULTS Both triazolam and DXM produced acute impairments in attention, working memory, episodic memory, and metacognition. Impairments observed following doses of 100-300 mg/70 kg DXM were generally smaller in magnitude than those observed after 0.5 mg/70 kg triazolam. Doses of DXM that impaired performance to the same extent as triazolam were in excess of 10-30 times the therapeutic dose of DXM. CONCLUSION The magnitude of the doses required for these effects and the absence of effects on some tasks within the 100-300 mg/70 kg dose range of DXM, speak to the relatively broad therapeutic window of over-the-counter DXM preparations when used appropriately. However, the administration of supratherapeutic doses of DXM resulted in acute cognitive impairments on all tasks that were examined. These findings are likely relevant to cases of high-dose DXM abuse. PMID:22989498

  17. Influence of the ventilatory mode on acute adverse effects and facial thermography after noninvasive ventilation

    PubMed Central

    Pontes, Suzy Maria Montenegro; Melo, Luiz Henrique de Paula; Maia, Nathalia Parente de Sousa; Nogueira, Andrea da Nóbrega Cirino; Vasconcelos, Thiago Brasileiro; Pereira, Eanes Delgado Barros; Bastos, Vasco Pinheiro Diógenes; Holanda, Marcelo Alcantara

    2017-01-01

    ABSTRACT Objective: To compare the incidence and intensity of acute adverse effects and the variation in the temperature of facial skin by thermography after the use of noninvasive ventilation (NIV). Methods: We included 20 healthy volunteers receiving NIV via oronasal mask for 1 h. The volunteers were randomly divided into two groups according to the ventilatory mode: bilevel positive airway pressure (BiPAP) or continuous positive airway pressure (CPAP). Facial thermography was performed in order to determine the temperature of the face where it was in contact with the mask and of the nasal dorsum at various time points. After removal of the mask, the volunteers completed a questionnaire about adverse effects of NIV. Results: The incidence and intensity of acute adverse effects were higher in the individuals receiving BiPAP than in those receiving CPAP (16.1% vs. 5.6%). Thermographic analysis showed a significant cooling of the facial skin in the two regions of interest immediately after removal of the mask. The more intense acute adverse effects occurred predominantly among the participants in whom the decrease in the mean temperature of the nasal dorsum was lower (14.4% vs. 7.2%). The thermographic visual analysis of the zones of cooling and heating on the face identified areas of hypoperfusion or reactive hyperemia. Conclusions: The use of BiPAP mode was associated with a higher incidence and intensity of NIV-related acute adverse effects. There was an association between acute adverse effects and less cooling of the nasal dorsum immediately after removal of the mask. Cutaneous thermography can be an additional tool to detect adverse effects that the use of NIV has on facial skin. PMID:28538774

  18. The Effects of Acute Stress on Core Executive Functions: A Meta-Analysis and Comparison with Cortisol

    PubMed Central

    Shields, Grant S.; Sazma, Matthew A.; Yonelinas, Andrew P.

    2016-01-01

    Core executive functions such as working memory, inhibition, and cognitive flexibility are integral to daily life. A growing body of research has suggested that acute stress may impair core executive functions. However, there are a number of inconsistencies in the literature, leading to uncertainty about how or even if acute stress influences core executive functions. We addressed this by conducting a meta-analysis of acute stress effects on working memory, inhibition, and cognitive flexibility. We found that stress impaired working memory and cognitive flexibility, whereas it had nuanced effects on inhibition. Many of these effects were moderated by other variables, such as sex. In addition, we compared effects of acute stress on core executive functions to effects of cortisol administration and found some striking differences. Our findings indicate that stress works through mechanisms aside from or in addition to cortisol to produce a state characterized by more reactive processing of salient stimuli but greater control over actions. We conclude by highlighting some important future directions for stress and executive function research. PMID:27371161

  19. Stimulatory effect of clebopride on human prolactin secretion.

    PubMed

    Perez-Lopez, F R; Legido, A; Sisskin, M; Abos, M D

    1980-11-01

    Serum levels of prolactin (PRL), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured in normally cycling women and normal men before and after oral admiministration of 1 mg of clebopride, a derivative of procainamide used in the treatment of gastrointestinal diseases. Clebopride produced a significant increase (P < 0.001) in serum PRL to a 6-fold peak as compared with basal levels. After 240 minutes the levels remained significantly higher (P < 0.05) than the mean basal level at -30 and 0 minutes. No significant effects of clebopride were noted upon the circulating levels of LH and FSH. The peak PRL response to clebopride was unaffected by pretreatment with 100 mg of nomifensine, although the secretory area from 120 to 210 minutes after clebopride was greater (P < 0.05) in the nomifensine-treated group than in the control experiment. When 5 mg of bromocriptine were given before clebopride, the PRL response was completely abolished as compared with the control experiment (P < 0.001). Our data provide new evidence that dopaminergic receptors of the adeylate cyclase system are involved in the regulation of PRL secretion, acting at the pituitary level rather than acting on the hypothalamus. The PRL-releasing activity of clebopride could be the explanation for the occasional menstrual disorders and galactorrhea registered in some cases of long-term treatment.

  20. Functional biomarkers for the acute effects of alcohol on the central nervous system in healthy volunteers

    PubMed Central

    Zoethout, Remco W M; Delgado, Wilson L; Ippel, Annelies E; Dahan, Albert; van Gerven, Joop M A

    2011-01-01

    The central nervous system (CNS) effects of acute alcohol administration have been frequently assessed. Such studies often use a wide range of methods to study each of these effects. Unfortunately, the sensitivity of these tests has not completely been ascertained. A literature search was performed to recognize the most useful tests (or biomarkers) for identifying the acute CNS effects of alcohol in healthy volunteers. All tests were grouped in clusters and functional domains. Afterwards, the effect of alcohol administration on these tests was scored as improvement, impairment or as no effect. Furthermore, dose–response relationships were established. A total number of 218 studies, describing 342 different tests (or test variants) were evaluated. Alcohol affected a wide range of CNS domains. Divided attention, focused attention, visuo-motor control and scales of feeling high and of subjective drug effects were identified as the most sensitive functional biomarkers for the acute CNS effects of alcohol. The large number of CNS tests that are used to determine the effects of alcohol interferes with the identification of the most sensitive ones and of drug–response relationships. Our results may be helpful in selecting rational biomarkers for studies investigating the acute CNS effects of alcohol or for future alcohol- interaction studies. PMID:21284693

  1. Constitutive stimulatory G protein activity in limb mesenchyme impairs bone growth.

    PubMed

    Karaca, Anara; Malladi, Vijayram Reddy; Zhu, Yan; Tafaj, Olta; Paltrinieri, Elena; Wu, Joy Y; He, Qing; Bastepe, Murat

    2018-05-01

    GNAS mutations leading to constitutively active stimulatory G protein alpha-subunit (Gsα) cause different tumors, fibrous dysplasia of bone, and McCune-Albright syndrome, which are typically not associated with short stature. Enhanced signaling of the parathyroid hormone/parathyroid hormone-related peptide receptor, which couples to multiple G proteins including Gsα, leads to short bones with delayed endochondral ossification. It has remained unknown whether constitutive Gsα activity also impairs bone growth. Here we generated mice expressing a constitutively active Gsα mutant (Gsα-R201H) conditionally upon Cre recombinase (cGsα R201H mice). Gsα-R201H was expressed in cultured bone marrow stromal cells from cGsα R201H mice upon adenoviral-Cre transduction. When crossed with mice in which Cre is expressed in a tamoxifen-regulatable fashion (CAGGCre-ER™), tamoxifen injection resulted in mosaic expression of the transgene in double mutant offspring. We then crossed the cGsα R201H mice with Prx1-Cre mice, in which Cre is expressed in early limb-bud mesenchyme. The double mutant offspring displayed short limbs at birth, with narrow hypertrophic chondrocyte zones in growth plates and delayed formation of secondary ossification center. Consistent with enhanced Gsα signaling, bone marrow stromal cells from these mice demonstrated increased levels of c-fos mRNA. Our findings indicate that constitutive Gsα activity during limb development disrupts endochondral ossification and bone growth. Given that Gsα haploinsufficiency also leads to short bones, as in patients with Albright's hereditary osteodystrophy, these results suggest that a tight control of Gsα activity is essential for normal growth plate physiology. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. ACUTE BEHAVORIAL EFFECTS FROM EXPOSURE TO TWO-STROKE ENGINE EXHAUST

    EPA Science Inventory

    Benefits of changing from two-stroke to four-stroke engines (and other remedial requirements) can be evaluated (monetized) from the standpoint of acute behavioral effects of human exposure to exhaust from these engines. The monetization process depends upon estimates of the magn...

  3. The effect of acute aerobic and resistance exercise on working memory.

    PubMed

    Pontifex, Matthew B; Hillman, Charles H; Fernhall, Bo; Thompson, Kelli M; Valentini, Teresa A

    2009-04-01

    The goal of this investigation was to assess the influence of acute bouts of aerobic versus resistance exercise on the executive control of working memory. Twenty-one young adult participants completed a cardiorespiratory fitness test and maximal strength tests. On subsequent days, task performance measures of reaction time (RT) and accuracy were collected while participants completed a modified Sternberg working memory task before the start of, immediately after, and 30 min after an intervention consisting of 30 min of either resistance or aerobic exercise and a seated rest control. Findings indicated shorter RT immediately and 30 min after acute aerobic exercise relative to the preexercise baseline with no such effects observed after resistance exercise or seated rest. Further, in the aerobic condition, a larger reduction in RT from the baseline occurred during task conditions requiring increased working memory capacity. Again, no effect was observed in the resistance exercise or the seated rest conditions. These data extend the current knowledge base by indicating that acute exercise-induced changes in cognition are disproportionately related to executive control and may be specific to the aerobic exercise domain.

  4. The effects of metallic engineered nanoparticles upon plant systems: An analytic examination of scientific evidence.

    PubMed

    Tolaymat, Thabet; Genaidy, Ash; Abdelraheem, Wael; Dionysiou, Dionysios; Andersen, Christian

    2017-02-01

    Recent evidence for the effects of metallic engineered nanoparticles (ENPs) on plants and plant systems was examined together with its implications for other constituents of the Society-Environment-Economy (SEE) system. In this study, we were particularly interested to determine whether or not metallic ENPs have both stimulatory and inhibitory effects upon plant performance. An emphasis was made to analyze the scientific evidence on investigations examining both types of effects in the same studies. Analysis of evidence demonstrated that metallic ENPs have both stimulatory and inhibitory effects mostly in well-controlled environments and soilless media. Nano zero-valent iron (nZVI) and Cu ENPs have potential for use as micronutrients for plant systems, keeping in mind the proper formulation at the right dose for each type of ENP. The concentration levels for the stimulatory effects of Cu ENPs are lower than for those for nZVI. Newer findings showed that extremely smaller concentrations of Au ENPs (smaller than those for nZVI and Cu ENPs) induce positive effects for plant growth, which is attributed to effects on secondary metabolites. Ag ENPs have demonstrated their usage as antimicrobial/pesticidal agents for plant protection; however, precautions should be taken to avoid higher concentrations not only for plant systems, but also, other constituents in the SEE. Further research is warranted to investigate the stimulatory and inhibitory effects of metallic ENPs in soil media in order to broaden the horizon of sustainable agriculture production in terms of higher and safer yields so as to meet the food requirements of human population. Copyright © 2016. Published by Elsevier B.V.

  5. Th1 stimulatory proteins of Leishmania donovani: comparative cellular and protective responses of rTriose phosphate isomerase, rProtein disulfide isomerase and rElongation factor-2 in combination with rHSP70 against visceral leishmaniasis.

    PubMed

    Jaiswal, Anil Kumar; Khare, Prashant; Joshi, Sumit; Kushawaha, Pramod Kumar; Sundar, Shyam; Dube, Anuradha

    2014-01-01

    In visceral leishmaniasis, the recovery from the disease is always associated with the generation of Th1-type of cellular responses. Based on this, we have previously identified several Th1-stimulatory proteins of Leishmania donovani -triose phosphate isomerase (TPI), protein disulfide isomerase (PDI) and elongation factor-2 (EL-2) etc. including heat shock protein 70 (HSP70) which induced Th1-type of cellular responses in both cured Leishmania patients/hamsters. Since, HSPs, being the logical targets for vaccines aimed at augmenting cellular immunity and can be early targets in the immune response against intracellular pathogens; they could be exploited as vaccine/adjuvant to induce long-term immunity more effectively. Therefore, in this study, we checked whether HSP70 can further enhance the immunogenicity and protective responses of the above said Th1-stimulatory proteins. Since, in most of the studies, immunogenicity of HSP70 of L. donovani was assessed in native condition, herein we generated recombinant HSP70 and tested its potential to stimulate immune responses in lymphocytes of cured Leishmania infected hamsters as well as in the peripheral blood mononuclear cells (PBMCs) of cured patients of VL either individually or in combination with above mentioned recombinant proteins. rLdHSP70 alone elicited strong cellular responses along with remarkable up-regulation of IFN-γ and IL-12 cytokines and extremely lower level of IL-4 and IL-10. Among the various combinations, rLdHSP70 + rLdPDI emerged as superior one augmenting improved cellular responses followed by rLdHSP70 + rLdEL-2. These combinations were further evaluated for its protective potential wherein rLdHSP70 + rLdPDI again conferred utmost protection (∼80%) followed by rLdHSP70 + rLdEL-2 (∼75%) and generated a strong cellular immune response with significant increase in the levels of iNOS transcript as well as IFN-γ and IL-12 cytokines which was further supported by the high level of IgG2 antibody

  6. Th1 Stimulatory Proteins of Leishmania donovani: Comparative Cellular and Protective Responses of rTriose Phosphate Isomerase, rProtein Disulfide Isomerase and rElongation Factor-2 in Combination with rHSP70 against Visceral Leishmaniasis

    PubMed Central

    Jaiswal, Anil Kumar; Khare, Prashant; Joshi, Sumit; Kushawaha, Pramod Kumar; Sundar, Shyam; Dube, Anuradha

    2014-01-01

    In visceral leishmaniasis, the recovery from the disease is always associated with the generation of Th1-type of cellular responses. Based on this, we have previously identified several Th1-stimulatory proteins of Leishmania donovani -triose phosphate isomerase (TPI), protein disulfide isomerase (PDI) and elongation factor-2 (EL-2) etc. including heat shock protein 70 (HSP70) which induced Th1-type of cellular responses in both cured Leishmania patients/hamsters. Since, HSPs, being the logical targets for vaccines aimed at augmenting cellular immunity and can be early targets in the immune response against intracellular pathogens; they could be exploited as vaccine/adjuvant to induce long-term immunity more effectively. Therefore, in this study, we checked whether HSP70 can further enhance the immunogenicity and protective responses of the above said Th1-stimulatory proteins. Since, in most of the studies, immunogenicity of HSP70 of L. donovani was assessed in native condition, herein we generated recombinant HSP70 and tested its potential to stimulate immune responses in lymphocytes of cured Leishmania infected hamsters as well as in the peripheral blood mononuclear cells (PBMCs) of cured patients of VL either individually or in combination with above mentioned recombinant proteins. rLdHSP70 alone elicited strong cellular responses along with remarkable up-regulation of IFN-γ and IL-12 cytokines and extremely lower level of IL-4 and IL-10. Among the various combinations, rLdHSP70 + rLdPDI emerged as superior one augmenting improved cellular responses followed by rLdHSP70 + rLdEL-2. These combinations were further evaluated for its protective potential wherein rLdHSP70 + rLdPDI again conferred utmost protection (∼80%) followed by rLdHSP70 + rLdEL-2 (∼75%) and generated a strong cellular immune response with significant increase in the levels of iNOS transcript as well as IFN-γ and IL-12 cytokines which was further supported by the high level of IgG2 antibody

  7. Tissue metabolic changes for effects of pirfenidone in rats of acute paraquat poisoning by GC-MS.

    PubMed

    Ma, Jianshe; Sun, Fa; Chen, Bingbao; Tu, Xiaoting; Peng, Xiufa; Wen, Congcong; Hu, Lufeng; Wang, Xianqin

    2017-12-01

    We developed a metabolomic method to evaluate the effect of pirfenidone on rats with acute paraquat (PQ) poisoning, through the analysis of various tissues (lung, liver, kidney, and heart), by gas chromatography-mass spectrometry (GC-MS). Thirty-eight rats were randomly divided into a control group, an acute PQ (20 mg kg -1 ) poisoning group, a pirfenidone (20 mg kg -1 ) treatment group, and a pirfenidone (40 mg kg -1 ) treatment group. Partial least squares-discriminate analysis (PLS-DA) revealed metabolic alterations in rat tissue samples from the two pirfenidone treatment groups after acute PQ poisoning. The PLS-DA 3D score chart showed that the rats in the acute PQ poisoning group were clearly distinguished from the rats in the control group. Also, the two pirfenidone treatment groups were distinguished from the acute PQ poisoning group and control group. Additionally, the pirfenidone (40 mg kg -1 ) treatment group was separated farther than the pirfenidone (20 mg kg -1 ) treatment group from the acute PQ poisoning group. Evaluation of the pathological changes in the rat tissues revealed that treatment with pirfenidone appeared to decrease pulmonary fibrosis in the acute PQ poisoning rats. The results indicate that pirfenidone induced beneficial metabolic alterations in the tissues of rats with acute PQ poisoning. Rats with acute PQ poisoning exhibited a certain reduction in biochemical indicators after treatment with pirfenidone, indicating that pirfenidone could protect liver and kidney function. Accordingly, the developed metabolomic approach proved to be useful to elucidate the effect of pirfenidone in rats of acute PQ poisoning.

  8. Thyroid receptor β involvement in the effects of acute nicotine on hippocampus-dependent memory.

    PubMed

    Leach, Prescott T; Kenney, Justin W; Connor, David A; Gould, Thomas J

    2015-06-01

    Cigarette smoking is common despite adverse health effects. Nicotine's effects on learning may contribute to addiction by enhancing drug-context associations. Effects of nicotine on learning could be direct or could occur by altering systems that modulate cognition. Because thyroid signaling can alter cognition and nicotine/smoking may change thyroid function, nicotine could affect learning through changes in thyroid signaling. These studies investigate the functional contributions of thyroid receptor (TR) subtypes β and α1 to nicotine-enhanced learning and characterize the effects of acute nicotine and learning on thyroid hormone levels. We conducted a high throughput screen of transcription factor activity to identify novel targets that may contribute to the effects of nicotine on learning. Based on these results, which showed that combined nicotine and learning uniquely acted to increase TR activation, we identified TRs as potential targets of nicotine. Further analyses were conducted to determine the individual and combined effects of nicotine and learning on thyroid hormone levels, but no changes were seen. Next, to determine the role of TRβ and TRα1 in the effects of nicotine on learning, mice lacking the TRβ or TRα1 gene and wildtype littermates were administered acute nicotine prior to fear conditioning. Nicotine enhanced contextual fear conditioning in TRα1 knockout mice and wildtypes from both lines but TRβ knockout mice did not show nicotine-enhanced learning. This finding supports involvement of TRβ signaling in the effect of acute nicotine on hippocampus-dependent memory. Acute nicotine enhances learning and these effects may involve processes regulated by the transcription factor TRβ. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Immunomodulatory effects of beta-glucan on neutrophil function in fathead minnows (Pimephales promelas Rafinesque, 1820).

    PubMed

    Palić, Dusan; Andreasen, Claire B; Herolt, Dawn M; Menzel, Bruce W; Roth, James A

    2006-01-01

    Stimulatory effects of yeast beta-1,3-1,6-glucans on neutrophils have long been recognized, but effects of glucans on degranulation of primary granules in fish neutrophils have not been previously reported. Neutrophil function was monitored during in vitro and in vivo application of glucans to non- (NS), acute- (AS) and chronically stressed (CS) fish. beta-Glucan proved to be a strong and quick (80%, 2 min) stimulant of degranulation. Dietary glucan increased degranulation in NS fish, and prevented a decrease in AS fish. Degranulation in CS fish returned to NS levels 3 days after the glucan diet was fed. Fathead minnows appear to be a useful model to investigate neutrophil degranulation in fish exposed to different environmental conditions and immunomodulators. Use of beta-glucans in fish diets prior to AS and during chronic stress can enhance neutrophil function, potentially increasing disease resistance and survival rates after transportation or exposure to poor water quality.

  10. Stimulatory role of interleukin 10 in CD8+ T cells through STATs in gastric cancer.

    PubMed

    Xi, Jianjun; Xu, Mingzheng; Song, Zongchang; Li, Hongqiang; Xu, Shumin; Wang, Chunmei; Song, Haihan; Bai, Jianwen

    2017-05-01

    CD8 + T cells are considered to be critical in tumor surveillance and elimination. Increased CD8 + T cell frequency and function is associated with better prognosis in cancer patients. Interleukin 10 is a cytokine with controversial roles in CD8 + T cell-mediated anti-tumor immunity. We therefore examined the interleukin 10 expression and consumption in CD8 + T cells harvested from the peripheral blood and resected tumors of gastric cancer patients of stages II-IV. We found that the gastric cancer patients presented significantly elevated frequencies of interleukin 10-expressing cells in both CD4 + and CD8 + T cells compared to healthy controls. But distinctive from the interleukin 10-expressing CD4 + T cells, which increased in frequency in advanced cancer, the interleukin 10-expressing CD8 + T cells did not increase with cancer stage in the peripheral blood and actually decreased with cancer stage in resected tumor. Interleukin 10 and interleukin 10 receptor expression was also enriched in interferon gamma-expressing activated CD8 + T cells. Compared to interleukin 10-nonexpressing CD8 + T cells, interleukin 10 receptor-expressing CD8 + T cells secreted significantly elevated interferon gamma levels. Treatment of anti-CD3/CD28-stimulated, purified CD8 + T cells with interleukin 10 alone could significantly enhance CD8 + T cell survival, an effect dependent on interleukin 10 receptor expression. Interleukin 10 also increased CD8 + T cell proliferation synergistically with interferon gamma but not alone. Analysis of downstream signal transducer and activator of transcription molecules showed that interleukin 10 treatment significantly increased the phosphorylation of signal transducer and activator of transcription 3 and signal transducer and activator of transcription 1 to lesser extent. Together, these results demonstrate that interleukin 10 possessed stimulatory roles in activated CD8 + T cells from gastric cancer patients.

  11. Acute Effect of Various Exercise Intensities on Cognitive Performance

    ERIC Educational Resources Information Center

    Ceylan, Halil Ibrahim; Saygin, Ozcan

    2018-01-01

    The aim of this study was to examine the acute effect of various exercise intensities on coincidence anticipation timing at different stimulus speeds. Fifteen male students who attend to Faculty of Sport Sciences at Mugla Sitki Kocman University, have been dealing with individual or team sports and having licenses for 5 or more years with no…

  12. Effect of acute and long-term oral tobacco use on oesophageal motility.

    PubMed

    Bhandarkar, P V; Shah, S K; Meshram, M; Abraham, P; Narayanan, T S; Bhatia, S J

    2000-09-01

    Nicotine administration is known to decrease lower oesophageal sphincter (LOS) pressure. Although a few studies have assessed the effect of tobacco on the LOS, the effect of acute and long-term oral tobacco use on oesophageal motility is not known. The study was designed to investigate the effect of acute and long-term oral tobacco use on LOS and distal oesophageal motility. Thirty-six healthy men (aged 18-65 years, median 34 years; 18 oral tobacco users, 18 non-tobacco users) underwent oesophageal manometry using a water-perfusion system. After baseline manometry, tobacco users were asked to keep 0.5 g tobacco in their mouth for 10 min; non-users of tobacco were kept in quiet surroundings for a similar period. Manometry was then repeated. The LOS basal pressures were similar in tobacco users and non-tobacco users (mean +/- SD 15.4 +/- 6.3 vs 13.4 +/- 5.3 mmHg). In the distal oesophageal body, the velocity (4.4 +/- 3.1 vs 4.9 +/- 2.6 cm/s), amplitude (92.7 +/- 38.3 vs 84.8 +/- 33.2 mmHg) and duration of contraction (2.1 +/- 0.7 vs 1.7 +/- 0.9 s) were similar in tobacco users and non-users. Acute tobacco use did not affect these parameters. The numbers of abnormal waves (triple peaks and non-transmitted contractions) were also similar in the two groups. Oral tobacco use does not appear to affect LOS pressures and distal oesophageal motility acutely or in the long term.

  13. Effects of acute and chronic psychological stress on isolated islets' insulin release

    PubMed Central

    Zardooz, Homeira; Zahediasl, Saleh; Rostamkhani, Fatemeh; Farrokhi, Babak; Nasiraei, Shiva; Kazeminezhad, Behrang; Gholampour, Roohollah

    2012-01-01

    This study investigated the effects of acute and chronic psychological stress on glucose-stimulated insulin secretion from isolated pancreatic islets. Male Wistar rats were divided into two control and stressed groups; each further was allocated into fed and fasted groups. Stress was induced by communication box for one (acute), fifteen and thirty (chronic) days. After islet isolation, their number, size and insulin output were assessed. Plasma corticosterone level was determined. In fasted animals, acute stress increased basal and post stress plasma corticosterone level, while 30 days stress decreased it compared to day 1. In fed rats, acute stress increased only post stress plasma corticosterone concentration, however, after 15 days stress, it was decreased compared to day 1. Acute stress did not change insulin output; however, the insulin output was higher in the fed acutely stressed rats at 8.3 and 16.7 mM glucose than fasted ones. Chronic stress increased insulin output on day 15 in the fasted animals but decreased it on day 30 in the fed animals at 8.3 and 16.7 mM glucose. In the fasted control rats insulin output was lower than fed ones. In the chronic stressed rats insulin output at 8.3 and 16.7 mM glucose was higher in the fasted than fed rats. The number of islets increased in the fasted rats following 15 days stress. This study indicated that the response of the isolated islets from acute and chronically stressed rats are different and depends on the feeding status. PMID:27385956

  14. γ-Tocotrienol as a Promising Countermeasure for Acute Radiation Syndrome: Current Status.

    PubMed

    Singh, Vijay K; Hauer-Jensen, Martin

    2016-05-03

    The hazard of ionizing radiation exposure due to nuclear accidents or terrorist attacks is ever increasing. Despite decades of research, still, there is a shortage of non-toxic, safe and effective medical countermeasures for radiological and nuclear emergency. To date, the U.S. Food and Drug Administration (U.S. FDA) has approved only two growth factors, Neupogen (granulocyte colony-stimulating factor (G-CSF), filgrastim) and Neulasta (PEGylated G-CSF, pegfilgrastim) for the treatment of hematopoietic acute radiation syndrome (H-ARS) following the Animal Efficacy Rule. Promising radioprotective efficacy results of γ-tocotrienol (GT3; a member of the vitamin E family) in the mouse model encouraged its further evaluation in the nonhuman primate (NHP) model. These studies demonstrated that GT3 significantly aided the recovery of radiation-induced neutropenia and thrombocytopenia compared to the vehicle controls; these results particularly significant after exposure to 5.8 or 6.5 Gray (Gy) whole body γ-irradiation. The stimulatory effect of GT3 on neutrophils and thrombocytes (platelets) was directly and positively correlated with dose; a 75 mg/kg dose was more effective compared to 37.5 mg/kg. GT3 was also effective against 6.5 Gy whole body γ-irradiation for improving neutrophils and thrombocytes. Moreover, a single administration of GT3 without any supportive care was equivalent, in terms of improving hematopoietic recovery, to multiple doses of Neupogen and two doses of Neulasta with full supportive care (including blood products) in the NHP model. GT3 may serve as an ultimate radioprotector for use in humans, particularly for military personnel and first responders. In brief, GT3 is a promising radiation countermeasure that ought to be further developed for U.S. FDA approval for the ARS indication.

  15. γ-Tocotrienol as a Promising Countermeasure for Acute Radiation Syndrome: Current Status

    PubMed Central

    Singh, Vijay K.; Hauer-Jensen, Martin

    2016-01-01

    The hazard of ionizing radiation exposure due to nuclear accidents or terrorist attacks is ever increasing. Despite decades of research, still, there is a shortage of non-toxic, safe and effective medical countermeasures for radiological and nuclear emergency. To date, the U.S. Food and Drug Administration (U.S. FDA) has approved only two growth factors, Neupogen (granulocyte colony-stimulating factor (G-CSF), filgrastim) and Neulasta (PEGylated G-CSF, pegfilgrastim) for the treatment of hematopoietic acute radiation syndrome (H-ARS) following the Animal Efficacy Rule. Promising radioprotective efficacy results of γ-tocotrienol (GT3; a member of the vitamin E family) in the mouse model encouraged its further evaluation in the nonhuman primate (NHP) model. These studies demonstrated that GT3 significantly aided the recovery of radiation-induced neutropenia and thrombocytopenia compared to the vehicle controls; these results particularly significant after exposure to 5.8 or 6.5 Gray (Gy) whole body γ-irradiation. The stimulatory effect of GT3 on neutrophils and thrombocytes (platelets) was directly and positively correlated with dose; a 75 mg/kg dose was more effective compared to 37.5 mg/kg. GT3 was also effective against 6.5 Gy whole body γ-irradiation for improving neutrophils and thrombocytes. Moreover, a single administration of GT3 without any supportive care was equivalent, in terms of improving hematopoietic recovery, to multiple doses of Neupogen and two doses of Neulasta with full supportive care (including blood products) in the NHP model. GT3 may serve as an ultimate radioprotector for use in humans, particularly for military personnel and first responders. In brief, GT3 is a promising radiation countermeasure that ought to be further developed for U.S. FDA approval for the ARS indication. PMID:27153057

  16. Acute Effect of Foam Rolling and Dynamic Stretching on Flexibility and Jump Height.

    PubMed

    Smith, Jason C; Pridgeon, Brooke; Hall, MacGregor C

    2018-04-04

    Smith, JC, Pridgeon, B, and Hall, MC. Acute effect of foam rolling and dynamic stretching on flexibility and jump height. J Strength Cond Res XX(X): 000-000, 2017-Dynamic stretching (DS) can acutely improve vertical jump (VJ) performance but its effect lasts no more than 5 minutes. Foam rolling (FR), a form of self-myofascial release, can acutely increase range of motion (ROM) with this effect lasting less than 10 minutes. Therefore, the purpose of this study was to evaluate the time course of these effects, separately and combined, on VJ height and ROM. Twenty-nine university students completed 4 different sessions (control, FR, DS, and combo) in a randomized order. After a warm-up and baseline assessments of VJ height and sit-and-reach, participants rested (control) and performed FR, DS, and the combination of FR and DS (combo). Vertical jump height and ROM were assessed every 5 minutes for 20 minutes after treatment. Mean scores at each time point were expressed as a percent change from baseline scores. Immediately after FR, sit-and-reach was significantly greater than control (p = 0.003). Vertical jump height immediately after treatment for DS and combo was significantly greater than the control and FR counterparts (p ≤ 0.002). Vertical jump height for DS and combo was also significantly greater than the control counterpart at 5 minutes after treatment (p < 0.001). At 15 minutes after treatment, the percent change in VJ height for the combo was significantly greater than the control counterpart (p = 0.002). Although FR has no effect on VJ performance, it can acutely increase ROM, but its effect was quickly dissipated. Foam rolling does not seem to enhance VJ height either alone or in combination with DS.

  17. Sex-specific respiratory effects of acute and chronic caffeine administration in newborn rats.

    PubMed

    Kouchi, Hayet; Uppari, NagaPraveena; Joseph, Vincent; Bairam, Aida

    2017-06-01

    Caffeine is widely used for the treatment of apnea of prematurity (AoP) but whether this effect varies with sex is unknown. To shed some light on this question, we present a summary of data obtained on the effects of caffeine on the respiratory chemoreflexes and apnea frequency in 1- and 12-days old male and female rats. Caffeine was either administered as a single acute injection (10mg/kg, i.p.) or for 10 consecutive days (7.5mg/kg/day between 3 and 12days of life by gavage, simulating its clinical use). Acute caffeine had little effects on breathing in 1-day old male and female rats. In 12-days old female rats caffeine reduced the response to hypercapnia (not hypoxia) compared to males. During the steady state of hypoxia females had a lower frequency of apneas than males, and acute injection of caffeine decreased the frequency of apnea, suppressing the differences between males and females. In 12-days old rats chronic administration of caffeine stimulated basal breathing and decreased the frequency of apnea similarly in males and females. In response to hypoxia, chronic caffeine administration also masked the difference in respiratory frequency between males and females observed in control rats. Female rats had lower frequency of apnea than males with or without caffeine treatment. These observations indicate that sex influences the respiratory responses to caffeine and this effect seems to depend on the modality of administration (acute vs chronic) and environmental oxygen (normoxia vs hypoxia). Copyright © 2017 Elsevier B.V. All rights reserved.

  18. The effect of long term combined yoga practice on the basal metabolic rate of healthy adults.

    PubMed

    Chaya, M S; Kurpad, A V; Nagendra, H R; Nagarathna, R

    2006-08-31

    Different procedures practiced in yoga have stimulatory or inhibitory effects on the basal metabolic rate when studied acutely. In daily life however, these procedures are usually practiced in combination. The purpose of the present study was to investigate the net change in the basal metabolic rate (BMR) of individuals actively engaging in a combination of yoga practices (asana or yogic postures, meditation and pranayama or breathing exercises) for a minimum period of six months, at a residential yoga education and research center at Bangalore. The measured BMR of individuals practicing yoga through a combination of practices was compared with that of control subjects who did not practice yoga but led similar lifestyles. The BMR of the yoga practitioners was significantly lower than that of the non-yoga group, and was lower by about 13 % when adjusted for body weight (P < 0.001). This difference persisted when the groups were stratified by gender; however, the difference in BMR adjusted for body weight was greater in women than men (about 8 and 18% respectively). In addition, the mean BMR of the yoga group was significantly lower than their predicted values, while the mean BMR of non-yoga group was comparable with their predicted values derived from 1985 WHO/FAO/UNU predictive equations. This study shows that there is a significantly reduced BMR, probably linked to reduced arousal, with the long term practice of yoga using a combination of stimulatory and inhibitory yogic practices.

  19. The effect of long term combined yoga practice on the basal metabolic rate of healthy adults

    PubMed Central

    Chaya, MS; Kurpad, AV; Nagendra, HR; Nagarathna, R

    2006-01-01

    Background Different procedures practiced in yoga have stimulatory or inhibitory effects on the basal metabolic rate when studied acutely. In daily life however, these procedures are usually practiced in combination. The purpose of the present study was to investigate the net change in the basal metabolic rate (BMR) of individuals actively engaging in a combination of yoga practices (asana or yogic postures, meditation and pranayama or breathing exercises) for a minimum period of six months, at a residential yoga education and research center at Bangalore. Methods The measured BMR of individuals practicing yoga through a combination of practices was compared with that of control subjects who did not practice yoga but led similar lifestyles. Results The BMR of the yoga practitioners was significantly lower than that of the non-yoga group, and was lower by about 13 % when adjusted for body weight (P < 0.001). This difference persisted when the groups were stratified by gender; however, the difference in BMR adjusted for body weight was greater in women than men (about 8 and 18% respectively). In addition, the mean BMR of the yoga group was significantly lower than their predicted values, while the mean BMR of non-yoga group was comparable with their predicted values derived from 1985 WHO/FAO/UNU predictive equations. Conclusion This study shows that there is a significantly reduced BMR, probably linked to reduced arousal, with the long term practice of yoga using a combination of stimulatory and inhibitory yogic practices. PMID:16945127

  20. Neurobehavorial effects of acute exposure to four solvents: meta-abalyses

    EPA Science Inventory

    Meta-and re-analyses of the available data for the neurobehavioral effects of acute inhalation exposure to toluene were reported by Benignus et al. (2007). The present study was designed to test the generality of the toluene results in as many other solvents as possible by furthe...

  1. Effects of Varenicline on Ethanol-Induced Conditioned Place Preference, Locomotor Stimulation, and Sensitization

    PubMed Central

    Gubner, Noah R.; McKinnon, Carrie S.; Phillips, Tamara J.

    2014-01-01

    Background Varenicline, a partial nicotinic acetylcholine receptor (nAChR) agonist, is a promising new drug for the treatment of alcohol (ethanol) dependence. Varenicline has been approved by the Food and Drug Administration as a smoking cessation therapeutic and has also been found to reduce ethanol consumption in humans and animal models of alcohol use. The current studies examined the hypotheses that varenicline attenuates the stimulant and sensitizing effects of ethanol, and reduces the motivational effects of ethanol-associated cues. The goal was to determine if these effects of varenicline contribute to its pharmacotherapeutic effects for alcohol dependence. In addition, effects of varenicline on acute stimulation and/or on the acquisition of sensitization would suggest a role for nAChR involvement in these effects of ethanol. Methods Dose-dependent effects of varenicline on the expression of ethanol-induced conditioned place preference (CPP), locomotor activation, and behavioral sensitization were examined. These measures model motivational effects of ethanol-associated cues, euphoric or stimulatory effects of ethanol, and ethanol-induced neuroadaptation. All studies used DBA/2J mice, an inbred strain with high sensitivity to these ethanol-related effects. Results Varenicline did not significantly attenuate the expression of ethanol-induced CPP. Varenicline reduced locomotor activity and had the most pronounced effect in the presence of ethanol, with the largest effect on acute ethanol-induced locomotor stimulation and a trend for varenicline to attenuate the expression of ethanol-induced sensitization. Conclusions Because varenicline did not attenuate the expression of ethanol-induced CPP, it may not be effective at reducing the motivational effects of ethanol-associated cues. This outcome suggests that reductions in the motivational effects of ethanol-associated cues may not be involved in how varenicline reduces ethanol consumption. However, varenicline

  2. Effects of acute and long-term typical or atypical neuroleptics on morphine-induced behavioural effects in mice.

    PubMed

    Hollais, André W; Patti, Camilla L; Zanin, Karina A; Fukushiro, Daniela F; Berro, Laís F; Carvalho, Rita C; Kameda, Sonia R; Frussa-Filho, Roberto

    2014-03-01

    1. It has been suggested that the high prevalence of drug abuse in schizophrenics is related to chronic treatment with typical neuroleptics and dopaminergic supersensitivity that develops as a consequence. Within this context, atypical neuroleptics do not seem to induce this phenomenon. In the present study, we investigated the effects of acute administration or withdrawal from long-term administration of haloperidol and/or ziprasidone on morphine-induced open-field behaviour in mice. 2. In the first experiment, mice were given a single injection of haloperidol (1 mg/kg, i.p.) or several doses of ziprasidone (2, 4 or 6 mg/kg, i.p.) and motor activity was quantified by the open-field test. The aim of the second experiment was to verify the effects of an acute injection of haloperidol (1 mg/kg) or ziprasidone (6 mg/kg) on 20 mg/kg morphine-induced behaviours in the open-field test. In the third experiment, mice were treated with 1 mg/kg haloperidol and/or 2, 4 or 6 mg/kg ziprasidone for 20 days. Seventy-two hours after the last injection, mice were injected with 20 mg/kg, i.p., morphine and then subjected to the open-field test. Acute haloperidol or ziprasidone decreased spontaneous general activity and abolished morphine-induced locomotor stimulation. 3. Withdrawal from haloperidol or ziprasidone did not modify morphine-elicited behaviours in the open-field test. The results suggest that withdrawal from neuroleptic treatments does not contribute to the acute effect of morphine in schizophrenic patients. © 2014 Wiley Publishing Asia Pty Ltd.

  3. Acute and long-term in vitro effects of zinc oxide nanoparticles.

    PubMed

    Annangi, Balasubramanyam; Rubio, Laura; Alaraby, Mohamed; Bach, Jordi; Marcos, Ricard; Hernández, Alba

    2016-09-01

    Since most of the toxic studies of zinc oxide nanoparticles (ZnO NPs) focused on acute and high-dose exposure conditions, the aim of the present study was to fill the existing knowledge gap of long-term effects of ZnO NPs at sub-toxic doses. To overcome this point, we have evaluated the toxic, genotoxic, and carcinogenic effects of ZnO NPs under long-term treatments (12 weeks), using a sub-toxic dose (1 µg/mL) according to acute 48-h exposure. Preliminarily, oxidative stress and genotoxic/oxidative DNA damage were determined under acute exposure and high-dose conditions. To determine the role of oxidative DNA damage, a wild-type mouse embryonic fibroblast (MEF Ogg1 (+/+)) and its isogenic 8-oxo-guanine DNA glycosylase 1 (Ogg1) knockout partner (MEF Ogg1 (-/-)) cell lines were used. Although short-term exposure (24-h) experiments demonstrated that ZnO NPs were able to induce ROS, genotoxicity, and oxidative DNA damage in both cell lines, no effects were obtained under long-term exposure scenario. Thus, 1 µg/mL exposure over 12 weeks was unable to induce genotoxicity as well as cellular transformation in both cell types, as indicated by the lack of observed morphological cell changes, variations in the secretion of matrix metalloproteinases, and anchorage-independent cell growth ability, regarded as cancer-like phenotypic hallmarks. Our results indicate that short-term effects of ZnO NP exposure are not replicated under long-term and sub-toxic dose conditions. All together, the lack of genotoxic/carcinogenic effects after chronic treatments seem to indicate a reduced risk associated with ZnO NP exposure.

  4. Acute analgesic effects of nicotine and tobacco in humans: a meta-analysis.

    PubMed

    Ditre, Joseph W; Heckman, Bryan W; Zale, Emily L; Kosiba, Jesse D; Maisto, Stephen A

    2016-07-01

    Although animal models have consistently demonstrated acute pain inhibitory effects of nicotine and tobacco, human experimental studies have yielded mixed results. The main goal of this meta-analysis was to quantify the effects of nicotine/tobacco administration on human experimental pain threshold and tolerance ratings. A search of PubMed and PsycINFO online databases identified 13 eligible articles, including k = 21 tests of pain tolerance (N = 393) and k = 15 tests of pain threshold (N = 339). Meta-analytic integration for both threshold and tolerance outcomes revealed that nicotine administered through tobacco smoke and other delivery systems (eg, patch, nasal spray) produced acute analgesic effects that may be characterized as small to medium in magnitude (Hedges g = 0.35, 95% confidence interval = 0.21-0.50). Publication bias-corrected estimates remained significant and indicated that these effects may be closer to small. Sex composition was observed to be a significant moderator, such that pain threshold effects were more robust among samples that included more men than women. These results help to clarify a mixed literature and may ultimately help to inform the treatment of both pain and nicotine dependence. Pain and tobacco smoking are both highly prevalent and comorbid conditions. Current smoking has been associated with more severe chronic pain and physical impairment. Acute nicotine-induced analgesia could make smoking more rewarding and harder to give up. Future research should use dynamic measures of experimental pain reactivity and further explore biopsychosocial mechanisms of action.

  5. Functional biomarkers for the acute effects of alcohol on the central nervous system in healthy volunteers.

    PubMed

    Zoethout, Remco W M; Delgado, Wilson L; Ippel, Annelies E; Dahan, Albert; van Gerven, Joop M A

    2011-03-01

    The central nervous system (CNS) effects of acute alcohol administration have been frequently assessed. Such studies often use a wide range of methods to study each of these effects. Unfortunately, the sensitivity of these tests has not completely been ascertained. A literature search was performed to recognize the most useful tests (or biomarkers) for identifying the acute CNS effects of alcohol in healthy volunteers. All tests were grouped in clusters and functional domains. Afterwards, the effect of alcohol administration on these tests was scored as improvement, impairment or as no effect. Furthermore, dose-response relationships were established. A total number of 218 studies, describing 342 different tests (or test variants) were evaluated. Alcohol affected a wide range of CNS domains. Divided attention, focused attention, visuo-motor control and scales of feeling high and of subjective drug effects were identified as the most sensitive functional biomarkers for the acute CNS effects of alcohol. The large number of CNS tests that are used to determine the effects of alcohol interferes with the identification of the most sensitive ones and of drug-response relationships. Our results may be helpful in selecting rational biomarkers for studies investigating the acute CNS effects of alcohol or for future alcohol- interaction studies. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

  6. Acute and Chronic Noradrenergic Effects on Cortical Excitability in Healthy Humans

    PubMed Central

    Kuo, Hsiao-I; Paulus, Walter; Batsikadze, Giorgi; Jamil, Asif; Kuo, Min-Fang

    2017-01-01

    Abstract Background Noradrenaline is a major neuromodulator in the central nervous system, and it is involved in the pathophysiology of diverse neuropsychiatric diseases. Previous transcranial magnetic stimulation studies suggested that acute application of selective noradrenaline reuptake inhibitors enhances cortical excitability in the human brain. However, other, such like clinical effects, usually require prolonged noradrenaline reuptake inhibitor treatment, which might go along with different physiological effects. Methods The purpose of this study was to investigate the acute and chronic effects of the selective noradrenaline reuptake inhibitor reboxetine on cortical excitability in healthy humans in a double-blind, placebo-controlled, randomized crossover study. Sixteen subjects were assessed with different transcranial magnetic stimulation measurements: motor thresholds, input-output curve, short-latency intracortical inhibition and intracortical facilitation, I-wave facilitation, and short-interval afferent inhibition before and after placebo or reboxetine (8 mg) single-dose administration. Afterwards, the same subjects took reboxetine (8 mg/d) consecutively for 21 days. During this period (subjects underwent 2 experimental sessions with identical transcranial magnetic stimulation measures under placebo or reboxetine), transcranial magnetic stimulation measurements were assessed before and after drug intake. Results Both single-dose and chronic administration of reboxetine increased cortical excitability; increased the slope of the input-output curve, intracortical facilitation, and I-wave facilitation; but decreased short-latency intracortical inhibition and short-interval afferent inhibition. Moreover, chronic reboxetine showed a larger enhancement of intracortical facilitation and I-wave facilitation compared with single-dose application. Conclusions The results show physiological mechanisms of noradrenergic enhancement possibly underlying the

  7. Acute effects of air pollution on asthma hospitalization in Shanghai, China.

    PubMed

    Cai, Jing; Zhao, Ang; Zhao, Jinzhuo; Chen, Renjie; Wang, Weibing; Ha, Sandie; Xu, Xiaohui; Kan, Haidong

    2014-08-01

    Air pollution has been accepted as an important contributor to asthma development and exacerbation. However, the evidence is limited in China. In this study, we investigated the acute effect of air pollution on asthma hospitalization in Shanghai, China. We applied over-dispersed generalized additive model adjusted for weather conditions, day of the week, long-term and seasonal trends. An interquartile range increase in the moving average concentrations of PM10, SO2, NO2 and BC on the concurrent day and previous day corresponded to 1.82%, 6.41%, 8.26% and 6.62% increase of asthmatic hospitalization, respectively. The effects of SO2 and NO2 were robust after adjustment for PM10. The associations appeared to be more evident in the cool season than in the warm season. Our results contribute to the limited data in the scientific literature on acute effects of air pollution on asthma in high exposure settings, which are typical in developing countries. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Acute effects of cocaine and cannabis on response inhibition in humans: an ERP investigation.

    PubMed

    Spronk, Desirée B; De Bruijn, Ellen R A; van Wel, Janelle H P; Ramaekers, Johannes G; Verkes, Robbert J

    2016-11-01

    Substance abuse has often been associated with alterations in response inhibition in humans. Not much research has examined how the acute effects of drugs modify the neurophysiological correlates of response inhibition, or how these effects interact with individual variation in trait levels of impulsivity and novelty seeking. This study investigated the effects of cocaine and cannabis on behavioural and event-related potential (ERP) correlates of response inhibition in 38 healthy drug using volunteers. A double-blind placebo-controlled randomized three-way crossover design was used. All subjects completed a standard Go/NoGo task after administration of the drugs. Compared with a placebo, cocaine yielded improved accuracy, quicker reaction times and an increased prefrontal NoGo-P3 ERP. Cannabis produced opposing results; slower reaction times, impaired accuracy and a reduction in the amplitude of the prefrontal NoGo-P3. Cannabis in addition decreased the amplitude of the parietally recorded P3, while cocaine did not affect this. Neither drugs specifically affected the N2 component, suggesting that pre-motor response inhibitory processes remain unaffected. Neither trait impulsivity nor novelty seeking interacted with drug-induced effects on measures of response inhibition. We conclude that acute drug effects on response inhibition seem to be specific to the later, evaluative stages of response inhibition. The acute effects of cannabis appeared less specific to response inhibition than those of cocaine. Together, the results show that the behavioural effects on response inhibition are reflected in electrophysiological correlates. This study did not support a substantial role of vulnerability personality traits in the acute intoxication stage. © 2015 Society for the Study of Addiction.

  9. Multigenerational Effects of Heavy Metals on Feeding, Growth, Initial Reproduction and Antioxidants in Caenorhabditis elegans

    PubMed Central

    Yu, ZhenYang; Zhang, Jing; Yin, DaQiang

    2016-01-01

    Earlier studies showed that toxicities of excessive metals lasted over generations. Yet, these studies mainly employed one-generation exposure, and the effects of multigenerational challenges need further studies. Presently, Caenorhabditis elegans were exposed to cadmium, copper, lead and zinc for four consecutive generations (G1 to G4) at environmental concentrations. The feeding, growth, initial reproduction, superoxide dismutase (SOD) and catalase (CAT) were determined. All data were represented in the percentage of that in control (POC), and POC in the control was normalized to 100%. In G1 and G2, the POC values in feeding, growth and initial reproduction were generally within 10% of the control (100%), indicating non-significant effects. The POC values in SOD and CAT were significantly higher than 100%, showing stimulatory effects. In G3 and G4, the POC values in feeding, growth and initial reproduction were significantly lower than 100%, showing inhibitory effects which were more severe in G4 than in G3. Meanwhile, SOD and CAT continuously showed stimulatory effects, and the stimulatory effects on SOD increased from G1 to G4. The effects with multigenerational challenges were different from those in one-generation exposure. The effects in later generations demonstrated the importance of multigenerational challenges in judging long-term influences of metals. PMID:27116222

  10. Effects of electroconvulsive therapy and magnetic seizure therapy on acute memory retrieval.

    PubMed

    Polster, Julia D; Kayser, Sarah; Bewernick, Bettina H; Hurlemann, René; Schlaepfer, Thomas E

    2015-03-01

    Electroconvulsive therapy (ECT) is currently the most effective treatment for severe depression. However, it is frequently associated with negative cognitive side effects. Magnetic seizure therapy (MST) depicts an alternative, although experimental, convulsive treatment for major depression. Initial results suggest comparable antidepressant effects accompanied by a better side effect profile. However, no studies up to now have addressed acute retrieval disruption after MST in comparison to ECT. Therefore, we intended to broaden insight into the side effect profile of MST compared to ECT by examining the disruption of acute verbal memory processes after treatment. Twenty depressed patients were randomly assigned to either MST (10 patients) or ECT (10 patients) treatment. On 2 treatment days and 2 treatment-free days, the patients memorized words using a controlled learning paradigm derived from the Batchelder and Riefer storage retrieval model. Four hours after memorization, the patients were asked to retrieve words freely (delayed recall) and a second time with the help of an additional cue constructed out of a hypernymic category (cued recall). By comparing memory performance on treatment days to control days, treatment-induced memory disruption was evaluated. After ECT, delayed recall was disturbed, whereas after MST, it was not. However, this difference in performance was no longer apparent upon cue application (cued recall). This study demonstrates that ECT-induced acute memory disruption measured by delayed recall is absent after MST, confirming its superior side effect profile. We hope that confirming advantages of MST over ECT will improve therapy options for patients with severe depression.

  11. Effect of HLA mismatch on acute graft-versus-host disease.

    PubMed

    Kanda, Junya

    2013-09-01

    HLA matching between donors and recipients is the most important factor associated with acute graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation. With improvements in GVHD prophylaxis and supportive care, transplantations from HLA mismatched donors are performed increasingly frequently, drawing greater attention to the effects of HLA mismatch. In related transplantation, HLA 1-antigen mismatch at the HLA-A, HLA-B, and HLA-DR loci is considered acceptable, but the incidence of severe acute GVHD under standard prophylaxis is higher than that for matched related and unrelated transplantation, highlighting the need for a modification of GVHD prophylaxis. Development of new GVHD prophylaxes has now made HLA 2-3-antigen mismatched related transplantation feasible, and has almost overcome the HLA barrier. In unrelated bone marrow or peripheral blood stem cell transplantation, donors matched for HLA-A, HLA-B, HLA-C, and HLA-DRB1 alleles are the most preferable. The impact of allele or antigen mismatch has been evaluated in a number of studies, but the results of these have not been consistent, partly due to differences in race and HLA distribution. The effects of HLA mismatch may differ depending on the year of transplantation and the form of GVHD prophylaxis administered. In cord blood transplantation, successful transplantation can be achieved with up to two HLA mismatches. In children, compared to the use of HLA mismatched units, the use of HLA-matched units is associated with a lower risk of acute GVHD and mortality, while in adults HLA mismatches may have a lower impact on outcome. Thus, the effect of HLA matching should be evaluated separately for different stem cell sources.

  12. The effects of acute nicotine on contextual safety discrimination.

    PubMed

    Kutlu, Munir G; Oliver, Chicora; Gould, Thomas J

    2014-11-01

    Anxiety disorders, such as post-traumatic stress disorder (PTSD), may be related to an inability to distinguish safe versus threatening environments and to extinguish fear memories. Given the high rate of cigarette smoking in patients with PTSD, as well as the recent finding that an acute dose of nicotine impairs extinction of contextual fear memory, we conducted a series of experiments to investigate the effect of acute nicotine in an animal model of contextual safety discrimination. Following saline or nicotine (at 0.0275, 0.045, 0.09 and 0.18 mg/kg) administration, C57BL/6J mice were trained in a contextual discrimination paradigm, in which the subjects received presentations of conditioned stimuli (CS) that co-terminated with a foot-shock in one context (context A (CXA)) and only CS presentations without foot-shock in a different context (context B (CXB)). Therefore, CXA was designated as the 'dangerous context', whereas CXB was designated as the 'safe context'. Our results suggested that saline-treated animals showed a strong discrimination between dangerous and safe contexts, while acute nicotine dose-dependently impaired contextual safety discrimination (Experiment 1). Furthermore, our results demonstrate that nicotine-induced impairment of contextual safety discrimination learning was not a result of increased generalized freezing (Experiment 2) or contingent on the common CS presentations in both contexts (Experiment 3). Finally, our results show that increasing the temporal gap between CXA and CXB during training abolished the impairing effects of nicotine (Experiment 4). The findings of this study may help link nicotine exposure to the safety learning deficits seen in anxiety disorder and PTSD patients. © The Author(s) 2014.

  13. Detrimental effects of acute hyperglycaemia on the rat heart.

    PubMed

    Mapanga, R F; Joseph, D; Symington, B; Garson, K-L; Kimar, C; Kelly-Laubscher, R; Essop, M Faadiel

    2014-03-01

    Hyperglycaemia is an important risk factor for acute myocardial infarction. It can lead to increased induction of non-oxidative glucose pathways (NOGPs) - polyol and hexosamine biosynthetic pathways, advanced glycation end products and protein kinase C - that may contribute to cardiovascular diseases onset. However, the precise underlying mechanisms remain poorly understood. Here we hypothesized that acute hyperglycaemia increases myocardial oxidative stress and NOGP activation resulting in cardiac dysfunction during ischaemia-reperfusion and that inhibition of, and/or shunting flux away from NOGPs [by benfotiamine (BFT) treatment], leads to cardioprotection. We employed several experimental systems: (i) Isolated rat hearts were perfused ex vivo with Krebs-Henseleit buffer containing 33 mm glucose vs. controls (11 mm glucose) ± global ischaemia and reperfusion ± BFT (first 20 min of reperfusion); (ii) Infarct size determination as per the ischaemic protocol, but with regional ischaemia and reperfusion ± BFT treatment; in separate experiments, NOGP inhibitors were also employed for (i) and (ii); and (iii) In vivo coronary ligations performed on streptozotocin-treated rats ± BFT treatment (early reperfusion). Acute hyperglycaemia generated myocardial oxidative stress, NOGP activation and apoptosis, but caused no impairment of cardiac function during pre-ischaemia, thereby priming hearts for later damage. Following ischaemia-reperfusion (under hyperglycaemic conditions), such effects were exacerbated together with cardiac contractile dysfunction. Moreover, inhibition of respective NOGPs and shunting away by BFT treatment (in part) improved cardiac function during ischaemia-reperfusion. Coordinate NOGP activation in response to acute hyperglycaemia results in contractile dysfunction during ischaemia-reperfusion, allowing for the development of novel cardioprotective agents. © 2013 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  14. Control Group Paradigms in Studies Investigating Acute Effects of Exercise on Cognitive Performance-An Experiment on Expectation-Driven Placebo Effects.

    PubMed

    Oberste, Max; Hartig, Philipp; Bloch, Wilhelm; Elsner, Benjamin; Predel, Hans-Georg; Ernst, Bernhard; Zimmer, Philipp

    2017-01-01

    Introduction: Many studies report improvements in cognitive performance following acute endurance exercise compared to control group treatment. These cognitive benefits are interpreted as a result of a physiological response to exercise. However, it was also hypothesized that expectation-driven placebo effects account for these positive effects. The purpose of this study was to investigate the differences between expectations for cognitive benefits toward acute endurance exercise and multiple control group treatments. Methods: Healthy individuals ( N = 247, 24.26 ± 3.88 years) were randomized to eight different groups watching videos of a moderate, a vigorous exercise treatment or one control group treatment (waiting, reading, video-watching, stretching, myofascial release workout, and very light exercise). Then, they were introduced to three commonly used cognitive test procedures in acute exercise-cognition research (Stroop-test, Trail-Making-test, Free-recall-task). Participants rated the effect they would expect on their performance in those tasks, if they had received the treatment shortly before the task, on an 11-point Likert scale. Results: No significantly different expectations for cognitive benefits toward acute moderate exercise and control group treatments could be revealed. Participants expected significantly worse performance following vigorous exercise compared to following waiting and stretching for all cognitive tests. Significantly worse performance after vigorous exercise compared to after very light exercise was expected for Stroop and Free-recall. For Free-recall, participants expected worse performance after vigorous exercise compared to myofascial release training as well. Conclusion: Our results indicate that expectation-driven placebo effects are unlikely to cause the reported greater cognitive improvements following acute moderate and vigorous endurance exercise compared to following common control group treatments.

  15. Control Group Paradigms in Studies Investigating Acute Effects of Exercise on Cognitive Performance–An Experiment on Expectation-Driven Placebo Effects

    PubMed Central

    Oberste, Max; Hartig, Philipp; Bloch, Wilhelm; Elsner, Benjamin; Predel, Hans-Georg; Ernst, Bernhard; Zimmer, Philipp

    2017-01-01

    Introduction: Many studies report improvements in cognitive performance following acute endurance exercise compared to control group treatment. These cognitive benefits are interpreted as a result of a physiological response to exercise. However, it was also hypothesized that expectation-driven placebo effects account for these positive effects. The purpose of this study was to investigate the differences between expectations for cognitive benefits toward acute endurance exercise and multiple control group treatments. Methods: Healthy individuals (N = 247, 24.26 ± 3.88 years) were randomized to eight different groups watching videos of a moderate, a vigorous exercise treatment or one control group treatment (waiting, reading, video-watching, stretching, myofascial release workout, and very light exercise). Then, they were introduced to three commonly used cognitive test procedures in acute exercise-cognition research (Stroop-test, Trail-Making-test, Free-recall-task). Participants rated the effect they would expect on their performance in those tasks, if they had received the treatment shortly before the task, on an 11-point Likert scale. Results: No significantly different expectations for cognitive benefits toward acute moderate exercise and control group treatments could be revealed. Participants expected significantly worse performance following vigorous exercise compared to following waiting and stretching for all cognitive tests. Significantly worse performance after vigorous exercise compared to after very light exercise was expected for Stroop and Free-recall. For Free-recall, participants expected worse performance after vigorous exercise compared to myofascial release training as well. Conclusion: Our results indicate that expectation-driven placebo effects are unlikely to cause the reported greater cognitive improvements following acute moderate and vigorous endurance exercise compared to following common control group treatments. PMID:29276483

  16. Cardiopulmonary Effects of Acute Stressful Exercise at Altitude of Individuals with Sickle Cell Trait (SCT)

    DTIC Science & Technology

    1989-06-01

    Annual Symposium on Blood. Stuttgart Germany: FK Schattauer Verlag, 1973; 91-94. Home M: Sickle cell anemia as a rheologic disease. Am J Med 1981; 70...AD___ AD-A222 948 CARDIOPULMONARY EFFECTS OF ACUTE STRESSFUL EXERCISE AT ALTITUDE OF INDIVIDUALS WITH SICKLE CELL TRAIT (SCT) FINAL REPORT Idelle M...Clawi’katiornj (U) Cardiopulmonlary Effects to Acute Stressful Exercise at Altitude of Individuals with - sickle Cell Trait (I1bAS) 12. PERSONAL. AUTHOR

  17. Ethylphenidate: availability, patterns of use, and acute effects of this novel psychoactive substance.

    PubMed

    Ho, James H; Bailey, George P; Archer, John R H; Dargan, Paul I; Wood, David M

    2015-10-01

    Ethylphenidate is a novel psychoactive substance that is an analogue of methylphenidate. This paper describes its availability, patterns of use, and acute effects. Searches of the scientific and grey literature (publicly accessible Internet resources) were undertaken, using the keywords "Ethylphenidate", "Ethyl phenidate", "Ethyl phenyl(piperidin-2-yl)acetate", and "Nopaine", to identify information on the prevalence and patterns of use, desired effects, and toxicity of ethylphenidate. An Internet snapshot survey was performed on 10 February 2015 to provide information on availability and cost of ethylphenidate. The literature search identified 1 case series of acute recreational ethylphenidate toxicity, 1 case report of ethylphenidate dependence, 1 qualitative analysis of user reports on Internet drug forums, 2 conference abstracts for surveillance studies, 1 report of two cases of ethylphenidate detected in post-mortem analyses, and 198 user reports on Internet discussion forums and social media sites. The Internet snapshot survey found 83 websites selling ethylphenidate, with purchase prices ranging from £28.20 ± 0.63 (€37.71 ± 0.85) per gram for a 500-mg amount to £2.64 ± 0.57 (€3.53 ± 0.77) per gram for 1 kg. The published cases and Internet user reports suggest the acute effects of ethylphenidate are similar to other stimulant drugs; the most common route of use was by nasal insufflation. The most common desired effects were euphoria, stimulation, and increased concentration, sociability, and energy levels; the most common unwanted effects included anxiety, palpitations, insomnia, and paranoia. This review of the scientific and grey literature has demonstrated that the acute harms associated with its use are stimulant in nature and that ethylphenidate is widely available to users over the Internet, with significant discounts for bulk purchases.

  18. Could piracetam potentiate behavioural effects of psychostimulants?

    PubMed

    Slais, Karel; Machalova, Alena; Landa, Leos; Vrskova, Dagmar; Sulcova, Alexandra

    2012-08-01

    Press and internet reports mention abuse of nootropic drug piracetam (PIR) in combination with psychostimulants methamphetamine (MET) or 4-methylenedioxymethamphetamine (MDMA). These combinations are believed to produce more profound desirable effects, while decreasing hangover. However, there is a lack of valid experimental studies on such drug-drug interactions in the scientific literature available. Our hypothesis proposes that a functional interaction exists between PIR and amphetamine psychostimulants (MET and MDMA) which can potentiate psychostimulant behavioural effects. Our hypothesis is supported by the results of our pilot experiment testing acute effects of drugs given to mice intraperitoneally (Vehicle, n=12; MET 2.5mg/kg, n=10; MDMA 2.5mg/kg, n=11; PIR 300 mg/kg, n=12; PIR+MET, n=12; PIR+MDMA, n=11) in the Open Field Test (Actitrack, Panlab, Spain). PIR given alone caused no significant changes in mouse locomotor/exploratory behaviour, whereas the same dose combined with either MET or MDMA significantly enhanced their stimulatory effects. Different possible neurobiological mechanism underlying drug-drug interaction of PIR with MET or MDMA are discussed, as modulation of dopaminergic, glutamatergic or cholinergic brain systems. However, the interaction with membrane phospholipids seems as the most plausible mechanism explaining PIR action on activities of neurotransmitter systems. Despite that our behavioural experiment cannot serve for explanation of the pharmacological mechanisms of these functional interactions, it shows that PIR effects can increase behavioural stimulation of amphetamine drugs. Thus, the reported combining of PIR with MET or MDMA by human abusers is not perhaps a coincidental phenomenon and may be based on existing PIR potential to intensify acute psychostimulant effects of these drugs of abuse. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Effect of acute alcohol intoxication on the metabolism and plasma kinetics of chlordiazepoxide.

    PubMed Central

    Whiting, B; Lawrence, J R; Skellern, G G; Meier, J

    1979-01-01

    1. The metabolism and plasma kinetics of chlordiazepoxide have been determined in a group of volunteers and in a group of patients with acute alcohol intoxication. 2. Using the SAAM 26 non-linear least squares fitting programme, all chlordiazepoxide plasma concentration v time data following oral administration could be analysed in terms of a one-compartment open model with metabolic conversion of chlordiazepoxide to desmethylchlordiazepoxide. 3. Acutely intoxicated patients showed a prolonged elimination of chlordiazepoxide and a reduced clearance when compared with alcohol-free volunteers. The elimination of desmethylchlordiazepoxide, on the other hand, appeared to be faster in the alcoholics. 4. Alcohol exerts significant effects on the metabolism of chlordiazepoxide in acutely intoxicated patients. PMID:760747

  20. Effect of carprofen, etodolac, meloxicam, or butorphanol in dogs with induced acute synovitis.

    PubMed

    Borer, Luc R; Peel, John E; Seewald, Wolfgang; Schawalder, Peter; Spreng, David E

    2003-11-01

    To compare the analgesic and anti-inflammatory effect of single doses of carprofen, etodolac, meloxicam, and butorphanol in dogs with induced acute synovitis (acute pain model) via kinetic gait analysis and orthopedic evaluation and examine measurement of serum C-reactive protein (CRP) concentration as an indicator of treatment efficacy. 12 Beagles and 6 additional Beagles that were used only in serum CRP analyses. Acute synovitis was induced in right stifle joints of dogs via intra-articular injection of monosodium urate solution. Treatments included butorphanol (0.2 mg/kg, i.v.), carprofen (4 mg/kg, PO), etodolac (17 mg/kg, PO), or meloxicam (0.2 mg/kg, PO); control dogs received no treatment. The procedure was repeated (3-week intervals) until all dogs received all treatments including control treatment. Lameness was assessed on a biomechanical force platform and via orthopedic evaluations of the stifle joints; blood was collected to monitor serum CRP concentration. Compared with control dogs, treated dogs had significantly different vertical ground reaction forces and weight-bearing scores. Greatest improvement in lameness was observed in carprofen-treated dogs. Etodolac had the fastest onset of action. Compared with butorphanol treatment, only carprofen and etodolac were associated with significantly lower pain scores. An increase in serum CRP concentration was detected after intra-articular injection in all dogs; this change was similar among groups. Carprofen, etodolac, and meloxicam had greater efficacy than butorphanol in relief of acute pain. Carprofen was most effective overall. In this acute pain model, serum CRP analysis was not useful to assess drug efficacy.

  1. Inhibitory effect of D3 dopamine receptors on neuropeptide Y‑induced migration in vascular smooth muscle cells.

    PubMed

    Xia, Xue-Wei; Zhou, Yong-Qiao; Luo, Hao; Zeng, Chunyu

    2017-10-01

    Abnormal migration of vascular smooth muscle cells (VSMCs) serves an important role in hypertension, atherosclerosis and restenosis following angioplasty, which is regulated numerous hormonal and humoral factors, including neuropeptide Y (NPY) and dopamine. Dopamine and NPY are both sympathetic neurotransmitters, and a previous study reported that NPY increased VSMC proliferation, while dopamine receptor inhibited it. Therefore, the authors wondered whether or not there is an inhibitory effect of dopamine receptor on NPY‑mediated VSMC migration. The present study demonstrated that stimulation with NPY dose‑dependence (10‑10‑10‑7M, 24 h) increased VSMC migration, the stimulatory effect of NPY was via the Y1 receptor. This is because, in the presence of the Y1 receptor antagonist, BIBP3226 (10‑7 M), the stimulatory effect of NPY on VSMC migration was blocked. Activation of the D3 receptor by PD128907 dose‑dependence (10‑11‑10‑8 M) reduced the stimulatory effect of NPY on VSMC migration. The effect of PD128907 was via the D3 receptor, because the inhibitory effect of PD128907 on NPY‑mediated migration was blocked by the D3 receptor antagonist, U99194. The authors' further study suggested that the inhibitory effect of the D3 receptor was via the PKA signaling pathway, in the presence of the PKA inhibitor, 14‑22 (10‑6 M), the inhibitory effect of PD128907 on VSMC migration was blocked. Moreover, the inhibitory effect of PD128907 was imitated by PKA activator, Sp‑cAMP [S], in the presence of Sp‑cAMP [S], the NPY‑mediated stimulatory effect on VSMC migration was abolished. The present study indicated that activation of the D3 receptor inhibits NPY Y1‑mediated migration on VSMCs, PKA is involved in the signaling pathway.

  2. Effects of a long-acting mutant bacterial cocaine esterase on acute cocaine toxicity in rats

    PubMed Central

    Collins, Gregory T.; Zaks, Matthew E.; Cunningham, Alyssa R.; St. Clair, Carley; Nichols, Joseph; Narasimhan, Diwahar; Ko, Mei-Chuan; Sunahara, Roger K.; Woods, James H.

    2011-01-01

    Background A longer acting, double mutant bacterial cocaine esterase (CocE T172R/G173Q; DM CocE) has been shown to protect mice from cocaine-induced lethality, inhibit the reinforcing effects of cocaine in rats, and reverse cocaine’s cardiovascular effects in rhesus monkeys. The current studies evaluated the effectiveness of DM CocE to protect against, and reverse cocaine’s cardiovascular, convulsant, and lethal effects in male and female rats. Methods Pretreatment studies were used to determine the effectiveness and in vivo duration of action for DM CocE to protect rats against the occurrence of cardiovascular changes, convulsion and lethality associated with acute cocaine toxicity. Posttreatment studies were used to evaluate the capacity of DM CocE to rescue rats from the cardiovascular and lethal effects of large doses of cocaine. In addition, male and female rats were studied to determine if there were any potential effects of sex on the capacity of DM CocE to protect against, or reverse acute cocaine toxicity in rats. Results Pretreatment with DM CocE dose-dependently protected rats against cocaine-induced cardiovascular changes, convulsion and lethality, with higher doses active for up to 4 hrs, and shifting cocaine-induced lethality at least 10-fold to the right. In addition to dose-dependently recovering rats from an otherwise lethal dose of cocaine, post-treatment with DM CocE also reversed the cardiovascular effects of cocaine. There were no sex-related differences in the effectiveness of DM CocE to protect against, or reverse acute cocaine toxicity. Conclusions Together, these results support the development of DM CocE for the treatment of acute cocaine toxicity. PMID:21481548

  3. U.S. EPA'S ACUTE REFERENCE EXPOSURE METHODOLOGY FOR ACUTE INHALATION EXPOSURES

    EPA Science Inventory

    The US EPA National Center for Environmental Assessment has developed a methodology to derive acute inhalation toxicity benchmarks, called acute reference exposures (AREs), for noncancer effects. The methodology provides guidance for the derivation of chemical-specific benchmark...

  4. Effects of Repeated Acute Stress in Obese and Non-Obese Rats

    DTIC Science & Technology

    2008-04-02

    22 . Corticosterone levels at time of sacrifice ......................................................... 11 0 Figure 23. Average daily food...minimize effects caused by order or time of day. Trunk blood was collected from all 40 animals to examine corticosterone levels in response to acute...were no effects of diet within Sprague- Dawleys on corticosterone level in those rats that had been re-exposed to restraint. Summary of Biological

  5. The effect of acute tryptophan depletion on mood and impulsivity in polydrug ecstasy users.

    PubMed

    Young, Simon N; Regoli, Martine; Leyton, Marco; Pihl, Robert O; Benkelfat, Chawki

    2014-02-01

    Several studies suggest users of 3,4-methylenedioxymethamphetamine (ecstasy) have low levels of serotonin. Low serotonin may make them susceptible to lowered mood. This work aims to study the acute effects on mood and impulsivity of lowering serotonin levels with acute tryptophan depletion in polydrug ecstasy users and to determine whether effects were different in men and women. In a double-blind cross-over study, participants who had used ecstasy at least 25 times (n = 13) and nonuser controls (n = 17) received a tryptophan-deficient amino acid mixture and a control amino acid mixture containing tryptophan, at least 1 week apart. Mood was measured using the profile of mood states, and impulsivity was measured with the Go/No-Go task. The main result shows that a lowering of mood after acute tryptophan depletion occurred only in female polydrug ecstasy users (n = 7), relative to controls (n = 9). Results from the Go/No-Go task suggested that impulsivity was not increased by acute tryptophan depletion in polydrug ecstasy users. The group sizes were small, when males and females were considered separately. Women polydrug ecstasy users appear to be more susceptible than men to the effects of lowered serotonin levels. If use of ecstasy alone or in conjunction with other drugs causes progressive damage of serotonin neurons, women polydrug ecstasy users may become susceptible to clinical depression.

  6. Comparison of the effects of acute and chronic psychological stress on metabolic features in rats*

    PubMed Central

    Rostamkhani, Fatemeh; Zardooz, Homeira; Zahediasl, Saleh; Farrokhi, Babak

    2012-01-01

    This study was aimed to compare the effects of acute and chronic psychological stress on metabolic factors. Forty-two male Wistar rats were divided into control and stressed groups. Stress was applied by a communication box acutely (1 d) and chronically (15 and 30 d). Blood sampling was carried out by retro-orbital-puncture method. The plasma levels of glucose, cholesterol, triglyceride, insulin, and corticosterone were measured. In addition, feed and water intake, latency to eat and drink, adrenal and body weights were determined. Acute and chronic psychological stress did not significantly change basal plasma corticosterone levels. However, immediately (1 min) after acute exposure to stress, plasma corticosterone level increased compared to that before stress exposure. Acute stress increased plasma insulin levels significantly. Fifteen days of stress exposure resulted in plasma glucose increase. Chronic stress significantly increased feed intake, latency to eat, and adrenal weight compared to acute stress. The body weights of both control and stressed groups increased markedly during the experiment. Homeostasis model assessment of insulin resistance (HOMA-IR) index did not change significantly in the stressed group. In conclusion, application of acute and chronic psychological stress leads to different metabolic and/or behavioral changes but the metabolic changes resulting from acute exposure to stress seem to be more pronounced. PMID:23125083

  7. Acute and medium term effects of a 10-week running intervention on mood state in apprentices

    PubMed Central

    Walter, Katrin; von Haaren, Birte; Löffler, Simone; Härtel, Sascha; Jansen, Carl-Philipp; Werner, Christian; Stumpp, Jürgen; Bös, Klaus; Hey, Stefan

    2013-01-01

    Exercise and physical activity have proven benefits for physical and psychological well-being. However, it is not clear if healthy young adults can enhance mood in everyday life through regular exercise. Earlier studies mainly showed positive effects of acute exercise and exercise programs on psychological well-being in children, older people and in clinical populations. Few studies controlled participants' physical activity in daily life, performed besides the exercise program, which can impact results. In addition the transition from mood enhancement induced by acute exercise to medium or long-term effects due to regular exercise is not yet determined. The purpose of this pilot study was to examine the acute effects of an aerobic running training on mood and trends in medium term changes of mood in everyday life of young adults. We conducted a 10-week aerobic endurance training with frequent mood assessments and continuous activity monitoring. 23 apprentices, separated into experimental and control group, were monitored over 12 weeks. To control the effectiveness of the aerobic exercise program, participants completed a progressive treadmill test pre and post the intervention period. The three basic mood dimensions energetic arousal, valence and calmness were assessed via electronic diaries. Participants had to rate their mood state frequently on 3 days a week at five times of measurement within 12 weeks. Participants' physical activity was assessed with accelerometers. All mood dimensions increased immediately after acute endurance exercise but results were not significant. The highest acute mood change could be observed in valence (p = 0.07; η2 = 0.27). However, no medium term effects in mood states could be observed after a few weeks of endurance training. Future studies should focus on the interaction between acute and medium term effects of exercise training on mood. The decreasing compliance over the course of the study requires the development of

  8. Rapid resolution of acute subdural hematoma and effects on the size of existent subdural hygroma: a case report.

    PubMed

    Coşar, Murat; Eser, Olcay; Aslan, Adem; Ela, Yüksel

    2007-07-01

    The diagnosis and management of acute subdural hematoma is important in neurosurgery practice. Rapid spontaneous resolution of acute subdural hematoma within a few hours is seen rarely on the CT scan. We present a case that enlarged the existent subdural hygroma showing rapid resolution of acute subdural hematoma with resolution in 9 hours after the trauma. Additionally, the follow-up CT scans in the 1st month showed the decrease of enlargement of subdural hygroma. The resolution of acute subdural hematoma and effect of acute subdural hematoma on subdural hygroma must be considered during management. The relation of acute subdural hematoma and subdural hygroma is important for the resolution and management of acute subdural hematoma.

  9. Time Scale Effects in Acute Association between Air-Pollution and Mortality

    EPA Science Inventory

    We used wavelet analysis and generalized additive models (GAM) to study timescale effects in the acute association between mortality and air-pollution. Daily averages of measured NO2 concentrations in the metropolitan Paris area are used as indicators of human exposure...

  10. Acute and Chronic Effects of Tributyltin on the Mysid Acanthomysis sculpta (Crustacea, Mysidacea).

    DTIC Science & Technology

    1986-05-01

    performed using a flowthrough tributyltin ( TBT ) dosing system ranging in concentrations from 0.03- to 0.52-pg/L TBT . The acute test was performed within a...juveniles . . . 19 12. Summary of chronic values in pg/L TBT . . . 26 viii INTRODUCTION Tributyltin ( TBT ) is commonly used as an antifouling toxicant in...AD-AI75 294 ACUTE AND CHRONIC EFFECTS OF TRIBUTYLTIN ON THE NYSID 1/1 ACRNTHOMYSIS SCULPT..(U) NAVAL OCEAN SYSTEMS CENTER SAN DIEGO CA B N DAVIDSON

  11. Acute alcohol effects on facial expressions of emotions in social drinkers: a systematic review

    PubMed Central

    Capito, Eva Susanne; Lautenbacher, Stefan; Horn-Hofmann, Claudia

    2017-01-01

    Background As known from everyday experience and experimental research, alcohol modulates emotions. Particularly regarding social interaction, the effects of alcohol on the facial expression of emotion might be of relevance. However, these effects have not been systematically studied. We performed a systematic review on acute alcohol effects on social drinkers’ facial expressions of induced positive and negative emotions. Materials and methods With a predefined algorithm, we searched three electronic databases (PubMed, PsycInfo, and Web of Science) for studies conducted on social drinkers that used acute alcohol administration, emotion induction, and standardized methods to record facial expressions. We excluded those studies that failed common quality standards, and finally selected 13 investigations for this review. Results Overall, alcohol exerted effects on facial expressions of emotions in social drinkers. These effects were not generally disinhibiting, but varied depending on the valence of emotion and on social interaction. Being consumed within social groups, alcohol mostly influenced facial expressions of emotions in a socially desirable way, thus underscoring the view of alcohol as social lubricant. However, methodical differences regarding alcohol administration between the studies complicated comparability. Conclusion Our review highlighted the relevance of emotional valence and social-context factors for acute alcohol effects on social drinkers’ facial expressions of emotions. Future research should investigate how these alcohol effects influence the development of problematic drinking behavior in social drinkers. PMID:29255375

  12. Interaction Effects of Acute Kidney Injury, Acute Respiratory Failure, and Sepsis on 30-Day Postoperative Mortality in Patients Undergoing High-Risk Intraabdominal General Surgical Procedures.

    PubMed

    Kim, Minjae; Brady, Joanne E; Li, Guohua

    2015-12-01

    Acute kidney injury (AKI), acute respiratory failure, and sepsis are distinct but related pathophysiologic processes. We hypothesized that these 3 processes may interact to synergistically increase the risk of short-term perioperative mortality in patients undergoing high-risk intraabdominal general surgery procedures. We performed a retrospective, observational cohort study of data (2005-2011) from the American College of Surgeons-National Surgical Quality Improvement Program, a high-quality surgical outcomes data set. High-risk procedures were those with a risk of AKI, acute respiratory failure, or sepsis greater than the average risk in all intraabdominal general surgery procedures. The effects of AKI, acute respiratory failure, and sepsis on 30-day mortality were assessed using a Cox proportional hazards model. Additive interactions were assessed with the relative excess risk due to interaction. Of 217,994 patients, AKI, acute respiratory failure, and sepsis developed in 1.3%, 3.7%, and 6.8%, respectively. The 30-day mortality risk with sepsis, acute respiratory failure, and AKI were 11.4%, 24.1%, and 25.1%, respectively, compared with 0.85% without these complications. The adjusted hazard ratios and 95% confidence intervals for a single complication (versus no complication) on mortality were 7.24 (6.46-8.11), 10.8 (8.56-13.6), and 14.2 (12.8-15.7) for sepsis, AKI, and acute respiratory failure, respectively. For 2 complications, the adjusted hazard ratios were 30.8 (28.0-33.9), 42.6 (34.3-52.9), and 65.2 (53.9-78.8) for acute respiratory failure/sepsis, AKI/sepsis, and acute respiratory failure/AKI, respectively. Finally, the adjusted hazard ratio for all 3 complications was 105 (92.8-118). Positive additive interactions, indicating synergism, were found for each combination of 2 complications. The relative excess risk due to interaction for all 3 complications was not statistically significant. In high-risk general surgery patients, the development of AKI

  13. [The effects of ethanol on the evolution of the acute benzodiazepine poisoning].

    PubMed

    Puha, Gabriela; Hurjui, J; Lupuşoru, Cătălina Elena; Sorodoc, L

    2011-01-01

    The depressing effects on the nervous central system (NCS) induced by benzodiazepines and ethanol are similar. The complications are rare in the benzodiazepine poisoning, but are a lot more frequent in association with other depressing drugs for the NCS (especially alcohol). We analyzed retrospectively patients with benzodiazepine poisoning admitted in the Internal Medicine Clinic - Toxicology during 2003 - 2009.The study attempted a complex evaluation of the consequences of acute and chronic alcoholism on the evolution of acute benzodiazepinepoisoning and the description of the clinic evolution and paraclinical particularities of the patients under investigation. 343 patients with benzodiazepine poisoning were admitted, 150 were tested through measurement of alcohol level, leading to values between 1 - 415 mg/dl. Chronic alcoholism in personal pathological antecedents of the patients determined a relative risk of intoxication 1.46 times higher. The hospitalization period varied from 1 to 8 days for patients with chronic alcoholism and from 1 to 14 days for patients with acute alcoholism, a statistically important difference. During the period under investigation, from the total of patients admitted for acute benzodiazepine poisoning, 2 deaths were registered. Of the two deaths, one patient showed ethanol coingestion.

  14. Corticosterone and dehydroepiandrosterone in songbird plasma and brain: effects of season and acute stress

    PubMed Central

    Newman, Amy E. M.; Soma, Kiran K.

    2010-01-01

    Prolonged increases in plasma glucocorticoids can exacerbate neurodegeneration. In rats, these neurodegenerative effects can be reduced by dehydroepiandrosterone (DHEA), an androgen precursor with anti-glucocorticoid actions. In song sparrows, season and acute restraint stress affect circulating levels of corticosterone and DHEA, and the effects of stress differ in plasma collected from the brachial and jugular veins. Jugular plasma is an indirect index of the neural steroidal milieu. Here, we directly measured corticosterone and DHEA in several brain regions and jugular plasma, and examined the effects of season and acute restraint stress (30 min) (n = 571 samples). Corticosterone levels were up to 10× lower in brain than in jugular plasma. In contrast, DHEA levels were up to 5× higher in brain than in jugular plasma and were highest in the hippocampus. Corticosterone and DHEA concentrations were strongly seasonally regulated in plasma but, surprisingly, not seasonally regulated in brain. Acute stress increased corticosterone levels in plasma and brain, except during the molt, when stress unexpectedly decreased corticosterone levels in the hippocampus. Acute stress increased DHEA levels in plasma during the molt but had no effects on DHEA levels in brain. This is the first study to measure (i) corticosterone or DHEA levels in the brain of adult songbirds and (ii) seasonal changes in corticosterone or DHEA levels in the brain of any species. These results highlight several critical differences between systemic and local steroid concentrations and the difficulty of using circulating steroid levels to infer local steroid levels within the brain. PMID:19473242

  15. Acute Effects of (Bis)tributyltin Oxide on Marine Organisms. Summary of Work Performed 1981 to 1983

    DTIC Science & Technology

    1989-05-01

    Diethyltin chloride Dimethyltin chloride Diphenyltin chloride Hethyltin chloride Phenyltin chloride TBT - Tributyltin TBTA Tributyltin acetate TBTB...IW^I^^^—^M^—M—i^^^^I^M—^^——M— — O A OOI < Technical Report 1299 May 1989 .,..,. r V:. rr\\^ Acute Effects of (Bis) tributyltin ...AGENCY ACCESSION NO. DN888 749 11. TITLE (include SecuriyClassilicalion) ACUTE EFFECTS OF (BIS) TRIBUTYLTIN OXIDE ON MARINE ORGANISMS Summary of

  16. Stimulatory effects of aluminum on growth of sugar maple seedlings

    Treesearch

    George A. Schier; Carolyn J. McQuattie

    2002-01-01

    To determine the effect of aluminum (Al) on sugar maple (Acer saccharum Marsh.), seedlings were grown in sand irrigated with nutrient solution (pH 3.8) containing 0, 2.5, 5, 10, 20, or 40 mg L-1 Al. Seedling growth was enhanced at 2.5 and 5mgL-1 Al. Although higher levels of Al reduced calcium (Ca) and...

  17. The acute potentiating effects of back squats on athlete performance.

    PubMed

    Crewther, Blair T; Kilduff, Liam P; Cook, Christian J; Middleton, Matt K; Bunce, Paul J; Yang, Guang-Zhong

    2011-12-01

    Crewther, BT, Kilduff, LP, Cook, CJ, Middleton, MK, Bunce, PJ, and Yang, G-Z. The acute potentiating effects of back squats on athlete performance. J Strength Cond Res 25(12): 3319-3325, 2011-This study examined the acute potentiating effects of back squats on athlete performance with a specific focus on movement specificity and the individual timing of potentiation. Nine subelite male rugby players performed 3 protocols on separate occasions using a randomized, crossover, and counterbalanced design. Each protocol consisted of performance testing before a single set of 3 repetition maximum (3RM) back squats, followed by retesting at ∼15 seconds, 4, 8, 12, and 16 minutes. The 3 tests were countermovement jumps (CMJs), sprint performance (5 and 10 m), and 3-m horizontal sled pushes with a 100-kg load. Relationships between the individual changes in salivary testosterone and cortisol concentrations and performance were also examined. The 3RM squats significantly (p < 0.001) improved CMJ height at 4 (3.9 ± 1.9%), 8 (3.5 ± 1.5%), and 12 (3.0 ± 1.4%) minutes compared with baseline values, but no temporal changes in sprinting and sled times were identified. On an individual level, the peak relative changes in CMJ height (6.4 ± 2.1%, p < 0.001) were greater than the 3-m sled (1.4 ± 0.6%), 5-m (2.6 ± 1.0%), and 10-m sprint tests (1.8 ± 1.0%). In conclusion, a single set of 3RM squats was found effective in acutely enhancing CMJ height in the study population, especially when the recovery period was individualized for each athlete. The study results also suggest that the potentiating effects of squats may exhibit some degree of movement specificity, being greater for those exercises with similar movement patterns. The current findings have practical implications for prescribing warm-up exercises, individualizing training programs, and for interpreting postactivation potentiation research.

  18. State/Trait Anxiety and Anxiolytic Effects of Acute Physical Exercises

    ERIC Educational Resources Information Center

    Guszkowska, Monika

    2009-01-01

    Study aim: To determine anxiolytic effects of acute physical exertions in relation to the initial anxiety state and trait in women. Material and methods: A group of 163 women aged 16-56 years, attending fitness clubs in Warsaw, participated in the study. They selected a single exercise to perform--strength, aerobic or mixed, lasting 30 to over 60…

  19. Age-related differences in pulmonary effects of acute and ...

    EPA Pesticide Factsheets

    Ozone (O3) is known to induce adverse pulmonary and systemic health effects. Importantly, children and older persons are considered at-risk populations for O3-induced dysfunction, yet the mechanisms accounting for the age-related pulmonary responses to O3 are uncertain. In this study, we examined age-related susceptibility to O3 using 1 mo (adolescent), 4 mo (young adult), 12 mo (adult) and 24 mo (senescent) male Brown Norway rats exposed to filtered air or O3 (0.25and 1.00 ppm), 6 h/day, two days/week for 1 week (acute) or 13 weeks (subchronic). Ventilatory function, assessed by whole-body plethysmography, and bronchoalveolar lavage fluid (BALF) biomarkers of injury and inflammation were used to examine O3-induced pulmonary effects.Relaxation time declined in all ages following the weekly exposures; however, this effect persisted only in the 24 mo rats following a five days recovery, demonstrating an inability to induce adaptation commonly seen with repeated O3 exposures. PenH was increased in all groups with an augmented response in the 4 mo rats following the subchronic O3 exposures. O3 led to increased breathing frequency and minute volume in the 1 and 4 mo animals. Markers ofpulmonary permeability were increased in all age groups. Elevations in BALF γ-glutamyl transferase activity and lung inflammation following an acute O3 exposure were noted in only the 1 and 4 mo rats, which likely received an increased effective O3 dose. These data demonstrate that ado

  20. Exposure to ammonia and acute respiratory effects in a urea fertilizer factory.

    PubMed

    Rahman, Md Hamidur; Bråtveit, Magne; Moen, Bente E

    2007-01-01

    Personal exposures to ammonia and acute respiratory effects were determined in workers at a urea fertilizer factory in Bangladesh. Full-shift personal exposure to ammonia was measured using a PAC III direct reading instrument and Drager diffusion tubes. Respiratory symptoms were elicited by a questionnaire study (n = 113), and preshift and postshift lung function (FVC, FEV1, and PEFR) were tested using spirometry (n = 88). Urea plant workers had higher mean exposure to ammonia and prevalence of acute respiratory symptoms than did workers in the ammonia plant. The symptoms with highest prevalence in the urea plant were chest tightness (33%) and cough (28%). FVC and FEV1 decreased significantly across the work shift among urea plant workers. The higher level of exposure to ammonia in the urea plant was associated with an increased prevalence of respiratory symptoms and an acute decline in lung function.

  1. Effects of acute sleep deprivation and caffeine supplementation on anaerobic performance.

    PubMed

    Moore, Joss; McDonald, Ciaran; McIntyre, Alan; Carmody, Kevin; Donne, Bernard

    2018-01-01

    Athletes involved in team sports may be subject to varying degrees of sleep deprivation either before or after training and competition. Despite the belief among athletes and coaches of the importance of adequate sleep for ensuing performance, the effect of sleep loss on team-sport anaerobic performance remains unclear. There is conflicting evidence in the scientific literature as to the impact of acute sleep deprivation and caffeine supplementation on anaerobic performance indices. The purpose of this study is to investigate the effect of 24 hours of acute sleep deprivation on anaerobic performance and the effect of caffeine supplementation on anaerobic performance in the sleep deprived state. 11 club level games players (n=11, 25±4 yr, 178±7.5 cm, 80.2±10.4 kg, 15.1±5.6% body fat) participated in a repeated measures double-blinded placebo control trial. Following familiarisation, each participant returned for testing on three separate occasions. One of the testing sessions took place following a night of normal sleep and the other two sessions took place following 24 hours of sleep deprivation with supplementation of either placebo or 6 mg.kg- 1 of caffeine. During each testing session participants performed the vertical jump height, 20-m straight sprint, Illinois speed agility test and 5-m shuttle run. No significant differences were detected comparing non sleep deprived and sleep deprived interventions in any of the assessed outcome measures. There were also no significant differences observed in any of the outcome measures when comparing caffeine and placebo data in the sleep deprived state. In this cohort of athletes, a 24-h period of acute sleep deprivation did not have any significant impact on anaerobic performance. Caffeine also did not have any effect of on anaerobic performance in the sleep-deprived state.

  2. The Chronic and Acute Effects of Exercise Upon Selected Blood Measures.

    ERIC Educational Resources Information Center

    Roitman, J. L.; Brewer, J. P.

    This study investigated the effects of chronic and acute exercise upon selected blood measures and indices. Nine male cross-country runners were studied. Red blood count, hemoglobin, and hematocrit were measured using standard laboratory techniques; mean corpuscular volume (MCV), mean corpuscular hemoglobin, and mean corpuscular hemoglobin…

  3. Marijuana's acute effects on cognitive bias for affective and marijuana cues.

    PubMed

    Metrik, Jane; Aston, Elizabeth R; Kahler, Christopher W; Rohsenow, Damaris J; McGeary, John E; Knopik, Valerie S

    2015-10-01

    Marijuana produces acute increases in positive subjective effects and decreased reactivity to negative affective stimuli, though may also acutely induce anxiety. Implicit attentional and evaluative processes may explicate marijuana's ability to acutely increase positive and negative emotions. This within-subjects study examined whether smoked marijuana with 2.7-3.0% delta-9-tetrahydrocannabinol (THC), relative to placebo, acutely changed attentional processing of rewarding and negative affective stimuli as well as marijuana-specific stimuli. On 2 separate days, regular marijuana users (N = 89) smoked placebo or active THC cigarette and completed subjective ratings of mood, intoxication, urge to smoke marijuana, and 2 experimental tasks: pleasantness rating (response latency and perceived pleasantness of affective and marijuana-related stimuli) and emotional Stroop (attentional bias to affective stimuli). On the pleasantness rating task, active marijuana increased response latency to negatively valenced and marijuana-related (vs. neutral) visual stimuli, beyond a general slowing of response. Active marijuana also increased pleasantness ratings of marijuana images, although to a lesser extent than placebo due to reduced marijuana urge after smoking. Overall, active marijuana did not acutely change processing of positive emotional stimuli. There was no evidence of attentional bias to affective word stimuli on the emotional Stroop task with the exception of attentional bias to positive word stimuli in the subgroup of marijuana users with cannabis dependence. Marijuana may increase allocation of attentional resources toward marijuana-specific and negatively valenced visual stimuli without altering processing of positively valenced stimuli. Marijuana-specific cues may be more attractive with higher levels of marijuana craving and less wanted with low craving levels. (c) 2015 APA, all rights reserved).

  4. The effect of activated protein C on experimental acute necrotizing pancreatitis

    PubMed Central

    Yamenel, Levent; Mas, Mehmet Refik; Comert, Bilgin; Isik, Ahmet Turan; Aydin, Sezai; Mas, Nuket; Deveci, Salih; Ozyurt, Mustafa; Tasci, Ilker; Unal, Tahir

    2005-01-01

    Introduction Acute pancreatitis is a local inflammatory process that leads to a systemic inflammatory response in the majority of cases. Bacterial contamination has been estimated to occur in 30–40% of patients with necrotizing pancreatitis. Development of pancreatic necrosis depends mainly on the degree of inflammation and on the microvascular circulation of the pancreatic tissue. Activated protein C (APC) is known to inhibit coagulation and inflammation, and to promote fibrinolysis in patients with severe sepsis. We investigated the effects of APC on histopathology, bacterial translocation, and systemic inflammation in experimental acute necrotizing pancreatitis. Materials and method Forty-five male Sprague-Dawley rats were studied. Rats were randomly allocated to three groups. Acute pancreatitis was induced in group II (positive control; n = 15) and group III (treatment; n = 15) rats by retrograde injection of taurocholate into the common biliopancreatic duct. Group I rats (sham; n = 15) received an injection of normal saline into the common biliopancreatic duct to mimic a pressure effect. Group III rats were treated with intravenous APC 6 hours after induction of pancreatitis. Pancreatic tissue and blood samples were obtained from all animals for histopathological examination and assessment of amylase, tumor necrosis factor-α, and IL-6 levels in serum. Bacterial translocation to pancreas and mesenteric lymph nodes was measured. Results Acute pancreatitis developed in all groups apart from group I (sham), as indicated by microscopic parenchymal necrosis, fat necrosis and abundant turbid peritoneal fluid. Histopathological pancreatitis scores in the APC-treated group were lower than in positive controls (10.31 ± 0.47 versus 14.00 ± 0.52; P < 0.001). Bacterial translocation to mesenteric lymph nodes and to pancreas in the APC-treated group was significantly decreased compared with controls (P < 0.02 and P < 0.007, respectively). Serum amylase, tumor necrosis

  5. Relationships between serum BDNF and the antidepressant effect of acute exercise in depressed women.

    PubMed

    Meyer, Jacob D; Koltyn, Kelli F; Stegner, Aaron J; Kim, Jee-Seon; Cook, Dane B

    2016-12-01

    Brain-derived neurotrophic factor (BDNF) has recently emerged as one potential mechanism with which exercise improves mood in major depressive disorder (MDD). This study examined the relationship between changes in serum total BDNF and mood following acute exercise in MDD. It was hypothesized that acute exercise would increase BDNF in an intensity-dependent manner and that changes in BDNF would be significantly related to improvement in depressed mood post-exercise. Twenty-four women (age: 38.6±14.0years) with MDD exercised for 30min on a stationary bicycle at light, moderate and hard exercise intensities and performed a quiet rest session using a within-subjects, randomized and counter-balanced design. Before, 10 and 30min after each session, participants completed the profile of mood states (POMS). Blood was drawn before and within 10min after completion of each session and serum total BDNF (sBDNF) was measured by enzyme-linked immunosorbent assay. Acute exercise-induced changes in POMS Depression and sBDNF were analyzed via 4 session (quiet rest, light, moderate, hard) by 2 measurement (pre, post) ANOVA. Secondary analyses examined the effects of baseline mood and antidepressant usage on sBDNF. Exercise resulted in an acute improvement in depressed mood that was not intensity dependent (p>0.05), resulting in significant acute increases in sBDNF (p=0.006) that were also not intensity-dependent (p>0.05). Acute changes in sBDNF were not significantly correlated to changes in POMS depression at 10m (r=-0.171, p=0.161) or 30m (r=-0.151, p=0.215) post-exercise. The fourteen participants taking antidepressant medications exhibited lower post-exercise sBDNF (p=0.015) than the participants not currently taking antidepressants, although mood responses were similar. Acute exercise is an effective mood-enhancing stimulus, although sBDNF does not appear to play a role in this short-term response. Patients who are not currently taking antidepressant medications and those who

  6. Effects of dietary fibre and protein on urea transport across the cecal mucosa of piglets.

    PubMed

    Stumpff, F; Lodemann, U; Van Kessel, A G; Pieper, R; Klingspor, S; Wolf, K; Martens, H; Zentek, J; Aschenbach, J R

    2013-12-01

    In ruminants, gastrointestinal recycling of urea is acutely enhanced by fibre-rich diets that lead to high ruminal concentration of short chain fatty acids (SCFA), while high ammonia has inhibitory effects. This study attempted to clarify if urea flux to the porcine cecum is similarly regulated. Thirty-two weaned piglets were fed diets containing protein (P) of poor prececal digestibility and fibre (F) at high (H) or low levels (L) in a 2 × 2 factorial design. After slaughter, cecal content was analyzed and the cecal mucosa incubated in Ussing chambers to measure the effect of pH, SCFA and NH4 (+) on the flux rates of urea, short-circuit current (I sc) and tissue conductance (G t). NH4 (+) significantly enhanced I sc (from 0.5 ± 0.2 to 1.2 ± 0.1 μEq cm(-2) h(-1)). No acute effects of SCFA or ammonia on urea flux were observed. Tissue conductance was significantly lower in the high dietary fibre groups irrespective of the protein content. Only the HP-LF group emerged as different from all others in terms of urea flux (74 ± 6 versus 53 ± 3 nmol cm(-2) h(-1)), associated with higher cecal ammonia concentration and reduced fecal consistency. The data suggest that as in the rumen, uptake of ammonia by the cecum may involve electrogenic transport of the ionic form (NH4 (+)). In contrast to findings in the rumen, neither a high fibre diet nor acute addition of SCFA enhanced urea transport across the pig cecum. Instead, a HP-LF diet had stimulatory effects. A potential role for urea recycling in stabilizing luminal pH is discussed.

  7. Comprehensive Study of Acute Effects and Recovery After Concussion

    DTIC Science & Technology

    2015-10-01

    1 AD______________ AWARD NUMBER: W81XWH-14-1-0561 TITLE: Comprehensive Study of Acute Effects and Recovery After Concussion PRINCIPAL... Concussion 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Michael McCrea, PhD, ABPP 5d. PROJECT NUMBER Professor & Director of Brain Injury Research...course of 3 years, the project is progressing on schedule. We baseline tested 545 football athletes from July 13, 2015 to Aug 21, 2015. We enrolled

  8. A QUANTITATIVE COMPARISON OF THE EFFECTS OF ACUTE INHALED TOLUENE IN HUMAN RATS

    EPA Science Inventory

    The effects of acute exposure to toluene have been explored more thoroughly than other hydrocarbon solvents. These effects have been experimentally studied in humans and other species, e.g., rats, as well as in a number of in vitro preparations. The existence ofdosimetric and eff...

  9. Effects of acute handling stress on short-term central expression of orexigenic/anorexigenic genes in zebrafish.

    PubMed

    Cortés, Raul; Teles, Mariana; Oliveira, Miguel; Fierro-Castro, Camino; Tort, Lluis; Cerdá-Reverter, José Miguel

    2018-02-01

    Physiological mechanisms driving stress response in vertebrates are evolutionarily conserved. These mechanisms involve the activation of both the hypothalamic-sympathetic-chromaffin cell (HSC) and the hypothalamic-pituitary-adrenal (HPA) axes. In fish, the reduction of food intake levels is a common feature of the behavioral response to stress but the central mechanisms coordinating the energetic response are not well understood yet. In this work, we explore the effects of acute stress on key central systems regulating food intake in fish as well as on total body cortisol and glucose levels. We show that acute stress induced a rapid increase in total body cortisol with no changes in body glucose, at the same time promoting a prompt central response by activating neuronal pathways. All three orexigenic peptides examined, i.e., neuropeptide y (npy), agouti-related protein (agrp), and ghrelin, increased their central expression level suggesting that these neuronal systems are not involved in the short-term feeding inhibitory effects of acute stress. By contrast, the anorexigenic precursors tested, i.e., cart peptides and pomc, exhibited increased expression after acute stress, suggesting their involvement in the anorexigenic effects.

  10. Global gene expression in the bovine corpus luteum is altered after stimulatory and superovulatory treatments.

    PubMed

    Fátima, Luciana A; Baruselli, Pietro S; Gimenes, Lindsay U; Binelli, Mario; Rennó, Francisco P; Murphy, Bruce D; Papa, Paula C

    2013-01-01

    Equine chorionic gonadotrophin (eCG) has been widely used in superovulation and artificial insemination programmes and usually promotes an increase in corpus luteum (CL) volume and stimulates progesterone production. Therefore, to identify eCG-regulated genes in the bovine CL, the transcriptome was evaluated by microarray analysis and the expression of selected genes was validated by qPCR and western blot. Eighteen Nelore crossbred cows were divided into control (n=5), stimulated (n=6) and superovulated groups (n=7). Ovulation was synchronised using a progesterone device-based protocol. Stimulated animals received 400 IU of eCG at device removal and superovulated animals received 2000 IU of eCG 4 days prior. Corpora lutea were collected 7 days after gonadotrophin-releasing hormone administration. Overall, 242 transcripts were upregulated and 111 transcripts were downregulated in stimulated cows (P ≤ 0.05) and 111 were upregulated and 113 downregulated in superovulated cows compared to the control animals (1.5-fold, P ≤ 0.05). Among the differentially expressed genes, many were involved in lipid biosynthesis and progesterone production, such as PPARG, STAR, prolactin receptors and follistatin. In conclusion, eCG modulates gene expression differently depending on the treatment, i.e. stimulatory or superovulatory. Our data contribute to the understanding of the pathways involved in increased progesterone levels observed after eCG treatment.

  11. Effects of a probiotic intervention in acute canine gastroenteritis--a controlled clinical trial.

    PubMed

    Herstad, H K; Nesheim, B B; L'Abée-Lund, T; Larsen, S; Skancke, E

    2010-01-01

    To evaluate the effect of a probiotic product in acute self-limiting gastroenteritis in dogs. Thirty-six dogs suffering from acute diarrhoea or acute diarrhoea and vomiting were included in the study. The trial was performed as a randomised, double blind and single centre study with stratified parallel group design. The animals were allocated to equal looking probiotic or placebo treatment by block randomisation with a fixed block size of six. The probiotic cocktail consisted of thermo-stabilised Lactobacillus acidophilus and live strains of Pediococcus acidilactici, Bacillus subtilis, Bacillus licheniformis and Lactobacillus farciminis. The time from initiation of treatment to the last abnormal stools was found to be significantly shorter (P = 0.04) in the probiotic group compared to placebo group, the mean time was 1.3 days and 2.2 days, respectively. The two groups were found nearly equal with regard to time from start of treatment to the last vomiting episode. The probiotic tested may reduce the convalescence time in acute self-limiting diarrhoea in dogs.

  12. The acute physiological and mood effects of tea and coffee: the role of caffeine level.

    PubMed

    Quinlan, P T; Lane, J; Moore, K L; Aspen, J; Rycroft, J A; O'Brien, D C

    2000-05-01

    The objective of this study was to determine the effect of caffeine level in tea and coffee on acute physiological responses and mood. Randomised full crossover design in subjects after overnight caffeine abstention was studied. In study 1 (n = 17) the caffeine level was manipulated naturalistically by preparing tea and coffee at different strengths (1 or 2 cups equivalent). Caffeine levels were 37.5 and 75 mg in tea, 75 and 150 mg in coffee, with water and no-drink controls. In study 2 (n = 15) caffeine level alone was manipulated (water, decaffeinated tea, plus 0, 25, 50, 100, and 200 mg caffeine). Beverage volume and temperature (55 degrees C) were constant. SBP, DBP, heart rate, skin temperature, skin conductance, and mood were monitored over each 3-h study session. In study 1, tea and coffee produced mild autonomic stimulation and an elevation in mood. There were no effects of tea vs. coffee or caffeine dose, despite a fourfold variation in the latter. Increasing beverage strength was associated with greater increases in DBP and energetic arousal. In study 2, caffeinated beverages increased SBP, DBP, and skin conductance and lowered heart rate and skin temperature compared to water. Significant dose-response relationships to caffeine were seen only for SBP, heart rate, and skin temperature. There were significant effects of caffeine on energetic arousal but no consistent dose-response effects. Caffeinated beverages acutely stimulate the autonomic nervous system and increase alertness. Although caffeine can exert dose-dependent effects on a number of acute autonomic responses, caffeine level is not an important factor. Factors besides caffeine may contribute to these acute effects.

  13. Acute effects of high- and low-intensity exercise bouts on leukocyte counts.

    PubMed

    Neves, Pedro Rogério Da Silva; Tenório, Thiago Ricardo Dos Santos; Lins, Tatiana Acioli; Muniz, Maria Tereza Cartaxo; Pithon-Curi, Tânia Cristina; Botero, João Paulo; Do Prado, Wagner Luiz

    2015-06-01

    It is widely accepted that physical exercise may bring about changes in the immune system. Even acute bouts of exercise can alter the number and function of leukocytes, but the degree of white blood cell trafficking depends on the intensity and duration of exercise. The aim of this study was to analyze the acute and short-term effects of exercise intensity on leukocyte counts and leukocyte subsets. Nine physically healthy, active young males (21.0 ± 1.9 years) underwent three experimental trials: high exercise intensity [80% peak oxygen consumption (VO 2peak )], low exercise intensity (40% VO 2peak ), and the control condition (no exercise). Blood samples were collected prior to exercise, immediately after exercise, and 2 hours after exercise. Two-way analysis of variance for repeated measures was used to evaluate differences between the trials and the time-points, and to compare times within trials. There was a greater increase in the leukocyte count after high-intensity exercise, compared to the control condition ( p  < 0.01) and low-intensity exercise ( p  < 0.01). This effect was still present 2 hours after passive recovery ( p  < 0.01). When the same participants were submitted to different exercise intensities, the acute and short-term effects of exercise on white blood cells were intensity-dependent immediately after exercise (i.e., lymphocytosis and monocytosis) and 2 hours after passive recovery (i.e., neutrophilia).

  14. Acute effects of physical exercise in type 2 diabetes: A review

    PubMed Central

    Asano, Ricardo Yukio; Sales, Marcelo Magalhães; Browne, Rodrigo Alberto Vieira; Moraes, José Fernando Vila Nova; Coelho Júnior, Hélio José; Moraes, Milton Rocha; Simões, Herbert Gustavo

    2014-01-01

    The literature has shown the efficiency of exercise in the control of type 2 diabetes (T2D), being suggested as one of the best kinds of non-pharmacological treatments for its population. Thus, the scientific production related to this phenomenon has growing exponentially. However, despite its advances, still there is a lack of studies that have carried out a review on the acute effects of physical exercise on metabolic and hemodynamic markers and possible control mechanisms of these indicators in individuals with T2D, not to mention that in a related way, these themes have been very little studied today. Therefore, the aim of this study was to organize and analyze the current scientific production about the acute effects of physical exercise on metabolic and hemodynamic markers and possible control mechanisms of these indicators in T2D individuals. For such, a research with the following keywords was performed: -exercise; diabetes and post-exercise hypotension; diabetes and excess post-exercise oxygen consumption; diabetes and acute effects in PUBMED, SCIELO and HIGHWIRE databases. From the analyzed studies, it is possible to conclude that, a single exercise session can promote an increase in the bioavailability of nitric oxide and elicit decreases in postexercise blood pressure. Furthermore, the metabolic stress from physical exercise can increase the oxidation of carbohydrate during the exercise and keep it, in high levels, the post exercise consumption of O², this phenomenon increases the rate of fat oxidation during recovery periods after exercise, improves glucose tolerance and insulin sensitivity and reduces glycemia between 2-72 h, which seems to be dependent on the exercise intensity and duration of the effort. PMID:25317243

  15. The effectiveness and experience of self-management following acute coronary syndrome: A review of the literature.

    PubMed

    Guo, Ping; Harris, Ruth

    2016-09-01

    To evaluate the effectiveness of interventions used to support self-management, and to explore patients' experiences after acute coronary syndrome in relation to self-management. Scoping review. Keyword search of CINAHL Plus, Medline, the Cochrane Library, and PsycINFO databases for studies conducted with adult population and published in English between 1993 and 2014. From title and abstract review, duplicated articles and obviously irrelevant studies were removed. The full texts of the remaining articles were assessed against the selection criteria. Studies were included if they were original research on: (1) effectiveness of self-management interventions among individuals following acute coronary syndrome; or (2) patients' experience of self-managing recovery from acute coronary syndrome. 44 articles (19 quantitative and 25 qualitative) were included. Most studies were conducted in western countries and quantitative studies were UK centric. Self-management interventions tended to be complex and include several components, including education and counselling, goal setting and problem solving skills which were mainly professional-led rather than patient-led. The review demonstrated variation in the effectiveness of self-management interventions in main outcomes assessed - anxiety and depression, quality of life and health behavioural outcomes. For most participants in the qualitative studies, acute coronary syndrome was unexpected and the recovery trajectory was a complex process. Experiences of making adjustment and adopting lifestyle changes following acute coronary syndrome were influenced by subjective life experiences and individual, sociocultural and environmental contexts. Participants' misunderstandings, misconceptions and confusion about disease processes and management were another influential factor. They emphasised a need for ongoing input and continued support from health professionals in their self-management of rehabilitation and recovery

  16. Crystal structure of human dual specificity phosphatase, JNK stimulatory phosphatase-1, at 1.5 A resolution.

    PubMed

    Yokota, Takehiro; Nara, Yukinori; Kashima, Akiko; Matsubara, Keiko; Misawa, Satoru; Kato, Ryohei; Sugio, Shigetoshi

    2007-02-01

    Human JNK stimulatory phosphatase-1 (JSP-1) is a novel member of dual specificity phosphatases. A C-terminus truncated JSP-1 was expressed in Escherichia coli and was crystallized using the sitting-drop vapor diffusion method. Thin-plate crystals obtained at 278 K belong to a monoclinic space group, C2, with unit-cell parameters a = 84.0 A, b = 49.3 A, c = 47.3 A, and beta = 119.5 degrees , and diffract up to 1.5 A resolution at 100 K. The structure of JSP-1 has a single compact (alpha/beta) domain, which consists of six alpha-helices and five beta-strands, and shows a conserved structural scaffold in regard to both DSPs and PTPs. A cleft formed by a PTP-loop at the active site is very shallow, and is occupied by one sulfonate compound, MES, at the bottom. In the binary complex structure of JSP-1 with MES, the conformations of three important segments in regard to the catalytic mechanism are not similar to those in PTP1B. JSP-1 has no loop corresponding to the Lys120-loop of PTP1B, and tryptophan residue corresponding to the substrate-stacking in PTP1B is substituted by alanine residue in JSP-1. Copyright 2006 Wiley-Liss, Inc.

  17. Effects of grape seed polyphenols on oxidative damage in liver tissue of acutely and chronically exercised rats.

    PubMed

    Belviranlı, Muaz; Gökbel, Hakkı; Okudan, Nilsel; Büyükbaş, Sadık

    2013-05-01

    The objective of the present study was to investigate the effects of grape seed extract (GSE) supplementation on oxidative stress and antioxidant defense markers in liver tissue of acutely and chronically exercised rats. Rats were randomly assigned to six groups: Control (C), Control Chronic Exercise (CE), Control Acute Exercise (AE), GSE-supplemented Control (GC), GSE-supplemented Chronic Exercise(GCE) and GSE-supplemented Acute Exercise (GAE). Rats in the chronic exercise groups were subjected to a six-week treadmill running and in the acute exercise groups performed an exhaustive running. Rats in the GSE supplemented groups received GSE (100 mg.kg(-1) .day(-1) ) in drinking water for 6 weeks. Liver tissues of the rats were taken for the analysis of malondialdehyde (MDA), nitric oxide (NO) levels and total antioxidant activity (AOA) and xanthine oxidase (XO) activities. MDA levels decreased with GSE supplementation in control groups but increased in acute and chronic exercise groups compared to their non-supplemented control. NO levels increased with GSE supplementation. XO activities were higher in AE group compared to the CE group. AOA decreased with GSE supplementation. In conclusion, while acute exercise triggers oxidative stress, chronic exercise has protective role against oxidative stress. GSE has a limited antioxidant effect on exercise-induced oxidative stress in liver tissue.

  18. Effects of alcohol on body-sway patterns in human subjects.

    PubMed

    Nieschalk, M; Ortmann, C; West, A; Schmäl, F; Stoll, W; Fechner, G

    1999-01-01

    The vestibulospinal aspects of vestibular function are commonly neglected in the evaluation of alcohol-induced intoxication. Thus, in the present study the effect of an acute intoxication with a low or moderate quantity of alcohol was examined with respect to the equilibrium in 30 healthy subjects. The blood alcohol concentration (BAC) was measured 30 min after the ingestion of the last alcohol, ranging between 0.22 and 1.59 per thousand. Stability of stance was quantified by static platform posturography in Romberg-test conditions with eyes open and eyes closed. Among other parameters, the average body sway path (SP) and area of body sway (SA) were assessed. Posturography revealed a significant increase in body sway. There was a positive correlation between SA (or SP) and BAC both with eyes open and eyes closed. Multiple group comparisons revealed that the large-alcohol-dose group (BAC > or = 1.0 per thousand) could be clearly differentiated from test cases with BAC lower than 0.8 per thousand. Sway area was the most sensitive parameter for detecting increased body sway after alcohol ingestion. The area increase, present not only with eyes closed but with eyes open, revealed an inadequate compensation of the ethanol-induced ataxia by visual stabilization. The Romberg's quotient, which denotes eyes closed relative to eyes open, remained constant. The increase in sway path with eyes closed showed an omnidirectional sway. A comparison of the sway pattern of subjects after acute ethanol ingestion with the data of patients with permanent cerebellar lesions suggested that the acute effect of alcohol resembles that of a lesion of the spinocerebellum. This finding contrasts with earlier studies, which postulated an acute effect of ethanol resembling that in patients with an atrophy of the anterior lobe of the cerebellum due to chronic alcohol abuse. In seven cases of the lower dose group (BAC < or = 0.8 per thousand), a reduction in body sway after alcohol ingestion was

  19. Acute Hypercortisolemia Exerts Depot-Specific Effects on Abdominal and Femoral Adipose Tissue Function

    PubMed Central

    O’Reilly, Michael W.; Bujalska, Iwona J.; Tomlinson, Jeremy W.; Arlt, Wiebke

    2017-01-01

    Context: Glucocorticoids have pleiotropic metabolic functions, and acute glucocorticoid excess affects fatty acid metabolism, increasing systemic lipolysis. Whether glucocorticoids exert adipose tissue depot-specific effects remains unclear. Objective: To provide an in vivo assessment of femoral and abdominal adipose tissue responses to acute glucocorticoid administration. Design and Outcome Measures: Nine healthy male volunteers were studied on two occasions, after a hydrocortisone infusion (0.2 mg/kg/min for 14 hours) and a saline infusion, respectively, given in randomized double-blind order. The subjects were studied in the fasting state and after a 75-g glucose drink with an in vivo assessment of femoral adipose tissue blood flow (ATBF) using radioactive xenon washout and of lipolysis and glucose uptake using the arteriovenous difference technique. In a separate study (same infusion design), eight additional healthy male subjects underwent assessment of fasting abdominal ATBF and lipolysis only. Lipolysis was assessed as the net release of nonesterified fatty acids (NEFAs) from femoral and abdominal subcutaneous adipose tissue. Results: Acute hypercortisolemia significantly increased basal and postprandial ATBF in femoral adipose tissue, but the femoral net NEFA release did not change. In abdominal adipose tissue, hypercortisolemia induced substantial increases in basal ATBF and NEFA release. Conclusions: Acute hypercortisolemia induces differential lipolysis and ATBF responses in abdominal and femoral adipose tissue, suggesting depot-specific glucocorticoid effects. Abdominal, but not femoral, adipose tissue contributes to the hypercortisolemia-induced systemic NEFA increase, with likely contributions from other adipose tissue sources and intravascular triglyceride hydrolysis. PMID:28323916

  20. Evaluation of Propranolol Effect on Experimental Acute and Chronic Toxoplasmosis Using Quantitative PCR

    PubMed Central

    Montazeri, Mahbobeh; Ebrahimzadeh, Mohammad Ali; Ahmadpour, Ehsan; Sharif, Mehdi; Sarvi, Shahabeddin

    2016-01-01

    Current therapies against toxoplasmosis are limited, and drugs have significant side effects and low efficacies. We evaluated the potential anti-Toxoplasma activity of propranolol at a dose of 2 or 3 mg/kg of body weight/day in vivo in the acute and chronic phases. Propranolol as a cell membrane-stabilizing agent is a suitable drug for inhibiting the entrance of Toxoplasma gondii tachyzoites into cells. The acute-phase assay was performed using propranolol, pyrimethamine, and propranolol plus pyrimethamine before (pretreatment) and after (posttreatment) intraperitoneal challenge with 1 × 103 tachyzoites of the virulent T. gondii strain RH in BALB/c mice. Also, in the chronic phase, treatment was performed 12 h before intraperitoneal challenge with 1 × 106 tachyzoites of the virulent strain RH of T. gondii in rats. One week (in the acute phase) and 2 months (in the chronic phase) after postinfection, tissues were isolated and DNA was extracted. Subsequently, parasite load was calculated using quantitative PCR (qPCR). In the acute phase, in both groups, significant anti-Toxoplasma activity was observed using propranolol (P < 0.001). Propranolol in the pretreatment group showed higher anti-Toxoplasma activity than propranolol in posttreatment in brain tissues, displaying therapeutic efficiency on toxoplasmosis. Also, propranolol combined with pyrimethamine reduced the parasite load as well as significantly increased survival of mice in the pretreatment group. In the chronic phase, anti-Toxoplasma activity and decreased parasite load in tissues were observed with propranolol. In conclusion, the presented results demonstrate that propranolol, as an orally available drug, is effective at low doses against acute and latent murine toxoplasmosis, and the efficiency of the drug is increased when it is used in combination therapy with pyrimethamine. PMID:27645234

  1. Effect of acute psychological stress on prefrontal GABA concentration determined by proton magnetic resonance spectroscopy.

    PubMed

    Hasler, Gregor; van der Veen, Jan Willem; Grillon, Christian; Drevets, Wayne C; Shen, Jun

    2010-10-01

    Impaired function of the central gamma-aminobutyric acid (GABA) system, which provides the brain's major inhibitory pathways, is thought to play an important role in the pathophysiology of anxiety disorders. The effect of acute psychological stress on the human GABA-ergic system is still unknown, however. The purpose of this study was to determine the effect of acute stress on prefrontal GABA levels. A recently developed noninvasive magnetic resonance spectroscopy method was used to measure changes in the GABA concentration of the prefrontal cortex in 10 healthy human subjects during a threat-of-shock condition and during a safe condition (two sessions on different days). The main outcome measure was the mean GABA concentration within a 3×3×2-cm(3) voxel selected from the medial prefrontal cortex. Prefrontal GABA decreased by approximately 18% in the threat-of-shock condition relative to the safe condition. This reduction was specific to GABA, since the concentrations of N-acetyl-aspartate, choline-containing compounds, and glutamate/glutamine levels obtained in the same spectra did not change significantly. This result appeared compatible with evidence from preclinical studies in rodents, which showed rapid presynaptic down-regulation of GABA-ergic neurotransmission in response to acute psychological stress. The molecular mechanism and functional significance of this reduced inhibitory effect of acute psychological stress in relation to impaired GABA-ergic function in anxiety disorders merit further investigation.

  2. Acute and Chronic Effects of Ethanol on Learning-Related Synaptic Plasticity

    PubMed Central

    Zorumski, Charles F.; Mennerick, Steven; Izumi, Yukitoshi

    2014-01-01

    Alcoholism is associated with acute and long-term cognitive dysfunction including memory impairment, resulting in substantial disability and cost to society. Thus, understanding how ethanol impairs cognition is essential for developing treatment strategies to dampen its adverse impact. Memory processing is thought to involve persistent, use-dependent changes in synaptic transmission, and ethanol alters the activity of multiple signaling molecules involved in synaptic processing, including modulation of the glutamate and gamma-aminobutyric acid (GABA) transmitter systems that mediate most fast excitatory and inhibitory transmission in the brain. Effects on glutamate and GABA receptors contribute to ethanol-induced changes in long-term potentiation (LTP) and long-term depression (LTD), forms of synaptic plasticity thought to underlie memory acquisition. In this paper, we review the effects of ethanol on learning-related forms of synaptic plasticity with emphasis on changes observed in the hippocampus, a brain region that is critical for encoding contextual and episodic memories. We also include studies in other brain regions as they pertain to altered cognitive and mental function. Comparison of effects in the hippocampus to other brain regions is instructive for understanding the complexities of ethanol’s acute and long-term pharmacological consequences. PMID:24447472

  3. TOWARD COST-BENEFIT ANALYSIS OF ACUTE BEHAVIORAL EFFECTS OF TOLUENE IN HUMANS

    EPA Science Inventory

    There is increasing interest in being able to express the consequences of exposure to potentially toxic compounds in monetary terms in order to evaluate potential cost-benefit relationships of controlling exposure. Behavioral effects of acute toluene exposure could be subjected ...

  4. Acute effects of aerobic exercise on cognitive function in individuals with Parkinson's disease.

    PubMed

    Silveira, Carolina R A; Roy, Eric A; Almeida, Quincy J

    2018-04-03

    Deficits in executive functions are highly prevalent in Parkinson's disease (PD). Although chronic physical exercise has been shown to improve executive functions in PD, evidence of acute exercise effects is limited. This study aimed to evaluate the effects of an acute bout of exercise on cognitive processes underlying executive functions in PD. Twenty individuals with PD were assessed in both a Control and an Exercise conditions. In each condition, individuals started performing a simple and a choice reaction time (RT) task. Subsequently, participants were asked to sit on a cycle ergometer (Control) or cycle (Exercise) for 20 min in counterbalanced order. Participants were asked to repeat both reaction time tasks after 15-min rest period in both conditions. While no differences were found in simple RT, participants showed faster choice RT post Exercise as well as Control conditions (p = .012). Participants had slower choice RT for target stimulus compared to non-target stimuli irrespective of time or experimental condition (p < .001). There was no change in accuracy following experimental conditions. Results suggest that individuals with PD may not respond behaviourally to a single bout of exercise. The lack of selective effects of exercise on cognition suggests that practice effects may have influenced previous research. Future studies should assess whether neurophysiological changes might occur after an acute bout of exercise in PD. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Persistent cerebrovascular effects of MDMA and acute responses to the drug.

    PubMed

    Ferrington, Linda; Kirilly, Eszter; McBean, Douglas E; Olverman, Henry J; Bagdy, György; Kelly, Paul A T

    2006-07-01

    Acutely, 3,4,-methylenedioxymethamphetamine (MDMA) induces cerebrovascular dysfunction [Quate et al., (2004)Psychopharmacol., 173, 287-295]. In the longer term the same single dose results in depletion of 5-hydroxytrptamine (5-HT) nerve terminals. In this study we examined the cerebrovascular consequences of this persistent neurodegeneration, and the acute effects of subsequent MDMA exposure, upon the relationship that normally exists between local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCMRglu). Dark agouti (DA) rats were pre-treated with 15 mg/kg i.p. MDMA or saline. Three weeks later, rats from each pre-treatment group were treated with an acute dose of MDMA (15 mg/kg i.p.) or saline. Quantitative autoradiographic imaging was used to measure LCBF or LCMRglu with [(14)C]-iodoantipyrine and [(14)C]-2-deoxyglucose, respectively. Serotonergic terminal depletion was assessed using radioligand binding with [(3)H]-paroxetine and immunohistochemistry. Three weeks after MDMA pre-treatment there were significant reductions in densities of 5-HT transporter (SERT)-positive fibres (-46%) and [(3)H]-paroxetine binding (-47%). In animals pre-treated with MDMA there were widespread significant decreases in LCMRglu, but no change in LCBF indicating a persistent loss of cerebrovascular constrictor tone. In both pre-treatment groups, acute MDMA produced significant increases in LCMRglu, while LCBF was significantly decreased. In 50% of MDMA-pre-treated rats, random areas of focal hyperaemia indicated a loss of autoregulatory capacity in response to MDMA-induced hypertension. These results suggest that cerebrovascular regulatory dysfunction resulting from acute exposure to MDMA is not diminished by previous exposure, despite a significant depletion in 5-HT terminals. However, there may be a sub-population, or individual circumstances, in which this dysfunction develops into a condition that might predispose to stroke.

  6. Chronic vs. Short-Term Acute O 3 Exposure Effects on Nocturnal Transpiration in Two Californian Oaks

    Treesearch

    Nancy Grulke; E. Paoletti; R. L. Heath

    2007-01-01

    We tested the effect of daytime chronic moderate ozone (O3) exposure, short-term acute exposure, and both chronic and acute O3 exposure combined on nocturnal transpiration in California black oak and blue oak seedlings. Chronic O3 exposure (70 ppb for 8 h/day) was implemented in open-top chambers for...

  7. Effects of acute corticosterone treatment on partner preferences in male and female zebra finches (Taeniopygia guttata).

    PubMed

    LaPlante, Kimberly A; Huremovic, Enida; Tomaszycki, Michelle L

    2014-04-01

    Stress alters physiology and behavior across species. Most research on the effects of stress on behavior uses chronic stressors, and most are correlational. The effects of acute stressors on physiology and behavior have been mixed. Here, we use zebra finches, a highly gregarious species that forms long-term pair bonds, to test the effects of an acute corticosterone (CORT) on opposite-sex partner preferences over a same-sex individual or a group (the latter is a highly appealing option). We had two competing hypotheses. First, we predicted that acute CORT would alter preferences for the opposite sex bird in both conditions in both sexes. However, since there is a sex difference in the effects of CORT on partner preferences in voles, these effects may be more pronounced in males than in females. To test our hypotheses, we administered 2 doses of CORT (10μg and 20μg) or vehicle (control) using a repeated measures design. In the male vs. female test, there was a significant Sex by Treatment interaction, such that in males, 10μg CORT increased preferences for a female over the male compared to when these same males were treated with saline at baseline. There were no effects of treatment in females. In the opposite-sex vs. group condition, there was an overall effect of Treatment, such that the 10μg dose increased preference for the opposite-sex individual over both saline treatments, regardless of sex. These findings further our understanding of the effects of an acute stressor on sexual partner preferences. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Acylated and unacylated ghrelin do not directly stimulate glucose transport in isolated rodent skeletal muscle.

    PubMed

    Cervone, Daniel T; Dyck, David J

    2017-07-01

    Emerging evidence implicates ghrelin, a gut-derived, orexigenic hormone, as a potential mediator of insulin-responsive peripheral tissue metabolism. However, in vitro and in vivo studies assessing ghrelin's direct influence on metabolism have been controversial, particularly due to confounding factors such as the secondary rise in growth hormone (GH) after ghrelin injection. Skeletal muscle is important in the insulin-stimulated clearance of glucose, and ghrelin's exponential rise prior to a meal could potentially facilitate this. This study was aimed at elucidating any direct stimulatory action that ghrelin may have on glucose transport and insulin signaling in isolated rat skeletal muscle, in the absence of confounding secondary factors. Oxidative soleus and glycolytic extensor digitorum longus skeletal muscles were isolated from male Sprague Dawley rats in the fed state and incubated with various concentrations of acylated and unacylated ghrelin in the presence or absence of insulin. Ghrelin did not stimulate glucose transport in either muscle type, with or without insulin. Moreover, GH had no acute, direct stimulatory effect on either basal or insulin-stimulated muscle glucose transport. In agreement with the lack of observed effect on glucose transport, ghrelin and GH also had no stimulatory effect on Ser 473 AKT or Thr 172 AMPK phosphorylation, two key signaling proteins involved in glucose transport. Furthermore, to our knowledge, we are among the first to show that ghrelin can act independent of its receptor and cause an increase in calmodulin-dependent protein kinase 2 (CaMKII) phosphorylation in glycolytic muscle, although this was not associated with an increase in glucose transport. We conclude that both acylated and unacylated ghrelin have no direct, acute influence on skeletal muscle glucose transport. Furthermore, the immediate rise in GH in response to ghrelin also does not appear to directly stimulate glucose transport in muscle. © 2017 The

  9. Acute pancreatitis.

    PubMed

    Talukdar, Rupjyoti; Vege, Santhi S

    2015-09-01

    To summarize recent data on classification systems, cause, risk factors, severity prediction, nutrition, and drug treatment of acute pancreatitis. Comparison of the Revised Atlanta Classification and Determinant Based Classification has shown heterogeneous results. Simvastatin has a protective effect against acute pancreatitis. Young black male, alcohol, smoldering symptoms, and subsequent diagnosis of chronic pancreatitis are risk factors associated with readmissions after acute pancreatitis. A reliable clinical or laboratory marker or a scoring system to predict severity is lacking. The PYTHON trial has shown that oral feeding with on demand nasoenteric tube feeding after 72 h is as good as nasoenteric tube feeding within 24 h in preventing infections in predicted severe acute pancreatitis. Male sex, multiple organ failure, extent of pancreatic necrosis, and heterogeneous collection are factors associated with failure of percutaneous drainage of pancreatic collections. The newly proposed classification systems of acute pancreatitis need to be evaluated more critically. New biomarkers are needed for severity prediction. Further well designed studies are required to assess the type of enteral nutritional formulations for acute pancreatitis. The optimal minimally invasive method or combination to debride the necrotic collections is evolving. There is a great need for a drug to treat the disease early on to prevent morbidity and mortality.

  10. Effect of chronic and acute low-frequency repetitive transcranial magnetic stimulation on spatial memory in rats.

    PubMed

    Li, Wei; Yang, Yuye; Ye, Qing; Yang, Bo; Wang, Zhengrong

    2007-03-15

    Repetitive transcranial magnetic stimulation (rTMS) is a novel, non-invasive neurological and psychiatric tool. The low-frequency (1 Hz or less) rTMS is likely to play a particular role in its mechanism of action with different effects in comparison with high-frequency (>1 Hz) rTMS. There is limited information regarding the effect of low-frequency rTMS on spatial memory. In our study, each male Wistar rat was daily given 300 stimuli (1.0 T, 200 micros) at a rate of 0.5 Hz or sham stimulation. We investigated the effects of chronic and acute rTMS on reference/working memory process in Morris water maze test with the hypothesis that the effect would differ by chronic or acute condition. Chronic low-frequency rTMS impaired the retrieval of spatial short- and long-term spatial reference memory but not acquisition process and working memory, whereas acute low-frequency rTMS predominantly induced no deficits in acquisition or short-term spatial reference memory as well as working memory except for long-term reference memory. In summary, chronic 0.5 Hz rTMS disrupts spatial short- and long-term reference memory function, but acute rTMS differently affects reference memory. Chronic low-frequency rTMS may be used to modulate reference memory. Treatment protocols using low-frequency rTMS in neurological and psychiatric disorders need to take into account the potential effect of chronic low-frequency rTMS on memory and other cognitive functions.

  11. Cost-effectiveness of emergency versus delayed laparoscopic cholecystectomy for acute gallbladder pathology.

    PubMed

    Sutton, A J; Vohra, R S; Hollyman, M; Marriott, P J; Buja, A; Alderson, D; Pasquali, S; Griffiths, E A

    2017-01-01

    The optimal timing of cholecystectomy for patients admitted with acute gallbladder pathology is unclear. Some studies have shown that emergency cholecystectomy during the index admission can reduce length of hospital stay with similar rates of conversion to open surgery, complications and mortality compared with a 'delayed' operation following discharge. Others have reported that cholecystectomy during the index acute admission results in higher morbidity, extended length of stay and increased costs. This study examined the cost-effectiveness of emergency versus delayed cholecystectomy for acute benign gallbladder disease. Using data from a prospective population-based cohort study examining the outcomes of cholecystectomy in the UK and Ireland, a model-based cost-utility analysis was conducted from the perspective of the UK National Health Service, with a 1-year time horizon for costs and outcomes. Probabilistic sensitivity analysis was used to investigate the impact of parameter uncertainty on the results obtained from the model. Emergency cholecystectomy was found to be less costly (£4570 versus £4720; €5484 versus €5664) and more effective (0·8868 versus 0·8662 QALYs) than delayed cholecystectomy. Probabilistic sensitivity analysis showed that the emergency strategy is more than 60 per cent likely to be cost-effective across willingness-to-pay values for the QALY from £0 to £100 000 (€0-120 000). Emergency cholecystectomy is less costly and more effective than delayed cholecystectomy. This approach is likely to be beneficial to patients in terms of improved health outcomes and to the healthcare provider owing to the reduced costs. © 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.

  12. Effects of the Acute and Chronic Ethanol Intoxication on Acetate Metabolism and Kinetics in the Rat Brain.

    PubMed

    Hsieh, Ya-Ju; Wu, Liang-Chih; Ke, Chien-Chih; Chang, Chi-Wei; Kuo, Jung-Wen; Huang, Wen-Sheng; Chen, Fu-Du; Yang, Bang-Hung; Tai, Hsiao-Ting; Chen, Sharon Chia-Ju; Liu, Ren-Shyan

    2018-02-01

    Ethanol (EtOH) intoxication inhibits glucose transport and decreases overall brain glucose metabolism; however, humans with long-term EtOH consumption were found to have a significant increase in [1- 11 C]-acetate uptake in the brain. The relationship between the cause and effect of [1- 11 C]-acetate kinetics and acute/chronic EtOH intoxication, however, is still unclear. [1- 11 C]-acetate positron emission tomography (PET) with dynamic measurement of K 1 and k 2 rate constants was used to investigate the changes in acetate metabolism in different brain regions of rats with acute or chronic EtOH intoxication. PET imaging demonstrated decreased [1- 11 C]-acetate uptake in rat brain with acute EtOH intoxication, but this increased with chronic EtOH intoxication. Tracer uptake rate constant K 1 and clearance rate constant k 2 were decreased in acutely intoxicated rats. No significant change was noted in K 1 and k 2 in chronic EtOH intoxication, although 6 of 7 brain regions showed slightly higher k 2 than baseline. These results indicate that acute EtOH intoxication accelerated acetate transport and metabolism in the rat brain, whereas chronic EtOH intoxication status showed no significant effect. In vivo PET study confirmed the modulatory role of EtOH, administered acutely or chronically, in [1- 11 C]-acetate kinetics and metabolism in the rat brain. Acute EtOH intoxication may inhibit the transport and metabolism of acetate in the brain, whereas chronic EtOH exposure may lead to the adaptation of the rat brain to EtOH in acetate utilization. [1- 11 C]-acetate PET imaging is a feasible approach to study the effect of EtOH on acetate metabolism in rat brain. Copyright © 2017 by the Research Society on Alcoholism.

  13. Methadone, monoamine oxidase, and depression: opioid distribution and acute effects on enzyme activity

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kaufmann, C.A.; Kreek, M.J.; Raghunath, J.

    1983-09-01

    Narcotic withdrawal is often accompanied by an atypical depression which responds to resumption of narcotics. It was hypothesized that methadone might exert its antidepressant effects through monoamine oxidase (MAO) inhibition. The current study examined /sub 3/H-methadone distribution in rat brain and effects on regional MAO activity with acute doses (2.5 mg/kg) which approximate those found during chronic methadone maintenance in man. Limbic areas (amygdala, basomedial hypothalamus, caudate-putamen, hippocampus, preoptic nucleus), as well as pituitary and liver were assayed for MAO activity and methadone concentration. MAO activities did not differ significantly in acute methadone or saline-treated cage-mates at 1 or 24more » hr. The concentrations of methadone at 1 hr ranged between 17 and 223 ng/100 mg wet wt tissue in the preoptic nucleus and pituitary, respectively. No significant correlation was found between change in MAO activity (MAO methadone/MAO saline) and methadone concentration in any region at 1 or 24 hr. This study does not support the hypothesis that methadone acts as an antidepressant through MAO inhibition, at least not following acute administration of this exogenous opioid.« less

  14. Effects of acute administration of selective serotonin reuptake inhibitors on sympathetic nerve activity

    PubMed Central

    Tiradentes, R.V.; Pires, J.G.P.; Silva, N.F.; Ramage, A.G.; Santuzzi, C.H.; Futuro, H.A.

    2014-01-01

    Serotonergic mechanisms have an important function in the central control of circulation. Here, the acute effects of three selective serotonin (5-HT) reuptake inhibitors (SSRIs) on autonomic and cardiorespiratory variables were measured in rats. Although SSRIs require 2-3 weeks to achieve their full antidepressant effects, it has been shown that they cause an immediate inhibition of 5-HT reuptake. Seventy male Wistar rats were anesthetized with urethane and instrumented to record blood pressure, heart rate, renal sympathetic nerve activity (RSNA), and respiratory frequency. At lower doses, the acute cardiovascular effects of fluoxetine, paroxetine and sertraline administered intravenously were insignificant and variable. At middle and higher doses, a general pattern was observed, with significant reductions in sympathetic nerve activity. At 10 min, fluoxetine (3 and 10 mg/kg) reduced RSNA by -33±4.7 and -31±5.4%, respectively, without changes in blood pressure; 3 and 10 mg/kg paroxetine reduced RSNA by -35±5.4 and -31±5.5%, respectively, with an increase in blood pressure +26.3±2.5; 3 mg/kg sertraline reduced RSNA by -59.4±8.6%, without changes in blood pressure. Sympathoinhibition began 5 min after injection and lasted approximately 30 min. For fluoxetine and sertraline, but not paroxetine, there was a reduction in heart rate that was nearly parallel to the sympathoinhibition. The effect of these drugs on the other variables was insignificant. In conclusion, acute peripheral administration of SSRIs caused early autonomic cardiovascular effects, particularly sympathoinhibition, as measured by RSNA. Although a peripheral action cannot be ruled out, such effects are presumably mostly central. PMID:25003632

  15. Acute and Chronic Effects of Endurance Running on Inflammatory Markers: A Systematic Review

    PubMed Central

    Barros, Edilberto S.; Nascimento, Dahan C.; Prestes, Jonato; Nóbrega, Otávio T.; Córdova, Claúdio; Sousa, Fernando; Boullosa, Daniel A.

    2017-01-01

    In order to understand the effect of endurance running on inflammation, it is necessary to quantify the extent to which acute and chronic running affects inflammatory mediators. The aim of this study was to summarize the literature on the effects of endurance running on inflammation mediators. Electronic searches were conducted on PubMED and Science Direct with no limits of date and language of publication. Randomized controlled trials (RCTs) and non-randomized controlled trials (NRCTs) investigating the acute and chronic effects of running on inflammation markers in runners were reviewed by two researchers for eligibility. The modified Downs and Black checklist for the assesssments of the methodological quality of studies was subsequently used. Fifty-one studies were finally included. There were no studies with elite athletes. Only two studies were chronic interventions. Results revealed that acute and chronic endurance running may affect anti- and pro-inflammatory markers but methodological differences between studies do not allow comparisons or generalization of the results. The information provided in this systematic review would help practitioners for better designing further studies while providing reference values for a better understanding of inflammatory responses after different running events. Further longitudinal studies are needed to identify the influence of training load parameters on inflammatory markers in runners of different levels and training background. PMID:29089897

  16. Protective effect of Clerodendrum colebrookianum Walp., on acute and chronic inflammation in rats

    PubMed Central

    Deb, Lokesh; Dey, Amitabha; Sakthivel, G.; Bhattamishra, Subrat Kumar; Dutta, Amitsankar

    2013-01-01

    Aim: To evaluate antioxidant, anti-inflammatory potential of the aqueous extracts and its aqueous, n-butanol, ethyl-acetate, and chloroform fractions of Clerodendrum colebrookianum Walp. leaves. Materials and Methods: In this present study, all the test samples were evaluated on in-vivo inflammatory model such as carrageenan and histamine-induced acute-inflammation and cotton pellet induced granuloma formation in albino male rats. Test samples were also employed in in-vitro assays like DPPH* free radical scavenging activity and COX inhibition assay. Results: The test samples at the dose of 200mg/kg/p.o. were found to cause significant inhibition of carrageenan and histamine-induced inflammation and cotton pallet-induced granuloma formation on acute and chronic inflammation in rats. The test samples, except n-butanol fraction, exhibited inhibitory effect for both COX-1 and COX-2, in in-vitro assay but their percentage of inhibition values differs from each other. The test samples (aqueous extracts, aqueous, n-butanol, ethyl-acetate, and chloroform fractions) at 100 μg concentration exhibits 54.37%, 33.88%, 62.85%, 56.28%, and 57.48% DPPH* radical-scavenging effect respectively in in-vitro antioxidant study. Conclusion: These observations established the anti-inflammatory effect of C. colebrookianum leaves in acute and chronic stages of inflammation by free radical scavenging and inhibition of COX-1 and COX-2. PMID:24014914

  17. Acute effects of energy drinks in medical students.

    PubMed

    García, Andrés; Romero, César; Arroyave, Cristhian; Giraldo, Fabián; Sánchez, Leidy; Sánchez, Julio

    2017-09-01

    To determine the acute effects of a variety of recognized energy drinks on medical students, based on the hypothesis that these beverages may affect negatively cardiovascular parameters, stress levels and working memory. Eighty young healthy medical students were included in the study. 62.5 % of the participants were male, and the age mean was 21.45 years. Each person was evaluated via measurement of systolic and diastolic blood pressure, electrocardiogram (ECG), heart rate, oxygen saturation, breath rate, temperature, STAI score (to assess anxiety state), salivary cortisol and N-back task score (to determine cognitive enhancement). These evaluations were performed before and following the intake of either carbonated water or one of three energy drinks containing caffeine in similar concentrations and an undetermined energy blend; A contained less sugar and no taurine. Thirty-minute SBP increased significantly in the A and C groups. The B group exhibited a diminution of the percentage of the 1-h SBP increase, an increase of 1-h DBP and QTc shortening. HR showed an increase in the percent change in the A and C groups. Cortisol salivary levels increased in the B group. The STAI test score decreased in the C group. The percent change in N-back scores increased in the A group. The data reinforce the need for further research on the acute and chronic effects of energy drinks to determine the actual risks and benefits. Consumers need to be more informed about the safety of these energy drinks, especially the young student population.

  18. A review of the acute subjective effects of MDMA/ecstasy.

    PubMed

    Baylen, Chelsea A; Rosenberg, Harold

    2006-07-01

    Although several relatively recent reviews have summarized the neuropsychiatric effects associated with chronic ecstasy use, there is no published comprehensive review of studies on the acute subjective effects (ASEs) of MDMA/ecstasy. The present study reviewed the prevalence, intensity and duration of ASEs collected from 24 studies that provided frequency data on the prevalence of self-reported ecstasy effects and/or provided data on the intensity of ecstasy effects. Although hundreds of ASEs have been reported following MDMA consumption, we identified a subset of effects reported repeatedly by meaningful proportions and large numbers of participants across multiple investigations, most of which were either emotional (e.g. anxiety, depression, closeness, fear, euphoria, calmness) or somatic (e.g. nausea/vomiting, bruxism, muscle aches/headache, sweating, numbness, body temperature changes, fatigue, dizziness, dry mouth, increased energy). Only one sexual ASE (sexual arousal/increased sensual awareness), one cognitive ASE (confused thought), one sensory-perceptual ASE (visual effects/changes in visual perception), one sleep-related ASE (sleeplessness) and one appetite-related ASE (decreased appetite) were reported across five or more investigations. Three factors-number of hours between ingestion and assessment, dose level, and gender-have been associated with the acute subjective experience of MDMA/ecstasy. This review provides useful information for clinicians and researchers who want to understand the desirable and undesirable ASEs that may motivate and restrain ecstasy use, for public health advocates who seek to reduce biomedical harms (e.g. fainting, dehydration, shortness of breath, bruxism) associated with recreational use of MDMA/ecstasy, and for educators who wish to design credible prevention messages that neither underestimate nor exaggerate users' experiences of this drug.

  19. High-affinity α4β2 nicotinic receptors mediate the impairing effects of acute nicotine on contextual fear extinction.

    PubMed

    Kutlu, Munir Gunes; Holliday, Erica; Gould, Thomas J

    2016-02-01

    Previously, studies from our lab have shown that while acute nicotine administered prior to training and testing enhances contextual fear conditioning, acute nicotine injections prior to extinction sessions impair extinction of contextual fear. Although there is also strong evidence showing that the acute nicotine's enhancing effects on contextual fear conditioning require high-affinity α4β2 nicotinic acetylcholine receptors (nAChRs), it is unknown which nAChR subtypes are involved in the acute nicotine-induced impairment of contextual fear extinction. In this study, we investigated the effects of acute nicotine administration on contextual fear extinction in knock-out (KO) mice lacking α4, β2 or α7 subtypes of nAChRs and their wild-type (WT) littermates. Both KO and WT mice were first trained and tested for contextual fear conditioning and received a daily contextual extinction session for 4 days. Subjects received intraperitoneal injections of nicotine (0.18 mg/kg) or saline 2-4 min prior to each extinction session. Our results showed that the mice that lack α4 and β2 subtypes of nAChRs showed normal contextual fear extinction but not the acute nicotine-induced impairment while the mice that lack the α7 subtype showed both normal contextual extinction and nicotine-induced impairment of contextual extinction. In addition, control experiments showed that acute nicotine-induced impairment of contextual fear extinction persisted when nicotine administration was ceased and repeated acute nicotine administrations alone did not induce freezing behavior in the absence of context-shock learning. These results clearly demonstrate that high-affinity α4β2 nAChRs are necessary for the effects of acute nicotine on contextual fear extinction. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. High-affinity α4β2 nicotinic receptors mediate the impairing effects of acute nicotine on contextual fear extinction

    PubMed Central

    Kutlu, Munir Gunes; Holliday, Erica; Gould, Thomas J.

    2015-01-01

    Previously, studies from our lab have shown that while acute nicotine administered prior to training and testing enhances contextual fear conditioning, acute nicotine injections prior to extinction sessions impair extinction of contextual fear. Although there is also strong evidence showing that the acute nicotine’s enhancing effects on contextual fear conditioning require high-affinity α4β2 nicotinic acetylcholine receptors (nAChRs), it is unknown which nAChR subtypes are involved in the acute nicotine-induced impairment of contextual fear extinction. In this study, we investigated the effects of acute nicotine administration on contextual fear extinction in knock-out (KO) mice lacking α4, β2 or α7 subtypes of nAChRs and their wild-type (WT) littermates. Both KO and WT mice were first trained and tested for contextual fear conditioning and received a daily contextual extinction session for 4 days. Subjects received intraperitoneal injections of nicotine (0.18 mg/kg) or saline 2–4 mins prior to each extinction session. Our results showed that the that mice lack α4 and β2 subtypes of nAChRs showed normal contextual fear extinction but not the acute nicotine-induced impairment while the mice that lack the α7 subtype showed both normal contextual extinction and nicotine-induced impairment of contextual extinction. In addition, control experiments showed that acute nicotine-induced impairment of contextual fear extinction persisted when nicotine administration was ceased and repeated acute nicotine administrations alone did not induce freezing behavior in the absence of context-shock learning. These results clearly demonstrate that high-affinity α4β2 nAChRs are necessary for the effects of acute nicotine on contextual fear extinction. PMID:26688111

  1. Experimental acute alcohol pancreatitis-related liver damage and endotoxemia: synbiotics but not metronidazole have a protective effect.

    PubMed

    Marotta, F; Barreto, R; Wu, C C; Naito, Y; Gelosa, F; Lorenzetti, A; Yoshioka, M; Fesce, E

    2005-01-01

    The aim of this study was to test the effect of gut manipulation by either novel synbiotics or by metronidazole on either endotoxemia or the severity of liver damage in the course of acute pancreatitis from alcohol ingestion. Sprague-Dawley rats were fed for 1 week through an intragastric tube a liquid diet with either: (i) 1 mL t.i.d. of a mixture of synbiotics (Lactobacillus acidophilus, Lactobacillus helveticus and Bifidobacterium in an enriched medium); (ii) 20 mg/kg t.i.d. metronidazole; or (iii) standard diet. Then, acute pancreatitis was induced by caerulein and when the disease was full-blown, rats were fed an alcohol-rich diet. Synbiotic and metronidazole treatment was given for a further 2 weeks. Transaminase and endotoxemia levels were measured before treatment, after 6 h, after 24 h and 2 weeks later, at the time the rats were killed. Liver samples were obtained for histological analysis. Synbiotics but not metronidazole improved the acute pancreatitis-induced increase in endotoxemia and transaminase levels. The addition of alcohol worsened these variables to a limited extent in the synbiotic-treated group, while metronidazole had a negative effect on liver damage. Gut flora pretreatment with synbiotics was able to effectively protect against endotoxin/bacterial translocation, as well as liver damage in the course of acute pancreatitis and concomitant heavy alcohol consumption. The beneficial effect of synbiotics on liver histology seems to be correlated with endotoxemia. Metronidazole did not produce such a beneficial effect; in fact, it further worsened liver damage when alcohol was added to the background of ongoing acute pancreatic inflammation.

  2. Rat brain CYP2D enzymatic metabolism alters acute and chronic haloperidol side-effects by different mechanisms.

    PubMed

    Miksys, Sharon; Wadji, Fariba Baghai; Tolledo, Edgor Cole; Remington, Gary; Nobrega, Jose N; Tyndale, Rachel F

    2017-08-01

    Risk for side-effects after acute (e.g. parkinsonism) or chronic (e.g. tardive dyskinesia) treatment with antipsychotics, including haloperidol, varies substantially among people. CYP2D can metabolize many antipsychotics and variable brain CYP2D metabolism can influence local drug and metabolite levels sufficiently to alter behavioral responses. Here we investigated a role for brain CYP2D in acutely and chronically administered haloperidol levels and side-effects in a rat model. Rat brain, but not liver, CYP2D activity was irreversibly inhibited with intracerebral propranolol and/or induced by seven days of subcutaneous nicotine pre-treatment. The role of variable brain CYP2D was investigated in rat models of acute (catalepsy) and chronic (vacuous chewing movements, VCMs) haloperidol side-effects. Selective inhibition and induction of brain, but not liver, CYP2D decreased and increased catalepsy after acute haloperidol, respectively. Catalepsy correlated with brain, but not hepatic, CYP2D enzyme activity. Inhibition of brain CYP2D increased VCMs after chronic haloperidol; VCMs correlated with brain, but not hepatic, CYP2D activity, haloperidol levels and lipid peroxidation. Baseline measures, hepatic CYP2D activity and plasma haloperidol levels were unchanged by brain CYP2D manipulations. Variable rat brain CYP2D alters side-effects from acute and chronic haloperidol in opposite directions; catalepsy appears to be enhanced by a brain CYP2D-derived metabolite while the parent haloperidol likely causes VCMs. These data provide novel mechanistic evidence for brain CYP2D altering side-effects of haloperidol and other antipsychotics metabolized by CYP2D, suggesting that variation in human brain CYP2D may be a risk factor for antipsychotic side-effects. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Improved Hepatoprotective Effect of Liposome-Encapsulated Astaxanthin in Lipopolysaccharide-Induced Acute Hepatotoxicity

    PubMed Central

    Chiu, Chun-Hung; Chang, Chun-Chao; Lin, Shiang-Ting; Chyau, Charng-Cherng; Peng, Robert Y.

    2016-01-01

    Lipopolysaccharide (LPS)-induced acute hepatotoxicity is significantly associated with oxidative stress. Astaxanthin (AST), a xanthophyll carotenoid, is well known for its potent antioxidant capacity. However, its drawbacks of poor aqueous solubility and low bioavailability have limited its utility. Liposome encapsulation is considered as an effective alternative use for the improvement of bioavailability of the hydrophobic compound. We hypothesized that AST encapsulated within liposomes (LA) apparently shows improved stability and transportability compared to that of free AST. To investigate whether LA administration can efficiently prevent the LPS-induced acute hepatotoxicity, male Sprague-Dawley rats (n = six per group) were orally administered liposome-encapsulated AST at 2, 5 or 10 mg/kg-day (LA-2, LA-5, and LA-10) for seven days and then were LPS-challenged (i.p., 5 mg/kg). The LA-10 administered group, but not the other groups, exhibited a significant amelioration of serum glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), blood urea nitrogen (BUN), creatinine (CRE), hepatic malondialdehyde (MDA) and glutathione peroxidase (GSH-Px), IL-6, and hepatic nuclear NF-κB and inducible nitric oxide synthase (iNOS), suggesting that LA at a 10 mg/kg-day dosage renders hepatoprotective effects. Moreover, the protective effects were even superior to that of positive control N-acetylcysteine (NAC, 200 mg/kg-day). Histopathologically, NAC, free AST, LA-2 and LA-5 partially, but LA-10 completely, alleviated the acute inflammatory status. These results indicate that hydrophobic AST after being properly encapsulated by liposomes improves bioavailability and can also function as potential drug delivery system in treating hepatotoxicity. PMID:27428953

  4. The Effect of Massage on Acute Postoperative Pain in Critically and Acutely Ill Adults Post-thoracic Surgery: Systematic Review and Meta-analysis of Randomized Controlled Trials.

    PubMed

    Boitor, Madalina; Gélinas, Céline; Richard-Lalonde, Melissa; Thombs, Brett D

    Critical care practice guidelines identify a lack of clear evidence on the effectiveness of massage for pain control. To assess the effect of massage on acute pain in critically and acutely ill adults post-thoracic surgery. Medline, Embase, CINAHL, PsychInfo, Web of Science, Scopus and Cochrane Library databases were searched. Eligible studies were randomized controlled trials (RCTs) evaluating the effect of massage compared to attention control/sham massage or standard care alone on acute pain intensity post-thoracic surgery. Twelve RCTs were included. Of these, nine evaluated massage in addition to standard analgesia, including 2 that compared massage to attention control/sham massage in the intensive care unit (ICU), 6 that compared massage to standard analgesia alone early post-ICU discharge, and 1 that compared massage to both attention control and standard care in the ICU. Patients receiving massage with analgesia reported less pain (0-10 scale) compared to attention control/sham massage (3 RCTs; N = 462; mean difference -0.80, 95% confidence interval [CI] -1.25 to -0.35; p < 0.001; I 2  = 13%) and standard care (7 RCTs; N = 1087; mean difference -0.85, 95% CI -1.28 to -0.42; p < 0.001; I 2  = 70%). Massage, in addition to pharmacological analgesia, reduces acute post-cardiac surgery pain intensity. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Deriving acute and chronic predicted no effect concentrations of pharmaceuticals and personal care products based on species sensitivity distributions.

    PubMed

    Zhao, Wenxing; Wang, Bin; Wang, Yujue; Deng, Shubo; Huang, Jun; Yu, Gang

    2017-10-01

    Pharmaceuticals and personal care products (PPCPs), as emerging contaminants, have been detected in various environmental matrices and caused adverse effects on human health and the ecosystem. But water quality criterias (WQCs) of PPCPs for protecting aquatic environment are lacking, which hinders the environmental management of these emerging contaminants. In the present study, in order to support their WQC derivation, acute and chronic hazardous concentrations for 5% of species (HC 5 s) of some frequently detected PPCPs in China were calculated based on acute and chronic species sensitivity distributions (SSDs), respectively, using both parametric (log-normal and log-logistic) and nonparametric bootstrap approaches. The groups of aquatic species used in SSDs included planktons, zooplanktons, invertebrates and vertebrates. Acute and chronic predicted no effect concentrations (PNECs) were derived from the HC 5 s. The acute PNECs of the selected PPCPs were in a range from 1.1 to 4993μg/L. While the chronic PNECs were one or two orders of magnitude lower than the acute PNECs, with a range from 0.02 to 298μg/L. Among these PPCPs, the compound with the highest acute effect on the aquatic environment was clarithromycin while erythromycin was the one with the highest chronic toxicity effect. Among the studied PPCPs, erythromycin caused a relatively higher aquatic ecological risk in China. This study helps derive WQCs of PPCPs in the aquatic environment, which is essential for environmental managment of these emerging contaminants. Copyright © 2017. Published by Elsevier Inc.

  6. Pre-mRNA Processing Factor Prp18 Is a Stimulatory Factor of Influenza Virus RNA Synthesis and Possesses Nucleoprotein Chaperone Activity.

    PubMed

    Minakuchi, M; Sugiyama, K; Kato, Y; Naito, T; Okuwaki, M; Kawaguchi, A; Nagata, K

    2017-02-01

    The genome of influenza virus (viral RNA [vRNA]) is associated with the nucleoprotein (NP) and viral RNA-dependent RNA polymerases and forms helical viral ribonucleoprotein (vRNP) complexes. The NP-vRNA complex is the biologically active template for RNA synthesis by the viral polymerase. Previously, we identified human pre-mRNA processing factor 18 (Prp18) as a stimulatory factor for viral RNA synthesis using a Saccharomyces cerevisiae replicon system and a single-gene deletion library of Saccharomyces cerevisiae (T. Naito, Y. Kiyasu, K. Sugiyama, A. Kimura, R. Nakano, A. Matsukage, and K. Nagata, Proc Natl Acad Sci USA, 104:18235-18240, 2007, https://doi.org/10.1073/pnas.0705856104). In infected Prp18 knockdown (KD) cells, the synthesis of vRNA, cRNA, and viral mRNAs was reduced. Prp18 was found to stimulate in vitro viral RNA synthesis through its interaction with NP. Analyses using in vitro RNA synthesis reactions revealed that Prp18 dissociates newly synthesized RNA from the template after the early elongation step to stimulate the elongation reaction. We found that Prp18 functions as a chaperone for NP to facilitate the formation of NP-RNA complexes. Based on these results, it is suggested that Prp18 accelerates influenza virus RNA synthesis as an NP chaperone for the processive elongation reaction. Templates for viral RNA synthesis of negative-stranded RNA viruses are not naked RNA but rather RNA encapsidated by viral nucleocapsid proteins forming vRNP complexes. However, viral basic proteins tend to aggregate under physiological ionic strength without chaperones. We identified the pre-mRNA processing factor Prp18 as a stimulatory factor for influenza virus RNA synthesis. We found that one of the targets of Prp18 is NP. Prp18 facilitates the elongation reaction of viral polymerases by preventing the deleterious annealing of newly synthesized RNA to the template. Prp18 functions as a chaperone for NP to stimulate the formation of NP-RNA complexes. Based on

  7. The cost-effectiveness of TheraBite® as treatment for acute myogenic temporomandibular disorder.

    PubMed

    Heres Diddens, Andreas; Kraaijenga, Sophie; Coupé, Veerle; Hilgers, Frans; van der Molen, Lisette; Smeele, Ludi; Retèl, Valesca

    2017-09-01

    Temporomandibular disorder (TMD) is a very common and costly pain problem concerning the temporomandibular joint. A previous study has shown that for the treatment of acute myogenic TMD, TheraBite® (TB) offers a faster and greater effect than usual care consisting of physical therapy (PT). This study estimates the cost-effectiveness of TB compared to PT. Differences in costs and quality-adjusted life-years (QALYs) between TB and PT are analyzed using a decision model. The point estimate for the incremental cost-effectiveness ratio is -28,068 EUR (-30,191 USD) per QALY (dominant) for TB versus PT. At the willingness-to-pay ratio of 20,000 EUR (21,513 USD) per QALY, TB has a 97% probability of being cost-effective compared to PT. TB is expected to be cost-effective compared to PT for the treatment of acute myogenic TMD, offering faster recovery of quality of life for patients, at a lower cost to society.

  8. Therapeutic Effect of Low Doses of Acenocoumarol in the Course of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats.

    PubMed

    Warzecha, Zygmunt; Sendur, Paweł; Ceranowicz, Piotr; Cieszkowski, Jakub; Dembiński, Marcin; Sendur, Ryszard; Bonior, Joanna; Jaworek, Jolanta; Ambroży, Tadeusz; Olszanecki, Rafał; Kuśnierz-Cabala, Beata; Tomasz, Kaczmarzyk; Tomaszewska, Romana; Dembiński, Artur

    2017-04-21

    Intravascular activation of coagulation is observed in acute pancreatitis and is related to the severity of this inflammation. The aim of our study was to evaluate the impact of acenocoumarol therapy on the course of acute pancreatitis induced in male rats by pancreatic ischemia followed by reperfusion. Acenocoumarol at a dose of 50, 100, or 150 µg/kg/dose was administered intragastrically once a day, starting the first dose 24 h after the initiation of pancreatic reperfusion. Histological examination showed that treatment with acenocoumarol reduces pancreatic edema, necrosis, and hemorrhages in rats with pancreatitis. Moreover, the administration of acenocoumarol decreased pancreatic inflammatory infiltration and vacuolization of pancreatic acinar cells. These findings were accompanied with a reduction in the serum activity of lipase and amylase, concentration of interleukin-1β, and plasma d-Dimer concentration. Moreover, the administration of acenocoumarol improved pancreatic blood flow and pancreatic DNA synthesis. Acenocoumarol given at a dose of 150 µg/kg/dose was the most effective in the treatment of early phase acute pancreatitis. However later, acenocoumarol given at the highest dose failed to exhibit any therapeutic effect; whereas lower doses of acenocoumarol were still effective in the treatment of acute pancreatitis. Treatment with acenocoumarol accelerates the recovery of ischemia/reperfusion-induced acute pancreatitis in rats.

  9. Therapeutic Effect of Low Doses of Acenocoumarol in the Course of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats

    PubMed Central

    Warzecha, Zygmunt; Sendur, Paweł; Ceranowicz, Piotr; Cieszkowski, Jakub; Dembiński, Marcin; Sendur, Ryszard; Bonior, Joanna; Jaworek, Jolanta; Ambroży, Tadeusz; Olszanecki, Rafał; Kuśnierz-Cabala, Beata; Tomasz, Kaczmarzyk; Tomaszewska, Romana; Dembiński, Artur

    2017-01-01

    Intravascular activation of coagulation is observed in acute pancreatitis and is related to the severity of this inflammation. The aim of our study was to evaluate the impact of acenocoumarol therapy on the course of acute pancreatitis induced in male rats by pancreatic ischemia followed by reperfusion. Acenocoumarol at a dose of 50, 100, or 150 µg/kg/dose was administered intragastrically once a day, starting the first dose 24 h after the initiation of pancreatic reperfusion. Results: Histological examination showed that treatment with acenocoumarol reduces pancreatic edema, necrosis, and hemorrhages in rats with pancreatitis. Moreover, the administration of acenocoumarol decreased pancreatic inflammatory infiltration and vacuolization of pancreatic acinar cells. These findings were accompanied with a reduction in the serum activity of lipase and amylase, concentration of interleukin-1β, and plasma d-Dimer concentration. Moreover, the administration of acenocoumarol improved pancreatic blood flow and pancreatic DNA synthesis. Acenocoumarol given at a dose of 150 µg/kg/dose was the most effective in the treatment of early phase acute pancreatitis. However later, acenocoumarol given at the highest dose failed to exhibit any therapeutic effect; whereas lower doses of acenocoumarol were still effective in the treatment of acute pancreatitis. Conclusion: Treatment with acenocoumarol accelerates the recovery of ischemia/reperfusion-induced acute pancreatitis in rats. PMID:28430136

  10. Differential effects of grape juice on gastric emptying and renal function from cisplatin-induced acute adverse toxicity.

    PubMed

    Ko, J-L; Tsai, C-H; Liu, T-C; Lin, M-Y; Lin, H-L; Ou, C-C

    2016-08-01

    Grape skin and seeds contain large amounts of phytochemicals such as polyphenols, resveratrol, and proanthocyanidins, which possess antioxidant activities. Cisplatin is widely used in the treatment of cancer. High doses of cisplatin have also been known to produce acute adverse effects. The aim of this study was to investigate the protective effects of antioxidant properties of whole grape juice (with skin and seeds) on cisplatin-induced acute gastrointestinal tract disorders and nephrotoxicity in Wistar rats. Gastric emptying is significantly increased in whole grape juice-pretreated rats when compared to cisplatin treatment alone. The expression of ghrelin mRNA of stomach is increased in rats with whole grape juice. However, pretreatment with whole grape juice did not reduce renal function markers in acute renal toxicity. No significant changes were recorded in the oxidative stress/antioxidant status parameters of any study group. In contrast, pretreatment with whole grape juice slightly improved tubular cell vacuolization, tubular dilatation, and cast formation in renal tubules. These results show that consumption of whole grape juice induces somewhat beneficial effects in preventing cisplatin-mediated dyspepsia but does not offer protection against cisplatin-induced acute renal toxicity. © The Author(s) 2015.

  11. The effects of intrathecal morphine encapsulated in L- and D-dipalmitoylphosphatidyl choline liposomes on acute nociception in rats.

    PubMed

    Nishiyama, T; Ho, R J; Shen, D D; Yaksh, T L

    2000-08-01

    Liposomes can serve as a sustained-release carrier system, permitting the spinal delivery of large opioid doses restricting the dose for acute systemic uptake. We evaluated the antinociceptive effects of morphine encapsulated in liposomes of two isomeric phospholipids, L-dipalmitoylphosphatidyl choline (L-DPPC) and D-dipalmitoylphosphatidyl choline (D-DPPC), in comparison with morphine in saline. Sprague-Dawley rats with chronic lumbar intrathecal catheters were tested for their acute nociceptive response using a hindpaw thermal escape test. Their general behavior, motor function, pinna reflex, and corneal reflex were also examined. The duration of antinociception was longer in both liposomal morphine groups than in the free morphine group. The peak antinociceptive effects were observed within 30 min after intrathecal morphine, L-DPPC or D-DPPC morphine injection. The rank order of the area under the effect-time curve for antinociception was L-DPPC morphine > D-DPPC morphine > morphine. The 50% effective dose was: 2.7 microg (morphine), 4.6 microg (L-DPPC morphine), and 6.4 microg (D-DPPC morphine). D-DPPC morphine had less side effects for a given antinociceptive AUC than morphine. In conclusion, L-DPPC and D-DPPC liposome encapsulation of morphine prolonged the antinociceptive effect on acute thermal stimulation and could decrease side effects, compared with morphine alone. Two isomers of liposome (L-dipalmitoylphosphatidyl choline and D-dipalmitoylphosphatidyl choline) encapsulation of morphine prolonged the analgesic effect on acute thermal-induced pain when administered intrathecally and could decrease side effects, compared with morphine alone.

  12. [Correlation of Plasma Co-stimulatory Molecules B7-H2 and B7-H3 with Platelet Auto-antibodies in Patients with Immune Thrombocytopenic Purpura].

    PubMed

    Zuo, Bin; Zhao, Yun-Xiao; Yang, Jian-Feng; He, Yang

    2015-08-01

    To investigate whether the plasma level of platelet auto- antibodies in ITP patients is related to that of co-stimulatory molecules sB7-H2 and sB7-H3. A total of 61 ITP patients and 25 healthy controls from the First Affiliated Hospital of Soochow University from June 2012 to August 2013 were enrolled in this study. The expression levels of platelet auto-antibodies against 5 glycoproteins (GPIX, GP Ib, GP IIIa, GPIIb and P-selectin) in plasma were detected by flow cytometric immuno-beads array, and the expression of soluable co-stimulatory molecules sB7-H2 and sB7-H3 was measured by ELISA. The plasma levels of 5 auto-antibodies against platelet membrance glycoproteins significantly increased in ITP patiens (P < 0.01). Compared with healthy controls, sB7-H2 levels increased (P < 0.05), while the sB7-H3 level did not significantly change (r = 0.13, P > 0.05). However, the correlation analysis showed that sB7-H3 negatively correlated with platelet P-selectin auto-antibody (r = -0.46, P < 0.05), and sB7-H2 and sB7-H3 significantly reduced in ITP patients with positive P-selectin auto-antibody (P < 0.01). In ITP patients, platelet counts negatively correlated with sB7-H2 (r = -0.3907, P < 0.01), but did not correlate with sB7-H3. Soluble costimulatory molecule sB7-H2 elevates in ITP patients, and the level of sB7-H3 is associated with auto-antibodies against P-selectin, suggesting that costimulatory molecules B7-H2 and B7-H3 may be involved in the pathogenesis of immune regulation abnormality in ITP.

  13. Effect of Acute Psychological Stress on Prefrontal GABA Concentration Determined by Proton Magnetic Resonance Spectroscopy

    PubMed Central

    Hasler, Gregor; van der Veen, Jan Willem; Grillon, Christian; Drevets, Wayne C.; Shen, Jun

    2011-01-01

    Objective Impaired function of the central gamma-aminobutyric acid (GABA) system, which provides the brain’s major inhibitory pathways, is thought to play an important role in the pathophysiology of anxiety disorders. The effect of acute psychological stress on the human GABA-ergic system is still unknown, however. The purpose of this study was to determine the effect of acute stress on prefrontal GABA levels. Method A recently developed noninvasive magnetic resonance spectroscopy method was used to measure changes in the GABA concentration of the prefrontal cortex in 10 healthy human subjects during a threat-of-shock condition and during a safe condition (two sessions on different days). The main outcome measure was the mean GABA concentration within a 3×3×2-cm3 voxel selected from the medial prefrontal cortex. Results Prefrontal GABA decreased by approximately 18% in the threat-of-shock condition relative to the safe condition. This reduction was specific to GABA, since the concentrations of N-acetyl-aspartate, choline-containing compounds, and glutamate/glutamine levels obtained in the same spectra did not change significantly. Conclusions This result appeared compatible with evidence from preclinical studies in rodents, which showed rapid presynaptic down-regulation of GABA-ergic neurotransmission in response to acute psychological stress. The molecular mechanism and functional significance of this reduced inhibitory effect of acute psychological stress in relation to impaired GABA-ergic function in anxiety disorders merit further investigation. PMID:20634372

  14. Neuroimaging studies of acute effects of THC and CBD in humans and animals: a systematic review.

    PubMed

    Batalla, A; Crippa, J A; Busatto, G F; Guimaraes, F S; Zuardi, A W; Valverde, O; Atakan, Z; McGuire, P K; Bhattacharyya, S; Martín-Santos, R

    2014-01-01

    In recent years, growing concerns about the effects of cannabis use on mental health have renewed interest in cannabis research. In particular, there has been a marked increase in the number of neuroimaging studies of the effects of cannabinoids. We conducted a systematic review to assess the impact of acute cannabis exposure on brain function in humans and in experimental animals. Papers published until June 2012 were included from EMBASE, Medline, PubMed and LILACS databases following a comprehensive search strategy and pre-determined set of criteria for article selection. Only pharmacological challenge studies involving the acute experimental administration of cannabinoids in occasional or naïve cannabis users, and naïve animals were considered. Two hundred and twenty-four studies were identified, of which 45 met our inclusion criteria. Twenty-four studies were in humans and 21 in animals. Most comprised studies of the acute effects of cannabinoids on brain functioning in the context of either resting state activity or activation during cognitive paradigms. In general, THC and CBD had opposite neurophysiological effects. There were also a smaller number of neurochemical imaging studies: overall, these did not support a central role for increased dopaminergic activity in THC-induced psychosis. There was a considerable degree of methodological heterogeneity in the imaging literature reviewed. Functional neuroimaging studies have provided extensive evidence for the acute modulation of brain function by cannabinoids, but further studies are needed in order to understand the neural mechanisms underlying these effects. Future studies should also consider the need for more standardised methodology and the replication of findings.

  15. Acute effects of electronic and tobacco cigarette smoking on complete blood count.

    PubMed

    Flouris, Andreas D; Poulianiti, Konstantina P; Chorti, Maria S; Jamurtas, Athanasios Z; Kouretas, Dimitrios; Owolabi, Emmanuel O; Tzatzarakis, Manolis N; Tsatsakis, Aristidis M; Koutedakis, Yiannis

    2012-10-01

    The World Health Organisation called for research assessing the safety of electronic cigarette (e-cigarette). We evaluated the acute effect of active and passive e-cigarette and tobacco cigarette smoking on complete blood count (CBC) markers in 15 smokers and 15 never-smokers, respectively. Smokers underwent a control session, an active tobacco cigarette smoking session, and an active e-cigarette smoking session. Never-smokers underwent a control session, a passive tobacco cigarette smoking session, and a passive e-cigarette smoking session. The results demonstrated that CBC indices remained unchanged during the control session and the active and passive e-cigarette smoking sessions (P>0.05). Active and passive tobacco cigarette smoking increased white blood cell, lymphocyte, and granulocyte counts for at least one hour in smokers and never smokers (P<0.05). It is concluded that acute active and passive smoking using the e-cigarettes tested in the current study does not influence CBC indices in smokers and never smokers, respectively. In contrast, acute active and passive tobacco cigarette smoking increase the secondary proteins of acute inflammatory load for at least one hour. More research is needed to evaluate chemical safety issues and other areas of consumer product safety of e-cigarettes, because the nicotine content in the liquids used may vary considerably. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Disentangling the effect of illness perceptions on health status in people with type 2 diabetes after an acute coronary event.

    PubMed

    Vos, Rimke Cathelijne; Kasteleyn, Marise Jeannine; Heijmans, Monique Johanna; de Leeuw, Elke; Schellevis, François Georges; Rijken, Mieke; Rutten, Guy Emile

    2018-03-02

    Chronically ill patients such as people with type 2 diabetes develop perceptions of their illness, which will influence their coping behaviour. Perceptions are formed once a health threat has been recognised. Many people with type 2 diabetes suffer from multimorbidity, for example the combination with cardiovascular disease. Perceptions of one illness may influence perceptions of the other condition. The aim of the current study was to evaluate the effect of an intervention in type 2 diabetes patients with a first acute coronary event on change in illness perceptions and whether this mediates the intervention effect on health status. The current study is a secondary data analysis of a RCT. Two hundred one participants were randomised (1:1 ratio) to the intervention (n = 101, three home visits) or control group (n = 100). Outcome variables were diabetes and acute coronary event perceptions, assessed with the two separate Brief Illness Perceptions Questionnaires (BIPQs); and health status (Euroqol Visual Analog Scale (EQ-VAS)). The intervention effect was analysed using ANCOVA. Linear regression analyses were used to assess whether illness perceptions mediated the intervention effect on health status. A positive intervention effect was found on the BIPQ diabetes items coherence and treatment control (F = 8.19, p = 0.005; F = 14.01, p < 0.001). No intervention effect was found on the other BIPQ diabetes items consequence, personal control, identity, illness concern and emotional representation. Regarding the acute coronary event, a positive intervention effect on treatment control was found (F = 7.81, p = 0.006). No intervention effect was found on the other items of the acute coronary event BIPQ. Better diabetes coherence was associated with improved health status, whereas perceiving more treatment control was not. The mediating effect of the diabetes perception 'coherence' on health status was not significant. Targeting illness

  17. Acute Versus Chronic Partial Sleep Deprivation in Middle-Aged People: Differential Effect on Performance and Sleepiness

    PubMed Central

    Philip, Pierre; Sagaspe, Patricia; Prague, Mélanie; Tassi, Patricia; Capelli, Aurore; Bioulac, Bernard; Commenges, Daniel; Taillard, Jacques

    2012-01-01

    Study Objective: To evaluate the effects of acute sleep deprivation and chronic sleep restriction on vigilance, performance, and self-perception of sleepiness. Design: Habitual night followed by 1 night of total sleep loss (acute sleep deprivation) or 5 consecutive nights of 4 hr of sleep (chronic sleep restriction) and recovery night. Participants: Eighteen healthy middle-aged male participants (age [(± standard deviation] = 49.7 ± 2.6 yr, range 46-55 yr). Measurements: Multiple sleep latency test trials, Karolinska Sleepiness Scale scores, simple reaction time test (lapses and 10% fastest reaction times), and nocturnal polysomnography data were recorded. Results: Objective and subjective sleepiness increased immediately in response to sleep restriction. Sleep latencies after the second and third nights of sleep restriction reached levels equivalent to those observed after acute sleep deprivation, whereas Karolinska Sleepiness Scale scores did not reach these levels. Lapse occurrence increased after the second day of sleep restriction and reached levels equivalent to those observed after acute sleep deprivation. A statistical model revealed that sleepiness and lapses did not progressively worsen across days of sleep restriction. Ten percent fastest reaction times (i.e., optimal alertness) were not affected by acute or chronic sleep deprivation. Recovery to baseline levels of alertness and performance occurred after 8-hr recovery night. Conclusions: In middle-aged study participants, sleep restriction induced a high increase in sleep propensity but adaptation to chronic sleep restriction occurred beyond day 3 of restriction. This sleepiness attenuation was underestimated by the participants. One recovery night restores daytime sleepiness and cognitive performance deficits induced by acute or chronic sleep deprivation. Citation: Philip P; Sagaspe P; Prague M; Tassi P; Capelli A; Bioulac B; Commenges D; Taillard J. Acute versus chronic partial sleep deprivation in

  18. Acute versus chronic partial sleep deprivation in middle-aged people: differential effect on performance and sleepiness.

    PubMed

    Philip, Pierre; Sagaspe, Patricia; Prague, Mélanie; Tassi, Patricia; Capelli, Aurore; Bioulac, Bernard; Commenges, Daniel; Taillard, Jacques

    2012-07-01

    To evaluate the effects of acute sleep deprivation and chronic sleep restriction on vigilance, performance, and self-perception of sleepiness. Habitual night followed by 1 night of total sleep loss (acute sleep deprivation) or 5 consecutive nights of 4 hr of sleep (chronic sleep restriction) and recovery night. Eighteen healthy middle-aged male participants (age [(± standard deviation] = 49.7 ± 2.6 yr, range 46-55 yr). Multiple sleep latency test trials, Karolinska Sleepiness Scale scores, simple reaction time test (lapses and 10% fastest reaction times), and nocturnal polysomnography data were recorded. Objective and subjective sleepiness increased immediately in response to sleep restriction. Sleep latencies after the second and third nights of sleep restriction reached levels equivalent to those observed after acute sleep deprivation, whereas Karolinska Sleepiness Scale scores did not reach these levels. Lapse occurrence increased after the second day of sleep restriction and reached levels equivalent to those observed after acute sleep deprivation. A statistical model revealed that sleepiness and lapses did not progressively worsen across days of sleep restriction. Ten percent fastest reaction times (i.e., optimal alertness) were not affected by acute or chronic sleep deprivation. Recovery to baseline levels of alertness and performance occurred after 8-hr recovery night. In middle-aged study participants, sleep restriction induced a high increase in sleep propensity but adaptation to chronic sleep restriction occurred beyond day 3 of restriction. This sleepiness attenuation was underestimated by the participants. One recovery night restores daytime sleepiness and cognitive performance deficits induced by acute or chronic sleep deprivation. Philip P; Sagaspe P; Prague M; Tassi P; Capelli A; Bioulac B; Commenges D; Taillard J. Acute versus chronic partial sleep deprivation in middle-aged people: differential effect on performance and sleepiness. SLEEP 2012;35(7):997-1002.

  19. Acute, intermediate intensity exercise, and speed and accuracy in working memory tasks: a meta-analytical comparison of effects.

    PubMed

    McMorris, Terry; Sproule, John; Turner, Anthony; Hale, Beverley J

    2011-03-01

    The purpose of this study was to compare, using meta-analytic techniques, the effect of acute, intermediate intensity exercise on the speed and accuracy of performance of working memory tasks. It was hypothesized that acute, intermediate intensity exercise would have a significant beneficial effect on response time and that effect sizes for response time and accuracy data would differ significantly. Random-effects meta-analysis showed a significant, beneficial effect size for response time, g=-1.41 (p<0.001) but a significant detrimental effect size, g=0.40 (p<0.01), for accuracy. There was a significant difference between effect sizes (Z(diff)=3.85, p<0.001). It was concluded that acute, intermediate intensity exercise has a strong beneficial effect on speed of response in working memory tasks but a low to moderate, detrimental one on accuracy. There was no support for a speed-accuracy trade-off. It was argued that exercise-induced increases in brain concentrations of catecholamines result in faster processing but increases in neural noise may negatively affect accuracy. 2010 Elsevier Inc. All rights reserved.

  20. Self-Reported Acute Health Effects and Exposure to Companion Animals.

    PubMed

    Krueger, W S; Hilborn, E D; Dufour, A P; Sams, E A; Wade, T J

    2016-06-01

    To understand the etiological burden of disease associated with acute health symptoms [e.g. gastrointestinal (GI), respiratory, dermatological], it is important to understand how common exposures influence these symptoms. Exposures to familiar and unfamiliar animals can result in a variety of health symptoms related to infection, irritation and allergy; however, few studies have examined this association in a large-scale cohort setting. Cross-sectional data collected from 50 507 participants in the United States enrolled from 2003 to 2009 were used to examine associations between animal contact and acute health symptoms during a 10-12 day period. Fixed-effects multivariable logistic regression estimated adjusted odds ratios (AORs) and 95% confident intervals (CI) for associations between animal exposures and outcomes of GI illness, respiratory illness and skin/eye symptoms. Two-thirds of the study population (63.2%) reported direct contact with animals, of which 7.7% had contact with at least one unfamiliar animal. Participants exposed to unfamiliar animals had significantly higher odds of self-reporting all three acute health symptoms, when compared to non-animal-exposed participants (GI: AOR = 1.4, CI = 1.2-1.7; respiratory: AOR = 1.5, CI = 1.2-1.8; and skin/eye: AOR = 1.9, CI = 1.6-2.3), as well as when compared to participants who only had contact with familiar animals. Specific contact with dogs, cats or pet birds was also significantly associated with at least one acute health symptom; AORs ranged from 1.1 to 1.5, when compared to participants not exposed to each animal. These results indicate that contact with animals, especially unfamiliar animals, was significantly associated with GI, respiratory and skin/eye symptoms. Such associations could be attributable to zoonotic infections and allergic reactions. Etiological models for acute health symptoms should consider contact with companion animals, particularly exposure to unfamiliar animals

  1. Development of acute tolerance to the EEG effect of propofol in rats.

    PubMed

    Ihmsen, H; Schywalsky, M; Tzabazis, A; Schwilden, H

    2005-09-01

    A previous study in rats with propofol suggested the development of acute tolerance to the EEG effect. The aim of this study was to evaluate acute tolerance by means of EEG-controlled closed-loop anaesthesia as this approach allows precise determination of drug requirement to maintain a defined drug effect. Ten male Sprague-Dawley rats [weight 402 (40) g, mean (SD)] were included in the study. The EEG was recorded with occipito-occipital needle electrodes and a modified median frequency (mMEF) of the EEG power spectrum was used as a pharmacodynamic control parameter. The propofol infusion rate was controlled by a model-based adaptive algorithm to maintain a set point of mMEF=3 (0.5) Hz for 90 min. The performance of the closed-loop system was characterized by the prediction error PE=(mMEF-set point)/set point. Plasma propofol concentrations were determined from arterial samples by HPLC. The chosen set point was successfully maintained in all rats. The median (SE) and absolute median values of PE were -5.0 (0.3) and 11.3 (0.2)% respectively. Propofol concentration increased significantly from 2.9 (2.2) microg ml(-1) at the beginning to 5.8 (3.8) microg ml(-1) at 90 min [mean (SD), P<0.05]. The cumulative dose increased linearly, with a mean infusion rate of 0.60 (0.16) mg kg(-1) min(-1). The minimum value of the mean arterial pressure during closed-loop administration of propofol was 130 (24) mm Hg, compared with a baseline value of 141 (12) mm Hg. The increase in propofol concentration at constant EEG effect indicates development of acute tolerance to the hypnotic effect of propofol.

  2. Acute effects of ingestion of black and green tea on lipoprotein oxidation.

    PubMed

    Hodgson, J M; Puddey, I B; Croft, K D; Burke, V; Mori, T A; Caccetta, R A; Beilin, L J

    2000-05-01

    Tea has been associated with a reduced risk of cardiovascular disease. One proposed mechanism of this risk reduction involves inhibition of lipoprotein oxidation in vivo by antioxidant polyphenolic compounds derived from tea. However, controlled interventions uniformly failed to show that ingestion of tea can inhibit LDL oxidation ex vivo. The absence of effects in previous studies may be due to the isolation of LDL particles from polyphenolic compounds that are present in the aqueous phase of serum. The objective of this study was to examine the acute effects of ingestion of black and green tea on ex vivo Cu(2+)-induced lipoprotein oxidation without prior isolation of lipoproteins from serum. The acute effects of 4 hot drinks-green tea and black tea (each at a dose equivalent to 4 standard cups), water matched to the teas for caffeine content, and water-were assessed in 20 healthy men by using a Latin-square design. The lag time to lipoprotein diene formation, slope of the propagation phase of the oxidation curve, and area under the oxidation curve were calculated. Urinary concentrations of 4-O-methylgallic acid were used as a marker of uptake and metabolism of polyphenolic compounds from tea. Significant increases in urinary 4-O-methylgallic acid for black and green tea (P < 0. 0001) were observed. Caffeine did not significantly influence lipoprotein oxidation. Compared with the water control, there was a greater lag time for black tea (5.4 +/- 2.9 min; P = 0.05) that was of borderline significance and a similar trend for green tea (4.4 +/- 2.8 min; P = 0.17). Slope and area under the oxidation curve were not altered. Black tea has a mild acute effect on ex vivo lipoprotein oxidation in human serum. 2000;71:-7.

  3. Suppression of in vivo polyclonal IgE responses by monoclonal antibody to the lymphokine B-cell stimulatory factor 1.

    PubMed Central

    Finkelman, F D; Katona, I M; Urban, J F; Snapper, C M; Ohara, J; Paul, W E

    1986-01-01

    The lymphokine B-cell stimulatory factor 1 (BSF-1) has been shown to greatly enhance the differentiation of lipopolysaccharide-activated B cells into IgG1- and IgE-secreting cells in vitro. To determine whether in vivo IgG1 and IgE antibody responses are BSF-1 dependent, the ability of a monoclonal rat IgG1 anti-BSF-1 antibody, 11B11, to affect polyclonal IgG1 and IgE production in mice infected with the nematode parasite Nippostrongylus brasiliensis or injected with a purified goat antibody to mouse IgD was studied. 11B11-containing ascites fluid or purified 11B11 strongly inhibited IgE production in both systems but did not affect IgG1 production, while control ascites or normal rat IgG1 had no IgE-inhibitory activity. These results indicate an important physiologic role for BSF-1 in the generation of IgE antibody responses and suggest means for limiting the production of antibodies responsible for allergic reactions without inhibiting protective antibody responses. PMID:3491987

  4. Anti-inflammatory effects of Simvastatin in patients with acute intracerebral hemorrhage in an intensive care unit

    PubMed Central

    Zhou, Xiurong; Chen, Jiafeng; Wang, Chengdong; Wu, Lili

    2017-01-01

    Intracerebral hemorrhage is one of the most common types of cerebrovascular disease in humans and often causes paralysis, a vegetative state and even death. Patients with acute intracerebral hemorrhage are frequently monitored in intensive care units (ICUs). Spontaneous intracerebral hemorrhage is associated with a higher rate of mortality and morbidity than other intracephalic diseases. The expression levels of inflammatory factors have important roles in inflammatory responses indicative of changes in a patient's condition and are therefore important in the monitoring and treatment of affected patients at the ICU as well as the development of therapeutic strategies for acute cerebral hemorrhage. The present study investigated the anti-inflammatory effects of Simvastatin in patients with acute intracerebral hemorrhage at an ICU, and inflammatory factors and cellular changes were systematically analyzed. The plasma concentrations of inflammatory factors, including interleukin (IL)-4, IL-6, IL-8 and IL-10, were evaluated by ELISAs. The plasma concentrations of inflammatory cellular changes were detected by using flow cytometry. The results demonstrated that after Simvastatin treatment of patients with acute cerebral hemorrhage at the ICU, the plasma concentrations of IL-4, IL-6, IL-8 and IL-10 were downregulated compared with those in placebo-treated controls. In addition, Simvastatin treatment at the ICU decreased lymphocytes, granulocytes and mononuclear cells in patients with acute cerebral hemorrhage. The levels of inflammatory factors were associated with brain edema in patients with acute cerebral hemorrhage treated at the ICU. In addition, the amount of bleeding was reduced in parallel with the inflammatory cell plasma concentration of lymphocytes, granulocytes and mononuclear cells. Importantly, Simvastatin treatment produced beneficial outcomes by improving brain edema and reducing the amount of bleeding. In conclusion, the present study demonstrated the

  5. COMPARING BEHAVIORAL DOSE-EFFECT CURVES FOR HUMANS AND LABORATORY ANIMALS ACUTELY EXPOSED TO TOLUENE.

    EPA Science Inventory

    The utility of laboratory animal data in toxicology depends upon the ability to generalize the results quantitatively to humans. To compare the acute behavioral effects of inhaled toluene in humans to those in animals, dose-effect curves were fitted by meta-analysis of published...

  6. Acute effects of The Stick on strength, power, and flexibility.

    PubMed

    Mikesky, Alan E; Bahamonde, Rafael E; Stanton, Katie; Alvey, Thurman; Fitton, Tom

    2002-08-01

    The Stick is a muscle massage device used by athletes, particularly track athletes, to improve performance. The purpose of this project was to assess the acute effects of The Stick on muscle strength, power, and flexibility. Thirty collegiate athletes consented to participate in a 4-week, double-blind study, which consisted of 4 testing sessions (1 familiarization and 3 data collection) scheduled 1 week apart. During each testing session subjects performed 4 measures in the following sequence: hamstring flexibility, vertical jump, flying-start 20-yard dash, and isokinetic knee extension at 90 degrees x s(-1). Two minutes of randomly assigned intervention treatment (visualization [control], mock insensible electrical stimulation [placebo], or massage using The Stick [experimental]) was performed immediately prior to each performance measure. Statistical analyses involved single-factor repeated measures analysis of variance (ANOVA) with Fisher's Least Significant Difference post-hoc test. None of the variables measured showed an acute improvement (p < or = 0.05) immediately following treatment with The Stick.

  7. Marijuana’s Acute Effects on Cognitive Bias for Affective and Marijuana Cues

    PubMed Central

    Metrik, Jane; Aston, Elizabeth R.; Kahler, Christopher W.; Rohsenow, Damaris J.; McGeary, John E.; Knopik, Valerie S.

    2015-01-01

    Marijuana produces acute increases in positive subjective effects and decreased reactivity to negative affective stimuli, though may also acutely induce anxiety. Implicit attentional and evaluative processes may explicate marijuana’s ability to acutely increase positive and negative emotions. This within-subjects study examined whether smoked marijuana with 2.7–3.0 % delta-9-tetrahydrocannabinol (THC), relative to placebo, acutely changed attentional processing of rewarding and negative affective stimuli as well as marijuana-specific stimuli. On two separate days, regular marijuana users (N=89) smoked placebo or active THC cigarette and completed subjective ratings of mood, intoxication, urge to smoke marijuana, and two experimental tasks: Pleasantness Rating (response latency and perceived pleasantness of affective and marijuana-related stimuli) and Emotional Stroop (attentional bias to affective stimuli). On the Pleasantness Rating task, active marijuana increased response latency to negatively-valenced and marijuana-related (vs. neutral) visual stimuli, beyond a general slowing of response. Active marijuana also increased pleasantness ratings of marijuana images, although to a lesser extent than placebo due to reduced marijuana urge after smoking. Overall, active marijuana did not acutely change processing of positive emotional stimuli. There was no evidence of attentional bias to affective word stimuli on the Emotional Stroop task with the exception of attentional bias to positive word stimuli in the subgroup of marijuana users with cannabis dependence. Marijuana may increase allocation of attentional resources towards marijuana-specific and negatively-valenced visual stimuli without altering processing of positively-valenced stimuli. Marijuana-specific cues may be more attractive with higher levels of marijuana craving and less wanted with low craving levels. PMID:26167716

  8. The effect of sand storms on acute asthma in Riyadh, Saudi Arabia.

    PubMed

    Alangari, Abdullah A; Riaz, Muhammad; Mahjoub, Mohamed Osman; Malhis, Nidal; Al-Tamimi, Saleh; Al-Modaihsh, Abdullah

    2015-01-01

    Major sand storms are frequent in the Middle East. This study aims to investigate the role of air particulate matter (PM) level in acute asthma in children in Riyadh, Saudi Arabia. An aerosol spectrometer was used to evaluate PM < 10μm in diameter (PM10) and PM < 2.5 μm in diameter (PM2.5) concentrations in the air every 30 minutes throughout February and March 2012 in Riyadh. Data on children 2-12 years of age presenting to the emergency department of a major children's hospital with acute asthma during the same period were collected including their acute asthma severity score. The median with interquartile range (IQR) levels of PM10 and PM2.5 were 454 μg/m(3) (309,864) and 108 μg/m(3) (72,192) respectively. There was no correlation between the average daily PM10 levels and the average number of children presenting with acute asthma per day (r = -0.14, P = 0.45), their daily asthma score (r = 0.014, P = 0.94), or admission rate ( r= -0.08, P = 0.65). This was also true for average daily PM2.5 levels. In addition, there was no difference in these variables between days with PM10 >1000 μg/m(3), representing major sand storms, plus the following 5 days and other days with PM10< 1000 μg/m(3). Sand storms, even major ones, had no significant impact on acute asthma exacerbations in children in Riyadh, Saudi Arabia. The very high levels of PM, however, deserve further studying especially of their long-term effects.

  9. The neurocircuitry of illicit psychostimulant addiction: acute and chronic effects in humans

    PubMed Central

    Taylor, Sara B; Lewis, Candace R; Olive, M Foster

    2013-01-01

    Illicit psychostimulant addiction remains a significant problem worldwide, despite decades of research into the neural underpinnings and various treatment approaches. The purpose of this review is to provide a succinct overview of the neurocircuitry involved in drug addiction, as well as the acute and chronic effects of cocaine and amphetamines within this circuitry in humans. Investigational pharmacological treatments for illicit psychostimulant addiction are also reviewed. Our current knowledge base clearly demonstrates that illicit psychostimulants produce lasting adaptive neural and behavioral changes that contribute to the progression and maintenance of addiction. However, attempts at generating pharmacological treatments for psychostimulant addiction have historically focused on intervening at the level of the acute effects of these drugs. The lack of approved pharmacological treatments for psychostimulant addiction highlights the need for new treatment strategies, especially those that prevent or ameliorate the adaptive neural, cognitive, and behavioral changes caused by chronic use of this class of illicit drugs. PMID:24648786

  10. Effects of Acute and Chronic Flunitrazepam on Delay Discounting in Pigeons

    PubMed Central

    Eppolito, Amy K; France, Charles P; Gerak, Lisa R

    2011-01-01

    Delay to delivery of a reinforcer can decrease responding for that reinforcer and increase responding for smaller reinforcers that are available concurrently and delivered without delay; acute administration of drugs can alter responding for large, delayed reinforcers, although the impact of chronic treatment on delay discounting is not well understood. In this experiment, the effects of repeated administration of the benzodiazepine flunitrazepam were studied in 6 pigeons responding on one key to receive food that was delivered immediately and on a second key to receive a larger amount of food that was delivered following delays which increased across a single session. Pigeons responded predominantly for the large reinforcer when there were no delays and when delays were short; however, as delays increased, responding for the large reinforcer decreased. Acutely, flunitrazepam (0.32, 1.0 and 3.2 mg/kg) dose-dependently increased responding for the large reinforcer, shifting the discounting curve rightward and upward. Repeated administration of flunitrazepam (0.32, 1.0 and 3.2 mg/kg, each for six sessions, separated by one session during which vehicle was administered) did not markedly alter its effects on responding for the large reinforcer, indicating that the development of tolerance to this effect of flunitrazepam is modest under these conditions. PMID:21541119

  11. [The effect of reamberin and alpha-lipoic acid on the tolerance to acute cerebral ischemia in experimental diabetes mellitus].

    PubMed

    Volchegorskii, I A; Miroshnichenko, I Yu; Rassokhina, L M; Faizullin, R M

    To study an effect of reamberin and α-lipoic acid (α-LA) on the tolerance of mice with experimental diabetes mellitus (DM) to acute cerebrovascular accident (ACVA) in mice experiments. The authors studied mice with alloxan diabetes and subtotal and total brain ischemia. In additional experimental series, an effect of reamberin and α-lipoic acid on the tolerance to acute hypoxic hypoxia and intensity of hyperglycemia in experimental DM was studied. The increased vulnerability of animals to ACVA due to hyperglycemia and increased sensitivity to acute hypoxic hypoxia was established. Reamberin and α-lipoic acid administered for 14 days in doses, which are equivalent to therapeutic range in humans, enhance the tolerance to ACVA and acute hypoxic hypoxia in mice with alloxan diabetes. These medications also decrease the intensity of hyperglycemia during concurrent insulin replacement therapy. The increased tolerance to ACVA in mice with alloxan diabetes caused by reamberin and alpha-lipoic acid is associated with an antihypoxic effect of these medications and does not depend on their effect on the intensity of hyperglycemia. Reamberin outperformed α-lipoic acid in the antihypoxic activity, protection against ACVA and the rate of onset of glucose reducing effect in experimental diabetes mellitus.

  12. Direct suppressive effect of acute metabolic and respiratory alkalosis on parathyroid hormone secretion in the dog.

    PubMed

    Lopez, Ignacio; Rodriguez, Mariano; Felsenfeld, Arnold J; Estepa, Jose Carlos; Aguilera-Tejero, Escolastico

    2003-08-01

    Acute alkalosis may directly affect PTH secretion. The effect of acute metabolic and respiratory alkalosis was studied in 20 dogs. PTH values were lower in the metabolic (5.6 +/- 0.8 pg/ml) and respiratory (1.8 +/- 0.6 pg/ml) alkalosis groups than in the control group (27 +/- 5 pg/ml). Acute alkalosis is an independent factor that decreases PTH values during normocalcemia and delays the PTH response to hypocalcemia. We recently showed that acute metabolic and respiratory acidosis stimulated PTH secretion. This study was designed to evaluate whether acute metabolic and respiratory alkalosis suppressed parathyroid hormone (PTH) secretion. Three groups of 10 dogs were studied: control, acute metabolic alkalosis, and acute respiratory alkalosis. Metabolic alkalosis was induced with an infusion of sodium bicarbonate and respiratory alkalosis by hyperventilation. Calcium chloride was infused to prevent alkalosis-induced hypocalcemia during the first 60 minutes. During the next 30 minutes, disodium EDTA was infused to induce hypocalcemia and to evaluate the PTH response to hypocalcemia. Because the infusion of sodium bicarbonate resulted in hypernatremia, the effect of hypernatremia was studied in an additional group that received hypertonic saline. After 60 minutes of a normocalcemic clamp, PTH values were less (p < 0.05) in the metabolic (5.6 +/- 0.8 pg/ml) and respiratory (1.8 +/- 0.6 pg/ml) alkalosis groups than in the control group (27 +/- 5 pg/ml); the respective blood pH values were 7.61 +/- 0.01, 7.59 +/- 0.02, and 7.39 +/- 0.02. The maximal PTH response to hypocalcemia was similar among the three groups. However, the maximal PTH response was observed after a decrease in ionized calcium of 0.20 mM in the control group but not until a decrease of 0.40 mM in the metabolic and respiratory alkalosis groups. In contrast to the metabolic alkalosis group, hypernatremia (157 +/- 2 mEq/liter) in the hypertonic saline group was associated with an increased PTH value (46

  13. The acute effects of cannabinoids on memory in humans: a review.

    PubMed

    Ranganathan, Mohini; D'Souza, Deepak Cyril

    2006-11-01

    Cannabis is one of the most frequently used substances. Cannabis and its constituent cannabinoids are known to impair several aspects of cognitive function, with the most robust effects on short-term episodic and working memory in humans. A large body of the work in this area occurred in the 1970s before the discovery of cannabinoid receptors. Recent advances in the knowledge of cannabinoid receptors' function have rekindled interest in examining effects of exogenous cannabinoids on memory and in understanding the mechanism of these effects. The literature about the acute effects of cannabinoids on memory tasks in humans is reviewed. The limitations of the human literature including issues of dose, route of administration, small sample sizes, sample selection, effects of other drug use, tolerance and dependence to cannabinoids, and the timing and sensitivity of psychological tests are discussed. Finally, the human literature is discussed against the backdrop of preclinical findings. Acute administration of Delta-9-THC transiently impairs immediate and delayed free recall of information presented after, but not before, drug administration in a dose- and delay-dependent manner. In particular, cannabinoids increase intrusion errors. These effects are more robust with the inhaled and intravenous route and correspond to peak drug levels. This profile of effects suggests that cannabinoids impair all stages of memory including encoding, consolidation, and retrieval. Several mechanisms, including effects on long-term potentiation and long-term depression and the inhibition of neurotransmitter (GABA, glutamate, acetyl choline, dopamine) release, have been implicated in the amnestic effects of cannabinoids. Future research in humans is necessary to characterize the neuroanatomical and neurochemical basis of the memory impairing effects of cannabinoids, to dissect out their effects on the various stages of memory and to bridge the expanding gap between the humans and

  14. Late effects awareness website for pediatric survivors of acute lymphocytic leukemia

    PubMed Central

    Navarro, Ana; Klonoff, Elizabeth A.

    2018-01-01

    Objectives Every day 43 children are newly diagnosed with cancer. Fortunately, almost 90% of these childhood cancer patients will survive. However, 60–90% of these survivors will experience late effects, health problems that occur months or years after treatment has ended. Late effects could occur as a result of the disease, its treatment, and patient-related factors. The two main objectives of this research are to: 1) Examine the existence of all web-based resources for childhood cancer survivors with acute lymphocytic leukemia which focus on medical and psychological aspects of late effects, and 2) Create an innovative website specifically designed to fill this void. Materials and methods A systematic literature review, followed by input from >20 different organizations, resulted in the creation of LEAP3 AHEAD (Late Effects Awareness for Patients, Physicians and the Public; Advancing Health and Eliminating All Disparities), a multi-dimensional website centering on late effects. Results An extensive review revealed 14 pediatric cancer websites, none of which focused exclusively on late effects. LEAP3 AHEAD is the first interactive website for acute lympocytic leukemia childhood cancer survivors and families, as well as physicians, and the public to: a) increase awareness about risks, detection, diagnosis, treatment, and prevention of medical and psychological late effects, b) provide suggestions to successfully reintegrate into schools, careers, and socially, and c) present opportunities including camps, scholarships, and pet therapy programs. Conclusion LEAP3 AHEAD is the first national website to provide a comprehensive, accessible, affordable, and multi-dimensional resource for pediatricians, internists, nurse practitioners, psychologists, survivors and their families, as well as the public about late effects. PMID:29451924

  15. Comparison of Acute Health Effects From Exposures to Diesel and Biodiesel Fuel Emissions.

    PubMed

    Mehus, Aaron A; Reed, Rustin J; Lee, Vivien S T; Littau, Sally R; Hu, Chengcheng; Lutz, Eric A; Burgess, Jefferey L

    2015-07-01

    To investigate the comparative acute health effects associated with exposures to diesel and 75% biodiesel/25% diesel (B75) blend fuel emissions. We analyzed multiple health endpoints in 48 healthy adults before and after exposures to diesel and B75 emissions in an underground mine setting-lung function, lung and systemic inflammation, novel biomarkers of exposure, and oxidative stress were assessed. B75 reduced respirable diesel particulate matter by 20%. Lung function declined significantly more after exposure to diesel emissions. Lung inflammatory cells along with sputum and plasma inflammatory mediators increased significantly to similar levels with both exposures. Urinary 8-hydroxydeoxyguanosine, a marker of oxidative stress, was not significantly changed after either exposure. Use of B75 lowered respirable diesel particulate matter exposure and some associated acute health effects, although lung and systemic inflammation were not reduced compared with diesel use.

  16. Sublethal and hormesis effects of imidacloprid on the soybean aphid Aphis glycines.

    PubMed

    Qu, Yanyan; Xiao, Da; Li, Jinyu; Chen, Zhou; Biondi, Antonio; Desneux, Nicolas; Gao, Xiwu; Song, Dunlun

    2015-04-01

    The soybean aphid, Aphis glycines Matsumura, is a major pest in soybean crop. Current management of this pest relies mainly on insecticides applications, and the neonicotinoid imidacloprid has been proposed as an effective insecticide to control A. glycines in soybean field. Imidacloprid at lethal concentrations not only exerts acute toxicity to A. glycines, but also cause various biological changes when aphids are chronically exposed to lower concentrations. In this study, we assessed the effects of a low-lethal (0.20 mg L(-1)) and two sublethal (0.05 and 0.10 mg L(-1)) imidacloprid concentrations on various A. glycines life history traits. Aphid exposure to 0.20 mg L(-1) imidacloprid caused slower juvenile development, shorter reproductive period, and reduced adult longevity, fecundity and total lifespan. Stimulatory effects, i.e. hormesis, on reproduction and immature development duration were observed in aphids exposed to the lower sublethal imidacloprid concentrations. Consequently, the net reproduction rate (R 0) was significantly higher than in the control aphids. These findings stress the importance of the actual imidacloprid concentration in its toxicological properties on A. glycines. Therefore, our results would be useful for assessing the overall effects of imidacloprid on A. glycines and for optimizing integrated pest management programs targeting this pest.

  17. Effect of acute psychological stress on response inhibition: An event-related potential study.

    PubMed

    Qi, Mingming; Gao, Heming; Liu, Guangyuan

    2017-04-14

    This study aimed to investigate the effect of acute psychological stress on response inhibition and its electrophysiological correlates using a dual-task paradigm. Acute stress was induced by a primary task (mental arithmetic task), which consisted of a stress block and a control block. Response inhibition was measured using a secondary task (Go/NoGo task). In each trial, a Go/NoGo stimulus was presented immediately after the mental arithmetic task. The results revealed increased subjective stress and negative affect for the stress relative to control block, suggesting that the mental arithmetic task triggered a reliable stress response. ERPs locked to the Go/NoGo stimuli revealed that decreased P2 and increased N2 components were evoked for the stress block compared to the control block. These results demonstrated that acute psychological stress alters the response inhibition process by reducing the early selective attention process and enhancing the cognitive control process. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Inhibitory Effects of Pretreatment with Radon on Acute Alcohol-Induced Hepatopathy in Mice

    PubMed Central

    Toyota, Teruaki; Kataoka, Takahiro; Nishiyama, Yuichi; Taguchi, Takehito; Yamaoka, Kiyonori

    2012-01-01

    We previously reported that radon inhalation activates antioxidative functions in the liver and inhibits carbon tetrachloride-induced hepatopathy in mice. In addition, it has been reported that reactive oxygen species contribute to alcohol-induced hepatopathy. In this study, we examined the inhibitory effects of radon inhalation on acute alcohol-induced hepatopathy in mice. C57BL/6J mice were subjected to intraperitoneal injection of 50% alcohol (5 g/kg bodyweight) after inhaling approximately 4000 Bq/m3 radon for 24 h. Alcohol administration significantly increased the activities of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) in serum, and the levels of triglyceride and lipid peroxide in the liver, suggesting acute alcohol-induced hepatopathy. Radon inhalation activated antioxidative functions in the liver. Furthermore, pretreatment with radon inhibited the depression of hepatic functions and antioxidative functions. These findings suggested that radon inhalation activated antioxidative functions in the liver and inhibited acute alcohol-induced hepatopathy in mice. PMID:23213269

  19. Effect of air pollution on onset of acute coronary syndrome in susceptible subgroups.

    PubMed

    Qorbani, M; Yunesian, M; Fotouhi, A; Zeraati, H; Sadeghian, S

    2012-06-01

    While long-term exposure to air pollutants is associated with an increase in heart diseases and mortality, little information is available about the short-term effects of air pollution. This case-crossover study assessed the relationship of particulate matter (PM10) and carbon monoxide (CO) levels with hospital admission for acute coronary syndrome in Tehran, Islamic Republic of Iran. We interviewed 250 patients with a first episode of acute coronary syndrome and obtained data from hospital records and Tehran Air Quality Control Company. The risk of acute coronary syndrome was significantly associated with elevated concentrations of CO the day before the event (OR 1.18; 95% CI: 1.03-1.34) but not significantly with PM10 (OR 1.00; 95% CI: 0.99-1.02). Stratification by age, sex, diabetes, hypertension and smoking status did not affect the results, but women were more susceptible than men to CO levels (OR for women/men 1.68; 95% CI: 1.25-2.26).

  20. Inhibitory effects of pretreatment with radon on acute alcohol-induced hepatopathy in mice.

    PubMed

    Toyota, Teruaki; Kataoka, Takahiro; Nishiyama, Yuichi; Taguchi, Takehito; Yamaoka, Kiyonori

    2012-01-01

    We previously reported that radon inhalation activates antioxidative functions in the liver and inhibits carbon tetrachloride-induced hepatopathy in mice. In addition, it has been reported that reactive oxygen species contribute to alcohol-induced hepatopathy. In this study, we examined the inhibitory effects of radon inhalation on acute alcohol-induced hepatopathy in mice. C57BL/6J mice were subjected to intraperitoneal injection of 50% alcohol (5 g/kg bodyweight) after inhaling approximately 4000 Bq/m(3) radon for 24 h. Alcohol administration significantly increased the activities of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) in serum, and the levels of triglyceride and lipid peroxide in the liver, suggesting acute alcohol-induced hepatopathy. Radon inhalation activated antioxidative functions in the liver. Furthermore, pretreatment with radon inhibited the depression of hepatic functions and antioxidative functions. These findings suggested that radon inhalation activated antioxidative functions in the liver and inhibited acute alcohol-induced hepatopathy in mice.

  1. Tyrosine receptor kinase B receptor activation reverses the impairing effects of acute nicotine on contextual fear extinction.

    PubMed

    Kutlu, Munir Gunes; Cole, Robert D; Connor, David A; Natwora, Brendan; Gould, Thomas J

    2018-03-01

    Anxiety and stress disorders have been linked to deficits in fear extinction. Our laboratory and others have demonstrated that acute nicotine impairs contextual fear extinction, suggesting that nicotine exposure may have negative effects on anxiety and stress disorder symptomatology. However, the neurobiological mechanisms underlying the acute nicotine-induced impairment of contextual fear extinction are unknown. Therefore, based on the previous studies showing that brain-derived neurotrophic factor is central for fear extinction learning and acute nicotine dysregulates brain-derived neurotrophic factor signaling, we hypothesized that the nicotine-induced impairment of contextual fear extinction may involve changes in tyrosine receptor kinase B signaling. To test this hypothesis, we systemically, intraperitoneally, injected C57BL/6J mice sub-threshold doses (2.5 and 4.0 mg/kg) of 7,8-dihydroxyflavone, a small-molecule tyrosine receptor kinase B agonist that fully mimics the effects of brain-derived neurotrophic factor, or vehicle an hour before each contextual fear extinction session. Mice also received injections, intraperitoneally, of acute nicotine (0.18 mg/kg) or saline 2-4 min before extinction sessions. While the animals that received only 7,8-dihydroxyflavone did not show any changes in contextual fear extinction, 4.0 mg/kg of 7,8-dihydroxyflavone ameliorated the extinction deficits in mice administered acute nicotine. Overall, these results suggest that acute nicotine-induced impairment of context extinction may be related to a disrupted brain-derived neurotrophic factor signaling.

  2. Protective effect of exercise and sildenafil on acute stress and cognitive function.

    PubMed

    Ozbeyli, Dilek; Gokalp, Ayse Gizem; Koral, Tolga; Ocal, Onur Yuksel; Dogan, Berkay; Akakin, Dilek; Yuksel, Meral; Kasimay, Ozgur

    2015-11-01

    There are contradictory results about the effects of exercise and sildenafil on cognitive functions. To investigate the effects of sildenafil pretreatment and chronic exercise on anxiety and cognitive functions. Wistar rats (n=42) were divided as sedentary and exercise groups. A moderate-intensity swimming exercise was performed for 6 weeks, 5 days/week, 1h/day. Some of the rats were administered orogastrically with sildenafil (25mg/kg/day) either acutely or chronically. Exposure to cat odor was used for induction of stress. The level of anxiety was evaluated by elevated plus maze test, while object recognition test was used to determine cognitive functions. Brain tissues were removed for the measurement of myeloperoxidase (MPO), malondialdehyde (MDA), nitric oxide levels, lucigenin-enhanced chemiluminescence, and for histological analysis. Increased MPO and MDA levels in sedentary-stressed rats were decreased with sildenafil applications. Chronic exercise inhibited the increase in MPO levels. Increased nitric oxide and lucigenin chemiluminescence levels in sedentary-stressed rats, were diminished with chronic sildenafil pretreatment. The time spent in the open arms of the plus maze was declined in sedentary-stressed rats, while chronic sildenafil pretreatment increased the time back to that in non-stressed rats. Acute sildenafil application to exercised rats prolonged the time spent in open arms as compared to non-treated exercise group. The time spent with the novel object, which was decreased in sedentary-stressed rats, was increased with sildenafil pretreatment. Our results suggest that sildenafil pretreatment or exercise exerts a protective effect against acute stress and improves cognitive functions by decreasing oxidative damage. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Acute Ozone-Induced Pulmonary and Systemic Metabolic Effects are Diminished in Adrenalectomized Rats

    EPA Science Inventory

    Acute ozone exposure increases circulating stress hormones and induces peripheral metabolic alterations in animals and humans. We hypothesized that the increase of adrenal-derived stress hormones is necessary for ozone-induced systemic metabolic effects and lung injury. Male Wis...

  4. Acute and subacute effects of the ultrasonic blade and electrosurgery on nerve physiology.

    PubMed

    Chen, Chaoyang; Kallakuri, Srinivasu; Cavanaugh, John M; Broughton, Duan; Clymer, Jeffrey W

    2015-01-01

    Ultrasonic blades have been shown to cause less acute electrophysiological damage when applied near nerves than monopolar electrosurgery (ES). This study was performed to determine whether the acute nerve damage observed for ES, as well as the relative lack of damage observed for ultrasonic dissection, extends through a subacute timeframe. Muscle incisions were made in rat with the Harmonic(®) Blade (HB) and ES at a distance of 2 mm from the sciatic nerve. Sham surgery was also performed which consisted of similar exposure of the sciatic nerve without use of an energized device. Electrophysiological function was assessed acutely over a 3-h period, and subacutely after a 7-day survival, by monitoring the sciatic nerve compound action potential (CAP), conduction velocity (CV), von Frey hair (VFH) stimulation force, leukocyte infiltration, and impaired axonal transport via β-amyloid precursor protein (β-APP) immunocytochemistry. During the acute period, ES produced significantly lower CAP and CV, and higher levels of leukocytes and β-APP than sham, whereas the ultrasonic blade was not significantly different from sham, and had significantly lower VFH force than ES. After the subacute survival, ES continued to display significantly lower CAP and CV, and higher levels of leukocytes and β-APP than sham, whereas ultrasonic blade had higher CAP and CV than sham, and lower VFH than ES. This study confirms that incisions made with an ultrasonic blade cause less acute nerve damage than monopolar ES, and are comparable to sham surgery at a distance of 2 mm from the sciatic nerve. The negative effects of electrosurgery extend through at least a 7-day survival period, whereas subacute recovery after application of the ultrasonic blade was comparable to that of sham surgery. For surgical procedures in the vicinity of vital nerves, use of the ultrasonic blade represents a lower risk than ES for both acute and subacute neural trauma.

  5. Leptin in the nucleus accumbens core disrupts acute cocaine effects: Implications for GSK3β connections.

    PubMed

    Lee, Jung Won; Kim, Wha Young; Cho, Bo Ram; Vezina, Paul; Kim, Jeong-Hoon

    2018-01-30

    An adipose-derived peptide hormone, leptin, has a regulatory role in reward-related behaviors produced by drugs of abuse. Although it is known that leptin modulates mesolimbic dopaminergic pathways, little is known about its direct role in the nucleus accumbens (NAcc). In the present study, we measured acute cocaine-induced locomotor activity in the rat and the phosphorylation levels of GSK3β after bilateral microinjections of leptin into the NAcc core. Interestingly, leptin in the NAcc core significantly disrupts acute cocaine's effects on both locomotor activity and signaling molecules. In order to further confirm the role of GSK3β in these processes, we microinjected S9 peptide, a small synthetic peptide acting as a competitive inhibitor against phosphorylation site of GSK3β, followed by leptin co-microinjection, and found that leptin's effects on cocaine were all nullified. These results indicate that leptin in the NAcc core has a negative regulatory role in acute cocaine' effects, and suggest that GSK3β may play a major role in mediating these processes. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Peripheral Serotonin 1B Receptor Transcription Predicts the Effect of Acute Tryptophan Depletion on Risky Decision-Making.

    PubMed

    Faulkner, Paul; Mancinelli, Federico; Lockwood, Patricia L; Matarin, Mar; Dolan, Raymond J; Wood, Nick W; Dayan, Peter; Roiser, Jonathan P

    2017-01-01

    The effects of acute tryptophan depletion on human decision-making suggest that serotonin modulates the processing of rewards and punishments. However, few studies have assessed which of the many types of serotonin receptors are responsible. Using a within-subject, double-blind, sham-controlled design in 26 subjects, we examined whether individual differences in serotonin system gene transcription, measured in peripheral blood, predicted the effect of acute tryptophan depletion on decision-making. Participants performed a task in which they chose between successive pairs of fixed, lower-stakes (control) and variable, higher-stakes (experimental) gambles, each involving wins or losses. In 21 participants, mRNA from 9 serotonin system genes was measured in whole blood prior to acute tryptophan depletion: 5-HT1B, 5-HT1F, 5-HT2A, 5-HT2B, 5-HT3A, 5-HT3E, 5-HT7 (serotonin receptors), 5-HTT (the serotonin transporter), and tryptophan hydroxylase 1. Acute tryptophan depletion did not significantly influence participants' sensitivity to probability, wins, or losses, although there was a trend for a lower tendency to choose experimental gambles overall following depletion. Significant positive correlations, which survived correction for multiple comparisons, were detected between baseline 5-HT1B mRNA levels and acute tryptophan depletion-induced increases in both the overall tendency to choose the experimental gamble and sensitivity to wins. No significant relationship was observed with any other peripheral serotonin system markers. Computational analyses of decision-making data provided results consistent with these findings. These results suggest that the 5-HT1B receptor may modulate the effects of acute tryptophan depletion on risky decision-making. Peripheral levels of serotonin markers may predict response to treatments that act upon the serotonin system, such as selective serotonin reuptake inhibitors. © The Author 2016. Published by Oxford University Press on behalf

  7. Acute Ozone-Induced Pulmonary and Systemic Metabolic Effects are Diminished in Adrenalectomized Rats#

    EPA Science Inventory

    Acute ozone exposure increases circulating stress hormones and induces metabolic alterations in animals and humans. We hypothesized that the increase of adrenal-derived stress hormones is necessary for both ozone-induced metabolic effects and lung injury. Male Wistar-Kyoto rats ...

  8. Acute virus control mediated by licensed NK cells sets primary CD8+ T cell dependence on CD27 costimulation1,2,3

    PubMed Central

    Teoh, Jeffrey J.; Gamache, Awndre E.; Gillespie, Alyssa L.; Stadnisky, Michael D.; Yagita, Hideo; Bullock, Timothy N.J.; Brown, Michael G.

    2016-01-01

    Natural killer (NK) cells represent a critical first-line of immune defense against a bevy of viral pathogens, and infection can provoke them to mediate both supportive and suppressive effects on virus-specific adaptive immunity. In mice expressing MHC I Dk, a major MCMV resistance factor and self-ligand of the inhibitory Ly49G2 (G2) receptor, licensed G2+ NK cells provide essential host resistance against murine (M)CMV infection. Additionally G2+ NK cell responses to MCMV increase the rate and extent of dendritic cell (DC) recovery, as well as early priming of CD8+ T-cell effectors in response to MCMV. However, relatively little is known about the NK-cell effect on co-stimulatory ligand patterns displayed by DCs, or ensuing effector and memory T-cell responses. Here we found that CD27-dependent CD8+ T-cell priming and differentiation is shaped by the efficiency of NK responses to virus infection. Surprisingly, differences in specific NK responses to MCMV in Dk-disparate mice failed to distinguish early DC co-stimulatory patterns. Nonetheless, while CD27 deficiency did not impede licensed NK-mediated resistance, both CD70 and CD27 were required to efficiently prime and regulate effector CD8+ T-cell differentiation in response to MCMV, which eventually resulted in biased memory T-cell precursor formation in Dk mice. In contrast, CD8+ T-cells accrued more slowly in non-Dk mice, and eventually differentiated into terminal effector cells regardless of CD27 stimulation. Disparity in this requirement for CD27 signaling indicates that specific virus control mediated by NK cells can shape DC co-stimulatory signals needed to prime CD8+ T cells and eventual T-cell fate decisions. PMID:27798162

  9. Protective effect of Tribulus terrestris fruit extract on cerulein-induced acute pancreatitis in mice.

    PubMed

    Borran, Mina; Minaiyan, Mohsen; Zolfaghari, Behzad; Mahzouni, Parvin

    2017-01-01

    Antioxidant, anti-inflammatory, analgesic and antimicrobial activities of Tribulus terrestris ( T. terrestris ) could be helpful in the treatment of acute pancreatitis; thus, this study was designed to investigate the effects of T. terrestris on cerulein-induced acute pancreatitis in mice. Three doses (100, 200 and 400 mg/kg) of T. terrestris hydro-alcoholic extract were administered both orally (60 minutes before pancreatitis induction, p.o.) and intra-peritoneally (30 minutes before pancreatitis induction, i.p.) to different groups of mice (n=6). Pancreatitis was induced by five injections (i.p.) of cerulein 50μg/kg body weight with 1 hr intervals. Animals were euthanized 5 hr after the last injection of cerulein and tissue injures were assessed biochemically and pathologically. T. terrestris extract 200 and 400mg/kg (p.o.) and T. terrestris extract 400 mg/kg (i.p.) reduced pancreatic tissue myeloperoxidase (MPO) activity and serum amylase and lipase levels and alleviated histological parameters. These data suggest that T. terrestris hydro-alcoholic extract was effective in protecting against experimental acute pancreatitis and possibly the efficacy depends on dose and route of administration.

  10. Protective effect of Tribulus terrestris fruit extract on cerulein-induced acute pancreatitis in mice

    PubMed Central

    Borran, Mina; Minaiyan, Mohsen; Zolfaghari, Behzad; Mahzouni, Parvin

    2017-01-01

    Objective: Antioxidant, anti-inflammatory, analgesic and antimicrobial activities of Tribulus terrestris (T. terrestris) could be helpful in the treatment of acute pancreatitis; thus, this study was designed to investigate the effects of T. terrestris on cerulein-induced acute pancreatitis in mice. Materials and Methods: Three doses (100, 200 and 400 mg/kg) of T. terrestris hydro-alcoholic extract were administered both orally (60 minutes before pancreatitis induction, p.o.) and intra-peritoneally (30 minutes before pancreatitis induction, i.p.) to different groups of mice (n=6). Pancreatitis was induced by five injections (i.p.) of cerulein 50μg/kg body weight with 1 hr intervals. Animals were euthanized 5 hr after the last injection of cerulein and tissue injures were assessed biochemically and pathologically. Results: T. terrestris extract 200 and 400mg/kg (p.o.) and T. terrestris extract 400 mg/kg (i.p.) reduced pancreatic tissue myeloperoxidase (MPO) activity and serum amylase and lipase levels and alleviated histological parameters. Conclusion: These data suggest that T. terrestris hydro-alcoholic extract was effective in protecting against experimental acute pancreatitis and possibly the efficacy depends on dose and route of administration. PMID:28748172

  11. Acute Alcohol Intoxication Exacerbates Rhabdomyolysis-Induced Acute Renal Failure in Rats.

    PubMed

    Tsai, Jen-Pi; Lee, Chung-Jen; Subeq, Yi-Maun; Lee, Ru-Ping; Hsu, Bang-Gee

    2017-01-01

    Traumatic and nontraumatic rhabdomyolysis can lead to acute renal failure (ARF), and acute alcohol intoxication can lead to multiple abnormalities of the renal tubules. We examined the effect of acute alcohol intoxication in a rat model of rhabdomyolysis and ARF. Intravenous injections of 5 g/kg ethanol were given to rats over 3 h, followed by glycerol-induced rhabdomyolysis. Biochemical parameters, including blood urea nitrogen (BUN), creatinine (Cre), glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and creatine phosphokinase (CPK), were measured before and after induction of rhabdomyolysis. Renal tissue injury score, renal tubular cell expression of E-cadherin, nuclear factor-κB (NF-κB), and inducible nitric oxide synthase (iNOS) were determined. Relative to rats in the vehicle group, rats in the glycerol-induced rhabdomyolysis group had significantly increased serum levels of BUN, Cre, GOT, GPT, and CPK, elevated renal tissue injury scores, increased expression of NF-κB and iNOS, and decreased expression of E-cadherin. Ethanol exacerbated all of these pathological responses. Our results suggest that acute alcohol intoxication exacerbates rhabdomyolysis-induced ARF through its pro-oxidant and inflammatory effects.

  12. Acute Alcohol Intoxication Exacerbates Rhabdomyolysis-Induced Acute Renal Failure in Rats

    PubMed Central

    Tsai, Jen-Pi; Lee, Chung-Jen; Subeq, Yi-Maun; Lee, Ru-Ping; Hsu, Bang-Gee

    2017-01-01

    Traumatic and nontraumatic rhabdomyolysis can lead to acute renal failure (ARF), and acute alcohol intoxication can lead to multiple abnormalities of the renal tubules. We examined the effect of acute alcohol intoxication in a rat model of rhabdomyolysis and ARF. Intravenous injections of 5 g/kg ethanol were given to rats over 3 h, followed by glycerol-induced rhabdomyolysis. Biochemical parameters, including blood urea nitrogen (BUN), creatinine (Cre), glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and creatine phosphokinase (CPK), were measured before and after induction of rhabdomyolysis. Renal tissue injury score, renal tubular cell expression of E-cadherin, nuclear factor-κB (NF-κB), and inducible nitric oxide synthase (iNOS) were determined. Relative to rats in the vehicle group, rats in the glycerol-induced rhabdomyolysis group had significantly increased serum levels of BUN, Cre, GOT, GPT, and CPK, elevated renal tissue injury scores, increased expression of NF-κB and iNOS, and decreased expression of E-cadherin. Ethanol exacerbated all of these pathological responses. Our results suggest that acute alcohol intoxication exacerbates rhabdomyolysis-induced ARF through its pro-oxidant and inflammatory effects. PMID:28824301

  13. Effect of acute and chronic exercise on plasma matrix metalloproteinase and total antioxidant levels

    PubMed Central

    Mergen-Dalyanoglu, Mukaddes; Turgut, Sebahat; Turgut, Günfer

    2017-01-01

    The relationship between acute and chronic exercise and expression of matrix metalloproteinases (MMPs) in muscles is unknown. There happen some alterations in the oxidant-antioxidant balance due to exercise. This study aimed to investigate the levels of MMP-1, tissue inhibitors of metalloproteinases (TIMP-1), hyaluronic acid (HA), total antioxidant status (TAS), and total oxidant status (TOS) following acute and chronic exercising in rats. Twenty-six Wistar Albino male rats were divided in to three groups: control, acute, and chronic groups. In acute group, treadmill exercise was performed 3 days/wk, 10 min/day for 1 week. In chronic group, exercise performed 7 days/wk, 60 min/day for 4 weeks. At the end of the experiment, plasma MMP-1, TIMP-1, HA, TAS, and TOS levels were measured. In current study, the MMP-1, TIMP-1, HA, and TOS levels not observed statistically significant difference among all groups, but in chronic group, there was a significantly difference (P<0.05) between the control and experimental groups in terms of TAS and oxidative stress index (OSI) levels. TAS, TOS, and OSI levels were significantly different between control and chronic exercise group (P<0.01, P<0.05, and P<0.01, respectively). According to these results, we can say acute and chronic exercise does not effect on plasma MMP-1, TIMP-1, and HA levels. PMID:29114524

  14. Abrupt opium discontinuation has no significant triggering effect on acute myocardial infarction.

    PubMed

    Masoomi, Mohammad; Zare, Jahangir; Nasri, Hamidreza; Mirzazadeh, Ali; Sheikhvatan, Mehrdad

    2011-04-01

    A deleterious effect of withdrawal symptoms due to abrupt discontinuation of opium on the cardiovascular system is one of the recent interesting topics in the cardiovascular field. The current study hypothesized that the withdrawal syndrome due to discontinuing opium might be an important trigger for the appearance of acute myocardial infarction. Eighty-one opium-addicted individuals who were candidates for cardiovascular clinical evaluation and consecutively hospitalized in the coronary care unit (CCU) ward of Shafa Hospital in Kerman between January and July 2009 were included in the study and categorized in the case group, including patients experiencing withdrawal symptoms within 6-12 h after the reduced or discontinued use of opium according to the Diagnostic and Statistical Manual of Mental Disorders-revised IV version (DSM-IV-R) criteria for opium dependence and withdrawal, and the control group, without opium withdrawal symptoms. The appearance of acute myocardial infarction was compared between the two groups using multivariable regression models. Acute myocardial infarction occurred in 50.0% of those with withdrawal symptoms and in 45.1% of patients without evidence of opium withdrawal (P = 0.669). Multivariable analysis showed that opium withdrawal symptoms were not a trigger for acute myocardial infarction adjusting for demographic characteristics, marital status, education level and common coronary artery disease risk profiles [odds ratio (OR) = 0.920, 95% confidence interval (CI) = 0.350-2.419, P = 0.866]. Also, daily dose of opium before reducing or discontinuing use did not predict the appearance of myocardial infarction in the presence of confounder variables (OR = 0.975, 95% CI = 0.832-1.143, P = 0.755). Withdrawal syndrome due to abrupt discontinuation of opium does not have a triggering role for appearance of acute myocardial infarction.

  15. Conceptual framework of acute care nurse practitioner role enactment, boundary work, and perceptions of team effectiveness.

    PubMed

    Kilpatrick, Kelley; Lavoie-Tremblay, Mélanie; Lamothe, Lise; Ritchie, Judith A; Doran, Diane

    2013-01-01

    This article describes a new conceptual framework for acute care nurse practitioner role enactment, boundary work and perceptions of team effectiveness. Acute care nurse practitioners contribute positively to patient care by enacting an expanded scope of practise. Researchers have found both positive and negative reactions to the introduction of acute care nurse practitioners in healthcare teams. The process of role enactment, shifting role boundaries, and perceptions of team effectiveness has been studied disparately. A framework linking team structures and processes to desirable outcomes is needed. Literature was obtained by searching CINAHL, PsycInfo, MedLine, PubMed, British Nursing Index, Cochrane Library, JSTOR Archive, Web of Science, and Google Scholar from 1985-2010. A descriptive multiple-case study was completed from March 2009-May 2009. A new conceptual framework describing how role enactment and boundary work affect perceptions of team effectiveness was developed by combining theoretical and empirical sources. The framework proposes proximal indicators used by team members to assess their team's performance. The framework identifies the inter-related dimensions and concepts that different stakeholders need to consider when introducing nurse practitioners in healthcare teams. Further study is needed to identify team-level outcomes that reflect the contributions of all providers to quality patient care, and explore the patients' and families' perceptions of team effectiveness following the introduction of acute care nurse practitioners. The new framework can guide decision-making and research related to the structures, processes, and outcomes of nurse practitioner roles in healthcare teams. © 2012 Blackwell Publishing Ltd.

  16. Effect of acute beer ingestion on the liver: studies in female mice.

    PubMed

    Kanuri, Giridhar; Wagnerberger, Sabine; Landmann, Marianne; Prigl, Eva; Hellerbrand, Claus; Bischoff, Stephan C; Bergheim, Ina

    2015-04-01

    The aim of the present study was to assess whether the effects of acute consumption of stout or pilsner beer on the liver differ from those of plain ethanol in a mouse model. Seven-week-old female C57BL/6J mice received either ethanol, stout or pilsner beer (ethanol content: 6 g/kg body weight) or isocaloric maltodextrin solution. Plasma alanine transaminase, markers of steatosis, lipogenesis, activation of the toll-like receptor-4 signaling cascade as well as lipid peroxidation and fibrogenesis in the liver were measured 12 h after acute ethanol or beer intake. Acute alcohol ingestion caused a marked ~11-fold increase in hepatic triglyceride accumulation in comparison to controls, whereas in mice exposed to stout and pilsner beer, hepatic triglyceride levels were increased only by ~6.5- and ~4-fold, respectively. mRNA expression of sterol regulatory element-binding protein 1c and fatty acid synthase in the liver did not differ between alcohol and beer groups. In contrast, expression of myeloid differentiation primary response gene 88, inducible nitric oxide synthases, but also the concentrations of 4-hydroxynonenal protein adducts, nuclear factor κB and plasminogen activator inhibitor-1 were induced in livers of ethanol treated mice but not in those exposed to the two beers. Taken together, our results suggest that acute ingestion of beer and herein especially of pilsner beer is less harmful to the liver than the ingestion of plain ethanol.

  17. Effects of acute caffeine withdrawal on Short Category Test performance in sleep-deprived individuals.

    PubMed

    Killgore, William D S; Kahn-Greene, Ellen T; Killgore, Desiree B; Kamimori, Gary H; Balkin, Thomas J

    2007-12-01

    Caffeine is a popular stimulant often used to counter the effects of sleep loss and fatigue. Withdrawal from caffeine may produce mild declines in simple cognitive capacities such as attention and concentration, but it is unclear whether more complex cognitive functions, such as abstract reasoning or concept formation, may be similarly affected. To assess the effect of acute caffeine withdrawal on executive functioning during sleep deprivation, 26 healthy volunteers were administered in double-blind form either repeated doses of caffeine or placebo over two nights of continuous wakefulness. The 108-item Short Category Test was administered after 56 hr. of total sleep deprivation (9 hr. post-caffeine administration). The caffeine group scored significantly more poorly, making approximately 57% more errors on the test than the placebo group. These findings suggest that acute caffeine withdrawal during prolonged sleep deprivation has an adverse effect on abstract reasoning and concept formation.

  18. Opposing acute and chronic behavioural effects of a beta-blocker, propranolol, in the rat.

    PubMed

    Salmon, P; Gray, J A

    1985-01-01

    Rats were trained over 40 days to lever-press for food reward under a schedule of differential reinforcement of low rates of response with a 20-s criterion (DRL 20), following seven sessions of continuous reinforcement. The effect of injecting a beta-adrenergic blocker, propranolol (5 mg/kg IP), before and at two different delays after each daily session of DRL were investigated. In Experiment I, rats drugged 5-8 min before every session earned fewer reinforcements compared to controls, and showed impaired temporal discrimination. In Experiment II, this result was not replicated, but similar effects were clear in animals drugged pre-session from the 15th day of acquisition. By contrast, an improved temporal discrimination, and increased number of reinforcements were seen in rats drugged 5-8 min after every session. In Experiment III, the post-session effects were replicated and found also in rats drugged 4-5.5 h after each session. These results suggest that propranolol has an acute effect on DRL responding which resembles that of anxiolytics, and a chronic effect which opposes the acute one.

  19. Acute effects of polychlorinated biphenyl-containing and -free transformer fluids on rat testicular steroidogenesis.

    PubMed Central

    Andric, S A; Kostic, T S; Dragisic, S M; Andric, N L; Stojilkovic, S S; Kovacevic, R Z

    2000-01-01

    Polychlorinated biphenyl (PCB)-based transformer fluids belong to a class of environmentally persistent mixtures with known toxic effects. Here, we studied the acute effects of Askarel (which contains Aroclor 1260) and two substitute transformer fluids (the silicone oil-based DC561 and the mineral oil-based ENOL C) on rat testicular steroidogenesis. Single intraperitoneal (ip; 10 mg/kg body weight) or bilateral intratesticular (itt; 25 microg/testis) injections of Askarel markedly decreased serum androgen levels 24 hr after administration. In acute testicular cultures from these animals, chorionic gonadotropin-stimulated progesterone and androgen productions were severely attenuated. When itt was injected or added in vitro, Askarel inhibited 3ss-hydroxysteroid dehydrogenase (3ssHSD), stimulated 17[alpha]-hydroxylase/lyase (P450c17), and did not affect 17ss-hydroxysteroid dehydrogenase in testicular postmitochondrial fractions. The ip-injected Askarel did not affect 3ssHSD, but inhibited P450c17, suggesting that a more intensive metabolism of peripherally injected Askarel reduces the circulating levels of active ingredients below the threshold needed for inhibition of 3ssHSD and generates a derivative that inhibits P450c17. In contrast to Askarel, itt-injection (25 microg/testis) of DC561 and ENOL C did not affect in vivo and in vitro steroidogenesis. These findings show the acute effects of Askarel, but not silicone and mineral oils, on testicular steroidogenesis. PMID:11049815

  20. Antagonistic Effect of Atorvastatin on High Fat Diet Induced Survival during Acute Chagas Disease

    PubMed Central

    Zhao, Dazhi; Lizardo, Kezia; Cui, Min Hui; Ambadipudi, Kamalakar; Lora, Jose; Jelicks, Linda A; Nagajyothi, Jyothi F

    2016-01-01

    Chagasic cardiomyopathy, which is seen in Chagas Disease, is the most severe and life-threatening manifestation of infection by the kinetoplastid Trypanosoma cruzi. Adipose tissue and diet play a major role in maintaining lipid homeostasis and regulating cardiac pathogenesis during the development of Chagas cardiomyopathy. We have previously reported that T. cruzi has a high affinity for lipoproteins and that the invasion rate of this parasite increases in the presence of cholesterol, suggesting that drugs that inhibit cholesterol synthesis, such as statins, could affect infection and the development of Chagasic cardiomyopathy. The dual epidemic of diabetes and obesity in Latin America, the endemic regions for Chagas Disease, has led to many patients in the endemic region of infection having hyperlipidemia that is being treated with statins such as atorvastatin. The current study was performed to examine using mice fed on either regular or high fat diet the effect of atorvastatin on T. cruzi infection-induced myocarditis and to evaluate the effect of this treatment during infection on adipose tissue physiology and cardiac pathology. Atorvastatin was found to regulate lipolysis and cardiac lipidopathy during acute T. cruzi infection in mice and to enhance tissue parasite load, cardiac LDL levels, inflammation, and mortality in during acute infection. Overall, these data suggest that statins, such as atorvastatin, have deleterious effects during acute Chagas disease. PMID:27416748

  1. Predicting the acute behavioral effects in rats inhaling toluene (or up to 24 hrs: Inhaled vs. internal dose metrics.

    EPA Science Inventory

    The acute toxicity oftoluene, a model volatile organic compound (VOC), depends on the concentration (C) and duration (t) ofexposure, and guidelines for acute exposures have traditionally used ext relationships to extrapolate protective and/or effective concentrations across durat...

  2. Stimulatory effect of boron and manganese salts on keratinocyte migration.

    PubMed

    Chebassier, Nathalie; Ouijja, El Houssein; Viegas, Isabelle; Dreno, Brigitte

    2004-01-01

    Keratinocyte proliferation and migration are essential for the reconstruction of the cutaneous barrier after skin injury. Interestingly, thermal waters which are rich in trace elements (e.g. boron and manganese), are known to be able to improve wound healing. In order to understand the mechanism of action of this effect, our study investigated the in vitro modulation of keratinocyte migration and proliferation by boron and manganese salts, which are present in high concentrations in a thermal water (Saint Gervais). Our in vitro study demonstrated that incubating keratinocytes for 24 h with boron salts at concentrations between 0.5 and 10 microg/ml or manganese salts at concentrations between 0.1 and 1.5 microg/ml accelerated wound closure compared with control medium (+20%). As this acceleration was not related to an increase in keratinocyte proliferation we suggest that boron and manganese act on wound healing mainly by increasing the migration of keratinocytes.

  3. Acute effects of coffee on endothelial function in healthy subjects.

    PubMed

    Buscemi, S; Verga, S; Batsis, J A; Donatelli, M; Tranchina, M R; Belmonte, S; Mattina, A; Re, A; Cerasola, G

    2010-05-01

    Coffee is the most widely consumed beverage in the world, but its effect on the cardiovascular system has not been fully understood. Coffee contains caffeine and antioxidants, which may influence endothelial function, both of which have not yet been investigated. The objective of this study was to investigate the acute effects of coffee on endothelial function measured by brachial artery flow-mediated dilation (FMD). A total of 20 (10 males and 10 females) healthy non-obese subjects underwent a double-blind, crossover study. Subjects ingested one cup of caffeinated (CC) and one cup of decaffeinated (DC) Italian espresso coffee in random order at 5- to 7-day intervals. Following CC ingestion, FMD decreased progressively and significantly (mean+/-s.e.m.: 0 min, 7.7+/-0.6; 30 min, 6.3+/-0.7; 60 min, 6.0+/-0.8%; ANOVA (analysis of variance), P<0.05), but it did not significantly increase after DC ingestion (0 min, 6.9+/-0.6; 30 min, 8.1+/-0.9; 60 min, 8.5+/-0.9%; P=0.115). Similarly, CC significantly increased both systolic and diastolic blood pressure; this effect was not observed after DC ingestion. Blood glucose concentrations remained unchanged after ingestion of both CC and DC, but insulin (0 min, 15.8+/-0.9; 60 min, 15.0+/-0.8 muU/ml; P<0.05) and C-peptide (0 min, 1.25+/-0.09; 60 min, 1.18+/-0.09 ng/ml; P<0.01) blood concentrations decreased significantly only after CC ingestion. CC acutely induced unfavorable cardiovascular effects, especially on endothelial function. In the fasting state, insulin secretion is also likely reduced after CC ingestion. Future studies will determine whether CC has detrimental clinically relevant effects, especially in unhealthy subjects.

  4. Acute effect of sidestream cigarette smoke extract on vascular endothelial function.

    PubMed

    Argacha, J F; Fontaine, D; Adamopoulos, D; Ajose, A; van de Borne, P; Fontaine, J; Berkenboom, G

    2008-09-01

    Acute exposure to passive smoking adversely affects vascular function by promoting oxidative stress and endothelial dysfunction. However, it is not known whether tobacco sidestream (SS) smoke has a greater deleterious effect on the endothelium than non-tobacco SS smoke and whether these effects are related to nicotinic endothelial stimulation. To test these hypotheses, endothelial-dependent relaxation and superoxide anion production were assessed in isolated rat aortas incubated with tobacco SS smoke, non-tobacco SS smoke, or pure nicotine. Tobacco SS smoke decreased the maximal relaxation to acetylcholine (Ach) from 79 +/- 6% to 57 +/- 7.3% (% inhibition of phenylephrine-induced plateau, P < 0.001) and increased superoxide anion production from 31 +/- 9.7 to 116 +/- 24 count/10 sec/mg (P < 0.01, lucigenin-enhanced chemiluminescence technique). The non-tobacco SS smoke extract had no significant effect on the response to Ach but increased superoxide anion production in the aortic wall to 133 +/- 2 count/10 sec/mg (P < 0.001). Furthermore, concentration-response curves to Ach and superoxide production remained unaltered with nicotine (0.001, 0.01, or 0.1 mM). In conclusion, despite similar increases in vascular wall superoxide production with tobacco and non-tobacco SS smoke, only the tobacco SS smoke extracts affected endothelium-dependent vasorelaxation. Nicotine alone does not reproduce the effects seen with tobacco SS smoke, suggesting that the acute endothelial toxicity of passive smoking cannot simply be ascribed to a nicotine-dependent mechanism.

  5. The acute management of haemorrhoids.

    PubMed

    Hardy, A; Cohen, C R G

    2014-10-01

    Although the acute thrombosis and strangulation of haemorrhoids is a common condition, there is no consensus as to its most effective treatment. A PubMed search was undertaken for papers describing the aetiology and treatment of the acute complications of haemorrhoids. The anatomy and treatments for strangulated internal haemorrhoids and thrombosed perianal varices are discussed. Studies of the effectiveness and complications of conservative and operative treatments are reviewed. Ambiguities exist in the terminology used to describe the two separate pathologies that make up the acute complications of haemorrhoids. These complications have traditionally been treated conservatively. There is evidence that early operative intervention for strangulated internal haemorrhoids is safe and effective. A suggested algorithm for treatment is given, based on the published literature.

  6. Effective control of acute myeloid leukaemia and acute lymphoblastic leukaemia progression by telomerase specific adoptive T-cell therapy.

    PubMed

    Sandri, Sara; De Sanctis, Francesco; Lamolinara, Alessia; Boschi, Federico; Poffe, Ornella; Trovato, Rosalinda; Fiore, Alessandra; Sartori, Sara; Sbarbati, Andrea; Bondanza, Attilio; Cesaro, Simone; Krampera, Mauro; Scupoli, Maria T; Nishimura, Michael I; Iezzi, Manuela; Sartoris, Silvia; Bronte, Vincenzo; Ugel, Stefano

    2017-10-20

    Telomerase (TERT) is a ribonucleoprotein enzyme that preserves the molecular organization at the ends of eukaryotic chromosomes. Since TERT deregulation is a common step in leukaemia, treatments targeting telomerase might be useful for the therapy of hematologic malignancies. Despite a large spectrum of potential drugs, their bench-to-bedside translation is quite limited, with only a therapeutic vaccine in the clinic and a telomerase inhibitor at late stage of preclinical validation. We recently demonstrated that the adoptive transfer of T cell transduced with an HLA-A2-restricted T-cell receptor (TCR), which recognize human TERT with high avidity, controls human B-cell chronic lymphocytic leukaemia (B-CLL) progression without severe side-effects in humanized mice. In the present report, we show the ability of our approach to limit the progression of more aggressive leukemic pathologies, such as acute myeloid leukaemia (AML) and B-cell acute lymphoblastic leukaemia (B-ALL). Together, our findings demonstrate that TERT-based adoptive cell therapy is a concrete platform of T cell-mediated immunotherapy for leukaemia treatment.

  7. Effective control of acute myeloid leukaemia and acute lymphoblastic leukaemia progression by telomerase specific adoptive T-cell therapy

    PubMed Central

    Lamolinara, Alessia; Boschi, Federico; Poffe, Ornella; Trovato, Rosalinda; Fiore, Alessandra; Sartori, Sara; Sbarbati, Andrea; Bondanza, Attilio; Cesaro, Simone; Krampera, Mauro; Scupoli, Maria T.; Nishimura, Michael I.; Iezzi, Manuela; Sartoris, Silvia; Bronte, Vincenzo; Ugel, Stefano

    2017-01-01

    Telomerase (TERT) is a ribonucleoprotein enzyme that preserves the molecular organization at the ends of eukaryotic chromosomes. Since TERT deregulation is a common step in leukaemia, treatments targeting telomerase might be useful for the therapy of hematologic malignancies. Despite a large spectrum of potential drugs, their bench-to-bedside translation is quite limited, with only a therapeutic vaccine in the clinic and a telomerase inhibitor at late stage of preclinical validation. We recently demonstrated that the adoptive transfer of T cell transduced with an HLA-A2-restricted T-cell receptor (TCR), which recognize human TERT with high avidity, controls human B-cell chronic lymphocytic leukaemia (B-CLL) progression without severe side-effects in humanized mice. In the present report, we show the ability of our approach to limit the progression of more aggressive leukemic pathologies, such as acute myeloid leukaemia (AML) and B-cell acute lymphoblastic leukaemia (B-ALL). Together, our findings demonstrate that TERT-based adoptive cell therapy is a concrete platform of T cell-mediated immunotherapy for leukaemia treatment. PMID:29152058

  8. Comparison of Acute Health Effects From Exposures to Diesel and Biodiesel Fuel Emissions

    PubMed Central

    Mehus, Aaron A.; Reed, Rustin J.; Lee, Vivien S. T.; Littau, Sally R.; Hu, Chengcheng; Lutz, Eric A.

    2015-01-01

    Objective: To investigate the comparative acute health effects associated with exposures to diesel and 75% biodiesel/25% diesel (B75) blend fuel emissions. Methods: We analyzed multiple health endpoints in 48 healthy adults before and after exposures to diesel and B75 emissions in an underground mine setting—lung function, lung and systemic inflammation, novel biomarkers of exposure, and oxidative stress were assessed. Results: B75 reduced respirable diesel particulate matter by 20%. Lung function declined significantly more after exposure to diesel emissions. Lung inflammatory cells along with sputum and plasma inflammatory mediators increased significantly to similar levels with both exposures. Urinary 8-hydroxydeoxyguanosine, a marker of oxidative stress, was not significantly changed after either exposure. Conclusions: Use of B75 lowered respirable diesel particulate matter exposure and some associated acute health effects, although lung and systemic inflammation were not reduced compared with diesel use. PMID:26147538

  9. Protective effects of C-phycocyanin on alcohol-induced acute liver injury in mice

    NASA Astrophysics Data System (ADS)

    Xia, Dong; Liu, Bing; Luan, Xiying; Sun, Junyan; Liu, Nana; Qin, Song; Du, Zhenning

    2016-03-01

    Excessive alcohol consumption leads to liver disease. Extensive evidence suggests that C-phycocyanin (C-PC), a chromophore phycocyanobilin derived from Spirulina platensis, exerts protective effects against chemical-induced organ damage. In this study, we investigated whether C-PC could protect against ethanol-induced acute liver injury. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (CHOL), low-density lipoprotein (LDL), liver homogenate malondialdehyde (MDA), superoxide dismutase (SOD) content were measured, and pathological examination of liver sections were examined. C-PC showed obvious inhibitory effects on serum ALT, AST, TG, CHOL, LDL and MDA, and SOD content significantly increased in the liver. The structure of hepatic lobules was clear, liver sinus returned to normal, and liver cell cords were arranged in neat rows. Cloudiness, swelling, inflammatory cell infiltration and spotty necrosis of liver cells were significantly reduced. Therefore, C-PC can significantly protect against ethanol-induced acute liver injury.

  10. Acute and chronic effects of four commercial herbicide formulations on Ceriodaphnia dubia

    USGS Publications Warehouse

    Ort, M. P.; Fairchild, J.F.; Finger, S.E.

    1994-01-01

    Toxicity tests with Ceriodaphnia dubia were conducted to determine acute (48 h) and chronic (7-day survival and reproduction) effects of four commonly used herbicide formulations. The 48-h LC50s in decreasing order of toxicity were 14.36 mg/L (Micro-Tech®), 15.93 mg/L (Bicep®), 32.99 mg/L (Extrazine®), and 35.36 mg/L (Lexone®). Reduced reproduction was detected at concentrations below 48-h LC50s for three of the formulations. The 7-day chronic values (ChV) based on reproduction were 17.68 mg/L (Micro-Tech®), 8.84 mg/L (Bicep®), 17.68 mg/L (Extrazine®), and 8.84 mg/L (Lexone®). The acute-to-chronic ratios (ACRs) for Micro-Tech® (0.81), Bicep® (1.80), Extrazine® (1.86), and Lexone® (4.00) indicate a relatively narrow range between acute and chronic sensitivity in daphnids. A comparison of these response data to environmental concentrations suggests these herbicides are not likely to directly impact invertebrates. Potential impacts on plants and human health should be of primary ecological and regulatory concern.

  11. Effect of acute and chronic administration of caffeine on pain-like behaviors in rats with partial sciatic nerve injury.

    PubMed

    Wu, Wei-Ping; Hao, Jing-Xia; Fredholm, Bertil B; Wiesenfeld-Hallin, Zsuzsanna; Xu, Xiao-Jun

    2006-07-10

    Caffeine, used in many pain medications as an adjuvant analgesic, is an adenosine A1 and A2A receptor antagonist. Here we examined the effects of acute or chronic caffeine administration in rats after partial sciatic nerve injury. The hindpaw response to mechanical or cold stimulation was assessed following photochemically induced sciatic nerve injury which leads to hypersensitivity to these stimuli. Caffeine was administered i.p. acutely or in the drinking water chronically. The mechanical and cold hypersensitivity of sciatic nerve-injured rats was dose-dependently alleviated by acute systemic administration of caffeine (10-80 mg/kg). The effect of caffeine was, however, associated with side effects including locomotor stimulation or depression. Chronic oral administration (average daily doses 27.5 mg/kg/day or 61.5 mg/kg/day for 2 weeks) of caffeine starting at the time of nerve injury did not significantly affect the development of pain-like behaviors. Thus, acute, but not long term, caffeine intake reduced neuropathic pain state in nerve-injured rats, but only at very high doses. The potential hyperalgesic effect of chronic A1 adenosine receptor blockade may have been compensated for by an antinociceptive effect of caffeine through antagonism of A2A receptors and tolerance development.

  12. Effect of nicardipine on somatosensory evoked potentials in patients with acute cerebral infarction.

    PubMed Central

    Yao, L P; Ding, D Y

    1990-01-01

    We evaluated the effect of nicardipine, a calcium channel blocker, on somatosensory evoked potentials (SEP) in 26 patients with acute cerebral infarction. Post treatment, 58% (15/26) of the N20 and P25 latencies were prolonged in the affected hemispheres; 8% (2/26) were shortened; and 35% (9/26) did not change. The mean N20 and P25 latencies were significantly prolonged two hours post treatment in the affected hemisphere (N20, P less than 0.01, P25 P less than 0.01). Nicardipine (Ni) had no effect on SEP components in the intact hemispheres. Seventy five per cent of the 12 patients with hypertension had a decrease in blood pressure (BP) after taking nicardipine, but there were no undesirable side effects or worsening of neurological signs. Our study demonstrates that nicardipine prolongs the latencies of short-latency components of SEP in the affected hemisphere after acute ischaemic stroke and also decreases BP. These observations suggest that nicardipine therapy might impair neuronal function in the ischaemic zone. PMID:2266363

  13. Effects of the Mitochondria-Targeted Antioxidant Mitoquinone in Murine Acute Pancreatitis

    PubMed Central

    Wen, Li; Szatmary, Peter; Mukherjee, Rajarshi; Armstrong, Jane; Chvanov, Michael; Tepikin, Alexei V.; Murphy, Michael P.; Sutton, Robert; Criddle, David N.

    2015-01-01

    Although oxidative stress has been strongly implicated in the development of acute pancreatitis (AP), antioxidant therapy in patients has so far been discouraging. The aim of this study was to assess potential protective effects of a mitochondria-targeted antioxidant, MitoQ, in experimental AP using in vitro and in vivo approaches. MitoQ blocked H2O2-induced intracellular ROS responses in murine pancreatic acinar cells, an action not shared by the control analogue dTPP. MitoQ did not reduce mitochondrial depolarisation induced by either cholecystokinin (CCK) or bile acid TLCS, and at 10 µM caused depolarisation per se. Both MitoQ and dTPP increased basal and CCK-induced cell death in a plate-reader assay. In a TLCS-induced AP model MitoQ treatment was not protective. In AP induced by caerulein hyperstimulation (CER-AP), MitoQ exerted mixed effects. Thus, partial amelioration of histopathology scores was observed, actions shared by dTPP, but without reduction of the biochemical markers pancreatic trypsin or serum amylase. Interestingly, lung myeloperoxidase and interleukin-6 were concurrently increased by MitoQ in CER-AP. MitoQ caused biphasic effects on ROS production in isolated polymorphonuclear leukocytes, inhibiting an acute increase but elevating later levels. Our results suggest that MitoQ would be inappropriate for AP therapy, consistent with prior antioxidant evaluations in this disease. PMID:25878403

  14. Effects of the mitochondria-targeted antioxidant mitoquinone in murine acute pancreatitis.

    PubMed

    Huang, Wei; Cash, Nicole; Wen, Li; Szatmary, Peter; Mukherjee, Rajarshi; Armstrong, Jane; Chvanov, Michael; Tepikin, Alexei V; Murphy, Michael P; Sutton, Robert; Criddle, David N

    2015-01-01

    Although oxidative stress has been strongly implicated in the development of acute pancreatitis (AP), antioxidant therapy in patients has so far been discouraging. The aim of this study was to assess potential protective effects of a mitochondria-targeted antioxidant, MitoQ, in experimental AP using in vitro and in vivo approaches. MitoQ blocked H2O2-induced intracellular ROS responses in murine pancreatic acinar cells, an action not shared by the control analogue dTPP. MitoQ did not reduce mitochondrial depolarisation induced by either cholecystokinin (CCK) or bile acid TLCS, and at 10 µM caused depolarisation per se. Both MitoQ and dTPP increased basal and CCK-induced cell death in a plate-reader assay. In a TLCS-induced AP model MitoQ treatment was not protective. In AP induced by caerulein hyperstimulation (CER-AP), MitoQ exerted mixed effects. Thus, partial amelioration of histopathology scores was observed, actions shared by dTPP, but without reduction of the biochemical markers pancreatic trypsin or serum amylase. Interestingly, lung myeloperoxidase and interleukin-6 were concurrently increased by MitoQ in CER-AP. MitoQ caused biphasic effects on ROS production in isolated polymorphonuclear leukocytes, inhibiting an acute increase but elevating later levels. Our results suggest that MitoQ would be inappropriate for AP therapy, consistent with prior antioxidant evaluations in this disease.

  15. Behavior Therapy for Tics in Children: Acute and Long-Term Effects on Psychiatric and Psychosocial Functioning

    PubMed Central

    Woods, Douglas W.; Piacentini, John C.; Scahill, Lawrence; Peterson, Alan L.; Wilhelm, Sabine; Chang, Susanna; Deckersbach, Thilo; McGuire, Joseph; Specht, Matt; Conelea, Christine A.; Rozenman, Michelle; Dzuria, James; Liu, Haibei; Levi-Pearl, Sue; Walkup, John T.

    2014-01-01

    Children (n = 126) ages 9 to 17 years with chronic tic or Tourette disorder were randomly assigned to receive either behavior therapy or a control treatment over 10 weeks. This study examined acute effects of behavior therapy on secondary psychiatric symptoms and psychosocial functioning and long-term effects on these measures for behavior therapy responders only. Baseline and end point assessments conducted by a masked independent evaluator assessed several secondary psychiatric symptoms and measures of psychosocial functioning. Responders to behavior therapy at the end of the acute phase were reassessed at 3-month and 6-month follow-up. Children in the behavior therapy and control conditions did not differentially improve on secondary psychiatric or psychosocial outcome measures at the end of the acute phase. At 6-month posttreatment, positive response to behavior therapy was associated with decreased anxiety, disruptive behavior, and family strain and improved social functioning. Behavior therapy is a tic-specific treatment for children with tic disorders. PMID:21555779

  16. [Clinical evaluation of Olbas oil effect on nasal mucosa in acute rhinitis patients during common cold].

    PubMed

    Zalewski, P; Olszewski, J; Olszewska-Ziaber, A; Zielińska-Bliźniewska, H; Pietkiewicz, P

    1997-01-01

    The aim of the study was the clinical evaluation of the effect of Olbas oil on nasal mucosa in patients with acute rhinitis during common cold. 15 patients with 2-3 days history of acute rhinitis during common cold, both sexes, in the age between 23-47 were investigated. All the examinations were done before using, after the first inhalation, and after 7 days of Olbas oil administration. The investigation before using Olbas oil was comprised of: history data, general and otorhinolaryngological examination with particular evaluation of nasal mucosa, anterior rhinomanometry, saccharin translocation time, olfactometry, microbiological cultures, histamine nasal provocation test. At the end, after 7 days of Olbas oil inhalation 3 times a day for 4 minutes 4 drops of Olbas oil applied into a handkerchief, all the test were done again, as at the beginning. The study showed a good of the effect of Olbas oil on nasal mucosa in patients with acute rhinitis during common cold.

  17. Acute effects of a glucose energy drink on behavioral control.

    PubMed

    Howard, Meagan A; Marczinski, Cecile A

    2010-12-01

    There has been a dramatic rise in the consumption of glucose energy drinks (e.g., Amp, Monster, and Red Bull) in the past decade, particularly among high school and college students. However, little laboratory research has examined the acute objective and subjective effects of energy drinks. The purpose of this study was to investigate the acute effects of a glucose energy drink (Red Bull) on cognitive functioning. Participants (N = 80) were randomly assigned to one of five conditions: 1.8 ml/kg energy drink, 3.6 ml/kg energy drink, 5.4 ml/kg energy drink, placebo beverage, or no drink. Participants completed a well-validated behavioral control task (the cued go/no-go task) and subjective measures of stimulation, sedation, and mental fatigue both before and 30 minutes following beverage administration. The results indicated that compared with the placebo and no drink conditions, the energy drink doses decreased reaction times on the behavioral control task, increased subjective ratings of stimulation and decreased ratings of mental fatigue. Greatest improvements in reaction times and subjective measures were observed with the lowest dose and improvements diminished as the dose increased. The findings suggest that energy drink consumption can improve cognitive performance on a behavioral control task, potentially explaining the dramatic rise in popularity of these controversial new beverages. PsycINFO Database Record (c) 2010 APA, all rights reserved.

  18. The Effects of Acute High-Intensity Interval Training on Hematological Parameters in Sedentary Subjects.

    PubMed

    Belviranli, Muaz; Okudan, Nilsel; Kabak, Banu

    2017-07-19

    The objective of the study was to determine the effects of acute high-intensity interval training (HIIT) on hematological parameters in sedentary men. Ten healthy, non-smoker, and sedentary men aged between 18 and 24 years participated in the study. All subjects performed four Wingate tests with 4 min intervals between the tests. Blood samples were collected at pre-exercise, immediately after, 3 and 6 h after the fourth Wingate test. Hematological parameters were analyzed in these samples. The results showed that hematocrit percentage, hemoglobin values, red cell count, mean cell volume, platelet count, total white cell count, and counts of the white cell subgroups increased immediately after the acute HIIT and their values began to return to resting levels 3 h after exercise, and completely returned to resting levels 6 h after exercise. In conclusion, acute HIIT causes an inflammatory response in blood.

  19. Effectiveness of acute geriatric units in the real world: the case of short-term mortality among seniors hospitalized for pneumonia.

    PubMed

    Ding, Yew Yoong; Abisheganaden, John; Chong, Wai Fung; Heng, Bee Hoon; Lim, Tow Keang

    2013-01-01

    We sought to compare the effectiveness of acute geriatric units with usual medical care in reducing short-term mortality among seniors hospitalized for pneumonia in the real world. In a retrospective cohort study, we merged chart and administrative data of seniors aged 65 years and older admitted to acute geriatric units and other medical units for pneumonia at three hospitals over 1 year. The outcome was 30-day mortality. Hierarchical logistic regression modeling was carried out to estimate the treatment effect of acute geriatric units for all seniors, those aged 80 years and older, and those with premorbid ambulation impairment, after adjusting for demographic and clinical characteristics, and accounting for clustering around hospitals. Among 2721 seniors, 30-day mortality was 25.5%. For those admitted to acute geriatric and other medical units, this was 24.2% and 25.8%, respectively. Using hierarchical logistic regression modeling, treatment in acute geriatric units was not associated with significant mortality reduction among all seniors (OR 0.72, 95% CI 0.52-1.00). However, significant mortality reduction was observed in the subgroups of those aged 80 years and older (OR 0.73, 95% CI 0.54-0.99), and with premorbid ambulation impairment (OR 0.65, 95% CI 0.46-0.93). Acute geriatric units reduced short-term mortality among seniors hospitalized for pneumonia who were aged 80 years and older or had premorbid ambulation impairment. Further research is required to determine if this beneficial effect extends to seniors hospitalized for other acute medical disorders. © 2012 Japan Geriatrics Society.

  20. TrpC5 Mediates Acute Leptin and Serotonin Effects via Pomc Neurons.

    PubMed

    Gao, Yong; Yao, Ting; Deng, Zhuo; Sohn, Jong-Woo; Sun, Jia; Huang, Yiru; Kong, Xingxing; Yu, Kai-Jiang; Wang, Rui-Tao; Chen, Hong; Guo, Hongbo; Yan, Jianqun; Cunningham, Kathryn A; Chang, Yongsheng; Liu, Tiemin; Williams, Kevin W

    2017-01-17

    The molecular mechanisms underlying acute leptin and serotonin 2C receptor-induced hypophagia remain unclear. Here, we show that neuronal and pro-opiomelanocortin (Pomc)-specific loss of transient receptor potential cation 5 (TrpC5) subunits is sufficient to decrease energy expenditure and increase food intake resulting in elevated body weight. Deficiency of Trpc5 subunits in Pomc neurons is also sufficient to block the anorexigenic effects of leptin and serotonin 2C receptor (Ht2Cr) agonists. The loss of acute anorexigenic effects of these receptors is concomitant with a blunted electrophysiological response to both leptin and Ht2Cr agonists in arcuate Pomc neurons. We also demonstrate that the Ht2Cr agonist lorcaserin-induced improvements in glucose and insulin tolerance are blocked by TrpC5 deficiency in Pomc neurons. Together, our results link TrpC5 subunits in the brain with leptin- and serotonin 2C receptor-dependent changes in neuronal activity, as well as energy balance, feeding behavior, and glucose metabolism. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Admission Glucose and Effect of Intra-Arterial Treatment in Patients With Acute Ischemic Stroke.

    PubMed

    Osei, Elizabeth; den Hertog, Heleen M; Berkhemer, Olvert A; Fransen, Puck S S; Roos, Yvo B W E M; Beumer, Debbie; van Oostenbrugge, Robert J; Schonewille, Wouter J; Boiten, Jelis; Zandbergen, Adrienne A M; Koudstaal, Peter J; Dippel, Diederik W J

    2017-05-01

    Hyperglycemia on admission is common after ischemic stroke. It is associated with unfavorable outcome after treatment with intravenous thrombolysis and after intra-arterial treatment. Whether hyperglycemia influences the effect of reperfusion treatment is unknown. We assessed whether increased admission serum glucose modifies the effect of intra-arterial treatment in patients with acute ischemic stroke. We used data from the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands). Hyperglycemia was defined as admission serum glucose >7.8 mmol/L. The primary outcome measure was the adjusted common odds ratio for a shift in the direction of a better outcome on the modified Rankin Scale at 90 days, estimated with ordinal logistic regression. Secondary outcome variable was symptomatic intracranial hemorrhage. We assessed treatment effect modification of hyperglycemia and admission serum glucose levels with multiplicative interaction factors and adjusted for prognostic variables. Four hundred eighty-seven patients were included. Mean admission serum glucose was 7.2 mmol/L (SD, 2.2). Fifty-seven of 226 patients (25%) randomized to intra-arterial treatment were hyperglycemic compared with 61 of 261 patients (23%) in the control group. The interaction of either hyperglycemia or admission serum glucose levels and treatment effect on modified Rankin Scale scores was not significant ( P =0.67 and P =0.87, respectively). The same applied for occurrence of symptomatic hemorrhage ( P =0.39 for hyperglycemia, P =0.39 for admission serum glucose). We found no evidence for effect modification of intra-arterial treatment by admission serum glucose in patients with acute ischemic stroke. URL: www.isrctn.com. Unique identifier: ISRCTN10888758. © 2017 American Heart Association, Inc.

  2. Stimulatory actions of IGF-I are mediated by IGF-IR cross-talk with GPER and DDR1 in mesothelioma and lung cancer cells.

    PubMed

    Avino, Silvia; De Marco, Paola; Cirillo, Francesca; Santolla, Maria Francesca; De Francesco, Ernestina Marianna; Perri, Maria Grazia; Rigiracciolo, Damiano; Dolce, Vincenza; Belfiore, Antonino; Maggiolini, Marcello; Lappano, Rosamaria; Vivacqua, Adele

    2016-08-16

    Insulin-like growth factor-I (IGF-I)/IGF-I receptor (IGF-IR) system has been largely involved in the pathogenesis and development of various tumors. We have previously demonstrated that IGF-IR cooperates with the G-protein estrogen receptor (GPER) and the collagen receptor discoidin domain 1 (DDR1) that are implicated in cancer progression. Here, we provide novel evidence regarding the molecular mechanisms through which IGF-I/IGF-IR signaling triggers a functional cross-talk with GPER and DDR1 in both mesothelioma and lung cancer cells. In particular, we show that IGF-I activates the transduction network mediated by IGF-IR leading to the up-regulation of GPER and its main target genes CTGF and EGR1 as well as the induction of DDR1 target genes like MATN-2, FBN-1, NOTCH 1 and HES-1. Of note, certain DDR1-mediated effects upon IGF-I stimulation required both IGF-IR and GPER as determined knocking-down the expression of these receptors. The aforementioned findings were nicely recapitulated in important biological outcomes like IGF-I promoted chemotaxis and migration of both mesothelioma and lung cancer cells. Overall, our data suggest that IGF-I/IGF-IR system triggers stimulatory actions through both GPER and DDR1 in aggressive tumors as mesothelioma and lung tumors. Hence, this novel signaling pathway may represent a further target in setting innovative anticancer strategies.

  3. Antiarrhythmic effect of uridine and uridine-5'-monophosphate in acute myocardial ischemia.

    PubMed

    Bul'on, V V; Krylova, I B; Selina, E N; Rodionova, O M; Evdokimova, N R; Sapronov, N S; Mironova, G D

    2014-10-01

    Experiments on rats with acute myocardial ischemia accompanied by early postocclusive arrhythmias have shown normalizing, energy-stabilizing, and antiarrhythmic effects of uridine and uridine-5'-monophosphate. The drugs decreased lactate and restored reserves of glycogen and creatine phosphate depleted by ischemia. Uridine and uridine-5'-monophosphate significantly decreased the severity of ventricular arrhythmias. Both drugs reduced the incidence and duration of fibrillation. Uridine -5'-monophosphate demonstrated most pronounced antifibrillatory effectiveness. We hypothesize that the antiarrhythmic effect of the drugs is determined by their capacity to activate energy metabolism.

  4. Neuroprotective effects of autophagy induced by rapamycin in rat acute spinal cord injury model.

    PubMed

    Wang, Zhen-Yu; Liu, Wen-Ge; Muharram, Akram; Wu, Zhao-Yan; Lin, Jian-Hua

    2014-01-01

    To explore the effects of rapamycin-induced autophagy on apoptosis in a rat model of acute spinal cord injury (SCI), and to explore the effect of rapamycin on apoptosis in primary spinal cord cell culture. SCI was induced at T10 in female adult Sprague-Dawley rats. After injury was induced, the rats were injected with rapamycin and/or methylprednisolone and were sacrificed at various days after injury. Apoptosis and autophagy were examined with TUNEL staining and electron microscopy. Hind limb function was assessed by the Gale scale. The expression of the apoptosis-related protein caspase-3 did not significantly increase until 21 days following injury, while increases in LC3II and LC3I began 10 days after injury, but then declined. TUNEL staining and electron microscopy confirmed that following injury autophagy occurred before apoptosis, but by 14 days after the injury, the level of autophagy had decreased significantly while the level of apoptosis showed a continued increase. Following treatment with rapamycin, apoptosis was significantly higher than in the vehicle control group, but significantly lower than in the sham-operated group, showing a protective effect of rapamycin. Gale scale grades in rats treated with rapamycin were significantly higher compared with the vehicle control group, suggesting a functional effect of rapamycin-induced inhibition of apoptosis. The results indicate that rapamycin significantly improved the prognosis of acute SCI in rats by inhibiting cell apoptosis. Rapamycin might be useful as a therapeutic agent for acute SCI. © 2014 S. Karger AG, Basel

  5. Detectable signals of episodic risk effects on acute HIV transmission: Strategies for analyzing transmission systems using genetic data

    PubMed Central

    Alam, Shah Jamal; Zhang, Xinyu; Romero-Severson, Ethan Obie; Henry, Christopher; Zhong, Lin; Volz, Erik M.; Brenner, Bluma G.; Koopman, James S.

    2013-01-01

    Episodic high-risk sexual behavior is common and can have a profound effect on HIV transmission. In a model of HIV transmission among men who have sex with men (MSM), changing the frequency, duration and contact rates of high-risk episodes can take endemic prevalence from zero to 50% and more than double transmissions during acute HIV infection (AHI). Undirected test and treat could be inefficient in the presence of strong episodic risk effects. Partner services approaches that use a variety of control options will be likely to have better effects under these conditions, but the question remains: What data will reveal if a population is experiencing episodic risk effects? HIV sequence data from Montreal reveals genetic clusters whose size distribution stabilizes over time and reflects the size distribution of acute infection outbreaks (AIOs). Surveillance provides complementary behavioral data. In order to use both types of data efficiently, it is essential to examine aspects of models that affect both the episodic risk effects and the shape of transmission trees. As a demonstration, we use a deterministic compartmental model of episodic risk to explore the determinants of the fraction of transmissions during acute HIV infection (AHI) at the endemic equilibrium. We use a corresponding individual-based model to observe AIO size distributions and patterns of transmission within AIO. Episodic risk parameters determining whether AHI transmission trees had longer chains, more clustered transmissions from single individuals, or different mixes of these were explored. Encouragingly for parameter estimation, AIO size distributions reflected the frequency of transmissions from acute infection across divergent parameter sets. Our results show that episodic risk dynamics influence both the size and duration of acute infection outbreaks, thus providing a possible link between genetic cluster size distributions and episodic risk dynamics. PMID:23438430

  6. The effect of acute exercise on pulsatile release of luteinizing hormone in women runners.

    PubMed

    Cumming, D C; Vickovic, M M; Wall, S R; Fluker, M R; Belcastro, A N

    1985-11-01

    Endurance exercise has been associated with reproductive dysfunction. We have previously suggested that pulsatile release of luteinizing hormone is impaired at rest in normal menstruating runners compared with sedentary women. To determine whether acute exercise had any effect on pulsatile release of luteinizing hormone we investigated serum luteinizing hormone levels in six normal menstruating runners at rest and after 60 minutes of running exercise. Exercise induced an increment in circulating luteinizing hormone levels greater than the change in hematocrit. The luteinizing hormone pulse frequency, calculated as the number of luteinizing hormone pulses per 6 hours, was reduced after exercise compared with values obtained at rest. There was no significant difference in pulse amplitude or area under the 6-hour curve between resting and postexercise situations. These data suggest that acute exercise has an inhibitory effect on luteinizing hormone pulsatile release at the hypothalamic level in eumenorrheic runners that is in addition to the previously described effect of training.

  7. Acute effects of coffee on skin blood flow and microvascular function.

    PubMed

    Tesselaar, Erik; Nezirevic Dernroth, Dzeneta; Farnebo, Simon

    2017-11-01

    Studies on the acute effects of coffee on the microcirculation have shown contradicting results. This study aimed to investigate if intake of caffeine-containing coffee changes blood flow and microvascular reactivity in the skin. We measured acute changes in cutaneous vascular conductance (CVC) in the forearm and the tip of the finger, the microvascular response to transdermal iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) and post-occlusive reactive hyperemia (PORH) in the skin, after intake of caffeinated or decaffeinated coffee. Vasodilatation during iontophoresis of ACh was significantly stronger after intake of caffeinated coffee compared to after intake of decaffeinated coffee (1.26±0.20PU/mmHg vs. 1.13±0.38PU/mmHg, P<0.001). Forearm CVC before and after PORH were not affected by caffeinated and decaffeinated coffee. After intake of caffeinated coffee, a more pronounced decrease in CVC in the fingertip was observed compared to after intake of decaffeinated coffee (-1.36PU/mmHg vs. -0.52PU/mmHg, P=0.002). Caffeine, as ingested by drinking caffeinated coffee acutely improves endothelium-dependent microvascular responses in the forearm skin, while endothelium-independent responses to PORH and SNP iontophoresis are not affected. Blood flow in the fingertip decreases markedly during the first hour after drinking caffeinated coffee compared to decaffeinated coffee. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. The Effects of Acute Exercise on Mood, Cognition, Neurophysiology, and Neurochemical Pathways: A Review

    PubMed Central

    Basso, Julia C.; Suzuki, Wendy A.

    2017-01-01

    A significant body of work has investigated the effects of acute exercise, defined as a single bout of physical activity, on mood and cognitive functions in humans. Several excellent recent reviews have summarized these findings; however, the neurobiological basis of these results has received less attention. In this review, we will first briefly summarize the cognitive and behavioral changes that occur with acute exercise in humans. We will then review the results from both human and animal model studies documenting the wide range of neurophysiological and neurochemical alterations that occur after a single bout of exercise. Finally, we will discuss the strengths, weaknesses, and missing elements in the current literature, as well as offer an acute exercise standardization protocol and provide possible goals for future research. PMID:29765853

  9. Cost-Effectiveness of Thrombolysis within 4.5 Hours of Acute Ischemic Stroke in China

    PubMed Central

    Zhao, Xingquan; Liao, Xiaoling; Wang, Chunjuan; Du, Wanliang; Liu, Gaifen; Liu, Liping; Wang, Chunxue; Wang, Yilong; Wang, Yongjun

    2014-01-01

    Background Previous economic studies conducted in developed countries showed intravenous tissue-type plasminogen activator (tPA) is cost-effective for acute ischemic stroke. The present study aimed to determine the cost-effectiveness of tPA treatment in China, the largest developing country. Methods A combination of decision tree and Markov model was developed to determine the cost-effectiveness of tPA treatment versus non-tPA treatment within 4.5 hours after stroke onset. Outcomes and costs data were derived from the database of Thrombolysis Implementation and Monitor of acute ischemic Stroke in China (TIMS-China) study. Efficacy data were derived from a pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Costs and quality-adjusted life-years (QALYs) were compared in both short term (2 years) and long term (30 years). One-way and probabilistic sensitivity analyses were performed to test the robustness of the results. Results Comparing to non-tPA treatment, tPA treatment within 4.5 hours led to a short-term gain of 0.101 QALYs at an additional cost of CNY 9,520 (US$ 1,460), yielding an incremental cost-effectiveness ratio (ICER) of CNY 94,300 (US$ 14,500) per QALY gained in 2 years; and to a long-term gain of 0.422 QALYs at an additional cost of CNY 6,530 (US$ 1,000), yielding an ICER of CNY 15,500 (US$ 2,380) per QALY gained in 30 years. Probabilistic sensitivity analysis showed that tPA treatment is cost-effective in 98.7% of the simulations at a willingness-to-pay threshold of CNY 105,000 (US$ 16,200) per QALY. Conclusions Intravenous tPA treatment within 4.5 hours is highly cost-effective for acute ischemic strokes in China. PMID:25329637

  10. Cost-effectiveness of thrombolysis within 4.5 hours of acute ischemic stroke in China.

    PubMed

    Pan, Yuesong; Chen, Qidong; Zhao, Xingquan; Liao, Xiaoling; Wang, Chunjuan; Du, Wanliang; Liu, Gaifen; Liu, Liping; Wang, Chunxue; Wang, Yilong; Wang, Yongjun

    2014-01-01

    Previous economic studies conducted in developed countries showed intravenous tissue-type plasminogen activator (tPA) is cost-effective for acute ischemic stroke. The present study aimed to determine the cost-effectiveness of tPA treatment in China, the largest developing country. A combination of decision tree and Markov model was developed to determine the cost-effectiveness of tPA treatment versus non-tPA treatment within 4.5 hours after stroke onset. Outcomes and costs data were derived from the database of Thrombolysis Implementation and Monitor of acute ischemic Stroke in China (TIMS-China) study. Efficacy data were derived from a pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Costs and quality-adjusted life-years (QALYs) were compared in both short term (2 years) and long term (30 years). One-way and probabilistic sensitivity analyses were performed to test the robustness of the results. Comparing to non-tPA treatment, tPA treatment within 4.5 hours led to a short-term gain of 0.101 QALYs at an additional cost of CNY 9,520 (US$ 1,460), yielding an incremental cost-effectiveness ratio (ICER) of CNY 94,300 (US$ 14,500) per QALY gained in 2 years; and to a long-term gain of 0.422 QALYs at an additional cost of CNY 6,530 (US$ 1,000), yielding an ICER of CNY 15,500 (US$ 2,380) per QALY gained in 30 years. Probabilistic sensitivity analysis showed that tPA treatment is cost-effective in 98.7% of the simulations at a willingness-to-pay threshold of CNY 105,000 (US$ 16,200) per QALY. Intravenous tPA treatment within 4.5 hours is highly cost-effective for acute ischemic strokes in China.

  11. Effect of acute gastric dilatation on gastric myoelectic and motor activity in dogs.

    PubMed

    Hall, J A; Solie, T N; Seim, H B; Twedt, D C

    1999-05-01

    To investigate the effects of experimentally induced acute gastric dilatation on electrical and mechanical activities of the stomach in dogs. 7 healthy dogs. Electrodes and strain-gauge force transducers were implanted on the serosal surface of the antrum and pylorus. Eight days later, baseline gastric electrical and contractile activities were recorded. The dogs were anesthetized and mechanically ventilated to maintain normocapnia while the stomach was distended (intragastric pressure, 30 mm Hg) for 180 minutes, using a thin compliant bag. Gastric electrical and contractile activities were recorded again on days 1 and 10 after dilatation. Recordings were analyzed to determine gastric slow-wave frequency, slow-wave dysrhythmia, propagation velocity of slow-waves, coupling of contractions to slow waves, motility index on the basis of relative contractile amplitudes, and onset of contractions after a standardized meal. Electrical or contractile activities were not significantly different 18 hours after acute gastric dilatation (day 1). Arrhythmias were evident before and after gastric dilatation in dogs from which food was withheld and in dogs after consumption of a meal. Variables for assessing gastric electrical and contractile activities were unaffected 18 hours after acute gastric dilatation. Analysis of results of this study indicated that altered electrical and contractile activities in dogs with short-term gastric dilatation are not likely to be secondary to the process of acute gastric dilatation.

  12. Self-regulation strategies may enhance the acute effect of exercise on smoking delay.

    PubMed

    Hatzigeorgiadis, Antonis; Pappa, Vassiliki; Tsiami, Anastasia; Tzatzaki, Theodora; Georgakouli, Kalliopi; Zourbanos, Nikos; Goudas, Marios; Chatzisarantis, Nikos; Theodorakis, Yannis

    2016-06-01

    The present study examined the acute effect of a moderate intensity aerobic exercise session combined with self-regulation on smoking delay in physically inactive smokers. Participants were 11 adults (5 males and 6 females) that completed three experimental conditions: control, exercise, and exercise using self-regulation strategies (SR). Following the experimental treatment smoking for the two exercise conditions delayed significantly more than for the control condition; in addition exercise SR delayed smoking marginally more that the plain exercise condition. Findings supported previous research that acute exercise reduces cravings to smoke, and suggests that the use of self-regulation strategies may strengthen exercise for smoking cessation interventions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Red Wine Prevents the Acute Negative Vascular Effects of Smoking.

    PubMed

    Schwarz, Viktoria; Bachelier, Katrin; Schirmer, Stephan H; Werner, Christian; Laufs, Ulrich; Böhm, Michael

    2017-01-01

    Moderate consumption of red wine is associated with fewer cardiovascular events. We investigated whether red wine consumption counteracts the adverse vascular effects of cigarette smoking. Participants smoked 3 cigarettes alone or after drinking a titrated volume of red wine. Clinical chemistry, blood counts, plasma cytokine enzyme-linked immunosorbent assays, immunomagnetic separation of CD14 + monocytes for gene expression analysis, fluorescence-activated cell sorting for microparticles, and isolation of circulating mononuclear cells to measure telomerase activity were performed, and urine cotinine levels were quantified. Compared with baseline, leukocytosis (P = .019), neutrophilia (P <.001), lymphopenia (P <.001), and eosinopenia (P = .008) were observed after only smoking. Endothelial and platelet-, monocyte-, and leukocyte-derived microparticles (P <.001 each) were elevated. In monocytes, messenger RNA expression of interleukin (IL)-6 (2.6- ± 0.57-fold), tumor necrosis factor alpha (2.2- ± 0.62-fold), and IL-1b (2.3- ± 0.44-fold) were upregulated, as was IL-6 (1.2 ± 0.12-fold) protein concentration in plasma. Smoking acutely inhibited mononuclear cell telomerase activity. Markers of endothelial damage, inflammation, and cellular aging were completely attenuated by red wine consumption. Cigarette smoke results in acute endothelial damage, vascular and systemic inflammation, and indicators of the cellular aging processes in otherwise healthy nonsmokers. Pretreatment with red wine was preventive. The findings underscore the magnitude of acute damage exerted by cigarette smoking in "occasional lifestyle smokers" and demonstrate the potential of red wine as a protective strategy to avert markers of vascular injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Effect of acute and repeated restraint stress on glucose oxidation to CO2 in hippocampal and cerebral cortex slices.

    PubMed

    Torres, I L; Gamaro, G D; Silveira-Cucco, S N; Michalowski, M B; Corrêa, J B; Perry, M L; Dalmaz, C

    2001-01-01

    It has been suggested that glucocorticoids released during stress might impair neuronal function by decreasing glucose uptake by hippocampal neurons. Previous work has demonstrated that glucose uptake is reduced in hippocampal and cerebral cortex slices 24 h after exposure to acute stress, while no effect was observed after repeated stress. Here, we report the effect of acute and repeated restraint stress on glucose oxidation to CO2 in hippocampal and cerebral cortex slices and on plasma glucose and corticosterone levels. Male adult Wistar rats were exposed to restraint 1 h/day for 50 days in the chronic model. In the acute model there was a single exposure. Immediately or 24 h after stress, the animals were sacrificed and the hippocampus and cerebral cortex were dissected, sliced, and incubated with Krebs buffer, pH 7.4, containing 5 mM glucose and 0.2 microCi D-[U-14C] glucose. CO2 production from glucose was estimated. Trunk blood was also collected, and both corticosterone and glucose were measured. The results showed that corticosterone levels after exposure to acute restraint were increased, but the increase was smaller when the animals were submitted to repeated stress. Blood glucose levels increased after both acute and repeated stress. However, glucose utilization, measured as CO2 production in hippocampal and cerebral cortex slices, was the same in stressed and control groups under conditions of both acute and chronic stress. We conclude that, although stress may induce a decrease in glucose uptake, this effect is not sufficient to affect the energy metabolism of these cells.

  15. Effects of acute and chronic exercise in patients with essential hypertension: benefits and risks.

    PubMed

    Gkaliagkousi, Eugenia; Gavriilaki, Eleni; Douma, Stella

    2015-04-01

    The importance of regular physical activity in essential hypertension has been extensively investigated over the last decades and has emerged as a major modifiable factor contributing to optimal blood pressure control. Aerobic exercise exerts its beneficial effects on the cardiovascular system by promoting traditional cardiovascular risk factor regulation, as well as by favorably regulating sympathetic nervous system (SNS) activity, molecular effects, cardiac, and vascular function. Benefits of resistance exercise need further validation. On the other hand, acute exercise is now an established trigger of acute cardiac events. A number of possible pathophysiological links have been proposed, including SNS, vascular function, coagulation, fibrinolysis, and platelet function. In order to fully interpret this knowledge into clinical practice, we need to better understand the role of exercise intensity and duration in this pathophysiological cascade and in special populations. Further studies in hypertensive patients are also warranted in order to clarify the possibly favorable effect of antihypertensive treatment on exercise-induced effects. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Pharmacological Effects of Niacin on Acute Hyperlipemia.

    PubMed

    la Paz, Sergio Montserrat-de; Bermudez, Beatriz; Naranjo, M Carmen; Lopez, Sergio; Abia, Rocio; Muriana, Francisco J G

    2016-01-01

    The well-known changes in modern lifestyle habits including over nutrition and physical inactivity have led to striking adverse effects on public health (e.g., obesity, diabetes, and metabolic syndrome) over recent decades. One noticeable consequence is exaggerated and prolonged state of postprandial hyperlipemia due to the ingestion of multiple fat-enriched meals during the course of a day. Postprandial (non-fasting) hyperlipemia is characterized by increased blood levels of exogenous triglycerides (TG) in the form of apolipoprotein (apo) B48-containing TG-rich lipoproteins (TRL), which have a causal role in the pathogenesis and progression of cardiovascular disease (CVD). The cardiovascular benefits of lifestyle modification (healthy diet and exercise) and conventional lipid-lowering therapies (e.g., statins, fibrates, and niacin) could involve their favourable effects on postprandial metabolism. Pharmacologically, niacin has been used as an athero-protective drug for five decades. Studies have since shown that niacin may decrease fasting levels of plasma verylow- density lipoproteins (VLDL), low-density lipoprotein cholesterol (LDL-C), and lipoprotein [a] (Lp[a]), while may increase high-density lipoprotein cholesterol (HDL-C). Herein, the purpose of this review was to provide an update on effects and mechanisms related to the pharmacological actions of niacin on acute hyperlipemia.

  17. Acute Effects of Lysergic Acid Diethylamide on Circulating Steroid Levels in Healthy Subjects.

    PubMed

    Strajhar, P; Schmid, Y; Liakoni, E; Dolder, P C; Rentsch, K M; Kratschmar, D V; Odermatt, A; Liechti, M E

    2016-03-01

    Lysergic acid diethylamide (LSD) is a serotonin 5-hydroxytryptamine-2A (5-HT2A ) receptor agonist that is used recreationally worldwide. Interest in LSD research in humans waned after the 1970s, although the use of LSD in psychiatric research and practice has recently gained increasing attention. LSD produces pronounced acute psychedelic effects, although its influence on plasma steroid levels over time has not yet been characterised in humans. The effects of LSD (200 μg) or placebo on plasma steroid levels were investigated in 16 healthy subjects using a randomised, double-blind, placebo-controlled, cross-over study design. Plasma concentration-time profiles were determined for 15 steroids using liquid-chromatography tandem mass-spectrometry. LSD increased plasma concentrations of the glucocorticoids cortisol, cortisone, corticosterone and 11-dehydrocorticosterone compared to placebo. The mean maximum concentration of LSD was reached at 1.7 h. Mean peak psychedelic effects were reached at 2.4 h, with significant alterations in mental state from 0.5 h to > 10 h. Mean maximal concentrations of cortisol and corticosterone were reached at 2.5 h and 1.9 h, and significant elevations were observed 1.5-6 h and 1-3 h after drug administration, respectively. LSD also significantly increased plasma concentrations of the androgen dehydroepiandrosterone but not other androgens, progestogens or mineralocorticoids compared to placebo. A close relationship was found between plasma LSD concentrations and changes in plasma cortisol and corticosterone and the psychotropic response to LSD, and no clockwise hysteresis was observed. In conclusion, LSD produces significant acute effects on circulating steroids, especially glucocorticoids. LSD-induced changes in circulating glucocorticoids were associated with plasma LSD concentrations over time and showed no acute pharmacological tolerance. © 2016 British Society for Neuroendocrinology.

  18. Acute toxicity of diphacinone in Northern bobwhite: Effects on survival and blood clotting

    USGS Publications Warehouse

    Rattner, Barnett A.; Horak, Katherine E.; Warner, Sarah E.; Johnston, John J.

    2010-01-01

    The anticoagulant rodenticide diphacinone was slightly toxic (acute oral LD50 2014 mg/kg) to Northern bobwhite (Colinus virginianus) in a 14-day acute toxicity trial. Precise and sensitive assays of blood clotting (prothrombin time, Russell?s Viper venom time, and thrombin clotting time) were adapted for use in quail, and this combination of assays is recommended to measure the effects of anticoagulant rodenticides. A single oral sublethal dose of diphacinone (434 mg/kg body weight) prolonged clotting time at 48 h post-dose compared to controls. At 783 mg/kg (approximate LD02), clotting time was prolonged at both 24 and 48 h post-dose. Prolongation of in vitro clotting time reflects impaired coagulation complex activity, and was detected before overt signs of toxicity were apparent at the greatest dosages (2868 and 3666 mg/kg) in the acute toxicity trial. These clotting time assays and toxicity data will assist in the development of a pharmacodynamic model to predict toxicity, and also facilitate rodenticide hazard and risk assessments in avian species.

  19. The effect of obesity on inflammatory cytokine and leptin production following acute mental stress.

    PubMed

    Caslin, H L; Franco, R L; Crabb, E B; Huang, C J; Bowen, M K; Acevedo, E O

    2016-02-01

    Obesity may contribute to cardiovascular disease (CVD) risk by eliciting chronic systemic inflammation and impairing the immune response to additional stressors. There has been little assessment of the effect of obesity on psychological stress, an independent risk factor for CVD. Therefore, it was of interest to examine interleukin-6, tumor necrosis factor-α, interleukin-1β (IL-1β), interleukin-1 receptor antagonist (IL-1Ra), and leptin following an acute mental stress task in nonobese and obese males. Twenty college-aged males (21.3 ± 0.56 years) volunteered to participate in a 20-min Stroop color-word and mirror-tracing task. Subjects were recruited for obese (body mass index: BMI > 30) and nonobese (BMI < 25) groups, and blood samples were collected for enzyme-linked immunosorbent assay analysis. The acute mental stress task elicited an increase in heart rate, catecholamines, and IL-1β in all subjects. Additionally, acute mental stress increased cortisol concentrations in the nonobese group. There was a significant reduction in leptin in obese subjects 30 min posttask compared with a decrease in nonobese subjects 120 min posttask. Interestingly, the relationship between the percent change in leptin and IL-1Ra at 120 min posttask in response to an acute mental stress task was only observed in nonobese individuals. This is the first study to suggest that adiposity in males may impact leptin and inflammatory signaling mechanisms following acute mental stress. © 2015 Society for Psychophysiological Research.

  20. Effect of Early Statin Treatment in Patients with Cardiogenic Shock Complicating Acute Myocardial Infarction

    PubMed Central

    Sim, Doo Sun; Cho, Kyung Hoon; Ahn, Youngkeun; Kim, Young Jo; Chae, Shung Chull; Hong, Taek Jong; Seong, In Whan; Chae, Jei Keon; Kim, Chong Jin; Cho, Myeong Chan; Rha, Seung-Woon; Bae, Jang Ho; Seung, Ki Bae; Park, Seung Jung

    2013-01-01

    Background and Objectives The benefit of early statin treatment following acute myocardial infarction (MI) complicated with cardiogenic shock (CS) has not been well studied. We sought to assess the effect of early statin therapy in patients with CS complicating acute MI. Subjects and Methods We studied 553 statin-naive patients with acute MI and CS (Killip class IV) who underwent revascularization therapy between November 2005 and January 2008 at 51 hospitals in the Korea Acute Myocardial Infarction Registry. Patients were divided into 2 groups: those who received statins during hospitalization (n=280) and those who did not (n=273). The influence of statin treatment on a 12-month clinical outcome was examined using a matched-pairs analysis (n=200 in each group) based on the propensity for receiving statin therapy during hospitalization. Results Before adjustment, patients receiving statin, compared to those not receiving statin, had a more favorable clinical profile, were less likely to suffer procedural complications, and more likely to receive adequate medical therapy. Patients receiving statin had lower unadjusted in-hospital mortality and composite rate of mortality, MI, and repeat revascularization at 12 months, which remained significantly lower after adjustment for patient risk, procedural characteristics, and treatment propensity. Conclusion In CS patients with acute MI undergoing revascularization therapy, early statin treatment initiated during hospitalization was associated with lower rates of in-hospital death and 12-month adverse cardiac events. PMID:23508129

  1. The acute management of haemorrhoids

    PubMed Central

    Cohen, CRG

    2014-01-01

    Introduction Although the acute thrombosis and strangulation of haemorrhoids is a common condition, there is no consensus as to its most effective treatment. Methods A PubMed search was undertaken for papers describing the aetiology and treatment of the acute complications of haemorrhoids. Results The anatomy and treatments for strangulated internal haemorrhoids and thrombosed perianal varices are discussed. Studies of the effectiveness and complications of conservative and operative treatments are reviewed. Conclusions Ambiguities exist in the terminology used to describe the two separate pathologies that make up the acute complications of haemorrhoids. These complications have traditionally been treated conservatively. There is evidence that early operative intervention for strangulated internal haemorrhoids is safe and effective. A suggested algorithm for treatment is given, based on the published literature. PMID:25245728

  2. The effect of acute and chronic exercise on cognitive function and academic performance in adolescents: A systematic review.

    PubMed

    Li, Joanna W; O'Connor, Helen; O'Dwyer, Nicholas; Orr, Rhonda

    2017-09-01

    To investigate whether exercise, proposed to enhance neuroplasticity and potentially cognitive function (CF) and academic performance (AP), may be beneficial during adolescence when important developmental changes occur. Systematic review evaluating the impact of acute or chronic exercise on CF and AP in adolescents (13-18 years). Nine databases (AMED, AusportMed, CINAHL, COCHRANE, Embase, Medline, Scopus, SPORTdiscus, Web of Science) were searched from earliest records to 31st October 2016, using keywords related to exercise, CF, AP and adolescents. Eligible studies included controlled trials examining the effect of any exercise intervention on CF, AP or both. Effect size (ES) (Hedges g) were calculated where possible. Ten papers (11 studies) were reviewed. Cognitive domains included: executive function (n=4), memory (n=4), attention/concentration (n=2), visuo-motor speed (n=1), logical sequencing (n=1) and psychometric aptitude (n=1). All papers, nine of 10 being acute studies, reported at least one parameter showing a significant effect of exercise in improving CF and AP. However, the CF parameters displayed substantial heterogeneity, with only 37% favouring acute and chronic exercise. Where ES could be calculated, 52% of the acute CF parameters favoured rest. Memory was the domain most consistently improved by exercise. Academic performance demonstrated a significant improvement with exercise in one of two acute studies and the only chronic study (p≤0.001). The evidence for the effect of exercise on CF and AP in adolescents is equivocal and limited in quantity and quality. Well-designed research is therefore warranted to determine the benefits of exercise in enhancing CF and AP and reducing sedentary behaviour. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  3. Effects of acute changes in salinity and temperature on routine metabolism and nitrogen excretion in gambusia (Gambusia affinis) and zebrafish (Danio rerio).

    PubMed

    Uliano, E; Cataldi, M; Carella, F; Migliaccio, O; Iaccarino, D; Agnisola, C

    2010-11-01

    Acute stress may affect metabolism and nitrogen excretion as part of the adaptive response that allows animals to face adverse environmental changes. In the present paper the acute effects of different salinities and temperatures on routine metabolism, spontaneous activity and excretion of ammonia and urea were studied in two freshwater fish: gambusia, Gambusia affinis and zebrafish, Danio rerio, acclimated to 27 degrees C. The effects on gill morphology were also evaluated. Five salinities (0 per thousand, 10 per thousand, 20 per thousand, 30 per thousand and 35 per thousand) were tested in gambusia, while four salinities were used in zebrafish (0 per thousand, 10 per thousand, 20 per thousand and 25 per thousand). Each salinity acute stress was tested alone or in combination with an acute temperature reduction to 20 degrees C. In gambusia, both salinity and temperature acute stress strongly stimulated urea excretion. Routine oxygen consumption was barely affected by acute salinity or temperature stress, and was reduced by the combined effects of temperature and high salinity. Gills maintained their structural integrity in all stressing conditions; hyperplasia and hypertrophy of mitochondria-rich cells were observed. In zebrafish, temperature and salinity acute changes, both alone and in combination, scarcely affected any parameter tested. The major effect observed was a reduction of nitrogen excretion at 20 degrees C-25 per thousand; under these extreme conditions a significant structural disruption of gills was observed. These results confirm the high tolerance to acute salinity and temperature stress in gambusia, and demonstrate the involvement of urea excretion modulation in the stress response in this species. Copyright 2010 Elsevier Inc. All rights reserved.

  4. A Multi-Center Controlled Study of the Acute and Chronic Effects of Cooling Therapy for MS

    NASA Technical Reports Server (NTRS)

    Luna, Bernadette; Schwid, Steven W.; Cutter, Gary; Murray, Ronald; Bowen, James; Pellegrino, Richard; Guisado, Raul; Webbon, Bruce W.; DeVincenzi, Donald (Technical Monitor)

    2000-01-01

    To determine the acute and chronic effects of cooling therapy on patients with MS using objective functional performance measures and self-assessed measures of fatigue. Cooling demyelinated nerves can reduce conduction block, potentially improving symptoms of MS. Significant acute and chronic effects of cooling have not been demonstrated in a multi-center, controlled, blinded study using objective measures of neurologic function. Patients (N=84) with definite MS, mild to moderate disability (EDSS less than 6.0), and self-reported heat sensitivity were enrolled at 5 study sites. Acute effects of cooling were assessed by randomly assigning subjects to high-dose or low-dose cooling for one hour using an active cooling vest and cap (Life Enhancement Technologies, Santa Clara, CA). Settings were individualized to maintain the cooling garments at 55 F for the high-dose treatment and 70 F for the low-dose treatment. Both patients and examining investigators were blinded to treatment assignments. The MSFC and visual acuity/contrast sensitivity were assessed before and 30 minutes after treatment. The following week, subjects had an identical visit with the alternate cooling treatment. Chronic effects of cooling were assessed by randomly assigning the same subjects to unblinded daily home cooling or observation for 4 weeks. All subjects completed the Rochester Fatigue Diary (RFD) twice weekly and subjective measures of strength, cognition, and energy level daily. At the end of the period, subjects completed the Modified Fatigue Impact Scale (MFIS) and underwent another high-dose cooling session with assessment of the MSFC and vision. After a one-week washout period, subjects crossed over to the alternate 4-week treatment. Oral temperatures were reduced with both acute treatments (0.8 +/- .06 F, high and 0.5 +/- .06 F, low). While mean MSFC did not change significantly during individual cooling sessions, post hoc analysis pooling the 3 high-dose cooling sessions revealed an

  5. Sex-specific effect of endothelin in the blood pressure response to acute angiotensin II in growth-restricted rats

    PubMed Central

    Intapad, Suttira; Ojeda, Norma B.; Varney, Elliott; Royals, Thomas P.; Alexander, Barbara T.

    2015-01-01

    The renal endothelin system contributes to sex differences in blood pressure with males demonstrating greater endothelin type-A receptor-mediated responses relative to females. Intrauterine growth restriction programs hypertension and enhanced renal sensitivity to acute angiotensin II in male growth-restricted rats. Endothelin is reported to work synergistically with angiotensin II. Thus, this study tested the hypothesis that endothelin augments the blood pressure response to acute angiotensin II in male growth-restricted rats. Systemic and renal hemodynamics were determined in response to acute angiotensin II (100 nanogram/kilogram/minute for 30 minutes) with and without the endothelin type-A receptor antagonist, ABT 627(10 nanogram/kilogram/minute for 30 minutes), in rats pretreated with enalapril (250 milligram/Liter for one week) to normalize the endogenous renin angiotensin system. Endothelin type-A receptor blockade reduced angiotensin II-mediated increases in blood pressure in male control and male growth-restricted rats. Endothelin type-A receptor blockade also abolished hyper-responsiveness to acute angiotensin II in male growth-restricted rats. Yet, blood pressure remained significantly elevated above baseline following endothelin type-A receptor blockade suggesting that factors in addition to endothelin contribute to the basic angiotensin II-induced pressor response in male rats. We also determined sex-specific effects of endothelin on acute angiotensin II-mediated hemodynamic responses. Endothelin type-A receptor blockade did not reduce acute angiotensin II-mediated increases in blood pressure in female control or growth-restricted rats, intact or ovariectomized. Thus, these data suggest that endothelin type-A receptor blockade contributes to hypersensitivity to acute angiotensin II in male growth-restricted rats and further supports the sex-specific effect of endothelin on blood pressure. PMID:26459423

  6. Possible mechanism of acute effect of ethanol on intestinal IgA expression in rat.

    PubMed

    Budec, Mirela; Koko, Vesna; Todorović, Vera; Marković, Dragana; Postić, Marija; Drndarević, Neda; Spasić, Andelka; Mitrović, Olivera

    2007-06-01

    The purpose of this study was to investigate the possible mechanism of acute effect of ethanol on IgA expression in rat intestine. To this end, adult female Wistar rats showing diestrus day 1 were treated with (a) ethanol (2 or 4 g/kg, i.p.); (b) N omega-nitro-L-arginine-methyl ester (L-NAME), which inhibits the activity of all isoforms of nitric oxide synthase, (30 mg/kg, s.c.) followed by ethanol 3 h later; and (c) L-NAME (30 mg/kg, s.c.) followed by saline 3 h later. Saline-injected and untreated rats were used as controls. The animals were sacrificed 0.5 h after ethanol administration. Intestinal expression of IgA was evaluated by both immunohistochemistry and Western immunoblotting. Morphometric analysis showed that acute ethanol treatment increased the number of IgA-immunoreactive cells in a dose-dependent manner. Pretreatment with L-NAME abolished this action of alcohol. Injection of L-NAME followed by saline had no influence on the number of IgA+cells. The results, obtained by Western immunoblotting, paralleled our immunohistochemical findings. Taken together, these data suggest that acute effect of ethanol on intestinal IgA might be mediated by endogenous nitric oxide.

  7. Acute effects of aflatoxin on northern bobwhites (Colinus virginianus).

    PubMed

    Moore, Deana L; Henke, Scott E; Fedynich, Alan M; Laurenz, Jamie C; Morgan, Robert

    2013-07-01

    Aflatoxin is a widely occurring and harmful mycotoxin produced by strains of Aspergillus spp. growing on vegetable matter. We investigated the concentration of aflatoxin needed to impair normal physiologic responses and induce acute morbidity and mortality in Northern Bobwhites (Colinus virginianus). Ten wild-caught adult bobwhites (five males and five females) from southern Texas were randomly assigned to each treatment group (0, 100, 500, 1,000, and 2,000 parts per billion (ppb) aflatoxin; n=50). We orally administered 100 μL of aflatoxin, derived from Aspergillus flavus, once per week for 4 wk and monitored bird mass, daily feed consumption, liver histology, and blood chemistries. An in vitro white blood cell proliferation test was conducted using spleen tissue to determine the effect of aflatoxin on the immune system. There was no mortality in the control groups, whereas mortalities occurred in all treatment groups except in the 100 ppb aflatoxin treatment. Immunosuppression, reduction in gamma-globulin, glucose, and gamma-glutamyltransferase blood levels, and abnormal liver histology were observed in aflatoxin-exposed quail. Blood chemistry indicated cellular damage to the liver and kidneys. We concluded that short-term, acute doses of aflatoxin as low as 100 ppb can be detrimental to the health of Northern Bobwhites.

  8. Evaluation of the acute dermal exposure of the ethanolic and hexanic extracts from leaves of Schinus molle var. areira L. in rats.

    PubMed

    Bras, Cristina; Gumilar, Fernanda; Gandini, Norberto; Minetti, Alejandra; Ferrero, Adriana

    2011-10-11

    Schinus molle var. areira L. (Anacardiaceae) is employed in herbal medicine for many conditions, including respiratory, urinary and menstrual disorders, and as a digestive stimulant, diuretic, astringent and antidepressant. It is also known for its topical use as wound healer, antiseptic, for skin disorders and as repellent and insecticide. In the present work, the acute dermal exposure to ethanolic and hexanic extracts from leaves of Schinus molle var. areira was studied in rats. A single dose of 2000 mg/kg of body weight of ethanolic and hexanic extracts from leaves was applied on the shaved skin of male and female rats. After 24h of exposure, the patch was removed and any sign of irritation was recorded. Behavioral and functional parameters in a functional observational battery and motor activity in an open field were assessed after the exposure to the extracts. Then, after 14 days of observation, animals were retested. Finally, histopathological studies were conducted on several organs. Slight signs of erythema and edema were observed in the skin site of exposure, but they disappeared after 48 h. The exposure to the hexanic extract produced an increase in parameters of activity, rearing and arousal assessed in the functional observational battery, which reversed after 14 days. On the other hand, the ethanolic extract caused an increase in locomotor activity, reflected in a higher number of rearings performed in the open field in the evaluation carried out on Day 14. No histopathological alterations were detected in the analyzed organs. The results show that the acute dermal exposure of the ethanolic and hexanic extracts from leaves of Schinus molle var. areira only causes a slight and reversible skin irritation, and a mild stimulatory effect in rats. All these indicate that the topical use of these extracts would be safe. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  9. Effect of early statin therapy after acute coronary syndromes: a concise review of the recent data.

    PubMed

    Bybee, Kevin A; Wright, R Scott; Kopecky, Stephen L

    2002-01-01

    HMG Co-A reductase inhibitors(statins) have been shown, in three large randomized trials, to decrease adverse cardiac events in patients with clinically evident coronary artery disease. All of these trials have excluded patients with an acute coronary syndrome within the three months prior to enrollment. Statin therapy is thought to stabilize coronary plaque and decrease the risk of plaque rupture. Statins have been shown to quickly reduce levels of LDL-C in addition to altering systemic inflammatory responses, improving endothelial function, and reducing platelet aggregation and activation. These mechanisms are potentially beneficial in the setting of acute coronary syndromes, a time of profound plaque instability. There is a growing body of evidence supporting the early initiation of statin therapy in the setting of acute coronary syndromes. This paper reviews the available data from randomized-controlled trials and observational studies evaluating the effect of early statin initiation during, or soon following, an acute coronary syndrome.

  10. [Cost effectiveness in treatment of acute myeloid leukemia].

    PubMed

    Nordmann, P; Schaffner, A; Dazzi, H

    2000-12-23

    Although the rise in health costs is a widely debated issue, in Switzerland it was until recently taken for granted that patients are given the best available treatment regardless of cost. An example of a disease requiring costly treatment is acute myelogenous leukaemia (AML). To relate cost to benefit we calculated expenditure per life years gained. To assess costs we determined the real cost of treatment up to total remission, followed by consolidation or withdrawal of treatment or death. For survival time exceeding the 2-year observation period we used data from recent literature. The average cost of treatment ranges up to 107,592 Swiss francs (CHF). In 1997 we treated 23 leukaemia patients at Zurich University Hospital and gained a total of 210 life years. This represents an average cost of CHF 11,741 per life year gained. Chief cost items were therapy and personnel costs for nursing staff, followed by hotel business and personnel costs for doctors and diagnosis. Our results for AML treatment are far removed from the $61,500 ranging up to $166,000 discussed in the literature as the "critical" QALY (quality adjusted life years) value. This is the first time the actual costs of AML therapy have been shown for a Swiss cohort. Despite high initial treatment costs and success only in a limited number of patients, the expenditure per QALY is surprisingly low and shows clearly the effectiveness of apparently costly acute medicine.

  11. Effect of chronic caffeine intake on choice reaction time, mood, and visual vigilance.

    PubMed

    Judelson, Daniel A; Armstrong, Lawrence E; Sökmen, Bülent; Roti, Melissa W; Casa, Douglas J; Kellogg, Mark D

    2005-08-07

    The stimulatory effects of acute caffeine intake on choice reaction time, mood state, and visual vigilance are well established. Little research exists, however, on the effects of chronic caffeine ingestion on psychomotor tasks. Therefore, the purpose of this study was to evaluate the effects of 5 days of controlled caffeine intake on cognitive and psychomotor performance. Three groups of 20 healthy males (age=22+/-3 years, mass=75.4+/-7.9 kg, body fat percentage=11.2+/-5.1%) twice completed a battery of cognitive and psychomotor tasks: after 6 days of 3 mg.kg(-1) day(-1) caffeine equilibration (Day 6), and after 5 days of experimental (0 [G0], 3 [G3], or 6 [G6] mg.kg(-1) day(-1)) caffeine intake (Day 11). Groups were randomized and stratified for age, mass, and body composition; all procedures were double-blind. Cognitive analyses involved a visual four-choice reaction time test, a mood state questionnaire, and a visual vigilance task. Experimental chronic caffeine intake did not significantly alter the number of correct responses or the mean latency of response for either the four-choice reaction time or the visual vigilance tasks. The Vigor-Activity subset of the mood state questionnaire was significantly greater in G3 than G0 or G6 on Day 11. All other mood constructs were unaffected by caffeine intake. In conclusion, few cognitive and psychomotor differences existed after 5 days of controlled caffeine ingestion between subjects consuming 0, 3, or 6 mg.kg(-1) day(-1) of caffeine, suggesting that chronic caffeine intake (1) has few perceptible effects on cognitive and psychomotor well-being and (2) may lead to a tolerance to some aspects of caffeine's acute effects.

  12. The role of GABAergic system on the inhibitory effect of ghrelin on food intake in neonatal chicks.

    PubMed

    Jonaidi, H; Abbassi, L; Yaghoobi, M M; Kaiya, H; Denbow, D M; Kamali, Y; Shojaei, B

    2012-06-27

    Ghrelin is a gut-brain peptide that has a stimulatory effect on food intake in mammals. In contrast, this peptide decreases food intake in neonatal chicks when injected intracerebroventricularly (ICV). In mammals, neuropeptide Y (NPY) mediates the orexigenic effect of ghrelin whereas in chicks it appears that corticotrophin releasing factor (CRF) is partially involved in the inhibitory effect of ghrelin on food intake. Gamma aminobutyric acid (GABA) has a stimulatory effect on food intake in mammals and birds. In this study we investigated whether the anorectic effect of ghrelin is mediated by the GABAergic system. In Experiment 1, 3h-fasted chicks were given an ICV injection of chicken ghrelin and picrotoxin, a GABA(A) receptors antagonist. Picrotoxin decreased food intake compared to the control chicks indicating a stimulatory effect of GABA(A) receptors on food intake. However, picrotoxin did not alter the inhibitory effect of ghrelin on food intake. In Experiment 2, THIP hydrochloride, a GABA(A) receptor agonist, was used in place of picrotoxin. THIP hydrochloride appeared to partially attenuate the decrease in food intake induced by ghrelin at 30 min postinjection. In Experiment 3, the effect of ICV injection of chicken ghrelin on gene expression of glutamate decarboxylase (GAD)(1) and GAD(2), GABA synthesis enzymes in the brain stem including hypothalamus, was investigated. The ICV injection of chicken ghrelin significantly reduced GAD(2) gene expression. These findings suggest that ghrelin may decrease food intake in neonatal chicks by reducing GABA synthesis and thereby GABA release within brain feeding centers. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  13. [Acute diuretic effect of ethanolic and aqueous extracts of Ceratopteris pteridoides (Hook) in normal rats].

    PubMed

    Alviz, Antistio Aníbal; Salas, Rubén Darío; Franco, Luis Alberto

    2013-01-01

    Ceratopteris pteridoides is a semiaquatic fern of the Parkeriacea family, widely used in the Colombian folk medicine as a diuretic and cholelithiasic, of which there are no scientific reports that validate its popular use. To evaluate the acute and short-term repeated-dose diuretic effect of the ethanolic and aqueous extracts of C. pteridoides in an in vivo model. The total ethanolic extract was obtained by maceration of the whole plant of C. pteridoides with ethanol and the aqueous extract by decoction at 60°C for 15 minutes. Both extracts were evaluated in preliminary phytochemical analysis and histological studies after the administration of the extracts for 8 consecutive days (1000 mg/Kg). The diuretic effect was evaluated using Wistar rats treated with the extracts (500 mg/Kg), using an acute and a short-term repeated-dose model, and quantifying water elimination, sodium and potassium excretion by atomic absorption spectrophotometry, and chloride excretion by mercurimetric titration. In the acute model both extracts showed significant diuretic, natriuretic, and kaliuretic effect compared to the control group. Whereas, a short-term repeated-dose administration showed a diuretic effect without elimination of electrolytes. The histopathologic study did not suggest a toxic effect in liver or kidney. The results represent evidence of the diuretic activity of C. pteridoides and give support the popular use given to this plant in the north coast of Colombia. Further studies are required to isolate and identify the compounds responsible for the activity and the mechanism of action involved.

  14. Acute Effects of Fine Particulate Air Pollution on ST Segment Height: A Longitudinal Study

    EPA Science Inventory

    Background: The mechanisms for the relationship between particulate air pollution and cardiac disease are not fully understood. Air pollution-induced myocardial ischemia is one of the potentially important mechanisms. Methods: We investigate the acute effects and the time cours...

  15. Acute asthma during pregnancy.

    PubMed Central

    Stenius-Aarniala, B. S.; Hedman, J.; Teramo, K. A.

    1996-01-01

    BACKGROUND: Acute asthma during pregnancy is potentially dangerous to the fetus. The aim of this study was to investigate the effect of an acute attack of asthma during pregnancy on the course of pregnancy or delivery, or the health of the newborn infant, and to identify undertreatment as a possible cause of the exacerbations. METHODS: Five hundred and four pregnant asthmatic subjects were prospectively followed and treated. The data on 47 patients with an attack of asthma during pregnancy were compared with those of 457 asthmatics with no recorded acute exacerbation and with 237 healthy parturients. RESULTS: Of 504 asthmatics, 177 patients were not initially treated with inhaled corticosteroids. Of these, 17% had an acute attack compared with only 4% of the 257 patients who had been on inhaled anti-inflammatory treatment from the start of pregnancy. There were no differences between the groups as to length of gestation, length of the third stage of labour, or amount of haemorrhage after delivery. No differences were observed between pregnancies with and without an exacerbation with regard to relative birth weight, incidence of malformations, hypoglycaemia, or need for phototherapy for jaundice during the neonatal period. CONCLUSIONS: Patients with inadequate inhaled anti-inflammatory treatment during pregnancy run a higher risk of suffering an acute attack of asthma than those treated with an anti-inflammatory agent. However, if the acute attack of asthma is relatively mild and promptly treated, it does not have a serious effect on the pregnancy, delivery, or the health of the newborn infant. PMID:8733495

  16. Acute effects of exposure to 56Fe and 16O particles on learning and memory

    USDA-ARS?s Scientific Manuscript database

    Although it has been shown that exposure to HZE particles disrupts cognitive performance when tested 2-4 weeks after irradiation, it has not been determined whether exposure to HZE particles can exert acute effects on cognitive performance; i.e., effects within 4-48 hrs after exposure. The present ...

  17. Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy

    PubMed Central

    Schmiegelow, Kjeld; Müller, Klaus; Mogensen, Signe Sloth; Mogensen, Pernille Rudebeck; Wolthers, Benjamin Ole; Stoltze, Ulrik Kristoffer; Tuckuviene, Ruta; Frandsen, Thomas

    2017-01-01

    During chemotherapy for childhood acute lymphoblastic leukemia, all organs can be affected by severe acute side effects, the most common being opportunistic infections, mucositis, central or peripheral neuropathy (or both), bone toxicities (including osteonecrosis), thromboembolism, sinusoidal obstruction syndrome, endocrinopathies (especially steroid-induced adrenal insufficiency and hyperglycemia), high-dose methotrexate-induced nephrotoxicity, asparaginase-associated hypersensitivity, pancreatitis, and hyperlipidemia. Few of the non-infectious acute toxicities are associated with clinically useful risk factors, and across study groups there has been wide diversity in toxicity definitions, capture strategies, and reporting, thus hampering meaningful comparisons of toxicity incidences for different leukemia protocols. Since treatment of acute lymphoblastic leukemia now yields 5-year overall survival rates above 90%, there is a need for strategies for assessing the burden of toxicities in the overall evaluation of anti-leukemic therapy programs. PMID:28413626

  18. The effect of acute exposure to hyperbaric oxygen on respiratory system mechanics in the rat.

    PubMed

    Rubini, Alessandro; Porzionato, Andrea; Zara, Susi; Cataldi, Amelia; Garetto, Giacomo; Bosco, Gerardo

    2013-10-01

    This study was designed to investigate the possible effects of acute hyperbaric hyperoxia on respiratory mechanics of anaesthetised, positive-pressure ventilated rats. We measured respiratory mechanics by the end-inflation occlusion method in nine rats previously acutely exposed to hyperbaric hyperoxia in a standard fashion. The method allows the measurements of respiratory system elastance and of both the "ohmic" and of the viscoelastic components of airway resistance, which respectively depend on the newtonian pressure dissipation due to the ohmic airway resistance to air flow, and on the viscoelastic pressure dissipation caused by respiratory system tissues stress-relaxation. The activities of inducible and endothelial NO-synthase in the lung's tissues (iNOS and eNOS respectively) also were investigated. Data were compared with those obtained in control animals. We found that the exposure to hyperbaric hyperoxia increased respiratory system elastance and both the "ohmic" and viscoelastic components of inspiratory resistances. These changes were accompanied by increased iNOS but not eNOS activities. Hyperbaric hyperoxia was shown to acutely induce detrimental effects on respiratory mechanics. A possible causative role was suggested for increased nitrogen reactive species production because of increased iNOS activity.

  19. Effect of multiple honey doses on non-specific acute cough in children. An open randomised study and literature review.

    PubMed

    Miceli Sopo, S; Greco, M; Monaco, S; Varrasi, G; Di Lorenzo, G; Simeone, G

    2015-01-01

    Honey is recommended for non-specific acute paediatric cough by the Australian guidelines. Current available randomised clinical trials evaluated the effects of a single evening dose of honey, but multiple doses outcomes have never been studied. To evaluate the effects of wildflower honey, given for three subsequent evenings, on non-specific acute paediatric cough, compared to dextromethorphan (DM) and levodropropizine (LDP), which are the most prescribed over-the-counter (OTC) antitussives in Italy. 134 children suffering from non-specific acute cough were randomised to receive for three subsequent evenings a mixture of milk (90ml) and wildflower honey (10ml) or a dose of DM or LDP adjusted for the specific age. The effectiveness was evaluated by a cough questionnaire answered by parents. Primary end-point efficacy was therapeutic success. The latter was defined as a decrease in cough questionnaire score greater than 50% after treatment compared with baseline values. Three children were excluded from the study, as their parents did not complete the questionnaire. Therapeutic success was achieved by 80% in the honey and milk group and 87% in OTC medication group (p=0.25). Milk and honey mixture seems to be at least as effective as DM or LDP in non-specific acute cough in children. These results are in line with previous studies, which reported the health effects of honey on paediatric cough, even if placebo effect cannot be totally excluded. Copyright © 2014 SEICAP. Published by Elsevier Espana. All rights reserved.

  20. Where did the acute medical trainees go? A review of the career pathways of acute care common stem acute medical trainees in London.

    PubMed

    Gowland, Emily; Ball, Karen Le; Bryant, Catherine; Birns, Jonathan

    2016-10-01

    Acute care common stem acute medicine (ACCS AM) training was designed to develop competent multi-skilled acute physicians to manage patients with multimorbidity from 'door to discharge' in an era of increasing acute hospital admissions. Recent surveys by the Royal College of Physicians have suggested that acute medical specialties are proving less attractive to trainees. However, data on the career pathways taken by trainees completing core acute medical training has been lacking. Using London as a region with a 100% fill rate for its ACCS AM training programme, this study showed only 14% of trainees go on to higher specialty training in acute internal medicine and a further 10% to pursue higher medical specialty training with dual accreditation with internal medicine. 16% of trainees switched from ACCS AM to emergency medicine or anaesthetics during core ACCS training, and intensive care medicine proved to be the most popular career choice for ACCS AM trainees (21%). The ACCS AM training programme therefore does not appear to be providing what it was set out to do and this paper discusses the potential causes and effects. © Royal College of Physicians 2016. All rights reserved.

  1. Effects of urtica dioica extract on experimental acute pancreatitis model in rats.

    PubMed

    Yilmaz, Baris; Basar, Omer; Aktas, Bora; Altinbas, Akif; Ekiz, Fuat; Büyükcam, Fatih; Albayrak, Aynur; Ginis, Zeynep; Oztürk, Gülfer; Coban, Sahin; Ucar, Engin; Kaya, Oskay; Yüksel, Osman; Caner, Sedat; Delibasi, Tuncay

    2014-01-01

    Acute pancreatitis is the acute inflammation of pancreas and peripancreatic tissues, and distant organs are also affected. The aim of this study was to investigate the effect of Urtica dioica extract (UDE) treatment on cerulein induced acute pancreatitis in rats. Twenty-one Wistar Albino rats were divided into three groups: Control, Pancreatitis, and UDE treatment group. In the control group no procedures were performed. In the pancreatitis and treatment groups, pancreatitis was induced with intraperitoneal injection of cerulein, followed by intraperitoneal injection of 1 ml saline (pancreatitis group) and 1 ml 5.2% UDE (treatment group). Pancreatic tissues were examined histopathologically. Pro-inflammatory cytokines (tumor necrosis factor-α), amylase and markers of apoptosis (M30, M65) were also measured in blood samples. Immunohistochemical staining was performed with Caspase-3 antibody. Histopathological findings in the UDE treatment group were less severe than in the pancreatitis group (5.7 vs 11.7, p = 0.010). TNF-α levels were not statistically different between treated and control groups (63.3 vs. 57.2, p = 0.141). UDE treatment was associated with less apoptosis [determined by M30, caspase-3 index (%)], (1.769 vs. 0.288, p = 0.056; 3% vs. 2.2%, p = 0.224; respectively). UDE treatment of pancreatitis merits further study.

  2. Effects of urtica dioica extract on experimental acute pancreatitis model in rats

    PubMed Central

    Yilmaz, Baris; Basar, Ömer; Aktas, Bora; Altinbas, Akif; Ekiz, Fuat; Büyükcam, Fatih; Albayrak, Aynur; Ginis, Zeynep; Öztürk, Gülfer; Coban, Sahin; Ucar, Engin; Kaya, Oskay; Yüksel, Osman; Caner, Sedat; Delibasi, Tuncay

    2014-01-01

    Acute pancreatitis is the acute inflammation of pancreas and peripancreatic tissues, and distant organs are also affected. The aim of this study was to investigate the effect of Urtica dioica extract (UDE) treatment on cerulein induced acute pancreatitis in rats. Twenty-one Wistar Albino rats were divided into three groups: Control, Pancreatitis, and UDE treatment group. In the control group no procedures were performed. In the pancreatitis and treatment groups, pancreatitis was induced with intraperitoneal injection of cerulein, followed by intraperitoneal injection of 1 ml saline (pancreatitis group) and 1 ml 5.2% UDE (treatment group). Pancreatic tissues were examined histopathologically. Pro-inflammatory cytokines (tumor necrosis factor-α), amylase and markers of apoptosis (M30, M65) were also measured in blood samples. Immunohistochemical staining was performed with Caspase-3 antibody. Histopathological findings in the UDE treatment group were less severe than in the pancreatitis group (5.7 vs 11.7, p = 0.010). TNF-α levels were not statistically different between treated and control groups (63.3 vs. 57.2, p = 0.141). UDE treatment was associated with less apoptosis [determined by M30, caspase-3 index (%)], (1.769 vs. 0.288, p = 0.056; 3% vs. 2.2%, p = 0.224; respectively). UDE treatment of pancreatitis merits further study. PMID:24995088

  3. Acute effects of head-down tilt and hypoxia on modulators of fluid homeostasis

    NASA Technical Reports Server (NTRS)

    Whitson, P. A.; Cintron, N. M.; Pietrzyk, R. A.; Scotto, P.; Loeppky, J. A.

    1994-01-01

    In an effort to understand the interaction between acute postural fluid shifts and hypoxia on hormonal regulation of fluid homeostasis, the authors measured the responses to head-down tilt with and without acute exposure to normobaric hypoxia. Plasma atrial natriuretic peptide (ANP), cyclic guanosine monophosphate (cGMP), cyclic adenosine monophosphate (cAMP), plasma aldosterone (ALD), and plasma renin activity (PRA) were measured in six healthy male volunteers who were exposed to a head-down tilt protocol during normoxia and hypoxia. The tilt protocol consisted of a 17 degrees head-up phase (30 minutes), a 28 degrees head-down phase (1 hour), and a 17 degrees head-up recovery period (2 hours, with the last hour normoxic in both experiments). Altitude equivalent to 14,828 ft was simulated by having the subjects breathe an inspired gas mixture with 13.9% oxygen. The results indicate that the postural fluid redistribution associated with a 60-minute head-down tilt induces the release of ANP and cGMP during both hypoxia and normoxia. Hypoxia increased cGMP, cAMP, ALD, and PRA throughout the protocol and significantly potentiated the increase in cGMP during head-down tilt. Hypoxia had no overall effect on the release of ANP, but appeared to attenuate the increase with head-down tilt. This study describes the acute effects of hypoxia on the endocrine response during fluid redistribution and suggests that the magnitude, but not the direction, of these changes with posture is affected by hypoxia.

  4. Acute and Cumulative Effects of Unmodified 50-nm Nano-ZnO on Mice.

    PubMed

    Kong, Tao; Zhang, Shu-Hui; Zhang, Ji-Liang; Hao, Xue-Qin; Yang, Fan; Zhang, Cai; Yang, Zi-Jun; Zhang, Meng-Yu; Wang, Jie

    2018-01-02

    Nanometer zinc oxide (nano-ZnO) is widely used in diverse industrial and agricultural fields. Due to the extensive contact humans have with these particles, it is crucial to understand the potential effects that nano-ZnO have on human health. Currently, information related to the toxicity and mechanisms of nano-ZnO is limited. The aim of the present study was to investigate acute and cumulative toxic effects of 50-nm unmodified ZnO in mice. This investigation will seek to establish median lethal dose (LD50), a cumulative coefficient, and target organs. The acute and cumulative toxicity was investigated by Karber's method and via a dose-increasing method, respectively. During the experiment, clinical signs, mortality, body weights, hematology, serum biochemistry, gross pathology, organ weight, and histopathology were examined. The LD50 was 5177-mg/kg·bw; the 95% confidence limits for the LD50 were 5116-5238-mg/kg·bw. It could be concluded that the liver, kidney, lung, and gastrointestinal tract were target organs for the 50-nm nano-ZnO acute oral treatment. The cumulative coefficient (K) was 1.9 which indicated that the cumulative toxicity was apparent. The results also indicated that the liver, kidney, lung, and pancrea were target organs for 50-nm nano-ZnO cumulative oral exposure and might be target organs for subchronic and chronic toxicity of oral administered 50-nm ZnO.

  5. Acute Effects of Online Mind-Body Skills Training on Resilience, Mindfulness, and Empathy.

    PubMed

    Kemper, Kathi J; Khirallah, Michael

    2015-10-01

    Some studies have begun to show benefits of brief in-person mind-body skills training. We evaluated the effects of 1-hour online elective mind-body skills training for health professionals on mindfulness, resilience, and empathy. Between May and November, 2014, we described enrollees for the most popular 1-hour modules in a new online mind-body skills training program; compared enrollees' baseline stress and burnout to normative samples; and assessed acute changes in mindfulness, resilience, and empathy. The 513 enrollees included dietitians, nurses, physicians, social workers, clinical trainees, and health researchers; about 1/4 were trainees. The most popular modules were the following: Introduction to Stress, Resilience, and the Relaxation Response (n = 261); Autogenic Training (n = 250); Guided Imagery and Hypnosis for Pain, Insomnia, and Changing Habits (n = 112); Introduction to Mindfulness (n = 112); and Mindfulness in Daily Life (n = 102). Initially, most enrollees met threshold criteria for burnout and reported moderate to high stress levels. Completing 1-hour modules was associated with significant acute improvements in stress (P < .001), mindfulness (P < .001), empathy (P = .01), and resilience (P < .01). Online mind-body skills training reaches diverse, stressed health professionals and is associated with acute improvements in stress, mindfulness, empathy, and resilience. Additional research is warranted to compare the long-term cost-effectiveness of different doses of online and in-person mind-body skills training for health professionals. © The Author(s) 2015.

  6. Detrimental effect of hypothermia during acute normovolaemic haemodilution in anaesthetized cats

    NASA Astrophysics Data System (ADS)

    Talwar, A.; Fahim, Mohammad

    Haemodynamic responses to hypothermia were studied at normal haematocrit and following the induction of acute normovolaemic haemodilution. Experiments were performed on 20 cats anaesthetized with a mixture of chloralose and urethane in two groups. In one group (n=10) the effects of hypothermia on various haemodynamic variables were studied at normal haematocrit (41.0+/-1.7%) and in the second group of cats (n=10) the effects of hypothermia on various haemodynamic variables were studied after the induction of acute normovolaemic haemodilution (14.0+/-1.0%). The haemodynamic variables left ventricular pressure, left ventricular contractility, arterial blood pressure, heart rate and right atrial pressure were recorded on a polygraph. Cardiac output was measured using a cardiac output computer. In both groups hypothermia was induced by surface cooling with the help of ice. Cardiovascular variables were recorded at each 1° C fall in body temperature. Hypothermia produced a significant (P<0.05) drop in heart rate, cardiac output, arterial blood pressure and left ventricular contractility in both groups. However, the percentage decrease in these variables in response to hypothermia was significantly (P<0.05) higher in cats with low haematocrit than in those with normal haematocrit. The severity of hypothermia - induced cardiovascular effects is evident from the drastic decrease in heart rate, cardiac output, arterial blood pressure and myocardial contractility in cats with low haematocrit, indicating a higher risk of circulatory failure under anaemic conditions at low temperatures.

  7. Acute anxiolytic effects of quetiapine during virtual reality exposure--a double-blind placebo-controlled trial in patients with specific phobia.

    PubMed

    Diemer, Julia; Domschke, Katharina; Mühlberger, Andreas; Winter, Bernward; Zavorotnyy, Maxim; Notzon, Swantje; Silling, Karen; Arolt, Volker; Zwanzger, Peter

    2013-11-01

    Anxiety disorders are among the most frequent psychiatric disorders. With regard to pharmacological treatment, antidepressants, the calcium modulator pregabalin and benzodiazepines are recommended according to current treatment guidelines. With regard to acute states of anxiety, so far practically only benzodiazepines provide an immediate anxiolytic effect. However, the risk of tolerance and dependency limits the use of this class of medication. Therefore, there is still a need for alternative pharmacologic strategies. Increasing evidence points towards anxiety-reducing properties of atypical antipsychotics, particularly quetiapine. Therefore, we aimed to evaluate the putative acute anxiolytic effects of this compound, choosing the induction of acute anxiety in patients with specific phobia as a model for the evaluation of ad-hoc anxiolytic properties in a proof-of-concept approach. In a randomized, double-blind, placebo-controlled study, 58 patients with arachnophobia were treated with a single dose of quetiapine XR or placebo prior to a virtual reality spider challenge procedure. Treatment effects were monitored using rating scales for acute anxiety as well as measurements of heart rate and skin conductance. Overall, quetiapine showed significant anxiolytic effects compared to placebo. However, effects were not seen on the primary outcome measure (VAS Anxiety), but were limited to somatic anxiety symptoms. Additionally, a significant reduction of skin conductance was observed. Further exploratory analyses hint towards a mediating role of the (COMT) val158met genotype on treatment response. The present results thus suggest a possible suitability of quetiapine in the acute treatment of anxiety, particularly with regard to somatic symptoms. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

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

    PubMed

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

    2006-03-01

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

  9. Effects of acute systemic inflammation on the interplay between sad mood and affective cognition.

    PubMed

    Benson, Sven; Brinkhoff, Alexandra; Lueg, Larissa; Roderigo, Till; Kribben, Andreas; Wilde, Benjamin; Witzke, Oliver; Engler, Harald; Schedlowski, Manfred; Elsenbruch, Sigrid

    2017-12-11

    Experimental endotoxemia is a translational model to study inflammatory mechanisms involved in the pathophysiology of mood disorders including depression. Disturbed affective cognition constitutes a core aspect in depression, but has never been studied in the context of inflammation. We combined experimental endotoxemia with an established experimental mood induction procedure to assess the interaction between acute inflammation and sad mood and their effects on affective cognition. In this randomized cross-over study, N = 15 healthy males received endotoxin (0.8 ng/kg lipopolysaccharide iv) on one study day and placebo an otherwise identical study day. The affective Go/Nogo task was conducted after experimental induction of neutral and sad mood. Inflammatory markers were assessed hourly. Endotoxin application induced a transient systemic inflammation, characterized by increased leukocyte counts, TNF-alpha and interleukin-6 plasma concentrations (all p < 0.01, interaction effects). Mood induction led to greater sadness ratings, with highest ratings when sad mood was induced during inflammation (p < 0.05, interaction effect). Based on a 2 (endotoxin vs. placebo) × 2 (sad vs. neutral mood) × 2 (sad vs. happy Go/Nogo target words) factorial design, we observed a significant target × endotoxin condition interaction (p < 0.01) reflecting slower responses to sad targets during endotoxemia. Additionally, we found a valence × mood interaction (p < 0.05), reflecting slower reaction times to sad targets in sad mood. In summary, acute inflammation and sad mood are risk factors for disturbed affective cognition. The results may reflect a mood-congruency effect, with prolonged and sustained processing of mood-congruent information during acute inflammation, which may contribute to depression risk.

  10. Effects of an acute bout of moderate-intensity exercise on postprandial lipemia and airway inflammation.

    PubMed

    Johnson, Ariel M; Kurti, Stephanie P; Smith, Joshua R; Rosenkranz, Sara K; Harms, Craig A

    2016-03-01

    A high-fat meal (HFM) induces an increase in blood lipids (postprandial lipemia; PPL), systemic inflammation, and acute airway inflammation. While acute exercise has been shown to have anti-inflammatory and lipid-lowering effects, it is unknown whether exercise prior to an HFM will translate to reduced airway inflammation post-HFM. Our purpose was to determine the effects of an acute bout of exercise on airway inflammation post-HFM and to identify whether any protective effect of exercise on airway inflammation was associated with a reduction in PPL or systemic inflammation. In a randomized cross-over study, 12 healthy, 18- to 29-year-old men (age, 23.0 ± 3.2 years; height, 178.9 ± 5.5 cm; weight, 78.5 ± 11.7 kg) consumed an HFM (1 g fat/1 kg body weight) 12 h following exercise (EX; 60 min at 60% maximal oxygen uptake) or without exercise (CON). Fractional exhaled nitric oxide (FENO; measure of airway inflammation), triglycerides (TG), and inflammatory markers (high-sensitivity C-reactive protein, tumor-necrosis factor-alpha, and interleukin-6) were measured while fasted at 2 h and 4 h post-HFM. FENO increased over time (2 h: CON, p = 0.001; EX, p = 0.002, but not by condition (p = 0.991). TG significantly increased 2 and 4 h post-HFM (p < 0.001), but was not significant between conditions (p = 0.256). Inflammatory markers did not significantly increase by time or condition (p > 0.05). There were no relationships between FENO and TG or systemic inflammatory markers for any time point or condition (p > 0.05). In summary, an acute bout of moderate-intensity exercise performed 12 h prior to an HFM did not change postprandial airway inflammation or lipemia in healthy, 18- to 29-year-old men.

  11. Pharmacological effects of ethanol on ingestive behavior of the preweanling rat

    PubMed Central

    Kozlov, Andrey P.; Nizhnikov, Michael E.; Varlinskaya, Elena I.; Spear, Norman E.

    2009-01-01

    The present study was designed to test the hypothesis that sensitivity of ingestive behavior of infant rat to the pharmacological effects of ethanol changes between postnatal (P) days 9 and 12. The intake of 0.1% saccharin and water, general motor activity, and myoclonic twitching activity were assessed following administration of three doses of ethanol (0, 0.25, 0.5g/kg) while fluids were free available to the animals. The 0.5g/kg dose of ethanol attenuated saccharin intake in P9 pups and enhanced saccharin intake in P12 rats. On P12 some sex-related differences emerged at 0.5g/kg of ethanol, with saccharin intake being higher in females than in their male counterparts. Taste reactivity probe revealed that 0.5 g/kg of ethanol increased taste responsiveness to saccharin on P12 but only to infusions presented at a high rate. The results of the present study indicate that ontogenetic changes in sensitivity to the effects of ethanol on ingestive behavior occur during the second postnatal week, with P9 animals being more sensitive to the inhibitory (sedative) effects on saccharin intake and P12 rats being more sensitive to the stimulatory effects of ethanol. We suggest that acute ethanol enhanced saccharin intake via sensitization of oral response to appetitive taste stimulation. PMID:19549546

  12. Acute and Chronic Effects of Aerobic and Resistance Exercise on Ambulatory Blood Pressure

    PubMed Central

    Cardoso, Crivaldo Gomes; Gomides, Ricardo Saraceni; Queiroz, Andréia Cristiane Carrenho; Pinto, Luiz Gustavo; da Silveira Lobo, Fernando; Tinucci, Tais; Mion, Décio; de Moraes Forjaz, Claudia Lucia

    2010-01-01

    Hypertension is a ubiquitous and serious disease. Regular exercise has been recommended as a strategy for the prevention and treatment of hypertension because of its effects in reducing clinical blood pressure; however, ambulatory blood pressure is a better predictor of target-organ damage than clinical blood pressure, and therefore studying the effects of exercise on ambulatory blood pressure is important as well. Moreover, different kinds of exercise might produce distinct effects that might differ between normotensive and hypertensive subjects. The aim of this study was to review the current literature on the acute and chronic effects of aerobic and resistance exercise on ambulatory blood pressure in normotensive and hypertensive subjects. It has been conclusively shown that a single episode of aerobic exercise reduces ambulatory blood pressure in hypertensive patients. Similarly, regular aerobic training also decreases ambulatory blood pressure in hypertensive individuals. In contrast, data on the effects of resistance exercise is both scarce and controversial. Nevertheless, studies suggest that resistance exercise might acutely decrease ambulatory blood pressure after exercise, and that this effect seems to be greater after low-intensity exercise and in patients receiving anti-hypertensive drugs. On the other hand, only two studies investigating resistance training in hypertensive patients have been conducted, and neither has demonstrated any hypotensive effect. Thus, based on current knowledge, aerobic training should be recommended to decrease ambulatory blood pressure in hypertensive individuals, while resistance exercise could be prescribed as a complementary strategy. PMID:20360924

  13. Medical Management of Acute Radiation Syndromes : Immunoprophylaxis by Antiradiation Vaccine

    NASA Astrophysics Data System (ADS)

    Popov, Dmitri; Maliev, Vecheslav; Jones, Jeffrey; Casey, Rachael; Kedar, Prasad

    Introduction: Traditionally, the treatment of Acute Radiation Syndrome (ARS) includes supportive therapy, cytokine therapy, blood component transfusions and even stem cell transplantation. Recommendations for ARS treatment are based on clinical symptoms, laboratory results, radiation exposure doses and information received from medical examinations. However, the current medical management of ARS does not include immune prophylaxis based on antiradiation vaccines or immune therapy with hyperimmune antiradiation serum. Immuneprophylaxis of ARS could result from stimulating the immune system via immunization with small doses of radiation toxins (Specific Radiation Determinants-SRD) that possess significant immuno-stimulatory properties. Methods: Principles of immuno-toxicology were used to derive this method of immune prophylaxis. An antiradiation vaccine containing a mixture of Hematotoxic, Neurotoxic and Non-bacterial (GI) radiation toxins, underwent modification into a toxoid forms of the original SRD radiation toxins. The vaccine was administered to animals at different times prior to irradiation. The animals were subjected to lethal doses of radiation that induced different forms of ARS at LD 100/30. Survival rates and clinical symptoms were observed in both control and vaccine-treated animals. Results: Vaccination with non-toxic doses of Radiation toxoids induced immunity from the elaborated Specific Radiation Determinant (SRD) toxins. Neutralization of radiation toxins by specific antiradiation antibodies resulted in significantly improved clinical symptoms in the severe forms of ARS and observed survival rates of 60-80% in animals subjected to lethal doses of radiation expected to induce different forms of ARS at LD 100/30. The most effective vaccination schedule for the antiradiation vaccine consisted of repeated injections 24 and 34 days before irradiation. The vaccine remained effective for the next two years, although the specific immune memory probably

  14. Effect of morphine and methadone acute treatment on immunological activity in mice: pharmacokinetic and pharmacodynamic correlates.

    PubMed

    Pacifici, R; Patrini, G; Venier, I; Parolaro, D; Zuccaro, P; Gori, E

    1994-06-01

    This report describes the 24-hr time course of the immunomodulatory effects of an acute s.c. injection of morphine in C57BL6 mice, and correlates these effects with the drug's analgesic properties and serum levels. Acute morphine treatment had a biphasic effect on various immune parameters: there was an increase in in vitro phagocytosis and the killing of Candida Albican cells by peritoneal polymorphonuclear leukocytes 20 and 40 min after the injection of morphine, 20 mg/kg, when analgesia and serum morphine concentrations were at their peak. Interestingly, 24 hr after morphine administration (when antinociception and morphine blood levels were no longer detectable) these parameters underwent a marked reduction. Similarly, macrophage-mediated inhibition of tumor cells proliferation was first stimulated (at 20 and 40 min) and then depressed (at 24 hr). Splenic natural killer cell cytotoxicity, determined by standard 51Cr release from YAC-1 target cells, also was evaluated. No differences in natural killer activity was observed at any of the monitored time points. In addition, we evaluated the immunomodulatory effects of an acute injection of methadone (a synthetic narcotic compound) at a dose inducing the same degree of analgesia as morphine. None of the tested immunoparameters were affected by the administration of methadone, which indicates the different drug-sensitivity of immunological correlates in vivo.

  15. Cost-effectiveness of endovascular versus open repair of acute complicated type B aortic dissections.

    PubMed

    Luebke, Thomas; Brunkwall, Jan

    2014-05-01

    This study weighed the cost and benefit of thoracic endovascular aortic repair (TEVAR) vs open repair (OR) in the treatment of an acute complicated type B aortic dissection by (TBAD) estimating the cost-effectiveness to determine an optimal treatment strategy based on the best currently available evidence. A cost-utility analysis from the perspective of the health system payer was performed using a decision analytic model. Within this model, the 1-year survival, quality-adjusted life-years (QALYs), and costs for a hypothetical cohort of patients with an acute complicated TBAD managed with TEVAR or OR were evaluated. Clinical effectiveness data, cost data, and transitional probabilities of different health states were derived from previously published high-quality studies or meta-analyses. Probabilistic sensitivity analyses were performed on uncertain model parameters. The base-case analysis showed, in terms of QALYs, that OR appeared to be more expensive (incremental cost of €17,252.60) and less effective (-0.19 QALYs) compared with TEVAR; hence, in terms of the incremental cost-effectiveness ratio, OR was dominated by TEVAR. As a result, the incremental cost-effectiveness ratio (ie, the cost per life-year saved) was not calculated. The average cost-effectiveness ratio of TEVAR and OR per QALY gained was €56,316.79 and €108,421.91, respectively. In probabilistic sensitivity analyses, TEVAR was economically dominant in 100% of cases. The probability that TEVAR was economically attractive at a willingness-to-pay threshold of €50,000/QALY gained was 100%. The present results suggest that TEVAR yielded more QALYs and was associated with lower 1-year costs compared with OR in patients with an acute complicated TBAD. As a result, from the cost-effectiveness point of view, TEVAR is the dominant therapy over OR for this disease under the predefined conditions. Copyright © 2014 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

  16. Predicting the neurobehavioral side effects of dexamethasone in pediatric acute lymphoblastic leukemia.

    PubMed

    Warris, Lidewij T; van den Akker, Erica L T; Aarsen, Femke K; Bierings, Marc B; van den Bos, Cor; Tissing, Wim J E; Sassen, Sebastiaan D T; Veening, Margreet A; Zwaan, Christian M; Pieters, Rob; van den Heuvel-Eibrink, Marry M

    2016-10-01

    Although dexamethasone is an effective treatment for acute lymphoblastic leukemia (ALL), it can induce a variety of serious neurobehavioral side effects. We hypothesized that these side effects are influenced by glucocorticoid sensitivity at the tissue level. We therefore prospectively studied whether we could predict the occurrence of these side effects using the very low-dose dexamethasone suppression test (DST) or by measuring trough levels of dexamethasone. Fifty pediatric patients (3-16 years of age) with acute lymphoblastic leukemia (ALL) were initially included during the maintenance phase (with dexamethasone) of the Dutch ALL treatment protocol. As a marker of glucocorticoid sensitivity, the salivary very low-dose DST was used. A post-dexamethasone cortisol level <2.0nmol/L was considered a hypersensitive response. The neurobehavioral endpoints consisted of questionnaires regarding psychosocial and sleeping problems administered before and during the course of dexamethasone (6mg/m(2)), and dexamethasone trough levels were measured during dexamethasone treatment. Patients with a hypersensitive response to dexamethasone had more behavioral problems (N=11), sleeping problems, and/or somnolence (N=12) (P<0.05 for all three endpoints). The positive predictive values of the DST for psychosocial problems and sleeping problems were 50% and 30%, respectively. Dexamethasone levels were not associated with neurobehavioral side effects. We conclude that neither the very low-dose DST nor measuring dexamethasone trough levels can accurately predict dexamethasone-induced neurobehavioral side effects. However, patients with glucocorticoid hypersensitivity experienced significantly more symptoms associated with dexamethasone-induced depression. Future studies should elucidate further the mechanisms by which neurobehavioral side effects are influenced by glucocorticoid sensitivity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Kupffer cells facilitate the acute effects of leptin on hepatic lipid metabolism.

    PubMed

    Metlakunta, Anantha; Huang, Wan; Stefanovic-Racic, Maja; Dedousis, Nikolaos; Sipula, Ian; O'Doherty, Robert M

    2017-01-01

    Leptin has potent effects on lipid metabolism in a number of peripheral tissues. In liver, an acute leptin infusion (~120 min) stimulates hepatic fatty acid oxidation (~30%) and reduces triglycerides (TG, ~40%), effects that are dependent on phosphoinositol-3-kinase (PI3K) activity. In the current study we addressed the hypothesis that leptin actions on liver-resident immune cells are required for these metabolic effects. Myeloid cell-specific deletion of the leptin receptor (ObR) in mice or depletion of liver Kupffer cells (KC) in rats in vivo prevented the acute effects of leptin on liver lipid metabolism, while the metabolic effects of leptin were maintained in mice lacking ObR in hepatocytes. Notably, liver TG were elevated in both lean and obese myeloid cell ObR, but the degree of obesity and insulin resistance induced by a high-fat diet was similar to control mice. In isolated primary hepatocytes (HEP), leptin had no effects on HEP lipid metabolism and only weakly stimulated PI3K. However, the coculture of KC with HEP restored leptin action on HEP fatty acid metabolism and stimulation of HEP PI3K. Notably, leptin stimulated the release from KC of a number of cytokines. However, the exposure of HEP to these cytokines individually [granulocyte macrophage colony-stimulating factor, IL-1α, IL-1β, IL-6, IL-10, and IL-18] or in combination had no effects on HEP lipid metabolism. Together, these data demonstrate a role for liver mononuclear cells in the regulation of liver lipid metabolism by leptin. Copyright © 2017 the American Physiological Society.

  18. The acute toxic effects of 1-alkyl-3-methylimidazolium nitrate ionic liquids on Chlorella vulgaris and Daphnia magna.

    PubMed

    Zhang, Cheng; Zhang, Shuai; Zhu, Lusheng; Wang, Jinhua; Wang, Jun; Zhou, Tongtong

    2017-10-01

    Given their increasingly widespread application, the toxic effects of ionic liquids (ILs) have become the subject of significant attention in recent years. Therefore, the present study assessed the acute toxic effects of 1-alkyl-3-methylimidazolium nitrate ([C n mim]NO 3 (n = 2, 4, 6, 8, 10, 12)) on Chlorella vulgaris and Daphnia magna. The sensitivity of the tested organism Daphnia magna and the investigated IL concentrations in water using high-performance liquid chromatography (HPLC) were also evaluated to demonstrate the reliability of the present study. The results illustrated that Daphnia magna is indeed sensitive to the reference toxicant and the investigated ILs were stable in the aquatic environment. The 50% effect concentration (EC 50 ) was used to represent the acute toxic effects on Chlorella vulgaris and Daphnia magna. With the increasing alkyl-chain lengths, the toxicity of the investigated ILs increased in both the test organisms. Accordingly, the alkyl-chain lengths can cause significantly toxic effects on aquatic organisms, and Daphnia magna are much more sensitive than Chlorella vulgaris to the imidazolium-based ILs used in the present study. Furthermore, the present study provides more information on the acute toxic effects of 1-alkyl-3-methylimidazolium nitrate. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. The effect of acute physical exercise on cytokine levels in patients with systemic lupus erythematosus.

    PubMed

    da Silva, A E; dos Reis-Neto, E Torres; da Silva, N P; Sato, E I

    2013-12-01

    Acute exercise increases IL-6, IL-10 and TNF-α levels in healthy subjects. There is no study evaluating the effect of exercise on cytokines level in systemic lupus erythematosus (SLE) patients. Our aim was to assess IL-10, IL-6 and TNF-α levels at baseline and after acute physical exercise in patients with SLE. In total, 27 female SLE patients and 30 healthy controls were evaluated. Serum levels of IL-10, IL-6 and TNF-α at baseline and soon after the ergospirometric test were measured by ELISA test. Student's t-tests and Mann-Whitney test were used for intra- and inter-group comparisons; p values <0.05 were considered significant. Patients with SLE presented worse ergospirometric parameters compared with controls: VO2max (25.78 ± 5.51 vs. 32.74 ± 5.85 ml/kg/min, p < 0.001); maximum heart rate (174.18 ± 12.36 vs. 185.15 ± 2.07 bpm, p = 0.001); maximum ventilation (65.51 ± 15.68 vs. 80.48 ± 18.98 l/min, p = 0.001) and maximum speed (7.70 ± 1.24 vs. 9.40 ± 1.22 km/h, p < 0.001). At baseline, SLE patients presented higher levels of IL-6 (2.38 ± 1.70 vs. 1.71 ± 0.29 pg/ml, p = 0.035) and IL-10 (1.09 ± 1.55 vs. 0.30 ± 0.11 pg/ml, p = 0.037) than controls. Acute exercise in controls increased IL-6 level (1.71 ± 0.29 vs. 2.01 ± 0.27 pg/ml, p = 0.003) without change in IL-10 and TNF-α levels. However, no significant change in cytokine levels was observed in SLE patients after acute exercise. This is the first study evaluating the effect of acute exercise on cytokine levels in patients with SLE. In contrast to healthy controls, acute physical exercise did not increase the levels of IL-6 in patients with SLE, and seems to be safe in those patients with inactive or mild active disease.

  20. The cost-effectiveness of nonoperative management versus laparoscopic appendectomy for the treatment of acute, uncomplicated appendicitis in children.

    PubMed

    Wu, James X; Sacks, Greg D; Dawes, Aaron J; DeUgarte, Daniel; Lee, Steven L

    2017-07-01

    Several studies have demonstrated the safety and short-term success of nonoperative management in children with acute, uncomplicated appendicitis. Nonoperative management spares the patients and their family the upfront cost and discomfort of surgery, but also risks recurrent appendicitis. Using decision-tree software, we evaluated the cost-effectiveness of nonoperative management versus routine laparoscopic appendectomy. Model variables were abstracted from a review of the literature, Healthcare Cost and Utilization Project, and Medicare Physician Fee schedule. Model uncertainty was assessed using both one-way and probabilistic sensitivity analyses. We used a $100,000 per quality adjusted life year (QALY) threshold for cost-effectiveness. Operative management cost $11,119 and yielded 23.56 quality-adjusted life months (QALMs). Nonoperative management cost $2277 less than operative management, but yielded 0.03 fewer QALMs. The incremental cost-to-effectiveness ratio of routine laparoscopic appendectomy was $910,800 per QALY gained. This greatly exceeds the $100,000/QALY threshold and was not cost-effective. One-way sensitivity analysis found that operative management would become cost-effective if the 1-year recurrence rate of acute appendicitis exceeded 39.8%. Probabilistic sensitivity analysis indicated that nonoperative management was cost-effective in 92% of simulations. Based on our model, nonoperative management is more cost-effective than routine laparoscopic appendectomy for children with acute, uncomplicated appendicitis. Cost-Effectiveness Study: Level II. Published by Elsevier Inc.

  1. Interacting Effects of Trait Anger and Acute Anger Arousal on Pain: The Role of Endogenous Opioids

    PubMed Central

    Bruehl, Stephen; Burns, John W.; Chung, Ok Yung; Chont, Melissa

    2011-01-01

    Objective Elevated trait anger (TRANG; heightened propensity to experience anger) is associated with greater pain responsiveness, possibly via associations with deficient endogenous opioid analgesia. This study tested whether acute anger arousal moderates the impact of TRANG on endogenous opioid analgesia. Methods 94 chronic low back pain participants (LBP) and 85 healthy controls received opioid blockade (8mg naloxone) or placebo in randomized, counterbalanced order in separate sessions. Participants were randomly assigned to undergo either a 5-minute anger recall interview (ARI) or neutral control interview (NCI) across both drug conditions. Immediately following the assigned interview, participants engaged sequentially in finger pressure and ischemic forearm pain tasks. Opioid blockade effects were derived (blockade minus placebo condition pain ratings) to index opioid antinociceptive function. Results Placebo condition TRANG × Interview interactions (p’s<.05) indicated that TRANG was hyperalgesic only in the context of acute anger arousal (ARI condition; p’s<.05). Blockade effect analyses suggested these hyperalgesic effects were related to deficient opioid analgesia. Significant TRANG × Interview interactions (p’s<.05) for both pain tasks indicated that elevated TRANG was associated with smaller blockade effects (less endogenous opioid analgesia) only in the ARI condition (p’s<.05). Results for ischemic task VAS intensity blockade effects suggested that associations between TRANG and impaired opioid function were most evident in LBP participants when experiencing anger (Type × Interview × TRANG Interaction; p<.05). Conclusions Results indicate that hyperalgesic effects of TRANG are most prominent when acute anger is aroused, and suggest that endogenous opioid mechanisms contribute. PMID:21862829

  2. Cost‐Effectiveness of Clopidogrel‐Aspirin Versus Aspirin Alone for Acute Transient Ischemic Attack and Minor Stroke

    PubMed Central

    Pan, Yuesong; Wang, Anxin; Liu, Gaifen; Zhao, Xingquan; Meng, Xia; Zhao, Kun; Liu, Liping; Wang, Chunxue; Johnston, S. Claiborne; Wang, Yilong; Wang, Yongjun

    2014-01-01

    Background Treatment with the combination of clopidogrel and aspirin taken soon after a transient ischemic attack (TIA) or minor stroke was shown to reduce the 90‐day risk of stroke in a large trial in China, but the cost‐effectiveness is unknown. This study sought to estimate the cost‐effectiveness of the clopidogrel‐aspirin regimen for acute TIA or minor stroke. Methods and Results A Markov model was created to determine the cost‐effectiveness of treatment of acute TIA or minor stroke patients with clopidogrel‐aspirin compared with aspirin alone. Inputs for the model were obtained from clinical trial data, claims databases, and the published literature. The main outcome measure was cost per quality‐adjusted life‐years (QALYs) gained. One‐way and multivariable probabilistic sensitivity analyses were performed to test the robustness of the findings. Compared with aspirin alone, clopidogrel‐aspirin resulted in a lifetime gain of 0.037 QALYs at an additional cost of CNY 1250 (US$ 192), yielding an incremental cost‐effectiveness ratio of CNY 33 800 (US$ 5200) per QALY gained. Probabilistic sensitivity analysis showed that clopidogrel‐aspirin therapy was more cost‐effective in 95.7% of the simulations at a willingness‐to‐pay threshold recommended by the World Health Organization of CNY 105 000 (US$ 16 200) per QALY. Conclusions Early 90‐day clopidogrel‐aspirin regimen for acute TIA or minor stroke is highly cost‐effective in China. Although clopidogrel is generic, Plavix is brand in China. If Plavix were generic, treatment with clopidogrel‐aspirin would have been cost saving. PMID:24904018

  3. Comparative Analysis of Cellular Immune Responses in Treated Leishmania Patients and Hamsters against Recombinant Th1 Stimulatory Proteins of Leishmania donovani

    PubMed Central

    Joshi, Sumit; Yadav, Narendra K.; Rawat, Keerti; Tripathi, Chandra Dev P.; Jaiswal, Anil K.; Khare, Prashant; Tandon, Rati; Baharia, Rajendra K.; Das, Sanchita; Gupta, Reema; Kushawaha, Pramod K.; Sundar, Shyam; Sahasrabuddhe, Amogh A.; Dube, Anuradha

    2016-01-01

    Our prior studies demonstrated that cellular response of T helper 1 (Th1) type was generated by a soluble antigenic fraction (ranging from 89.9 to 97.1 kDa) of Leishmania donovani promastigote, in treated Leishmania patients as well as hamsters and showed significant prophylactic potential against experimental visceral leishmaniasis (VL). Eighteen Th1 stimulatory proteins were identified through proteomic analysis of this subfraction, out of which 15 were developed as recombinant proteins. In the present work, we have evaluated these 15 recombinant proteins simultaneously for their comparative cellular responses in treated Leishmania patients and hamsters. Six proteins viz. elongation factor-2, enolase, aldolase, triose phosphate isomerase, protein disulfide isomerase, and p45 emerged as most immunogenic as they produced a significant lymphoproliferative response, nitric oxide generation and Th1 cytokine response in PBMCs and lymphocytes of treated Leishmania patients and hamsters respectively. The results suggested that these proteins may be exploited for developing a successful poly-protein and/or poly-epitope vaccine against VL. PMID:27047452

  4. Influence of acute bupropion pre-treatment on the effects of intranasal cocaine.

    PubMed

    Stoops, William W; Lile, Joshua A; Glaser, Paul E A; Hays, Lon R; Rush, Craig R

    2012-06-01

    The aim of this experiment was to determine the influence of acute bupropion pre-treatment on subject-rated effects and choice of intranasal cocaine versus money. A randomized, within-subject, placebo-controlled, double-blind experiment. An out-patient research unit. Eight cocaine-using adults. Subjects completed nine experimental sessions in which they were pre-treated with 0, 100 or 200 mg oral immediate release bupropion. Ninety minutes later they sampled an intranasal cocaine dose [4 (placebo), 15 or 45 mg] and made six choices between that dose and an alternative reinforcer (US$0.25), available on independent, concurrent progressive ratio schedules. Subjects also completed a battery of subject-rated, performance and physiological measures following the sample doses of cocaine. After 0 mg bupropion, the high dose of cocaine (45 mg) was chosen five of six times on average compared to 2.25 of six choices for placebo cocaine (4 mg) (P < 0.05). Active bupropion reduced choice of 45 mg cocaine to 3.13 (100 mg) or 4.00 (200 mg) out of six drug choices on average. Bupropion also consistently enhanced positive subject-rated effects of cocaine (e.g. good effects; willing to take again) while having no effects of its own. The atypical antidepressant, bupropion, acutely appears to reduce preference for intranasal cocaine versus a small amount of money but to increase reported positive experiences of the drug. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.

  5. Differential regulation of gonadotropin-releasing hormone (GnRH) neuron activity and membrane properties by acutely-applied estradiol: dependence on dose and estrogen receptor subtype

    PubMed Central

    Chu, Zhiguo; Andrade, Josefa; Shupnik, Margaret A.; Moenter, Suzanne M.

    2009-01-01

    GnRH neurons are critical to controlling fertility. In vivo, estradiol can inhibit or stimulate GnRH release depending on concentration and physiological state. We examined rapid, non-genomic effects of estradiol. Whole-cell recordings were made of GnRH neurons in brain slices from ovariectomized mice with ionotropic GABA and glutamate receptors blocked. Estradiol was bath-applied and measurements completed within 15 min. Estradiol from high physiological (preovulatory) concentrations (100pM) to 100nM enhanced action potential firing, reduced afterhyperpolarizing potential (AHP) and increased slow afterdepolarization (sADP) amplitudes, and reduced IAHP and enhanced IADP. The reduction of IAHP was occluded by prior blockade of calcium-activated potassium channels. These effects were mimicked by an estrogen receptor (ER) β-specific agonist and were blocked by the classical receptor antagonist ICI182780. ERα or GPR30 agonists had no effect. The acute stimulatory effect of high physiological estradiol on firing rate was dependent on signaling via protein kinase A. In contrast, low physiological levels of estradiol (10pM) did not affect intrinsic properties. Without blockade of ionotropic GABA and glutamate receptors, however, 10pM estradiol reduced firing of GnRH neurons; this was mimicked by an ERα agonist. ERα agonists reduced the frequency of GABA transmission to GnRH neurons; GABA can excite to these cells. In contrast, ERβ agonists increased GABA transmission and postsynaptic response. These data suggest rapid intrinsic and network modulation of GnRH neurons by estradiol is dependent upon both dose and receptor subtype. In cooperation with genomic actions, non-genomic effects may play a role in feedback regulation of GnRH secretion. PMID:19403828

  6. Dutch courage? Effects of acute alcohol consumption on self-ratings and observer ratings of foreign language skills.

    PubMed

    Renner, Fritz; Kersbergen, Inge; Field, Matt; Werthmann, Jessica

    2018-01-01

    A popular belief is that alcohol improves the ability to speak in a foreign language. The effect of acute alcohol consumption on perceived foreign language performance and actual foreign language performance in foreign language learners has not been investigated. The aim of the current study was to test the effects of acute alcohol consumption on self-rated and observer-rated verbal foreign language performance in participants who have recently learned this language. Fifty native German speakers who had recently learned Dutch were randomized to receive either a low dose of alcohol or a control beverage that contained no alcohol. Following the experimental manipulation, participants took part in a standardized discussion in Dutch with a blinded experimenter. The discussion was audio-recorded and foreign language skills were subsequently rated by two native Dutch speakers who were blind to the experimental condition (observer-rating). Participants also rated their own individual Dutch language skills during the discussion (self-rating). Participants who consumed alcohol had significantly better observer-ratings for their Dutch language, specifically better pronunciation, compared with those who did not consume alcohol. However, alcohol had no effect on self-ratings of Dutch language skills. Acute alcohol consumption may have beneficial effects on the pronunciation of a foreign language in people who have recently learned that language.

  7. Acute and chronic effects of cannabinoids on effort-related decision-making and reward learning: an evaluation of the cannabis 'amotivational' hypotheses.

    PubMed

    Lawn, Will; Freeman, Tom P; Pope, Rebecca A; Joye, Alyssa; Harvey, Lisa; Hindocha, Chandni; Mokrysz, Claire; Moss, Abigail; Wall, Matthew B; Bloomfield, Michael Ap; Das, Ravi K; Morgan, Celia Ja; Nutt, David J; Curran, H Valerie

    2016-10-01

    Anecdotally, both acute and chronic cannabis use have been associated with apathy, amotivation, and other reward processing deficits. To date, empirical support for these effects is limited, and no previous studies have assessed both acute effects of Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), as well as associations with cannabis dependence. The objectives of this study were (1) to examine acute effects of cannabis with CBD (Cann + CBD) and without CBD (Cann-CBD) on effort-related decision-making and (2) to examine associations between cannabis dependence, effort-related decision-making and reward learning. In study 1, 17 participants each received three acute vaporized treatments, namely Cann-CBD (8 mg THC), Cann + CBD (8 mg THC + 10 mg CBD) and matched placebo, followed by a 50 % dose top-up 1.5 h later, and completed the Effort Expenditure for Rewards Task (EEfRT). In study 2, 20 cannabis-dependent participants were compared with 20 non-dependent, drug-using control participants on the EEfRT and the Probabilistic Reward Task (PRT) in a non-intoxicated state. Cann-CBD reduced the likelihood of high-effort choices relative to placebo (p = 0.042) and increased sensitivity to expected value compared to both placebo (p = 0.014) and Cann + CBD (p = 0.006). The cannabis-dependent and control groups did not differ on the EEfRT. However, the cannabis-dependent group exhibited a weaker response bias than the control group on the PRT (p = 0.007). Cannabis acutely induced a transient amotivational state and CBD influenced the effects of THC on expected value. In contrast, cannabis dependence was associated with preserved motivation alongside impaired reward learning, although confounding factors, including depression, cannot be disregarded. This is the first well powered, fully controlled study to objectively demonstrate the acute amotivational effects of THC.

  8. The Effects of Modified Constraint-Induced Movement Therapy in Acute Subcortical Cerebral Infarction.

    PubMed

    Yu, Changshen; Wang, Wanjun; Zhang, Yue; Wang, Yizhao; Hou, Weijia; Liu, Shoufeng; Gao, Chunlin; Wang, Chen; Mo, Lidong; Wu, Jialing

    2017-01-01

    Background : Constraint-induced movement therapy (CIMT) promotes upper extremity recovery post stroke, however, it is difficult to implement clinically due to its high resource demand and safety of the restraint. Therefore, we propose that modified CIMT (mCIMT) be used to treat individuals with acute subcortical infarction. Objective : To evaluate the therapeutic effects of mCIMT in patients with acute subcortical infarction, and investigate the possible mechanisms underlying the effect. Methods : The role of mCIMT was investigated in 26 individuals experiencing subcortical infarction in the preceding 14 days. Patients were randomly assigned to either mCIMT or standard therapy. mCIMT group was treated daily for 3 h over 10 consecutive working days, using a mitt on the unaffected arm for up to 30% of waking hours. The control group was treated with an equal dose of occupational therapy and physical therapy. During the 3-month follow-up, the motor functions of the affected limb were assessed by the Wolf Motor Function Test (WMFT) and Motor Activity Log (MAL). Altered cortical excitability was assessed via transcranial magnetic stimulation (TMS). Results : Treatment significantly improved the movement in the mCIMT group compared with the control group. The mean WMF score was significantly higher in the mCIMT group compared with the control group. Further, the appearance of motor-evoked potentials (MEPs) were significantly higher in the mCIMT group compared with the baseline data. A significant change in ipsilesional silent period (SP) occurred in the mCIMT group compared with the control group. However, we found no difference between two groups in motor function or electrophysiological parameters after 3 months of follow-up. Conclusions : mCIMT resulted in significant functional changes in timed movement immediately following treatment in patients with acute subcortical infarction. Further, early mCIMT improved ipsilesional cortical excitability. However, no long

  9. The protective effects of acute cardiovascular exercise on the interference of procedural memory.

    PubMed

    Jo, J S; Chen, J; Riechman, S; Roig, M; Wright, D L

    2018-04-10

    Numerous studies have reported a positive impact of acute exercise for procedural skill memory. Previous work has revealed this effect, but these findings are confounded by a potential contribution of a night of sleep to the reported exercise-mediated reduction in interference. Thus, it remains unclear if exposure to a brief bout of exercise can provide protection to a newly acquired motor memory. The primary objective of the present study was to examine if a single bout of moderate-intensity cardiovascular exercise after practice of a novel motor sequence reduces the susceptibility to retroactive interference. To address this shortcoming, 17 individuals in a control condition practiced a novel motor sequence that was followed by test after a 6-h wake-filled interval. A separate group of 17 individuals experienced practice with an interfering motor sequence 45 min after practice with the original sequence and were then administered test trials 6 h later. One additional group of 12 participants was exposed to an acute bout of exercise immediately after practice with the original motor sequence but prior to practice with the interfering motor sequence and the subsequent test. In comparison with the control condition, increased response times were revealed during the 6-h test for the individuals that were exposed to interference. The introduction of an acute bout of exercise between the practice of the two motor sequences produced a reduction in interference from practice with the second task at the time of test, however, this effect was not statistically significant. These data reinforce the hypothesis that while there may be a contribution from exercise to post-practice consolidation of procedural skills which is independent of sleep, sleep may interact with exercise to strengthen the effects of the latter on procedural memory.

  10. [Protective effect of curcumin on oleic-induced acute lung injury in rats].

    PubMed

    Zhu, Rui-fang; Zhou, Min; He, Jian-lin; Ding, Fu-yun; Yu, Shu-qin; Xu, Guang-lin

    2008-09-01

    To investigate the effect of curcumine on acute lung injury induced by oleic acid in rat and the possible mechanism of action. The rats were divided into 6 groups randomly: normal group, control group, curcumine groups (5, 10, 20 mg x kg(-1)) and dexamethasone group (1 mg x kg(-1)). During the experiment, acute lung injury was induced by oleic acid in rat. The changes of dynamic lung compliance were recorded by anrise 2005 pulmonary function test apparatus, light microscope was used to examine histological changes and lung index as well as wet to dry weight ratio was calculated by weighting method. Lung vascular permeability and protein level in BALF were detected by ultraviolet spectrophotometry, and the concentrations of TNF-alpha, IL-6 and IL-10 in BALF were measured by enzyme linked immunosorbent assay (ELISA). The result showed that the changes of pulmonary compliance were inhibited and pulmonary function was improved by curcumine. The OA-induced elevation of lung index was restrained, as well as wet to dry weight ratio, lung vascular permeability, protein level, TNF-alpha (250.4 +/- 21.6 vs. 172.53 +/- 14.88, 122.2 +/- 10.98, 108.69 +/- 3.39) ng x L(-1), IL-6 (763.6 +/- 88.33 vs. 207.41 +/- 15.55, 172.13 +/- 21.91, 142.92 +/- 4.32) ng x L(-1) in BALF in curcumine groups, IL-10 (98.90 +/- 2.99 vs. 208.44 +/- 16.30, 218.43 +/- 6.23, 252.70 +/- 20.58) ng x L(-1) in BALF was increased, respectively significantly. Light microscope findings shown that the impairment in curcumine groups was far less severe than that in model groups. Pretreatment of curcumine showed beneficial effect on acute lung injury induced by oleic acid in rats. The mediation of both proinflammatory factor and anti-inflammatory factor by curcumine may be involved in mechanism of action of curcumine effects.

  11. Acute psychoactive effects of intravenous ketamine during treatment of mood disorders: Analysis of the Clinician Administered Dissociative State Scale.

    PubMed

    van Schalkwyk, Gerrit I; Wilkinson, Samuel T; Davidson, Larry; Silverman, Wendy K; Sanacora, Gerard

    2018-02-01

    Ketamine has rapid-acting antidepressant effects. Frequently, ketamine administration also causes acute psychoactive effects - in trials, these effects are commonly measured using the Clinician Administered Dissociative State Scale (CADSS). However, the CADSS was not designed for this specific purpose, having been validated in other clinical contexts, and anecdotally does not appear to fully capture ketamine's acute psychoactive effects. Data were obtained from 110 individuals with mood disorders (predominantly major depressive disorder) who underwent intravenous ketamine infusion. An exploratory factor analysis (EFA) was performed on the CADSS, along with assessment of internal consistency. Qualitative methods were used to conduct in-depth interviews with a subset of these participants to identify key features of the acute ketamine experience, including aspects that may not be captured by the CADSS. The mean total score of the CADSS was low at 7.7 (SD 9.2). Analysis of internal consistency showed a Cronbach's alpha of 0.74. Five CADSS items had low correlations with the total score. EFA lead to a one-factor solution containing 16 items. Five of the six highest loading items involved perceptual disturbances, either of time or sensation. Qualitative analyses of 10 patient narratives revealed two phenomena not captured on the CADSS: disinhibition and a sense of peace. This study was by limited by the absence of other ratings of the participants' experience. Findings suggest that the CADSS partially captures the acute effects of ketamine administration. Further research may seek to validate a revised version of the CADSS that more accurately measures these effects. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Warfarin affects acute inflammatory response induced by subcutaneous polyvinyl sponge implantation in rats.

    PubMed

    Mirkov, Ivana; Popov Aleksandrov, Aleksandra; Demenesku, Jelena; Ninkov, Marina; Mileusnic, Dina; Kataranovski, Dragan; Kataranovski, Milena

    2017-09-01

    Warfarin (WF) is an anticoagulant which also affects physiological processes other than hemostasis. Our previous investigations showed the effect of WF which gained access to the organism via skin on resting peripheral blood granulocytes. Based on these data, the aim of the present study was to examine whether WF could modulate the inflammatory processes as well. To this aim the effect of WF on the inflammatory response induced by subcutaneous sponge implantation in rats was examined. Warfarin-soaked polyvinyl sponges (WF-sponges) were implanted subcutaneously and cell infiltration into sponges, the levels of nitric oxide (NO) and inflammatory cytokines tumor necrosis factor (TNF) and interleukin-6 (IL-6) production by sponge cells were measured as parameters of inflammation. T cell infiltration and cytokine interferon-γ (IFN-γ), interleukin-17 (IL-17) and interleukin-10 (IL-10) were measured at day 7 post implantation. Warfarin exerted both stimulatory and suppressive effects depending on the parameter examined. Flow cytometry of cells recovered from sponges showed higher numbers of granulocytes (HIS48 + cells) at days 1 and 3 post implantation and CD11b + cells at day 1 compared to control sponges. Cells from WF-sponges had an increased NO production (Griess reaction) at days 1 and 7. In contrast, lower levels of TNF (measured by ELISA) production by cells recovered from WF-soaked sponges were found in the early (day one) phase of reaction with unchanged levels at other time points. While IL-6 production by cells recovered from WF-soaked sponges was decreased at day 1, it was increased at day 7. Higher T cell numbers were noted in WF sponges at day 7 post implantation, and recovered cells produced more IFN-γ and IL-17, while IL-10 production remained unchanged. Warfarin affects some of the parameters of inflammatory reaction induced by subcutaneous polyvinyl sponge implantation. Differential (both stimulatory as well as inhibitory) effects of WF on

  13. Acute mercurial pneumonitis

    PubMed Central

    Milne, James; Christophers, Allen; Silva, Pamela De

    1970-01-01

    Milne, J., Christophers, A., and de Silva, Pamela (1970).Brit. J. industr. Med.,27, 334-338. Acute mercurial pneumonitis. Mercury vapour has been shown to cause acute effects on the lung when inhaled in high concentrations. Four men, exposed to mercury inside a tank, developed, hours later, signs and symptoms of an acute febrile illness with severe pulmonary irritation, characterized by fever, rigors, cough, dyspnoea, and tightness in the chest. A review of the literature revealed that this syndrome had been described and investigated previously in fewer than 20 cases during the past 40 years, and is apparently little known. Fatalities have been described, particularly in children, and necropsy evidence has consistently revealed the pattern of an acute diffuse interstitial pneumonitis, accompanied by profuse fibrinous exudation and erosion of the bronchial and bronchiolar lining. The two common features in all reports are the heating of mercury or the entering into a confined space, or both. Adequate respiratory protection by an efficient air-supplied respirator is mandatory in industrial circumstances of the kind described in this report. PMID:5488692

  14. Transgenic Mice with Increased Astrocyte Expression of IL-6 Show Altered Effects of Acute Ethanol on Synaptic Function

    PubMed Central

    Hernandez, Ruben V.; Puro, Alana C.; Manos, Jessica C.; Huitron-Resendiz, Salvador; Reyes, Kenneth C.; Liu, Kevin; Vo, Khanh; Roberts, Amanda J.; Gruol, Donna L.

    2015-01-01

    A growing body of evidence has revealed that resident cells of the central nervous system (CNS), and particularly the glial cells, comprise a neuroimmune system that serves a number of functions in the normal CNS and during adverse conditions. Cells of the neuroimmune system regulate CNS functions through the production of signaling factors, referred to as neuroimmune factors. Recent studies show that ethanol can activate cells of the neuroimmune system, resulting in the elevated production of neuroimmune factors, including the cytokine interleukin-6 (IL-6). Here we analyzed the consequences of this CNS action of ethanol using transgenic mice that express elevated levels of IL-6 through increased astrocyte expression (IL-6-tg) to model the increased IL-6 expression that occurs with ethanol use. Results show that increased IL-6 expression induces neuroadaptive changes that alter the effects of ethanol. In hippocampal slices from non-transgenic (non-tg) littermate control mice, synaptically evoked dendritic field excitatory postsynaptic potential (fEPSP) and somatic population spike (PS) at the Schaffer collateral to CA1 pyramidal neuron synapse were reduced by acute ethanol (20 or 60 mM). In contrast, acute ethanol enhanced the fEPSP and PS in hippocampal slices from IL-6 tg mice. Long-term synaptic plasticity of the fEPSP (i.e., LTP) showed the expected dose-dependent reduction by acute ethanol in non-tg hippocampal slices, whereas LTP in the IL-6 tg hippocampal slices was resistant to this depressive effect of acute ethanol. Consistent with altered effects of acute ethanol on synaptic function in the IL-6 tg mice, EEG recordings showed a higher level of CNS activity in the IL-6 tg mice than in the non-tg mice during the period of withdrawal from an acute high dose of ethanol. These results suggest a potential role for neuroadaptive effects of ethanol-induced astrocyte production of IL-6 as a mediator or modulator of the actions of ethanol on the CNS, including

  15. Multiple therapeutic effects of progranulin on experimental acute ischaemic stroke.

    PubMed

    Kanazawa, Masato; Kawamura, Kunio; Takahashi, Tetsuya; Miura, Minami; Tanaka, Yoshinori; Koyama, Misaki; Toriyabe, Masafumi; Igarashi, Hironaka; Nakada, Tsutomu; Nishihara, Masugi; Nishizawa, Masatoyo; Shimohata, Takayoshi

    2015-07-01

    In the central nervous system, progranulin, a glycoprotein growth factor, plays a crucial role in maintaining physiological functions, and progranulin gene mutations cause TAR DNA-binding protein-43-positive frontotemporal lobar degeneration. Although several studies have reported that progranulin plays a protective role against ischaemic brain injury, little is known about temporal changes in the expression level, cellular localization, and glycosylation status of progranulin after acute focal cerebral ischaemia. In addition, the precise mechanisms by which progranulin exerts protective effects on ischaemic brain injury remains unknown. Furthermore, the therapeutic potential of progranulin against acute focal cerebral ischaemia, including combination treatment with tissue plasminogen activator, remains to be elucidated. In the present study, we aimed to determine temporal changes in the expression and localization of progranulin after ischaemia as well as the therapeutic effects of progranulin on ischaemic brain injury using in vitro and in vivo models. First, we demonstrated a dynamic change in progranulin expression in ischaemic Sprague-Dawley rats, including increased levels of progranulin expression in microglia within the ischaemic core, and increased levels of progranulin expression in viable neurons as well as induction of progranulin expression in endothelial cells within the ischaemic penumbra. We also demonstrated that the fully glycosylated mature secretory isoform of progranulin (∼88 kDa) decreased, whereas the glycosylated immature isoform of progranulin (58-68 kDa) markedly increased at 24 h and 72 h after reperfusion. In vitro experiments using primary cells from C57BL/6 mice revealed that the glycosylated immature isoform was secreted only from the microglia. Second, we demonstrated that progranulin could protect against acute focal cerebral ischaemia by a variety of mechanisms including attenuation of blood-brain barrier disruption

  16. Stimulatory actions of IGF-I are mediated by IGF-IR cross-talk with GPER and DDR1 in mesothelioma and lung cancer cells

    PubMed Central

    Cirillo, Francesca; Santolla, Maria Francesca; Francesco, Ernestina Marianna De; Perri, Maria Grazia; Rigiracciolo, Damiano; Dolce, Vincenza; Belfiore, Antonino; Maggiolini, Marcello; Lappano, Rosamaria; Vivacqua, Adele

    2016-01-01

    Insulin-like growth factor-I (IGF-I)/IGF-I receptor (IGF-IR) system has been largely involved in the pathogenesis and development of various tumors. We have previously demonstrated that IGF-IR cooperates with the G-protein estrogen receptor (GPER) and the collagen receptor discoidin domain 1 (DDR1) that are implicated in cancer progression. Here, we provide novel evidence regarding the molecular mechanisms through which IGF-I/IGF-IR signaling triggers a functional cross-talk with GPER and DDR1 in both mesothelioma and lung cancer cells. In particular, we show that IGF-I activates the transduction network mediated by IGF-IR leading to the up-regulation of GPER and its main target genes CTGF and EGR1 as well as the induction of DDR1 target genes like MATN-2, FBN-1, NOTCH 1 and HES-1. Of note, certain DDR1-mediated effects upon IGF-I stimulation required both IGF-IR and GPER as determined knocking-down the expression of these receptors. The aforementioned findings were nicely recapitulated in important biological outcomes like IGF-I promoted chemotaxis and migration of both mesothelioma and lung cancer cells. Overall, our data suggest that IGF-I/IGF-IR system triggers stimulatory actions through both GPER and DDR1 in aggressive tumors as mesothelioma and lung tumors. Hence, this novel signaling pathway may represent a further target in setting innovative anticancer strategies. PMID:27384677

  17. Short-term Resource Utilization and Cost-Effectiveness of Comprehensive Geriatric Assessment in Acute Hospital Care for Severely Frail Elderly Patients.

    PubMed

    Ekerstad, Niklas; Karlson, Björn W; Andersson, David; Husberg, Magnus; Carlsson, Per; Heintz, Emelie; Alwin, Jenny

    2018-05-18

    The objective of this study was to estimate the 3-month within-trial cost-effectiveness of comprehensive geriatric assessment (CGA) in acute medical care for frail elderly patients compared to usual medical care, by estimating health-related quality of life and costs from a societal perspective. Clinical, prospective, controlled, 1-center intervention trial with 2 parallel groups. Structured, systematic interdisciplinary CGA-based care in an acute elderly care unit. If the patient fulfilled the inclusion criteria, and there was a bed available at the CGA unit, the patient was included in the intervention group. If no bed was available at the CGA unit, the patient was included in the control group and admitted to a conventional acute medical care unit. A large county hospital in western Sweden. The trial included 408 frail elderly patients, 75 years or older, in need of acute in-hospital treatment. The patients were allocated to the intervention group (n = 206) or control group (n = 202). Mean age of the patients was 85.7 years, and 56% were female. The primary outcome was the adjusted incremental cost-effectiveness ratio associated with the intervention compared to the control at the 3-month follow-up. We undertook cost-effectiveness analysis, adjusted by regression analyses, including hospital, primary, and municipal care costs and effects. The difference in the mean adjusted quality-adjusted life years gained between groups at 3 months was 0.0252 [95% confidence interval (CI): 0.0082-0.0422]. The incremental cost, that is, the difference between the groups, was -3226 US dollars (95% CI: -6167 to -285). The results indicate that the care in a CGA unit for acutely ill frail elderly patients is likely to be cost-effective compared to conventional care after 3 months. Copyright © 2018 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

  18. Evaluation of acute toxicity, genotoxicity and inhibitory effect on acute inflammation of an ethanol extract of Morus alba L. (Moraceae) in mice.

    PubMed

    Oliveira, Alisson Macário de; Nascimento, Matheus Ferreira do; Ferreira, Magda Rhayanny Assunção; Moura, Danielle Feijó de; Souza, Talita Giselly Dos Santos; Silva, Gabriela Cavalcante da; Ramos, Eduardo Henrique da Silva; Paiva, Patrícia Maria Guedes; Medeiros, Paloma Lys de; Silva, Teresinha Gonçalves da; Soares, Luiz Alberto Lira; Chagas, Cristiano Aparecido; Souza, Ivone Antônia de; Napoleão, Thiago Henrique

    2016-12-24

    Morus alba L. (white mulberry) is used in traditional medicine worldwide, including Brazil. The leaves of this plant are used to treat inflammatory disorders. Universal interest in this plant necessitates studies on the toxicological safety and scientific substantiation of the medicinal properties of M. alba. In previous work, we investigated the acute toxicity of orally administered M. alba ethanol extract in mice. This work was designed to investigate the ethanol extract obtained from M. alba leaves for acute toxicity when intraperitoneally administered, in vivo genotoxicity, and potential to reduce acute inflammation. In order to further investigate the constituents of the extract, we also obtained the high-performance liquid chromatography (HPLC) fingerprint of the extract. Phytochemical analysis by thin layer chromatography (TLC) was performed and the results were used to obtain the HPLC fingerprint. Acute toxicity of 300 and 2000mg/kg b.w. i.p. doses administered to mice for 14 days was evaluated. Genotoxicity was evaluated by counting the number of micronucleated polychromatic erythrocytes in the blood of mice that either received or did not receive the extract at 75, 150 and 300mg/kg b.w. per os. The anti-inflammatory effect of the same doses administered per os was investigated using the carrageenan air pouch model. The TLC analysis of the extract revealed the presence of a remarkable amount of flavonoids and cinnamic acids. The HPLC fingerprint showed the presence of one major peak corresponding to chlorogenic acid and two smaller peaks corresponding to flavonoids. In the toxicity assays, there were no deaths or deviations in behavior of treated mice as compared to the control at any dose. However, biochemical, hematological, and histological analyses showed that intraperitoneal injection caused several forms of damage to the mice, which were not observed in case of oral administration, studied in our previous work. Oral administration of the extract did

  19. ACUTE EFFECT OF ETHANOL ON HEPATIC RETICULAR G6Pase AND Ca2+ POOL

    PubMed Central

    Jacobs-Harper, Amy; Crumbly, Ashlee; Romani, Andrea

    2012-01-01

    Background Hydrolysis of glucose 6-phosphate via glucose 6-phosphatase enlarges the reticular Ca2+ pool of the hepatocyte. Exposure of liver cells to ethanol impairs reticular Ca2+ homeostasis. The present study investigated the effect of acute ethanol administration on glucose 6-phosphate supported Ca2+ accumulation in liver cells. Methods Total microsomes were isolated from rat livers acutely perfused with varying doses of ethanol (0.01%, 0.1%, or 1% v/v) for 8 minutes. Calcium uptake was assessed by 45Ca redistribution. Inorganic phosphate (Pi) formation was measured as an indicator of glucose 6-phosphatase hydrolytic activity. Results Glucose 6-phosphate-supported Ca2+ uptake decreased in a manner directly proportional to the dose of ethanol infused in the liver whereas Ca2+ uptake via SERCA pumps was decreased by ~25% only at the highest dose of alcohol administered. The reduced accumulation of Ca2+ within the microsomes resulted in a smaller IP3-induced Ca2+ release. Kinetic assessment of IP3 and passive Ca2+ release indicated a faster mobilization in microsomes from ethanol-treated livers, suggesting alcohol-induced alteration of Ca2+ releasing mechanisms. Pre-treatment of livers with chloromethiazole or dithio-threitol, but not 4-methyl-pyrazole prevented the inhibitory effect of ethanol on glucose 6-phosphatase activity and Ca2+ homeostasis. Conclusions Liver glucose 6-phosphatase activity and IP3-mediated Ca2+ release are rapidly inhibited following acute (8 min) exposure to ethanol, thus compromising the ability of the endoplasmic reticulum to dynamically modulate Ca2+ homeostasis in the hepatocyte. The protective effect of chloromethiazole and di-thio-threitol suggests that the inhibitory effect of ethanol is mediated through its metabolism via reticular cyP4502E1 and consequent free radicals formation. PMID:22958133

  20. Acute effects of triazolam on false recognition.

    PubMed

    Mintzer, M Z; Griffiths, R R

    2000-12-01

    Neuropsychological, neuroimaging, and electrophysiological techniques have been applied to the study of false recognition; however, psychopharmacological techniques have not been applied. Benzodiazepine sedative/anxiolytic drugs produce memory deficits similar to those observed in organic amnesia and may be useful tools for studying normal and abnormal memory mechanisms. The present double-blind, placebo-controlled repeated measures study examined the acute effects of orally administered triazolam (Halcion; 0.125 and 0.25 mg/70 kg), a benzodiazepine hypnotic, on performance in the Deese (1959)/Roediger-McDermott (1995) false recognition paradigm in 24 healthy volunteers. Paralleling previous demonstrations in amnesic patients, triazolam produced significant dose-related reductions in false recognition rates to nonstudied words associatively related to studied words, suggesting that false recognition relies on normal memory mechanisms impaired in benzodiazepine-induced amnesia. The results also suggested that relative to placebo, triazolam reduced participants' reliance on memory for item-specific versus list-common semantic information and reduced participants' use of remember versus know responses.

  1. Predicting the acute behavioral effects in rats inhaling toluene for up to 24 hrs: Inhaled vs, internal dose metrics and tolerance.

    EPA Science Inventory

    The acute toxicity of toluene, a model volatile organic compound (VOC), depends on the concentration (C) and duration (t) of exposure, and guidelines for acute exposures have traditionally used extrelationships to extrapolate protective and/or effective concentrations across dura...

  2. Acute effects of cocaine and cannabis on reversal learning as a function of COMT and DRD2 genotype.

    PubMed

    Spronk, Desirée B; Van der Schaaf, Marieke E; Cools, Roshan; De Bruijn, Ellen R A; Franke, Barbara; van Wel, Janelle H P; Ramaekers, Johannes G; Verkes, Robbert J

    2016-01-01

    Long-term cannabis and cocaine use has been associated with impairments in reversal learning. However, how acute cannabis and cocaine administration affect reversal learning in humans is not known. In this study, we aimed to establish the acute effects of administration of cannabis and cocaine on valence-dependent reversal learning as a function of DRD2 Taq1A (rs1800497) and COMT Val108/158Met (rs4680) genotype. A double-blind placebo-controlled randomized 3-way crossover design was used. Sixty-one regular poly-drug users completed a deterministic reversal learning task under the influence of cocaine, cannabis, and placebo that enabled assessment of both reward- and punishment-based reversal learning. Proportion correct on the reversal learning task was increased by cocaine, but decreased by cannabis. Effects of cocaine depended on the DRD2 genotype, as increases in proportion correct were seen only in the A1 carriers, and not in the A2/A2 homozygotes. COMT genotype did not modulate drug-induced effects on reversal learning. These data indicate that acute administration of cannabis and cocaine has opposite effects on reversal learning. The effects of cocaine, but not cannabis, depend on interindividual genetic differences in the dopamine D2 receptor gene.

  3. The Effects of Injury Magnitude on the Kinetics of the Acute Phase Response

    PubMed Central

    Bauzá, Graciela; Miller, Glenn; Kaseje, Neema; Wigner, Nathan A.; Wang, Zhongyan; Gerstenfeld, Louis C.; Burke, Peter A.

    2013-01-01

    Background The acute-phase response (APR) is critical to the body's ability to successfully respond to injury. A murine model of closed unilateral femur fractures and bilateral femur fracture were used to study the effect of injury magnitude on this response. Methods Standardized unilateral femur fracture and bilateral femur fracture in mice were performed. The femur fracture sites, livers, and serum were harvested over time after injury. Changes in mRNA expression of cytokines, hepatic acute-phase proteins, and serum cytokines overtime were measured. Results There was a rapid and short-lived hepatic APR to fracture injuries. The overall pattern in both models was similar. Both acute-phase proteins' mRNA (fibrinogen-γ and serum amyloid A-3) showed increased mRNA expression over baseline within the first 48 hours and their levels positively correlated with the extent of injury. However, increased severity of injury resulted in a delayed induction of the APR. A similar effect on the gene expression of cytokines (interleukin [IL]-1β, IL-6, and tumor necrosis factor-α) at the fracture site was seen. Serum IL-6 levels increased with increased injury and showed no delay between injury models. Conclusions Greater severity of injury resulted in a delayed induction of the liver's APR and a diminished expression of cytokines at the fracture site. Serum IL-6 levels were calibrated to the extent of the injury, and changes may represent mechanisms by which the local organ responses to injury are regulated by the injury magnitude. PMID:20693926

  4. The acute effect of ethanol on adrenal cortex in female rats--possible role of nitric oxide.

    PubMed

    Dikić, Dragoslava; Budeč, Mirela; Vranješ-Durić, Sanja; Koko, Vesna; Vignjević, Sanja; Mitrović, Olivera

    2011-01-01

    The present study was designed to investigate a possible role of endogenous nitric oxide (NO) in the adrenal response to an acute alcohol administration in female rats. To this end, N(ω)-nitro-L-arginine-methyl ester (L-NAME), a competitive inhibitor of all isoforms of NO synthase, was used. Adult female Wistar rats showing diestrus Day 1 were treated with: (a) ethanol (2 or 4 g/kg, intraperitoneally); (b) L-NAME (30 or 50 mg/kg, subcutaneously) followed by either ethanol or saline 3 h later. Untreated and saline-injected rats were used as controls. The animals were killed 30 min after last injection. Adrenal cortex was analyzed morphometrically, and plasma levels of adrenocorticotropic hormone (ACTH) and serum concentrations of corticosterone were determined. Acute ethanol treatment enhanced the levels of ACTH and corticosterone in a dose-dependent manner. Stereological analysis revealed that acute alcohol administration induced a significant increase in absolute volume of the cortex and the zona fasciculata (ZF). In addition, ethanol at a dose of 4 g/kg increased volume density and length of the capillaries in the ZF. However, other stereological parameters were unaffected by alcohol exposure. Pretreatment with both doses of L-NAME had no effect on ethanol-induced changes. Obtained findings indicate that acute ethanol treatment stimulates the activity of the adrenal cortex and that this effect is not mediated by endogenous NO in female rats under these experimental conditions.

  5. Acute antidepressant effects of right unilateral ultra-brief ECT: a double-blind randomised controlled trial.

    PubMed

    Mayur, Prashanth; Byth, Karen; Harris, Anthony

    2013-07-01

    Shortening the pulse width to 0.3 ms holds neurophysiological and clinical promise of making ECT safer by limiting cognitive side effects. However, the antidepressant effects of right ultra-brief unilateral ECT are under contention. In an acute ECT course, antidepressant equivalence of ultra-brief right unilateral ECT to the high-dose brief pulse right unilateral ECT was investigated. Severely depressed patients were randomised to 1 ms-brief pulse (n=18) or 0.3 ms ultra-brief pulse (n=17) right unilateral ECT, both at high-dose (6 times threshold stimulus dose) given thrice weekly. Depression severity was measured using the Montgomery Asberg Depression Rating Scale at baseline, after 8 treatments and after the acute course of ECT. Depression severity declined equally in both groups: F (1.27,41.97)=0.31, p=0.63. Median time in days to remission (95%CI) was in brief pulse ECT: 26 (18.6-33.4) and ultra-brief pulse ECT:28 (17.9-38.0). The small sample study in the study increases the likelihood of type 2 error. In severe depression, high-dose ultra-brief right unilateral ECT appears to show matching acute antidepressant response to an equally high-dose brief pulse right unilateral ECT. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. A CHRNA5 Smoking Risk Variant Decreases the Aversive Effects of Nicotine in Humans.

    PubMed

    Jensen, Kevin P; DeVito, Elise E; Herman, Aryeh I; Valentine, Gerald W; Gelernter, Joel; Sofuoglu, Mehmet

    2015-11-01

    Genome-wide association studies have implicated the CHRNA5-CHRNA3-CHRNB4 gene cluster in risk for heavy smoking and several smoking-related disorders. The heavy smoking risk allele might reduce the aversive effects of nicotine, but this hypothesis has not been tested in humans. We evaluated the effects of a candidate causal variant in CHRNA5, rs16969968, on the acute response to nicotine in European American (EA) and African American (AA) smokers (n=192; 50% AA; 73% male). Following overnight abstinence from nicotine, participants completed a protocol that included an intravenous (IV) dose of saline and two escalating IV doses of nicotine. The outcomes evaluated were the aversive, pleasurable, and stimulatory ratings of nicotine's effects, cardiovascular reactivity to nicotine, withdrawal severity, and cognitive performance before and after the nicotine administration session. The heavy smoking risk allele (rs16969968*A; frequency=28% (EA) and 6% (AA)) was associated with lower ratings of aversive effects (P<5 × 10(-8)) with marked specificity. This effect was evident in EA and AA subjects analyzed as separate groups and was most robust at the highest nicotine dose. Rs16969968*A was also associated with greater improvement on a measure of cognitive control (Stroop Task) following nicotine administration. These findings support differential aversive response to nicotine as one likely mechanism for the association of CHRNA5-CHRNA3-CHRNB4 with heavy smoking.

  7. Diurnal Spectral Sensitivity of the Acute Alerting Effects of Light

    PubMed Central

    Rahman, Shadab A.; Flynn-Evans, Erin E.; Aeschbach, Daniel; Brainard, George C.; Czeisler, Charles A.; Lockley, Steven W.

    2014-01-01

    Study Objectives: Previous studies have demonstrated short-wavelength sensitivity for the acute alerting response to nocturnal light exposure. We assessed daytime spectral sensitivity in alertness, performance, and waking electroencephalogram (EEG). Design: Between-subjects (n = 8 per group). Setting: Inpatient intensive physiologic monitoring unit. Participants: Sixteen healthy young adults (mean age ± standard deviation = 23.8 ± 2.7 y). Interventions: Equal photon density exposure (2.8 × 1013 photons/cm2/s) to monochromatic 460 nm (blue) or 555 nm (green) light for 6.5 h centered in the middle of the 16-h episode of wakefulness during the biological day. Results were compared retrospectively to 16 individuals who were administered the same light exposure during the night. Measurements and Results: Daytime and nighttime 460-nm light exposure significantly improved auditory reaction time (P < 0.01 and P < 0.05, respectively) and reduced attentional lapses (P < 0.05), and improved EEG correlates of alertness compared to 555-nm exposure. Whereas subjective sleepiness ratings did not differ between the two spectral conditions during the daytime (P > 0.05), 460-nm light exposure at night significantly reduced subjective sleepiness compared to 555-nm light exposure at night (P < 0.05). Moreover, nighttime 460-nm exposure improved alertness to near-daytime levels. Conclusions: The alerting effects of short-wavelength 460-nm light are mediated by counteracting both the circadian drive for sleepiness and homeostatic sleep pressure at night, but only via reducing the effects of homeostatic sleep pressure during the day. Citation: Rahman SA; Flynn-Evans EE; Aeschbach D; Brainard GC; Czeisler CA; Lockley SW. Diurnal spectral sensitivity of the acute alerting effects of light. SLEEP 2014;37(2):271-281. PMID:24501435

  8. The effects of a multiflavonoid supplement on vascular and hemodynamic parameters following acute exercise.

    PubMed

    Kappus, Rebecca M; Curry, Chelsea D; McAnulty, Steve; Welsh, Janice; Morris, David; Nieman, David C; Soukup, Jeffrey; Collier, Scott R

    2011-01-01

    Antioxidants can decrease oxidative stress and combined with acute exercise they may lead to further decreases in blood pressure. The purpose of this study was to investigate the effects of 2 weeks of antioxidant supplementation on vascular distensibility and cardiovascular hemodynamics during postexercise hypotension. Twenty young subjects were randomized to placebo (n = 10) or antioxidant supplementation (n = 10) for two weeks. Antioxidant status, vascular distensibility, and hemodynamics were obtained before, immediately, and 30 minutes after an acute bout of aerobic exercise both before and after supplementation. Two weeks of antioxidant supplementation resulted in a greater systolic blood pressure (SBP) decrease during postexercise hypotension (PEH) and significant decreases in augmentation index versus placebo (12.5% versus 3.5%, resp.). Also ferric-reducing ability of plasma (FRAP) increased significantly (interaction P = 0.024) after supplementation. Supplementation showed an additive effect on PEH associated with increased FRAP values and decreases in systolic blood pressure and augmentation index.

  9. The Effects of a Multiflavonoid Supplement on Vascular and Hemodynamic Parameters following Acute Exercise

    PubMed Central

    Kappus, Rebecca M.; Curry, Chelsea D.; McAnulty, Steve; Welsh, Janice; Morris, David; Nieman, David C.; Soukup, Jeffrey; Collier, Scott R.

    2011-01-01

    Antioxidants can decrease oxidative stress and combined with acute exercise they may lead to further decreases in blood pressure. The purpose of this study was to investigate the effects of 2 weeks of antioxidant supplementation on vascular distensibility and cardiovascular hemodynamics during postexercise hypotension. Methods. Twenty young subjects were randomized to placebo (n = 10) or antioxidant supplementation (n = 10) for two weeks. Antioxidant status, vascular distensibility, and hemodynamics were obtained before, immediately, and 30 minutes after an acute bout of aerobic exercise both before and after supplementation. Results. Two weeks of antioxidant supplementation resulted in a greater systolic blood pressure (SBP) decrease during postexercise hypotension (PEH) and significant decreases in augmentation index versus placebo (12.5% versus 3.5%, resp.). Also ferric-reducing ability of plasma (FRAP) increased significantly (interaction P = 0.024) after supplementation. Conclusion. Supplementation showed an additive effect on PEH associated with increased FRAP values and decreases in systolic blood pressure and augmentation index. PMID:22191012

  10. Recent advances on the stimulatory effects of metals in breast cancer.

    PubMed

    Lappano, Rosamaria; Malaguarnera, Roberta; Belfiore, Antonino; Maggiolini, Marcello

    2017-12-05

    Certain environmental chemicals may accumulate in human serum and tissues eliciting estrogenic and/or carcinogenic effects. Therefore, there is heightened interest in determining whether environmental chemicals may increase the risk for endocrine-related tumors like breast cancer. For instance, metals as cadmium, zinc, copper, iron, nickel and aluminum have been shown to mimic estrogen action. Moreover, the exposure to these chemicals has been reported to stimulate diverse malignancies including breast cancer, which is the most common tumor in women worldwide. In this review, we summarize the epidemiologic and experimental evidence regarding the association between the exposure to some trace elements and breast cancer risk. We also address recent insights on the molecular mechanisms involved by metals in breast tumorigenesis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Effect of social networks and well-being on acute care needs.

    PubMed

    Sintonen, Sanna; Pehkonen, Aini

    2014-01-01

    The effect of social surroundings has been noted as an important component of the well-being of elderly people. A strong social network and strong and steady relationships are necessary for coping when illness or functional limitations occur in later life. Vulnerability can affect well-being and functioning particularly when sudden life changes occur. The objective of this study was to analyse how the determinants of social well-being affect individual acute care needs when sudden life changes occur. Empirical evidence was collected using a cross-sectional mail survey in Finland in January 2011 among individuals aged 55-79 years. The age-stratified random sample covered 3000 individuals, and the eventual response rate was 56% (1680). Complete responses were received from 1282 respondents (42.7%). The study focuses on the compactness of social networks, social disability, the stability of social relationships and the fear of loneliness as well as how these factors influence acute care needs. The measurement was based on a latent factor structure, and the key concepts were measured using two ordinal items. The results of the structural model suggest that the need for care is directly affected by social disability and the fear of loneliness. In addition, social disability is a determinant of the fear of loneliness and therefore plays an important role if sudden life changes occur. The compactness of social networks decreases social disability and partly diminishes the fear of loneliness and therefore has an indirect effect on the need for care. The stability of social relationships was influenced by the social networks and disability, but was an insignificant predictor of care needs. To conclude, social networks and well-being can decrease care needs, and supportive actions should be targeted to avoid loneliness and social isolation so that the informal network could be applied as an aspect of care-giving when acute life changes occur. © 2013 John Wiley & Sons Ltd.

  12. Pharmacologic therapy for acute pancreatitis

    PubMed Central

    Kambhampati, Swetha; Park, Walter; Habtezion, Aida

    2014-01-01

    While conservative management such as fluid, bowel rest, and antibiotics is the mainstay of current acute pancreatitis management, there is a lot of promise in pharmacologic therapies that target various aspects of the pathogenesis of pancreatitis. Extensive review of preclinical studies, which include assessment of therapies such as anti-secretory agents, protease inhibitors, anti-inflammatory agents, and anti-oxidants are discussed. Many of these studies have shown therapeutic benefit and improved survival in experimental models. Based on available preclinical studies, we discuss potential novel targeted pharmacologic approaches that may offer promise in the treatment of acute pancreatitis. To date a variety of clinical studies have assessed the translational potential of animal model effective experimental therapies and have shown either failure or mixed results in human studies. Despite these discouraging clinical studies, there is a great clinical need and there exist several preclinical effective therapies that await investigation in patients. Better understanding of acute pancreatitis pathophysiology and lessons learned from past clinical studies are likely to offer a great foundation upon which to expand future therapies in acute pancreatitis. PMID:25493000

  13. Acute Effects of Carbohydrate Supplementation on Intermittent Sports Performance.

    PubMed

    Baker, Lindsay B; Rollo, Ian; Stein, Kimberly W; Jeukendrup, Asker E

    2015-07-14

    Intermittent sports (e.g., team sports) are diverse in their rules and regulations but similar in the pattern of play; that is, intermittent high-intensity movements and the execution of sport-specific skills over a prolonged period of time (~1-2 h). Performance during intermittent sports is dependent upon a combination of anaerobic and aerobic energy systems, both of which rely on muscle glycogen and/or blood glucose as an important substrate for energy production. The aims of this paper are to review: (1) potential biological mechanisms by which carbohydrate may impact intermittent sport performance; (2) the acute effects of carbohydrate ingestion on intermittent sport performance, including intermittent high-intensity exercise capacity, sprinting, jumping, skill, change of direction speed, and cognition; and (3) what recommendations can be derived for carbohydrate intake before/during exercise in intermittent sports based on the available evidence. The most researched intermittent sport is soccer but some sport-specific studies have also been conducted in other sports (e.g., rugby, field hockey, basketball, American football, and racquet sports). Carbohydrate ingestion before/during exercise has been shown in most studies to enhance intermittent high-intensity exercise capacity. However, studies have shown mixed results with regards to the acute effects of carbohydrate intake on sprinting, jumping, skill, change of direction speed, and cognition. In most of these studies the amount of carbohydrate consumed was ~30-60 g/h in the form of a 6%-7% carbohydrate solution comprised of sucrose, glucose, and/or maltodextrin. The magnitude of the impact that carbohydrate ingestion has on intermittent sport performance is likely dependent on the carbohydrate status of the individual; that is, carbohydrate ingestion has the greatest impact on performance under circumstances eliciting fatigue and/or hypoglycemia. Accordingly, carbohydrate ingestion before and during a game

  14. Strain-Dependent Effects of Acute Alcohol on Synaptic Vesicle Recycling and Post-Tetanic Potentiation in Medial Glutamate Inputs to the Mouse Basolateral Amygdala.

    PubMed

    Gioia, Dominic A; McCool, Brian

    2017-04-01

    Inbred mouse strains are differentially sensitive to the acute effects of ethanol (EtOH) and are useful tools for examining how unique genomes differentially affect alcohol-related behaviors and physiology. DBA/2J mice have been shown to be sensitive to the acute anxiolytic effects of alcohol as well as the anxiogenic effects of withdrawal from chronic alcohol exposure, while B6 mice are resistant to both. Considering that the basolateral amygdala (BLA) is an important brain region for the acute and chronic effects of EtOH on fear and anxiety related behaviors, we hypothesized that there would be strain-dependent differences in the acute effects of EtOH in BLA slices. We utilized patch clamp electrophysiology in BLA coronal slices from 4 inbred mouse strains (A/J, BALBcJ, C57BL/6J, and DBA/2J) to examine how genetic background influences acute EtOH effects on synaptic vesicle recycling and post-tetanic potentiation (PTP) in response to low (2 Hz)- and high (40 Hz)-frequency stimulation. We found that EtOH inhibited synaptic vesicle recycling in a strain- and stimulation frequency-dependent manner. Vesicle recycling in DBA/2J and BALBcJ cells was inhibited by acute EtOH during both low- and high-frequency stimulation, while recycling measured from A/J cells was sensitive only during high-frequency stimulation. Recycling at C57BL/6J synapses was insensitive to EtOH regardless of stimulation frequency. We additionally found that cells from DBA/2J and BALBcJ mice were sensitive to EtOH-mediated inhibition of PTP. Acute EtOH application inhibited vesicle recycling and PTP at glutamatergic synapses in both a strain- and frequency-dependent fashion. Several presynaptic proteins that contribute to synaptic vesicle priming in addition to PTP have been implicated in alcohol-related behaviors, including Munc13, Munc18, and RIM proteins, making them potential candidates for the molecular mechanism controlling these effects. Copyright © 2017 by the Research Society on

  15. Developmental Effects of Acute, Chronic, and Withdrawal from Chronic Nicotine on Fear Conditioning

    PubMed Central

    Portugal, George S.; Wilkinson, Derek S.; Turner, Jill R.; Blendy, Julie A.; Gould, Thomas J.

    2012-01-01

    Pre-adolescence and adolescence are developmental periods associated with increased vulnerability for tobacco addiction, and exposure to tobacco during these periods may lead to long-lasting changes in behavioral and neuronal plasticity. The present study examined the short- and long-term effects of nicotine and nicotine withdrawal on fear conditioning in pre-adolescent, adolescent, and adult mice, and potential underlying substrates that may mediate the developmental effects of nicotine, such as changes in nicotinic acetylcholine receptor (nAChR) binding, CREB expression, and nicotine metabolism. Age-related differences existed in sensitivity to the effects of acute nicotine, chronic nicotine and nicotine withdrawal on contextual fear conditioning (no changes in cued fear conditioning were seen); younger mice were more sensitive to the acute effects and less sensitive to the effects of nicotine withdrawal 24 hours post treatment cessation. Developmental differences in nAChR binding were associated with the effects of nicotine withdrawal on contextual learning. Developmental differences in nicotine metabolism and CREB expression were also observed, but were not related to the effects of nicotine withdrawal on contextual learning 24 hours post treatment. Chronic nicotine exposure during pre-adolescence or adolescence, however, produced long-lasting impairments in contextual learning that were observed during adulthood, whereas adult chronic nicotine exposure did not. These developmental effects could be related to changes in CREB. Overall, there is a developmental shift in the effects of nicotine on hippocampus-dependent learning and developmental exposure to nicotine results in adult cognitive deficits; these changes in cognition may play an important role in the development and maintenance of nicotine addiction. PMID:22521799

  16. Effect of acute aerobic exercise on vaccine efficacy in older adults.

    PubMed

    Ranadive, Sushant Mohan; Cook, Marc; Kappus, Rebecca Marie; Yan, Huimin; Lane, Abbi Danielle; Woods, Jeffery A; Wilund, Kenneth R; Iwamoto, Gary; Vanar, Vishwas; Tandon, Rudhir; Fernhall, Bo

    2014-03-01

    The most effective way of avoiding influenza is through influenza vaccination. However, the vaccine is ineffective in about 25% of the older population. Immunosenescence with advancing age results in inadequate protection from disease because of ineffective responses to vaccination. Recently, a number of strategies have been tested to improve the efficacy of a vaccine in older adults. An acute bout of moderate aerobic exercise may increase the efficacy of the vaccine in young individuals, but there are limited efficacy data in older adults who would benefit most. This study sought to evaluate whether acute moderate-intensity endurance exercise immediately before influenza vaccination would increase the efficacy of the vaccine. Fifty-nine healthy volunteers between 55 and 75 yr of age were randomly allocated to an exercise or control group. Antibody titers were measured at baseline before exercise and 4 wk after vaccination. C-reactive protein (CRP) and interleukin-6 (IL-6) were measured at 24 and 48 h after vaccination. Delta CRP and IL-6 at 24 and 48 h were significantly higher after vaccination as compared to the sham injection. There were no differences in the levels of antibody titers against the H3N2 influenza strain between groups. However, women in the exercise group had a significantly higher antibody response against the H1N1 influenza strain as compared to the men, probably because of lower prevaccine titers. There were no significant differences in seroprotection between groups. Acute moderate aerobic exercise was not immunostimulatory in healthy older men but may serve as a vaccine adjuvant in older women.

  17. Behavioral economic analysis of stress effects on acute motivation for alcohol.

    PubMed

    Owens, Max M; Ray, Lara A; MacKillop, James

    2015-01-01

    Due to issues of definition and measurement, the heavy emphasis on subjective craving in the measurement of acute motivation for alcohol and other drugs remains controversial. Behavioral economic approaches have increasingly been applied to better understand acute drug motivation, particularly using demand curve modeling via purchase tasks to characterize the perceived reinforcing value of the drug. This approach has focused on using putatively more objective indices of motivation, such as units of consumption, monetary expenditure, and price sensitivity. To extend this line of research, the current study used an alcohol purchase task to determine if, compared to a neutral induction, a personalized stress induction would increase alcohol demand in a sample of heavy drinkers. The stress induction significantly increased multiple measures of the reinforcing value of alcohol to the individual, including consumption at zero price (intensity), the maximum total amount of money spent on alcohol (Omax), the first price where consumption was reduced to zero (breakpoint), and the general responsiveness of consumption to increases in price (elasticity). These measures correlated only modestly with craving and mood. Self-reported income was largely unrelated to demand but moderated the influence of stress on Omax. Moderation based on CRH-BP genotype (rs10055255) was present for Omax, with T allele homozygotes exhibiting more pronounced increases in response to stress. These results provide further support for a behavioral economic approach to measuring acute drug motivation. The findings also highlight the potential relevance of income and genetic factors in understanding state effects on the perceived reinforcing value of alcohol. © Society for the Experimental Analysis of Behavior.

  18. Modifications in adrenal hormones response to ethanol by prior ethanol dependence.

    PubMed

    Guaza, C; Borrell, S

    1985-03-01

    Ethanol was administered to rats by means of a liquid diet for 16 days; after an ethanol-free interval of four weeks, animals received a test (IP) dose of ethanol (2 g/kg), and the adrenocortical and adrenomedullary responses were evaluated. Chronically ethanol-exposed animals showed tolerance to the stimulatory effect of ethanol in the pituitary-adrenal axis. Likewise, previously dependent rats showed tolerance to the increase in the activity of the adrenomedullary function induced by acute administration of the drug. Our results indicate that chronic ethanol ingestion can induce persistent changes after complete alcohol abstinence.

  19. Brain Function in Young Patients Receiving Methotrexate for Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2017-07-19

    Childhood B Acute Lymphoblastic Leukemia; Childhood T Acute Lymphoblastic Leukemia; Cognitive Side Effects of Cancer Therapy; Long-Term Effects Secondary to Cancer Therapy in Children; Neurotoxicity Syndrome; Psychological Impact of Cancer; Untreated Childhood Acute Lymphoblastic Leukemia

  20. Effects of acute psychological stress on placebo and nocebo responses in a clinically relevant model of visceroception.

    PubMed

    Roderigo, Till; Benson, Sven; Schöls, Margarita; Hetkamp, Madeleine; Schedlowski, Manfred; Enck, Paul; Elsenbruch, Sigrid

    2017-08-01

    There is evidence to suggest a role of emotions in placebo and nocebo effects, but whether acute psychological stress changes the magnitude of placebo or nocebo responses has not been tested. In a clinically relevant model of visceroception, we assessed effects of acute psychological stress on changes in urgency and pain in response to positive or negative treatment suggestions. In 120 healthy volunteers, perceived urge-to-defecate and pain in response to individually calibrated rectal distensions were measured with visual analogue scales during a BASELINE. Participants then underwent the Trier Social Stress Test (N = 60) or a simple cognitive task (control, N = 60) and were randomized to positive (placebo), negative (nocebo), or neutral treatment information regarding intravenous administration of saline. The series of distensions was repeated, and changes in visual analogue scales from BASELINE to TEST were compared between groups using analysis of covariance and planned post hoc tests. Treatment information emerged as a main factor (P <0.001), supporting treatment information effects for both urgency and pain. Effects for urgency were modulated by stress (interaction effect: P <0.05): Positive information reduced urgency (P = 0.025), while negative information increased urgency (P = 0.026) only in stressed groups. For pain, effects of stress emerged for nocebo responses, which were only evident in stressed groups (P = 0.009). This is the first experimental study supporting effects of acute psychological stress on placebo and nocebo responses in visceroception. Results call for mechanistic as well as patient studies to assess how psychological stress shapes patients' treatment expectations and thereby affects health outcomes.

  1. Cost-effectiveness of clopidogrel-aspirin versus aspirin alone for acute transient ischemic attack and minor stroke.

    PubMed

    Pan, Yuesong; Wang, Anxin; Liu, Gaifen; Zhao, Xingquan; Meng, Xia; Zhao, Kun; Liu, Liping; Wang, Chunxue; Johnston, S Claiborne; Wang, Yilong; Wang, Yongjun

    2014-06-05

    Treatment with the combination of clopidogrel and aspirin taken soon after a transient ischemic attack (TIA) or minor stroke was shown to reduce the 90-day risk of stroke in a large trial in China, but the cost-effectiveness is unknown. This study sought to estimate the cost-effectiveness of the clopidogrel-aspirin regimen for acute TIA or minor stroke. A Markov model was created to determine the cost-effectiveness of treatment of acute TIA or minor stroke patients with clopidogrel-aspirin compared with aspirin alone. Inputs for the model were obtained from clinical trial data, claims databases, and the published literature. The main outcome measure was cost per quality-adjusted life-years (QALYs) gained. One-way and multivariable probabilistic sensitivity analyses were performed to test the robustness of the findings. Compared with aspirin alone, clopidogrel-aspirin resulted in a lifetime gain of 0.037 QALYs at an additional cost of CNY 1250 (US$ 192), yielding an incremental cost-effectiveness ratio of CNY 33 800 (US$ 5200) per QALY gained. Probabilistic sensitivity analysis showed that clopidogrel-aspirin therapy was more cost-effective in 95.7% of the simulations at a willingness-to-pay threshold recommended by the World Health Organization of CNY 105 000 (US$ 16 200) per QALY. Early 90-day clopidogrel-aspirin regimen for acute TIA or minor stroke is highly cost-effective in China. Although clopidogrel is generic, Plavix is brand in China. If Plavix were generic, treatment with clopidogrel-aspirin would have been cost saving. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  2. The acute effects of grape polyphenols supplementation on endothelial function in adults: meta-analyses of controlled trials.

    PubMed

    Li, Shao-Hua; Tian, Hong-Bo; Zhao, Hong-Jin; Chen, Liang-Hua; Cui, Lian-Qun

    2013-01-01

    The acute effects of grape polyphenols on endothelial function in adults are inconsistent. Here, we performed meta-analyses to determine these acute effects as measured by flow-mediated dilation (FMD). Trials were searched in PubMed, Embase and the Cochrane Library database. Summary estimates of weighted mean differences (WMDs) and 95% CIs were obtained by using random-effects models. Meta-regression and subgroup analyses were performed to identify the source of heterogeneity. The protocol details of our meta-analysis have been submitted to the PROSPERO register and our registration number is CRD42013004157. Nine studies were included in the present meta-analyses. The results showed that the FMD level was significantly increased in the initial 120 min after intake of grape polyphenols as compared with controls. Meta-regression and subgroup analyses were performed and showed that a health status was the main effect modifier of the significant heterogeneity. Subgroups indicated that intake of grape polyphenols could significantly increase FMD in healthy subjects, and the increased FMD appeared to be more obviously in subjects with high cardiovascular risk factors. Moreover, the peak effect of grape polyphenols on FMD in healthy subjects was found 30 min after ingestion, which was different from the effect in subjects with high cardiovascular risk factors, in whom the peak effect was found 60 min after ingestion. Endothelial function can be significantly improved in healthy adults in the initial 2 h after intake of grape polyphenols. The acute effect of grape polyphenols on endothelial function may be more significant but the peak effect is delayed in subjects with a smoking history or coronary heart disease as compared with the healthy subjects.

  3. Effect of TPA on ion fluxes and DNA synthesis in vascular smooth muscle cells

    PubMed Central

    1985-01-01

    Previous reports have suggested that phorbol esters can decrease the affinity of epidermal growth factor (EGF) for its cellular receptors. Investigations of the consequences of the interaction between phorbol esters and EGF, however, have been limited to EGF-stimulated Na/H exchange in A431 cells (Whitely, B., D. Cassel, Y.-X. Zuang, and L. Glaser, 1984, J. Cell Biol., 99:1162-1166). In the present study, the effect of the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA) on EGF-stimulated ion transport and DNA synthesis was determined in cultured vascular smooth muscle cells (A7r5). It was found that TPA stimulated Na/H exchange when added alone (half-maximal stimulatory concentration, 25 nM). However, when cells were pretreated with TPA and then challenged with EGF, TPA significantly inhibited EGF-stimulated Na/H exchange (78%; half-maximal inhibition [Ki] at 2.5 nM). Subsequently the effects of TPA on Na/K/Cl co-transport were measured. TPA was observed to inhibit Na/K/Cl co-transport (half-maximal inhibitory concentration, 50 nM) and also to inhibit EGF-stimulated Na/K/Cl co-transport (100%; Ki at 5 nM). Finally, the effects of TPA on DNA synthesis were assessed. TPA had a modest stimulatory effect on DNA synthesis (half-maximal stimulatory concentration, 6 nM), but had a significant inhibitory effect on EGF-stimulated DNA synthesis (56%; Ki at 5 nM). These findings suggest that the inhibitory effect of TPA on EGF-receptor functions goes beyond previously reported effects on Na/H exchange in A431 cells and extends to EGF-stimulation of Na/K/Cl co- transport and DNA synthesis in vascular smooth muscle cells. PMID:2410432

  4. The acute effects of 3,4-methylenedioxymethamphetamine and d-methamphetamine on human cognitive functioning.

    PubMed

    Stough, Con; King, Rebecca; Papafotiou, Katherine; Swann, Phillip; Ogden, Edward; Wesnes, Keith; Downey, Luke A

    2012-04-01

    This study investigated the acute (3-h) and 24-h post-dose cognitive effects of oral 3,4-methylenedioxymethamphetamine (MDMA), d-methamphetamine, and placebo in a within-subject double-blind laboratory-based study in order to compare the effect of these two commonly used illicit drugs on a large number of recreational drug users. Sixty-one abstinent recreational users of illicit drugs comprised the participant sample, with 33 females and 28 males, mean age 25.45 years. The three testing sessions involved oral consumption of 100 mg MDMA, 0.42 mg/kg d-methamphetamine, or a matching placebo. The drug administration was counter-balanced, double-blind, and medically supervised. Cognitive performance was assessed during drug peak (3 h) and at 24 h post-dosing time-points. Blood samples were also taken to quantify the levels of drug present at the cognitive testing time-points. Blood concentrations of both methamphetamine and MDMA at drug peak samples were consistent with levels observed in previous studies. The major findings concern poorer performance in the MDMA condition at peak concentration for the trail-making measures and an index of working memory (trend level), and more accurate performance on a choice reaction task within the methamphetamine condition. Most of the differences in performance between the MDMA, methamphetamine, and placebo treatments diminished by the 24-h testing time-point, although some performance improvements subsisted for choice reaction time for the methamphetamine condition. Further research into the acute effects of amphetamine preparations is necessary to further quantify the acute disruption of aspects of human functioning crucial to complex activities such as attention, selective memory, and psychomotor performance.

  5. Effect of Fetal Membrane-Derived Mesenchymal Stem Cell Transplantation in Rats With Acute and Chronic Pancreatitis.

    PubMed

    Kawakubo, Kazumichi; Ohnishi, Shunsuke; Fujita, Hirotoshi; Kuwatani, Masaki; Onishi, Reizo; Masamune, Atsushi; Takeda, Hiroshi; Sakamoto, Naoya

    2016-01-01

    Mesenchymal stem cells (MSCs) are a valuable cell source in regenerative medicine and can be isolated from fetal membranes (FMs), particularly amniotic membranes. We investigated the effect of rat FM-derived MSCs (rFM-MSCs) and human amnion-derived MSCs (hAMSCs) on the inflammatory reaction in vitro and therapeutic effects in rats with acute and chronic pancreatitis. Effect of rFM-MSCs or hAMSC-conditioned medium was investigated in vitro. Acute pancreatitis was induced by intraductal injection of 4% taurocholate, and rFM-MSCs were transplanted intravenously. Chronic pancreatitis was induced by intravenous injection of 5 mg/kg dibutyltin dichloride, and hAMSCs were transplanted intravenously. The inflammatory reaction of macrophages induced by lipopolysaccharide and trypsin was significantly suppressed by rFM-MSC coculture. Pancreatic acinar cell injury induced by cerulein was significantly ameliorated by hAMSC-conditioned medium. Pancreatic stellate cell activation induced by tumor necrosis factor-α was significantly decreased by hAMSC-conditioned medium. Transplantation of rFM-MSCs significantly reduced the histological score and infiltration of CD68-positive macrophages in the rat pancreas. The hAMSC transplantation significantly decreased the expression of MCP-1 and attenuated the downregulation of amylase expression in the pancreas. Transplantation of FM-MSCs and AMSCs suppressed the inflammatory reaction of acute and chronic pancreatitis in rats.

  6. Experimental Effects of Acute Exercise on Iconic Memory, Short-Term Episodic, and Long-Term Episodic Memory.

    PubMed

    Yanes, Danielle; Loprinzi, Paul D

    2018-06-11

    The present experiment evaluated the effects of acute exercise on iconic memory and short- and long-term episodic memory. A two-arm, parallel-group randomized experiment was employed ( n = 20 per group; M age = 21 year). The experimental group engaged in an acute bout of moderate-intensity treadmill exercise for 15 min, while the control group engaged in a seated, time-matched computer task. Afterwards, the participants engaged in a paragraph-level episodic memory task (20 min delay and 24 h delay recall) as well as an iconic memory task, which involved 10 trials (at various speeds from 100 ms to 800 ms) of recalling letters from a 3 × 3 array matrix. For iconic memory, there was a significant main effect for time (F = 42.9, p < 0.001, η² p = 0.53) and a trend towards a group × time interaction (F = 2.90, p = 0.09, η² p = 0.07), but no main effect for group (F = 0.82, p = 0.37, η² p = 0.02). The experimental group had higher episodic memory scores at both the baseline (19.22 vs. 17.20) and follow-up (18.15 vs. 15.77), but these results were not statistically significant. These findings provide some suggestive evidence hinting towards an iconic memory and episodic benefit from acute exercise engagement.

  7. Losartan exerts no protective effects against acute pulmonary embolism-induced hemodynamic changes.

    PubMed

    Dias, Carlos A; Neto-Neves, Evandro M; Montenegro, Marcelo F; Tanus-Santos, Jose E

    2012-02-01

    The acute obstruction of pulmonary vessels by venous thrombi is a critical condition named acute pulmonary embolism (APE). During massive APE, severe pulmonary hypertension may lead to death secondary to right heart failure and circulatory shock. APE-induced pulmonary hypertension is aggravated by active pulmonary vasoconstriction. While blocking the effects of some vasoconstrictors exerts beneficial effects, no previous study has examined whether angiotensin II receptor blockers protect against the hemodynamic changes associated with APE. We examined the effects exerted by losartan on APE-induced hemodynamic changes. Hemodynamic evaluations were performed in non-embolized lambs treated with saline (n = 4) and in lambs that were embolized with silicon microspheres and treated with losartan (30 mg/kg followed by 1 mg/kg/h, n = 5) or saline (n = 7) infusions. The plasma and lung angiotensin-converting enzyme (ACE) activity were assessed using a fluorometric method. APE increased mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance index (PVRI) by 21 ± 2 mmHg and 375 ± 20 dyn s cm⁻⁵ m⁻², respectively (P < 0.05). Losartan decreased MPAP significantly (by approximately 15%), without significant changes in PVRI and tended to decrease cardiac index (P > 0.05). Lung and plasma ACE activity were similar in both embolized and non-embolized animals. Our findings show evidence of lack of activation of the renin-angiotensin system during APE. The lack of significant effects of losartan on the pulmonary vascular resistance suggests that losartan does not protect against the hemodynamic changes found during APE.

  8. Effect of Acute Negative and Positive Energy Balance on Basal Very-Low Density Lipoprotein Triglyceride Metabolism in Women

    PubMed Central

    Bellou, Elena; Maraki, Maria; Magkos, Faidon; Botonaki, Helena; Panagiotakos, Demosthenes B.; Kavouras, Stavros A.; Sidossis, Labros S.

    2013-01-01

    Background Acute reduction in dietary energy intake reduces very low-density lipoprotein triglyceride (VLDL-TG) concentration. Although chronic dietary energy surplus and obesity are associated with hypertriglyceridemia, the effect of acute overfeeding on VLDL-TG metabolism is not known. Objective The aim of the present study was to investigate the effects of acute negative and positive energy balance on VLDL-TG metabolism in healthy women. Design Ten healthy women (age: 22.0±2.9 years, BMI: 21.2±1.3 kg/m2) underwent a stable isotopically labeled tracer infusion study to determine basal VLDL-TG kinetics after performing, in random order, three experimental trials on the previous day: i) isocaloric feeding (control) ii) hypocaloric feeding with a dietary energy restriction of 2.89±0.42 MJ and iii) hypercaloric feeding with a dietary energy surplus of 2.91±0.32 MJ. The three diets had the same macronutrient composition. Results Fasting plasma VLDL-TG concentrations decreased by ∼26% after hypocaloric feeding relative to the control trial (P = 0.037), owing to decreased hepatic VLDL-TG secretion rate (by 21%, P = 0.023) and increased VLDL-TG plasma clearance rate (by ∼12%, P = 0.016). Hypercaloric feeding increased plasma glucose concentration (P = 0.042) but had no effect on VLDL-TG concentration and kinetics compared to the control trial. Conclusion Acute dietary energy deficit (∼3MJ) leads to hypotriglyceridemia via a combination of decreased hepatic VLDL-TG secretion and increased VLDL-TG clearance. On the other hand, acute dietary energy surplus (∼3MJ) does not affect basal VLDL-TG metabolism but disrupts glucose homeostasis in healthy women. PMID:23533676

  9. Synergistic effects of Isatis tinctoria L. and tacrolimus in the prevention of acute heart rejection in mice.

    PubMed

    Wang, Yongzhi; Qin, Qing; Chen, Jibing; Kuang, Xiaocong; Xia, Junjie; Xie, Baiyi; Wang, Feng; Liang, Hua; Qi, Zhongquan

    2009-12-01

    Although immunosuppressive treatments are available for acute cardiac rejection no viable treatment exists for long-term cardiac graft failure. Moreover, the extended use of calcineurin inhibitor immunosuppressants, the mainstay of current treatment for cardiac transplantation, leads to significant side effects such as nephrotoxicity and an increased risk of cardiac disease. Because some agents used in Traditional Chinese Medicine (TCM) have strong immunosuppressive effects coupled with low toxicity, we investigated the effect of Compound K (K), the synthesized analogue of highly unsaturated fatty acids from Isatis tinctoria L., either as a single treatment or combined with tacrolimus (FK-506) on acute cardiac allograft rejection. We compared the ability of K alone, or in combination with FK-506, to inhibit acute heart transplant rejection both in vitro and in vivo. We found that the inhibition of lymphocyte proliferation was positively correlated with K concentration. K significantly reduced IL-2 and IFN-gamma expression levels and significantly inhibited lymphocyte proliferation in both a lymphocyte transformation test and a mixed lymphocyte reaction (MLR). We also found that the inhibitory effect of a combination of K and a sub-therapeutic dose of FK-506 (SubFK-506) was stronger than that of full-dose FK-506 alone. Oral administration of K reduced acute cardiac allograft rejection in mice and had no apparent toxicity. In vivo, the immunosuppressive effect of K combined with a half-dose of FK-506 was equivalent to that of a full-dose of FK-506 alone. K combined with a half-dose of FK-506 reduced the expression levels of IL-2 and IFN-gamma (both within the graft and in the recipients' serum) more effectively than a full-dose of FK-506. These results show that K has significant immunosuppressive effects both in vitro and in vivo. When used as a combination therapy with FK-506 we see a powerful inhibition of rejection with no obvious toxic side effects. The

  10. Protective effect of ALDH2 against cyclophosphamide-induced acute hepatotoxicity via attenuating oxidative stress and reactive aldehydes.

    PubMed

    Zhai, Xiaoxuan; Zhang, Zhenxiao; Liu, Wenwen; Liu, Baoshan; Zhang, Rui; Wang, Wenjun; Zheng, Wen; Xu, Feng; Wang, Jiali; Chen, Yuguo

    2018-04-30

    Cyclophosphamide (CY) is a widely used chemotherapeutic agent that is associated with severe side effects, such as hepatotoxicity and nephrotoxicity. However, the extent, mechanisms and potential prevention and treatment strategies of CY-induced acute hepatotoxicity and nephrotoxicity are largely unknown. In this study, we determined the existence and extent of CY-induced acute hepatotoxicity and nephrotoxicity, and demonstrated the effect of ALDH2 on CY-induced acute tissue toxicity and related mechanisms. Adult male C57BL/6J (wide-type, WT) and ALDH2 -/- (KO) mice were divided into four groups: WT, WT + CY, KO + CY and WT + CY + Alda-1. Biochemical analysis showed that plasma ALT was increased by 35.8% in KO + CY group and decreased by 21.1% in WT + CY + Alda-1 group compared to WT + CY group (P < 0.05, respectively). However, there was no significant difference among WT, WT + CY and KO + CY groups regarding plasma renal marker enzymes, including blood urea nitrogen (BUN), creatinine and cystatin C (CysC). Levels of reactive oxygen species (ROS) and toxic aldehydes (acrolein, 4-hydroxynonenol and malondialdehyde) were increased significantly in KO + CY group and decreased significantly in WT + CY + Alda-1 group compared to WT + CY group (P < 0.05, respectively). These findings demonstrate that CY could induce acute hepatotoxicity without nephrotoxicity, and ALDH2 plays a protective role in CY-induced acute hepatotoxicity. The underlying mechanisms are associated with attenuating oxidative stress and detoxifying reactive aldehydes. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Protective Effects of Lithospermum erythrorhizon Against Cerulein-Induced Acute Pancreatitis.

    PubMed

    Choi, Sun Bok; Bae, Gi-Sang; Jo, Il-Joo; Seo, Seung-Hee; Kim, Dong-Goo; Shin, Joon-Yeon; Hong, Seung-Heon; Choi, Byung-Min; Park, Sang-Hyun; Song, Ho-Joon; Park, Sung-Joo

    2015-01-01

    We aimed to evaluate the anti-inflammatory and inhibitory effects of Lithospermum erythrorhizon (LE) on cerulein-induced acute pancreatitis (AP) in a mouse model. Acute pancreatitis was induced via intraperitoneal injection of cerulein (50 μg/kg) every hour for 6 times. In the LE, water extract (100, 250, or 500 mg/kg) was administered intraperitoneally 1 hour before the first injection of cerulein. Six hours after AP, blood, the pancreas, and the lung were harvested for further examination. In addition, pancreatic acinar cells were isolated using a collagenase method, and then, we investigated the acinar cell viability and cytokine productions. Treatment with LE reduced pancreatic damage and AP-associated lung injury and attenuated the severity of AP, as evidenced by the reduction in neutrophil infiltration, serum amylase and lipase levels, trypsin activity, and proinflammatory cytokine expression. In addition, treatment with LE inhibited high mobility group box 1 expression in the pancreas during AP. In accordance with in vivo data, LE inhibited the cerulein-induced acinar cell death, cytokine productions, and high-mobility group box 1 expression. Furthermore, LE also inhibited the activation of p38 mitogen-activated protein kinases. These results suggest that LE plays a protective role during the development of AP by inhibiting the activation of p38.

  12. Acute effect of vigorous aerobic exercise on the inhibitory control in adolescents

    PubMed Central

    Browne, Rodrigo Alberto Vieira; Costa, Eduardo Caldas; Sales, Marcelo Magalhães; Fonteles, André Igor; de Moraes, José Fernando Vila Nova; Barros, Jônatas de França

    2016-01-01

    Abstract Objective: To assess the acute effect of vigorous aerobic exercise on the inhibitory control in adolescents. Methods: Controlled, randomized study with crossover design. Twenty pubertal individuals underwent two 30-minute sessions: (1) aerobic exercise session performed between 65% and 75% of heart rate reserve, divided into 5 min of warm-up, 20 min at the target intensity and 5 min of cool down; and (2) control session watching a cartoon. Before and after the sessions, the computerized Stroop test-Testinpacs™ was applied to evaluate the inhibitory control. Reaction time (ms) and errors (n) were recorded. Results: The control session reaction time showed no significant difference. On the other hand, the reaction time of the exercise session decreased after the intervention (p<0.001). The number of errors made at the exercise session were lower than in the control session (p=0.011). Additionally, there was a positive association between reaction time (Δ) of the exercise session and age (r 2=0.404, p=0.003). Conclusions: Vigorous aerobic exercise seems to promote acute improvement in the inhibitory control in adolescents. The effect of exercise on the inhibitory control performance was associated with age, showing that it was reduced at older age ranges. PMID:26564328

  13. Acute behavioural and neurotoxic effects of MDMA plus cocaine in adolescent mice.

    PubMed

    Daza-Losada, M; Rodríguez-Arias, M; Maldonado, C; Aguilar, M A; Guerri, C; Miñarro, J

    2009-01-01

    The poly-drug pattern is the most common among those observed in MDMA users, with cocaine being a frequently associated drug. This study evaluates the acute effects of MDMA (5, 10 and 20 mg/kg), alone or in combination with cocaine (25 mg/kg), on motor activity, anxiety (elevated plus maze and social interaction test), memory and brain monoamines in adolescent mice. Both drugs, administered alone or concurrently, produced hyperactivity and a decrease in social contacts. However, an anxiolytic effect, studied by means of the elevated plus maze and expressed as an increase in the time spent on the open arms, was observed only in those animals treated with cocaine and MDMA. The passive avoidance task was affected only with the highest MDMA dose (20 mg/kg). Mice treated with MDMA did not present significant changes in brain monoamines, while those receiving MDMA and cocaine showed a decrease in DA in the striatum, which was accompanied by an increase in the serotonin concentration in the striatum and cortex 30 min after acute administration. In conclusion, the combined use of MDMA and cocaine produces a predominance of serotonin over DA, which is associated with an anxiolytic profile, defensive behaviours and fewer social contacts.

  14. The effects of extracorporeal shockwave on acute high-energy long bone fractures of the lower extremity.

    PubMed

    Wang, Ching-Jen; Liu, Hao-Chen; Fu, Te-Hu

    2007-02-01

    High-energy long bone fractures of the lower extremity are at risk of poor fracture healing and high rate of non-union. Extracorporeal shockwave was shown effective to heal non-union of long bone fracture. However, the effect of shockwave on acute fractures is unknown. The purpose of this study was to investigate the effects of shockwave on acute high-energy fractures of the lower extremity. Between January and October 2004, 56 patients with 59 acute high-energy fractures were enrolled in this study. Patients were randomly divided into two groups with 28 patients with 28 fractures in the study group and 28 patients with 31 fractures in the control group. Both groups showed similar age, gender, type of fracture and follow-up time. Patients in the study group received open reduction and internal fixation and shockwave treatment immediately after surgery on odd-numbered days of the week, whereas, patients in the control group received open reduction and internal fixation without shockwave treatment on even-numbered days of the week. Postoperative managements were similarly performed in both groups including crutch walking with non-weight bearing on the affected limb until fracture healing shown on radiographs. The evaluation parameters included clinical assessments of pain score and weight bearing status of the affected leg and serial radiographs at 3, 6 and 12 months. The primary end-point is the rate of non-union at 12 months, and the secondary end point is the rate of fracture healing at 3, 6 and 12 months. At 12 months, the rate of non-union was 11% for the study group versus 20% for the control group (P < 0.001). Significantly, better rate of fracture healing was noted in the study group than the control group at 3, 6 and 12 months (P < 0.001). Extracorporeal shockwave is effective on promoting fracture healing and decreasing the rate of non-union in acute high-energy fractures of the lower extremity.

  15. Effect of acute lateral hemisection of the spinal cord on spinal neurons of postural networks

    PubMed Central

    Zelenin, P. V.; Lyalka, V. F.; Orlovsky, G. N.; Deliagina, T. G.

    2016-01-01

    In quadrupeds, acute lateral hemisection of the spinal cord (LHS) severely impairs postural functions, which recover over time. Postural limb reflexes (PLRs) represent a substantial component of postural corrections in intact animals. The aim of the present study was to characterize the effects of acute LHS on two populations of spinal neurons (F and E) mediating PLRs. For this purpose, in decerebrate rabbits, responses of individual neurons from L5 to stimulation causing PLRs were recorded before and during reversible LHS (caused by temporal cold block of signal transmission in lateral spinal pathways at L1), as well as after acute surgical (Sur) LHS at L1. Results obtained after Sur-LHS were compared to control data obtained in our previous study. We found that acute LHS caused disappearance of PLRs on the affected side. It also changed a proportion of different types of neurons on that side. A significant decrease and increase in the proportion of F- and non-modulated neurons, respectively, was found. LHS caused a significant decrease in most parameters of activity in F-neurons located in the ventral horn on the lesioned side and in E-neurons of the dorsal horn on both sides. These changes were caused by a significant decrease in the efficacy of posture-related sensory input from the ipsilateral limb to F-neurons, and from the contralateral limb to both F- and E-neurons. These distortions in operation of postural networks underlie the impairment of postural control after acute LHS, and represent a starting point for the subsequent recovery of postural functions. PMID:27702647

  16. Acute marijuana effects on rCBF and cognition: a PET study.

    PubMed

    O'Leary, D S; Block, R I; Flaum, M; Schultz, S K; Boles Ponto, L L; Watkins, G L; Hurtig, R R; Andreasen, N C; Hichwa, R D

    2000-11-27

    The effects of smoking marijuana on cognition and brain function were assessed with PET using H2(15)O. Regional cerebral blood flow (rCBF) was measured in five recreational users before and after smoking a marijuana cigarette, as they repeatedly performed an auditory attention task. Blood flow increased following smoking in a number of paralimbic brain regions (e.g. orbital frontal lobes, insula, temporal poles) and in anterior cingulate and cerebellum. Large reductions in rCBF were observed in temporal lobe regions that are sensitive to auditory attention effects. Brain regions showing increased rCBF may mediate the intoxicating and mood-related effects of smoking marijuana, whereas reduction of task-related rCBF in temporal lobe cortices may account for the impaired cognitive functions associated with acute intoxication.

  17. Effect of combined oral doses of Δ(9)-tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) on acute and anticipatory nausea in rat models.

    PubMed

    Rock, Erin M; Connolly, Cassidy; Limebeer, Cheryl L; Parker, Linda A

    2016-09-01

    The purpose of this study was to evaluate the potential of oral combined cannabis constituents to reduce nausea. The objective of this study was to determine the effect of combining subthreshold oral doses of Δ(9)-tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) on acute and anticipatory nausea in rat models of conditioned gaping. The potential of intragastric (i.g.) administration of THC, CBDA, or combined doses, to interfere with acute nausea-induced conditioned gaping (acute nausea) or the expression of contextually elicited conditioned gaping (anticipatory nausea), was evaluated. For acute nausea, i.g. administration of subthreshold doses of THC (0.5 and 1 mg/kg) or CBDA (0.5 and 1 μg/kg) significantly suppressed acute nausea-induced gaping, whereas higher individual doses of both THC and CBDA were maximally effective. Combined i.g. administration of higher doses of THC and CBDA (2.5 mg/kg THC-2.5 μg/kg CBDA; 10 mg/kg THC-10 μg/kg CBDA; 20 mg/kg THC-20 μg/kg CBDA) also enhanced positive hedonic reactions elicited by saccharin solution during conditioning. For anticipatory nausea, combined subthreshold i.g. doses of THC (0.1 mg/kg) and CBDA (0.1 μg/kg) suppressed contextually elicited conditioned gaping. When administered i.g., THC was effective on its own at doses ranging from 1 to 10 mg/kg, but CBDA was only effective at 10 μg/kg. THC alone was equally effective by intraperitoneal (i.p.) and i.g. administration, whereas CBDA alone was more effective by i.p. administration (Rock et al. in Psychopharmacol (Berl) 232:4445-4454, 2015) than by i.g. administration. Oral administration of subthreshold doses of THC and CBDA may be an effective new treatment for acute nausea and anticipatory nausea and appetite enhancement in chemotherapy patients.

  18. NEUROCHEMICAL EFFECTS OF CHRONIC DIETARY AND REPEATED HIGH-LEVEL ACUTE EXPOSURE TO CHLORPYRIFOS IN RATS.

    EPA Science Inventory

    Lots of information is available surrounding the acute toxicity of anticholinesterase pesticides, but these have been very few detailed studies on the chronic effects of these pesticides. Humans are exposed on a chronic basis and some humans believe that have been affected advers...

  19. Acute Stress Dysregulates the LPP ERP Response to Emotional Pictures and Impairs Sustained Attention: Time-Sensitive Effects

    PubMed Central

    Alomari, Rima A.; Fernandez, Mercedes; Banks, Jonathan B.; Acosta, Juliana; Tartar, Jaime L.

    2015-01-01

    Stress can increase emotional vigilance at the cost of a decrease in attention towards non-emotional stimuli. However, the time-dependent effects of acute stress on emotion processing are uncertain. We tested the effects of acute stress on subsequent emotion processing up to 40 min following an acute stressor. Our measure of emotion processing was the late positive potential (LPP) component of the visual event-related potential (ERP), and our measure of non-emotional attention was the sustained attention to response task (SART). We also measured cortisol levels before and after the socially evaluated cold pressor test (SECPT) induction. We found that the effects of stress on the LPP ERP emotion measure were time sensitive. Specifically, the LPP ERP was only altered in the late time-point (30–40 min post-stress) when cortisol was at its highest level. Here, the LPP no longer discriminated between the emotional and non-emotional picture categories, most likely because neutral pictures were perceived as emotional. Moreover, compared to the non-stress condition, the stress-condition showed impaired performance on the SART. Our results support the idea that a limit in attention resources after an emotional stressor is associated with the brain incorrectly processing non-emotional stimuli as emotional and interferes with sustained attention. PMID:26010485

  20. Acute Stress Dysregulates the LPP ERP Response to Emotional Pictures and Impairs Sustained Attention: Time-Sensitive Effects.

    PubMed

    Alomari, Rima A; Fernandez, Mercedes; Banks, Jonathan B; Acosta, Juliana; Tartar, Jaime L

    2015-05-20

    Stress can increase emotional vigilance at the cost of a decrease in attention towards non-emotional stimuli. However, the time-dependent effects of acute stress on emotion processing are uncertain. We tested the effects of acute stress on subsequent emotion processing up to 40 min following an acute stressor. Our measure of emotion processing was the late positive potential (LPP) component of the visual event-related potential (ERP), and our measure of non-emotional attention was the sustained attention to response task (SART). We also measured cortisol levels before and after the socially evaluated cold pressor test (SECPT) induction. We found that the effects of stress on the LPP ERP emotion measure were time sensitive. Specifically, the LPP ERP was only altered in the late time-point (30-40 min post-stress) when cortisol was at its highest level. Here, the LPP no longer discriminated between the emotional and non-emotional picture categories, most likely because neutral pictures were perceived as emotional. Moreover, compared to the non-stress condition, the stress-condition showed impaired performance on the SART. Our results support the idea that a limit in attention resources after an emotional stressor is associated with the brain incorrectly processing non-emotional stimuli as emotional and interferes with sustained attention.

  1. [Experimental study of acute brain swelling under acute intracranial hypertension (author's transl)].

    PubMed

    Shigemori, M; Watanabe, M; Kuramoto, S

    1976-12-01

    There are many problems about the cause, pathophysiology and treatment of acute brain swelling under intracranial hypertension frequently encountered in the neurosurgical clinics. Generally, rapid increase of the cerebral vasoparesis caused by unknown etiology is thought to be the main cause of acute brain swelling under intracranial hypertension. Moreover, disturbance of the cerebral venous circulatory system is discussed recently by many authors. But, research from the point of systemic respiration and hemodynamics is necessary for resolving these problems. This experiment was designed to study the effects of respiration and hemodynamics on the cerebral vasoparesis. Using 22 adult dogs, acute intracranial hypertension was produced by epidural balloon inflation sustained at the level of 300 - 400 mmH2O. Simultaneously with measurement of intracranial pressure at the epidural space, superior sagittal sinus pressure, respirogram, systemic blood pressure (femoral artery), central venous pressure, common carotid blood flow, EKG and bipolar lead EEG were monitored continuously. The experimental group was divided by the respiratory loading into 5 groups as follows: control (6 cases), 10% CO2 hypercapnia (4 cases), 10% O2 hypoxia (4 cases), stenosis of airway (5 cases), 100% O2-controled respiration (3 cases). 1) Cerebral vasoparesis under acute intracranial hypertension took place earlier and showed more rapid progression in groups of stenosis of airway, hypercapnia and hypoxia than control group of spontaneous respiration in room air. No occurrence of cerebral vasoparesis was found out in a group of 100% O2 controlled respiration. It is proved that increased airway resistance or asphyxia, hypercapnia and hypoxia have strictly reference to the occurrence and progression of cerebral vasoparesis and for the prevention of cerebral vasoparesis, correct 100% O2 cont rolled respiration is effective. 2) From the hemodynamic change, the progression of rapid increase of cerebral

  2. Effects of Acute Alcohol Consumption on the Processing of Emotion in Faces: Implications for Understanding Alcohol-Related Aggression

    PubMed Central

    Attwood, Angela S.; Munafò, Marcus R.

    2016-01-01

    The negative consequences of chronic alcohol abuse are well known, but heavy episodic consumption ("binge drinking") is also associated with significant personal and societal harms. Aggressive tendencies are increased after alcohol but the mechanisms underlying these changes are not fully understood. While effects on behavioural control are likely to be important, other effects may be involved given the widespread action of alcohol. Altered processing of social signals is associated with changes in social behaviours, including aggression, but until recently there has been little research investigating the effects of acute alcohol consumption on these outcomes. Recent work investigating the effects of acute alcohol on emotional face processing has suggested reduced sensitivity to submissive signals (sad faces) and increased perceptual bias towards provocative signals (angry faces) after alcohol consumption, which may play a role in alcohol-related aggression. Here we discuss a putative mechanism that may explain how alcohol consumption influences emotional processing and subsequent aggressive responding, via disruption of OFC-amygdala connectivity. While the importance of emotional processing on social behaviours is well established, research into acute alcohol consumption and emotional processing is still in its infancy. Further research is needed and we outline a research agenda to address gaps in the literature. PMID:24920135

  3. Rapid adaptation of the stimulatory effect of CO2 on brain norepinephrine metabolism.

    PubMed

    Stone, E A

    1983-12-01

    The present study examined the effects of exposure of rats to elevated environmental levels of CO2 on norepinephrine metabolism in the hypothalamus and other regions of the brain. In confirmation of previous findings by others CO2 at 10 or 15% was found to elevate both dopa accumulation after dopa decarboxylase inhibition and norepinephrine utilization after tyrosine hydroxylase inhibition. These effects however were found to be transient occurring only during the first 30 min of 2.5 h exposure. In this regard CO2 differs from another form of stress, restraint which produces a sustained 2.5 h increase of dopa accumulation and NE accumulation. Restraint was also more effective than CO2 in depleting endogenous stores of hypothalamic NE. The factor responsible for the adaptation of the catecholamine response to CO2 was not identified although it was shown not to be hypothermia and it was reversed by a 2 h CO2-free recovery period.

  4. Acute Ethanol Withdrawal Impairs Contextual Learning and Enhances Cued Learning

    PubMed Central

    Tipps, Megan E.; Raybuck, Jonathan D.; Buck, Kari J.; Lattal, K. Matthew

    2014-01-01

    Background Alcohol affects many of the brain regions and neural processes that support learning and memory, and these effects are thought to underlie, at least in part, the development of addiction. Although much work has been done regarding the effects of alcohol intoxication on learning and memory, little is known about the effects of acute withdrawal from a single alcohol exposure. Methods We assess the effects of acute ethanol withdrawal (6 h post-injection with 4 g/kg ethanol) on two forms of fear conditioning (delay and trace fear conditioning) in C57BL/6J and DBA/2J mice. The influence of a number of experimental parameters (pre- and post-training withdrawal exposure; foreground/background processing; training strength; non-associative effects) is also investigated. Results Acute ethanol withdrawal during training had a bidirectional effect on fear conditioned responses, decreasing contextual responses and increasing cued responses. These effects were apparent for both trace and delay conditioning in DBA/2J mice and for trace conditioning in C57BL/6J mice; however, C57BL/6J mice were selectively resistant to the effects of acute withdrawal on delay cued responses. Conclusions Our results show that acute withdrawal from a single, initial ethanol exposure is sufficient to alter long-term learning in mice. In addition, the differences between the strains and conditioning paradigms used suggest that specific learning processes can be differentially affected by acute withdrawal in a manner that is distinct from the reported effects of both alcohol intoxication and withdrawal following chronic alcohol exposure. Thus, our results suggest a unique effect of acute alcohol withdrawal on learning and memory processes. PMID:25684050

  5. Acute, subacute toxicity and mutagenic effects of anacardic acids from cashew (Anacardium occidentale Linn.) in mice.

    PubMed

    Carvalho, Ana Laura Nicoletti; Annoni, Raquel; Silva, Paula Regina Pereira; Borelli, Primavera; Fock, Ricardo Ambrósio; Trevisan, Maria Teresa Salles; Mauad, Thais

    2011-06-01

    Anacardium occidentale Linn. (cashew) is a Brazilian plant that is usually consumed in natura and is used in folk medicine. Anacardic acids (AAs) in the cashew nut shell liquid are biologically active as gastroprotectors, inhibitors of the activity of various deleterious enzymes, antitumor agents and antioxidants. Yet, there are no reports of toxicity testing to guarantee their use in vivo models. We evaluated AAs biosafety by measuring the acute, subacute and mutagenic effects of AAs administration in BALB/c mice. In acute tests, BALB/c mice received a single oral dose of 2000 mg/kg, whereas animals in subacute tests received 300, 600 and 1000 mg/kg for 30 days. Hematological, biochemical and histological analyses were performed in all animals. Mutagenicity was measured with the acute micronucleus test 24h after oral administration of 250 mg/kg AAs. Our results showed that the AAs acute minimum lethal dose in BALB/c mice is higher than 2000 mg/kg since this concentration did not produce any symptoms. In subacute tests, females which received the highest doses (600 or 1000 mg/kg) were more susceptible, which was seen by slightly decreased hematocrit and hemoglobin levels coupled with a moderate increase in urea. Anacardic acids did not produce any mutagenic effects. The data indicate that doses less than 300 mg/kg did not produce biochemical and hematological alterations in BALB/c mice. Additional studies must be conducted to investigate the pharmacological potential of this natural substance in order to ensure their safe use in vivo. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  6. Sulfonylureas suppress the stimulatory action of Mg-nucleotides on Kir6.2/SUR1 but not Kir6.2/SUR2A KATP channels: a mechanistic study.

    PubMed

    Proks, Peter; de Wet, Heidi; Ashcroft, Frances M

    2014-11-01

    Sulfonylureas, which stimulate insulin secretion from pancreatic β-cells, are widely used to treat both type 2 diabetes and neonatal diabetes. These drugs mediate their effects by binding to the sulfonylurea receptor subunit (SUR) of the ATP-sensitive K(+) (KATP) channel and inducing channel closure. The mechanism of channel inhibition is unusually complex. First, sulfonylureas act as partial antagonists of channel activity, and second, their effect is modulated by MgADP. We analyzed the molecular basis of the interactions between the sulfonylurea gliclazide and Mg-nucleotides on β-cell and cardiac types of KATP channel (Kir6.2/SUR1 and Kir6.2/SUR2A, respectively) heterologously expressed in Xenopus laevis oocytes. The SUR2A-Y1206S mutation was used to confer gliclazide sensitivity on SUR2A. We found that both MgATP and MgADP increased gliclazide inhibition of Kir6.2/SUR1 channels and reduced inhibition of Kir6.2/SUR2A-Y1206S. The latter effect can be attributed to stabilization of the cardiac channel open state by Mg-nucleotides. Using a Kir6.2 mutation that renders the KATP channel insensitive to nucleotide inhibition (Kir6.2-G334D), we showed that gliclazide abolishes the stimulatory effects of MgADP and MgATP on β-cell KATP channels. Detailed analysis suggests that the drug both reduces nucleotide binding to SUR1 and impairs the efficacy with which nucleotide binding is translated into pore opening. Mutation of one (or both) of the Walker A lysines in the catalytic site of the nucleotide-binding domains of SUR1 may have a similar effect to gliclazide on MgADP binding and transduction, but it does not appear to impair MgATP binding. Our results have implications for the therapeutic use of sulfonylureas. © 2014 Proks et al.

  7. Effect of switching to risperidone after unsuccessful treatment with aripiprazole on plasma monoamine metabolites level in the treatment of acute schizophrenia.

    PubMed

    Miura, Itaru; Takeuchi, Satoshi; Katsumi, Akihiko; Kanno, Keiko; Watanabe, Kenya; Mashiko, Hirobumi; Niwa, Shin-Ichi

    2012-09-01

    In the treatment of acute schizophrenia, risperidone and aripiprazole are both placed the first line antipsychotics. These two antipsychotics have different pharmacological effects. We investigated the effects of risperidone on plasma levels of homovanillic acid (HVA) and 3-methoxy-4hydroxyphenylglycol after unsuccessful aripiprazole treatment in acute schizophrenia. Ten Japanese patients with acute schizophrenia were enrolled to this study. Plasma levels of monoamine metabolites were analyzed with high-performance liquid chromatography with electrochemical detection. Risperidone improved the symptoms and 4 of 10 patients were responders. Risperidone showed a tendency to decrease plasma HVA (pHVA) levels in responders (p = 0.068), but not in non-responders (p = 1.0). At baseline, pHVA levels of responders were significantly higher than that of non-responders (p = 0.033). A trend for negative correlation was found between pHVA at baseline and the changes in Positive and Negative Syndrome Scale-Total (p = 0.061, r = -0.61). Our results suggest that high pHVA level before switching may predict good response to the second line antipsychotics after unsuccessful first antipsychotic treatment. If aripiprazole is not effective in acute schizophrenia, switching to risperidone may be effective and reasonable strategy for improving symptoms. Copyright © 2012 John Wiley & Sons, Ltd.

  8. Opposing Effects of Acute versus Chronic Blockade of Frontal Cortex Somatostatin-Positive Inhibitory Neurons on Behavioral Emotionality in Mice

    PubMed Central

    Soumier, Amelie; Sibille, Etienne

    2014-01-01

    Reduced expression of somatostatin (SST) is reported across chronic brain conditions including major depression and normal aging. SST is a signaling neuropeptide and marker of gamma-amino butyric acid (GABA) neurons, which specifically inhibit pyramidal neuron dendrites. Studies in auditory cortex suggest that chronic reduction in dendritic inhibition induces compensatory homeostatic adaptations that oppose the effects of acute inhibition. Whether such mechanisms occur in frontal cortex (FC) and affect behavioral outcome is not known. Here, we used two complementary viral vector strategies to examine the effects of acute vs chronic inhibition of SST-positive neurons on behavioral emotionality in adult mice. SST-IRES-Cre mice were injected in FC (prelimbic/precingulate) with CRE-dependent adeno-associated viral (AAV) vector encoding the engineered Gi/o-coupled human muscarinic M4 designer receptor exclusively activated by a designer drug (DREADD-hM4Di) or a control reporter (AAV-DIO-mCherry) for acute or chronic cellular inhibition. A separate cohort was injected with CRE-dependent AAV vectors expressing diphtheria toxin (DTA) to selectively ablate FC SST neurons. Mice were assessed for anxiety- and depressive-like behaviors (defined as emotionality). Results indicate that acute inhibition of FC SST neurons increased behavioral emotionality, whereas chronic inhibition decreased behavioral emotionality. Furthermore, ablation of FC SST neurons also decreased behavioral emotionality under baseline condition and after chronic stress. Together, our results reveal opposite effects of acute and chronic inhibition of FC SST neurons on behavioral emotionality and suggest the recruitment of homeostatic plasticity mechanisms that have implications for understanding the neurobiology of chronic brain conditions affecting dendritic-targeting inhibitory neurons. PMID:24690741

  9. Opposing effects of acute versus chronic blockade of frontal cortex somatostatin-positive inhibitory neurons on behavioral emotionality in mice.

    PubMed

    Soumier, Amelie; Sibille, Etienne

    2014-08-01

    Reduced expression of somatostatin (SST) is reported across chronic brain conditions including major depression and normal aging. SST is a signaling neuropeptide and marker of gamma-amino butyric acid (GABA) neurons, which specifically inhibit pyramidal neuron dendrites. Studies in auditory cortex suggest that chronic reduction in dendritic inhibition induces compensatory homeostatic adaptations that oppose the effects of acute inhibition. Whether such mechanisms occur in frontal cortex (FC) and affect behavioral outcome is not known. Here, we used two complementary viral vector strategies to examine the effects of acute vs chronic inhibition of SST-positive neurons on behavioral emotionality in adult mice. SST-IRES-Cre mice were injected in FC (prelimbic/precingulate) with CRE-dependent adeno-associated viral (AAV) vector encoding the engineered Gi/o-coupled human muscarinic M4 designer receptor exclusively activated by a designer drug (DREADD-hM4Di) or a control reporter (AAV-DIO-mCherry) for acute or chronic cellular inhibition. A separate cohort was injected with CRE-dependent AAV vectors expressing diphtheria toxin (DTA) to selectively ablate FC SST neurons. Mice were assessed for anxiety- and depressive-like behaviors (defined as emotionality). Results indicate that acute inhibition of FC SST neurons increased behavioral emotionality, whereas chronic inhibition decreased behavioral emotionality. Furthermore, ablation of FC SST neurons also decreased behavioral emotionality under baseline condition and after chronic stress. Together, our results reveal opposite effects of acute and chronic inhibition of FC SST neurons on behavioral emotionality and suggest the recruitment of homeostatic plasticity mechanisms that have implications for understanding the neurobiology of chronic brain conditions affecting dendritic-targeting inhibitory neurons.

  10. Effects of subcutaneous and intracerebroventricular injection of physostigmine on the acute corneal nociception in rats.

    PubMed

    Tamaddonfard, Esmaeal; Hamzeh-Gooshchi, Nasrin

    2010-01-01

    The present study investigated the effects of subcutaneous (sc) and intracerebroventricular (icv) injections of physostigmine (a cholinesterase inhibitor), atropine (an antagonist of muscarinic cholinergic receptors) and hexamethonium (an antagonist of nicotinic cholinergic receptors) on the acute corneal nociception in rats. Local application of 5 M NaCl solution on the corneal surface of the eye produced a significant nociceptive behavior, characterized by eye wiping. The number of eye wipes was counted during the first 30 s. The sc (0.25, 0.5 and 1 mg/kg) and icv (1.25, 2.5, 5 and 10 μg) injections of physostigmine significantly (p < 0.05) decreased the number of eye wipes. Atropine and hexamethonium at (2 mg/kg, sc and 20 μg, icv) had no effects when used alone, however, atropine, but not hexamethonium prevented the antinociception induced by physostigmine (sc and icv). The results of this study indicate that the central muscarinic, but not nicotinic receptors might be involved in the antinociceptive effect of physostigmine in the acute corneal model of pain in rats.

  11. Effects of acute lorazepam administration on aminergic activity in normal elderly subjects: relationship to performance effects and apolipoprotein genotype.

    PubMed

    Pomara, Nunzio; Willoughby, Lisa M; Hashim, Audrey; Sershen, Henry; Sidtis, John J; Wesnes, Keith; Greenblatt, David J; Lajtha, Abel

    2004-07-01

    The effects of acute lorazepam challenges on plasma (p) HVA, MHPG, and 5-HIAA, and their relationship to drug-induced cognitive and motor deficits and the apolipoprotein (APOE)-epsilon4 allele were examined. Eighteen healthy elderly (8 epsilon4 carriers) received placebo or acute oral lorazepam doses (0.5 mg or 1 mg) in random sequence, 1-week apart. Cognitive assessment and plasma levels of pHVA, pMHPG, and p5-HIAA were determined at baseline and at 1, 2.5, and 5 h postchallenge. There was no drug-to-placebo difference in monoamine levels and no consistent relationship between changes in monoamine levels and cognitive performance, regardless of epsilon4 status. However, the 1.0 mg dose increased p5-HIAA in epsilon4 carriers, whereas it caused a reduction in noncarriers. Higher baseline pMHPG and p5-HIAA levels were associated with better baseline memory. The epsilon4 allele may modulate the effect of lorazepam on p5-HIAA, but further studies are needed to confirm this finding and elucidate its possible significance.

  12. Acute Alcohol Effects on Repetition Priming and Word Recognition Memory with Equivalent Memory Cues

    ERIC Educational Resources Information Center

    Ray, Suchismita; Bates, Marsha E.

    2006-01-01

    Acute alcohol intoxication effects on memory were examined using a recollection-based word recognition memory task and a repetition priming task of memory for the same information without explicit reference to the study context. Memory cues were equivalent across tasks; encoding was manipulated by varying the frequency of occurrence (FOC) of words…

  13. Cost-effectiveness of rehabilitation after an acute coronary event: a randomised controlled trial.

    PubMed

    Briffa, Tom G; Eckermann, Simon D; Griffiths, Alison D; Harris, Phillip J; Heath, M Rose; Freedman, Saul B; Donaldson, Lana T; Briffa, N Kathryn; Keech, Anthony C

    2005-11-07

    To estimate the incremental effects on cost and quality of life of cardiac rehabilitation after an acute coronary syndrome. Open randomised controlled trial with 1 year's follow-up. Analysis was on an intention-to-treat basis. Two tertiary hospitals in Sydney. 18 sessions of comprehensive exercise-based outpatient cardiac rehabilitation or conventional care as provided by the treating doctor. 113 patients aged 41-75 years who were self-caring and literate in English. Patients with uncompensated heart failure, uncontrolled arrhythmias, severe and symptomatic aortic stenosis or physical impairment were excluded. Costs (hospitalisations, medication use, outpatient visits, investigations, and personal expenses); and measures of quality of life. Incremental cost per quality-adjusted life year (QALY) saved at 1 year (this estimate combines within-study utility effects with reported 1-year risk of survival and treatment effects of rehabilitation on mortality). Sensitivity analyses around a base case estimate included alternative assumptions of no treatment effect on survival, 3 years of treatment effect on survival and variations in utility. The estimated incremental cost per QALY saved for rehabilitation relative to standard care was 42,535 US dollars when modelling included the reported treatment effect on survival. This increased to 70,580 US dollars per QALY saved if treatment effect on survival was not included. The results were sensitive to variations in utility and ranged from 19,685 US dollars per QALY saved to rehabilitation not being cost-effective. The effects on quality of life tend to reinforce treatment advantages on survival for patients having postdischarge rehabilitation after an acute coronary syndrome. The estimated base case incremental cost per QALY saved is consistent with those historically accepted by decision making authorities such as the Pharmaceutical Benefits Advisory Committee.

  14. The acute effects of body position strategies and respiratory therapy in paralyzed patients with acute lung injury

    PubMed Central

    Davis, Kenneth; Johannigman, Jay A; Campbell, Robert S; Marraccini, Ann; Luchette, Fred A; Frame, Scott B; Branson, Richard D

    2001-01-01

    Background: Routine turning of critically ill patients is a standard of care. In recent years, specialized beds that provide automated turning have been introduced. These beds have been reported to improve lung function, reduce hospital-acquired pneumonia, and facilitate secretion removal. This trial was designed to measure the physiological effects of routine turning and respiratory therapy in comparison with continuous lateral rotation (CLR). Methods: The study was a prospective, quasi-experimental, random assignment, trial with patients serving as their own controls. Paralyzed, sedated patients with acute respiratory distress syndrome were eligible for study. Patients were randomized to receive four turning and secretion management regimens in random sequence for 6 h each over a period of 24 h: (1) routine turning every 2 h from the left to right lateral position; (2) routine turning every 2 h from the left to right lateral position including a 15-min period of manual percussion and postural drainage (P&PD); (3) CLR with a specialized bed that turned patients from left to right lateral position, pausing at each position for 2 min; and (4) CLR with a specialized bed that turned patients from left to right lateral position pausing at each position for 2 min, and a 15-min period of percussion provided by the pneumatic cushions of the bed every 2 h. Results: Nineteen patients were entered into the study. There were no statistically significant differences in the measured cardiorespiratory variables. There was a tendency for the ratio of partial pressure of arterial oxygen to fractional inspired oxygen concentration (PaO2/FIO2) to increase (174 ± 31 versus 188 ± 36; P = 0.068) and for the ratio of deadspace to tidal volume (Vd/Vt) to decrease (0.62 ± 0.18 versus 0.59 ± 0.18; P = 0.19) during periods of CLR, but these differences did not achieve statistical significance. There were statistically significant increases in sputum volume during the periods of CLR. The

  15. Effect of zinc intake on hepatic autophagy during acute alcohol intoxication.

    PubMed

    Liuzzi, Juan P; Narayanan, Vijaya; Doan, Huong; Yoo, Changwon

    2018-04-01

    Autophagy is a conserved mechanism that plays a housekeeping role by eliminating protein aggregates and damaged organelles. Recent studies have demonstrated that acute ethanol intoxication induces hepatic autophagy in mice. The effect of dietary zinc intake on hepatic autophagic flux during ethanol intoxication has not been evaluated using animal models. Herein, we investigated whether zinc deficiency and excess can affect autophagic flux in the liver in mice and in human hepatoma cells acutely exposed to ethanol. A mouse model of binge ethanol feeding was utilized to analyze the effect of low, adequate, and high zinc intake on hepatic autophagic flux during ethanol intoxication. Autophagic flux was inferred by analyzing LC3II/LC3I ratio, protein levels of p62/SQSTM1, Beclin1 and Atg7, and phosphorylation of 4EBP1. In addition, the degradation of the fusion protein LC3-GFP and the formation of autophagosomes and autolysosomes were evaluated in cells. Ethanol treatment stimulated autophagy in mice and cells. High zinc intake resulted in enhanced autophagy in mice exposed to ethanol. Conversely, zinc deficiency was consistently associated with impaired ethanol-induced autophagy in mice and cells. Zinc-deficient mice exhibited a high degree of ethanol-driven steatosis. Furthermore, zinc depletion increased apoptosis in cells exposed to ethanol. The results of this study suggest that adequate zinc intake is necessary for proper stimulation of autophagy by ethanol. Poor zinc status is commonly found among alcoholics and could likely contribute to faulty autophagy.

  16. Effects of methylphenidate on acute math performance in children with attention-deficit hyperactivity disorder.

    PubMed

    Grizenko, Natalie; Cai, Emmy; Jolicoeur, Claude; Ter-Stepanian, Mariam; Joober, Ridha

    2013-11-01

    Examine the short-term (acute) effects of methylphenidate (MPH) on math performance in children with attention-deficit hyperactivity disorder (ADHD) and what factors predict improvement in math performance. One hundred ninety-eight children with ADHD participated in a double-blind, placebo-controlled, randomized crossover MPH trial. Math response to MPH was determined through administration of math problems adjusted to their academic level during the Restricted Academic Situation Scale (RASS). Student t tests were conducted to assess change in math performance with psychostimulants. Correlation between change on the RASS and change on the math performance was also examined. Linear regression was performed to determine predictor variables. Children with ADHD improved significantly in their math with MPH (P < 0.001). The degree of improvement on the RASS (which evaluates motor activity and orientation to task) and on math performance on MPH was highly correlated. A child's age at baseline and Wechsler Individual Achievement Test (WIAT)-Numerical Operations standard scores at baseline accounted for 15% of variances for acute math improvement. MPH improves acute math performance in children with ADHD. Younger children with lower math scores (as assessed by the WIAT) improved most on math scores when given psychostimulants. NCT00483106.

  17. Metoclopramide for Acute Migraine Treatment in the Emergency Department: An Effective Alternative to Opioids.

    PubMed

    Najjar, Mejdi; Hall, Tyler; Estupinan, Blanca

    2017-04-20

    In light of recent warnings by the United States (US) Surgeon General and Centers for Disease Control (CDC) guidelines for recommending more prudent use of opioid narcotics, the search for a non-opioid alternative for aborting acute migraines is particularly relevant. The CDC also estimates the prevalence of opioid dependence may be as high as 26% among patients prescribed opioids for chronic pain, not due to cancer, in the primary care setting. Given such staggering data, it is imperative that we, as caretakers, not foster opioid dependence but rather continue to investigate non-opioid therapies for the management of acute migraines in the emergent care settings. Our literature review demonstrates that metoclopramide should be used more frequently as first-line therapy for an acute migraine over opioids. The use of opioids specifically has been discouraged as migraine treatment by the American Headache Society citing "insufficient evidence" as the main reason. Metoclopramide, specifically using the 10 mg dose, has been cited as "highly likely to be effective" by the same guidelines. Another major issue with opioids is the growing potential for abuse, thus minimizing the use of these drugs for only special circumstances would be beneficial overall.

  18. Effect of paracetamol (acetaminophen) on body temperature in acute stroke: A meta-analysis.

    PubMed

    Fang, Junjie; Chen, Chensong; Cheng, Hongsen; Wang, Ren; Ma, Linhao

    2017-10-01

    The objective of this study was to assess the efficacy of paracetamol (acetaminophen) on body temperature in acute stroke. Medline, Cochrane Central Register of Controlled Trials, EMBASE, Chinese BioMedical Literature Database, China National Knowledge Infrastructure, and the World Health Organization (WHO) International Clinical Trials Registry Platform were searched electronically. Relevant journals and references of studies included were hand-searched for randomized controlled trials (RCT) and controlled clinical trials (CCT) regarding the efficacy of paracetamol (acetaminophen) on body temperature in acute stroke. Two reviewers independently performed data extraction and quality assessment. Data were analyzed using RevMan 5.3 software by the Cochrane Collaboration. Five studies were included. To compare the efficacy of paracetamol (acetaminophen) in acute stroke, the pooled RR (Risk Ratio) and its 95% CI of body temperature reduction at 24h from the start of treatment were -0.3 (95% CI: -0.52 to -0.08), with statistical significance (P=0.007). Consistently, the pooled RR (Risk Ratio) and its 95% CI of body temperature at 24h from the start of treatment were -0.22 (-0.29, -0.15), with statistical significance (P<0.00001). When analyzing the body temperature reduction after 5days from the start of treatment, the pooled RR (Risk Ratio) and its 95% CI were 0.04 (95% CI: -0.20 to 0.29), with no statistical significance (P=0.73). For functional outcome (mRS≤2) analysis, the pooled RR and its 95% CI were 1.08 (0.88, 1.32), with no statistical significance (P=0.45). In addition, the difference of serious adverse events between acetaminophen and placebo was 0.86 (95% CI: 0.62 to 1.2), with no statistical significance (P=0.27). Acetaminophen was revealed to have some favorable influence in body temperature reduction in acute stroke, but showed no important effect on improving functional outcome and reducing adverse events of patients. What is already known on this

  19. The Acute Effects of Grape Polyphenols Supplementation on Endothelial Function in Adults: Meta-Analyses of Controlled Trials

    PubMed Central

    Li, Shao-Hua; Tian, Hong-Bo; Zhao, Hong-Jin; Chen, Liang-Hua; Cui, Lian-Qun

    2013-01-01

    Background The acute effects of grape polyphenols on endothelial function in adults are inconsistent. Here, we performed meta-analyses to determine these acute effects as measured by flow-mediated dilation (FMD). Methods Trials were searched in PubMed, Embase and the Cochrane Library database. Summary estimates of weighted mean differences (WMDs) and 95% CIs were obtained by using random-effects models. Meta-regression and subgroup analyses were performed to identify the source of heterogeneity. The protocol details of our meta-analysis have been submitted to the PROSPERO register and our registration number is CRD42013004157. Results Nine studies were included in the present meta-analyses. The results showed that the FMD level was significantly increased in the initial 120 min after intake of grape polyphenols as compared with controls. Meta-regression and subgroup analyses were performed and showed that a health status was the main effect modifier of the significant heterogeneity. Subgroups indicated that intake of grape polyphenols could significantly increase FMD in healthy subjects, and the increased FMD appeared to be more obviously in subjects with high cardiovascular risk factors. Moreover, the peak effect of grape polyphenols on FMD in healthy subjects was found 30 min after ingestion, which was different from the effect in subjects with high cardiovascular risk factors, in whom the peak effect was found 60 min after ingestion. Conclusions Endothelial function can be significantly improved in healthy adults in the initial 2 h after intake of grape polyphenols. The acute effect of grape polyphenols on endothelial function may be more significant but the peak effect is delayed in subjects with a smoking history or coronary heart disease as compared with the healthy subjects. PMID:23894543

  20. [Cost-effectiveness of consolidation treatments for acute myeloid leukemia in high-risk pediatric patients within the Colombian healthcare system].

    PubMed

    García, Mario; Chicaíza, Liliana Alejandra; Quitián, Hoover; Linares, Adriana; Ramírez, Óscar

    2015-01-01

    Acute myeloid leukemia represents about 20% of leukemias in minors under 18 years old. At present, there are only two consolidation treatment alternatives: Chemotherapy and stem-cell transplantation. To evaluate the cost-effectiveness of unrelated and related hematopoietic stem cell transplantations, versus chemotherapy consolidation in pediatric patients with high-risk acute myeloid leukemia. A decision tree was constructed with life-years gained as the outcome. Costs and probabilities were extracted from the literature. Probabilistic sensitivity analyses and acceptability curves were computed. The cost-effectiveness threshold was three times the 2010 per capita gross domestic product. When compared to consolidation chemotherapy cycles, related and unrelated hematopoietic stem-cell transplantation had incremental cost-effectiveness ratios of COP$ 9,226,421 (USD$ 4,820) and COP$ 6,544,116 (USD$ 3,419) respectively, which are lower than the per capita gross domestic product (COP$ 12,047,418, USD$ 6,294). Transplant proved to be cost-effective in 70% of the simulations and had a higher probability of the willingness to pay being over than COP$ 7,200,000 (USD$ 3,762). In Colombia, related and unrelated hematopoietic stem-cell transplants are cost-effective alternatives to consolidation treatment for high-risk acute myeloid leukemia in pediatric patients.