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Sample records for acid-induced writhing test

  1. Isobolographic analysis of interaction between cyclooxygenase inhibitors and tramadol in acetic acid-induced writhing in mice.

    PubMed

    Satyanarayana, Padi S V; Jain, Naveen K; Singh, Amarjit; Kulkarni, Shrinivas K

    2004-07-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) and opioids are the most commonly used analgesics in the management of acute and chronic pain. Combined use of NSAIDs and opioids has been indicated for achieving better analgesia with reduced side effects. The present study was aimed at evaluating the combination of different NSAIDs, which inhibit cyclooxygenase (COX) enzymes and tramadol against acetic acid-induced writhing in mice. The expected beneficial effect of combination regimen was analyzed by isobolographic analysis. The oral and intrathecally administered tramadol, a mu-opioid and naproxen, a nonselective COX inhibitor produced dose-dependent antinociception, however, rofecoxib, a selective COX-2 inhibitor lacked analgesic efficacy in writhing test. Isobolographic analysis showed synergistic or supra-additive interactions for the combinations of naproxen and tramadol after oral and intrathecal administration. However, similar interaction was not observed when tramadol was combined with rofecoxib. Pretreatment with naloxone partially reversed the antinociceptive effect of tramadol per se and its combination with naproxen without modifying the per se effect of NSAID. The results demonstrated marked synergistic interaction between naproxen and tramadol and such interaction involved opioid as well as non-opioid mechanisms of tramadol and inhibition of COX-1 but not COX-2 by naproxen.

  2. Tipepidine enhances the antinociceptive-like action of carbamazepine in the acetic acid writhing test.

    PubMed

    Kawaura, Kazuaki; Miki, Risa; Urashima, Yuri; Honda, Sokichi; Shehata, Ahmed M; Soeda, Fumio; Shirasaki, Tetsuya; Takahama, Kazuo

    2011-01-25

    Several antidepressants have been used to treat severe pain in clinics. Recently, we reported that the centrally acting non-narcotic antitussive (cough suppressant drug), tipepidine produces an antidepressant-like effect in the forced swimming test, although the mechanism of action appears to be quite different from that of known antidepressants. In the present study, we investigated whether a combination of tipepidine and carbamazepine acts synergistically to induce an antinociceptive effect in the acetic acid-induced writhing test in mice. Prior to studying the combination of tipepidine and carbamazepine, the analgesic action of tipepidine alone was also examined in mice. Tipepidine at 5-40mg/kg i.p. significantly reduced the number of writhes induced by acetic acid in mice. Carbamazepine at 20mg/kg i.p. also significantly reduced the writhing reaction. Furthermore, co-administration of carbamazepine (5 and 10mg/kg, i.p.) and tipepidine (2.5mg/kg i.p.) significantly decreased the number of writhes induced by acetic acid. This finding suggests that a combination of carbamazepine and tipepidine may be a new strategy for the treatment of neuropathic pain such as what occurs in trigeminal neuralgia, because the use of carbamazepine is often limited by its adverse effects and by reduction of its analgesic efficacy by microsomal enzyme induction. PMID:21114989

  3. Analgesic and Anti-Inflammatory Properties of Gelsolin in Acetic Acid Induced Writhing, Tail Immersion and Carrageenan Induced Paw Edema in Mice

    PubMed Central

    Gupta, Ashok Kumar; Parasar, Devraj; Sagar, Amin; Choudhary, Vikas; Chopra, Bhupinder Singh; Garg, Renu; Ashish; Khatri, Neeraj

    2015-01-01

    Plasma gelsolin levels significantly decline in several disease conditions, since gelsolin gets scavenged when it depolymerizes and caps filamentous actin released in the circulation following tissue injury. It is well established that our body require/implement inflammatory and analgesic responses to protect against cell damage and injury to the tissue. This study was envisaged to examine analgesic and anti-inflammatory activity of exogenous gelsolin (8 mg/mouse) in mice models of pain and acute inflammation. Administration of gelsolin in acetic acid-induced writhing and tail immersion tests not only demonstrated a significant reduction in the number of acetic acid-induced writhing effects, but also exhibited an analgesic activity in tail immersion test in mice as compared to placebo treated mice. Additionally, anti-inflammatory function of gelsolin (8 mg/mouse) compared with anti-inflammatory drug diclofenac sodium (10 mg/kg)] was confirmed in the carrageenan injection induced paw edema where latter was measured by vernier caliper and fluorescent tomography imaging. Interestingly, results showed that plasma gelsolin was capable of reducing severity of inflammation in mice comparable to diclofenac sodium. Analysis of cytokines and histo-pathological examinations of tissue revealed administration of gelsolin and diclofenac sodium significantly reduced production of pro-inflammatory cytokines, TNF-α and IL-6. Additionally, carrageenan groups pretreated with diclofenac sodium or gelsolin showed a marked decrease in edema and infiltration of inflammatory cells in paw tissue. Our study provides evidence that administration of gelsolin can effectively reduce the pain and inflammation in mice model. PMID:26426535

  4. Anti-Inflammatory and Analgesic Effects of Pyeongwisan on LPS-Stimulated Murine Macrophages and Mouse Models of Acetic Acid-Induced Writhing Response and Xylene-Induced Ear Edema

    PubMed Central

    Oh, You-Chang; Jeong, Yun Hee; Cho, Won-Kyung; Ha, Jeong-Ho; Gu, Min Jung; Ma, Jin Yeul

    2015-01-01

    Pyeongwisan (PW) is an herbal medication used in traditional East Asian medicine to treat anorexia, abdominal distension, borborygmus and diarrhea caused by gastric catarrh, atony and dilatation. However, its effects on inflammation-related diseases are unknown. In this study, we investigated the biological effects of PW on lipopolysaccharide (LPS)-mediated inflammation in macrophages and on local inflammation in vivo. We investigated the biological effects of PW on the production of inflammatory mediators, pro-inflammatory cytokines and related products as well as the activation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) in LPS-stimulated macrophages. Additionally, we evaluated the analgesic effect on the acetic acid-induced writhing response and the inhibitory activity on xylene-induced ear edema in mice. PW showed anti-inflammatory effects by inhibiting the production of nitric oxide (NO), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and interleukin-1β (IL-1β). In addition, PW strongly suppressed inducible nitric oxide synthase (iNOS), a NO synthesis enzyme, induced heme oxygenase-1 (HO-1) expression and inhibited NF-κB activation and MAPK phosphorylation. Also, PW suppressed TNF-α, IL-6 and IL-1β cytokine production in LPS-stimulated peritoneal macrophage cells. Furthermore, PW showed an analgesic effect on the writhing response and an inhibitory effect on mice ear edema. We demonstrated the anti-inflammatory effects and inhibitory mechanism in macrophages as well as inhibitory activity of PW in vivo for the first time. Our results suggest the potential value of PW as an inflammatory therapeutic agent developed from a natural substance. PMID:25569097

  5. Coupling of twist and writhe in short DNA loops

    NASA Astrophysics Data System (ADS)

    Medalion, Shlomi; Rappaport, Shay M.; Rabin, Yitzhak

    2010-01-01

    While bending and twist can be treated as independent degrees of freedom for linear DNA molecules, the loop closure constraint introduces a coupling between these variables in circular DNA. We performed Monte Carlo simulations of wormlike rods with both bending and twist rigidity in order to study the coupling between the writhe and twist distributions for various DNA lengths. We find that for sufficiently short DNA, the writhe distribution differs from that of a model with bending energy only. We show that the factorization approximation introduced by previous researchers coincides, within numerical accuracy, with our simulation results, and conclude that the closure constraint is fully accounted for by the White-Fuller relation. Experimental tests of our results for short DNA plasmids are proposed.

  6. The Writhe of Helical Structures in the Solar Corona

    NASA Technical Reports Server (NTRS)

    Toeroek, T.; Berger, M. A.; Kliem, B.

    2010-01-01

    Context. Helicity is a fundamental property of magnetic fields, conserved in ideal MHD. In flux rope topology, it consists of twist and writhe helicity. Despite the common occurrence of helical structures in the solar atmosphere, little is known about how their shape relates to the writhe, which fraction of helicity is contained in writhe, and how much helicity is exchanged between twist and writhe when they erupt. Aims. Here we perform a quantitative investigation of these questions relevant for coronal flux ropes. Methods. The decomposition of the writhe of a curve into local and nonlocal components greatly facilitates its computation. We use it to study the relation between writhe and projected S shape of helical curves and to measure writhe and twist in numerical simulations of flux rope instabilities. The results are discussed with regard to filament eruptions and coronal mass ejections (CMEs). Results. (1) We demonstrate that the relation between writhe and projected S shape is not unique in principle, but that the ambiguity does not affect low-lying structures, thus supporting the established empirical rule which associates stable forward (reverse) S shaped structures low in the corona with positive (negative) helicity. (2) Kink-unstable erupting flux ropes are found to transform a far smaller fraction of their twist helicity into writhe helicity than often assumed. (3) Confined flux rope eruptions tend to show stronger writhe at low heights than ejective eruptions (CMEs). This argues against suggestions that the writhing facilitates the rise of the rope through the overlying field. (4) Erupting filaments which are S shaped already before the eruption and keep the sign of their axis writhe (which is expected if field of one chirality dominates the source volume of the eruption), must reverse their S shape in the course of the rise. Implications for the occurrence of the helical kink instability in such events are discussed.

  7. Twisting and Writhing with George Ellery Hale

    NASA Astrophysics Data System (ADS)

    Canfield, Richard C.

    2013-06-01

    Early in his productive career in astronomy, George Ellery Hale developed innovative solar instrumentation that allowed him to make narrow-band images. Among the solar phenomena he discovered were sunspot vortices, which he attributed to storms akin to cyclones in our own atmosphere. Using the concept of magnetic helicity, physicists and mathematicians describe the topology of magnetic fields, including twisting and writhing. Our contemporary understanding of Hale's vortices as a consequence of large-scale twist in sunspot magnetic fields hinges on a key property of helicity: conservation. I will describe the critical role that this property plays, when applied to twist and writhe, in a fundamental aspect of global solar magnetism: the hemispheric and solar cycle dependences of active region electric currents with respect to magnetic fields. With the advent of unbroken sequences of high-resolution magnetic images, such as those presently available from the Helioseismic and Magnetic Imager on Solar Dynamics Observatory, the flux of magnetic helicity through the photosphere can be observed quantitatively. As magnetic flux tubes buoy up through the convection zone, buffeted and shredded by turbulence, they break up into fragments by repeated random bifurcation. We track these rising flux fragments in the photosphere, and calculate the flux of energy and magnetic helicity there. Using a quantitative model of coronal currents, we also track connections between these fragments to calculate the energy and magnetic helicity stored at topological interfaces that are in some ways analogous to the storage of stress at faults in the Earth's crust. Comparison of these values to solar flares and interplanetary coronal mass ejections implies that this is the primary storage mechanism for energy and magnetic helicity released in those phenomena, and suggests a useful tool for quantitative prediction of geomagnetic storms.

  8. The extended polar writhe: a tool for open curves mechanics

    NASA Astrophysics Data System (ADS)

    Prior, Christopher B.; Neukirch, Sébastien

    2016-05-01

    A measure of the writhing of a curve is introduced and is used to extend the Călugăreanu decomposition for closed curves, as well as the polar decomposition for curves bound between planes. The new writhe measure is also shown to be able to assess changes in linking due to belt-trick and knotting type deformations, and further its utility is illustrated on examples taken from elastic rod parameter-continuation studies. Finally C++ and mathematica codes are made available and shown to be faster than existing algorithms for the numerical computation of the writhe.

  9. Aconitine-induced writhing as a method for assessing aspirin-like analgesic activity.

    PubMed

    Bhalla, T N; Bhargava, K P

    1980-01-01

    A painful writhing syndrome is produced by aconitine when given intraperitoneally. It is similar to that induced by other chemical agent viz. phenylquinone, acetic acid, and bradykinin. Aconitine writhing is quick to appear, shows greater frequency and longer duration than that induced by other agents. The nonnarcotic analgesics more selectively antagonize the aconitine writhing than orally-administered narcotic analgesics. Thus the aconitine writhing method is a very suitable method for the selective screening of the aspirin type of analgesic agent.

  10. Conservation of writhe helicity under anti-parallel reconnection

    PubMed Central

    Laing, Christian E.; Ricca, Renzo L.; Sumners, De Witt L.

    2015-01-01

    Reconnection is a fundamental event in many areas of science, from the interaction of vortices in classical and quantum fluids, and magnetic flux tubes in magnetohydrodynamics and plasma physics, to the recombination in polymer physics and DNA biology. By using fundamental results in topological fluid mechanics, the helicity of a flux tube can be calculated in terms of writhe and twist contributions. Here we show that the writhe is conserved under anti-parallel reconnection. Hence, for a pair of interacting flux tubes of equal flux, if the twist of the reconnected tube is the sum of the original twists of the interacting tubes, then helicity is conserved during reconnection. Thus, any deviation from helicity conservation is entirely due to the intrinsic twist inserted or deleted locally at the reconnection site. This result has important implications for helicity and energy considerations in various physical contexts. PMID:25820408

  11. [The influence of high pressure on the 3-indoleacetic-acid-induced curvature of Avena coleoptiles in the Went-test].

    PubMed

    Chrometzka, P

    1967-12-01

    1. High atmospheric pressure causes an increase of the 3-indoleacetic-acid-induced curvature of Avena coleoptiles in the Went-test, regardless of whether the applied gas is nitrogen, hydrogen, oxygen, or air. 2. The highest increase was caused by high pressure of oxygen, the lowest by lack of oxygen. 3. The high pressure effect was also observed with coleoptiles which were treated 20 hours prior to the test and which were then kept under normal pressure. 4. High pressure of oxygen for a long period (20 hours) had a poisonous effect on the coleoptiles. They ceased to grow. Preliminary studies have shown that the respiration is enhanced if the coleoptiles have been kept under high pressure. PMID:24554325

  12. The evolution of writhe in kink-unstable flux ropes and erupting filaments

    NASA Astrophysics Data System (ADS)

    Török, T.; Kliem, B.; Berger, M. A.; Linton, M. G.; Démoulin, P.; van Driel-Gesztelyi, L.

    2014-06-01

    The helical kink instability of a twisted magnetic flux tube has been suggested as a trigger mechanism for solar filament eruptions and coronal mass ejections (CMEs). In order to investigate if estimations of the pre-emptive twist can be obtained from observations of writhe in such events, we quantitatively analyze the conversion of twist into writhe in the course of the instability, using numerical simulations. We consider the line tied, cylindrically symmetric Gold-Hoyle flux rope model and measure the writhe using the formulae by Berger and Prior which express the quantity as a single integral in space. We find that the amount of twist converted into writhe does not simply scale with the initial flux rope twist, but depends mainly on the growth rates of the instability eigenmodes of higher longitudinal order than the basic mode. The saturation levels of the writhe, as well as the shapes of the kinked flux ropes, are very similar for considerable ranges of initial flux rope twists, which essentially precludes estimations of pre-eruptive twist from measurements of writhe. However, our simulations suggest an upper twist limit of ˜6π for the majority of filaments prior to their eruption.

  13. TWIST, WRITHE, AND HELICITY IN THE INNER PENUMBRA OF A SUNSPOT

    SciTech Connect

    Ruiz Cobo, B.; Puschmann, K. G. E-mail: kgp@aip.de

    2012-02-01

    The aim of this work is the determination of the twist, writhe, and self-magnetic helicity of penumbral filaments located in an inner sunspot penumbra. For this purpose, we inverted data taken with the spectropolarimeter on board Hinode with the SIR (Stokes Inversion based on Response function) code. For the construction of a three-dimensional geometrical model we applied a genetic algorithm minimizing the divergence of B-vector and the net magnetohydrodynamic force, consequently a force-free solution would be reached if possible. We estimated two proxies to the magnetic helicity frequently used in literature: the force-free parameter {alpha}{sub z} and the current helicity term h{sub c{sub z}}. We show that both proxies are only qualitative indicators of the local twist as the magnetic field in the area under study significantly departs from a force-free configuration. The local twist shows significant values only at the borders of bright penumbral filaments with opposite signs on each side. These locations are precisely correlated to large electric currents. The average twist (and writhe) of penumbral structures is very small. The spines (dark filaments in the background) show a nearly zero writhe. The writhe per unit length of the intraspines diminishes with increasing length of the tube axes. Thus, the axes of tubes related to intraspines are less wrung when the tubes are more horizontal. As the writhe of the spines is very small, we can conclude that the writhe reaches only significant values when the tube includes the border of an intraspine.

  14. The influence of neuropeptides on Malpighian tubule writhing and its significance for excretion.

    PubMed

    Coast, G M

    1998-01-01

    Diuretic peptides (locustakinin and Locusta-DH) increase the spontaneous contractile activity of visceral muscle fibers associated with Malpighian tubules from the migratory locust (Locusta migratoria) at concentrations that increase urine production. Muscle activity is shown to assist the flow of material in the tubule lumen, but is not essential for diuresis. Tubule writhing also serves to reduce unstirred layers (USLs) at the basolateral surface of the epithelium and thereby facilitates the excretion of solutes entering the lumen by passive diffusion. PMID:9533634

  15. Dynamics of Bacillus subtilis helical macrofiber morphogenesis: writhing, folding, close packing, and contraction.

    PubMed Central

    Mendelson, N H

    1982-01-01

    Helical Bacillus subtilis macrofibers are highly ordered structures consisting of individual cells packed in a geometry remarkably similar to that found in helically twisted yarns (G. A. Carnaby, in J. W. S. Hearle et al., ed., The Mechanics of Flexible Fibre Assemblies, p. 99-112, 1980; N. H. Mendelson, Proc. Natl. Acad. Sci. U.S.A. 75:2478-2482, 1978). The growth and formation of macrofibers were studied with time-lapse microscopy methods. The basic growth mode consisted of fiber elongation, folding, and the helical wrapping together of the folded portion into a tight helical fiber. This sequence was reiterated at both ends of the structure, resulting in terminal loops. Macrofiber growth was accompanied by the helical turning of the structure along its long axis. Right-handed structures turned clockwise and left-handed ones turned counterclockwise when viewed along the length of a fiber looking toward a loop end. Helical turning forced the individual cellular filaments into a close-packing arrangement during growth. Tension was evident within the structures and they writhed as they elongated. Tension was relieved by folding, which occurred when writhing became so violent that the structure touched itself, forming a loop. When the multistranded structure produced by repeated folding cycles became too rigid for additional folding, the morphogenesis of a ball-like structure began. The dynamics of helical macrofiber formation was interpreted in terms of stress-strain deformations. In view of the similarities between macrofiber structures and those found in multifilament yarns and cables, the physics of helical macrofiber structure and also growth may be suitable for analysis developed in these fields concerning the mechanics of flexible fiber assemblies (C. P. Buckley; J. W. S. Hearle; and J. J. Thwaites, in J. W. S. Hearle et al., ed., The Mechanics of Flexible Fibre Assemblies, p. 1-97, 1980). Images PMID:6806245

  16. OBSERVATIONS FROM SDO, HINODE, AND STEREO OF A TWISTING AND WRITHING START TO A SOLAR-FILAMENT-ERUPTION CASCADE

    SciTech Connect

    Sterling, Alphonse C.; Moore, Ronald L.; Hara, Hirohisa E-mail: ron.moore@nasa.gov

    2012-12-10

    We analyze data from SDO (AIA, HMI), Hinode (SOT, XRT, EIS), and STEREO (EUVI) of a solar eruption sequence of 2011 June 1 near 16:00 UT, with an emphasis on the early evolution toward eruption. Ultimately, the sequence consisted of three emission bursts and two filament ejections. SDO/AIA 304 A images show absorbing-material strands initially in close proximity which over {approx}20 minutes form a twisted structure, presumably a flux rope with {approx}10{sup 29} erg of free energy that triggers the resulting evolution. A jump in the filament/flux rope's displacement (average velocity {approx}20 km s{sup -1}) and the first burst of emission accompanies the flux-rope formation. After {approx}20 more minutes, the flux rope/filament kinks and writhes, followed by a semi-steady state where the flux rope/filament rises at ({approx}5 km s{sup -1}) for {approx}10 minutes. Then the writhed flux rope/filament again becomes MHD unstable and violently erupts, along with rapid (50 km s{sup -1}) ejection of the filament and the second burst of emission. That ejection removed a field that had been restraining a second filament, which subsequently erupts as the second filament ejection accompanied by the third (final) burst of emission. Magnetograms from SDO/HMI and Hinode/SOT, and other data, reveal several possible causes for initiating the flux-rope-building reconnection, but we are not able to say which is dominant. Our observations are consistent with magnetic reconnection initiating the first burst and the flux-rope formation, with MHD processes initiating the further dynamics. Both filament ejections are consistent with the standard model for solar eruptions.

  17. Observations from Hinode and SDO of a Twisting and Writhing Start to a Solar-filament-eruption Cascade

    NASA Technical Reports Server (NTRS)

    Sterling, Alphonse C.; Moore, Ronald L.; Hara, Hirohisa

    2013-01-01

    Active region eruption of 1 June 2011. Ejective eruption. GOES class C4.1 flare. SDO/AIA, various filters (94, 131, 171, 193, 211, 304, 335 Ang.) High time cadence (24 s) and high spatial resolution (0 .6 pixels). SDO/HMI line-of-sight magnetograms. Hinode observed the onset, and the later decay phase. There are two filament eruptions (filament 1 and filament 2). Filament 1 has slow rise with steps, as in several previous cases. GOES "episodes" play role of "microflares" in other events; that is, filament jumps <=> intensity peaks. Episode 1 brightening: Accompanied by filament 1 s initial motions. (Rest of talk.) Filament 1 becomes unstable, and.. Episode 2 brightening: Flare ribbons following filament 1 s fast liftoff. This destabilizes neighboring filament 2, and... Episode 3 brightening: Flare ribbons of whole system following filament 2 s eruption.Something leads to reconnection; not totally clear what. Reconnection -> twisted flux rope in approx.20 min; episode 1 microflare (flare ribbons; TC) and filament jump. Twist -> writhe, via kink instability; filament-trajectory plateau, approx. 20 min. Writhe -> jump and eruption of filament 1, via instability; episode 2 microflare (flare ribbons; TC). (E.g., Williams et al.) First eruption -> second filament eruption (episode 3 flare ribbons; TC). (E.g., Sterling, Moore; Liu et al.; Torok et al.; Schrijver & Title.). Estimate amount of free energy in newly-twisted field (cf. Moore 1988): where we have taken L and r = 50, 3 arcsec. Energy of the total system is likely 1030 ergs or more. So "no" is answer to question. Additional energy comes from remainder of sheared large loop, shear (free energy) of second filament, etc. (Normally assumed situation.) Some history of twist-induced instability in filament eruptions: e.g., Sakurai, Torok & Kliem, Fan & Gibson, Gilbert et al., van Driel-Gesztelyi et al. Criterion : Kink instability for line-tied tube (Hood & Priest): 2.5pi; for Titov & Demoulin loop (Torok et al

  18. Minocycline ameliorates prenatal valproic acid induced autistic behaviour, biochemistry and blood brain barrier impairments in rats.

    PubMed

    Kumar, Hariom; Sharma, Bhupesh

    2016-01-01

    Autism is a neurodevelopment disorder. One percent worldwide population suffers with autism and males suffer more than females. Microglia plays an important role in neurodevelopment, neuropsychiatric and neurodegenerative disorders. The present study has been designed to investigate the role of minocycline in prenatal valproic acid induced autism in rats. Animals with prenatal valproic acid have reduced social interaction (three chamber social behaviour apparatus), spontaneous alteration (Y-Maze), exploratory activity (Hole board test), intestinal motility, serotonin levels (both in prefrontal cortex and ileum) and prefrontal cortex mitochondrial complex activity (complexes I, II, IV). Furthermore, prenatal valproic acid treated animals have shown an increase in locomotion (actophotometer), anxiety (elevated plus maze), brain oxidative stress (thiobarbituric acid reactive species, glutathione, catalase), nitrosative stress (nitrite/nitrate), inflammation (both in brain and ileum myeloperoxidase activity), calcium and blood brain barrier permeability. Treatment with minocycline significantly attenuated prenatal valproic acid induced reduction in social interaction, spontaneous alteration, exploratory activity intestinal motility, serotonin levels and prefrontal cortex mitochondrial complex activity. Furthermore, minocycline has also attenuated prenatal valproic acid induced increase in locomotion, anxiety, brain oxidative and nitrosative stress, inflammation, calcium and blood brain barrier permeability. Thus, it may be concluded that prenatal valproic acid has induced autistic behaviour, biochemistry and blood brain barrier impairment in animals, which were significantly attenuated by minocycline. Minocycline should be explored further for its therapeutic benefits in autism.

  19. Minocycline ameliorates prenatal valproic acid induced autistic behaviour, biochemistry and blood brain barrier impairments in rats.

    PubMed

    Kumar, Hariom; Sharma, Bhupesh

    2016-01-01

    Autism is a neurodevelopment disorder. One percent worldwide population suffers with autism and males suffer more than females. Microglia plays an important role in neurodevelopment, neuropsychiatric and neurodegenerative disorders. The present study has been designed to investigate the role of minocycline in prenatal valproic acid induced autism in rats. Animals with prenatal valproic acid have reduced social interaction (three chamber social behaviour apparatus), spontaneous alteration (Y-Maze), exploratory activity (Hole board test), intestinal motility, serotonin levels (both in prefrontal cortex and ileum) and prefrontal cortex mitochondrial complex activity (complexes I, II, IV). Furthermore, prenatal valproic acid treated animals have shown an increase in locomotion (actophotometer), anxiety (elevated plus maze), brain oxidative stress (thiobarbituric acid reactive species, glutathione, catalase), nitrosative stress (nitrite/nitrate), inflammation (both in brain and ileum myeloperoxidase activity), calcium and blood brain barrier permeability. Treatment with minocycline significantly attenuated prenatal valproic acid induced reduction in social interaction, spontaneous alteration, exploratory activity intestinal motility, serotonin levels and prefrontal cortex mitochondrial complex activity. Furthermore, minocycline has also attenuated prenatal valproic acid induced increase in locomotion, anxiety, brain oxidative and nitrosative stress, inflammation, calcium and blood brain barrier permeability. Thus, it may be concluded that prenatal valproic acid has induced autistic behaviour, biochemistry and blood brain barrier impairment in animals, which were significantly attenuated by minocycline. Minocycline should be explored further for its therapeutic benefits in autism. PMID:26551768

  20. Amoxicillin/clavulanic acid-induced pemphigus vulgaris: case report.

    PubMed

    Baroni, Adone; Russo, Teresa; Faccenda, Franco; Piccolo, Vincenzo

    2012-01-01

    Drug-induced pemphigus is a well-established variety of pemphigus, presenting with clinical and histopathologic features identical to idiopathic form. Medical history plays a fundamental role in the diagnosis of drug-induced pemphigus. A large variety of drugs have been implicated in its pathogenesis and they may induce acantholysis via biochemical and/or immune mechanism. We present a case of a 69-year-old woman affected by amoxicillin/clavulanic acid-induced pemphigus and discuss its pathogenetic mechanism.

  1. Role of opioid system in modulation of pain sensitivity under conditons of low and high environmental temperature.

    PubMed

    Kolotilova, A B; Guzevatikh, L S; Valujskikh, D V; Emel'yanova, T G

    2008-06-01

    The dependence of pain sensitivity in acetic acid-induced writhing test on environmental temperature was described by a bell-shaped curve. The maximum number of writhings was observed in thermoneutral environment and minimum in hot and cold environment. Under conditions of opioid receptor blockade with naloxone, naltrindole, norbinaltorphimine, analgesia is partially mediated by micro-, delta-, and kappa-opioid receptors.

  2. Comparative neuroprotective profile of statins in quinolinic acid induced neurotoxicity in rats.

    PubMed

    Kalonia, Harikesh; Kumar, Puneet; Kumar, Anil

    2011-01-01

    A possible neuroprotective role has been recently suggested for 3H3MGCoA reductase inhibitors (statins). Here, we sought to determine neuroprotective effect of statins in quinolinic acid induced neurotoxicity in rats. Rats were surgically administered quinolinic acid and treated with Atorvastatin (10, 20 mg/kg), simvastatin (15, 30 mg/kg) and fluvastatin (5, 10 mg/kg) once daily up to 3 weeks. Atorvastatin (10, 20 mg/kg), simvastatin (30 mg/kg) and fluvastatin (10 mg/kg) treatment significantly attenuated the quinolinic acid induced behavioral (locomotor activity, rotarod performance and beam walk test), biochemical (lipid peroxidation, nitrite concentration, SOD and catalase), mitochondrial enzyme complex alterations in rats suggesting their free radical scavenging potential. Additionally, atorvastatin (10, 20 mg/kg), simvastatin (30 mg/kg) and fluvastatin (10 mg/kg) significantly decrease the TNF-α level and striatal lesion volume in quinolinic acid treated animals indicating their anti-inflammatory effects. In comparing the protective effect of different statins, atorvastatin is effective at both the doses while simvastatin and fluvastatins at respective lower doses were not able to produce the protective effect in quinolinic acid treated animals. These modulations can account, at least partly, for the beneficial effect of statins in our rodent model of striatal degeneration. Our findings show that statins could be explored as possible neuroprotective agents for neurodegenerative disorders such as HD. PMID:20696189

  3. Licofelone attenuates quinolinic acid induced Huntington like symptoms: possible behavioral, biochemical and cellular alterations.

    PubMed

    Kalonia, Harikesh; Kumar, Puneet; Kumar, Anil

    2011-03-30

    Cyclo-oxygenase and lipoxygenase enzymes are involved in arachidonic acid metabolism. Emerging evidence indicates that cyclo-oxygenase and lipoxygenase inhibitors prevent neurodegenerative processes and related complications. Therefore, the present study has been designed to explore the neuroprotective potential of licofelone (dual COX-2/5-LOX inhibitor) against quinolinic acid induced Huntington like symptom in rats. Intrastriatal administration of quinolinic acid significantly caused reduction in body weight and motor function (locomotor activity, rotarod performance and beam walk test), oxidative defense (as evidenced by increased lipid peroxidation, nitrite concentration and decreased endogenous antioxidant enzymes), alteration in mitochondrial enzyme complex (I, II and IV) activities, raised TNF-α level and striatal lesion volume as compared to sham treated animals. Licofelone (2.5, 5 and 10 mg/kg) treatment significantly improved body weight, locomotor activity, rotarod performance, balance beam walk performance, oxidative defense, mitochondrial enzyme complex activities and attenuated TNF-α level and striatal lesion as compared to control (quinolinic acid). The present study highlights that licofelone attenuates behavioral, biochemical and cellular alterations against quinolinic acid induced neurotoxicity and this could be an important therapeutic avenue to ameliorate the Huntington like symptoms. PMID:21237233

  4. γ-Hydroxybutyric Acid-Induced Electrographic Seizures

    PubMed Central

    Cheung, Joseph; Lucey, Brendan P.; Duntley, Stephen P.; Darken, Rachel S.

    2014-01-01

    We describe a case of absence-like electrographic seizures during NREM sleep in a patient who was taking sodium oxybate, a sodium salt of γ-hydroxybutyric acid (GHB). An overnight full montage electroencephalography (EEG) study revealed numerous frontally predominant rhythmic 1.5-2 Hz sharp waves and spike-wave activity during stage N2 and N3 sleep at the peak dose time for sodium oxybate, resembling atypical absence-like electrographic seizures. The patient was later weaned off sodium oxybate, and a repeat study did not show any such electrographic seizures. Absence-like seizures induced by GHB had previously been described in experimental animal models. We present the first reported human case of absence-like electrographic seizure associated with sodium oxybate. Citation: Cheung J, Lucey BP, Duntley SP, Darken RS. γ-hydroxybutyric acid-induced electrographic seizures. J Clin Sleep Med 2014;10(7):811-812. PMID:25024661

  5. Increased isoprostane levels in oleic acid-induced lung injury

    SciTech Connect

    Ono, Koichi; Koizumi, Tomonobu; Tsushima, Kenji; Yoshikawa, Sumiko; Yokoyama, Toshiki; Nakagawa, Rikimaru; Obata, Toru

    2009-10-16

    The present study was performed to examine a role of oxidative stress in oleic acid-induced lung injury model. Fifteen anesthetized sheep were ventilated and instrumented with a lung lymph fistula and vascular catheters for blood gas analysis and measurement of isoprostanes (8-epi prostaglandin F2{alpha}). Following stable baseline measurements, oleic acid (0.08 ml/kg) was administered and observed 4 h. Isoprostane was measured by gas chromatography mass spectrometry with the isotope dilution method. Isoprostane levels in plasma and lung lymph were significantly increased 2 h after oleic acid administration and then decreased at 4 h. The percent increases in isoprostane levels in plasma and lung lymph at 2 h were significantly correlated with deteriorated oxygenation at the same time point, respectively. These findings suggest that oxidative stress is involved in the pathogenesis of the pulmonary fat embolism-induced acute lung injury model in sheep and that the increase relates with the deteriorated oxygenation.

  6. Proteomic study on usnic-acid-induced hepatotoxicity in rats.

    PubMed

    Liu, Qian; Zhao, Xiaoping; Lu, Xiaoyan; Fan, Xiaohui; Wang, Yi

    2012-07-25

    Usnic acid, a lichen metabolite, is used as a dietary supplement for weight loss. However, clinical studies have shown that usnic acid causes hepatotoxicity. The present study aims to investigate the mechanism of usnic acid hepatotoxicity in vivo. Two-dimensional gel electrophoresis coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was used to analyze the expression profiles of differentially regulated and expressed proteins in rat liver after usnic acid administration. The results reveal the differential expression of 10 proteins in usnic-acid-treated rats compared to the normal controls. These proteins are associated with oxidative stress, lipid metabolism, and several other molecular pathways. The endoplasmic reticulum and mitochondria may be the primary targets of usnic-acid-induced hepatotoxicity.

  7. Unsaturated fatty acids induce non-canonical autophagy

    PubMed Central

    Niso-Santano, Mireia; Malik, Shoaib Ahmad; Pietrocola, Federico; Bravo-San Pedro, José Manuel; Mariño, Guillermo; Cianfanelli, Valentina; Ben-Younès, Amena; Troncoso, Rodrigo; Markaki, Maria; Sica, Valentina; Izzo, Valentina; Chaba, Kariman; Bauvy, Chantal; Dupont, Nicolas; Kepp, Oliver; Rockenfeller, Patrick; Wolinski, Heimo; Madeo, Frank; Lavandero, Sergio; Codogno, Patrice; Harper, Francis; Pierron, Gérard; Tavernarakis, Nektarios; Cecconi, Francesco; Maiuri, Maria Chiara; Galluzzi, Lorenzo; Kroemer, Guido

    2015-01-01

    To obtain mechanistic insights into the cross talk between lipolysis and autophagy, two key metabolic responses to starvation, we screened the autophagy-inducing potential of a panel of fatty acids in human cancer cells. Both saturated and unsaturated fatty acids such as palmitate and oleate, respectively, triggered autophagy, but the underlying molecular mechanisms differed. Oleate, but not palmitate, stimulated an autophagic response that required an intact Golgi apparatus. Conversely, autophagy triggered by palmitate, but not oleate, required AMPK, PKR and JNK1 and involved the activation of the BECN1/PIK3C3 lipid kinase complex. Accordingly, the downregulation of BECN1 and PIK3C3 abolished palmitate-induced, but not oleate-induced, autophagy in human cancer cells. Moreover, Becn1+/− mice as well as yeast cells and nematodes lacking the ortholog of human BECN1 mounted an autophagic response to oleate, but not palmitate. Thus, unsaturated fatty acids induce a non-canonical, phylogenetically conserved, autophagic response that in mammalian cells relies on the Golgi apparatus. PMID:25586377

  8. Characterization of salicylic acid-induced genes in Chinese cabbage.

    PubMed

    Park, Y-S; Min, H-J; Ryang, S-H; Oh, K-J; Cha, J-S; Kim, H Y; Cho, T-J

    2003-06-01

    Salicylic acid is a messenger molecule in the activation of defense responses in plants. In this study, we isolated four cDNA clones representing salicylic acid-induced genes in Chinese cabbage (Brassica rapa subsp. pekinensis) by subtractive hybridization. Of the four clones, the BC5-2 clone encodes a putative glucosyltransferase protein. The BC5-3 clone is highly similar to an Arabidopsis gene encoding a putative metal-binding farnesylated protein. The BC6-1 clone is a chitinase gene with similarities to a rapeseed class IV chitinase. Class IV chitinases have deletions in the chitin-binding and catalytic domains and the BC6-1 chitinase has an additional deletion in the catalytic domain. The BCP8-1 clone is most homologous to an Arabidopsis gene that contains a tandem array of two thiJ-like sequences. These four cabbage genes were barely expressed in healthy leaves, but were strongly induced by salicylic acid and benzothiadiazole. Expression of the three genes represented by the BC5-2, BC5-3 and BCP8-1 clones were also induced by Pseudomonas syringae pv. tomato, a nonhost pathogen that elicits a hypersensitive response in Chinese cabbage. None of these four genes, however, was strongly induced by methyl jasmonate or by ethylene.

  9. Sulfuric acid-induced corrosion of aluminum surfaces

    SciTech Connect

    Dai, Q.; Freedman, A.; Robinson, G.N.

    1995-12-01

    The sulfuric acid-induced corrosion of smooth (2 nm average roughness) aluminum surfaces has been studied in real times using an in situ Fourier transform infrared reflection absorption spectrometer and a quartz crystal microbalance. Submicron thick, 35 to 55 weight percent (5 to 12 molal), sulfuric acid films were formed on room temperature metal surfaces by the reaction of gas-phase SO{sub 3} and H{sub 2}O vapor in a flowing gas system at a total pressure of {approximately}200 Torr. The deposition of the acid films and subsequent changes in their chemical composition resulting from corrosion of the aluminum substrate could be monitored using characteristic infrared absorption features. The corrosion process always significantly perturbed the spectral signature of the films from that which was observed on inert gold surfaces. Using changes in spectral features that are linked to the production of Al{sup 3+} as indicators of corrosion, the authors conclude the rate of corrosion of the metal is strongly enhanced by both higher relative humidities and increased rates of sulfuric acid deposition.

  10. Computerized image analysis for acetic acid induced intraepithelial lesions

    NASA Astrophysics Data System (ADS)

    Li, Wenjing; Ferris, Daron G.; Lieberman, Rich W.

    2008-03-01

    Cervical Intraepithelial Neoplasia (CIN) exhibits certain morphologic features that can be identified during a visual inspection exam. Immature and dysphasic cervical squamous epithelium turns white after application of acetic acid during the exam. The whitening process occurs visually over several minutes and subjectively discriminates between dysphasic and normal tissue. Digital imaging technologies allow us to assist the physician analyzing the acetic acid induced lesions (acetowhite region) in a fully automatic way. This paper reports a study designed to measure multiple parameters of the acetowhitening process from two images captured with a digital colposcope. One image is captured before the acetic acid application, and the other is captured after the acetic acid application. The spatial change of the acetowhitening is extracted using color and texture information in the post acetic acid image; the temporal change is extracted from the intensity and color changes between the post acetic acid and pre acetic acid images with an automatic alignment. The imaging and data analysis system has been evaluated with a total of 99 human subjects and demonstrate its potential to screening underserved women where access to skilled colposcopists is limited.

  11. Sphingoid bases inhibit acid-induced demineralization of hydroxyapatite.

    PubMed

    Valentijn-Benz, Marianne; van 't Hof, Wim; Bikker, Floris J; Nazmi, Kamran; Brand, Henk S; Sotres, Javier; Lindh, Liselott; Arnebrant, Thomas; Veerman, Enno C I

    2015-01-01

    Calcium hydroxyapatite (HAp), the main constituent of dental enamel, is inherently susceptible to the etching and dissolving action of acids, resulting in tooth decay such as dental caries and dental erosion. Since the prevalence of erosive wear is gradually increasing, there is urgent need for agents that protect the enamel against erosive attacks. In the present study we studied in vitro the anti-erosive effects of a number of sphingolipids and sphingoid bases, which form the backbone of sphingolipids. Pretreatment of HAp discs with sphingosine, phytosphingosine (PHS), PHS phosphate and sphinganine significantly protected these against acid-induced demineralization by 80 ± 17%, 78 ± 17%, 78 ± 7% and 81 ± 8%, respectively (p < 0.001). On the other hand, sphingomyelin, acetyl PHS, octanoyl PHS and stearoyl PHS had no anti-erosive effects. Atomic force measurement revealed that HAp discs treated with PHS were almost completely and homogeneously covered by patches of PHS. This suggests that PHS and other sphingoid bases form layers on the surface of HAp, which act as diffusion barriers against H(+) ions. In principle, these anti-erosive properties make PHS and related sphingosines promising and attractive candidates as ingredients in oral care products.

  12. Formic acid and acetic acid induce a programmed cell death in pathogenic Candida species.

    PubMed

    Lastauskienė, Eglė; Zinkevičienė, Auksė; Girkontaitė, Irutė; Kaunietis, Arnoldas; Kvedarienė, Violeta

    2014-09-01

    Cutaneous fungal infections are common and widespread. Antifungal agents used for the treatment of these infections often have undesirable side effects. Furthermore, increased resistance of the microorganisms to the antifungal drugs becomes the growing problem. Accordingly, the search for natural antifungal compounds continues to receive attention. Apoptosis is highly regulated programmed cell death. During yeast cell apoptosis, amino acids and peptides are released and can stimulate regeneration of human epithelium cells. Thus, detection of chemical compounds inducing apoptosis in yeast and nontoxic for humans is of great medical relevance. The aim of this study was to detect chemical compound inducing apoptosis in pathogenic Candida species with the lowest toxicity to the mammalian cells. Five chemical compounds--acetic acid, sodium bicarbonate, potassium carbonate, lithium acetate, and formic acid--were tested for evaluation of antifungal activity on C. albicans, C. guilliermondii, and C. lusitaniae. The results showed that acetic acid and formic acid at the lowest concentrations induced yeast cells death. Apoptosis analysis revealed that cells death was accompanied by activation of caspase. Minimal inhibitory concentrations of potassium carbonate and sodium bicarbonate induced Candida cells necrosis. Toxicity test with mammalian cell cultures showed that formic acid has the lowest effect on the growth of Jurkat and NIH 3T3 cells. In conclusion, our results show that a low concentration of formic acid induces apoptosis-like programmed cell death in the Candida yeast and has a minimal effect on the survivability of mammalian cells, suggesting potential applications in the treatment of these infections. PMID:24752490

  13. Chrysophanic Acid Induces Necrosis but not Necroptosis in Human Renal Cell Carcinoma Caki-2 Cells

    PubMed Central

    Choi, Joon-Seok

    2016-01-01

    Background: Chrysophanic acid, also known as chrysophanol, has a number of biological activities. It enhances memory and learning abilities, raises superoxide dismutase activity, and has anti-cancer effects in several model systems. According to previous reports, chrysophanic acid-induced cell death shares features of necrotic cell death. However, the molecular and cellular processes underlying chrysophanic acid-induced cell death remain poorly understood. Methods: Chrysophanic acid-induced cell death was monitored by cell viability assay and Annexin V-propidium iodide (PI) staining of renal cell carcinoma Caki-2 cells. The induction of intracellular reactive oxygen species (ROS) by chrysophanic acid and the suppression of ROS by anti-oxidants were evaluated by 2′,7′-dichlorofluorescin diacetate staining. The expression and phosphorylation of proteins that are involved in apoptosis and necroptosis were detected by immunoblotting. Results: The extent of chrysophanic acid-induced cell death was concentration and time dependent, and dead cells mainly appeared in the PI-positive population, which is a major feature of necrosis, upon fluorescence-activated cell sorting analysis. Chrysophanic acid-induced cell death was associated with the generation of intracellular ROS, and this effect was reversed by pretreatment with N-acetyl cysteine. Chrysophanic acid-induced cell death was not associated with changes in apoptotic or necroptotic marker proteins. Conclusions: The cell death induced by chrysophanic acid resembled neither apoptotic nor necroptotic cell death in human renal cell carcinoma Caki-2 cells. PMID:27390736

  14. Allicin alleviates inflammation of trinitrobenzenesulfonic acid-induced rats and suppresses P38 and JNK pathways in Caco-2 cells.

    PubMed

    Li, Chen; Lun, Weijian; Zhao, Xinmei; Lei, Shan; Guo, Yandong; Ma, Jiayi; Zhi, Fachao

    2015-01-01

    Background. Allicin has anti-inflammatory, antioxidative and proapoptotic properties. Aims. To evaluate the effects and investigate the mechanism of allicin on trinitrobenzenesulfonic acid-induced colitis, specifically with mesalazine or sulfasalazine. Methods. 80 rats were divided equally into 8 groups: control; trinitrobenzenesulfonic acid; allicin prevention; allicin; mesalazine; sulfasalazine; allicin + sulfasalazine, and mesalazine + allicin. Systemic and colonic inflammation parameters were analysed. In addition, protein and culture medium of Caco-2 cells treated with various concentrations of IL-1β or allicin were collected for investigation of IL-8, NF-κB p65 P38, ERK, and JNK. One-way ANOVA and Kruskal-Wallis H test were used for parametric and nonparametric tests, respectively. Results. Allicin reduced the body weight loss of trinitrobenzenesulfonic acid-induced rats, histological score, serum TNF-α and IL-1β levels, and colon IL-1β mRNA level and induced serum IL-4 level, particularly in combination with mesalazine. In addition, 1 ng/mL IL-1β stimulated the P38, ERK, and JNK pathways, whereas pretreatment with allicin depressed this phenomenon, except for the ERK pathway. Conclusions. The inflammation induced by trinitrobenzenesulfonic acid is mitigated significantly by allicin treatment, particularly combined with mesalazine. Allicin inhibits the P38 and JNK pathways and the expression of NF-κB which explained the potential anti-inflammatory mechanisms of allicin. PMID:25729217

  15. Unsaturated fatty acids induce calcium influx into keratinocytes and cause abnormal differentiation of epidermis.

    PubMed

    Katsuta, Yuji; Iida, Toshii; Inomata, Shinji; Denda, Mitsuhiro

    2005-05-01

    Abnormal follicular keratinization is involved in comedogenesis in acne vulgaris. We recently demonstrated that calcium influx into epidermal keratinocytes is associated with impaired skin barrier function and epidermal proliferation. Based on these results, we hypothesized that sebum components affect calcium dynamics in the keratinocyte and consequently induce abnormal keratinization. To test this idea, we first observed the effects of topical application of sebum components, triglycerides (triolein), saturated fatty acids (palmitic acid and stearic acid), and unsaturated fatty acids (oleic acid and palmitoleic acid) on hairless mouse skin. Neither triglyceride nor saturated fatty acids affected the skin surface morphology or epidermal proliferation. On the other hand, application of unsaturated fatty acids, oleic acid, and palmitoleic acid induced scaly skin, abnormal keratinization, and epidermal hyperplasia. Application of triglycerides and saturated fatty acids on cultured human keratinocytes did not affect the intracellular calcium concentration ([Ca(2+)](i)), whereas unsaturated fatty acids increased the [Ca(2+)](i) of the keratinocytes. Moreover, application of oleic acid on hairless mouse skin induced an abnormal calcium distribution in the epidermis. These results suggest that unsaturated fatty acids in sebum alter the calcium dynamics in epidermal keratinocytes and induce abnormal follicular keratinization.

  16. Anti-osteoporosis activity of naringin in the retinoic acid-induced osteoporosis model.

    PubMed

    Wei, Min; Yang, Zhonglin; Li, Ping; Zhang, Yabo; Sse, Wing Cho

    2007-01-01

    Isoflavonoids isolated from plants have been confirmed to fight osteoporosis and promote bone health. However, few studies have been conducted to describe the anti-osteoporosis activity of botanical flavonone. Based on the experimental outcomes, we demonstrated the ability of naringin to fight osteoporosis in vitro. We developed a retinoic acid-induced osteoporosis model of rats to assess whether naringin has similar bioactivity against osteoporosis in vitro. After a 14-day supplement of retinoic acid to induce osteoporosis, SD rats were administered naringin. A blood test showed that naringin-treated rats experienced significantly lower activity of serum alkaline phosphatase and had higher femur bone mineral density, compared to untreated rats. All three dosages of naringin improved the decrease in bone weight coefficient, the length and the diameter of the bone, the content of bone ash, calcium, and phosphorus content induced by retinoic acid. The data of histomorphological metrology of naringin groups showed no difference as compared to normal control rats. These outcomes suggest that naringin offer a potential in the management of osteoporosis in vitro. PMID:17708632

  17. Inhibition of ascorbic acid-induced modifications in lens proteins by peptides.

    PubMed

    Argirova, Mariana; Argirov, Ognyan

    2003-03-01

    The effects of three dipeptides L-phenylalanyl-glybine, glycyl-L-phenylalanine,and aspartame (L-aspartyl-L-phenylalanine, methyl ester) as inhibitors of the ascorbic acid-induced modifications in lens proteins were studied. Their efficiency was compared to that of two known inhibitors--aminoguanidine and carnosine. The tested dipeptides diminished protein carbonyl content by 32-58% and most moderated the formation of chromophores, as measured by the absorbency at 325 nm of the glycated proteins. The appearance of non-tryptophan fluorescence (excitation 340 nm/emission 410 nm) was observed for proteins glycated with ascorbic acid. All of the dipeptides examined, as well as aminoguanidine, decreased this glycation-related fluorescence. The potential inhibitors prevented the intensive formation of very high molecular weight aggregates. A competitive mechanism of their inhibitory effect was proposed, based on the reactivity of individual substances toward ascorbic acid. These findings indicate that they have a potential for use as alternatives for aminoguanidine as an anti-glycation agent.

  18. Bile acids but not acidic acids induce Barrett's esophagus.

    PubMed

    Sun, Dongfeng; Wang, Xiao; Gai, Zhibo; Song, Xiaoming; Jia, Xinyong; Tian, Hui

    2015-01-01

    Barrett's esophagus (BE) is associated with the development of esophageal adenocarcinoma (EAC). Bile acids (BAs) refluxing into the esophagus contribute to esophageal injury, which results in BE and subsequent EAC. We developed two animal models to test the role of BAs in the pathogenesis of BE. We surgically generated BA reflux, with or without gastric acid, in rats. In a second experiment, we fed animals separately with BAs and gastric acid. Pathologic changes were examined and the expression of Muc2 and Cdx2 in BE tissue was tested by immunostaining. Inflammatory factors in the plasma, as well as differentiation genes in BE were examined through highly sensitive ELISA and semi-quantitative RT-PCR techniques. We found that BAs are sufficient for the induction of esophagitis and Barrett's-like metaplasia in the esophagus. Overexpression of inflammatory cells, IL-6, and TNF-α was observed both in animals fed with BAs and surgically generated BA reflux. Furthermore, elevated levels of Cdx2, Muc2, Bmp4, Kit19, and Tff2 (differentiation genes in BE) were found in BA-treated rats. In conclusion, BAs, but not gastric acid, are a major causative factor for BE. We confirmed that BAs contribute to the development of BE by inducing the inflammatory response in the esophagus. Inhibiting BAs may be a promising therapy for BE.

  19. Acid-induced aggregation propensity of nivolumab is dependent on the Fc.

    PubMed

    Liu, Boning; Guo, Huaizu; Xu, Jin; Qin, Ting; Xu, Lu; Zhang, Junjie; Guo, Qingcheng; Zhang, Dapeng; Qian, Weizhu; Li, Bohua; Dai, Jianxin; Hou, Sheng; Guo, Yajun; Wang, Hao

    2016-01-01

    Nivolumab, an anti-programmed death (PD)1 IgG4 antibody, has shown notable success as a cancer treatment. Here, we report that nivolumab was susceptible to aggregation during manufacturing, particularly in routine purification steps. Our experimental results showed that exposure to low pH caused aggregation of nivolumab, and the Fc was primarily responsible for an acid-induced unfolding phenomenon. To compare the intrinsic propensity of acid-induced aggregation for other IgGs subclasses, tocilizumab (IgG1), panitumumab (IgG2) and atezolizumab (aglyco-IgG1) were also investigated. The accurate pH threshold of acid-induced aggregation for individual IgG Fc subclasses was identified and ranked as: IgG1 < aglyco-IgG1 < IgG2 < IgG4. This result was cross-validated by thermostability and conformation analysis. We also assessed the effect of several protein stabilizers on nivolumab, and found mannitol ameliorated the acid-induced aggregation of the molecule. Our results provide valuable insight into downstream manufacturing process development, especially for immune checkpoint modulating molecules with a human IgG4 backbone. PMID:27310175

  20. MICROARRAY ANALYSIS OF DICHLOROACETIC ACID-INDUCED CHANGES IN GENE EXPRESSION

    EPA Science Inventory


    MICROARRAY ANALYSIS OF DICHLOROACETIC ACID-INDUCED CHANGES IN GENE EXPRESSION

    Dichloroacetic acid (DCA) is a major by-product of water disinfection by chlorination. Several studies have demonstrated the hepatocarcinogenicity of DCA in rodents when administered in dri...

  1. Valproic Acid Induced Hyperammonemia in a Long Time Treated Patient

    PubMed Central

    Seide, Margaret; Stern, Robert G.

    2016-01-01

    We report a case of a patient who had been on long time valproic acid for treatment of bipolar affective disorder. While being an inpatient, serology ammonia level testing revealed a very high ammonia level despite being asymptomatic. Dual therapy of carnitine and lactulose was provided to the patient for treatment of the hyperammonemia. It should also be noted that, during this treatment, valproic acid was not stopped. Consequently, this case illustrates that patients can present asymptomatically despite very high ammonia levels and hyperammonemia can occur in chronic valproic acid despite not increasing the dose of the medication and psychiatrists do not need to discontinue valproic acid in the presence of elevated levels of ammonia if the patient shows no signs of encephalopathy or delirium. PMID:27516916

  2. Valproic Acid Induced Hyperammonemia in a Long Time Treated Patient.

    PubMed

    Aiyer, Rohit; Seide, Margaret; Stern, Robert G

    2016-01-01

    We report a case of a patient who had been on long time valproic acid for treatment of bipolar affective disorder. While being an inpatient, serology ammonia level testing revealed a very high ammonia level despite being asymptomatic. Dual therapy of carnitine and lactulose was provided to the patient for treatment of the hyperammonemia. It should also be noted that, during this treatment, valproic acid was not stopped. Consequently, this case illustrates that patients can present asymptomatically despite very high ammonia levels and hyperammonemia can occur in chronic valproic acid despite not increasing the dose of the medication and psychiatrists do not need to discontinue valproic acid in the presence of elevated levels of ammonia if the patient shows no signs of encephalopathy or delirium. PMID:27516916

  3. Human myeloblastic leukemia cells (HL-60) express a membrane receptor for estrogen that signals and modulates retinoic acid-induced cell differentiation

    SciTech Connect

    Kauss, M. Ariel; Reiterer, Gudrun; Bunaciu, Rodica P.; Yen, Andrew

    2008-10-01

    Estrogen receptors are historically perceived as nuclear ligand activated transcription factors. An estrogen receptor has now been found localized to the plasma membrane of human myeloblastic leukemia cells (HL-60). Its expression occurs throughout the cell cycle, progressively increasing as cells mature from G{sub 1} to S to G{sub 2}/M. To ascertain that the receptor functioned, the effect of ligands, including a non-internalizable estradiol-BSA conjugate and tamoxifen, an antagonist of nuclear estrogen receptor function, were tested. The ligands caused activation of the ERK MAPK pathway. They also modulated the effect of retinoic acid, an inducer of MAPK dependent terminal differentiation along the myeloid lineage in these cells. In particular the ligands inhibited retinoic acid-induced inducible oxidative metabolism, a functional marker of terminal myeloid cell differentiation. To a lesser degree they also diminished retinoic acid-induced earlier markers of cell differentiation, namely CD38 and CD11b. However, they did not regulate retinoic acid-induced G{sub 0} cell cycle arrest. There is thus a membrane localized estrogen receptor in HL-60 myeloblastic leukemia cells that can cause ERK activation and modulates the response of these cells to retinoic acid, indicating crosstalk between the membrane estrogen and retinoic acid evoked pathways relevant to propulsion of cell differentiation.

  4. Luteolin prevents uric acid-induced pancreatic β-cell dysfunction

    PubMed Central

    Ding, Ying; Shi, Xuhui; Shuai, Xuanyu; Xu, Yuemei; Liu, Yun; Liang, Xiubin; Wei, Dong; Su, Dongming

    2014-01-01

    Abstract Elevated uric acid causes direct injury to pancreatic β-cells. In this study, we examined the effects of luteolin, an important antioxidant, on uric acid-induced β-cell dysfunction. We first evaluated the effect of luteolin on nitric oxide (NO) formation in uric acid-stimulated Min6 cells using the Griess method. Next, we performed transient transfection and reporter assays to measure transcriptional activity of nuclear factor (NF)-κB. Western blotting assays were also performed to assess the effect of luteolin on the expression of MafA and inducible NO synthase (iNOS) in uric acid-treated cells. Finally, we evaluated the effect of luteolin on uric acid-induced inhibition of glucose-stimulated insulin secretion (GSIS) in Min6 cells and freshly isolated mouse pancreatic islets. We found that luteolin significantly inhibited uric acid-induced NO production, which was well correlated with reduced expression of iNOS mRNA and protein. Furthermore, decreased activity of NF-κB was implicated in inhibition by luteolin of increased iNOS expression induced by uric acid. Besides, luteolin significantly increased MafA expression in Min6 cells exposed to uric acid, which was reversed by overexpression of iNOS. Moreover, luteolin prevented uric acid-induced inhibition of GSIS in both Min6 cells and mouse islets. In conclusion, luteolin protects pancreatic β-cells from uric acid-induced dysfunction and may confer benefit on the protection of pancreatic β-cells in hyperuricemia-associated diabetes. PMID:25050113

  5. Topiramate increases the risk of valproic acid-induced encephalopathy.

    PubMed

    Noh, Young; Kim, Dong Wook; Chu, Kon; Lee, Soon-Tae; Jung, Keun-Hwa; Moon, Hye-Jin; Lee, Sang Kun

    2013-01-01

    Metabolic encephalopathy is a rare but serious complication of valproic acid (VPA) therapy that usually presents with impaired consciousness or increased seizure frequency. Although it has been suggested that topiramate (TPM) increases the risk of VPA-induced encephalopathy, the additional risk in patients receiving TPM therapy has not been evaluated. We reviewed all adult patients who took VPA between January 2005 and February 2009 at the Seoul National University Hospital and identified patients with VPA-induced encephalopathy based on clinical and electroencephalography (EEG) data. Information on sex, age, serum ammonia level, serum VPA level, liver function test, and EEG was collected from patient registry and medical data. We enrolled 8,372 patients who received VPA therapy and 1,236 patients who received VPA/TPM combination therapy. We identified 11 patients with VPA-induced encephalopathy (0.13%), 7 of whom received a combination therapy of VPA and TPM. The odds ratio of VPA-induced encephalopathy with TPM over that without TPM was 10.16. There were no significant differences in sex distribution, number of antiepileptic agents, ammonia level, VPA serum level, underlying diseases, dosage of VPA, duration of VPA treatment, treatment of encephalopathy, and outcomes between the two groups. Our study showed that the prevalence of VPA-induced encephalopathy is approximately 0.1% among patients treated with VPA and that the risk of this condition, although still low, can increase by approximately 10 times in the presence of TPM therapy. Based on these results, we suggest that TPM should be carefully used in patients receiving VPA treatment.

  6. Monomethylarsonous acid induces transformation of human bladder cells

    SciTech Connect

    Bredfeldt, Tiffany G.; Jagadish, Bhumasamudram; Eblin, Kylee E.; Mash, Eugene A.; Gandolfi, A. Jay . E-mail: gandolfi@pharmacy.arizona.edu

    2006-10-01

    Arsenic is a human bladder carcinogen. Arsenic is methylated to both monomethyl and dimethyl metabolites which have been detected in human urine. The trivalent methylated arsenicals are more toxic than inorganic arsenic. It is unknown if these trivalent methylated metabolites can directly cause malignant transformation in human cells. The goal of this study is determine if monomethylarsonous acid (MMA{sup III}) can induce malignant transformation in a human bladder urothelial cell line. To address this goal, a non-tumorigenic human urothelial cell line (UROtsa) was continuously exposed to 0.05 {mu}M MMA{sup III} for 52 weeks. Hyperproliferation was the first phenotypic change observed in exposed UROtsa (URO-MSC). After 12 weeks of exposure, doubling time had decreased from 42 h in unexposed control cells to 27 h in URO-MSC. Hyperproliferation continued to be a quality possessed by the URO-MSC cells after both 24 and 52 weeks of exposure to MMA{sup III}, which had a 40-50% reduction in doubling time. Throughout the 52-week exposure, URO-MSC cells retained an epithelial morphology with subtle morphological differences from control cells. 24 weeks of MMA{sup III} exposure was required to induce anchorage-independent growth as detected by colony formation in soft agar, a characteristic not found in UROtsa cells. To further substantiate that malignant transformation had occurred, URO-MSC cells were tested after 24 and 52 weeks of exposure to MMA{sup III} for the ability to form tumors in SCID mice. Enhanced tumorigenicity in SCID mouse xenografts was observed after 52 weeks of treatment with MMA{sup III}. These observations are the first demonstration of MMA{sup III}-induced malignant transformation in a human bladder urothelial cell line and provide important evidence that MMA{sup III} may be carcinogenic in human tissues.

  7. Orexin A attenuates palmitic acid-induced hypothalamic cell death.

    PubMed

    Duffy, Cayla M; Nixon, Joshua P; Butterick, Tammy A

    2016-09-01

    Palmitic acid (PA), an abundant dietary saturated fatty acid, contributes to obesity and hypothalamic dysregulation in part through increase in oxidative stress, insulin resistance, and neuroinflammation. Increased production of reactive oxygen species (ROS) as a result of PA exposure contributes to the onset of neuronal apoptosis. Additionally, high fat diets lead to changes in hypothalamic gene expression profiles including suppression of the anti-apoptotic protein B cell lymphoma 2 (Bcl-2) and upregulation of the pro-apoptotic protein B cell lymphoma 2 associated X protein (Bax). Orexin A (OXA), a hypothalamic peptide important in obesity resistance, also contributes to neuroprotection. Prior studies have demonstrated that OXA attenuates oxidative stress induced cell death. We hypothesized that OXA would be neuroprotective against PA induced cell death. To test this, we treated an immortalized hypothalamic cell line (designated mHypoA-1/2) with OXA and PA. We demonstrate that OXA attenuates PA-induced hypothalamic cell death via reduced caspase-3/7 apoptosis, stabilization of Bcl-2 gene expression, and reduced Bax/Bcl-2 gene expression ratio. We also found that OXA inhibits ROS production after PA exposure. Finally, we show that PA exposure in mHypoA-1/2 cells significantly reduces basal respiration, maximum respiration, ATP production, and reserve capacity. However, OXA treatment reverses PA-induced changes in intracellular metabolism, increasing basal respiration, maximum respiration, ATP production, and reserve capacity. Collectively, these results support that OXA protects against PA-induced hypothalamic dysregulation, and may represent one mechanism through which OXA can ameliorate effects of obesogenic diet on brain health. PMID:27449757

  8. Protective Effect of Ocimum basilicum Essential Oil Against Acetic Acid-Induced Colitis in Rats.

    PubMed

    Rashidian, Amir; Roohi, Parnia; Mehrzadi, Saeed; Ghannadi, Ali Reza; Minaiyan, Mohsen

    2016-10-01

    Ocimum basilicum L has been traditionally used for the treatment of inflammatory bowel disease in Iran. This study investigates the ameliorative effect of Ocimum basilicum essential oil on an acetic acid-induced colitis model in rats. Ocimum basilicum essential oil with 2 doses (200 and 400 μL/kg) significantly ameliorated wet weight/length ratio of colonic tissue compared to the control group. Higher doses of essential oil (200 and 400 μL/kg) significantly reduced ulcer severity, ulcer area, and ulcer index. On the other hand, histological examination revealed the diminution of total colitis index as a marker for inflammatory cell infiltration in the colonic segments of rats treated with Ocimum basilicum essential oil (200 and 400 μL/kg). The increased level of myeloperoxidase was significantly decreased after the treatment with the essential oil (200 and 400 μL/kg). These results suggest that Ocimum basilicum exhibits protective effect against acetic acid-induced colitis.

  9. Interactions between the Influenza A Virus RNA Polymerase Components and Retinoic Acid-Inducible Gene I

    PubMed Central

    Li, Weizhong; Chen, Hongjun; Sutton, Troy; Obadan, Adebimpe

    2014-01-01

    ABSTRACT The influenza A virus genome possesses eight negative-strand RNA segments in the form of viral ribonucleoprotein particles (vRNPs) in association with the three viral RNA polymerase subunits (PB2, PB1, and PA) and the nucleoprotein (NP). Through interactions with multiple host factors, the RNP subunits play vital roles in replication, host adaptation, interspecies transmission, and pathogenicity. In order to gain insight into the potential roles of RNP subunits in the modulation of the host's innate immune response, the interactions of each RNP subunit with retinoic acid-inducible gene I protein (RIG-I) from mammalian and avian species were investigated. Studies using coimmunoprecipitation (co-IP), bimolecular fluorescence complementation (BiFc), and colocalization using confocal microscopy provided direct evidence for the RNA-independent binding of PB2, PB1, and PA with RIG-I from various hosts (human, swine, mouse, and duck). In contrast, the binding of NP with RIG-I was found to be RNA dependent. Expression of the viral NS1 protein, which interacts with RIG-I, did not interfere with the association of RNA polymerase subunits with RIG-I. The association of each individual virus polymerase component with RIG-I failed to significantly affect the interferon (IFN) induction elicited by RIG-I and 5′ triphosphate (5′ppp) RNA in reporter assays, quantitative reverse transcription-PCR (RT-PCR), and IRF3 phosphorylation tests. Taken together, these findings indicate that viral RNA polymerase components PB2, PB1, and PA directly target RIG-I, but the exact biological significance of these interactions in the replication and pathogenicity of influenza A virus needs to be further clarified. IMPORTANCE RIG-I is an important RNA sensor to elicit the innate immune response in mammals and some bird species (such as duck) upon influenza A virus infection. Although the 5′-triphosphate double-stranded RNA (dsRNA) panhandle structure at the end of viral genome RNA is

  10. Protective effect of hispidulin on kainic acid-induced seizures and neurotoxicity in rats.

    PubMed

    Lin, Tzu Yu; Lu, Cheng Wei; Wang, Su Jane; Huang, Shu Kuei

    2015-05-15

    Hispidulin is a flavonoid compound which is an active ingredient in a number of traditional Chinese medicinal herbs, and it has been reported to inhibit glutamate release. The purpose of this study was to investigate whether hispidulin protects against seizures induced by kainic acid, a glutamate analog with excitotoxic properties. The results indicated that intraperitoneally administering hispidulin (10 or 50mg/kg) to rats 30 min before intraperitoneally injecting kainic acid (15 mg/kg) increased seizure latency and decreased seizure score. In addition, hispidulin substantially attenuated kainic acid-induced hippocampal neuronal cell death, and this protective effect was accompanied by the suppression of microglial activation and the production of proinflammatory cytokines such as interleukin-1β, interleukin-6, and tumor necrosis factor-α in the hippocampus. Moreover, hispidulin reduced kainic acid-induced c-Fos expression and the activation of mitogen-activated protein kinases in the hippocampus. These data suggest that hispidulin has considerable antiepileptic, neuroprotective, and antiinflammatory effects on kainic acid-induced seizures in rats. PMID:25746462

  11. Houttuyniae Herba Attenuates Kainic Acid-Induced Neurotoxicity via Calcium Response Modulation in the Mouse Hippocampus.

    PubMed

    Kim, Hyo Geun; Jeong, Hyun Uk; Hong, Sung In; Oh, Myung Sook

    2015-12-01

    Epilepsy is a complex neurological disorder characterized by the repeated occurrence of electrical activity known as seizures. This activity induces increased intracellular calcium, which ultimately leads to neuronal damage. Houttuyniae Herba, the aerial part of Houttuynia cordata, has various pharmacological effects and is widely used as a traditional herb. In the present study, we evaluated the protective effects of Houttuyniae Herba water extract on kainic acid-induced neurotoxicity. Kainic acid directly acts on calcium release, resulting in seizure behavior, neuronal damage, and cognitive impairment. In a rat primary hippocampal culture system, Houttuyniae Herba water extract significantly protected neuronal cells from kainic acid toxicity. In a seizure model where mice received intracerebellar kainic acid injections, Houttuyniae Herba water extract treatment resulted in a lower seizure stage score, ameliorated cognitive impairment, protected neuronal cells against kainic acid-induced toxicity, and suppressed neuronal degeneration in the hippocampus. In addition, Houttuyniae Herba water extract regulated increases in the intracellular calcium level, its related downstream pathways (reactive oxygen species production and mitochondrial dysfunction), and calcium/calmodulin complex kinase type II immunoreactivity in the mouse hippocampus, which resulted from calcium influx stimulation induced by kainic acid. These results demonstrate the neuroprotective effects of Houttuyniae Herba water extract through inhibition of calcium generation in a kainic acid-induced epileptic model. PMID:26366753

  12. Changes in saccharin preference behavior as a primary outcome to evaluate pain and analgesia in acetic acid-induced visceral pain in mice

    PubMed Central

    de la Puente, Beatriz; Romero-Alejo, Elizabeth; Vela, José Miguel; Merlos, Manuel; Zamanillo, Daniel; Portillo-Salido, Enrique

    2015-01-01

    Reflex-based procedures are important measures in preclinical pain studies that evaluate stimulated behaviors. These procedures, however, are insufficient to capture the complexity of the pain experience, which is often associated with the depression of several innate behaviors. While recent studies have made efforts to evidence the suppression of some positively motivated behaviors in certain pain models, they are still far from being routinely used as readouts for analgesic screening. Here, we characterized and compared the effect of the analgesic ibuprofen (Ibu) and the stimulant, caffeine, in assays of acute pain-stimulated and pain-depressed behavior. Intraperitoneal injection of acetic acid (AA) served as a noxious stimulus to stimulate a writhing response or depress saccharin preference and locomotor activity (LMA) in mice. AA injection caused the maximum number of writhes between 5 and 20 minutes after administration, and writhing almost disappeared 1 hour later. AA-treated mice showed signs of depression-like behaviors after writhing resolution, as evidenced by reduced locomotion and saccharin preference for at least 4 and 6 hours, respectively. Depression-like behaviors resolved within 24 hours after AA administration. A dose of Ibu (40 mg/kg) – inactive to reduce AA-induced abdominal writhing – administered before or after AA injection significantly reverted pain-induced saccharin preference deficit. The same dose of Ibu also significantly reverted the AA-depressed LMA, but only when it was administered after AA injection. Caffeine restored locomotion – but not saccharin preference – in AA-treated mice, thus suggesting that the reduction in saccharin preference – but not in locomotion – was specifically sensitive to analgesics. In conclusion, AA-induced acute pain attenuated saccharin preference and LMA beyond the resolution of writhing behavior, and the changes in the expression of hedonic behavior, such as sweet taste preference, can be

  13. Changes in saccharin preference behavior as a primary outcome to evaluate pain and analgesia in acetic acid-induced visceral pain in mice.

    PubMed

    de la Puente, Beatriz; Romero-Alejo, Elizabeth; Vela, José Miguel; Merlos, Manuel; Zamanillo, Daniel; Portillo-Salido, Enrique

    2015-01-01

    Reflex-based procedures are important measures in preclinical pain studies that evaluate stimulated behaviors. These procedures, however, are insufficient to capture the complexity of the pain experience, which is often associated with the depression of several innate behaviors. While recent studies have made efforts to evidence the suppression of some positively motivated behaviors in certain pain models, they are still far from being routinely used as readouts for analgesic screening. Here, we characterized and compared the effect of the analgesic ibuprofen (Ibu) and the stimulant, caffeine, in assays of acute pain-stimulated and pain-depressed behavior. Intraperitoneal injection of acetic acid (AA) served as a noxious stimulus to stimulate a writhing response or depress saccharin preference and locomotor activity (LMA) in mice. AA injection caused the maximum number of writhes between 5 and 20 minutes after administration, and writhing almost disappeared 1 hour later. AA-treated mice showed signs of depression-like behaviors after writhing resolution, as evidenced by reduced locomotion and saccharin preference for at least 4 and 6 hours, respectively. Depression-like behaviors resolved within 24 hours after AA administration. A dose of Ibu (40 mg/kg) - inactive to reduce AA-induced abdominal writhing - administered before or after AA injection significantly reverted pain-induced saccharin preference deficit. The same dose of Ibu also significantly reverted the AA-depressed LMA, but only when it was administered after AA injection. Caffeine restored locomotion - but not saccharin preference - in AA-treated mice, thus suggesting that the reduction in saccharin preference - but not in locomotion - was specifically sensitive to analgesics. In conclusion, AA-induced acute pain attenuated saccharin preference and LMA beyond the resolution of writhing behavior, and the changes in the expression of hedonic behavior, such as sweet taste preference, can be used as a more

  14. Platelet-Rich Plasma in Treatment of Zoledronic Acid-Induced Bisphosphonate-related Osteonecrosis of the Jaws

    PubMed Central

    Sarkarat, Farzin; Kalantar Motamedi, Mohammad Hosein; Jahanbani, Jahanfar; Sepehri, Dena; Kahali, Roozbeh; Nematollahi, Zahra

    2014-01-01

    Background: Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is a well-known challenging entity warranting management. Platelet-Rich Plasma (PRP) plays an important role in bone biology by enhancing bone repair and regeneration. Objectives: The aim of this animal study was to evaluate the effects of PRP on zoledronic acid-induced BRONJ. Materials and Methods: Seven rats were given 0.04 mg Zoledronic acid intravenously once a week for five weeks. Two weeks later, the animals underwent extraction of their first lower molars, bilaterally. After clinical confirmation of the osteonecrosis, PRP was injected randomly into one of the extraction sockets of each rat. Three weeks later, all rats were sacrificed in order to obtain histological sections. The analysis of epithelialization was performed by McNamar’s test, and the analysis of osteogenesis and angiogenesis was performed by the Wilcoxon Sign Rank test. P value was set at 0.05. Results: We found no significant differences between the two groups regarding the amount of epithelialization, angiogenesis or sequestrum formation (P > 0.05), but a significant difference was seen between the two groups regarding the amount of existing vital bone (P < 0.05). Conclusions: Our study demonstrates positive results (preservation or regeneration of bone) using PRP in treatment of BRONJ. Although PRP may enhance osseous regeneration, long-term follow-ups are required to confirm its benefits. PMID:25032151

  15. Benfotiamine attenuates nicotine and uric acid-induced vascular endothelial dysfunction in the rat.

    PubMed

    Balakumar, Pitchai; Sharma, Ramica; Singh, Manjeet

    2008-01-01

    The study has been designed to investigate the effect of benfotiamine, a thiamine derivative, in nicotine and uric acid-induced vascular endothelial dysfunction (VED) in rats. Nicotine (2 mg kg(-1)day(-1), i.p., 4 weeks) and uric acid (150 mg kg(-1)day(-1), i.p., 3 weeks) were administered to produce VED in rats. The development of VED was assessed by employing isolated aortic ring preparation and estimating serum and aortic concentration of nitrite/nitrate. Further, the integrity of vascular endothelium was assessed using the scanning electron microscopy (SEM) of thoracic aorta. Moreover, the oxidative stress was assessed by estimating serum thiobarbituric acid reactive substances (TBARS) and aortic superoxide anion generation. The administration of nicotine and uric acid produced VED by impairing the integrity of vascular endothelium and subsequently decreasing serum and aortic concentration of nitrite/nitrate and attenuating acetylcholine-induced endothelium dependent relaxation. Further, nicotine and uric acid produced oxidative stress, which was assessed in terms of increase in serum TBARS and aortic superoxide generation. However, treatment with benfotiamine (70 mg kg(-1)day(-1), p.o.) or atorvastatin (30 mg kg(-1)day(-1) p.o., a standard agent) markedly prevented nicotine and uric acid-induced VED and oxidative stress by improving the integrity of vascular endothelium, increasing the concentration of serum and aortic nitrite/nitrate, enhancing the acetylcholine-induced endothelium dependent relaxation and decreasing serum TBARS and aortic superoxide anion generation. Thus, it may be concluded that benfotiamine reduces the oxidative stress and consequently improves the integrity of vascular endothelium and enhances the generation of nitric oxide to prevent nicotine and uric acid-induced experimental VED. PMID:18951979

  16. Lipopolysaccharide Stimulates Butyric Acid-Induced Apoptosis in Human Peripheral Blood Mononuclear Cells

    PubMed Central

    Kurita-Ochiai, Tomoko; Fukushima, Kazuo; Ochiai, Kuniyasu

    1999-01-01

    We previously reported that butyric acid, an extracellular metabolite from periodontopathic bacteria, induced apoptosis in murine thymocytes, splenic T cells, and human Jurkat T cells. In this study, we examined the ability of butyric acid to induce apoptosis in peripheral blood mononuclear cells (PBMC) and the effect of bacterial lipopolysaccharide (LPS) on this apoptosis. Butyric acid significantly inhibited the anti-CD3 monoclonal antibody- and concanavalin A-induced proliferative responses in a dose-dependent fashion. This inhibition of PBMC growth by butyric acid depended on apoptosis in vitro. It was characterized by internucleosomal DNA digestion and revealed by gel electrophoresis followed by a colorimetric DNA fragmentation assay to occur in a concentration-dependent fashion. Butyric acid-induced PBMC apoptosis was accompanied by caspase-3 protease activity but not by caspase-1 protease activity. LPS potentiated butyric acid-induced PBMC apoptosis in a dose-dependent manner. Flow-cytometric analysis revealed that LPS increased the proportion of sub-G1 cells and the number of late-stage apoptotic cells induced by butyric acid. Annexin V binding experiments with fractionated subpopulations of PBMC in flow cytometory revealed that LPS accelerated the butyric acid-induced CD3+-T-cell apoptosis followed by similar levels of both CD4+- and CD8+-T-cell apoptosis. The addition of LPS to PBMC cultures did not cause DNA fragmentation, suggesting that LPS was unable to induce PBMC apoptosis directly. These data suggest that LPS, in combination with butyric acid, potentiates CD3+ PBMC T-cell apoptosis and plays a role in the apoptotic depletion of CD4+ and CD8+ cells. PMID:9864191

  17. The acid-induced folded state of Sac7d is the native state.

    PubMed Central

    Bedell, J. L.; McCrary, B. S.; Edmondson, S. P.; Shriver, J. W.

    2000-01-01

    Sac7d unfolds at low pH in the absence of salt, with the greatest extent of unfolding obtained at pH 2. We have previously shown that the acid unfolded protein is induced to refold by decreasing the pH to 0 or by addition of salt (McCrary BS, Bedell J. Edmondson SP, Shriver JW, 1998, J Mol Biol 276:203-224). Both near-ultraviolet circular dichroism spectra and ANS fluorescence enhancements indicate that the acid- and salt-induced folded states have a native fold and are not molten globular. 1H,15N heteronuclear single quantum coherence NMR spectra confirm that the native, acid-, and salt-induced folded states are essentially identical. The most significant differences in amide 1H and 15N chemical shifts are attributed to hydrogen bonding to titrating carboxyl side chains and through-bond inductive effects. The 1H NMR chemical shifts of protons affected by ring currents in the hydrophobic core of the acid- and salt-induced folded states are identical to those observed in the native. The radius of gyration of the acid-induced folded state at pH 0 is shown to be identical to that of the native state at pH 7 by small angle X-ray scattering. We conclude that acid-induced collapse of Sac7d does not lead to a molten globule but proceeds directly to the native state. The folding of Sac7d as a function of pH and anion concentration is summarized with a phase diagram that is similar to those observed for other proteins that undergo acid-induced folding except that the A-state is encompassed by the native state. These results demonstrate that formation of a molten globule is not a general property of proteins that are refolded by acid. PMID:11106160

  18. Clavulanic acid induces penile erection and yawning in male rats: comparison with apomorphine.

    PubMed

    Sanna, Fabrizio; Melis, Maria Rosaria; Angioni, Laura; Argiolas, Antonio

    2013-02-01

    The beta-lactamase inhibitor clavulanic acid induced penile erection and yawning in a dose dependent manner when given intraperitoneally (IP, 0.05-5mg/kg), perorally (OS, 0.1-5mg/kg) and intracereboventricularly (ICV, 0.01-5 μg/rat) to male rats. The effect resembles that of the dopamine receptor agonist apomorphine given subcutaneously (SC) (0.02-0.25mg/kg), although the responses of the latter followed a U inverted dose-response curve, disappearing at doses higher than 0.1mg/kg. Clavulanic acid responses were reduced by about 55% by haloperidol, a dopamine D2 receptor antagonist (0.1mg/kg IP), and by d(CH(2))(5)Tyr(Me)(2)-Orn(8)-vasotocin, an oxytocin receptor antagonist (2 μg/rat ICV), both given 15 min before clavulanic acid. A higher reduction of clavulanic acid responses (more than 80%) was also found with morphine, an opioid receptor agonist (5mg/kg IP), and with mianserin, a serotonin 5HT(2c) receptor antagonist (0.2mg/kg SC). In contrast, no reduction was found with naloxone, an opioid receptor antagonist (1mg/kg IP). The ability of haloperidol, d(CH(2))(5)Tyr(Me)(2)-Orn(8)-vasotocin and morphine to reduce clavulanic acid induced penile erection and yawning suggests that clavulanic acid induces these responses, at least in part, by increasing central dopaminergic neurotransmission. Dopamine in turn activates oxytocinergic neurotransmission and centrally released oxytocin induces penile erection and yawning. However, since both penile erection and yawning episodes were reduced not only by the blockade of central dopamine and oxytocin receptors and by the stimulation of opioid receptors, which inhibits oxytocinergic neurotransmission, but also by mianserin, an increase of central serotonin neurotransmission is also likely to participate in these clavulanic acid responses.

  19. Unsaturated fatty acid-induced non-canonical autophagy: unusual? or unappreciated?

    PubMed Central

    Bankaitis, Vytas A

    2015-01-01

    The breakdown of cellular components via autophagy is crucial for cellular homeostasis. In this issue of The EMBO Journal, Niso-Santano et al (2015) report the important observation that feeding cells with saturated or unsaturated fatty acids triggers mechanistically distinct autophagic responses. Feeding cells saturated fatty acid induced the canonical, BECN1/PI3K-dependent autophagy pathway. Conversely, the unsaturated fatty acid oleate triggered autophagic responses that were independent of the BECN1/PI3K complex, but that required a functional Golgi system. PMID:25762589

  20. Intravenous anesthetic propofol suppresses prostaglandin E2 and cysteinyl leukotriene production and reduces edema formation in arachidonic acid-induced ear inflammation.

    PubMed

    Inada, Takefumi; Hirota, Kiichi; Shingu, Koh

    2015-01-01

    Propofol is an intravenous drug widely used for anesthesia and sedation. Previously, propofol was shown to inhibit cyclo-oxygenase (COX) and 5-lipoxygenase (5-LOX) activities. Because these enzyme-inhibiting effects have only been demonstrated in vitro, this study sought to ascertain whether similar effects might also be observed in vivo. In the current studies, effects of propofol were tested in a murine model of arachidonic acid-induced ear inflammation. Specifically, propofol - as a pre-treatment -- was intraperitoneally and then topical application of arachidonic acid was performed. After 1 h, tissue biopsies were collected and tested for the presence of edema and for levels of inflammatory mediators. The results indicated that the administration of propofol significantly suppressed ear edema formation, tissue myeloperoxidase activity, and tissue production of both prostaglandin E2 and cysteinyl leukotrienes. From the data, it can be concluded that propofol could exert anti-COX and anti-5-LOX activities in an in vivo model and that these activities in turn could have, at least in part, suppressed arachidonic acid-induced edema formation in the ear.

  1. Global analysis of the acid-induced and urea-induced unfolding of staphylococcal nuclease and two of its variants.

    PubMed

    Ionescu, R M; Eftink, M R

    1997-02-01

    We have studied the equilibrium unfolding staphylococcal nuclease and two of its variants, V66W and V66W', over two perturbation axes (acid-induced unfolding as a function of urea concentration and urea-induced unfolding as a function of pH). The transitions were monitored by simultaneous measurements of circular dichroism and fluorescence. With this multidimensional array of data (2 perturbation axes and 2 signals), we present a strategy of performing a global analysis, over as many as 12 individual data sets, to test various models for the unfolding process, to determine with greater confidence the pertinent thermodynamic parameters, and to characterize unfolding intermediates. For example, wildtype nuclease shows a cooperative two-state transition with either urea or pH as denaturant, but the global fits are improved when the model is expanded to include a pH dependence of the urea m value or when two distinct classes of protonic groups are considered. The best fit for wild-type nuclease is with delta G degree 0,UN = 6.4 kcal/mol at pH 7, with the acid-induced unfolding being triggered by protonation of three to five carboxylate groups (with possible contribution from His121), and with the urea m = 2.5 kcal mol-1 M-1. V66W' lacks the last 13 amino acids on the C-terminus, has a tryptophan at position 66, has a predominantly beta-sheet structure, and is less stable than the wild type. For V66W', delta G degree 0,UN = 1.6 kcal/mol, m = 1.2 kcal mol-1 M-1, and there are two or three groups responsible for acid unfolding. V66W, a full-length mutant with two tryptophan residues, unfolds via a three-state mechanism: native reversible intermediate reversible unfolded. It appears that its beta-barrel subdomain retains structure in the intermediate state. Assuming that the unfolding of V66W' and the beta-barrel subdomain of V66W can be described by the same thermodynamic parameters, a global analysis enabled a description of the alpha subdomain of V66W with delta G

  2. Olodaterol attenuates citric acid-induced cough in naïve and ovalbumin-sensitized and challenged guinea pigs.

    PubMed

    Wex, Eva; Bouyssou, Thierry

    2015-01-01

    Excessive coughing is a common feature of airway diseases. Different G-protein coupled receptors, including β2-adrenergic receptors (β2-AR), have been implicated in the molecular mechanisms underlying the cough reflex. However, the potential antitussive property of β2-AR agonists in patients with respiratory disease is a matter of ongoing debate. The aim of our study was to test the efficacy of the long-acting β2-AR agonist olodaterol with regard to its antitussive property in a pre-clinical model of citric acid-induced cough in guinea pigs and to compare the results to different clinically relevant β2-AR agonists. In our study β2-AR agonists were intratracheally administered, as dry powder, into the lungs of naïve or ovalbumin-sensitized guinea pigs 15 minutes prior to induction of cough by exposure to citric acid. Cough events were counted over 15 minutes during the citric acid exposure. Olodaterol dose-dependently inhibited the number of cough events in naïve and even more potently and with a greater maximal efficacy in ovalbumin-sensitized guinea pigs (p < 0.01). Formoterol and salmeterol showed a trend towards reducing cough. On the contrary, indacaterol demonstrated pro-tussive properties as it significantly increased the number of coughs, both in naïve and ovalbumin-sensitized animals (p < 0.001). In conclusion, olodaterol, at doses eliciting bronchodilation, showed antitussive properties in a model of citric acid-induced cough in naïve and ovalbumin-sensitized guinea pigs. This is in agreement with pre-clinical and clinical studies showing antitussive efficacy of β2-AR agonists. Indacaterol increased the number of coughs in this model, which concurs with clinical data where a transient cough has been observed after indacaterol inhalation. While the antitussive properties of β2-AR agonists can be explained by their ability to lead to the cAMP-induced hyperpolarization of the neuron membrane thereby inhibiting sensory nerve activation and the

  3. Olodaterol Attenuates Citric Acid-Induced Cough in Naïve and Ovalbumin-Sensitized and Challenged Guinea Pigs

    PubMed Central

    Wex, Eva; Bouyssou, Thierry

    2015-01-01

    Excessive coughing is a common feature of airway diseases. Different G-protein coupled receptors, including β2-adrenergic receptors (β2-AR), have been implicated in the molecular mechanisms underlying the cough reflex. However, the potential antitussive property of β2-AR agonists in patients with respiratory disease is a matter of ongoing debate. The aim of our study was to test the efficacy of the long-acting β2-AR agonist olodaterol with regard to its antitussive property in a pre-clinical model of citric acid-induced cough in guinea pigs and to compare the results to different clinically relevant β2-AR agonists. In our study β2-AR agonists were intratracheally administered, as dry powder, into the lungs of naïve or ovalbumin-sensitized guinea pigs 15 minutes prior to induction of cough by exposure to citric acid. Cough events were counted over 15 minutes during the citric acid exposure. Olodaterol dose-dependently inhibited the number of cough events in naïve and even more potently and with a greater maximal efficacy in ovalbumin-sensitized guinea pigs (p < 0.01). Formoterol and salmeterol showed a trend towards reducing cough. On the contrary, indacaterol demonstrated pro-tussive properties as it significantly increased the number of coughs, both in naïve and ovalbumin-sensitized animals (p < 0.001). In conclusion, olodaterol, at doses eliciting bronchodilation, showed antitussive properties in a model of citric acid-induced cough in naïve and ovalbumin-sensitized guinea pigs. This is in agreement with pre-clinical and clinical studies showing antitussive efficacy of β2-AR agonists. Indacaterol increased the number of coughs in this model, which concurs with clinical data where a transient cough has been observed after indacaterol inhalation. While the antitussive properties of β2-AR agonists can be explained by their ability to lead to the cAMP-induced hyperpolarization of the neuron membrane thereby inhibiting sensory nerve activation and the

  4. Role of hepatocyte S6K1 in palmitic acid-induced endoplasmic reticulum stress, lipotoxicity, insulin resistance and in oleic acid-induced protection.

    PubMed

    Pardo, Virginia; González-Rodríguez, Águeda; Muntané, Jordi; Kozma, Sara C; Valverde, Ángela M

    2015-06-01

    The excess of saturated free fatty acids, such as palmitic acid, that induces lipotoxicity in hepatocytes, has been implicated in the development of non-alcoholic fatty liver disease also associated with insulin resistance. By contrast, oleic acid, a monounsaturated fatty acid, attenuates the effects of palmitic acid. We evaluated whether palmitic acid is directly associated with both insulin resistance and lipoapoptosis in mouse and human hepatocytes and the impact of oleic acid in the molecular mechanisms that mediate both processes. In human and mouse hepatocytes palmitic acid at a lipotoxic concentration triggered early activation of endoplasmic reticulum (ER) stress-related kinases, induced the apoptotic transcription factor CHOP, activated caspase 3 and increased the percentage of apoptotic cells. These effects concurred with decreased IR/IRS1/Akt insulin pathway. Oleic acid suppressed the toxic effects of palmitic acid on ER stress activation, lipoapoptosis and insulin resistance. Besides, oleic acid suppressed palmitic acid-induced activation of S6K1. This protection was mimicked by pharmacological or genetic inhibition of S6K1 in hepatocytes. In conclusion, this is the first study highlighting the activation of S6K1 by palmitic acid as a common and novel mechanism by which its inhibition by oleic acid prevents ER stress, lipoapoptosis and insulin resistance in hepatocytes.

  5. Standardized Extract of Bacopa monniera Attenuates Okadaic Acid Induced Memory Dysfunction in Rats: Effect on Nrf2 Pathway

    PubMed Central

    Nagarajan, Rajasekar; Hanif, Kashif; Siddiqui, Hefazat Husain; Nath, Chandishwar

    2013-01-01

    The aim of the present study is to investigate the effect of standardized extract of Bacopa monnieri (memory enhancer) and Melatonin (an antioxidant) on nuclear factor erythroid 2 related factor 2 (Nrf2) pathway in Okadaic acid induced memory impaired rats. OKA (200 ng) was administered intracerebroventricularly (ICV) to induce memory impairment in rats. Bacopa monnieri (BM-40 and 80 mg/kg) and Melatonin (20 mg/kg) were administered 1 hr before OKA injection and continued daily up to day 13. Memory functions were assessed by Morris water maze test on days 13–15. Rats were sacrificed for biochemical estimations of oxidative stress, neuroinflammation, apoptosis, and molecular studies of Nrf2, HO1, and GCLC expressions in cerebral cortex and hippocampus brain regions. OKA caused a significant memory deficit with oxidative stress, neuroinflammation, and neuronal loss which was concomitant with attenuated expression of Nrf2, HO1, and GCLC. Treatment with BM and Melatonin significantly improved memory dysfunction in OKA rats as shown by decreased latency time and path length. The treatments also restored Nrf2, HO1, and GCLC expressions and decreased oxidative stress, neuroinflammation, and neuronal loss. Thus strengthening the endogenous defense through Nrf2 modulation plays a key role in the protective effect of BM and Melatonin in OKA induced memory impairment in rats. PMID:24078822

  6. Effect of ethanolic extract of leaves of Paederia foetida Linn. on acetic acid induced colitis in albino rats

    PubMed Central

    Das, Swarnamoni; Kanodia, Lalit; Mukherjee, Apurba; Hakim, Abdul

    2013-01-01

    Objectives: To evaluate the effect of ethanolic extract of leaves of Paederia foetida on acetic acid induced colitis in albino rats. Materials and Methods: Ethanolic extract of Paederia foetida (EEPF) was prepared by percolation method. Acute toxicity test was done by using Organization for Economic Cooperation and Development guidelines. Albino rats were divided into four groups of five animals each. Groups A and B received 3% gum acacia. Groups C and D received EEPF 500 mg/kg body weight (BW) and 5-aminosalisylic acid 100 mg/kg BW respectively. Colitis was induced by transrectal administration of 4% acetic acid on 5th day. All animals were sacrificed after 48 h of colitis induction and distal 10 cm of the colon was dissected. Colon was weighed for disease activity index (DAI) and scored macroscopically and microscopically. Biochemical assessment of tissue myeloperoxidase (MPO), catalase (CAT) and superoxide dismutase (SOD) was done in colonic tissue homogenate and malondialdehyde (MDA) was estimated in serum. Results: P. foetida showed significant (P < 0.05) reduction in DAI, macroscopic and microscopic lesion score as well as significant (P < 0.05) improvement in MPO, MDA, CAT, and SOD level as compared to Group B. Conclusions: The ethanolic extract of leaves of P. foetida showed significant amelioration of experimentally induced colitis, which may be attributed to its anti-inflammatory and antioxidant property. PMID:24130378

  7. Obestatin Accelerates the Healing of Acetic Acid-Induced Colitis in Rats.

    PubMed

    Matuszyk, Aleksandra; Ceranowicz, Piotr; Warzecha, Zygmunt; Cieszkowski, Jakub; Bonior, Joanna; Jaworek, Jolanta; Kuśnierz-Cabala, Beata; Konturek, Peter; Ambroży, Tadeusz; Dembiński, Artur

    2016-01-01

    Obestatin, a 23-amino acid peptide derived from the proghrelin, has been shown to exhibit some protective and therapeutic effects in the gut. The aim of present study was to determine the effect of obestatin administration on the course of acetic acid-induced colitis in rats. Materials and Methods. Studies have been performed on male Wistar rats. Colitis was induced by a rectal enema with 3.5% acetic acid solution. Obestatin was administered intraperitoneally twice a day at a dose of 8 nmol/kg, starting 24 h after the induction of colitis. Seven or 14 days after the induction of colitis, the healing rate of the colon was evaluated. Results. Treatment with obestatin after induction of colitis accelerated the healing of colonic wall damage and this effect was associated with a decrease in the colitis-evoked increase in mucosal activity of myeloperoxidase and content of interleukin-1β. Moreover, obestatin administration significantly reversed the colitis-evoked decrease in mucosal blood flow and DNA synthesis. Conclusion. Administration of exogenous obestatin exhibits therapeutic effects in the course of acetic acid-induced colitis and this effect is related, at least in part, to the obestatin-evoked anti-inflammatory effect, an improvement of local blood flow, and an increase in cell proliferation in colonic mucosa.

  8. Exogenous Ghrelin Accelerates the Healing of Acetic Acid-Induced Colitis in Rats

    PubMed Central

    Matuszyk, Aleksandra; Ceranowicz, Piotr; Warzecha, Zygmunt; Cieszkowski, Jakub; Ceranowicz, Dagmara; Gałązka, Krystyna; Bonior, Joanna; Jaworek, Jolanta; Bartuś, Krzysztof; Gil, Krzysztof; Olszanecki, Rafał; Dembiński, Artur

    2016-01-01

    Previous studies have shown that ghrelin reduces colonic inflammation induced by trinitrobenzene sulfonic acid and dextran sodium sulfate. In the present study we determined the effect of treatment with ghrelin on the course of acetic acid-induced colitis in rats. Rectal administration of 3% acetic acid solution led to induction of colitis in all animals. Damage of the colonic wall was accompanied by an increase in mucosal concentration of pro-inflammatory interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), as well mucosal activity of myeloperoxidase. Moreover, induction of colitis led to a reduction in colonic blood flow and DNA synthesis. Administration of ghrelin after induction of colitis led to faster regeneration of the colonic wall and reduction in colonic levels of IL-1β, TNF-α, and myeloperoxidase. In addition, treatment with ghrelin improved mucosal DNA synthesis and blood flow. Our study disclosed that ghrelin exhibits a strong anti-inflammatory and healing effect in acetic acid-induced colitis. Our current observation in association with previous findings that ghrelin exhibits curative effect in trinitrobenzene sulfonic acid- and dextran sodium sulfate-induced colitis suggest that therapeutic effect of ghrelin in the colon is universal and independent of the primary cause of colitis. PMID:27598133

  9. Exogenous Ghrelin Accelerates the Healing of Acetic Acid-Induced Colitis in Rats.

    PubMed

    Matuszyk, Aleksandra; Ceranowicz, Piotr; Warzecha, Zygmunt; Cieszkowski, Jakub; Ceranowicz, Dagmara; Gałązka, Krystyna; Bonior, Joanna; Jaworek, Jolanta; Bartuś, Krzysztof; Gil, Krzysztof; Olszanecki, Rafał; Dembiński, Artur

    2016-01-01

    Previous studies have shown that ghrelin reduces colonic inflammation induced by trinitrobenzene sulfonic acid and dextran sodium sulfate. In the present study we determined the effect of treatment with ghrelin on the course of acetic acid-induced colitis in rats. Rectal administration of 3% acetic acid solution led to induction of colitis in all animals. Damage of the colonic wall was accompanied by an increase in mucosal concentration of pro-inflammatory interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), as well mucosal activity of myeloperoxidase. Moreover, induction of colitis led to a reduction in colonic blood flow and DNA synthesis. Administration of ghrelin after induction of colitis led to faster regeneration of the colonic wall and reduction in colonic levels of IL-1β, TNF-α, and myeloperoxidase. In addition, treatment with ghrelin improved mucosal DNA synthesis and blood flow. Our study disclosed that ghrelin exhibits a strong anti-inflammatory and healing effect in acetic acid-induced colitis. Our current observation in association with previous findings that ghrelin exhibits curative effect in trinitrobenzene sulfonic acid- and dextran sodium sulfate-induced colitis suggest that therapeutic effect of ghrelin in the colon is universal and independent of the primary cause of colitis. PMID:27598133

  10. Icariin, a major constituent from Epimedium brevicornum, attenuates ibotenic acid-induced excitotoxicity in rat hippocampus.

    PubMed

    Zong, Nan; Li, Fei; Deng, Yuanyuan; Shi, Jingshan; Jin, Feng; Gong, Qihai

    2016-10-15

    Excitotoxicity is one of the most extensively studied causes of neuronal death and plays an important role in Alzheimer's disease (AD). Icariin is a flavonoid component of a traditional Chinese medicine reported to possess a broad spectrum of pharmacological effects. The present study was designed to investigate the effects of icariin against learning and memory impairment induced by excitotoxicity. Here, we demonstrated that rats receiving intracerebroventricular injection of excitatory neurotoxin ibotenic acid exhibited impaired learning and memory. Oral administration of icariin at doses of 20 and 40mg/kg rescued behavioral performance and protected against neurotoxicity in rat hippocampus by suppressing ibotenic acid induced pro-apoptosis. Furthermore, Western blott of hippocampal specimens revealed that icariin up-regulated the expression of calbindin-D28k protein following ibotenic acid administration. Additionally, icariin inhibited mitogen-activated protein kinase (MAPK) family phosphorylation and nuclear factor kappa B (NF-κB) signaling, implicating the MAPK signaling and NF-κB signaling pathways were involved in the mechanism underlying icariin-mediated neuroprotection against ibotenic acid-induced excitotoxicity. These data suggested that icariin could be a potential agent for treatment of excitotoxicity-related diseases, including AD. PMID:27368415

  11. Nucleic acid-induced antiviral immunity in invertebrates: an evolutionary perspective.

    PubMed

    Wang, Pei-Hui; Weng, Shao-Ping; He, Jian-Guo

    2015-02-01

    Nucleic acids derived from viral pathogens are typical pathogen associated molecular patterns (PAMPs). In mammals, the recognition of viral nucleic acids by pattern recognition receptors (PRRs), which include Toll-like receptors (TLRs) and retinoic acid-inducible gene (RIG)-I-like receptors (RLRs), induces the release of inflammatory cytokines and type I interferons (IFNs) through the activation of nuclear factor κB (NF-κB) and interferon regulatory factor (IRF) 3/7 pathways, triggering the host antiviral state. However, whether nucleic acids can induce similar antiviral immunity in invertebrates remains ambiguous. Several studies have reported that nucleic acid mimics, especially dsRNA mimic poly(I:C), can strongly induce non-specific antiviral immune responses in insects, shrimp, and oyster. This behavior shows multiple similarities to the hallmarks of mammalian IFN responses. In this review, we highlight the current understanding of nucleic acid-induced antiviral immunity in invertebrates. We also discuss the potential recognition and regulatory mechanisms that confer non-specific antiviral immunity on invertebrate hosts.

  12. Protective Effect of Ocimum basilicum Essential Oil Against Acetic Acid-Induced Colitis in Rats.

    PubMed

    Rashidian, Amir; Roohi, Parnia; Mehrzadi, Saeed; Ghannadi, Ali Reza; Minaiyan, Mohsen

    2016-10-01

    Ocimum basilicum L has been traditionally used for the treatment of inflammatory bowel disease in Iran. This study investigates the ameliorative effect of Ocimum basilicum essential oil on an acetic acid-induced colitis model in rats. Ocimum basilicum essential oil with 2 doses (200 and 400 μL/kg) significantly ameliorated wet weight/length ratio of colonic tissue compared to the control group. Higher doses of essential oil (200 and 400 μL/kg) significantly reduced ulcer severity, ulcer area, and ulcer index. On the other hand, histological examination revealed the diminution of total colitis index as a marker for inflammatory cell infiltration in the colonic segments of rats treated with Ocimum basilicum essential oil (200 and 400 μL/kg). The increased level of myeloperoxidase was significantly decreased after the treatment with the essential oil (200 and 400 μL/kg). These results suggest that Ocimum basilicum exhibits protective effect against acetic acid-induced colitis. PMID:26620574

  13. Icariin, a major constituent from Epimedium brevicornum, attenuates ibotenic acid-induced excitotoxicity in rat hippocampus.

    PubMed

    Zong, Nan; Li, Fei; Deng, Yuanyuan; Shi, Jingshan; Jin, Feng; Gong, Qihai

    2016-10-15

    Excitotoxicity is one of the most extensively studied causes of neuronal death and plays an important role in Alzheimer's disease (AD). Icariin is a flavonoid component of a traditional Chinese medicine reported to possess a broad spectrum of pharmacological effects. The present study was designed to investigate the effects of icariin against learning and memory impairment induced by excitotoxicity. Here, we demonstrated that rats receiving intracerebroventricular injection of excitatory neurotoxin ibotenic acid exhibited impaired learning and memory. Oral administration of icariin at doses of 20 and 40mg/kg rescued behavioral performance and protected against neurotoxicity in rat hippocampus by suppressing ibotenic acid induced pro-apoptosis. Furthermore, Western blott of hippocampal specimens revealed that icariin up-regulated the expression of calbindin-D28k protein following ibotenic acid administration. Additionally, icariin inhibited mitogen-activated protein kinase (MAPK) family phosphorylation and nuclear factor kappa B (NF-κB) signaling, implicating the MAPK signaling and NF-κB signaling pathways were involved in the mechanism underlying icariin-mediated neuroprotection against ibotenic acid-induced excitotoxicity. These data suggested that icariin could be a potential agent for treatment of excitotoxicity-related diseases, including AD.

  14. Salicylic acid induces mitochondrial injury by inhibiting ferrochelatase heme biosynthesis activity.

    PubMed

    Gupta, Vipul; Liu, Shujie; Ando, Hideki; Ishii, Ryohei; Tateno, Shumpei; Kaneko, Yuki; Yugami, Masato; Sakamoto, Satoshi; Yamaguchi, Yuki; Nureki, Osamu; Handa, Hiroshi

    2013-12-01

    Salicylic acid is a classic nonsteroidal anti-inflammatory drug. Although salicylic acid also induces mitochondrial injury, the mechanism of its antimitochondrial activity is not well understood. In this study, by using a one-step affinity purification scheme with salicylic acid-immobilized beads, ferrochelatase (FECH), a homodimeric enzyme involved in heme biosynthesis in mitochondria, was identified as a new molecular target of salicylic acid. Moreover, the cocrystal structure of the FECH-salicylic acid complex was determined. Structural and biochemical studies showed that salicylic acid binds to the dimer interface of FECH in two possible orientations and inhibits its enzymatic activity. Mutational analysis confirmed that Trp301 and Leu311, hydrophobic amino acid residues located at the dimer interface, are directly involved in salicylic acid binding. On a gel filtration column, salicylic acid caused a shift in the elution profile of FECH, indicating that its conformational change is induced by salicylic acid binding. In cultured human cells, salicylic acid treatment or FECH knockdown inhibited heme synthesis, whereas salicylic acid did not exert its inhibitory effect in FECH knockdown cells. Concordantly, salicylic acid treatment or FECH knockdown inhibited heme synthesis in zebrafish embryos. Strikingly, the salicylic acid-induced effect in zebrafish was partially rescued by FECH overexpression. Taken together, these findings illustrate that FECH is responsible for salicylic acid-induced inhibition of heme synthesis, which may contribute to its antimitochondrial and anti-inflammatory function. This study establishes a novel aspect of the complex pharmacological effects of salicylic acid.

  15. Bovine chromosomal regions affecting rheological traits in acid-induced skim milk gels.

    PubMed

    Glantz, M; Gustavsson, F; Bertelsen, H P; Stålhammar, H; Lindmark-Månsson, H; Paulsson, M; Bendixen, C; Gregersen, V R

    2015-02-01

    The production of fermented milk products has increased worldwide during the last decade and is expected to continue to increase during the coming decade. The quality of these products may be optimized through breeding practices; however, the relations between cow genetics and technological properties of acid milk gels are not fully known. Therefore, the aim of this study was to identify chromosomal regions affecting acid-induced coagulation properties and possible candidate genes. Skim milk samples from 377 Swedish Red cows were rheologically analyzed for acid-induced coagulation properties using low-amplitude oscillation measurements. The resulting traits, including gel strength, coagulation time, and yield stress, were used to conduct a genome-wide association study. Single nucleotide polymorphisms (SNP) were identified using the BovineHD SNPChip (Illumina Inc., San Diego, CA), resulting in almost 621,000 segregating markers. The genome was scanned for putative quantitative trait loci (QTL) regions, haplotypes based on highly associated SNP were inferred, and the additive genetic effects of haplotypes within each QTL region were analyzed using mixed models. A total of 8 genomic regions were identified, with large effects of the significant haplotype explaining between 4.8 and 9.8% of the phenotypic variance of the studied traits. One major QTL was identified to overlap between gel strength and yield stress, the QTL identified with the most significant SNP closest to the gene coding for κ-casein (CSN3). In addition, a chromosome-wide significant region affecting yield stress on BTA 11 was identified to be colocated with PAEP, coding for β-lactoglobulin. Furthermore, the coagulation properties of the genetic variants within the 2 genes were compared with the coagulation properties identified by the patterns of the haplotypes within the regions, and it was discovered that the haplotypes were more diverse and in one case slightly better at explaining the

  16. Valproic Acid-Induced Severe Acute Pancreatitis with Pseudocyst Formation: Report of a Case

    PubMed Central

    Khamrui, Sujan; Kataria, Mohnish; Biswas, Jayanta; Saha, Suman

    2015-01-01

    Valproic acid is the most widely used anti-epilep­tic drug in children, and it is probably the most frequent cause of drug-induced acute pancreatitis. Outcomes for patients with valproic acid-associated pancreatitis vary from full recovery after discontinuation of the drug to severe acute pancreatitis and death. Here, we present a case of valproic acid-induced severe acute pancreatitis with pseudocyst formation in a 10-year-old girl with cerebral palsy and generalized tonic-clonic seizure. There was no resolution of the pseudocyst after discontinuation of valproic acid. The patient became symptomatic with a progressive increase in the size of the pseudocyst. She was successfully treated with cystogastrostomy and was well at 12-month follow-up. PMID:26366333

  17. Effect of zinc sulphate on acetic acid-induced gastric ulceration in rats.

    PubMed

    Li, K M

    1990-09-01

    The effects of zinc sulphate on gastric ulcer healing rate and mucosal mucus content of acetic acid-induced ulceration in rats have been assessed. Daily treatment with zinc sulphate progressively accelerated ulcer healing in a dose-dependent manner with a significant increase observed on day 15 after ulcer induction in rats treated with 44 and 88 mg kg-1 zinc sulphate. A significant increase in gastric mucosal adherent mucus was also observed in those animals treated with 88 mg kg-1 zinc sulphate. The results suggest that a minimum treatment period of 15 days is needed for the zinc sulphate to be effective, and that zinc ions may promote gastric ulcer healing by enhancing mucus formation to prevent acid back-diffusion into the gastric mucosa.

  18. Esophageal Submucosal Injection of Capsaicin but Not Acid Induces Symptoms in Normal Subjects

    PubMed Central

    Lee, Robert H; Korsapati, Hariprasad; Bhalla, Vikas; Varki, Nissi; Mittal, Ravinder K

    2016-01-01

    Background/Aims Transient receptor potential vanilloid-1 (TRPV1) is a candidate for mediating acid-induced symptoms in the esophagus. We conducted studies to determine if the presence of acid in the mucosa/submucosa and direct activation of TRPV1 by capsaicin elicited symptoms in normal healthy subjects. We also studied the presence of TRPV1 receptors in the esophagus. Methods Unsedated endoscopy was performed on healthy subjects with no symptoms. Using a sclerotherapy needle, normal saline (pH 2.0–7.5) was injected into the mucosa/submucosa, 5 cm above the Z line. In a separate group of healthy subjects, injection of capsaicin and vehicle was also studied. Quality of symptoms was reported using the McGill Pain Questionnaire, and symptom intensity using the visual analogue scale (VAS). Immunohistochemistry was performed on 8 surgical esophagus specimens using TRPV1 antibody. Results Acid injection either did not elicit or elicited mild symptoms in subjects at all pH solutions. Capsaicin but not the vehicle elicited severe heartburn/chest pain in all subjects. Mean VAS for capsaicin was 91 ± 3 and symptoms lasted for 25 ± 1 minutes. Immunohistochemistry revealed a linear TRPV1 staining pattern between the epithelial layer and the submucosa that extended into the papillae. Eighty-five percent of papillae stained positive for TRPV1 with a mean 1.1 positive papillae per high-powered field. Conclusions The mechanism of acid-induced heartburn and chest pain is not the simple interaction of hydrogen ions with afferents located in the esophageal mucosa and submucosa. TRPV1 receptors are present in the lamina propria and their activation induces heartburn and chest pain. PMID:26932896

  19. Proteomic investigation into betulinic acid-induced apoptosis of human cervical cancer HeLa cells.

    PubMed

    Xu, Tao; Pang, Qiuying; Zhou, Dong; Zhang, Aiqin; Luo, Shaman; Wang, Yang; Yan, Xiufeng

    2014-01-01

    Betulinic acid is a pentacyclic triterpenoid that exhibits anticancer functions in human cancer cells. This study provides evidence that betulinic acid is highly effective against the human cervical cancer cell line HeLa by inducing dose- and time-dependent apoptosis. The apoptotic process was further investigated using a proteomics approach to reveal protein expression changes in HeLa cells following betulinic acid treatment. Proteomic analysis revealed that there were six up- and thirty down-regulated proteins in betulinic acid-induced HeLa cells, and these proteins were then subjected to functional pathway analysis using multiple analysis software. UDP-glucose 6-dehydrogenase, 6-phosphogluconate dehydrogenase decarboxylating, chain A Horf6-a novel human peroxidase enzyme that involved in redox process, was found to be down-regulated during the apoptosis process of the oxidative stress response pathway. Consistent with our results at the protein level, an increase in intracellular reactive oxygen species was observed in betulinic acid-treated cells. The proteins glucose-regulated protein and cargo-selection protein TIP47, which are involved in the endoplasmic reticulum pathway, were up-regulated by betulinic acid treatment. Meanwhile, 14-3-3 family proteins, including 14-3-3β and 14-3-3ε, were down-regulated in response to betulinic acid treatment, which is consistent with the decrease in expression of the target genes 14-3-3β and 14-3-3ε. Furthermore, it was found that the antiapoptotic bcl-2 gene was down-regulated while the proapoptotic bax gene was up-regulated after betulinic acid treatment in HeLa cells. These results suggest that betulinic acid induces apoptosis of HeLa cells by triggering both the endoplasmic reticulum pathway and the ROS-mediated mitochondrial pathway.

  20. Neuroprotective effects of butterbur and rough aster against kainic Acid-induced oxidative stress in mice.

    PubMed

    Oh, Sang Hee; Sok, Dai-Eun; Kim, Mee Ree

    2005-01-01

    The separate and combined neuroprotective effects of rough aster (Aster scaber) and butterbur (Petasite japonicus) extracts against oxidative damage in the brain of mice challenged with kainic acid were examined by comparing behavioral changes and biochemical parameters of oxidative stress. Rough aster butanol extract (400 mg/kg) and/or butterbur butanol extract (150 or 400 mg/kg) were administered to male ICR mice, 6-8 weeks old, through a gavage for 4 days consecutively, and on day 4, kainic acid (50 mg/kg) was administered intraperitoneally. Compared with the vehicle-treated control, no significant changes in body and brain weight were observed in mice administered rough aster or butterbur butanol extract. Administration of kainic acid only, causing a lethality of approximately 54%, resulted in a significant decrease of total glutathione level and increase of thiobarbituric acid-reactive substances (TBARS) value in brain tissue. The administration of butterbur or rough aster extract (400 mg/kg) decreased the lethality (50%) of kainic acid to 25%, alleviated the behavioral signs of neurotoxicity, restored the cytosolic glutathione level of brain homogenate to approximately 80% (P < .05), and reduced kainic acid-induced increases in TBARS values. In contrast to no significant neuroprotection by butterbur extract at a low dose (150 mg/kg), the combination of rough aster extract and butterbur extract reduced the lethality to 12.5%. Moreover, the combination delayed the onset time of behavioral signs by twofold, and significantly preserved the level of cytosolic glutathione peroxidase and glutathione reductase activities. However, the other biochemical parameters were not altered significantly by the combination. Thus, the combination of two vegetable extracts significantly increased the neuroprotective action against kainic acid-induced neurotoxicity. Based on these findings, the combination of butterbur extract and rough aster extract contains a functional agent or

  1. Antinociceptive activity of Polygonum hydropiper.

    PubMed

    Rahman, Eva; Goni, S A; Rahman, M T; Ahmed, M

    2002-12-01

    The hexane, ethylacetate and methanol extracts of Polygonum hydropiper whole plant administered to mice at doses of 250 and 500 mg/kg, showed a significant activity on acetic acid-induced writhing. Within the tested extracts, the ethylacetate one showed the most significant activity.

  2. Twisting and Writhing with George Ellery Hale

    NASA Astrophysics Data System (ADS)

    Canfield, Richard C.

    2013-07-01

    Early in his productive career in astronomy, George Ellery Hale developed innovative instrumentation that allowed him to image the magnetically-dominated solar chromosphere. Among the solar phenomena he discovered were sunspot vortices, which he attributed to storms akin to cyclones in our own atmosphere. Much more recently, physicists discovered a quantity that is very well conserved in ideal magnetohydrodynamics: magnetic helicity. Our contemporary understanding of Hale's vortices as a consequence of large-scale twist in sunspot magnetic fields hinges on this conservation. I will review the crucial role that this property plays in the hemispheric and solar cycle dependences of Hales vortices, as well as solar flares and CMEs.

  3. Adipokines enhance oleic acid-induced proliferation of vascular smooth muscle cells by inducing CD36 expression.

    PubMed

    Schlich, Raphaela; Lamers, Daniela; Eckel, Jürgen; Sell, Henrike

    2015-01-01

    Adipose tissue is not only releasing lipids but also various adipokines that are both dysregulated in the obese state and may contribute to obesity-associated vascular dysfunction and cardiovascular risk. We have previously shown that the combination of adipocyte-conditioned medium (CM) and oleic acid (OA) increases proliferation of human vascular smooth muscle cells (VSMC) in a synergistic way. We identified vascular endothelial growth factor (VEGF) as a component within CM that is responsible for most of the observed effects. In this study, we investigate novel mechanisms that underlie the combined effects of adipokine and oleic acid-induced proliferation of VSMC. Oleic acid leads to significant lipid accumulation in VSMC that is further enhanced by the combined treatment with CM. Accordingly CM stimulates CD36 expression in VSMC while OA is not affecting CD36. Silencing of CD36 was established and prevents lipid accumulation in all tested conditions. CD36 silencing also abrogates CM- and OA-induced proliferation and considerably reduces proliferation induced by the combination of CM and OA. At the same time, VEGF secretion and VEGF-receptor 1 (VEGF-R1) by VSMC was not affected by CD36 silencing. However, VEGF was not able to induce any proliferation in VSMC after CD36 silencing that also blunted VEGF-induced extracellular signal-regulated kinase (ERK) activation. Finally, combined silencing of CD36 together with a blocking antibody against VEGF prevented most of CMOA-induced proliferation. In conclusion, our results demonstrate that CD36 is mediating CM-induced proliferation of VSMC. Induction of CD36 by adipokines enhances the response of VSMC towards VEGF and OA.

  4. Stability of the acetic acid-induced bladder irritation model in alpha chloralose-anesthetized female cats.

    PubMed

    Kullmann, F Aura; Wells, Grace I; Langdale, Christopher L; Zheng, Jihong; Thor, Karl B

    2013-01-01

    Time- and vehicle-related variability of bladder and urethral rhabdosphincter (URS) activity as well as cardiorespiratory and blood chemistry values were examined in the acetic acid-induced bladder irritation model in α-chloralose-anesthetized female cats. Additionally, bladder and urethra were evaluated histologically using Mason trichrome and toluidine blue staining. Urodynamic, cardiovascular and respiratory parameters were collected during intravesical saline infusion followed by acetic acid (0.5%) to irritate the bladder. One hour after starting acetic acid infusion, a protocol consisting of a cystometrogram, continuous infusion-induced rhythmic voiding contractions, and a 5 min "quiet period" (bladder emptied without infusion) was precisely repeated every 30 minutes. Administration of vehicle (saline i.v.) occurred 15 minutes after starting each of the first 7 cystometrograms and duloxetine (1mg/kg i.v.) after the 8(th). Acetic acid infusion into the bladder increased URS-EMG activity, bladder contraction frequency, and decreased contraction amplitude and capacity, compared to saline. Bladder activity and URS activity stabilized within 1 and 2 hours, respectively. Duloxetine administration significantly decreased bladder contraction frequency and increased URS-EMG activity to levels similar to previous reports. Cardiorespiratory parameters and blood gas levels remained consistent throughout the experiment. The epithelium of the bladder and urethra were greatly damaged and edema and infiltration of neutrophils in the lamina propria of urethra were observed. These data provide an ample evaluation of the health of the animals, stability of voiding function and appropriateness of the model for testing drugs designed to evaluate lower urinary tract as well as cardiovascular and respiratory systems function. PMID:24040064

  5. DIBROMOACETIC ACID-INDUCED ELEVATIONS IN CIRCULATING ESTRADIOL: EFFECTS IN BOTH CYCLING AND OVARIECTOMIZED/STEROID-PRIMED FEMALE RATS

    EPA Science Inventory

    RTD-03-031
    Goldman, JM and Murr, AS. Dibromoacetic Acid-induced Elevations in Circulating Estradiol: Effects in Both Cycling and Ovariectomized/Steroid-primed Female Rats. Reproductive Toxicology (in press).

    Abstract

    Oral exposures to high concentrations of th...

  6. Gallic acid induces apoptosis in EGFR-mutant non-small cell lung cancers by accelerating EGFR turnover.

    PubMed

    Nam, Boas; Rho, Jin Kyung; Shin, Dong-Myung; Son, Jaekyoung

    2016-10-01

    Gallic acid is a common botanic phenolic compound, which is present in plants and foods worldwide. Gallic acid is implicated in various biological processes such as cell growth and apoptosis. Indeed, gallic acid has been shown to induce apoptosis in many cancer types. However, the molecular mechanisms of gallic acid-induced apoptosis in cancer, particularly lung cancer, are still unclear. Here, we report that gallic acid induces apoptosis in EGFR-mutant non-small cell lung cancer (NSCLC) cells, but not in EGFR-WT NSCLC cells. Treatment with gallic acid resulted in a significant reduction in proliferation and induction of apoptosis, only in EGFR-mutant NSCLC cells. Interestingly, treatment with gallic acid led to a robust decrease in EGFR levels, which is critical for NSCLC survival. Treatment with gallic acid had no significant effect on transcription, but induced EGFR turnover. Indeed, treatment with a proteasome inhibitor dramatically reversed gallic acid-induced EGFR downregulation. Moreover, treatment with gallic acid induced EGFR turnover leading to apoptosis in EGFR-TKI (tyrosine kinase inhibitor)-resistant cell lines, which are dependent on EGFR signaling for survival. Thus, these studies suggest that gallic acid can induce apoptosis in EGFR-dependent lung cancers that are dependent on EGFR for growth and survival via acceleration of EGFR turnover.

  7. Gallic acid induces apoptosis in EGFR-mutant non-small cell lung cancers by accelerating EGFR turnover.

    PubMed

    Nam, Boas; Rho, Jin Kyung; Shin, Dong-Myung; Son, Jaekyoung

    2016-10-01

    Gallic acid is a common botanic phenolic compound, which is present in plants and foods worldwide. Gallic acid is implicated in various biological processes such as cell growth and apoptosis. Indeed, gallic acid has been shown to induce apoptosis in many cancer types. However, the molecular mechanisms of gallic acid-induced apoptosis in cancer, particularly lung cancer, are still unclear. Here, we report that gallic acid induces apoptosis in EGFR-mutant non-small cell lung cancer (NSCLC) cells, but not in EGFR-WT NSCLC cells. Treatment with gallic acid resulted in a significant reduction in proliferation and induction of apoptosis, only in EGFR-mutant NSCLC cells. Interestingly, treatment with gallic acid led to a robust decrease in EGFR levels, which is critical for NSCLC survival. Treatment with gallic acid had no significant effect on transcription, but induced EGFR turnover. Indeed, treatment with a proteasome inhibitor dramatically reversed gallic acid-induced EGFR downregulation. Moreover, treatment with gallic acid induced EGFR turnover leading to apoptosis in EGFR-TKI (tyrosine kinase inhibitor)-resistant cell lines, which are dependent on EGFR signaling for survival. Thus, these studies suggest that gallic acid can induce apoptosis in EGFR-dependent lung cancers that are dependent on EGFR for growth and survival via acceleration of EGFR turnover. PMID:27597244

  8. DIBROMOACETIC ACID-INDUCED ELEVATIONS OF ESTRADIOL IN THE CYCLING AND OVARIECTOMOZED/ESTRADIOL-IMPLANTED FEMALE RAT

    EPA Science Inventory

    Goldman, JM and Murr, AS. Dibromoacetic Acid-induced Elevations of Estradiol in Both Cycling and Ovariectomized / Estradiol-implanted Female Rats

    ABSTRACT
    Haloacetic acids are one of the principal classes of disinfection by-products generated by the chlorination of mun...

  9. Phenylethanoids in the herb of Plantago lanceolata and inhibitory effect on arachidonic acid-induced mouse ear edema.

    PubMed

    Murai, M; Tamayama, Y; Nishibe, S

    1995-10-01

    The five phenylethanoids, acteoside (1), cistanoside F (2), lavandulifolioside (3), plantamajoside (4) and isoacteoside (5) were isolated from the herb of Plantago lanceolata L. (Plantaginaceae). Compounds 1, the major phenylethanoid in the herb of P. lanceolata L., and 4, the major phenylethanoid in the herb of P. asiatica L., showed inhibitory effects on arachidonic acid-induced mouse ear edema. PMID:7480214

  10. Effect of a novel NK1 receptor selective antagonist (NKP608) on citric acid induced cough and airway obstruction.

    PubMed

    El-Hashim, A Z; Wyss, D; Lewis, C

    2004-01-01

    The effects of an orally administered novel and selective NK1 antagonist, NKP608, on cough and airway obstruction, induced by citric acid in guinea pigs, were investigated. Guinea pigs were pre-treated with 0.03, 0.3 and 1 mg kg(-1) of NKP608, the NK2 antagonist, SR48968 or both 2 h prior to challenge with citric acid (0.6 M) for a 10 min period. Guinea pigs pre-treated with 0.03, 0.3 and 1mgkg(-1) of NKP608 exhibited a significant reduction of 77, 74 and 79%, respectively, in the numbers of cough compared to vehicle pre-treated animals (P<0.05). SR48968, 10 mg kg(-1), alone did not significantly affect the citric acid-induced cough but when co-administered with 1 mg kg(-1) of NKP608, there was a significant 90% reduction in cough. NKP608 did not significantly reduce the citric acid-induced increase in Penh at any of the doses used. SR48968 significantly reduced the citric acid induced airway obstruction by about 50%. However, when SR48968 was co-administered with NKP608, there was a greater (73%) decrease in the airway obstruction compared with SR48968 alone. These data show that NKP608, a selective NK1 receptor antagonist, is a potent inhibitor of citric acid induced cough in guinea pigs and may therefore have value in the therapy of clinical cough.

  11. Phenylethanoids in the herb of Plantago lanceolata and inhibitory effect on arachidonic acid-induced mouse ear edema.

    PubMed

    Murai, M; Tamayama, Y; Nishibe, S

    1995-10-01

    The five phenylethanoids, acteoside (1), cistanoside F (2), lavandulifolioside (3), plantamajoside (4) and isoacteoside (5) were isolated from the herb of Plantago lanceolata L. (Plantaginaceae). Compounds 1, the major phenylethanoid in the herb of P. lanceolata L., and 4, the major phenylethanoid in the herb of P. asiatica L., showed inhibitory effects on arachidonic acid-induced mouse ear edema.

  12. Multiple copies of a bile acid-inducible gene in Eubacterium sp. strain VPI 12708.

    PubMed Central

    Gopal-Srivastava, R; Mallonee, D H; White, W B; Hylemon, P B

    1990-01-01

    Eubacterium sp. strain VPI 12708 is an anaerobic intestinal bacterium which possesses inducible bile acid 7-dehydroxylation activity. Several new polypeptides are produced in this strain following induction with cholic acid. Genes coding for two copies of a bile acid-inducible 27,000-dalton polypeptide (baiA1 and baiA2) have been previously cloned and sequenced. We now report on a gene coding for a third copy of this 27,000-dalton polypeptide (baiA3). The baiA3 gene has been cloned in lambda DASH on an 11.2-kilobase DNA fragment from a partial Sau3A digest of the Eubacterium DNA. DNA sequence analysis of the baiA3 gene revealed 100% homology with the baiA1 gene within the coding region of the 27,000-dalton polypeptides. The baiA2 gene shares 81% sequence identity with the other two genes at the nucleotide level. The flanking nucleotide sequences associated with the baiA1 and baiA3 genes are identical for 930 bases in the 5' direction from the initiation codon and for at least 325 bases in the 3' direction from the stop codon, including the putative promoter regions for the genes. An additional open reading frame (occupying from 621 to 648 bases, depending on the correct start codon) was found in the identical 5' regions associated with the baiA1 and baiA3 clones. The 5' sequence 930 bases upstream from the baiA1 and baiA3 genes was totally divergent. The baiA2 gene, which is part of a large bile acid-inducible operon, showed no homology with the other two genes either in the 5' or 3' direction from the polypeptide coding region, except for a 15-base-pair presumed ribosome-binding site in the 5' region. These studies strongly suggest that a gene duplication (baiA1 and baiA3) has occurred and is stably maintained in this bacterium. Images PMID:2376563

  13. Rho Kinase ROCK2 Mediates Acid-Induced NADPH Oxidase NOX5-S Expression in Human Esophageal Adenocarcinoma Cells

    PubMed Central

    Cao, Weibiao

    2016-01-01

    Mechanisms of the progression from Barrett’s esophagus (BE) to esophageal adenocarcinoma (EA) are not fully understood. We have shown that NOX5-S may be involved in this progression. However, how acid upregulates NOX5-S is not well known. We found that acid-induced increase in NOX5-S expression was significantly decreased by the Rho kinase (ROCK) inhibitor Y27632 in BE mucosal biopsies and FLO-1 EA cells. In addition, acid treatment significantly increased the Rho kinase activity in FLO-1 cells. The acid-induced increase in NOX5-S expression and H2O2 production was significantly decreased by knockdown of Rho kinase ROCK2, but not by knockdown of ROCK1. Conversely, the overexpression of the constitutively active ROCK2, but not the constitutively active ROCK1, significantly enhanced the NOX5-S expression and H2O2 production. Moreover, the acid-induced increase in Rho kinase activity and in NOX5-S mRNA expression was blocked by the removal of calcium in both FLO-1 and OE33 cells. The calcium ionophore A23187 significantly increased the Rho kinase activity and NOX5-S mRNA expression. We conclude that acid-induced increase in NOX5-S expression and H2O2 production may depend on the activation of ROCK2, but not ROCK1, in EA cells. The acid-induced activation of Rho kinase may be mediated by the intracellular calcium increase. It is possible that persistent acid reflux present in BE patients may increase the intracellular calcium, activate ROCK2 and thereby upregulate NOX5-S. High levels of reactive oxygen species derived from NOX5-S may cause DNA damage and thereby contribute to the progression from BE to EA. PMID:26901778

  14. Primary and secondary genetic responses after folic acid-induced acute renal injury in the mouse.

    PubMed

    Calvet, J P; Chadwick, L J

    1994-12-01

    Folic acid-induced acute renal injury results in dramatic changes in gene expression. Among the genes affected by folic acid treatment are the primary response genes, c-fos and c-myc, which are thought to function to initiate cell cycle events. In this report, changes in the expression of three other genes in response to folic acid injury have been investigated: ornithine decarboxylase, epidermal growth factor (EGF), and sulfated glycoprotein-2 (SGP-2). Renal injury was found to cause a rapid decrease in EGF mRNA, which remained absent for several days after the initial injury, gradually returning to normal levels over an approximately 3-wk regeneration and recovery period. Ornithine decarboxylase mRNA showed a similar decrease. In contrast, folic acid caused a rapid increase in SGP-2 mRNA, which peaked several days after treatment, decreasing to normal levels over the 3-wk period. The mRNAs for the primary response genes were superinduced in the injured kidneys in the presence of the protein synthesis inhibitor cycloheximide. In contrast, the changes in EGF and SGP-2 mRNA levels were blocked by cycloheximide, indicating that these responses required new protein synthesis during the first few hours after folic acid injury. The opposite but parallel responses in the expression of the EGF and SGP-2 genes suggest that their regulation is coupled to the initial injury-induced dedifferentiation and subsequent return to the fully differentiated state.

  15. On the molecular mechanisms of the acid-induced dissociation of hydroxy-apatite in water.

    PubMed

    Hochrein, Oliver; Zahn, Dirk

    2011-06-01

    The enamel/saliva interface is mimicked by the comparably much simpler model of (001) surfaces of hydroxy-apatite ( Ca(10)(PO(4))(6)(OH)(2) ) in contact with aqueous solution. At neutral pH, the dissociation of ions is penalized by more than 150 kJ mol(-1) giving rise to very stable apatite-water interfaces. This picture changes drastically with decreasing pH, as the protonation of phosphate and hydroxide ions lowers the free energy of calcium ions dissociation. Our simulations suggest the mechanism of acid-induced apatite decomposition to i) require a considerable degree of protonation of the apatite surface. The first ion dissociation step ii) involves calcium ions which electrostatic binding has been locally destabilized through phosphate and hydroxide protonation. The depletion of calcium ions embedding the anions then allows iii) the dissociation of the anionic species. Along this line, the protective role of fluoride in caries prevention is related to the stabilization of the calcium triangles embedding the OH(-)/F(-) ions.

  16. PDIA3 Knockdown Exacerbates Free Fatty Acid-Induced Hepatocyte Steatosis and Apoptosis

    PubMed Central

    Yu, Chao-hui; Xu, Cheng-fu; Xu, Lei; Li, You-ming; Chen, Wei-xing

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) has emerged as one of the most common chronic liver disease over the past decades. Endoplasmic reticulum stress (ERS) plays a pivotal role during the development of NAFLD. This study aims to analyze the potential role of protein disulfide isomerase A3 precursor (PDIA3), one of the ER chaperones, in free fatty acid-induced cell model of NAFLD. Human liver L02 cell line was treated with sodium palmitate for 24 hours, which developed severe intracellular lipid accumulation. The increased protein level of PDIA3 was detected via immunoblotting analysis in the fat loaded cell models of NAFLD. siRNA-mediated knockdown of PDIA3 in L02 cells not only increased the cellular lipid accumulation, but also exacerbated hepatocytes apoptosis induced by sodium palmitate. Further investigation revealed that knockdown of PDIA3 up-regulated protein expression of fatty acid synthase (FAS), a key enzyme involved in fatty acid synthesis. PDIA3 knockdown also up-regulated key molecules of ERS pathway, including glucose-regulated protein 78 (GRP78), phospho-PKR-like ER kinase (p-PERK), and C/EBP homologous protein (CHOP). Our results suggested that ER chaperone PDIA3 plays a pivotal role in FFA-induced hepatocyte steatosis and apoptosis. PMID:26214517

  17. Anacardic acid induces apoptosis-like cell death in the rice blast fungus Magnaporthe oryzae.

    PubMed

    Muzaffar, Suhail; Bose, Chinchu; Banerji, Ashok; Nair, Bipin G; Chattoo, Bharat B

    2016-01-01

    Anacardic acid (6-pentadecylsalicylic acid), extracted from cashew nut shell liquid, is a natural phenolic lipid well known for its strong antibacterial, antioxidant, and anticancer activities. Its effect has been well studied in bacterial and mammalian systems but remains largely unexplored in fungi. The present study identifies antifungal, cytotoxic, and antioxidant activities of anacardic acid in the rice blast fungus Magnaporthe oryzae. It was found that anacardic acid causes inhibition of conidial germination and mycelial growth in this ascomycetous fungus. Phosphatidylserine externalization, chromatin condensation, DNA degradation, and loss of mitochondrial membrane potential suggest that growth inhibition of fungus is mainly caused by apoptosis-like cell death. Broad-spectrum caspase inhibitor Z-VAD-FMK treatment indicated that anacardic acid induces caspase-independent apoptosis in M. oryzae. Expression of a predicted ortholog of apoptosis-inducing factor (AIF) was upregulated during the process of apoptosis, suggesting the possibility of mitochondria dependent apoptosis via activation of apoptosis-inducing factor. Anacardic acid treatment leads to decrease in reactive oxygen species rather than increase in reactive oxygen species (ROS) accumulation normally observed during apoptosis, confirming the antioxidant properties of anacardic acid as suggested by earlier reports. Our study also shows that anacardic acid renders the fungus highly sensitive to DNA damaging agents like ethyl methanesulfonate (EMS). Treatment of rice leaves with anacardic acid prevents M. oryzae from infecting the plant without affecting the leaf, suggesting that anacardic acid can be an effective antifungal agent. PMID:26381667

  18. Ethanol promotes saturated fatty acid-induced hepatoxicity through endoplasmic reticulum (ER) stress response.

    PubMed

    Yi, Hong-Wei; Ma, Yu-Xiang; Wang, Xiao-Ning; Wang, Cui-Fen; Lu, Jian; Cao, Wei; Wu, Xu-Dong

    2015-04-01

    Serum palmitic acid (PA), a type of saturated fatty acid, causes lipid accumulation and induces toxicity in hepatocytes. Ethanol (EtOH) is metabolized by the liver and induces hepatic injury and inflammation. Herein, we analyzed the effects of EtOH on PA-induced lipotoxicity in the liver. Our results indicated that EtOH aggravated PA-induced apoptosis and lipid accumulation in primary rat hepatocytes in dose-dependent manner. EtOH intensified PA-caused endoplasmic reticulum (ER) stress response in vitro and in vivo, and the expressions of CHOP, ATF4, and XBP-1 in nucleus were significantly increased. EtOH also increased PA-caused cleaved caspase-3 in cytoplasm. In wild type and CHOP(-/-) mice treated with EtOH and high fat diet (HFD), EtOH worsened the HFD-induced liver injury and dyslipidemia, while CHOP knockout blocked toxic effects of EtOH and PA. Our study suggested that targeting UPR-signaling pathways is a promising, novel approach to reducing EtOH and saturated fatty acid-induced metabolic complications.

  19. Saturated phosphatidic acids mediate saturated fatty acid-induced vascular calcification and lipotoxicity.

    PubMed

    Masuda, Masashi; Miyazaki-Anzai, Shinobu; Keenan, Audrey L; Okamura, Kayo; Kendrick, Jessica; Chonchol, Michel; Offermanns, Stefan; Ntambi, James M; Kuro-O, Makoto; Miyazaki, Makoto

    2015-12-01

    Recent evidence indicates that saturated fatty acid-induced (SFA-induced) lipotoxicity contributes to the pathogenesis of cardiovascular and metabolic diseases; however, the molecular mechanisms that underlie SFA-induced lipotoxicity remain unclear. Here, we have shown that repression of stearoyl-CoA desaturase (SCD) enzymes, which regulate the intracellular balance of SFAs and unsaturated FAs, and the subsequent accumulation of SFAs in vascular smooth muscle cells (VSMCs), are characteristic events in the development of vascular calcification. We evaluated whether SMC-specific inhibition of SCD and the resulting SFA accumulation plays a causative role in the pathogenesis of vascular calcification and generated mice with SMC-specific deletion of both Scd1 and Scd2. Mice lacking both SCD1 and SCD2 in SMCs displayed severe vascular calcification with increased ER stress. Moreover, we employed shRNA library screening and radiolabeling approaches, as well as in vitro and in vivo lipidomic analysis, and determined that fully saturated phosphatidic acids such as 1,2-distearoyl-PA (18:0/18:0-PA) mediate SFA-induced lipotoxicity and vascular calcification. Together, these results identify a key lipogenic pathway in SMCs that mediates vascular calcification. PMID:26517697

  20. Phosphoenolpyruvate carboxykinase is an acid-induced, chromosomally encoded virulence factor in Agrobacterium tumefaciens.

    PubMed

    Liu, Pu; Wood, Derek; Nester, Eugene W

    2005-09-01

    The pckA gene, encoding phosphoenolpyruvate carboxykinase, catalyzes the reversible decarboxylation and phosphorylation of oxaloacetate to form phosphoenolpyruvate. Located on the circular chromosome of Agrobacterium, this locus is adjacent to the loci chvG and chvI, encoding a two-component regulatory system that has been shown to be important in virulence. Using a reporter gene fusion, studies showed that the pckA gene is induced by acidic pH but not by acetosyringone. This acid induction is regulated by the chvG-chvI regulatory system, which controls acid-inducible genes. A pckA mutant had no demonstrable PckA enzyme activity and grew on AB minimal medium with glucose but did not grow on the same medium with succinate as the sole carbon source and was more inhibited in its growth than the wild-type strain by an acidic environment. A pckA mutant was highly attenuated in tumor-inducing ability on tobacco leaf disks and was severely attenuated in vir gene expression. Although vir gene induction was completely restored when a constitutive virG gene was introduced into the mutant strain, virulence was only partially restored. These results suggest that avirulence may be due to a combination of the inhibition of this mutant in the acidic plant wound environment and the poor induction of the vir genes. PMID:16109945

  1. SV40 enhancer activation during retinoic acid-induced differentiation of F9 embryonal carcinoma cells.

    PubMed Central

    Sleigh, M J; Lockett, T J

    1985-01-01

    The transient expression vector pSV2CAT, which carries the bacterial chloramphenicol acetyl transferase (CAT) gene under the control of the SV40 early promoter, was used to transfect the murine embryonal carcinoma cell line F9 at various times during the retinoic acid-induced differentiation of these cells. Expression of the CAT gene under SV40 promoter control was found to increase markedly on F9 cell differentiation, measured relative to expression from the thymidine kinase promoter in the same cells. A series of constructs was prepared to identify the features of the SV40 early promoter required for transcription in differentiated and undifferentiated cells, as well as the factors limiting transcription in each case. The increased transcription seen on F9 cell differentiation was not observed when cells were transfected with molecules lacking a functional enhancer. It appears that as embryonal carcinoma cells differentiate, increased SV40 transcription results from enhancer sequence activation. In both differentiated and undifferentiated cell types the level of transcription was found to be limited by the availability and/or activity of cellular factors necessary for enhancer function. Images Fig. 1. PMID:3004973

  2. Bile acid induced colonic irritation stimulates intracolonic nitric oxide release in humans.

    PubMed Central

    Casellas, F; Mourelle, M; Papo, M; Guarner, F; Antolin, M; Armengol, J R; Malagelada, J R

    1996-01-01

    AIM--To measure the intracolonic release of nitric oxide end products (nitrates plus nitrites) and eicosanoids in response to intraluminal irritation with deoxycholic acid (DCA). PATIENTS--Seven patients with irritable bowel syndrome. METHODS--The left colon was perfused with a solution with or without 3 mM deoxycholic acid. Aspirates were assayed for eicosanoids by specific radioimmuno-assay, and for nitrates plus nitrites by the Griess reaction. To confirm that stimulated colonic mucosa can produce nitric oxide (NO), ancillary studies were performed in vitro using samples of normal mucosa obtained from five surgically resected colons. Samples were incubated for 30 minutes in Kreb's solution, 3 mM DCA or DCA with 1 mM L-nitro-arginine-methyl-ester (L-NAME) to inhibit the NO synthase. Finally, NO synthase activity was measured in five samples of human colonic mucosa. RESULTS--Intracolonic release of nitrates plus nitrites was basally undetectable in six of seven patients. Bile acid considerably increased the release of prostaglandin E2 and nitrates plus nitrites (p < 0.01). By contrast, no increase in thromboxane and leukotriene was seen. In vitro mucosal incubation with DCA increased the production of NO synthase products, which was blocked by L-NAME. Activity of Ca+2 independent NO synthase was detectable in four of five samples of human colonic mucosa. CONCLUSION--The human colonic mucosa responds to bile acid induced irritation by a surge in NO generation via NO synthase. PMID:8707118

  3. A West Nile virus mutant with increased resistance to acid-induced inactivation.

    PubMed

    Martín-Acebes, Miguel A; Saiz, Juan-Carlos

    2011-04-01

    West Nile virus (WNV) is a mosquito-borne flavivirus responsible for epidemics of febrile illness, meningitis, encephalitis and flaccid paralysis. WNV gains entry into host cells through endocytosis. The acid pH inside endosomes triggers rapid conformational rearrangements of the flavivirus envelope (E) glycoprotein that result in fusion of the endosomal membrane with the virion envelope. Conformational rearrangements of the E glycoprotein can be induced by acid exposure in solution in the absence of target membranes, thus causing a loss of infectivity. Following a genetic approach to study this process, a WNV mutant with increased resistance to acid-induced inactivation was isolated and its complete genome was sequenced. A single amino acid substitution, T70I, in the E glycoprotein was found to be responsible for the increased acid resistance, which was linked to an increase in the sensitivity of infection to the chemical rise of endosomal pH, suggesting that the mutant required a more acid pH inside the endosomes for fusion. No alterations in viral infection kinetics, plaque size or induced mortality rates in mice of the mutant were noted. However, by means of virus competition assays, a reduction in viral fitness under standard culture conditions was observed for the mutant. These results provide new evidence of the adaptive flexibility to environmental factors--pH variation in this case--of WNV populations. Implications of the T70I replacement on the E glycoprotein structure-function relationship are discussed.

  4. Neuroprotective effects of MK-801 on L-2-chloropropionic acid-induced neurotoxicity.

    PubMed

    Williams, R E; Lock, E A; Bachelard, H S

    2001-02-01

    L-2-Chloropropionic acid is selectively toxic to the cerebellum in rats; the granule cell necrosis observed within 48 h can be prevented by prior administration of MK-801. Short-term treatment (2 h) with L-2-chloropropionic acid has also been shown to activate the mitochondrial pyruvate dehydrogenase complex in fasted adult rats. This study aimed to investigate the effect of prior exposure to MK-801 on the biochemical and neurotoxicological effects of L-2-chloropropionic acid. Extracts were prepared from the forebrain and cerebellum of animals that had been treated with L-2-chloropropionic acid, with and without prior treatment with MK-801, and were analysed using magnetic resonance spectroscopy and amino acid analysis. Glucose metabolism was studied by monitoring the metabolism of [1-(13)C]-glucose using GC/MS. L-2-Chloropropionic acid caused increased glucose metabolism in both brain regions 6 h after administration, confirming activation of the pyruvate dehydrogenase complex, which was not prevented by MK-801. After 48 h an increase in lactate and a decrease in N-acetylaspartate was observed only in the cerebellum, whereas phosphocreatine and ATP decreased in both tissues. MK-801 prevented the changes in lactate and N:-acetylaspartate, but not those on the energy state. These studies suggest that L-2-chloropropionic acid-induced neurotoxicity is only partly mediated by the NMDA subtype of glutamate receptor.

  5. Saturated phosphatidic acids mediate saturated fatty acid-induced vascular calcification and lipotoxicity.

    PubMed

    Masuda, Masashi; Miyazaki-Anzai, Shinobu; Keenan, Audrey L; Okamura, Kayo; Kendrick, Jessica; Chonchol, Michel; Offermanns, Stefan; Ntambi, James M; Kuro-O, Makoto; Miyazaki, Makoto

    2015-10-26

    Recent evidence indicates that saturated fatty acid-induced (SFA-induced) lipotoxicity contributes to the pathogenesis of cardiovascular and metabolic diseases; however, the molecular mechanisms that underlie SFA-induced lipotoxicity remain unclear. Here, we have shown that repression of stearoyl-CoA desaturase (SCD) enzymes, which regulate the intracellular balance of SFAs and unsaturated FAs, and the subsequent accumulation of SFAs in vascular smooth muscle cells (VSMCs), are characteristic events in the development of vascular calcification. We evaluated whether SMC-specific inhibition of SCD and the resulting SFA accumulation plays a causative role in the pathogenesis of vascular calcification and generated mice with SMC-specific deletion of both Scd1 and Scd2. Mice lacking both SCD1 and SCD2 in SMCs displayed severe vascular calcification with increased ER stress. Moreover, we employed shRNA library screening and radiolabeling approaches, as well as in vitro and in vivo lipidomic analysis, and determined that fully saturated phosphatidic acids such as 1,2-distearoyl-PA (18:0/18:0-PA) mediate SFA-induced lipotoxicity and vascular calcification. Together, these results identify a key lipogenic pathway in SMCs that mediates vascular calcification.

  6. Role of neurosteroids in experimental 3-nitropropionic acid induced neurotoxicity in rats.

    PubMed

    Kumar, Pushpender; Kumar, Puneet; Khan, Aamir; Deshmukh, Rahul; Lal Sharma, Pyare

    2014-01-15

    Huntington's disease is an autosomal dominant, progressive, and fatal neurodegenerative disease characterized by motor and non-motor symptoms. Systemic administration of 3-nitropropionic acid, a complex II inhibitor of the electron transport chain induces selective striatal lesions in rodents. Neurosteroids are synthesized in central nervous system, able to modulate GABAA receptor function and has been reported to have neuroprotective action. The present study has been designed to investigate the role of neurosteroids such as progesterone and pregnenolone which are positive and negative modulators of GABA respectively against 3-nitropropionic acid induced experimental Huntington's disease. Systemic administration of 3-nitropropionic acid (10mg/kg i.p.) for 14 days significantly reduced body weight, locomotor activity, motor coordination, balance beam walk performance, antioxidant defense enzymes (reduced glutathione and catalase) and significantly increase oxidative stress markers (lipid peroxidation and nitrite level) in striatum and cortex. 3-Nitropropionic acid treatment also increases pro-inflammatory cytokines (TNF-α and IL-1β) level in striatum. Progesterone (10, 20mg/kg/day i.p.) treatments for 14 days significantly reversed the behavioral, antioxidant defense enzymes, oxidative stress marker and pro-inflammatory cytokines as compared to the 3-Nitropropionic acid treated group. Pregnenolone (1 and 2mg/kg i.p.), a negative modulator of GABAA pretreatment significantly reversed the protective effect of progesterone on behavioral and biochemical parameters. The results of the present study suggest that the positive GABAergic modulation may be beneficial for the treatment of motor disorder. PMID:24333475

  7. Folic acid induces salicylic acid-dependent immunity in Arabidopsis and enhances susceptibility to Alternaria brassicicola.

    PubMed

    Wittek, Finni; Kanawati, Basem; Wenig, Marion; Hoffmann, Thomas; Franz-Oberdorf, Katrin; Schwab, Wilfried; Schmitt-Kopplin, Philippe; Vlot, A Corina

    2015-08-01

    Folates are essential for one-carbon transfer reactions in all organisms and contribute, for example, to de novo DNA synthesis. Here, we detected the folate precursors 7,8-dihydropteroate (DHP) and 4-amino-4-deoxychorismate (ADC) in extracts from Arabidopsis thaliana plants by Fourier transform ion cyclotron resonance-mass spectrometry. The accumulation of DHP, but not ADC, was induced after infection of plants with Pseudomonas syringae delivering the effector protein AvrRpm1. Application of folic acid or the DHP precursor 7,8-dihydroneopterin (DHN) enhanced resistance in Arabidopsis to P. syringae and elevated the transcript accumulation of the salicylic acid (SA) marker gene pathogenesis-related1 in both the treated and systemic untreated leaves. DHN- and folic acid-induced systemic resistance was dependent on SA biosynthesis and signalling. Similar to SA, folic acid application locally enhanced Arabidopsis susceptibility to the necrotrophic fungus Alternaria brassicicola. Together, the data associate the folic acid pathway with innate immunity in Arabidopsis, simultaneously activating local and systemic SA-dependent resistance to P. syringae and suppressing local resistance to A. brassicicola.

  8. Effect of galactose on acid induced molten globule state of Soybean Agglutinin: Biophysical approach

    NASA Astrophysics Data System (ADS)

    Alam, Parvez; Naseem, Farha; Abdelhameed, Ali Saber; Khan, Rizwan Hasan

    2015-11-01

    In the present study the formation of molten globule-like unfolding intermediate Soybean Agglutinin (SBA) in acidic pH range has been established with the help of acrylamide quenching, intrinsic fluorescence, ANS fluorescence measurement, far UV CD and dynamic light scattering measurement. A marked increase in ANS fluorescence was observed at pH 2.2. Ksv of acrylamide quenching was found to be higher at pH 2.2 than that of native SBA at pH 7. Far UV CD spectra of pH induced state suggest that SBA shows significant retention of secondary structure closure to native. Hydrodynamic radius of SBA at pH 2.2 was found be more as compared to native state and also in other pH induced states. Further we checked the effect of galactose on the molten globule state of SBA. This study suggests that SBA exist as molten globule at pH 2.2 and this study will help in acid induced molten globule state of other proteins.

  9. Functional analysis of a tannic-acid-inducible and hypoviral-regulated small heat-shock protein Hsp24 from the chestnut blight fungus Cryphonectria parasitica.

    PubMed

    Baek, Jin-Ho; Park, Jin-Ah; Kim, Jung-Mi; Oh, Jung-Mi; Park, Seung-Moon; Kim, Dae-Hyuk

    2014-01-01

    A small heat-shock protein gene, CpHsp24, of Cryphonectria parasitica was selected based on its expression pattern, which showed that it was tannic acid inducible and that its induction was severely hampered by a hypovirus. The predicted protein sequence of CpHsp24 consisted of a hallmark α-crystalline domain flanked by a variable N-terminal and a short C-terminal region. Disruption of CpHsp24 resulted in a slow growth rate under standard growth conditions. The CpHsp24-null mutant showed enhanced sensitivity to heat shock, which was consistent with Northern and Western analyses displaying the heat-shock induction of the CpHsp24 gene and protein, respectively. Virulence tests on the excised bark revealed a severe decrease in the necrotic area of the CpHsp24-null mutant. When the hypovirus was transferred, virus-containing CpHsp24-null progeny displayed severely retarded growth patterns with hypovirulent characteristics of reduced pigmentation and sporulation. Because the tannic-acid-inducible and hypoviral-suppressible expression and the severely impaired virulence are also characteristics of the laccase3 gene (lac3), lac3 expression in the CpHsp24-null mutant was also examined. The resulting lac3 induction was severely affected in the CpHsp24-null mutant, suggesting that CpHsp24 is important for lac3 induction and that CpHsp24 may act as a molecular chaperone for the lac3 protein.

  10. Tachykinin inhibition of acid-induced gastric hyperaemia in the rat.

    PubMed Central

    Heinemann, A.; Jocic, M.; Herzeg, G.; Holzer, P.

    1996-01-01

    1. Primary afferent neurones releasing the vasodilator, calcitonin gene-related peptide, mediate the gastric hyperaemic response to acid back-diffusion. The tachykinins neurokinin A (NKA) and substance P (SP) are located in the same neurones and are co-released with calcitonin gene-related peptide. In this study we investigated the effect and possible role of tachykinins in the acid-evoked gastric vasodilatation in urethane-anaesthetized rats. 2. Gastric acid back-diffusion, induced by perfusing the stomach with 15% ethanol in the presence of 0.05 M HCl, increased gastric mucosal blood flow by 60-90%, as determined by the hydrogen clearance technique. NKA and SP (0.14-3.78 nmol min-1 kg-1, infused intra-aortically) inhibited the gastric mucosal hyperaemic response to acid back-diffusion in a dose-dependent manner, an effect that was accompanied by aggravation of ethanol/acid-induced macroscopic haemorrhagic lesions. 3. The inhibitory effect of NKA (1.26 nmol min-1 kg-1) on the acid-induced gastric mucosal vasodilatation was prevented by the tachykinin NK2 receptor antagonists, MEN 10,627 (200 nmol kg-1) but left unaltered by the NK1 receptor antagonist, SR 140,333 (300 nmol kg-1) and the mast-cell stabilizer, ketotifen (4.6 mumol kg-1). 4. Under basal conditions, with 0.05 M HCl being perfused through the stomach, NKA (1.26 nmol min-1 kg-1) reduced gastric mucosal blood flow by about 25%, an effect that was abolished by SR 140,333 but not MEN 10,627 or ketotifen. 5. SR 140,333, MEN 10,627 or ketotifen had no significant effect on basal gastric mucosal blood flow nor did they modify the gastric mucosal hyperaemic reaction to acid back-diffusion. 6. The effect of NKA (1.26 nmol min-1 kg-1) in causing vasoconstriction and inhibiting the vasodilator response to acid back-diffusion was also seen when blood flow in the left gastric artery was measured with the ultrasonic transit time shift technique. 7. Arginine vasopressin (AVP, 0.1 nmol min-1 kg-1) induced gastric

  11. Loss of n-6 fatty acid induced pediatric obesity protects against acute murine colitis

    PubMed Central

    Nagy-Szakal, Dorottya; Mir, Sabina A. V.; Harris, R. Alan; Dowd, Scot E.; Yamada, Takeshi; Lacorazza, H. Daniel; Tatevian, Nina; Smith, C. Wayne; de Zoeten, Edwin F.; Klein, John; Kellermayer, Richard

    2015-01-01

    Dietary influences may affect microbiome composition and host immune responses, thereby modulating propensity toward inflammatory bowel diseases (IBDs): Crohn disease (CD) and ulcerative colitis (UC). Dietary n-6 fatty acids have been associated with UC in prospective studies. However, the critical developmental period when (n-6) consumption may induce UC is not known. We examined the effects of transiently increased n-6 consumption during pediatric development on subsequent dextran-sulfate-sodium (DSS)-induced acute murine colitis. The animals transiently became obese then rapidly lost this phenotype. Interestingly, mice were protected against DSS colitis 40 days after n-6 consumption. The transient high n-6-induced protection against colitis was fat type- and dietary reversal-dependent and could be transferred to germ-free mice by fecal microbiota transplantation. We also detected decreased numbers of chemokine receptor (Cxcr)5+ CD4+ T cells in the mesenteric lymph nodes (MLNs) of transiently n-6-fed mice. Further experiments revealed that anti-chemokine ligand (Cxcl)13 (the ligand of Cxcr5) antibody treatment decreased DSS colitis severity, implicating the importance of the Cxcr5-Cxcl13 pathway in mammalian colitis. Consecutively, we found elevated CXCL13 concentrations (CD: 1.8-fold, P = 0.0077; UC: 1.9-fold, P = 0.056) in the serum of untreated pediatric IBD patients. The human serologic observations supported the translational relevance of our findings.—Nagy-Szakal, D., Mir, S. A. V., Harris, R. A., Dowd, S. E., Yamada, T., Lacorazza, H. D., Tatevian, N., Smith, C. W., de Zoeten, E. F., Klein, J., Kellermayer, R. Loss of n-6 fatty acid induced pediatric obesity protects against acute murine colitis. PMID:25903104

  12. Helicobacter pylori impedes acid-induced tightening of gastric epithelial junctions

    PubMed Central

    Marcus, Elizabeth A.; Vagin, Olga; Tokhtaeva, Elmira; Sachs, George

    2013-01-01

    Gastric infection by Helicobacter pylori is the most common cause of ulcer disease and gastric cancer. The mechanism of progression from gastritis and inflammation to ulcers and cancer in a fraction of those infected is not definitively known. Significant acidity is unique to the gastric environment and is required for ulcer development. The interplay between gastric acidity and H. pylori pathogenesis is important in progression to advanced disease. The aim of this study was to characterize the impact of acid on gastric epithelial integrity and cytokine release and how H. pylori infection alters these responses. Human gastric epithelial (HGE-20) cells were grown on porous inserts, and survival, barrier function, and cytokine release were studied at various apical pH levels in the presence and absence of H. pylori. With apical acidity, gastric epithelial cells demonstrate increased barrier function, as evidenced by increased transepithelial electrical resistance (TEER) and decreased paracellular permeability. This effect is reduced in the presence of wild-type, but not urease knockout, H. pylori. The epithelial inflammatory response is also modulated by acidity and H. pylori infection. Without H. pylori, epithelial IL-8 release decreases in acid, while IL-6 release increases. In the presence of H. pylori, acidic pH diminishes the magnitude of the previously reported increase in IL-8 and IL-6 release. H. pylori interferes with the gastric epithelial response to acid, contributing to altered barrier function and inflammatory response. H. pylori diminishes acid-induced tightening of cell junctions in a urease-dependent manner, suggesting that local pH elevation promotes barrier compromise and progression to mucosal damage. PMID:23989011

  13. Intrarenal renin-angiotensin system mediates fatty acid-induced ER stress in the kidney.

    PubMed

    Li, Chunling; Lin, Yu; Luo, Renfei; Chen, Shaoming; Wang, Feifei; Zheng, Peili; Levi, Moshe; Yang, Tianxin; Wang, Weidong

    2016-03-01

    Obesity-related kidney disease is related to caloric excess promoting deleterious cellular responses. Accumulation of saturated free fatty acids in tubular cells produces lipotoxicity involving significant cellular dysfunction and injury. The objectives of this study were to elucidate the role of renin-angiotensin system (RAS) activation in saturated fatty acid-induced endoplasmic reticulum (ER) stress in cultured human proximal tubule epithelial cells (HK2) and in mice fed with a high-fat diet. Treatment with saturated fatty acid palmitic acid (PA; 0.8 mM) for 24 h induced ER stress in HK2, leading to an unfolded protein response as reflected by increased expressions of the ER chaperone binding immunoglobulin protein (BiP) and proapoptotic transcription factor C/EBP homologous protein (CHOP) protein as evaluated by immunoblotting. PA treatment also induced increased protein expression of inositol requiring protein 1α (IRE1α), phosphorylated eukaryotic initiation factor-α (eIF2α), and activating transcription factor 4 (ATF4) as well as activation of caspase-3. PA treatment was associated with increased angiotensin II levels in cultured medium. The angiotensin II type 1 receptor (AT1R) blocker valsartan or renin inhibitor aliskiren dramatically suppressed PA-induced upregulation of BiP, CHOP, IRE1α, p-eIF2α, and ATF4 in HK2 cells. In contrast, valsartan or aliskiren did not prevent ER stress induced by tunicamycin. C57BL/6 mice fed with a high-fat diet for 14 wk exhibited increased protein expressions of BiP and CHOP compared with control mice, which were significantly attenuated by the valsartan treatment. Increased angiotensin II levels in serum and urine were observed in mice fed with a high-fat diet when compared with controls. It is suggested that the intrarenal RAS activation may play an important role in diabetic kidney injury via mediating ER stress induced by saturated fatty acid. PMID:26672616

  14. Diets Rich in Saturated and Polyunsaturated Fatty Acids Induce Morphological Alterations in the Rat Ventral Prostate

    PubMed Central

    Furriel, Angélica; Campos-Silva, Pamella; Silva, Paola Cariello Guedes Picarote; Costa, Waldemar Silva; Sampaio, Francisco José Barcellos; Gregório, Bianca Martins

    2014-01-01

    Aim To evaluate the influence of dietary lipid quality on the body mass, carbohydrate metabolism and morphology of the rat ventral prostate. Materials and Methods Wistar rats were divided into four groups: SC (standard chow), HF-S (high-fat diet rich in saturated fatty acids), HF-P (high-fat diet rich in polyunsaturated fatty acids) and HF-SP (high-fat diet rich in saturated and polyunsaturated fatty acids). We analyzed body mass, fat mass deposits, plasma blood, insulin resistance and the ventral prostate structure. Results Groups that received high-fat diets were heavier and presented larger fat deposits than SC group. The HF-S and HF-SP groups had higher glucose, insulin and total cholesterol serum levels and insulin resistance compared with the SC. The acinar area, epithelium height and area density of the lumen were higher in the HF-SP than in the other groups. The epithelium area density and epithelial cell proliferation were greater in the HF-P and HF-SP than in the SC group. All of the groups that received high-fat diets had greater area density of the stroma, area density of smooth muscle cells and stromal cell proliferation compared with the SC group. Conclusion Diets rich in saturated and/or polyunsaturated fatty acids induced overweight. Independently of insulin resistance, polyunsaturated fatty acids increased prostate stromal and epithelial cell proliferation. Saturated fatty acids influenced only stromal cellular proliferation. These structural and morphometric alterations may be considered risk factors for the development of adverse remodeling process in the rat ventral prostate. PMID:25029463

  15. A dual inhibitor of cyclooxygenase and 5-lipoxygenase protects against kainic acid-induced brain injury.

    PubMed

    Minutoli, Letteria; Marini, Herbert; Rinaldi, Mariagrazia; Bitto, Alessandra; Irrera, Natasha; Pizzino, Gabriele; Pallio, Giovanni; Calò, Margherita; Adamo, Elena Bianca; Trichilo, Vincenzo; Interdonato, Monica; Galfo, Federica; Squadrito, Francesco; Altavilla, Domenica

    2015-06-01

    Systemic administration of kainic acid causes inflammation and apoptosis in the brain, resulting in neuronal loss. Dual cyclooxygenase/5-lipoxygenase (COX/5-LOX) inhibitors could represent a possible neuroprotective approach in preventing glutamate excitotoxicity. Consequently, we investigated the effects of a dual inhibitor of COX/5-LOX following intraperitoneal administration of kainic acid (KA, 10 mg/kg) in rats. Animals were randomized to receive either the dual inhibitor of COX/5-LOX (flavocoxid, 20 mg/kg i.p.) or its vehicle (1 ml/kg i.p.) 30 min after KA administration. Sham brain injury rats were used as controls. We evaluated protein expression of phosphorylated extracellular signal-regulated kinase (p-ERK1/2) and tumor necrosis factor alpha (TNF-α) as well as levels of malondialdehyde (MDA), prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) in the hippocampus. Animals were also observed for monitoring behavioral changes according to Racine Scale. Finally, histological analysis and brain edema evaluation were carried out. Treatment with the dual inhibitor of COX/5-LOX decreased protein expression of p-ERK1/2 and TNF-α in hippocampus, markedly reduced MDA, LTB4 and PGE2 hippocampal levels, and also ameliorated brain edema. Histological analysis showed a reduction in cell damage in rats treated with the dual inhibitor of COX/5-LOX, particularly in hippocampal subregion CA3c. Moreover, flavocoxid significantly improved behavioral signs following kainic acid administration. Our results suggest that dual inhibition of COX/5-LOX by flavocoxid has neuroprotective effects during kainic acid-induced excitotoxicity. PMID:25893744

  16. Bile acid-induced necrosis in primary human hepatocytes and in patients with obstructive cholestasis

    SciTech Connect

    Woolbright, Benjamin L.; Dorko, Kenneth; Antoine, Daniel J.; Clarke, Joanna I.; Gholami, Parviz; Li, Feng; Kumer, Sean C.; Schmitt, Timothy M.; Forster, Jameson; Fan, Fang; Jenkins, Rosalind E.; Park, B. Kevin; Hagenbuch, Bruno; Olyaee, Mojtaba; Jaeschke, Hartmut

    2015-03-15

    Accumulation of bile acids is a major mediator of cholestatic liver injury. Recent studies indicate bile acid composition between humans and rodents is dramatically different, as humans have a higher percent of glycine conjugated bile acids and increased chenodeoxycholate content, which increases the hydrophobicity index of bile acids. This increase may lead to direct toxicity that kills hepatocytes, and promotes inflammation. To address this issue, this study assessed how pathophysiological concentrations of bile acids measured in cholestatic patients affected primary human hepatocytes. Individual bile acid levels were determined in serum and bile by UPLC/QTOFMS in patients with extrahepatic cholestasis with, or without, concurrent increases in serum transaminases. Bile acid levels increased in serum of patients with liver injury, while biliary levels decreased, implicating infarction of the biliary tracts. To assess bile acid-induced toxicity in man, primary human hepatocytes were treated with relevant concentrations, derived from patient data, of the model bile acid glycochenodeoxycholic acid (GCDC). Treatment with GCDC resulted in necrosis with no increase in apoptotic parameters. This was recapitulated by treatment with biliary bile acid concentrations, but not serum concentrations. Marked elevations in serum full-length cytokeratin-18, high mobility group box 1 protein (HMGB1), and acetylated HMGB1 confirmed inflammatory necrosis in injured patients; only modest elevations in caspase-cleaved cytokeratin-18 were observed. These data suggest human hepatocytes are more resistant to human-relevant bile acids than rodent hepatocytes, and die through necrosis when exposed to bile acids. These mechanisms of cholestasis in humans are fundamentally different to mechanisms observed in rodent models. - Highlights: • Cholestatic liver injury is due to cytoplasmic bile acid accumulation in hepatocytes. • Primary human hepatocytes are resistant to BA-induced injury

  17. Bile Acid-Induced Necrosis in Primary Human Hepatocytes and in Patients with Obstructive Cholestasis

    PubMed Central

    Woolbright, Benjamin L.; Dorko, Kenneth; Antoine, Daniel J.; Clarke, Joanna I.; Gholami, Parviz; Li, Feng; Kumer, Sean C.; Schmitt, Timothy M.; Forster, Jameson; Fan, Fang; Jenkins, Rosalind E.; Park, B. Kevin; Hagenbuch, Bruno; Olyaee, Mojtaba; Jaeschke, Hartmut

    2015-01-01

    Accumulation of bile acids is a major mediator of cholestatic liver injury. Recent studies indicate bile acid composition between humans and rodents is dramatically different, as humans have a higher percent of glycine conjugated bile acids and increased chenodeoxycholate content, which increases the hydrophobicity index of bile acids. This increase may lead to direct toxicity that kills hepatocytes, and promotes inflammation. To address this issue, this study assessed how pathophysiological concentrations of bile acids measured in cholestatic patients affected primary human hepatocytes. Individual bile acid levels were determined in serum and bile by UPLC/QTOFMS in patients with extrahepatic cholestasis with, or without, concurrent increases in serum transaminases. Bile acid levels increased in serum of patients with liver injury, while biliary levels decreased, implicating infarction of the biliary tracts. To assess bile acid-induced toxicity in man, primary human hepatocytes were treated with relevant concentrations, derived from patient data, of the model bile acid glycochenodeoxycholic acid (GCDC). Treatment with GCDC resulted in necrosis with no increase in apoptotic parameters. This was recapitulated by treatment with biliary bile acid concentrations, but not serum concentrations. Marked elevations in serum full-length cytokeratin-18, high mobility group box1 protein (HMGB1), and acetylated HMGB1 confirmed inflammatory necrosis in injured patients; only modest elevations in caspase-cleaved cytokeratin-18 were observed. These data suggest human hepatocytes are more resistant to human-relevant bile acids than rodent hepatocytes, and die through necrosis when exposed to bile acids. These mechanisms of cholestasis in humans are fundamentally different to mechanisms observed in rodent models. PMID:25636263

  18. Human sweet taste receptor mediates acid-induced sweetness of miraculin.

    PubMed

    Koizumi, Ayako; Tsuchiya, Asami; Nakajima, Ken-ichiro; Ito, Keisuke; Terada, Tohru; Shimizu-Ibuka, Akiko; Briand, Loïc; Asakura, Tomiko; Misaka, Takumi; Abe, Keiko

    2011-10-01

    Miraculin (MCL) is a homodimeric protein isolated from the red berries of Richadella dulcifica. MCL, although flat in taste at neutral pH, has taste-modifying activity to convert sour stimuli to sweetness. Once MCL is held on the tongue, strong sweetness is sensed over 1 h each time we taste a sour solution. Nevertheless, no molecular mechanism underlying the taste-modifying activity has been clarified. In this study, we succeeded in quantitatively evaluating the acid-induced sweetness of MCL using a cell-based assay system and found that MCL activated hT1R2-hT1R3 pH-dependently as the pH decreased from 6.5 to 4.8, and that the receptor activation occurred every time an acid solution was applied. Although MCL per se is sensory-inactive at pH 6.7 or higher, it suppressed the response of hT1R2-hT1R3 to other sweeteners at neutral pH and enhanced the response at weakly acidic pH. Using human/mouse chimeric receptors and molecular modeling, we revealed that the amino-terminal domain of hT1R2 is required for the response to MCL. Our data suggest that MCL binds hT1R2-hT1R3 as an antagonist at neutral pH and functionally changes into an agonist at acidic pH, and we conclude this may cause its taste-modifying activity. PMID:21949380

  19. Role of ion transporters in the bile acid-induced esophageal injury.

    PubMed

    Laczkó, Dorottya; Rosztóczy, András; Birkás, Klaudia; Katona, Máté; Rakonczay, Zoltán; Tiszlavicz, László; Róka, Richárd; Wittmann, Tibor; Hegyi, Péter; Venglovecz, Viktória

    2016-07-01

    Barrett's esophagus (BE) is considered to be the most severe complication of gastro-esophageal reflux disease (GERD), in which the prolonged, repetitive episodes of combined acidic and biliary reflux result in the replacement of the squamous esophageal lining by columnar epithelium. Therefore, the acid-extruding mechanisms of esophageal epithelial cells (EECs) may play an important role in the defense. Our aim was to identify the presence of acid/base transporters on EECs and to investigate the effect of bile acids on their expressions and functions. Human EEC lines (CP-A and CP-D) were acutely exposed to bile acid cocktail (BAC) and the changes in intracellular pH (pHi) and Ca(2+) concentration ([Ca(2+)]i) were measured by microfluorometry. mRNA and protein expression of ion transporters was investigated by RT-PCR, Western blot, and immunohistochemistry. We have identified the presence of a Na(+)/H(+) exchanger (NHE), Na(+)/HCO3 (-) cotransporter (NBC), and a Cl(-)-dependent HCO3 (-) secretory mechanism in CP-A and CP-D cells. Acute administration of BAC stimulated HCO3 (-) secretion in both cell lines and the NHE activity in CP-D cells by an inositol triphosphate-dependent calcium release. Chronic administration of BAC to EECs increased the expression of ion transporters compared with nontreated cells. A similar expression pattern was observed in biopsy samples from BE compared with normal epithelium. We have shown that acute administration of bile acids differently alters ion transport mechanisms of EECs, whereas chronic exposure to bile acids increases the expression of acid/base transporters. We speculate that these adaptive processes of EECs represent an important mucosal defense against the bile acid-induced epithelial injury. PMID:27198194

  20. Human sweet taste receptor mediates acid-induced sweetness of miraculin

    PubMed Central

    Koizumi, Ayako; Tsuchiya, Asami; Nakajima, Ken-ichiro; Ito, Keisuke; Terada, Tohru; Shimizu-Ibuka, Akiko; Briand, Loïc; Asakura, Tomiko; Misaka, Takumi; Abe, Keiko

    2011-01-01

    Miraculin (MCL) is a homodimeric protein isolated from the red berries of Richadella dulcifica. MCL, although flat in taste at neutral pH, has taste-modifying activity to convert sour stimuli to sweetness. Once MCL is held on the tongue, strong sweetness is sensed over 1 h each time we taste a sour solution. Nevertheless, no molecular mechanism underlying the taste-modifying activity has been clarified. In this study, we succeeded in quantitatively evaluating the acid-induced sweetness of MCL using a cell-based assay system and found that MCL activated hT1R2-hT1R3 pH-dependently as the pH decreased from 6.5 to 4.8, and that the receptor activation occurred every time an acid solution was applied. Although MCL per se is sensory-inactive at pH 6.7 or higher, it suppressed the response of hT1R2-hT1R3 to other sweeteners at neutral pH and enhanced the response at weakly acidic pH. Using human/mouse chimeric receptors and molecular modeling, we revealed that the amino-terminal domain of hT1R2 is required for the response to MCL. Our data suggest that MCL binds hT1R2-hT1R3 as an antagonist at neutral pH and functionally changes into an agonist at acidic pH, and we conclude this may cause its taste-modifying activity. PMID:21949380

  1. Antinociceptive effect of aqueous extracts from the bark of Croton guatemalensis Lotsy in mice.

    PubMed

    Del Carmen, Rejón-Orantes José; Willam, Hernández Macías John; Del Carmen, Grajales Morales Azucena; Nataly, Jiménez-García; Stefany, Coutiño Ochoa Samantha; Anahi, Cañas Avalos; Domingo, Parcero Torres Jorge; Leonardo, Gordillo Páez; Miguel, Pérez de la Mora

    2016-01-01

    Croton guatemalensis Lotsy (CGL), known as "copalchi" in Chiapas, Mexico, is used for the treatment of fever, abdominal pain and malaria and also as a remedy for chills and for treating rheumatism. The aim of this study was to evaluate whether aqueous extracts from the bark of this plant possesses indeed antinociceptive properties by using two different animal models of nociception, the acetic acid-induced writhing test and the hot plate model. The results showed that i.p. administration of this extract (0, 100, 200 and 400 mg/kg) 30 min prior testing had significant dose-dependent antinociceptive effects in the acetic acid-induced writhing test and that the reduction of writhings (85.5 % as compared to the control) at the highest dose tested is similar to that exhibited by dipyrone (250 mg/kg). This effect was not reversed by naloxone, a non-selective opioid receptor antagonist, suggesting that the endogenous opioid system does not underlie the antinociceptive effects of CGL in the acetic acid-induced writhing test. No effects were however observed in the hot-plate model. Our results indicate that aqueous extracts from Croton guatemalensis bark contain pharmacologically active constituents endowed with antinociceptive activity. It is suggested that cyclooxygenase inhibition might be at least partially involved in the antinociceptive effects of this extract.

  2. Antinociceptive effect of aqueous extracts from the bark of Croton guatemalensis Lotsy in mice.

    PubMed

    Del Carmen, Rejón-Orantes José; Willam, Hernández Macías John; Del Carmen, Grajales Morales Azucena; Nataly, Jiménez-García; Stefany, Coutiño Ochoa Samantha; Anahi, Cañas Avalos; Domingo, Parcero Torres Jorge; Leonardo, Gordillo Páez; Miguel, Pérez de la Mora

    2016-01-01

    Croton guatemalensis Lotsy (CGL), known as "copalchi" in Chiapas, Mexico, is used for the treatment of fever, abdominal pain and malaria and also as a remedy for chills and for treating rheumatism. The aim of this study was to evaluate whether aqueous extracts from the bark of this plant possesses indeed antinociceptive properties by using two different animal models of nociception, the acetic acid-induced writhing test and the hot plate model. The results showed that i.p. administration of this extract (0, 100, 200 and 400 mg/kg) 30 min prior testing had significant dose-dependent antinociceptive effects in the acetic acid-induced writhing test and that the reduction of writhings (85.5 % as compared to the control) at the highest dose tested is similar to that exhibited by dipyrone (250 mg/kg). This effect was not reversed by naloxone, a non-selective opioid receptor antagonist, suggesting that the endogenous opioid system does not underlie the antinociceptive effects of CGL in the acetic acid-induced writhing test. No effects were however observed in the hot-plate model. Our results indicate that aqueous extracts from Croton guatemalensis bark contain pharmacologically active constituents endowed with antinociceptive activity. It is suggested that cyclooxygenase inhibition might be at least partially involved in the antinociceptive effects of this extract. PMID:27051428

  3. Antinociceptive effect of aqueous extracts from the bark of Croton guatemalensis Lotsy in mice

    PubMed Central

    del Carmen, Rejón-Orantes José; Willam, Hernández Macías John; del Carmen, Grajales Morales Azucena; Nataly, Jiménez-García; Stefany, Coutiño Ochoa Samantha; Anahi, Cañas Avalos; Domingo, Parcero Torres Jorge; Leonardo, Gordillo Páez; Miguel, Pérez de la Mora

    2016-01-01

    Croton guatemalensis Lotsy (CGL), known as “copalchi” in Chiapas, Mexico, is used for the treatment of fever, abdominal pain and malaria and also as a remedy for chills and for treating rheumatism. The aim of this study was to evaluate whether aqueous extracts from the bark of this plant possesses indeed antinociceptive properties by using two different animal models of nociception, the acetic acid-induced writhing test and the hot plate model. The results showed that i.p. administration of this extract (0, 100, 200 and 400 mg/kg) 30 min prior testing had significant dose-dependent antinociceptive effects in the acetic acid-induced writhing test and that the reduction of writhings (85.5 % as compared to the control) at the highest dose tested is similar to that exhibited by dipyrone (250 mg/kg). This effect was not reversed by naloxone, a non-selective opioid receptor antagonist, suggesting that the endogenous opioid system does not underlie the antinociceptive effects of CGL in the acetic acid-induced writhing test. No effects were however observed in the hot-plate model. Our results indicate that aqueous extracts from Croton guatemalensis bark contain pharmacologically active constituents endowed with antinociceptive activity. It is suggested that cyclooxygenase inhibition might be at least partially involved in the antinociceptive effects of this extract. PMID:27051428

  4. The influence of pretreatment with ghrelin on the development of acetic-acid-induced colitis in rats.

    PubMed

    Maduzia, D; Matuszyk, A; Ceranowicz, D; Warzecha, Z; Ceranowicz, P; Fyderek, K; Galazka, K; Dembinski, A

    2015-12-01

    Ghrelin has been primarily shown to exhibit protective and therapeutic effect in the gut. Pretreatment with ghrelin inhibits the development of acute pancreatitis and accelerates pancreatic recovery in the course of this disease. In the stomach, ghrelin reduces gastric mucosal damage induced by ethanol, stress or alendronate, as well as accelerates the healing of acetic acid-induced gastric and duodenal ulcer. The aim of present studies was to investigate the effect of pretreatment with ghrelin on the development of acetic acid-induced colitis. Studies have been performed on male Wistar rats. Animals were treated intraperitoneally with saline (control) or ghrelin (4, 8 or 16 nmol/kg/dose). Saline or ghrelin was given twice: 8 and 1 h before induction of colitis. Colitis was induced by a rectal enema with 1 ml of 4% solution of acetic acid and the severity of colitis was assessed 1 or 24 hours after induction of inflammation. Rectal administration of acetic acid induced colitis in all animals. Damage of colonic wall was seen at the macroscopic and microscopic level. This effect was accompanied by a reduction in colonic blood flow and mucosal DNA synthesis. Moreover, induction of colitis significantly increased mucosal concentration of pro-inflammatory interleukin-1β (IL-1β), activity of myeloperoxidase and concentration of malondialdehyde (MDA). Mucosal activity of superoxide dismutase (SOD) was reduced. Pretreatment with ghrelin reduced the area and grade of mucosal damage. This effect was accompanied by an improvement of blood flow, DNA synthesis and SOD activity in colonic mucosa. Moreover, ghrelin administration reduced mucosal concentration of IL-1β and MDA, as well as decreased mucosal activity of myeloperoxidase. Administration of ghrelin protects the large bowel against the development of the acetic acid-induced colitis and this effect seems to be related to the ghrelin-evoked anti-inflammatory and anti-oxidative effects.

  5. The influence of pretreatment with ghrelin on the development of acetic-acid-induced colitis in rats.

    PubMed

    Maduzia, D; Matuszyk, A; Ceranowicz, D; Warzecha, Z; Ceranowicz, P; Fyderek, K; Galazka, K; Dembinski, A

    2015-12-01

    Ghrelin has been primarily shown to exhibit protective and therapeutic effect in the gut. Pretreatment with ghrelin inhibits the development of acute pancreatitis and accelerates pancreatic recovery in the course of this disease. In the stomach, ghrelin reduces gastric mucosal damage induced by ethanol, stress or alendronate, as well as accelerates the healing of acetic acid-induced gastric and duodenal ulcer. The aim of present studies was to investigate the effect of pretreatment with ghrelin on the development of acetic acid-induced colitis. Studies have been performed on male Wistar rats. Animals were treated intraperitoneally with saline (control) or ghrelin (4, 8 or 16 nmol/kg/dose). Saline or ghrelin was given twice: 8 and 1 h before induction of colitis. Colitis was induced by a rectal enema with 1 ml of 4% solution of acetic acid and the severity of colitis was assessed 1 or 24 hours after induction of inflammation. Rectal administration of acetic acid induced colitis in all animals. Damage of colonic wall was seen at the macroscopic and microscopic level. This effect was accompanied by a reduction in colonic blood flow and mucosal DNA synthesis. Moreover, induction of colitis significantly increased mucosal concentration of pro-inflammatory interleukin-1β (IL-1β), activity of myeloperoxidase and concentration of malondialdehyde (MDA). Mucosal activity of superoxide dismutase (SOD) was reduced. Pretreatment with ghrelin reduced the area and grade of mucosal damage. This effect was accompanied by an improvement of blood flow, DNA synthesis and SOD activity in colonic mucosa. Moreover, ghrelin administration reduced mucosal concentration of IL-1β and MDA, as well as decreased mucosal activity of myeloperoxidase. Administration of ghrelin protects the large bowel against the development of the acetic acid-induced colitis and this effect seems to be related to the ghrelin-evoked anti-inflammatory and anti-oxidative effects. PMID:26769837

  6. Attenuation of proinflammatory cytokines and apoptotic process by verapamil and diltiazem against quinolinic acid induced Huntington like alterations in rats.

    PubMed

    Kalonia, Harikesh; Kumar, Puneet; Kumar, Anil

    2011-02-01

    Huntington disease is a neurodegenerative disease with complex pathophysiology. Recently, role of neuroinflammation and interplay between various other cellular cascades have been suggested to be involved in pathophysiology of Huntington disease. Involvement of calcium overload mediated oxidative damage and excitotoxicity have been suggested to play a central role in quinolinic acid induced Huntington like symptoms. The present study has been carried out to investigate the neuroprotective effect of calcium channel blockers (verapamil and diltiazem) against quinolinic acid induced dysfunction in motor, biochemical and neuroinflammatory signaling in rats. Intrastriatal quinolinic acid administration leads to significant motor [locomotor (72% reduction), rotarod (55% reduction), balance beam walk performance] dysfunction coupled with the marked oxidative damage and increased neuroinflammatory markers [TNF-α (140%), IL-6 (115%), caspase-3(75%)] levels in striatum as compared to the sham treatment. Verapamil (10 and 20mg/kg), diltiazem (10 and 20mg/kg) drug treatment for 21days resulted in a significant improvement in the motor function (improvement in locomotor activity, rotarod and balance beam walk performance). Further, verapamil (10 and 20mg/kg), diltiazem (10 and 20mg/kg) treatment significantly attenuated oxidative damage, level of proinflammatory mediators (TNF-α IL-6 and caspase-3) in quinolinic acid treated animals. Results of the present study demonstrate that protective effect of these calcium channel blockers (verapamil, diltiazem) might be due to their inhibitory action on different neuroinflammatory pathways against quinolinic acid induced Huntington disease like symptoms in rats. PMID:21112316

  7. Effect of CMC Molecular Weight on Acid-Induced Gelation of Heated WPI-CMC Soluble Complex.

    PubMed

    Huan, Yan; Zhang, Sha; Vardhanabhuti, Bongkosh

    2016-02-01

    Acid-induced gelation properties of heated whey protein isolate (WPI) and carboxymethylcellulose (CMC) soluble complex were investigated as a function of CMC molecular weight (270, 680, and 750 kDa) and concentrations (0% to 0.125%). Heated WPI-CMC soluble complex with 6% protein was made by heating biopolymers together at pH 7.0 and 85 °C for 30 min and diluted to 5% protein before acid-induced gelation. Acid-induced gel formed from heated WPI-CMC complexes exhibited increased hardness and decreased water holding capacity with increasing CMC concentrations but gel strength decreased at higher CMC content. The highest gel strength was observed with CMC 750 k at 0.05%. Gels with low CMC concentration showed homogenous microstructure which was independent of CMC molecular weight, while increasing CMC concentration led to microphase separation with higher CMC molecular weight showing more extensive phase separation. When heated WPI-CMC complexes were prepared at 9% protein the acid gels showed improved gel hardness and water holding capacity, which was supported by the more interconnected protein network with less porosity when compared to complexes heated at 6% protein. It is concluded that protein concentration and biopolymer ratio during complex formation are the major factors affecting gel properties while the effect of CMC molecular weight was less significant.

  8. Anti-inflammatory and analgesic potential of a novel steroidal derivative from Bryophyllum pinnatum.

    PubMed

    Afzal, Muhammad; Gupta, Gaurav; Kazmi, Imran; Rahman, Mahfoozur; Afzal, Obaid; Alam, Jahangir; Hakeem, Khalidur Rahman; Pravez, Mohammad; Gupta, Ritu; Anwar, Firoz

    2012-07-01

    A new steroidal derivative, urs Stigmast-4, 20 (21), 23-trien-3-one and other four compounds were isolated from the leaves of Bryophyllum pinnatum. The structure of this new steroid was elucidated and established by standard spectroscopic methods. Carrageenan induced paw edema model was used for anti-inflammatory and acetic acid induced model used for analgesic activity. This new steroidal compound was found to be active in reducing inflammation (% inhibition 87.29 and 84.45 respectively) when compared with diclofenac. Further, it showed 75.72% protection in analgesic activity in acetic acid induced writhing test in mice. In conclusion the % inhibition against carrageenan induced rat paw edema and % protection against acetic acid induced writhings showed by new compound revealed that the anti-inflammatory and analgesic activity of aqueous extract B. pinnatum are mainly due to the presence of this steroidal compound.

  9. Anti-inflammatory and analgesic potential of a novel steroidal derivative from Bryophyllum pinnatum.

    PubMed

    Afzal, Muhammad; Gupta, Gaurav; Kazmi, Imran; Rahman, Mahfoozur; Afzal, Obaid; Alam, Jahangir; Hakeem, Khalidur Rahman; Pravez, Mohammad; Gupta, Ritu; Anwar, Firoz

    2012-07-01

    A new steroidal derivative, urs Stigmast-4, 20 (21), 23-trien-3-one and other four compounds were isolated from the leaves of Bryophyllum pinnatum. The structure of this new steroid was elucidated and established by standard spectroscopic methods. Carrageenan induced paw edema model was used for anti-inflammatory and acetic acid induced model used for analgesic activity. This new steroidal compound was found to be active in reducing inflammation (% inhibition 87.29 and 84.45 respectively) when compared with diclofenac. Further, it showed 75.72% protection in analgesic activity in acetic acid induced writhing test in mice. In conclusion the % inhibition against carrageenan induced rat paw edema and % protection against acetic acid induced writhings showed by new compound revealed that the anti-inflammatory and analgesic activity of aqueous extract B. pinnatum are mainly due to the presence of this steroidal compound. PMID:22465504

  10. Analgesic activity of Calotropis gigantea flower.

    PubMed

    Pathak, A K; Argal, A

    2007-01-01

    The alcoholic extract of the flowers of Calotropis gigantea was administered orally and explored for its analgesic activity in chemical and thermal models in mice. In acetic acid induced writhing test, an inhibition of 20.97% and 43.0% in the number of writhes was observed at the doses of 250 and 500 mg/kg, respectively. In the hot plate method the paw licking time was delayed. The analgesic effect was observed after 30 min of dose administration which reached its maximum after 90 min.

  11. Genetic parameters for rennet- and acid-induced coagulation properties in milk from Swedish Red dairy cows.

    PubMed

    Gustavsson, F; Glantz, M; Poulsen, N A; Wadsö, L; Stålhammar, H; Andrén, A; Lindmark Månsson, H; Larsen, L B; Paulsson, M; Fikse, W F

    2014-01-01

    Milk coagulation is an important processing trait, being the basis for production of both cheese and fermented products. There is interest in including technological properties of these products in the breeding goal for dairy cattle. The aim of the present study was therefore to estimate genetic parameters for milk coagulation properties, including both rennet- and acid-induced coagulation, in Swedish Red dairy cattle using genomic relationships. Morning milk samples and blood samples were collected from 395 Swedish Red cows that were selected to be as genetically unrelated as possible. Using a rheometer, milk samples were analyzed for rennet- and acid-induced coagulation properties, including gel strength (G'), coagulation time, and yield stress (YS). In addition to the technological traits, milk composition was analyzed. A binary trait was created to reflect that milk samples that had not coagulated 40min after rennet addition were considered noncoagulating milk. The cows were genotyped by using the Illumina BovineHD BeadChip (Illumina Inc., San Diego, CA). Almost 600,000 markers remained after quality control and were used to construct a matrix of genomic relationships among the cows. Multivariate models including fixed effects of herd, lactation stage, and parity were fitted using the ASReml software to obtain estimates of heritabilities and genetic and phenotypic correlations. Heritability estimates (h(2)) for G' and YS in rennet and acid gels were found to be high (h(2)=0.38-0.62) and the genetic correlations between rennet-induced and acid-induced coagulation properties were weak but favorable, with the exception of YSrennet with G'acid and YSacid, both of which were strong. The high heritability (h(2)=0.45) for milk coagulating ability expressed as a binary trait suggests that noncoagulation could be eliminated through breeding. Additionally, the results indicated that the current breeding objective could increase the frequency of noncoagulating milk and

  12. Mitochondrial genome depletion in human liver cells abolishes bile acid-induced apoptosis: role of the Akt/mTOR survival pathway and Bcl-2 family proteins.

    PubMed

    Marin, Jose J G; Hernandez, Alicia; Revuelta, Isabel E; Gonzalez-Sanchez, Ester; Gonzalez-Buitrago, Jose M; Perez, Maria J

    2013-08-01

    Acute accumulation of bile acids in hepatocytes may cause cell death. However, during long-term exposure due to prolonged cholestasis, hepatocytes may develop a certain degree of chemoresistance to these compounds. Because mitochondrial adaptation to persistent oxidative stress may be involved in this process, here we have investigated the effects of complete mitochondrial genome depletion on the response to bile acid-induced hepatocellular injury. A subline (Rho) of human hepatoma SK-Hep-1 cells totally depleted of mitochondrial DNA (mtDNA) was obtained, and bile acid-induced concentration-dependent activation of apoptosis/necrosis and survival signaling pathways was studied. In the absence of changes in intracellular ATP content, Rho cells were highly resistant to bile acid-induced apoptosis and partially resistant to bile acid-induced necrosis. In Rho cells, both basal and bile acid-induced generation of reactive oxygen species (ROS), such as hydrogen peroxide and superoxide anion, was decreased. Bile acid-induced proapoptotic signals were also decreased, as evidenced by a reduction in the expression ratios Bax-α/Bcl-2, Bcl-xS/Bcl-2, and Bcl-xS/Bcl-xL. This was mainly due to a downregulation of Bax-α and Bcl-xS. Moreover, in these cells the Akt/mTOR pathway was constitutively activated in a ROS-independent manner and remained similarly activated in the presence of bile acid treatment. In contrast, ERK1/2 activation was constitutively reduced and was not activated by incubation with bile acids. In conclusion, these results suggest that impaired mitochondrial function associated with mtDNA alterations, which may occur in liver cells during prolonged cholestasis, may activate mechanisms of cell survival accounting for an enhanced resistance of hepatocytes to bile acid-induced apoptosis. PMID:23597504

  13. Nicotinic acid induces secretion of prostaglandin D2 in human macrophages: an in vitro model of the niacin flush.

    PubMed

    Meyers, C Daniel; Liu, Paul; Kamanna, Vaijinath S; Kashyap, Moti L

    2007-06-01

    Nicotinic acid is a safe, broad-spectrum lipid agent shown to prevent cardiovascular disease, yet its widespread use is limited by the prostaglandin D2 (PGD2) mediated niacin flush. Previous research suggests that nicotinic acid-induced PGD2 secretion is mediated by the skin, but the exact cell type remains unclear. We hypothesized that macrophages are a source of nicotinic acid-induced PGD2 secretion and performed a series of experiments to confirm this. Nicotinic acid (0.1-3 mM) induced PGD2 secretion in cultured human macrophages, but not monocytes or endothelial cells. The PGD2 secretion was dependent on the concentration of nicotinic acid and the time of exposure. Nicotinuric acid, but not nicotinamide, also induced PGD2 secretion. Pre-incubation of the cells with aspirin (100 microM) entirely prevented the nicotinic acid effects on PGD2 secretion. The PGD2 secreting effects of nicotinic acid were additive to the effects of the calcium ionophore A23187 (6 microM), but were independent of extra cellular calcium. These findings, combined with recent in vivo work, provide evidence that macrophages play a significant role in mediating the niacin flush and may lead to better strategies to eliminate this limiting side effect.

  14. Effects of tumour necrosis factor-alpha synthesis inhibitors on rat trinitrobenzene sulphonic acid-induced chronic colitis.

    PubMed

    Bobin-Dubigeon, C; Collin, X; Grimaud, N; Robert, J M; Le Baut, G; Petit, J Y

    2001-11-01

    The fact that tumour necrosis factor-alpha (TNF-alpha) is clearly involved in the pathogenesis of intestinal bowel disease, especially Crohn's disease, suggests that TNF-alpha synthesis inhibitors could be beneficial for treatment. The present study assessed the effect of chronic oral gavage of two in vitro TNF-alpha synthesis inhibitors, JM 34 maleate or [N-(4,6-dimethylpyridin-2-yl)-furane-2-carboxamide)] maleate and XC 21 or (N-betapicolyl-tetrafluorophtalimide), on colonic inflammation in trinitrobenzene sulphonic acid-induced colitis in rats. Rats received JM 34 maleate (100 mg/kg) and XC 21 (50 mg/kg) 1 h before colitis induction and then daily for 8 days by oral gavage. The colon was removed on day 8 and processed for clinical score, myeloperoxidase activity, and soluble TNF-alpha release. Treatment with XC 21, as well as dexamethasone and sulphasalazine, reduced colonic damage and decreased (except with dexamethasone) the incidence of diarrhoea. JM 34 maleate failed to improve the clinical signs of chronic colitis. After trinitrobenzene sulphonic acid-induced colitis, myeloperoxidase activity and TNF-alpha colonic mucosal production were substantially increased compared to the control (saline instillation). Both of these inflammatory indicators were then significantly decreased (P< or =0.05) after the four chronic treatments (JM 34 maleate, XC 21, sulphasalazine, and dexamethasone). XC 21 appeared to be as efficient as sulphasalazine in improving colonic inflammation. PMID:11716848

  15. Retinoic acid induced growth arrest of human breast carcinoma cells requires protein kinase C alpha expression and activity.

    PubMed

    Cho, Y; Tighe, A P; Talmage, D A

    1997-09-01

    Retinoic acid inhibits proliferation of hormone-dependent, but not hormone-independent breast cancer cells. Retinoic acid-induced changes in cellular proliferation and differentiation are associated with disturbances in growth factor signaling and frequently with changes in protein kinase C expression. PKC delta, epsilon, and zeta are expressed in both hormone-dependent (T-47D) and hormone-independent (MDA-MB-231) cell lines. Retinoic acid arrested T-47D proliferation, induced PKC alpha expression and concomitantly repressed PKC zeta expression. The changes in PKC alpha and PKC zeta reflect retinoic acid-induced changes in mRNA. In contrast, retinoic acid had no effect on growth, or PKC expression in MDA-MB-231 cells. Growth arrest and the induction of PKC alpha, but not the reduction in PKC zeta, resulted from selective activation of RAR alpha. In total, these results support an important role for PKC alpha in mediating the anti-proliferative action of retinoids on human breast carcinoma cells.

  16. Protective effect of Agave americana Linn. leaf extract in acetic acid-induced ulcerative colitis in rats

    PubMed Central

    Mannasaheb, Basheerahmed A.A.; Kulkarni, Preeti V.; Sangreskopp, Mashood Ahmed; Savant, Chetan; Mohan, Anjana

    2015-01-01

    Introduction: Natural plants always provide core compounds for new drug development. In the present life and food style, inflammatory bowel disease has become common and needs a lead compound for its drug development. Aim: To evaluate the effect of Agave americana Linn. leaf extract in acetic acid-induced ulcerative colitis in rats based on its traditional anti-inflammatory use. Materials and Methods: Male Wistar rats were pretreated with A. americana leaf extract in the dose of 200 and 400 mg/kg p.o. daily for 7 days. On 8th day, 2 ml of 4% v/v acetic acid in saline was instilled into rats’ rectum. Prednisolone was used as standard drug and it was administered on the day of acetic acid instillation and continued for 3 days. Extract treatment was continued till 11th day. Body weight, ulcer score, colonic muscle contraction, antioxidant activity and histopathology were studied. Statistical analysis was performed using Parametric one-way analysis of variance followed by Tukey's posttest. Results: A. americana have retained total body weight significantly (P < 0.01) and decreased colon weight/length ratio. Extract have shown a significant decrease (P < 0.001) in ulcer scores, myeloperoxidase, lipid peroxidase activity. Further, extract have shown significant improvement in colonic muscle contraction, histopathology of colon etc., which is comparable with standard drug. Conclusion: A. americana possess protective effect against acetic acid-induced colitis in rats. PMID:26730148

  17. [Analgesic properties of morpholinoethylimidazobenzimidazole derivative RU-1205].

    PubMed

    Spasov, A A; Grechko, O Iu; Shtareva, D M; Anisimova, V A

    2013-01-01

    We have studied the analgesic activity of a morpholinoethylimidazobenzimidazole derivative (RU-1205) in comparison to butorphanol. It is established that the test compound exhibits a pronounced analgesic activity, which exceeded that ofbutorphanol six times in the hot-plate test and was comparable to the reference drug effect in the tail-flick and acetic acid-induced writhing tests. It is established that the analgesic action of RU-1205 is based on the kappa-opioidergic mechanism. PMID:24432563

  18. A comparative study of the antitussive activity of levodropropizine and dropropizine in the citric acid-induced cough model in normal subjects.

    PubMed

    Fumagalli, G; Cordaro, C I; Vanasia, M; Balzarotti, C; Camusso, L; Caiazzo, G; Maghini, L; Mazzocchi, M; Zennaro, M

    1992-01-01

    Levodropropizine is the levo-rotatory (S)-enantiomer of dropropizine, a racemic non-opiate antitussive agent which has been used clinically for many years. Compared with the racemic drug, levodropropizine exhibits in animal models similar antitussive activity but considerably lower central nervous system (CNS) depressant effects. It is also less likely to cause sedation in treated patients. Since the comparative antitussive potency of the two drugs in clinical experimental models has not been evaluated, the authors performed a randomized, double blind, cross over investigation in which the effects of single oral doses (60 and 90 mg) of levodropropizine and dropropizine were assessed by using the citric acid-induced cough model in eight normal volunteers. Stimulation tests involved inhalation of individual cumulative doses of citric acid (6.3 to 53.3 mg) which at pre-study assessment had been found to induce reproducibly at least ten coughs over a 30 sec period. Each subject was studied by repeating the citric acid stimulation test four times (0 h, 1 h, 2 h and 6 h) on each of five different days separated by intervals of at least three days. In the absence of drug administration (control session), cough response to citric inhalation was remarkably reproducible throughout the 6 h period of observation. A marked and statistically significant reduction in cough response (to about one third--one sixth of the pre-drug values) was observed 1 h after intake for both compounds. At subsequent testing 2 h and 6 h after dosing, cough response was still depressed and did not differ significantly from that observed at 1 h.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. A comparative study of the antitussive activity of levodropropizine and dropropizine in the citric acid-induced cough model in normal subjects.

    PubMed

    Fumagalli, G; Cordaro, C I; Vanasia, M; Balzarotti, C; Camusso, L; Caiazzo, G; Maghini, L; Mazzocchi, M; Zennaro, M

    1992-01-01

    Levodropropizine is the levo-rotatory (S)-enantiomer of dropropizine, a racemic non-opiate antitussive agent which has been used clinically for many years. Compared with the racemic drug, levodropropizine exhibits in animal models similar antitussive activity but considerably lower central nervous system (CNS) depressant effects. It is also less likely to cause sedation in treated patients. Since the comparative antitussive potency of the two drugs in clinical experimental models has not been evaluated, the authors performed a randomized, double blind, cross over investigation in which the effects of single oral doses (60 and 90 mg) of levodropropizine and dropropizine were assessed by using the citric acid-induced cough model in eight normal volunteers. Stimulation tests involved inhalation of individual cumulative doses of citric acid (6.3 to 53.3 mg) which at pre-study assessment had been found to induce reproducibly at least ten coughs over a 30 sec period. Each subject was studied by repeating the citric acid stimulation test four times (0 h, 1 h, 2 h and 6 h) on each of five different days separated by intervals of at least three days. In the absence of drug administration (control session), cough response to citric inhalation was remarkably reproducible throughout the 6 h period of observation. A marked and statistically significant reduction in cough response (to about one third--one sixth of the pre-drug values) was observed 1 h after intake for both compounds. At subsequent testing 2 h and 6 h after dosing, cough response was still depressed and did not differ significantly from that observed at 1 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1295724

  20. Antinociceptive and Anti-Inflammatory Activities of the Ethanolic Extract from Synadenium umbellatum Pax. (Euphorbiaceae) Leaves and Its Fractions

    PubMed Central

    Borges, Rodrigo; Nascimento, Marcus Vinícius Mariano; de Carvalho, Adryano Augustto Valladão; Valadares, Marize Campos; de Paula, José Realino; Costa, Elson Alves; da Cunha, Luiz Carlos

    2013-01-01

    Synadenium umbellatum Pax., popularly known in Brazil as “cola-nota,” “avelós,” “cancerola,” and “milagrosa”, is a plant species used in folk medicine for the treatment of inflammation, pain, and several diseases. This study aimed to investigate the antinociceptive and anti-inflammatory activities of the ethanolic extract from Synadenium umbellatum Pax. leaves (EES) and its hexane (HF), chloroform (CF), and methanol/water (MF) fractions using the acetic acid-induced abdominal writhing test, formalin-induced paw licking test, tail flick test, croton oil-induced ear edema test, and carrageenan-induced peritonitis test. EES and MF reduced the number of acetic acid-induced abdominal writhes, while CF and HF did not. EES effect on acetic acid-induced abdominal writhing was reversed with a pretreatment with naloxone. EES reduced licking time in both phases of the formalin-induced paw licking test, but did not prolong the latency in the tail flick test. These results show that EES presented antinociceptive activity, probably involving the opioid system, anti-inflammatory activity in the croton oil-induced ear edema test, and leukocyte migration into the intraperitoneal cavity. MF also presented anti-inflammatory activity in the croton oil-induced ear edema test. In conclusion, EES and MF have antinociceptive activity involving the opioid system and anti-inflammatory activity. PMID:23401717

  1. Combinatorial localized dissolution analysis: Application to acid-induced dissolution of dental enamel and the effect of surface treatments.

    PubMed

    Parker, Alexander S; Al Botros, Rehab; Kinnear, Sophie L; Snowden, Michael E; McKelvey, Kim; Ashcroft, Alexander T; Carvell, Mel; Joiner, Andrew; Peruffo, Massimo; Philpotts, Carol; Unwin, Patrick R

    2016-08-15

    A combination of scanning electrochemical cell microscopy (SECCM) and atomic force microscopy (AFM) is used to quantitatively study the acid-induced dissolution of dental enamel. A micron-scale liquid meniscus formed at the end of a dual barrelled pipette, which constitutes the SECCM probe, is brought into contact with the enamel surface for a defined period. Dissolution occurs at the interface of the meniscus and the enamel surface, under conditions of well-defined mass transport, creating etch pits that are then analysed via AFM. This technique is applied to bovine dental enamel, and the effect of various treatments of the enamel surface on acid dissolution (1mM HNO3) is studied. The treatments investigated are zinc ions, fluoride ions and the two combined. A finite element method (FEM) simulation of SECCM mass transport and interfacial reactivity, allows the intrinsic rate constant for acid-induced dissolution to be quantitatively determined. The dissolution of enamel, in terms of Ca(2+) flux ( [Formula: see text] ), is first order with respect to the interfacial proton concentration and given by the following rate law: [Formula: see text] , with k0=0.099±0.008cms(-1). Treating the enamel with either fluoride or zinc ions slows the dissolution rate, although in this model system the partly protective barrier only extends around 10-20nm into the enamel surface, so that after a period of a few seconds dissolution of modified surfaces tends towards that of native enamel. A combination of both treatments exhibits the greatest protection to the enamel surface, but the effect is again transient.

  2. Combinatorial localized dissolution analysis: Application to acid-induced dissolution of dental enamel and the effect of surface treatments.

    PubMed

    Parker, Alexander S; Al Botros, Rehab; Kinnear, Sophie L; Snowden, Michael E; McKelvey, Kim; Ashcroft, Alexander T; Carvell, Mel; Joiner, Andrew; Peruffo, Massimo; Philpotts, Carol; Unwin, Patrick R

    2016-08-15

    A combination of scanning electrochemical cell microscopy (SECCM) and atomic force microscopy (AFM) is used to quantitatively study the acid-induced dissolution of dental enamel. A micron-scale liquid meniscus formed at the end of a dual barrelled pipette, which constitutes the SECCM probe, is brought into contact with the enamel surface for a defined period. Dissolution occurs at the interface of the meniscus and the enamel surface, under conditions of well-defined mass transport, creating etch pits that are then analysed via AFM. This technique is applied to bovine dental enamel, and the effect of various treatments of the enamel surface on acid dissolution (1mM HNO3) is studied. The treatments investigated are zinc ions, fluoride ions and the two combined. A finite element method (FEM) simulation of SECCM mass transport and interfacial reactivity, allows the intrinsic rate constant for acid-induced dissolution to be quantitatively determined. The dissolution of enamel, in terms of Ca(2+) flux ( [Formula: see text] ), is first order with respect to the interfacial proton concentration and given by the following rate law: [Formula: see text] , with k0=0.099±0.008cms(-1). Treating the enamel with either fluoride or zinc ions slows the dissolution rate, although in this model system the partly protective barrier only extends around 10-20nm into the enamel surface, so that after a period of a few seconds dissolution of modified surfaces tends towards that of native enamel. A combination of both treatments exhibits the greatest protection to the enamel surface, but the effect is again transient. PMID:27209395

  3. L-arginine augments the antioxidant effect of garlic against acetic acid-induced ulcerative colitis in rats.

    PubMed

    Harisa, Gamal Eldin I; Abo-Salem, Osama M; El-Sayed, El-Sayed M; Taha, Ehab I; El-Halawany, Nermin

    2009-10-01

    Garlic contains many sulfhydryl compounds that act as antioxidants. However, the role of nitric oxide (NO) in inflammation is controversial. The aim of the present study is to investigate the possible protective effect of garlic against acetic acid-induced ulcerative colitis in rats, as well as the probable modulatory effect of L-arginine (NO precursor) on garlic activity. Intra-rectal inoculation of rats with 4% acetic acid for 3 consecutive days caused a significant increase in the colon weight and marked decrease in the colon length. In addition, acetic acid induced a significant increase in serum levels of nitrate as well as colonic tissue content of malondialdehyde (MDA). Moreover, colonic tissue contents of glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were markedly reduced. On the other hand, pre-treatment of rats with garlic (0.25 g/kgbwt, orally) for 4 consecutive weeks and 3 days during induction of colitis significantly reduced the increase in the colon weight induced by acetic acid and ameliorated alterations in oxidant and antioxidant parameters. Interestingly, oral co-administration of garlic (0.25 g/kgbwt) and L-arginine (625 mg/kgbwt) for the same period of garlic administration mitigated the changes in both colon weight and length induced by acetic acid and increased garlic effect on colon tissue contents of MDA and GSH. In conclusion, L-arginine can augment the protective effect of garlic against ulcerative colitis; an effect that might be mainly attributed to its NO donating property resulting in enhancement of garlic antioxidant effect. Further studies will be needed to determine which one of the active ingredients of garlic has the main antioxidant effect to be used with L-arginine. PMID:19783514

  4. Acid-induced molten globule state of a prion protein: crucial role of Strand 1-Helix 1-Strand 2 segment.

    PubMed

    Honda, Ryo P; Yamaguchi, Kei-ichi; Kuwata, Kazuo

    2014-10-31

    The conversion of a cellular prion protein (PrP(C)) to its pathogenic isoform (PrP(Sc)) is a critical event in the pathogenesis of prion diseases. Pathogenic conversion is usually associated with the oligomerization process; therefore, the conformational characteristics of the pre-oligomer state may provide insights into the conversion process. Previous studies indicate that PrP(C) is prone to oligomer formation at low pH, but the conformation of the pre-oligomer state remains unknown. In this study, we systematically analyzed the acid-induced conformational changes of PrP(C) and discovered a unique acid-induced molten globule state at pH 2.0 termed the "A-state." We characterized the structure of the A-state using far/near-UV CD, 1-anilino-8-naphthalene sulfonate fluorescence, size exclusion chromatography, and NMR. Deuterium exchange experiments with NMR detection revealed its first unique structure ever reported thus far; i.e. the Strand 1-Helix 1-Strand 2 segment at the N terminus was preferentially unfolded, whereas the Helix 2-Helix 3 segment at the C terminus remained marginally stable. This conformational change could be triggered by the protonation of Asp(144), Asp(147), and Glu(196), followed by disruption of key salt bridges in PrP(C). Moreover, the initial population of the A-state at low pH (pH 2.0-5.0) was well correlated with the rate of the β-rich oligomer formation, suggesting that the A-state is the pre-oligomer state. Thus, the specific conformation of the A-state would provide crucial insights into the mechanisms of oligomerization and further pathogenic conversion as well as facilitating the design of novel medical chaperones for treating prion diseases. PMID:25217639

  5. Piroxicam attenuates 3-nitropropionic acid-induced brain oxidative stress and behavioral alteration in mice.

    PubMed

    C, Jadiswami; H M, Megha; Dhadde, Shivsharan B; Durg, Sharanbasappa; Potadar, Pandharinath P; B S, Thippeswamy; V P, Veerapur

    2014-12-01

    3-Nitropropionic acid (3-NP) is a fungal toxin that produces Huntington's disease like symptoms in both animals and humans. Piroxicam, a non-selective cyclooxygenase (COX) inhibitor, used as anti-inflammatory agent and also known to decrease free oxygen radical production. In this study, the effect of piroxicam was evaluated against 3-NP-induced brain oxidative stress and behavioral alteration in mice. Adult male Swiss albino mice were injected with vehicle/piroxicam (10 and 20 mg/kg, i.p.) 30 min before 3-NP challenge (15 mg/kg, i.p.) regularly for 14 days. Body weights of the mice were measured on alternative days of the experiment. At the end of the treatment schedule, mice were evaluated for behavioral alterations (movement analysis, locomotor test, beam walking test and hanging wire test) and brain homogenates were used for the estimation of oxidative stress markers (lipid peroxidation, reduced glutathione and catalase). Administration of 3-NP significantly altered the behavioral activities and brain antioxidant status in mice. Piroxicam, at both the tested doses, caused a significant reversal of 3-NP-induced behavioral alterations and oxidative stress in mice. These findings suggest piroxicam protects the mice against 3-NP-induced brain oxidative stress and behavioral alteration. The antioxidant properties of piroxicam may be responsible for the observed beneficial actions. PMID:25191831

  6. Effects of ginsenosides on opioid-induced hyperalgesia in mice.

    PubMed

    Li, Peng; Tang, Minke; Li, Hui; Huang, Xinjie; Chen, Lei; Zhai, Haifeng

    2014-07-01

    Opioid-induced hyperalgesia (OIH) is characterized by nociceptive sensitization caused by the cessation of chronic opioid use. OIH can limit the clinical use of opioid analgesics and complicate withdrawal from opioid addiction. In this study, we investigated the effects of Re, Rg1, and Rb1 ginsenosides, the bioactive components of ginseng, on OIH. OIH was achieved in mice after subcutaneous administration of morphine for 7 consecutive days three times per day. During withdrawal (days 8 and 9), these mice were administered Re, Rg1, or Rb1 intragastrically two times per day. On the test day (day 10), mice were subjected to the thermal sensitivity test and the acetic acid-induced writhing test. Re (300 mg/kg) inhibited OIH in both the thermal sensitivity test and the acetic acid-induced writhing test. However, the Rg1 and Rb1 ginsenosides failed to prevent OIH in either test. Furthermore, Rg1 showed a tendency to aggravate OIH in the acetic acid-induced writhing test. Our data suggested that the ginsenoside Re, but not Rg1 or Rb1, may contribute toward reversal of OIH.

  7. Neuroprotective effect of caffeic acid phenethyl ester in 3-nitropropionic acid-induced striatal neurotoxicity

    PubMed Central

    Bak, Jia; Kim, Hee Jung; Kim, Seong Yun

    2016-01-01

    Caffeic acid phenethyl ester (CAPE), derived from honeybee hives, is a bioactive compound with strong antioxidant activity. This study was designed to test the neuroprotective effect of CAPE in 3-nitropropionic acid (3NP)-induced striatal neurotoxicity, a chemical model of Huntington's disease (HD). Initially, to test CAPE's antioxidant activity, a 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid (ABTS) antioxidant assay was employed, and CAPE showed a strong direct radical-scavenging eff ect. In addition, CAPE provided protection from 3NP-induced neuronal cell death in cultured striatal neurons. Based on these observations, the in vivo therapeutic potential of CAPE in 3NP-induced HD was tested. For this purpose, male C57BL/6 mice were repeatedly given 3NP to induce HD-like pathogenesis, and 30 mg/kg of CAPE or vehicle (5% dimethyl sulfoxide and 95% peanut oil) was administered daily. CAPE did not cause changes in body weight, but it reduced mortality by 29%. In addition, compared to the vehicle-treated group, robustly reduced striatal damage was observed in the CAPE-treated animals, and the 3NP-induced behavioral defi cits on the rotarod test were signifi cantly rescued after the CAPE treatment. Furthermore, immunohistochemical data showed that immunoreactivity to glial fibrillary acidic protein (GFAP) and CD45, markers for astrocyte and microglia activation, respectively, were strikingly reduced. Combined, these data unequivocally indicate that CAPE has a strong antioxidant eff ect and can be used as a potential therapeutic agent against HD. PMID:27162482

  8. Arsanilic acid-induced blindness in swine: electroretinographic and visually evoked responses.

    PubMed

    Witzel, D A; Smith, E L; Beerwinkle, K R; Johnson, J H

    1976-05-01

    Arsanilic acid (1,000 ppm) caused blindness in pigs within 25 to 30 days. The visually evoked response was "nonrecordable" in blind pigs, but was consistently recordable in normal pigs. The electroretinographic response was recordable in both normal and blind pigs, and significant differences were not apparent between results of tests of the 2 groups. Optic disk atrophy was noted ophthalmoscopically; lesions of the optic nerve are probably responsible for the nonrecordable visually evoked response.

  9. Neuroprotective effect of caffeic acid phenethyl ester in 3-nitropropionic acid-induced striatal neurotoxicity.

    PubMed

    Bak, Jia; Kim, Hee Jung; Kim, Seong Yun; Choi, Yun-Sik

    2016-05-01

    Caffeic acid phenethyl ester (CAPE), derived from honeybee hives, is a bioactive compound with strong antioxidant activity. This study was designed to test the neuroprotective effect of CAPE in 3-nitropropionic acid (3NP)-induced striatal neurotoxicity, a chemical model of Huntington's disease (HD). Initially, to test CAPE's antioxidant activity, a 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid (ABTS) antioxidant assay was employed, and CAPE showed a strong direct radical-scavenging eff ect. In addition, CAPE provided protection from 3NP-induced neuronal cell death in cultured striatal neurons. Based on these observations, the in vivo therapeutic potential of CAPE in 3NP-induced HD was tested. For this purpose, male C57BL/6 mice were repeatedly given 3NP to induce HD-like pathogenesis, and 30 mg/kg of CAPE or vehicle (5% dimethyl sulfoxide and 95% peanut oil) was administered daily. CAPE did not cause changes in body weight, but it reduced mortality by 29%. In addition, compared to the vehicle-treated group, robustly reduced striatal damage was observed in the CAPE-treated animals, and the 3NP-induced behavioral defi cits on the rotarod test were signifi cantly rescued after the CAPE treatment. Furthermore, immunohistochemical data showed that immunoreactivity to glial fibrillary acidic protein (GFAP) and CD45, markers for astrocyte and microglia activation, respectively, were strikingly reduced. Combined, these data unequivocally indicate that CAPE has a strong antioxidant eff ect and can be used as a potential therapeutic agent against HD. PMID:27162482

  10. Fuzzy approach for improved recognition of citric acid induced piglet coughing from continuous registration

    NASA Astrophysics Data System (ADS)

    Van Hirtum, A.; Berckmans, D.

    2003-09-01

    A natural acoustic indicator of animal welfare is the appearance (or absence) of coughing in the animal habitat. A sound-database of 5319 individual sounds including 2034 coughs was collected on six healthy piglets containing both animal vocalizations and background noises. Each of the test animals was repeatedly placed in a laboratory installation where coughing was induced by nebulization of citric acid. A two-class classification into 'cough' or 'other' was performed by the application of a distance function to a fast Fourier spectral sound analysis. This resulted in a positive cough recognition of 92%. For the whole sound-database however there was a misclassification of 21%. As spectral information up to 10000 Hz is available, an improved overall classification on the same database is obtained by applying the distance function to nine frequency ranges and combining the achieved distance-values in fuzzy rules. For each frequency range clustering threshold is determined by fuzzy c-means clustering.

  11. Functional evaluation of iodoacetic acid induced photoreceptor degeneration in the cat.

    PubMed

    Nan, Yan; Zhang, Qin; Ren, Chaoran; Huang, Xin; Gao, Jie; Li, Xiaoxin; Pu, Mingliang

    2013-06-01

    Iodoacetic acid (IAA) has been applied to different species to acutely induce photoreceptor degeneration. The purpose of the present study was to use this toxin to thoroughly eliminate photoreceptors and induce complete blindness in the cat. IAA was delivered by single ear vein injection (20 mg kg(-1)). Six months after the IAA treatment, functional evaluations including pupillary light reflex (PLR), electroretinogram (ERG), visual behavior tests were performed. Morphological examinations were carried out after the functional evaluation. The present result shows that, six months after the IAA application, animals lost visual functions and became completely blind. High dose IAA application via ear vein delivery created an acute and reliable complete photoreceptor degeneration model in the cat. This model can be applied to genetic and cellular therapies for visual function restoration. PMID:23657794

  12. Mast cells in citric acid-induced cough of guinea pigs

    SciTech Connect

    Lai, Y.-L. . E-mail: tiger@ha.mc.ntu.edu.tw; Lin, T.-Y.

    2005-01-01

    It was demonstrated previously that mast cells play an important role in citric acid (CA)-induced airway constriction. To investigate the role of mast cells in CA-induced cough, three experiments were carried out in this study. In the first experiment, 59 guinea pigs were employed and we used compound 48/80 to deplete mast cells, cromolyn sodium to stabilize mast cells, MK-886 to inhibit leukotriene synthesis, pyrilamine to antagonize histamine H{sub 1} receptor, methysergide to antagonize serotonin receptor, and indomethacin to inhibit cyclooxygenase. In the second experiment, 56 compound 48/80-pretreated animals were divided into two parts; the first one was used to test the role of exogenous leukotriene (LT) C{sub 4}, while the second one to test the role of exogenous histamine in CA-induced cough. Each animal with one of the above pretreatments was exposed sequentially to saline (baseline) and CA (0.6 M) aerosol, each for 3 min. Then, cough was recorded for 12 min using a barometric body plethysmograph. In the third experiment, the activation of mast cells upon CA inhalation was investigated by determining arterial plasma histamine concentration in 17 animals. Exposure to CA induced a marked increase in cough number. Compound 48/80, cromolyn sodium, MK-886 and pyrilamine, but not indomethacin or methysergide, significantly attenuated CA-induced cough. Injection of LTC{sub 4} or histamine caused a significant increase in CA-induced cough in compound 48/80-pretreated animals. In addition, CA inhalation caused significant increase in plasma histamine concentration, which was blocked by compound 48/80 pretreatment. These results suggest that mast cells play an important role in CA aerosol inhalation-induced cough via perhaps mediators LTs and histamine.

  13. Lysophosphatidic acid induces anxiety-like behavior via its receptors in mice.

    PubMed

    Yamada, Misa; Tsukagoshi, Mai; Hashimoto, Tomio; Oka, Jun-Ichiro; Saitoh, Akiyoshi; Yamada, Mitsuhiko

    2015-03-01

    Lysophosphatidic acid (LPA) is a potent bioactive lipid mediator with diverse biological properties. We previously found altered expression of the LPA-related genes in rodents after treatment with sertraline, which is widely used to treat anxiety disorders and depression. However, little is known about the behavioral effects of LPA. In the present study, we investigated the behavioral effects of intracerebroventricular injection of LPA in adult mice. LPA did not significantly affect spontaneous locomotor activity, suggesting that LPA does not induce hyperactivity, ataxia, or sedation. We next investigated the emotional effects of LPA via the hole-board test. LPA significantly increased the number of head-dips in a dose- and time-related manner. A significant induction of head-dip counts occurred 15 and 30 min after LPA administration. To clarify the involvement of LPA receptors, we examined the effect of the non-selective LPA1-4 receptor antagonist, 1-bromo-3(S)-hydroxy-4-(palmitoyloxy)butyl-phosphonate (BrP-LPA) co-administered with LPA. BrP-LPA dose-dependently inhibited LPA-induced head-dip counts. We next investigated anxiety-like behavior via the elevated plus-maze test. LPA significantly reduced the percentage of time spent in the open arms and BrP-LPA dose-dependently inhibited this anxiety-like behavior. In conclusion, LPA induced anxiety-like behavior in mice via LPA receptors. Our results suggest that LPA signaling plays an important role in regulating anxiety in mice.

  14. BPC-15 reduces trinitrobenzene sulfonic acid-induced colonic damage in rats.

    PubMed

    Veljaca, M; Lesch, C A; Pllana, R; Sanchez, B; Chan, K; Guglietta, A

    1995-01-01

    The effect of BPC-15 (Booly Protection Compound-15) was evaluated in a rat model of colonic injury. A single intracolonic administration of trinitrobenzene sulfonic acid (TNBS) dissolved in ethanol induces severe colonic damage, which is characterized by areas of necrosis surrounded by areas of acute inflammation. The damage is associated with high myeloperoxidase (MPO) activity, mainly as a reflection of neutrophilic infiltration into the damaged tissue. In this study, 1 hr before a single intracolonic administration of 50 mg/kg of TNBS in 50% ethanol, the animals were treated with one of the following doses of BPC-15: 0.0001, 0.001, 0.01, 0.1, 1 or 10 nmol/kg administered i.p. or with a dose of 10 nmol/kg administered intracolonically. The animals were sacrificed 3 days later and the extent of colonic necrosis and hyperemia was measured with an image analyzer. The i.p. administration of BPC-15 significantly reduced the extent of TNBS-induced colonic damage in a dose-dependent manner. This was associated with a statistically significant and dose-dependent reduction in colonic tissue MPO activity. At the dose tested (10 nmol/kg), intracolonic administration of BPC-15 did not significantly reduce either the extent of the colonic damage or the increase in MPO activity induced by TNBS. In conclusion, this study showed that i.p. administration of BPC-15 reduced TNBS-induced colonic damage in rats. PMID:7815358

  15. Hippocampal neuropathology of domoic acid-induced epilepsy in California sea lions (Zalophus californianus).

    PubMed

    Buckmaster, Paul S; Wen, Xiling; Toyoda, Izumi; Gulland, Frances M D; Van Bonn, William

    2014-05-01

    California sea lions (Zalophus californianus) are abundant human-sized carnivores with large gyrencephalic brains. They develop epilepsy after experiencing status epilepticus when naturally exposed to domoic acid. We tested whether sea lions previously exposed to DA (chronic DA sea lions) display hippocampal neuropathology similar to that of human patients with temporal lobe epilepsy. Hippocampi were obtained from control and chronic DA sea lions. Stereology was used to estimate numbers of Nissl-stained neurons per hippocampus in the granule cell layer, hilus, and pyramidal cell layer of CA3, CA2, and CA1 subfields. Adjacent sections were processed for somatostatin immunoreactivity or Timm-stained, and the extent of mossy fiber sprouting was measured stereologically. Chronic DA sea lions displayed hippocampal neuron loss in patterns and extents similar but not identical to those reported previously for human patients with temporal lobe epilepsy. Similar to human patients, hippocampal sclerosis in sea lions was unilateral in 79% of cases, mossy fiber sprouting was a common neuropathological abnormality, and somatostatin-immunoreactive axons were exuberant in the dentate gyrus despite loss of immunopositive hilar neurons. Thus, hippocampal neuropathology of chronic DA sea lions is similar to that of human patients with temporal lobe epilepsy. PMID:24638960

  16. Hippocampal neuropathology of domoic acid-induced epilepsy in California sea lions (Zalophus californianus)

    PubMed Central

    Buckmaster, Paul S.; Wen, Xiling; Toyoda, Izumi; Gulland, Frances M. D.; Van Bonn, William

    2014-01-01

    California sea lions (Zalophus californianus) are abundant human-sized carnivores with large gyrencephalic brains. They develop epilepsy after experiencing status epilepticus when naturally exposed to domoic acid. We tested whether sea lions previously exposed to DA (chronic DA sea lions) display hippocampal neuropathology similar to that of human patients with temporal lobe epilepsy. Hippocampi were obtained from control and chronic DA sea lions. Stereology was used to estimate numbers of Nissl-stained neurons per hippocampus in the granule cell layer, hilus, and the pyramidal cell layer of CA3, CA2, and CA1 subfields. Adjacent sections were processed for somatostatin-immunoreactivity or Timm-stained, and the extent of mossy fiber sprouting was measured stereologically. Chronic DA sea lions displayed hippocampal neuron loss in patterns and extents similar but not identical to those reported previously for human patients with temporal lobe epilepsy. Similar to human patients, hippocampal sclerosis in sea lions was unilateral in 79% of cases, mossy fiber sprouting was a common neuropathological abnormality, and somatostatin-immunoreactive axons were exuberant in the dentate gyrus despite loss of immunopositive hilar neurons. Thus, hippocampal neuropathology of chronic DA sea lions is similar to that of human patients with temporal lobe epilepsy. PMID:24638960

  17. DL-β-Aminobutyric Acid-Induced Resistance in Soybean against Aphis glycines Matsumura (Hemiptera: Aphididae)

    PubMed Central

    Zhong, Yunpeng; Wang, Biao; Yan, Junhui; Cheng, Linjing; Yao, Luming; Xiao, Liang; Wu, Tianlong

    2014-01-01

    Priming can improve plant innate capability to deal with the stresses caused by both biotic and abiotic factors. In this study, the effect of DL-β-amino-n-butyric acid (BABA) against Aphis glycines Matsumura, the soybean aphid (SA) was evaluated. We found that 25 mM BABA as a root drench had minimal adverse impact on plant growth and also efficiently protected soybean from SA infestation. In both choice and non-choice tests, SA number was significantly decreased to a low level in soybean seedlings drenched with 25 mM BABA compared to the control counterparts. BABA treatment resulted in a significant increase in the activities of several defense enzymes, such as phenylalanine ammonia-lyase (PAL), peroxidase (POX), polyphenol oxidase (PPO), chitinase (CHI), and β-1, 3-glucanase (GLU) in soybean seedlings attacked by aphid. Meanwhile, the induction of 15 defense-related genes by aphid, such as AOS, CHS, MMP2, NPR1-1, NPR1-2, and PR genes, were significantly augmented in BABA-treated soybean seedlings. Our study suggest that BABA application is a promising way to enhance soybean resistance against SA. PMID:24454805

  18. Prevention of Polyglycolic Acid-Induced Peritoneal Adhesions Using Alginate in a Rat Model

    PubMed Central

    Matoba, Mari; Hashimoto, Ayumi; Tanzawa, Ayumi; Orikasa, Taichi; Ikeda, Junki; Iwame, Yoshizumi; Ozamoto, Yuki; Miyamoto, Hiroe; Yoshida, Chiko; Hashimoto, Toru; Torii, Hiroko; Takamori, Hideki; Morita, Shinichiro; Tsujimoto, Hiroyuki; Hagiwara, Akeo

    2015-01-01

    Postoperative intra-abdominal or intrathoracic adhesions sometimes cause significant morbidity. We have designed three types of alginate-based treatments using strongly cross-linked (SL), weakly cross-linked (WL), and non-cross-linked (NL) alginate with calcium gluconate. In rat experiments, we compared the antiadhesive effects of the three types of alginate-based treatments, fibrin glue treatment (a standard treatment), and no treatment against adhesions caused by polyglycolic acid (PGA) mesh (PGA-induced adhesions). The antiadhesive materials were set on the PGA sheet fixed on the parietal peritoneum of the abdomen. Fifty-six days later, the adhesions were evaluated macroscopically by the adhesion scores and microscopically by hematoxylin-eosin staining and immunostaining. We also tested the fibroblast growth on the surface of the antiadhesive materials in vitro. The antiadhesive effects of WL and NL were superior to the no treatment and fibrin glue treatment. A microscopic evaluation confirmed that the PGA sheet was covered by a peritoneal layer constructed of well-differentiated mesothelial cells, and the inflammation was most improved in the NL and WL. The fibroblast growth was inhibited most on the surfaces of the NL and WL. These results suggest that either the WL or NL treatments are suitable for preventing PGA-induced adhesions compared to SL or the conventional treatment. PMID:26078949

  19. Hippocampal neuropathology of domoic acid-induced epilepsy in California sea lions (Zalophus californianus).

    PubMed

    Buckmaster, Paul S; Wen, Xiling; Toyoda, Izumi; Gulland, Frances M D; Van Bonn, William

    2014-05-01

    California sea lions (Zalophus californianus) are abundant human-sized carnivores with large gyrencephalic brains. They develop epilepsy after experiencing status epilepticus when naturally exposed to domoic acid. We tested whether sea lions previously exposed to DA (chronic DA sea lions) display hippocampal neuropathology similar to that of human patients with temporal lobe epilepsy. Hippocampi were obtained from control and chronic DA sea lions. Stereology was used to estimate numbers of Nissl-stained neurons per hippocampus in the granule cell layer, hilus, and pyramidal cell layer of CA3, CA2, and CA1 subfields. Adjacent sections were processed for somatostatin immunoreactivity or Timm-stained, and the extent of mossy fiber sprouting was measured stereologically. Chronic DA sea lions displayed hippocampal neuron loss in patterns and extents similar but not identical to those reported previously for human patients with temporal lobe epilepsy. Similar to human patients, hippocampal sclerosis in sea lions was unilateral in 79% of cases, mossy fiber sprouting was a common neuropathological abnormality, and somatostatin-immunoreactive axons were exuberant in the dentate gyrus despite loss of immunopositive hilar neurons. Thus, hippocampal neuropathology of chronic DA sea lions is similar to that of human patients with temporal lobe epilepsy.

  20. The amphiphilic alkyl ester derivatives of l-ascorbic acid induce reorganization of phospholipid vesicles.

    PubMed

    Giudice, Francesca; Ambroggio, Ernesto E; Mottola, Milagro; Fanani, Maria Laura

    2016-09-01

    l-ascorbic acid alkyl esters (ASCn) are lipophilic forms of vitamin C, which maintain some of its antioxidant power. Those properties make this drug family attractive to be used in pharmacological preparations protecting other redox-sensible drugs or designed to reduce possible toxic oxidative processes. In this work, we tested the ability of l-ascorbic acid alkyl esters (ASCn) to modulate the structure, permeability, and rheological properties of phospholipid bilayers. The ASCn studied here (ASC16, ASC14, and ASC12) alter the structural integrity as well as the rheological properties of phospholipid membranes without showing any evident detergent activity. ASC14 appeared as the most efficient drug in destabilize the membrane structure of nano- and micro-size phospholipid liposomes inducing vesicle content leakage and shape elongation on giant unilamellar vesicles. It also was the most potent enhancer of membrane microviscosity and surface water structuring. Only ASC16 induced the formation of drug-enriched condensed domains after its incorporation into the lipid bilayer, while ASC12 appeared as the less membrane-disturbing compound, likely because of its poor, and more superficial, partition into the membrane. We also found that incorporation of ASCn into the lipid bilayers enhanced the reduction of membrane components, compared with soluble vitamin C. Our study shows that ASCn compounds, which vary in the length of the acyl chain, show different effects on phospholipid vesicles used as biomembrane models. Those variances may account for subtly differences in the effectiveness on their pharmacological applications. PMID:27342371

  1. Bile acids induce uncoupling protein 1-dependent thermogenesis and stimulate energy expenditure at thermoneutrality in mice.

    PubMed

    Zietak, Marika; Kozak, Leslie P

    2016-03-01

    It has been proposed that diet-induced obesity at thermoneutrality (TN; 29°C) is reduced by a UCP1-dependent thermogenesis; however, it has not been shown how UCP1-dependent thermogenesis can be activated in the absence of sympathetic activity. A recent study provides such a mechanism by showing that dietary bile acids (BAs) suppress obesity in mice fed a high-fat diet (HFD) by a mechanism dependent on type 2 deiodinase (DIO2); however, neither a role for UCP1 nor the influence of sympathetic activity was properly assessed. To test whether the effects of BAs on adiposity are independent of Ucp1 and cold-activated thermogenesis, obesity phenotypes were determined in C57BL6/J.(+)/(+) (WT) and C57BL6/J.Ucp1.(-)/(-) mice (Ucp1-KO) housed at TN and fed a HFD with or without 0.5% (wt/wt) cholic acid (CA) for 9 wk. CA in a HFD reduced adiposity and hepatic lipogenesis and improved glucose tolerance in WT but not in Ucp1-KO mice and was accompanied by increases in food intake and energy expenditure (EE). In iBAT, CA increased Ucp1 mRNA and protein levels 1.5- and twofold, respectively, and increased DIO2 and TGR5 protein levels in WT mice. Despite enhanced Dio2 expression in Ucp1-KO and Ucp1-KO-CA treated mice, this did not enhance the ability of BAs to reduce obesity. By comparing the effects of BAs on WT and Ucp1-KO mice at TN, our study showed that BAs suppress diet-induced obesity by increasing EE through a mechanism dependent on Ucp1 expression, which is likely independent of adrenergic signaling. PMID:26714852

  2. Modeling and analysis of retinoic acid induced differentiation of uncommitted precursor cells.

    PubMed

    Tasseff, Ryan; Nayak, Satyaprakash; Song, Sang Ok; Yen, Andrew; Varner, Jeffrey D

    2011-05-01

    Manipulation of differentiation programs has therapeutic potential in a spectrum of human cancers and neurodegenerative disorders. In this study, we integrated computational and experimental methods to unravel the response of a lineage uncommitted precursor cell-line, HL-60, to Retinoic Acid (RA). HL-60 is a human myeloblastic leukemia cell-line used extensively to study human differentiation programs. Initially, we focused on the role of the BLR1 receptor in RA-induced differentiation and G1/0-arrest in HL-60. BLR1, a putative G protein-coupled receptor expressed following RA exposure, is required for RA-induced cell-cycle arrest and differentiation and causes persistent MAPK signaling. A mathematical model of RA-induced cell-cycle arrest and differentiation was formulated and tested against BLR1 wild-type (wt) knock-out and knock-in HL-60 cell-lines with and without RA. The current model described the dynamics of 729 proteins and protein complexes interconnected by 1356 interactions. An ensemble strategy was used to compensate for uncertain model parameters. The ensemble of HL-60 models recapitulated the positive feedback between BLR1 and MAPK signaling. The ensemble of models also correctly predicted Rb and p47phox regulation and the correlation between p21-CDK4-cyclin D formation and G1/0-arrest following exposure to RA. Finally, we investigated the robustness of the HL-60 network architecture to structural perturbations and generated experimentally testable hypotheses for future study. Taken together, the model presented here was a first step toward a systematic framework for analysis of programmed differentiation. These studies also demonstrated that mechanistic network modeling can help prioritize experimental directions by generating falsifiable hypotheses despite uncertainty.

  3. Neuroprotective effect of curcumin on okadaic acid induced memory impairment in mice.

    PubMed

    Rajasekar, N; Dwivedi, Subhash; Tota, Santosh Kumar; Kamat, Pradeep Kumar; Hanif, Kashif; Nath, Chandishwar; Shukla, Rakesh

    2013-09-01

    Okadaic acid (OKA) has been observed to cause memory impairment in human subjects having seafood contaminated with dinoflagellate (Helicondria okadai). OKA induces tau hyperphosphorylation and oxidative stress leading to memory impairment as our previous study has shown. Curcumin a natural antioxidant has demonstrated neuroprotection in various models of neurodegeneration. However, the effect of curcumin has not been explored in OKA induced memory impairment. Therefore, present study evaluated the effect of curcumin on OKA (100ng, intracerebrally) induced memory impairment in male Swiss albino mice as evaluated in Morris water maze (MWM) and passive avoidance tests (PAT). OKA administration resulted in memory impairment with a decreased cerebral blood flow (CBF) (measured by laser doppler flowmetry), ATP level and increased mitochondrial (Ca(2+))i, neuroinflammation (increased TNF-α, IL-1β, COX-2 and GFAP), oxidative-nitrosative stress, increased Caspase-9 and cholinergic dysfunction (decreased AChE activity/expression and α7 nicotinic acetylcholine receptor expression) in cerebral cortex and hippocampus of mice brain. Oral administration of curcumin (50mg/kg) for 13 days significantly improved memory function in both MWM and PAT along with brain energy metabolism, CBF and cholinergic function. It decreased mitochondrial (Ca(2+))i, and ameliorated neuroinflammation and oxidative-nitrostative stress in different brain regions of OKA treated mice. Curcumin also inhibited astrocyte activation as evidenced by decreased GFAP expression. This neuroprotective effect of curcumin is due to its potent anti-oxidant action thus confirming previous studies. Therefore, use of curcumin should be encouraged in people consuming sea food (contaminated with dinoflagellates) to prevent cognitive impairment.

  4. Mast cell mediators in citric acid-induced airway constriction of guinea pigs

    SciTech Connect

    Lin, C.-H.; Lai, Y.-L. . E-mail: tiger@ha.mc.ntu.edu.tw

    2005-08-15

    We demonstrated previously that mast cells play an important role in citric acid (CA)-induced airway constriction. In this study, we further investigated the underlying mediator(s) for this type of airway constriction. At first, to examine effects caused by blocking agents, 67 young Hartley guinea pigs were divided into 7 groups: saline + CA; methysergide (serotonin receptor antagonist) + CA; MK-886 (leukotriene synthesis inhibitor) + CA; mepyramine (histamine H{sub 1} receptor antagonist) + CA; indomethacin (cyclooxygenase inhibitor) + CA; cromolyn sodium (mast cell stabilizer) + CA; and compound 48/80 (mast cell degranulating agent) + CA. Then, we tested whether leukotriene C{sub 4} (LTC{sub 4}) or histamine enhances CA-induced airway constriction in compound 48/80-pretreated guinea pigs. We measured dynamic respiratory compliance (Crs) and forced expiratory volume in 0.1 s (FEV{sub 0.1}) during either baseline or recovery period. In addition, we detected histamine level, an index of pulmonary mast cell degranulation, in bronchoalveolar lavage (BAL) samples. Citric acid aerosol inhalation caused decreases in Crs and FEV{sub 0.1}, indicating airway constriction in the control group. This airway constriction was significantly attenuated by MK-886, mepyramine, cromolyn sodium, and compound 48/80, but not by either methysergide or indomethacin. Both LTC{sub 4} and histamine infusion significantly increased the magnitude of CA-induced airway constriction in compound 48/80-pretreated guinea pigs. Citric acid inhalation caused significant increase in histamine level in the BAL sample, which was significantly suppressed by compound 48/80. These results suggest that leukotrienes and histamine originating from mast cells play an important role in CA inhalation-induced noncholinergic airway constriction.

  5. The bisphosphonate alendronate improves the damage associated with trinitrobenzenesulfonic acid-induced colitis in rats

    PubMed Central

    Ballester, I; Daddaoua, A; López-Posadas, R; Nieto, A; Suárez, M D; Zarzuelo, A; Martínez-Augustin, O; de Medina, F Sánchez

    2007-01-01

    Background and purpose: The nitrogen-containing bisphosphonates are drugs used successfully in the treatment of osteoporosis. They act inhibiting farnesyl diphosphate synthase. This mechanism may also produce anti-inflammatory effects. The therapeutic activity of alendronate was tested in vivo using a model of inflammatory bowel disease. Experimental approach: The trinitrobenzenesulfonic acid model of colitis in the rat was used. Rats were treated orally with alendronate and its efficacy compared with that of oral sulphasalazine or vehicle, starting 2 h after colitis induction. The status of the animals was assessed 5 days later. Key results: Alendronate treatment (25 or 75 mg kg-1 day-1) resulted in a decrease in the colonic damage score and loss of body weight (at 25 mg kg-1 day-1 only). This was associated to a dramatic reduction in the mRNA levels of interleukin 1β (IL-1β), monocyte chemoattractant protein 1 (MCP-1) and interleukin 1 receptor antagonist (IL-1ra). The magnitude of the beneficial effect was comparable to that of sulphasalazine (at a 6-20 fold higher dose). Thus sulphasalazine post-treatment reduced the mRNA levels of IL-1β/IL-1ra and MCP-1 to the same extent as alendronate and additionally lowered colonic alkaline phosphatase activity, but failed to affect body weight loss or colonic damage score. Alendronate failed to exert beneficial effects when administered intraperitoneally. Conclusions and Implications: Oral but not intraperitoneal alendronate significantly protected the colon in experimental rat colitis. Inflammatory bowel disease patients might benefit from exposure to oral alendronate. PMID:17375077

  6. Alleviating Effects of Bushen-Yizhi Formula on Ibotenic Acid-Induced Cholinergic Impairments in Rat

    PubMed Central

    Hou, Xue-Qin; Zhang, Lei; Yang, Cong; Rong, Cui-Ping; He, Wen-Qing; Zhang, Chun-Xia; Li, Shi; Su, Ru-Yu; Chang, Xiang; Qin, Ji-Huan; Chen, Yun-Bo

    2015-01-01

    Abstract This study explored the curative effect and underlying mechanisms of a traditional Chinese medicine compound prescription, Bushen-Yizhi formula (BSYZ), in ibotenic acid (IBO)-induced rats. Morris water maze and novel object recognition tests showed that BSYZ significantly improved spatial and object memory. Brain immunohistochemistry staining showed that BSYZ significantly up-regulated expression of choline acetyltransferase (ChAT) and nerve growth factor (NGF) in the hippocampus and cortex. The protein tyrosine kinase high-affinity receptor TrkA was slightly increased in the hippocampus and cortex, and significantly enhanced in the nucleus basalis of Meynert (NBM) after BSYZ intervention. The immunoreactivity of the p75 low-affinity receptor in BSYZ-treated rats was significantly strengthened in the cortex. Similar expression trends of nerve growth factor (NGF), TrkA, and p75 mRNA were observed in the hippocampus and cortex. Additionally, BSYZ reversed IBO-induced disorders of acetylcholine (ACh) levels, ChAT, and cholinesterase (ChE) in the cortex, which was consistent with the changes in mRNA levels of ChAT and acetylcholinesterase (AChE). Expression of ChAT and AChE proteins and mRNA in the hippocampus was up-regulated, whereas the apoptosis-relative protein cleaved caspase-3 was decreased after administration of BSYZ. Moreover, changes in cell death were confirmed by histological morphology. Thus, the results indicated that the BSYZ formula could ameliorate memory impairments in IBO-induced rats, and it exerted its therapeutic action probably by modulating cholinergic pathways, NGF signaling, and anti-apoptosis. Overall, it is suggested that the BSYZ formula might be a potential therapeutic approach for the treatment of Alzheimer's disease (AD) and other cholinergic impairment-related diseases. PMID:25482164

  7. Biocontrol agents-mediated suppression of oxalic acid induced cell death during Sclerotinia sclerotiorum-pea interaction.

    PubMed

    Jain, Akansha; Singh, Akanksha; Singh, Surendra; Sarma, Birinchi Kumar; Singh, Harikesh Bahadur

    2015-05-01

    Oxalic acid (OA) is an important pathogenic factor during early Sclerotinia sclerotiorum-host interaction and might work by reducing hydrogen peroxide production (H2 O2 ). In the present investigation, oxalic acid-induced cell death in pea was studied. Pea plants treated with biocontrol agents (BCAs) viz., Pseudomonas aeruginosa PJHU15, Bacillus subtilis BHHU100, and Trichoderma harzianum TNHU27 either singly and/or in consortium acted on S. sclerotiorum indirectly by enabling plants to inhibit the OA-mediated suppression of oxidative burst via induction of H2 O2 . Our results showed that BCA treated plants upon treatment with culture filtrate of the pathogen, conferred the resistance via. significantly decreasing relative cell death of pea against S. sclerotiorum compared to control plants without BCA treatment but treated with the culture filtrate of the pathogen. The results obtained from the present study indicate that the microbes especially in consortia play significant role in protection against S. sclerotiorum by modulating oxidative burst and partially enhancing tolerance by increasing the H2 O2 generation, which is otherwise suppressed by OA produced by the pathogen.

  8. Stearic acid induces proinflammatory cytokine production partly through activation of lactate-HIF1α pathway in chondrocytes.

    PubMed

    Miao, Hongming; Chen, Liang; Hao, Lijun; Zhang, Xuan; Chen, Yujuan; Ruan, Zhihua; Liang, Houjie

    2015-01-01

    The biomechanics stress and chronic inflammation in obesity are causally linked to osteoarthritis. However, the metabolic factors mediating obesity-related osteoarthritis are still obscure. Here we scanned and identified at least two elevated metabolites (stearic acid and lactate) from the plasma of diet-induced obese mice. We found that stearic acid potentiated LDH-a-dependent production of lactate, which further stabilized HIF1α protein and increased VEGF and proinflammatory cytokine expression in primary mouse chondrocytes. Treatment with LDH-a and HIF1α inhibitors notably attenuated stearic acid-or high fat diet-stimulated proinflammatory cytokine production in vitro and in vivo. Furthermore, positive correlation of plasma lactate, cartilage HIF1α and cytokine levels with the body mass index was observed in subjects with osteoarthritis. In conclusion, saturated free fatty acid induced proinflammatory cytokine production partly through activation of a novel lactate-HIF1α pathway in chondrocytes. Our findings hold promise of developing novel clinical strategies for the management of obesity-related diseases such as osteoarthritis.

  9. Possible protective role of pregnenolone-16 alpha-carbonitrile in lithocholic acid-induced hepatotoxicity through enhanced hepatic lipogenesis.

    PubMed

    Miyata, Masaaki; Nomoto, Masahiro; Sotodate, Fumiaki; Mizuki, Tomohiro; Hori, Wataru; Nagayasu, Miho; Yokokawa, Shinya; Ninomiya, Shin-ichi; Yamazoe, Yasushi

    2010-06-25

    Lithocholic acid (LCA) feeding causes both liver parenchymal and cholestatic damages in experimental animals. Although pregnenolone-16 alpha-carbonitrile (PCN)-mediated protection against LCA-induced hepatocyte injury may be explained by induction of drug metabolizing enzymes, the protection from the delayed cholestasis remains incompletely understood. Thus, the PCN-mediated protective mechanism has been studied from the point of modification of lipid metabolism. At an early stage of LCA feeding, an imbalance of biliary bile acid and phospholipid excretion was observed. Co-treatment with PCN reversed the increase in serum alanine aminotransferase (ALT) as well as alkaline phosphatase (ALP) activities and hepatic hydrophobic bile acid levels. LCA feeding decreased hepatic mRNA levels of several fatty acid- and phospholipid-related genes before elevation of serum ALT and ALP activities. On the other hand, PCN co-treatment reversed the decrease in the mRNA levels and hepatic levels of phospholipids, triglycerides and free fatty acids. PCN co-treatment also reversed the decrease in biliary phospholipid output in LCA-fed mice. Treatment with PCN alone increased hepatic phospholipid, triglyceride and free fatty acid concentrations. Hepatic fatty acid and phosphatidylcholine synthetic activities increased in mice treated with PCN alone or PCN and LCA, compared to control mice, whereas these activities decreased in LCA-fed mice. These results suggest the possibility that PCN-mediated stimulation of lipogenesis contributes to the protection from lithocholic acid-induced hepatotoxicity.

  10. Protective Effect of Cod (Gadus macrocephalus) Skin Collagen Peptides on Acetic Acid-Induced Gastric Ulcer in Rats.

    PubMed

    Niu, Huina; Wang, Zhicong; Hou, Hu; Zhang, Zhaohui; Li, Bafang

    2016-07-01

    This research was performed to explore the protective effect of cod skin collagen peptides (CCP) on gastric ulcer induced by acetic acid. The CCP were fractionated into low molecular CCP (LMCCP, Mw < 3 kDa) and high molecular CCP (HMCCP, Mw > 3 kDa). In HMCCP and LMCCP, glycine of accounted for about one-third of the total amino acids without cysteine and tryptophan, and hydrophobic amino acids accounted for about 50%. After 21 d CCP treatment (60 or 300 mg/kg, p.o./daily), the healing effects on acetic acid-induced gastric ulcers were evaluated by macroscopic measure, microscopic measure, and immune histochemistry. Moreover, the expression levels of the growth factors, such as vascular endothelial growth factor, epidermal growth factor, transforming growth factor β1 (TGFβ1), and the heat shock protein 70 (HSP70) was detected. The results showed that both LMCCP and HMCCP could significantly decrease the ulcer areas and promote the healing of the lesions. They also could improve the levels of hexosamine, glutathione, superoxide dismutase, and glutathione peroxidase, and reduce the content of malondialdehyde and inducible nitric oxide synthase. In addition, the expression level of TGFβ1 gene and HSP70 mRNA was significantly improved by the treatment. It suggested that CCP could be able to improve symptoms of gastric ulcer and probably be used in the treatment of gastric ulcer. PMID:27219644

  11. Phenylbutyric acid induces the cellular senescence through an Akt/p21{sup WAF1} signaling pathway

    SciTech Connect

    Kim, Hag Dong; Jang, Chang-Young; Choe, Jeong Min; Sohn, Jeongwon; Kim, Joon

    2012-06-01

    Highlights: Black-Right-Pointing-Pointer Phenylbutyric acid induces cellular senescence. Black-Right-Pointing-Pointer Phenylbutyric acid activates Akt kinase. Black-Right-Pointing-Pointer The knockdown of PERK also can induce cellular senescence. Black-Right-Pointing-Pointer Akt/p21{sup WAF1} pathway activates in PERK knockdown induced cellular senescence. -- Abstract: It has been well known that three sentinel proteins - PERK, ATF6 and IRE1 - initiate the unfolded protein response (UPR) in the presence of misfolded or unfolded proteins in the ER. Recent studies have demonstrated that upregulation of UPR in cancer cells is required to survive and proliferate. Here, we showed that long exposure to 4-phenylbutyric acid (PBA), a chemical chaperone that can reduce retention of unfolded and misfolded proteins in ER, induced cellular senescence in cancer cells such as MCF7 and HT1080. In addition, we found that treatment with PBA activates Akt, which results in p21{sup WAF1} induction. Interestingly, the depletion of PERK but not ATF6 and IRE1 also induces cellular senescence, which was rescued by additional depletion of Akt. This suggests that Akt pathway is downstream of PERK in PBA induced cellular senescence. Taken together, these results show that PBA induces cellular senescence via activation of the Akt/p21{sup WAF1} pathway by PERK inhibition.

  12. Neuroprotective effects of trans-caryophyllene against kainic acid induced seizure activity and oxidative stress in mice.

    PubMed

    Liu, Hao; Song, Zhi; Liao, Daguang; Zhang, Tianyi; Liu, Feng; Zhuang, Kai; Luo, Kui; Yang, Liang

    2015-01-01

    Trans-caryophyllene (TC), a component of essential oil found in many flowering plants, has shown its neuroprotective effects in various neurological disorders. However, the effects of TC on epilepsy haven't been reported before. In this study, we investigated the effect of TC on kainic acid-induced seizure activity caused by oxidative stress and pro-inflammation. We found that TC pretreatment significantly decreased seizure activity score compared to kainic acid treated group. Importantly, TC pretreatment leads to lowering the mortality in kainic acid treated mice. In addition, TC was found to significantly inhibit KA-induced generation of malondialdehyde. TC pretreatment also preserved the activity of GPx, SOD, and CAT. Notably, our data shows that an important property of TC is its capacity to exert cerebral anti-inflammatory effects by mitigating the expression of proinflammatory cytokines, such as TNF-α and IL-1β. These data suggest that TC has a potential protective effect on chemical induced seizure and brain damage. PMID:25417010

  13. A new 5-lipoxygenase selective inhibitor derived from Artocarpus communis strongly inhibits arachidonic acid-induced ear edema.

    PubMed

    Koshihara, Y; Fujimoto, Y; Inoue, H

    1988-06-01

    Natural compounds isolated from the Indonesian plant, Artocarpus communis, inhibit 5-lipoxygenase of cultured mastocytoma cells. One of five compounds, AC-5-1, strongly inhibits 5-lipoxygenase with a half-inhibition dose of 5 +/- 0.12 X 10(-8) M. However, prostaglandin synthesizing activity is not inhibited until 10(-5) M. AC-5-1 is a highly selective inhibitor for 5-lipoxygenase. The AC-5-1 at 10(-5) M inhibits 96% of leukotriene C4 synthesis of mouse peritoneal cells facilitated by calcium-ionophore. Arachidonic acid-induced ear edema of mice, an in vivo inflammatory model, involving leukotriene induction, is strongly inhibited by AC-5-1 in a dose-dependent manner. The inhibition is the strongest of any inhibitors of 5-lipoxygenase reported previously. Since the natural compound AC-5-1 can selectively inhibit 5-lipoxygenase and affect in vivo inflammation, it will be interesting to investigate the role of leukotrienes on inflammation and other physiological processes.

  14. DFT study of the molecular mechanism of Lewis acid induced [4 + 3] cycloadditions of 2-alkylacroleins with cyclopentadiene.

    PubMed

    Domingo, Luis R; Arnó, Manuel; Sáez, José A

    2009-08-21

    The mechanism of the Lewis acid (AlCl(3)) induced [4 + 3] cycloaddition of 2-methylacrolein with cyclopentadiene (Cp) [ J. Am. Chem. Soc. 2004, 126, 2692] has been examined here through DFT calculations at the MPW1K(DCM)/6-31+G** level. Formation of these seven-membered carbocycles is a domino process that comprises three consecutive reactions. The first one is a polar Diels-Alder reaction that is initialized by the nucleophilic attack of Cp to the beta-conjugated position of acrolein, yielding the formation of the endo and exo [4 + 2] cycloadducts. The corresponding LA-[4 + 2] cycloadduct complexes equilibrate through a skeleton rearrangement with a low free activation energy with two seven-membered zwitterionic intermediates, which undergo a rapid intramolecular hydride shift to yield irreversibly the formally endo and exo [4 + 3] cycloadducts. A comparative analysis of this mechanism with that for the Lewis acid induced [4 + 3] cycloadditions of 2-silyloxyacroleins allows establishment of the requirements for the formation of the seven-membered carbocycles.

  15. Relationship between the acid-induced cough response and airway responsiveness and obstruction in children with asthma.

    PubMed Central

    Shimizu, T.; Mochizuki, H.; Tokuyama, K.; Morikawa, A.

    1996-01-01

    BACKGROUND: In children with asthma little is known about the direct effect of the bronchoconstrictor and bronchodilator response on the cough threshold, or the relationship between bronchial responsiveness and the cough threshold. A study was undertaken to determine the effect of histamine-induced bronchoconstriction and salbutamol-induced bronchodilatation on the cough threshold in response to inhaled acetic acid, and to examine the relationship between the acetic acid cough threshold and bronchial hyperresponsiveness to histamine in children with asthma. METHODS: Nineteen children with asthma (16 boys) of mean (SE) age 10.6 (0.6) years were enrolled in the study. On day 1 each underwent a histamine inhalation challenge to determine the provocative concentration causing a fall in forced expiratory volume in one second (FEV1) of more than 20% (PC20) as an index of individual bronchial hyperresponsiveness. On day 2 the acetic acid cough threshold was determined before and just after the inhalation of the PC20 concentration of histamine, and then salbutamol (1 mg/m2) was inhaled to relieve the bronchoconstriction. Ten of the 19 patients (eight boys) of mean age 12.2 (0.7) years also tried acetic acid inhalation challenge just after salbutamol inhalation. RESULTS: There was no relationship between the bronchial responsiveness to histamine and acetic acid cough threshold in these patients. The acetic acid cough threshold after histamine inhalation was similar to that before histamine, although FEV1 decreased after histamine. In the 10 patients who also tried acetic acid inhalation challenge after salbutamol the cough threshold did not change. CONCLUSIONS: These findings suggest that acid-induced cough sensitivity and bronchomotor tone are independently regulated in children with asthma. PMID:8779132

  16. Dietary interesterified fat enriched with palmitic acid induces atherosclerosis by impairing macrophage cholesterol efflux and eliciting inflammation.

    PubMed

    Afonso, Milessa Silva; Lavrador, Maria Silvia Ferrari; Koike, Marcia Kiyomi; Cintra, Dennys Esper; Ferreira, Fabiana Dias; Nunes, Valeria Sutti; Castilho, Gabriela; Gioielli, Luiz Antonio; Paula Bombo, Renata; Catanozi, Sergio; Caldini, Elia Garcia; Damaceno-Rodrigues, Nilsa Regina; Passarelli, Marisa; Nakandakare, Edna Regina; Lottenberg, Ana Maria

    2016-06-01

    Interesterified fats are currently being used to replace trans fatty acids. However, their impact on biological pathways involved in the atherosclerosis development was not investigated. Weaning male LDLr-KO mice were fed for 16weeks on a high-fat diet (40% energy as fat) containing polyunsaturated (PUFA), TRANS, palmitic (PALM), palmitic interesterified (PALM INTER), stearic (STEAR) or stearic interesterified (STEAR INTER). Plasma lipids, lipoprotein profile, arterial lesion area, macrophage infiltration, collagen content and inflammatory response modulation were determined. Macrophage cholesterol efflux and the arterial expression of cholesterol uptake and efflux receptors were also performed. The interesterification process did not alter plasma lipid concentrations. Although PALM INTER did not increase plasma cholesterol concentration as much as TRANS, the cholesterol enrichment in the LDL particle was similar in both groups. Moreover, PALM INTER induced the highest IL-1β, MCP-1 and IL-6 secretion from peritoneal macrophages as compared to others. This inflammatory response elicited by PALM INTER was confirmed in arterial wall, as compared to PALM. These deleterious effects of PALM INTER culminate in higher atherosclerotic lesion, macrophage infiltration and collagen content than PALM, STEAR, STEAR INTER and PUFA. These events can partially be attributed to a macrophage cholesterol accumulation, promoted by apoAI and HDL2-mediated cholesterol efflux impairment and increased Olr-1 and decreased Abca1 and Nr1h3 expressions in the arterial wall. Interesterified fats containing palmitic acid induce atherosclerosis development by promoting cholesterol accumulation in LDL particles and macrophagic cells, activating the inflammatory process in LDLr-KO mice.

  17. Priming by Hexanoic Acid Induce Activation of Mevalonic and Linolenic Pathways and Promotes the Emission of Plant Volatiles

    PubMed Central

    Llorens, Eugenio; Camañes, Gemma; Lapeña, Leonor; García-Agustín, Pilar

    2016-01-01

    Hexanoic acid (Hx) is a short natural monocarboxylic acid present in some fruits and plants. Previous studies reported that soil drench application of this acid induces effective resistance in tomato plants against Botrytis cinerea and Pseudomonas syringae and in citrus against Alternaria alternata and Xanthomonas citri. In this work, we performed an in deep study of the metabolic changes produced in citrus by the application of Hx in response to the challenge pathogen A. alternata, focusing on the response of the plant. Moreover, we used 13C labeled hexanoic to analyze its behavior inside the plants. Finally, we studied the volatile emission of the treated plants after the challenge inoculation. Drench application of 13C labeled hexanoic demonstrated that this molecule stays in the roots and is not mobilized to the leaves, suggesting long distance induction of resistance. Moreover, the study of the metabolic profile showed an alteration of more than 200 molecules differentially induced by the application of the compound and the inoculation with the fungus. Bioinformatics analysis of data showed that most of these altered molecules could be related with the mevalonic and linolenic pathways suggesting the implication of these pathways in the induced resistance mediated by Hx. Finally, the application of this compound showed an enhancement of the emission of 17 volatile metabolites. Taken together, this study indicates that after the application of Hx this compound remains in the roots, provoking molecular changes that may trigger the defensive response in the rest of the plant mediated by changes in the mevalonic and linolenic pathways and enhancing the emission of volatile compounds, suggesting for the first time the implication of mevalonic pathway in response to hexanoic application. PMID:27148319

  18. Excitatory amino acid transporter 2 downregulation correlates with thalamic neuronal death following kainic acid-induced status epilepticus in rat.

    PubMed

    Sakurai, Masashi; Kurokawa, Haruna; Shimada, Akinori; Nakamura, Kazuhiro; Miyata, Hajime; Morita, Takehito

    2015-02-01

    Recurrent seizures without interictal resumption (status epilepticus) have been reported to induce neuronal death in the midline thalamic region that has functional roles in memory and decision-making; however, the pathogenesis underlying status epilepticus-induced thalamic neuronal death is yet to be determined. We performed histological and immunohistochemical studies as well as cerebral blood flow measurement using 4.7 tesla magnetic resonance imaging spectrometer on midline thalamic region in Sprague-Dawley rats (n = 75, male, 7 weeks after birth, body weight 250-300 g) treated with intraperitoneal injection of kainic acid (10 mg/kg) to induce status epilepticus (n = 55) or normal saline solution (n = 20). Histological study using paraffin-embedded specimens revealed neuronal death showing ischemic-like changes and Fluoro-Jade C positivity with calcium deposition in the midline thalamic region of epileptic rats. The distribution of neuronal death was associated with focal loss of immunoreactivity for excitatory amino acid transporter 2 (EAAT2), stronger immunoreaction for glutamate and increase in number of Iba-1-positive microglial cells showing swollen cytoplasm and long processes. Double immunofluorescence study demonstrated co-expression of interleukin-1 beta (IL-1β) and inducible nitric oxide synthase (iNOS) within microglial cells, and loss of EAAT2 immunoreactivity in reactive astrocytes. These microglial alterations and astrocytic EAAT2 downregulation were also observed in tissue without obvious neuronal death in kainic acid-treated rats. These results suggest the possible role of glutamate excitotoxicity in neuronal death in the midline thalamic region following kainic acid-induced status epilepticus due to astrocytic EAAT2 downregulation following microglial activation showing upregulation of IL-1β and iNOS.

  19. Anti-inflammatory effect of Moringa oleifera Lam. seeds on acetic acid-induced acute colitis in rats

    PubMed Central

    Minaiyan, Mohsen; Asghari, Gholamreza; Taheri, Diana; Saeidi, Mozhgan; Nasr-Esfahani, Salar

    2014-01-01

    Objective: Anti-inflammatory, immuno-modulatory, and antioxidant properties of Moringa oleifera Lam. suggest that it might have beneficial effects on colitis. The present study was performed to investigate the anticolitis effect of Moringa oleifera seeds hydro-alcoholic extract (MSHE) and its chloroform fraction (MCF) on acetic acid-induced colitis in rats. Materials and Methods: Both MSHE and MCF with three increasing doses (50, 100, and 200 mg/kg) were administered orally to separate groups of male Wistar rats, 2 h before ulcer induction (using acetic acid 4%) and continued for 5 days. Prednisolone (4 mg/kg) and normal saline (1 ml/kg) were used in reference and control groups, respectively. All rats were sacrificed 24 h after the last dose (at day 6) and tissue injuries were assessed macroscopically and pathologically. Results: Extracts with three doses mentioned before were effective to reduce weight of distal colon (8 cm) as a marker for inflammation and tissue edema. Three doses of MSHE and two greater doses of MCF (100 and 200 mg/kg) were effective to reduce ulcer severity, area, and index as well as mucosal inflammation severity and extent, crypt damage, invasion involvement, total colitis index, and MPO activity compared with controls. MCF (50 mg/kg) was not significantly effective in reducing evaluated parameters of colitis compared with controls. Conclusion: It is concluded that MSHE and MCF were both effective to treat experimental colitis and this might be attributed to their similar major components, biophenols and flavonoids. Since the efficacy was evident even in low doses of MSHE, presence of active constituents with high potency in seeds is persuasive. PMID:25050310

  20. The Healing Effect of Teucrium polium in Acetic Acid-Induced Ulcerative Colitis in the Dog as an Animal Model

    PubMed Central

    Mehrabani, Davood; Bahrami, Faranak; Hosseini, Seyed Vahid; Ashraf, Mohammad Javad; Tanideh, Nader; Rezaianzadeh, Abbas; Amini, Masoud; Amini, Afshin

    2012-01-01

    BACKGROUND Inflammatory bowel diseases (IBD), which include ulcerative colitis (UC) and Crohn’s disease (CD), are debilitating and chronic disorders with unpredictable courses and complicated treatment measures. Therefore, an efficient treatment protocol seems necessary as therapeutic prophylaxis for these disorders. This study aims to determine the healing effect of Teucrium polium (T. polium) in acetic acid-induced UC in an experimental dog model. METHODS From September to December 2010, eight male (20-25 kg) crossbred dogs were used for induction of UC by 6% acetic acid, transrectally. After one week, three biopsies (10, 20 and 30 cm proximal to the anal verge) were taken from the colon of each animal for histological studies. In the presence of UC, 400 mg/kg/day of T. polium extract was administered orally and transrectally (via enema) for 30 days in six of the dogs. The remaining two dogs were used as controls and did not receive T. polium. Multiple biopsies were taken 7, 14, and 30 days after discontinuation of T. polium in the same manner as before treatment. RESULTS After administration of acetic acid, we noted the presence of multiple ulcers, diffuse inflammation, PMN infiltration in the lamina propria, glandular destruction and goblet cell depletion. Treatment with T. polium restored the colonic architecture with an increased number of healthy cells and a reduction in inflammatory cells. Damage of the surface epithelial cells and mucosal layer of the lumen were reversed, which lead to faster ulcer healing. CONCLUSION T. polium may be a treatment choice for UC and can broaden the current therapy options for UC. PMID:24829634

  1. Functional and cellular characterization of human Retinoic Acid Induced 1 (RAI1) mutations associated with Smith-Magenis Syndrome

    PubMed Central

    2010-01-01

    Background Smith-Magenis Syndrome is a contiguous gene syndrome in which the dosage sensitive gene has been identified: the Retinoic Acid Induced 1 (RAI1). Little is known about the function of human RAI1. Results We generated the full-length cDNA of the wild type protein and five mutated forms: RAI1-HA 2687delC, RAI1-HA 3103delC, RAI1 R960X, RAI1-HA Q1562R, and RAI1-HA S1808N. Four of them have been previously associated with SMS clinical phenotype. Molecular weight, subcellular localization and transcription factor activity of the wild type and mutant forms were studied by western blot, immunofluorescence and luciferase assays respectively. The wild type protein and the two missense mutations presented a higher molecular weight than expected, localized to the nucleus and activated transcription of a reporter gene. The frameshift mutations generated a truncated polypeptide with transcription factor activity but abnormal subcellular localization, and the same was true for the 1-960aa N-terminal half of RAI1. Two different C-terminal halves of the RAI1 protein (1038aa-end and 1229aa-end) were able to localize into the nucleus but had no transactivation activity. Conclusion Our results indicate that transcription factor activity and subcellular localization signals reside in two separate domains of the protein and both are essential for the correct functionality of RAI1. The pathogenic outcome of some of the mutated forms can be explained by the dissociation of these two domains. PMID:20738874

  2. Retinoic Acid Induced 1, RAI1: A Dosage Sensitive Gene Related to Neurobehavioral Alterations Including Autistic Behavior

    PubMed Central

    Carmona-Mora, Paulina; Walz, Katherina

    2010-01-01

    Genomic structural changes, such as gene Copy Number Variations (CNVs) are extremely abundant in the human genome. An enormous effort is currently ongoing to recognize and catalogue human CNVs and their associations with abnormal phenotypic outcomes. Recently, several reports related neuropsychiatric diseases (i.e. autism spectrum disorders, schizophrenia, mental retardation, behavioral problems, epilepsy) with specific CNV. Moreover, for some conditions, both the deletion and duplication of the same genomic segment are related to the phenotype. Syndromes associated with CNVs (microdeletion and microduplication) have long been known to display specific neurobehavioral traits. It is important to note that not every gene is susceptible to gene dosage changes and there are only a few dosage sensitive genes. Smith-Magenis (SMS) and Potocki-Lupski (PTLS) syndromes are associated with a reciprocal microdeletion and microduplication within chromosome 17p11.2. in humans. The dosage sensitive gene responsible for most phenotypes in SMS has been identified: the Retinoic Acid Induced 1 (RAI1). Studies on mouse models and humans suggest that RAI1 is likely the dosage sensitive gene responsible for clinical features in PTLS. In addition, the human RAI1 gene has been implicated in several neurobehavioral traits as spinocerebellar ataxia (SCA2), schizophrenia and non syndromic autism. In this review we discuss the evidence of RAI1 as a dosage sensitive gene, its relationship with different neurobehavioral traits, gene structure and mutations, and what is known about its molecular and cellular function, as a first step in the elucidation of the mechanisms that relate dosage sensitive genes with abnormal neurobehavioral outcomes. PMID:21629438

  3. Protective Effect of the Methanolic Extract of Malva parviflora L. leaves on Acetic Acid-induced Ulcerative Colitis in Rats

    PubMed Central

    Dugani, Aisha; Dakhil, Bushra; Treesh, Soad

    2016-01-01

    Background/Aims: Inflammatory bowel disease (IBD) is a general term describing chronic, idiopathic relapsing, inflammatory conditions of the gastrointestinal tract of unknown etiology. Previous studies have indicated that Malva parviflora leaf extract possesses anti-inflammatory, antioxidant, and antiulcerogenic activity. activity. This work aimed to investigatee the anti-inflammatory effect of the methanolic (MEMP) and aqueous (AEMP) extracts of M. parviflora leaves on acetic acid-induced colitis in rats. Materials and Methods: 42 male Wistar albino rats were divided into seven groups (n = 6). Group I: Normal saline control group with no colitis; Group II: Acetic acid colitis group; Group III: 100 mg/kg/5 d MEMP; Group IV: 200 mg/kg/5 d.MEMP; Group V: 100 mg/kg/5 d AEMP; Group VI: 200 mg/kg/5 d AEMP; Group VII: Prednisolone group (2 mg/kg/5 d). Treatments were followed by induction of colitis using intrarectal instillation of 2 mL of 4% acetic acid. Colon damage was evaluated macroscopically (spleen weight/body weight, colon weight/length ratio) and the histological changes were also recorded. Results: The results of this study showed that acetic acid caused severe inflammation of the colon and a significant increase in spleen weight/body weight, and an increase in colon weight/length ratio compared with normal control group. Pretreatment with MEMP and AEMP for 5 days followed by induction of colitis resulted in a significant attenuation of spleen weight and colon weight/length ratio compared with acetic acid control group. Methanolic extract provided better anticolitic effect than aqueous extract; the effect was prominent at the dose of 200 mg/kg. Histopathological findings confirmed the protective effect of the MEMP. Conclusion: In conclusion, MEMP could ameliorate mucosal damage in experimentally induced colitis when given orally. PMID:27184642

  4. Sida rhomboidea.Roxb extract alleviates pathophysiological changes in experimental in vivo and in vitro models of high fat diet/fatty acid induced non-alcoholic steatohepatitis.

    PubMed

    Thounaojam, Menaka C; Jadeja, Ravirajsinh N; Dandekar, Deven S; Devkar, Ranjitsinh V; Ramachandran, A V

    2012-03-01

    The present study was aim to evaluate protective role of Sida rhomboidea.Roxb (SR) extract against high fat diet/fatty acid induced pathophysiological alterations in experimental model of non-alcoholic steatohepatitis (NASH). Effect of SR extract on plasma levels of markers of hepatic damage, plasma and hepatic lipids, mitochondrial oxidative stress, status of enzymatic and non-enzymatic antioxidants and histopathological changes in liver tissue were evaluated in high fat diet fed C57BL/6J mice. Also, the effect of SR supplementation on lipid accumulation, lipid peroxidation, cytotoxicity and cell viability were evaluated in oleic acid treated HepG2 cells. Supplementation of NASH mice with SR extract prevented high fat diet induced elevation in plasma marker enzymes of liver damage, plasma and hepatic lipids, mitochondrial oxidative stress and compromised enzymatic and non-enzymatic antioxidant status. Further, addition of SR extract to in vitro HepG2 cells minimized oleic acid induced lipid accumulation, higher lipid peroxidation, cytotoxicity and reduced cell viability. These in vivo and in vitro studies suggest that SR extract has the potential of preventing high fat/fatty acid induced NASH mainly due to its hypolipidemic and antioxidant activities.

  5. Anti-inflammatory effects of nesfatin-1 in rats with acetic acid - induced colitis and underlying mechanisms.

    PubMed

    Ozturk, C C; Oktay, S; Yuksel, M; Akakin, D; Yarat, A; Kasimay Cakir, O

    2015-10-01

    Mucosal balance impairment, bacterial over-proliferation, cytokines, inflammatory mediators are known as responsible for inflammatory bowel disease. Besides known anorexigenic, neuroprotective, and anti-apoptotic effects, the major effect of nesfatin-1 on colitis is unknown. Our aim was to investigate the possible anti-inflammatory effects of nesfatin-1 in acetic acid induced colitis model and potential underlying mechanisms. Male Spraque-Dawley rats were anesthetized by intraperitoneal ketamine (100 mg/kg) and chlorpromazine (0.75 mg/kg). For nesfatin-1 and antagonist applications some of the rats were intracerebroventricularly (i.c.v.) cannulated. In colitis group, intrarectally (i.r.) 4% acetic acid solution (1 ml) and 10 minutes later i.c.v. nesfatin-1 (0.05 μg/5 μl) or vehicle (5 μl) were administered. Treatments continued for 3 days. In control group, physiological saline solution was used intrarectally. To identify the underlying effective mechanism of nesfatin-1, rats were divided into 3 subgroups, 5 minutes following colitis induction; i.c.v. atosiban (oxytocin receptor antagonist), SHU9119 (melanocortin receptor antagonist) or GHSR-1a antagonist (ghrelin receptor antagonist) were administered, 5 minutes later nesfatin-1 was administered for 3 days. On the fourth day, rats were decapitated, and colon tissues were sampled. Macroscopic and microscopic damage scores of distal colon, and colonic tissue malondialdehyde, glutathione, myeloperoxidase, superoxide dismutase, catalase, luminol and lucigenin chemiluminescence measurements were analysed. The increased myeloperoxidase activity, malondialdehyde levels, luminol and lucigenin chemiluminescence measurements, macroscopic and microscopic damage scores with colitis induction (P < 0.05 - 0.001) were decreased with nesfatin-1 treatment (P < 0.05 - 0.001). Nesfatin-1 may show this effect by inhibiting neutrophil infiltration through tissues and by decreasing formation of free oxygen radicals. Atosiban and

  6. Docosahexaenoic acid and other fatty acids induce a decrease in pHi in Jurkat T-cells

    PubMed Central

    Aires, Virginie; Hichami, Aziz; Moutairou, Kabirou; Khan, Naim Akhtar

    2003-01-01

    Docosahexaenoic acid (DHA) induced rapid (t1/2=33 s) and dose-dependent decreases in pHi in BCECF-loaded human (Jurkat) T-cells. Addition of 5-(N,N-dimethyl)-amiloride, an inhibitor of Na+/H+ exchanger, prolonged DHA-induced acidification as a function of time, indicating that the exchanger is implicated in pHi recovery. Other fatty acids like oleic acid, arachidonic acid, eicosapentaenoic acid, but not palmitic acid, also induced a fall in pHi in these cells. To assess the role of calcium in the DHA-induced acidification, we conducted experiments in Ca2+-free (0% Ca2+) and Ca2+-containing (100% Ca2+) buffer. We observed that there was no difference in the degree of DHA-induced transient acidification in both the experimental conditions, though pHi recovery was faster in 0% Ca2+ medium than that in 100% Ca2+ medium. In the presence of BAPTA, a calcium chelator, a rapid recovery of DHA-induced acidosis was observed. Furthermore, addition of CaCl2 into 0% Ca2+ medium curtailed DHA-evoked rapid pHi recovery. In 0% Ca2+ medium, containing BAPTA, DHA did not evoke increases in [Ca2+]i, though this fatty acid still induced a rapid acidification in these cells. These observations suggest that calcium is implicated in the long-lasting DHA-induced acidosis. DHA-induced rapid acidification may be due to its deprotonation in the plasma membrane (flip-flop model), as suggested by the following observations: (1) DHA with a –COOH group induced intracellular acidification, but this fatty acid with a –COOCH3 group failed to do so, and (2) DHA, but not propionic acid, -induced acidification was completely reversed by addition of fatty acid-free bovine serum albumin in these cells. These results suggest that DHA induces acidosis via deprotonation and Ca2+ mobilization in human T-cells. PMID:14645139

  7. Blueberry polyphenols attenuate kainic acid-induced decrements in cognition and alter inflammatory gene expression in rat hippocampus

    PubMed Central

    Shukitt-Hale, Barbara; Lau, Francis C.; Carey, Amanda N.; Galli, Rachel L.; Spangler, Edward L.; Ingram, Donald K.; Joseph, James A.

    2016-01-01

    Cognitive impairment in age-related neurodegenerative diseases such as Alzheimer's disease may be partly due to long-term exposure and increased susceptibility to inflammatory insults. In the current study, we investigated whether polyphenols in blueberries can reduce the deleterious effects of inflammation induced by central administration of kainic acid by altering the expression of genes associated with inflammation. To this end, 4-month-old male Fischer-344 (F344) rats were fed a control, 0.015% piroxicam (an NSAID) or 2% blueberry diet for 8 weeks before either Ringer's buffer or kainic acid was bilaterally micro-infused into the hippocampus. Two weeks later, following behavioral evaluation, the rats were killed and total RNA from the hippocampus was extracted and used in real-time quantitative RT-PCR (qRT-PCR) to analyze the expression of inflammation-related genes. Kainic acid had deleterious effects on cognitive behavior as kainic acid-injected rats on the control diet exhibited increased latencies to find a hidden platform in the Morris water maze compared to Ringer's buffer-injected rats and utilized non-spatial strategies during probe trials. The blueberry diet, and to a lesser degree the piroxicam diet, was able to improve cognitive performance. Immunohistochemical analyses of OX-6 expression revealed that kainic acid produced an inflammatory response by increasing the OX-6 positive areas in the hippocampus of kainic acid-injected rats. Kainic acid up-regulated the expression of the inflammatory cytokines IL-1β and TNF-α, the neurotrophic factor IGF-1, and the transcription factor NF-κB. Blueberry and piroxicam supplementations were found to attenuate the kainic acid-induced increase in the expression of IL-1β, TNF-α, and NF-κB, while only blueberry was able to augment the increased IGF-1 expression. These results indicate that blueberry polyphenols attenuate learning impairments following neurotoxic insult and exert anti-inflammatory actions

  8. Antinociceptive activity of Astragalus gummifer gum (gum tragacanth) through the adrenergic system: A in vivo study in mice

    PubMed Central

    Bagheri, Seyyed Majid; Keyhani, Leila; Heydari, Mehrangiz; Dashti-R, Mohammad Hossein

    2015-01-01

    Background: In Iranian traditional medicine, gum obtained from Astragalus gummifer and some other species of Astragalus was used as analgesic agent. Objective: In this study, we investigated the antinociceptive effect of several concentrations (125, 250, and 500 μg/kg body weight) of Astragalus gummifer gum (AGG) on thermal and acetic acid induced pain in mice. Materials and Methods: AGG was dissolved in distillated water and injected i.p to male mice 15 minute before the onset of experiment. Writhing and hot-plate tests were applied to study the analgesic effect of AGG and compared with that of diclofenac sodium (30 mg/kg, i.p.) or morphine (8 mg/kg, i.p). To investigate the mechanisms involved in antinociception, yohimbine, naloxone, glibenclamide, and theophylline were used in writhing test. These drugs were injected intraperitoneally 15 min before the administration of AGG. The number of writhes were counted in 30 minutes and analyzed. Results: AGG exhibited a significant antinociceptive effect and the most effective dose of AGG was 500 μg/kg. The most maximum possible effect (%MPE) was observed (117.4%) 15 min after drug administration. The %inhibition of acetic acid-induced writhing in AGG 125, 250 and 500 was 47%, 50% and 54% vs %15 of control and 66.3% of diclofenac sodium group. The antinociceptive effect induced by this gum in the writhing test was reversed by the systemic administration of yohimbine (α2-adrenergic antagonist), but naloxone, glibenclamide, and theophylline did not reverse this effect. Conclusions: The findings of this study indicated that AGG induced its antinociceptive through the adrenergic system. PMID:25878459

  9. Evaluation of antinociceptive effects of Tragia plukenetii: A possible mechanism.

    PubMed

    Venkatesh, Sama; Fatima, Saba

    2013-07-01

    Tragia plukenetii R.Smith. (Euphorbiaceae) is an erect, prostate herb with sparsely hispid stinging hairs. In the present study, ethanolic extract and its fractions of T. plukenetii aerial parts were evaluated for antinociceptive and central nervous system (CNS) depressant effects. Among all the extracts, chloroform extract has produced significant analgesic activity at a test dose of 250 mg/kg in acetic acid induced writhing test and Eddy's hotplate test. The analgesic effect of chloroform extract (68.83% inhibition) is comparable with aspirin (72.09% inhibition) in acetic acid induced writhing test. Chloroform extract significantly increased the latency time in hotplate test. In the study of CNS depressant effect, the chloroform extract was found to produce a significant (P < 0.01) reduction of the exploratory capacity and depressant effect in locomotor activity. From the point of CNS depressant and good protective effect on chemical and thermal pain stimuli, indicates that T. plukenetii chloroform extract may have morphinomimetic properties. The naloxone is not able to alter the T. plukenetii induced antinociceptive effect in writhing and hotplate test. Thus, the observed antinociceptive activity of T. plukenetii might have resulted from the activation of peripheral receptors. PMID:24501531

  10. NT79: A novel neurotensin analog with selective behavioral effects.

    PubMed

    Boules, Mona; Liang, Yanqi; Briody, Siobhan; Miura, Tomofumi; Fauq, Irfan; Oliveros, Alfredo; Wilson, Mina; Khaniyev, Shaheen; Williams, Katrina; Li, Zhimin; Qi, Yanfei; Katovich, Michael; Richelson, Elliott

    2010-01-13

    Neurotensin, a tridecapeptide, is widely distributed in the brain and gastrointestinal tract. It possesses analgesic, hypothermic, and antipsychotic-like properties. Neurotensin's effects are mediated mainly through two receptor subtypes, NTS1 and NTS2. Activation of NTS1 has been implicated in most of the pharmacological effects of neurotensin but is associated with hypothermia and hypotension. We report on a novel neurotensin analog with higher selectivity to NTS2, namely, NT79, which exhibits selective behavioral effects. NT79 was tested in animal models for pain (thermal-hot plate test; visceral-acetic acid-induced writhing test), and in animal models that are predictive of antipsychotic-like effects (apomorphine-induced climbing; d-amphetamine-induced hyperactivity; disruption of prepulse inhibition). Its effects on body temperature and on blood pressure were also determined. Neurochemical changes in extracellular neurotransmitters were measured using in vivo microdialysis while the rats were simultaneously evaluated for acetic acid-induced writhing with and without pretreatment with NT79. Binding data at molecularly cloned hNTS1 and hNTS2 suggest selectivity for hNTS2. NT79 blocked the acetic acid-induced writhing with an ED(50) of 0.14 microg/kg while having no effect on thermal nociception. The writhing was paralleled by an increase in 5-HT which was attenuated by NT79. NT79 demonstrated antipsychotic-like effects by blocking apomorphine-induced climbing, d-amphetamine-induced hyperactivity, and reducing d-amphetamine- and DOI-induced disruption of prepulse inhibition. Uniquely, it caused no significant hypothermia and was without effect on blood pressure. NT79, with its higher selectivity to NTS2, may be potentially useful to treat visceral pain, and psychosis without concomitant side effects of hypothermia or hypotension.

  11. Schistosoma mansoni: possible involvement of protein kinase C in linoleic acid-induced proteolytic enzyme release from cercariae.

    PubMed

    Matsumura, K; Mitsui, Y; Sato, K; Sakamoto, M; Aoki, Y

    1991-04-01

    antagonist, trifluoperazine (TFP), a better calmodulin antagonist on schistosome, or by verapamil, a Ca2+ channel blocker. Linoleic acid-induced release of enzyme was partially inhibited by 0.5 and 5 mM of EGTA and by 1 to 100 microM of H-7. While it was not inhibited by N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide (H-8) and N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA-1004), inhibitors of cyclic nucleotide-dependent protein kinase which were used as negative controls of H-7, W-7, TFP, 8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate (TMB-8), an intracellular Ca2+ antagonist, and verapamil.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2015870

  12. The Na+/H+ Exchanger Controls Deoxycholic Acid-Induced Apoptosis by a H+-Activated, Na+-Dependent Ionic Shift in Esophageal Cells

    PubMed Central

    Goldman, Aaron; Chen, HwuDauRw; Khan, Mohammad R.; Roesly, Heather; Hill, Kimberly A.; Shahidullah, Mohammad; Mandal, Amritlal; Delamere, Nicholas A.; Dvorak, Katerina

    2011-01-01

    Apoptosis resistance is a hallmark of cancer cells. Typically, bile acids induce apoptosis. However during gastrointestinal (GI) tumorigenesis the cancer cells develop resistance to bile acid-induced cell death. To understand how bile acids induce apoptosis resistance we first need to identify the molecular pathways that initiate apoptosis in response to bile acid exposure. In this study we examined the mechanism of deoxycholic acid (DCA)-induced apoptosis, specifically the role of Na+/H+ exchanger (NHE) and Na+ influx in esophageal cells. In vitro studies revealed that the exposure of esophageal cells (JH-EsoAd1, CP-A) to DCA (0.2 mM -0.5 mM) caused lysosomal membrane perturbation and transient cytoplasmic acidification. Fluorescence microscopy in conjunction with atomic absorption spectrophotometry demonstrated that this effect on lysosomes correlated with influx of Na+, subsequent loss of intracellular K+, an increase of Ca2+ and apoptosis. However, ethylisopropyl-amiloride (EIPA), a selective inhibitor of NHE, prevented Na+, K+ and Ca2+ changes and caspase 3/7 activation induced by DCA. Ouabain and amphotericin B, two drugs that increase intracellular Na+ levels, induced similar changes as DCA (ion imbalance, caspase3/7 activation). On the contrary, DCA-induced cell death was inhibited by medium with low a Na+ concentrations. In the same experiments, we exposed rat ileum ex-vivo to DCA with or without EIPA. Severe tissue damage and caspase-3 activation was observed after DCA treatment, but EIPA almost fully prevented this response. In summary, NHE-mediated Na+ influx is a critical step leading to DCA-induced apoptosis. Cells tolerate acidification but evade DCA-induced apoptosis if NHE is inhibited. Our data suggests that suppression of NHE by endogenous or exogenous inhibitors may lead to apoptosis resistance during GI tumorigenesis. PMID:21887327

  13. The role of amino acid-induced mammalian target of rapamycin complex 1(mTORC1) signaling in insulin resistance

    PubMed Central

    Yoon, Mee-Sup; Choi, Cheol Soo

    2016-01-01

    Mammalian target of rapamycin (mTOR) controls cell growth and metabolism in response to nutrients, energy, and growth factors. Recent findings have placed the lysosome at the core of mTOR complex 1 (mTORC1) regulation by amino acids. Two parallel pathways, Rag GTPase-Ragulator and Vps34-phospholipase D1 (PLD1), regulate mTOR activation on the lysosome. This review describes the recent advances in understanding amino acid-induced mTOR signaling with a particular focus on the role of mTOR in insulin resistance. PMID:27534530

  14. The anti-nociceptive potential of tilmicosin against chemical-induced but not thermal-induced pain in mice.

    PubMed

    El-Mahmoudy, A; Gheith, I

    2016-03-01

    The aim of the present study was to assess the analgesic activity of the macrolide antibiotic tilmicosin at dose levels of 20 and 40 mg/kg of body weight, subcutaneously, against chemical- and thermal-induced acute pains, using acetic acid-induced writhing, formalin-induced pain, hot-plate, and tail-flick models in mice. Tilmicosin showed a dose-dependent significant decrease in the number of writhes in the acetic acid-induced writhing test and significant decrease in hind paw-licking time in the late phase of the formalin test. However, it did not cause any significant changes in the reaction times to heat stimuli in the hot-plate and tail-flick models. In chemically-induced pains, both dose levels of tilmicosin showed significant effects compared to those of the corresponding standard peripheral analgesic, acetylsalicylic acid (200 mg/kg of body weight, subcutaneously) being 26.37±2.88 and 43.64±3.85% vs. 73.35±1.44% in acetic acid test; and 19.23±3.85 and 44.90±1.80% vs. 73.63±2.39% in the late phase of formalin test, respectively. These results may indicate that tilmicosin possesses a significant peripheral but not central analgesic potential that may be beneficial in symptomatic relief of pain when it is used in therapy, in addition to its well-established antibacterial effect.

  15. Resistance to butyrate impairs bile acid-induced apoptosis in human colon adenocarcinoma cells via up-regulation of Bcl-2 and inactivation of Bax.

    PubMed

    Barrasa, Juan I; Santiago-Gómez, Angélica; Olmo, Nieves; Lizarbe, María Antonia; Turnay, Javier

    2012-12-01

    A critical risk factor in colorectal carcinogenesis and tumor therapy is the resistance to the apoptotic effects of different compounds from the intestinal lumen, among them butyrate (main regulator of colonic epithelium homeostasis). Insensitivity to butyrate-induced apoptosis yields resistance to other agents, as bile acids or chemotherapy drugs, allowing the selective growth of malignant cell subpopulations. Here we analyze bile acid-induced apoptosis in a butyrate-resistant human colon adenocarcinoma cell line (BCS-TC2.BR2) to determine the mechanisms that underlay the resistance to these agents in comparison with their parental butyrate-sensitive BCS-TC2 cells. This study demonstrates that DCA and CDCA still induce apoptosis in butyrate-resistant cells through increased ROS production by activation of membrane-associated enzymes and subsequent triggering of the intrinsic mitochondrial apoptotic pathway. Although this mechanism is similar to that described in butyrate-sensitive cells, cell viability is significantly higher in resistant cells. Moreover, butyrate-resistant cells show higher Bcl-2 levels that confer resistance to bile acid-induced apoptosis sequestering Bax and avoiding Bax-dependent pore formation in the mitochondria. We have confirmed that this resistance is reverted using the Bcl-2 inhibitor ABT-263, thus demonstrating that the lower sensitivity of butyrate-resistant cells to the apoptotic effects of bile acids is mainly due to increased Bcl-2 levels.

  16. Synergic Interaction of Rifaximin and Mutaflor (Escherichia coli Nissle 1917) in the Treatment of Acetic Acid-Induced Colitis in Rats.

    PubMed

    Dembiński, Artur; Warzecha, Zygmunt; Ceranowicz, Piotr; Dembiński, Marcin; Cieszkowski, Jakub; Gosiewski, Tomasz; Bulanda, Małgorzata; Kuśnierz-Cabala, Beata; Gałązka, Krystyna; Konturek, Peter Christopher

    2016-01-01

    Background. Inflammatory bowel disease results from the dysregulation of immune response to environmental and microbial agents in genetically susceptible individuals. The aim of the present study was to examine the effect of rifaximin and/or Mutaflor (Escherichia coli Nissle 1917, EcN) administration on the healing of acetic acid-induced colitis. Methods. Colitis was induced in male Wistar rats by rectal enema with 3.5% acetic acid solution. Rifaximin (50 mg/kg/dose) and/or Mutaflor (10(9) CFU/dose) were given intragastrically once a day. The severity of colitis was assessed at the 8th day after induction of inflammation. Results. Treatment with rifaximin significantly accelerated the healing of colonic damage. This effect was associated with significant reversion of the acetic acid-evoked decrease in mucosal blood flow and DNA synthesis. Moreover, administration of rifaximin significantly reduced concentration of proinflammatory TNF-α and activity of myeloperoxidase in colonic mucosa. Mutaflor given alone was without significant effect on activity of colitis. In contrast, Mutaflor given in combination with rifaximin significantly enhanced therapeutic effect of rifaximin. Moreover, Mutaflor led to settle of the colon by EcN and this effect was augmented by pretreatment with rifaximin. Conclusion. Rifaximin and Mutaflor exhibit synergic anti-inflammatory and therapeutic effect in acetic acid-induced colitis in rats. PMID:27433160

  17. Baicalein, a Constituent of Scutellaria baicalensis, Reduces Glutamate Release and Protects Neuronal Cell Against Kainic Acid-Induced Excitotoxicity in Rats.

    PubMed

    Chang, Yi; Lu, Cheng Wei; Lin, Tzu Yu; Huang, Shu Kuei; Wang, Su Jane

    2016-01-01

    Interest in the health benefits of flavonoids, particularly their effects on neurodegenerative disease, is increasing. This study evaluated the role of baicalein, a flavonoid compound isolated from the traditional Chinese medicine Scutellaria baicalensis, in glutamate release and glutamate neurotoxicity in the rat hippocampus. In the rat hippocampal nerve terminals (synaptosomes), baicalein inhibits depolarization-induced glutamate release, and this phenomenon is prevented by chelating the extracellular Ca[Formula: see text] ions and blocking presynaptic Cav2.2 (N-type) and Cav2.1 (P/Q-type) channel activity. In slice preparations, whole cell patch-clamp experiments revealed that baicalein reduced the frequency of miniature excitatory postsynaptic currents, without affecting their amplitude. In a kainic acid rat model, intraperitoneally administering baicalein to rats before the kainic acid intraperitoneal injection substantially attenuated kainic acid-induced neuronal cell death, c-Fos expression, and the activation of the mammalian target of rapamycin in the hippocampus. This study is the first to demonstrate that the natural compound baicalein inhibits glutamate release from hippocampal nerve terminals, and executes a protective action against kainic acid-induced excitotoxicity in vivo. The findings enhance the understanding of baicalein's action in the brain, and suggest that this natural compound is valuable for treating brain disorders related to glutamate excitotoxicity. PMID:27430911

  18. Alpha-Linolenic Acid-Induced Increase in Neurogenesis is a Key Factor in the Improvement in the Passive Avoidance Task After Soman Exposure.

    PubMed

    Piermartiri, Tetsade C B; Pan, Hongna; Chen, Jun; McDonough, John; Grunberg, Neil; Apland, James P; Marini, Ann M

    2015-09-01

    Exposure to organophosphorous (OP) nerve agents such as soman inhibits the critical enzyme acetylcholinesterase (AChE) leading to excessive acetylcholine accumulation in synapses, resulting in cholinergic crisis, status epilepticus and brain damage in survivors. The hippocampus is profoundly damaged after soman exposure leading to long-term memory deficits. We have previously shown that treatment with three sequential doses of alpha-linolenic acid, an essential omega-3 polyunsaturated fatty acid, increases brain plasticity in naïve animals. However, the effects of this dosing schedule administered after a brain insult and the underlying molecular mechanisms in the hippocampus are unknown. We now show that injection of three sequential doses of alpha-linolenic acid after soman exposure increases the endogenous expression of mature BDNF, activates Akt and the mammalian target of rapamycin complex 1 (mTORC1), increases neurogenesis in the subgranular zone of the dentate gyrus, increases retention latency in the passive avoidance task and increases animal survival. In sharp contrast, while soman exposure also increases mature BDNF, this increase did not activate downstream signaling pathways or neurogenesis. Administration of the inhibitor of mTORC1, rapamycin, blocked the alpha-linolenic acid-induced neurogenesis and the enhanced retention latency but did not affect animal survival. Our results suggest that alpha-linolenic acid induces a long-lasting neurorestorative effect that involves activation of mTORC1 possibly via a BDNF-TrkB-mediated mechanism. PMID:25920465

  19. Use of Activated Carbon in Packaging to Attenuate Formaldehyde-Induced and Formic Acid-Induced Degradation and Reduce Gelatin Cross-Linking in Solid Dosage Forms.

    PubMed

    Colgan, Stephen T; Zelesky, Todd C; Chen, Raymond; Likar, Michael D; MacDonald, Bruce C; Hawkins, Joel M; Carroll, Sophia C; Johnson, Gail M; Space, J Sean; Jensen, James F; DeMatteo, Vincent A

    2016-07-01

    Formaldehyde and formic acid are reactive impurities found in commonly used excipients and can be responsible for limiting drug product shelf-life. Described here is the use of activated carbon in drug product packaging to attenuate formaldehyde-induced and formic acid-induced drug degradation in tablets and cross-linking in hard gelatin capsules. Several pharmaceutical products with known or potential vulnerabilities to formaldehyde-induced or formic acid-induced degradation or gelatin cross-linking were subjected to accelerated stability challenges in the presence and absence of activated carbon. The effects of time and storage conditions were determined. For all of the products studied, activated carbon attenuated drug degradation or gelatin cross-linking. This novel use of activated carbon in pharmaceutical packaging may be useful for enhancing the chemical stability of drug products or the dissolution stability of gelatin-containing dosage forms and may allow for the 1) extension of a drug product's shelf-life when the limiting attribute is a degradation product induced by a reactive impurity, 2) marketing of a drug product in hotter and more humid climatic zones than currently supported without the use of activated carbon, and 3) enhanced dissolution stability of products that are vulnerable to gelatin cross-linking.

  20. Synergic Interaction of Rifaximin and Mutaflor (Escherichia coli Nissle 1917) in the Treatment of Acetic Acid-Induced Colitis in Rats

    PubMed Central

    Warzecha, Zygmunt; Ceranowicz, Piotr; Dembiński, Marcin; Cieszkowski, Jakub; Bulanda, Małgorzata; Kuśnierz-Cabala, Beata; Gałązka, Krystyna; Konturek, Peter Christopher

    2016-01-01

    Background. Inflammatory bowel disease results from the dysregulation of immune response to environmental and microbial agents in genetically susceptible individuals. The aim of the present study was to examine the effect of rifaximin and/or Mutaflor (Escherichia coli Nissle 1917, EcN) administration on the healing of acetic acid-induced colitis. Methods. Colitis was induced in male Wistar rats by rectal enema with 3.5% acetic acid solution. Rifaximin (50 mg/kg/dose) and/or Mutaflor (109 CFU/dose) were given intragastrically once a day. The severity of colitis was assessed at the 8th day after induction of inflammation. Results. Treatment with rifaximin significantly accelerated the healing of colonic damage. This effect was associated with significant reversion of the acetic acid-evoked decrease in mucosal blood flow and DNA synthesis. Moreover, administration of rifaximin significantly reduced concentration of proinflammatory TNF-α and activity of myeloperoxidase in colonic mucosa. Mutaflor given alone was without significant effect on activity of colitis. In contrast, Mutaflor given in combination with rifaximin significantly enhanced therapeutic effect of rifaximin. Moreover, Mutaflor led to settle of the colon by EcN and this effect was augmented by pretreatment with rifaximin. Conclusion. Rifaximin and Mutaflor exhibit synergic anti-inflammatory and therapeutic effect in acetic acid-induced colitis in rats. PMID:27433160

  1. Analgesic, anti-inflammatory and anti-diarrheal activities of ethanolic leaf extract of Typhonium trilobatum L. Schott

    PubMed Central

    Ali, Khadem; Ashraf, Ayesha; Nath Biswas, Nripendra

    2012-01-01

    Objective To explore the efficacy of ethanolic leaf extract of Typhonium trilobatum L. Schott in treating diarrhea, pain and inflammation using experimental models. Methods In the present study, acetic acid-induced writhing, xylene-induced ear edema and castor oil-induced diarrheal model were used to evaluate the analgesic, anti-inflammatory and anti-diarrheal activities, respectively. Acute toxicity test was carried out to fix the safe doses of the plant extract. Results The plant extract demonstrated a significant inhibition of writhing (P<0.01) compared with the control group in acetic acid-induced writhing test in mice. The extract also significantly inhibited the xylene induced ear edema formation (P<0.05). In anti-diarrheal test, the extract significantly decreased the frequency of defecation and increased the mean latent period (P<0.01) in castor oil-induced diarrheal model mice at the doses of 250 and 500 mg/kg body weight. Conclusions These results suggest that the extract possesses significant analgesic, anti-inflammatory and anti-diarrheal activities that support to the ethnopharmacological uses of this plant. PMID:23570002

  2. Confocal Raman micro-spectroscopy for rapid and label-free detection of maleic acid-induced variations in human sperm

    PubMed Central

    Li, Ning; Chen, Diling; Xu, Yan; Liu, Songhao; Zhang, Heming

    2014-01-01

    Confocal Raman microspectroscopy is a valuable analytical tool in biological and medical research, allowing the detection of sample variations without external labels or extensive preparation. To determine whether this method can assess the effect of maleic acid on sperm, we prepared human sperm samples incubated in different concentrations of maleic acid, after which Raman spectra from the various regions of sperm cells were recorded. Following the maleic acid treatment, Raman spectra indicated significant changes. Combined with other means, we found that the structures and chemical compositions of sperm membranes were damaged, and even the sperm DNA was damaged by the incorporation of maleic acid. Thus, this technique can be used for detection and identification of maleic acid-induced changes in human sperm at a molecular level. Although this particular application of Raman microspectroscopy still requires further validation, it has potentially promise as a diagnostic tool for reproductive medicine. PMID:24877025

  3. Yogurt containing Lactobacillus gasseri OLL 2716 (LG21 yogurt) accelerated the healing of acetic acid-induced gastric ulcer in rats.

    PubMed

    Uchida, Masayuki; Shimizu, Kimiko; Kurakazu, Keiko

    2010-01-01

    We have reported that LG21 yogurt containing Lactobacillus gasseri OLL 2716 (LG21 yogurt) inhibits the formation of HCl-induced acute gastric lesions through the generation of prostaglandin E₂. This study aimed to determine the role of viable Lactobacillus in the healing of acetic acid-induced chronic gastric ulcer. LG21 yogurt or γ-ray radiated LG21 yogurt was administered orally twice a day for 10 d at a dose of 5 ml/kg. LG21 yogurt significantly accelerated the healing of the ulcer, but γ-ray radiated LG21 yogurt did not. However, both yogurts significantly inhibited HCl-induced gastric erosive lesions and enhanced the generation of gastric mucosal prostaglandin E₂. From the above results, it was found that viable bacteria are needed to accelerate the healing of chronic gastric ulcer, but not to inhibit gastric lesions.

  4. Chemometrics-assisted Spectrofluorimetric Determination of Two Co-administered Drugs of Major Interaction, Methotrexate and Aspirin, in Human Urine Following Acid-induced Hydrolysis.

    PubMed

    Maher, Hadir M; Ragab, Marwa A A; El-Kimary, Eman I

    2015-01-01

    Methotrexate (MTX) is widely used to treat rheumatoid arthritis (RA), mostly along with non-steroidal anti-inflammatory drugs (NSAIDs), the most common of which is aspirin or acetyl salicylic acid (ASA). Since NSAIDs impair MTX clearance and increase its toxicity, it was necessary to develop a simple and reliable method for the monitoring of MTX levels in urine samples, when coadministered with ASA. The method was based on the spectrofluorimetric measurement of the acid-induced hydrolysis product of MTX, 4-amino-4-deoxy-10-methylpteroic acid (AMP), along with the strongly fluorescent salicylic acid (SA), a product of acid-induced hydrolysis of aspirin and its metabolites in urine. The overlapping emission spectra were resolved using the derivative method (D method). In addition, the corresponding derivative emission spectra were convoluted using discrete Fourier functions, 8-points sin xi polynomials, (D/FF method) for better elimination of interferences. Validation of the developed methods was carried out according to the ICH guidelines. Moreover, the data obtained using derivative and convoluted derivative spectra were treated using the non-parametric Theil's method (NP), compared with the least-squares parametric regression method (LSP). The results treated with Theil's method were more accurate and precise compared with LSP since the former is less affected by the outliers. This work offers the potential of both derivative and convolution using discrete Fourier functions in addition to the effectiveness of using the NP regression analysis of data. The high sensitivity obtained by the proposed methods was promising for measuring low concentration levels of the two drugs in urine samples. These methods were efficiently used to measure the drugs in human urine samples following their co-administration. PMID:26234512

  5. Isobolographic Analysis of the Interaction Between Tapentadol and Ketorolac in a Mouse Model of Visceral Pain.

    PubMed

    Zapata-Morales, Juan R; Aragon-Martinez, Othoniel H; Adriana Soto-Castro, Tely; Alonso-Castro, Ángel J; Castañeda-Santana, Demian I; Isiordia-Espinoza, Mario A

    2016-06-01

    Preclinical Research The aim of this experimental assay was to assess the antinociceptive interaction between tapentadol and ketorolac in the acetic acid-induced writhing model in mice. Tapentadol (5.62-31.6 mg/kg ip) or ketorolac (5.62-31.6 mg/kg ip) were administered 15 min before the acetic acid administration. The ED50 values of the individual drugs were determined and different proportions (tapentadol-ketorolac in 1:1, 3:1, and 1:3) were assayed in combination in the writhing test. Isobolographic analysis and the interaction index demonstrated an antinociceptive synergistic interaction between tapentadol and ketorolac in all combination. Thus, the experimental ED50 values were lower when compared with their theoretical ED50 values. These data suggest that the tapentadol-ketorolac combination produces an antinociceptive synergistic interaction in the mouse acetic acid-induced writhing model. Drug Dev Res 77 : 187-191, 2016.   © 2016 Wiley Periodicals, Inc. PMID:27169518

  6. Isobolographic Analysis of the Interaction Between Tapentadol and Ketorolac in a Mouse Model of Visceral Pain.

    PubMed

    Zapata-Morales, Juan R; Aragon-Martinez, Othoniel H; Adriana Soto-Castro, Tely; Alonso-Castro, Ángel J; Castañeda-Santana, Demian I; Isiordia-Espinoza, Mario A

    2016-06-01

    Preclinical Research The aim of this experimental assay was to assess the antinociceptive interaction between tapentadol and ketorolac in the acetic acid-induced writhing model in mice. Tapentadol (5.62-31.6 mg/kg ip) or ketorolac (5.62-31.6 mg/kg ip) were administered 15 min before the acetic acid administration. The ED50 values of the individual drugs were determined and different proportions (tapentadol-ketorolac in 1:1, 3:1, and 1:3) were assayed in combination in the writhing test. Isobolographic analysis and the interaction index demonstrated an antinociceptive synergistic interaction between tapentadol and ketorolac in all combination. Thus, the experimental ED50 values were lower when compared with their theoretical ED50 values. These data suggest that the tapentadol-ketorolac combination produces an antinociceptive synergistic interaction in the mouse acetic acid-induced writhing model. Drug Dev Res 77 : 187-191, 2016.   © 2016 Wiley Periodicals, Inc.

  7. Bile acids induce glucagon-like peptide 2 secretion with limited effects on intestinal adaptation in early weaned pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Early weaning is a stressful event characterized by a transient period of intestinal atrophy that may be mediated by reduced secretion of glucagon-like peptide (GLP) 2. We tested whether enterally fed bile acids or plant sterols could increase nutrient-dependent GLP-2 secretion and improve intestina...

  8. Developmental Subchronic Exposure to Diphenylarsinic Acid Induced Increased Exploratory Behavior, Impaired Learning Behavior, and Decreased Cerebellar Glutathione Concentration in Rats

    PubMed Central

    Negishi, Takayuki; Matsunaga, Yuki

    2013-01-01

    In Japan, people using water from the well contaminated with high-level arsenic developed neurological, mostly cerebellar, symptoms, where diphenylarsinic acid (DPAA) was a major compound. Here, we investigated the adverse effects of developmental exposure to 20mg/l DPAA in drinking water (early period [0–6 weeks of age] and/or late period [7–12]) on behavior and cerebellar development in male rats. In the open field test at 6 weeks of age, early exposure to DPAA significantly increased exploratory behaviors. At 12 weeks of age, late exposure to DPAA similarly increased exploratory behavior independent of the early exposure although a 6-week recovery from DPAA could reverse that change. In the passive avoidance test at 6 weeks of age, early exposure to DPAA significantly decreased the avoidance performance. Even at 12 weeks of age, early exposure to DPAA significantly decreased the test performance, which was independent of the late exposure to DPAA. These results suggest that the DPAA-induced increase in exploratory behavior is transient, whereas the DPAA-induced impairment of passive avoidance is long lasting. At 6 weeks of age, early exposure to DPAA significantly reduced the concentration of cerebellar total glutathione. At 12 weeks of age, late, but not early, exposure to DPAA also significantly reduced the concentration of cerebellar glutathione, which might be a primary cause of oxidative stress. Early exposure to DPAA induced late-onset suppressed expression of NMDAR1 and PSD95 protein at 12 weeks of age, indicating impaired glutamatergic system in the cerebellum of rats developmentally exposed to DPAA. PMID:24008832

  9. CNS activity of Calotropis gigantea roots.

    PubMed

    Argal, Ameeta; Pathak, Anupam Kumar

    2006-06-15

    Alcoholic extract of peeled roots of Calotropis gigantea R.Br. (Asclepiadaceae) was tested orally in albino rats at the dose level of 250 and 500 mg/kg bodyweight for CNS activity. Prominent analgesic activity was observed in Eddy's hot plate method and acetic acid induced writhings. The paw licking time was delayed and the numbers of writhings were greatly reduced. Significant anticonvulsant activity was seen as there was a delay in the onset of pentylenetetrazole induced convulsions as well as decrease in its severity. The extract treated rats spent more time in the open arm of EPM showing its antianxiety activity. There was a decrease in the locomotor activity. The fall off time (motor coordination) was also decreased. A potentiation in the pentobarbitone-induced sleep due to the sedative effect of the extract was observed. No mortality was seen upto the dose of 1 g/kg. These results show the analgesic, anticonvulsant, anxiolytic and sedative effect of the extract.

  10. A new coumarin derivative, IMM-H004, attenuates okadaic acid-induced spatial memory impairment in rats

    PubMed Central

    Song, Xiu-yun; Wang, Ying-ying; Chu, Shi-feng; Hu, Jin-feng; Yang, Peng-fei; Zuo, Wei; Song, Lian-kun; Zhang, Shuai; Chen, Nai-hong

    2016-01-01

    Aim: A novel coumarin derivative 7-hydroxy-5-methoxy-4-methyl-3-(4-methylpiperazin-1-yl)-coumarin (IMM-H004) has shown anti-apoptotic, anti-inflammatory and neuroprotective activities. In this study we investigated the effects of IMM-H004 on spatial memory in rats treated with okadaic acid (OKA), which was used to imitate Alzheimer's disease (AD)-like symptoms. Methods: SD rats were administered IMM-H004 (8 mg·kg−1·d−1, ig) or donepezil (positive control, 1 mg·kg−1·d−1, ig) for 25 d. On d 8 and 9, OKA (200 ng) was microinjected into the right ventricle. Morris water maze test was used to evaluate the spatial memory impairments. Tau and β-amyloid (Aβ) pathology in the hippocampus was detected using Western blot and immunohistochemistry. TUNEL staining was used to detect cell apoptosis. Results: OKA-treated rats showed significant impairments of spatial memory in Morris water maze test, which were largely reversed by administration of IMM-H004 or donepezil. Furthermore, OKA-treated rats exhibited significantly increased phosphorylation of tau, deposits of Aβ protein and cell apoptosis in the hippocampus, which were also reversed by administration of IMM-H004 or donepezil. Conclusion: Administration of IMM-H004 or donepezil protects rats against OKA-induced spatial memory impairments via attenuating tau or Aβ pathology. Thus, IMM-H004 may be developed as a therapeutic agent for the treatment of AD. PMID:26838073

  11. NADPH Oxidase NOX5-S and Nuclear Factor κB1 Mediate Acid-Induced Microsomal Prostaglandin E Synthase-1 Expression in Barrett’s Esophageal Adenocarcinoma Cells

    PubMed Central

    Zhou, Xiaoxu; Li, Dan; Resnick, Murray B.; Wands, Jack

    2013-01-01

    The mechanisms of progression from Barrett’s esophagus (BE) to esophageal adenocarcinoma (EA) are not known. Cycloxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) has been shown to be important in esophageal tumorigenesis. We have shown that COX-2 mediates acid-induced PGE2 production. The prostaglandin E synthase (PGES) responsible for acid-induced PGE2 production in BE, however, is not known. We found that microsomal PGES1 (mPGES1), mPGES2, and cytosolic PGES (cPGES) were present in FLO EA cells. Pulsed acid treatment significantly increased mPGES1 mRNA and protein levels but had little or no effect on mPGES2 or cPGES mRNA. Knockdown of mPGES1 by mPGES1 small interfering RNA (siRNA) blocked acid-induced increase in PGE2 production and thymidine incorporation. Knockdown of NADPH oxidase, NOX5-S, a variant lacking calcium-binding domains, by NOX5 siRNA significantly inhibited acid-induced increase in mPGES1 expression, thymidine incorporation, and PGE2 production. Overexpression of NOX5-S significantly increased the luciferase activity in FLO cells transfected with a nuclear factor κB (NF-κB) in vivo activation reporter plasmid pNF-κB-Luc. Knockdown of NF-κB1 p50 by p50 siRNA significantly decreased acid-induced increase in mPGES1 expression, thymidine incorporation, and PGE2 production. Two novel NF-κB binding elements, GGAGTCTCCC and CGGGACACCC, were identified in the mPGES1 gene promoter. We conclude that mPGES1 mediates acid-induced increase in PGE2 production and cell proliferation. Acid-induced mPGES1 expression depends on activation of NOX5-S and NF-κB1 p50. Microsomal PGES1 may be a potential target to prevent or treat EA. PMID:23439561

  12. Retinoic acid-induced AP-1 transcriptional activity regulates B16 mouse melanoma growth inhibition and differentiation.

    PubMed

    Huang, Ying; Boskovic, Goran; Niles, Richard M

    2003-02-01

    Retinoic acid (RA) inhibits growth and induces differentiation of B16 mouse melanoma cells. These effects are accompanied by a large increase in PKCalpha mRNA and protein levels and surprisingly an increase in activating protein-1 (AP-1) transcriptional activity. To further investigate the RA-induced AP-1 activity we established clones of B16 cells stably expressing an AP-1-luciferase reporter gene. Treatment of these clones with phorbol dibutyrate increased AP-1 activity which peaked at 2-4 h and returned to baseline level by 24 h. In contrast, RA treatment resulted in a slow increase in AP-1 activity that reached a maximum level at 48 h and was maintained for the duration of the treatment. We tested the importance of the RA-induced AP-1 activity by establishing clones which stably express a dominant negative fos gene (A-fos) and have greatly diminished AP-1 activity. Growth rates of untreated A-fos expressing cells were similar to wt B16 and clones not expressing A-fos. However, clones expressing the dominant-negative fos had a markedly decreased sensitivity to RA-induced inhibition of anchorage-dependent and -independent growth. Treatment of wt B16 cells for 48 h with RA increased melanin production by two to fourfold, but this effect was completely lost in the A-fos clones. The ability of RA to induce RARbeta and PKCalpha expression was retained in A-fos clones, suggesting that A-fos was not interfering with RAR transcription activation functions. We tested whether the RA-induced AP-1 activity might be mediated by the ERK1/2 MAPK pathway. Inhibition of ERK1/2 phosphorylation stimulated AP-1 activity, which was not additive to that induced by RA. This finding raises the possibility that this MAPK pathway may be a target of retinoid action. Our observations suggest that AP-1 transcriptional activity induced by RA likely plays an important role in the biological changes mediated by this retinoid in B16 melanoma cells. PMID:12494454

  13. Inhibitory effect of fangchinoline on excitatory amino acids-induced neurotoxicity in cultured rat cerebellar granule cells.

    PubMed

    Kim, S D; Oh, S K; Kim, H S; Seong, Y H

    2001-04-01

    Glutamate receptors-mediated excitotoxicity is believed to play a role in the pathophysiology of neurodegenerative diseases. The present study was performed to evaluate the inhibitory effect of fangchinoline, a bis-benzylisoquinoline alkaloid, which has a characteristic as a Ca2+ channel blocker, on excitatory amino acids (EAAs)-induced neurotoxicity in cultured rat cerebellar granule neuron. Fangchinoline (1 and 5 microM) inhibited glutamate (1 mM), N-methyl-D-aspartate (NMDA; 1 mM) and kainate (100 microM)-induced neuronal cell death which was measured by trypan blue exclusion test. Fangchinoline (1 and 5 microM) inhibited glutamate release into medium induced by NMDA (1 mM) and kainate (100 microM), which was measured by HPLC. And fangchinoline (5 microM) inhibited glutamate (1 mM)-induced elevation of intracellular calcium concentration. These results suggest that inhibition of Ca2+ influx by fangchinoline may contribute to the beneficial effects on neurodegenerative effect of glutamate in pathophysiological conditions. PMID:11339637

  14. Effect of gums on the rheological characteristics and microstructure of acid-induced SPI-gum mixed gels.

    PubMed

    Chang, Yuan-Yuan; Li, Dong; Wang, Li-Jun; Bi, Chong-Hao; Adhikari, Benu

    2014-08-01

    The effect of addition of xanthan gum (XG) and guar gum (GG) on the rheological properties and microstructure of glucono-δ-lactone induced soy protein isolate (SPI)-XG gels and SPI-GG gels was investigated using steady and dynamic rheological tests, creep-recovery and confocal laser scanning microscopy (CLSM). Results showed that the apparent viscosity of SPI-gum (XG, GG) mixed solutions increased with the increase in the gum (XG, GG) concentration. The storage (G') and loss (G″) moduli of SPI-gum (XG, GG) mixed gels increased in the presence and increase in the gum (XG, GG) concentration. The Burger's model fitted the creep recovery data well (R(2)>0.919) and showed that both the instantaneous and equilibrium (retarded) elastic components of this model increased with the increase in SPI and gum concentrations. The proportion occupied by gum in mixed gels was found to increase with the increase in the concentration of gums which increased the density of protein aggregates in the mixed gels.

  15. Comparative effects of curcumin and its analog on alcohol- and polyunsaturated fatty acid-induced alterations in circulatory lipid profiles.

    PubMed

    Rukkumani, Rajagopalan; Aruna, Kode; Varma, Penumathsa Suresh; Rajasekaran, Kallikat Narayanan; Menon, Venugopal P

    2005-01-01

    Excessive alcohol intake induces hyperlipidemia. Studies suggest that natural principles and their analogs are known to possess anti-hyperlipidemic properties. In the present work we tested the effect of curcumin, an active principle of turmeric (Curcuma longa), and a curcumin analog on alcohol- and thermally oxidized polyunsaturated fatty acid (deltaPUFA)- induced hyperlipidemia. Male albino Wistar rats were used for the experimental study. Anti-hyperlipidemic activity of curcumin and curcumin analog was evaluated by analyzing the levels of cholesterol, triglycerides (TGs), phospholipids (PLs), and free fatty acids (FFAs). The results showed that the levels of cholesterol, TGs, PLs, and FFAs were increased significantly in alcohol-, deltaPUFA-, and alcohol + deltaPUFA-treated groups, which were brought down significantly on treatment with either of the curcuminoids. Curcumin analog treatment was found to be more effective than curcumin treatment. From the results obtained, we conclude that both curcumin and its analog effectively protect the system against alcohol- and deltaPUFA-induced hyperlipidemia and are possible candidates for the treatment of hyperlipidemia.

  16. Protective effects of bupivacaine against kainic acid-induced seizure and neuronal cell death in the rat hippocampus.

    PubMed

    Chiu, Kuan Ming; Wu, Chia Chan; Wang, Ming Jiuh; Lee, Ming Yi; Wang, Su Jane

    2015-01-01

    The excessive release of glutamate is a critical element in the neuropathology of epilepsy, and bupivacaine, a local anesthetic agent, has been shown to inhibit the release of glutamate in rat cerebrocortical nerve terminals. This study investigated whether bupivacaine produces antiseizure and antiexcitotoxic effects using a kainic acid (KA) rat model, an animal model used for temporal lobe epilepsy, and excitotoxic neurodegeneration experiments. The results showed that administering bupivacaine (0.4 mg/kg or 2 mg/kg) intraperitoneally to rats 30 min before intraperitoneal injection of KA (15 mg/kg) increased seizure latency and reduced the seizure score. In addition, bupivacaine attenuated KA-induced hippocampal neuronal cell death, and this protective effect was accompanied by the inhibition of microglial activation and production of proinflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in the hippocampus. Moreover, bupivacaine shortened the latency of escaping onto the platform in the Morris water maze learning performance test. Collectively, these data suggest that bupivacaine has therapeutic potential for treating epilepsy.

  17. Benefits of agomelatine in behavioral, neurochemical and blood brain barrier alterations in prenatal valproic acid induced autism spectrum disorder.

    PubMed

    Kumar, Hariom; Sharma, B M; Sharma, Bhupesh

    2015-12-01

    Valproic acid administration during gestational period causes behavior and biochemical deficits similar to those observed in humans with autism spectrum disorder. Although worldwide prevalence of autism spectrum disorder has been increased continuously, therapeutic agents to ameliorate the social impairment are very limited. The present study has been structured to investigate the therapeutic potential of melatonin receptor agonist, agomelatine in prenatal valproic acid (Pre-VPA) induced autism spectrum disorder in animals. Pre-VPA has produced reduction in social interaction (three chamber social behavior apparatus), spontaneous alteration (Y-Maze), exploratory activity (Hole board test), intestinal motility, serotonin levels (prefrontal cortex and ileum) and prefrontal cortex mitochondrial complex activity (complex I, II, IV). Furthermore, Pre-VPA has increased locomotor activity (actophotometer), anxiety, brain oxidative stress (thiobarbituric acid reactive species, glutathione, and catalase), nitrosative stress (nitrite/nitrate), inflammation (brain and ileum myeloperoxidase activity), calcium levels and blood brain barrier leakage in animals. Treatment with agomelatine has significantly attenuated Pre-VPA induced reduction in social interaction, spontaneous alteration, exploratory activity intestinal motility, serotonin levels and prefrontal cortex mitochondrial complex activity. Furthermore, agomelatine also attenuated Pre-VPA induced increase in locomotion, anxiety, brain oxidative stress, nitrosative stress, inflammation, calcium levels and blood brain barrier leakage. It is concluded that, Pre-VPA has induced autism spectrum disorder, which was attenuated by agomelatine. Agomelatine has shown ameliorative effect on behavioral, neurochemical and blood brain barrier alteration in Pre-VPA exposed animals. Thus melatonin receptor agonists may provide beneficial therapeutic strategy for managing autism spectrum disorder.

  18. Effects of inulin/oligofructose on the thermal stability and acid-induced gelation of soy proteins.

    PubMed

    Tseng, Y-C; Xiong, Y L; Boatright, W L

    2008-03-01

    Differential scanning calorimetry (DSC) and dynamic oscillatory shear testing were performed to study the influence of inulin (Raftiline HP-gel and Raftiline ST-gel) and oligofructose (Raftilose P95) on the thermal stability and gelation (using glucono-delta-lactone [GDL] as a coagulant) of soy protein isolate (SPI) dispersions. Addition of 10% (w/v) inulin/oligofructose or sucrose increased (P < 0.05) the peak denaturation temperatures (T(m)) of 7S and 11S soy proteins in SPI dispersion (5%[w/v], pH 7.0) by an average of 1.9 and 2.3 degrees C, respectively. GDL induced SPI thermal gelation, and the gel rheology was affected by both the pH decline and the specific temperature of heating. Addition of inulin/oligofructose (8%, w/v) improved the gelling properties of preheated SPI dispersion (8%, w/v) coagulated with GDL, showing 14.4 to 45.6% increase (P < 0.05) in gel rigidity (G' value) at the end of heating (81 degrees C). Microstructural examination revealed a denser protein cross-linking structure and reduced pore sizes in SPI gels containing inulin/oligofructose. In general, inulin was more capable of improving SPI gelation than oligofructose, suggesting that the degree of fructose polymerization in the fructans was of thermal and rheological importance.

  19. Nitroxyl inhibits overt pain-like behavior in mice: role of cGMP/PKG/ATP-sensitive potassium channel signaling pathway

    PubMed Central

    Staurengo-Ferrari, Larissa; Zarpelon, Ana C.; Longhi-Balbinot, Daniela T.; Marchesi, Mario; Cunha, Thiago M.; Alves-Filho, José C.; Cunha, Fernando Q.; Ferreira, Sergio H.; Casagrande, Rubia; Miranda, Katrina M.; Verri, Waldiceu A.

    2014-01-01

    Background Several lines of evidence have indicated that nitric oxide (NO) plays complex and diverse roles in modulation of pain/analgesia. However, the roles of charged and uncharged congeners of NO are less well understood. In the present study, the antinociceptive effect of the nitroxyl (HNO) donor, Angeli’s salt (Na2N2O3; AS) was investigated in models of overt pain-like behavior. Moreover, whether the antinociceptive effect of nitroxyl was dependent on the activation of cGMP (cyclic guanosine monophosphate)/PKG (protein kinase G)/ATP-sensitive potassium channels was addressed. Methods The antinociceptive effect of AS was evaluated on phenyl-p-benzoquinone (PBQ)- and acetic acid-induced writhings and via the formalin test. In addition, pharmacological treatments targeting guanylate cyclase (ODQ), PKG (KT5923) and ATP-sensitive potassium channel (glybenclamide) were used. Results PBQ and acetic acid induced significant writhing responses over 20 min. The nociceptive response in these models were significantly reduced in a dose-dependent manner by subcutaneous pre-treatment with AS. Furthermore, AS also inhibited both phases of the formalin test. Subsequently, the inhibitory effect of AS in writhing and flinching responses were prevented by ODQ, KT5823 and glybenclamide, although these inhibitors alone did not alter the writhing score. Furthermore, pretreatment with L-cysteine, an HNO scavenger, confirmed that the antinociceptive effect of AS depends on HNO. Conclusion The present study demonstrates the efficacy of a nitroxyl donor and its analgesic mechanisms in overt pain-like behavior by activating the cGMP/PKG/ATP-sensitive potassium channel (K+) signaling pathway. PMID:24948073

  20. Astaxanthin improves behavioral disorder and oxidative stress in prenatal valproic acid-induced mice model of autism.

    PubMed

    Al-Amin, Md Mamun; Rahman, Md Mahbubur; Khan, Fazlur Rahman; Zaman, Fahmida; Mahmud Reza, Hasan

    2015-06-01

    Prenatal exposure to valproic acid on gestational day 12.5 may lead to the impaired behavior in the offspring, which is similar to the human autistic symptoms. To the contrary, astaxanthin shows neuroprotective effect by its antioxidant mechanism. We aimed to (i) develop mice model of autism and (ii) investigate the effect of astaxanthin on such model animals. Valproic acid (600 mg/kg) was administered intraperitoneally to the pregnant mice on gestational day 12.5. Prenatal valproic acid-exposed mice were divided into 2 groups on postnatal day 25 and astaxanthin (2mg/kg) was given to the experimental group (VPA_AST, n=10) while saline was given to the control group (VPA, n=10) for 4 weeks. Behavioral test including social interaction, open field and hot-plate were conducted on postnatal day 25 and oxidative stress markers such as lipid peroxidation, advanced protein oxidation product, nitric oxide, glutathione, and activity of superoxide dismutase and catalase were estimated on postnatal day 26 to confirm mice model of autism and on postnatal day 56 to assess the effect of astaxanthin. On postnatal day 25, prenatal valproic acid-exposed mice exhibited (i) delayed eye opening (ii) longer latency to respond painful stimuli, (iii) poor sociability and social novelty and (iv) high level of anxiety. In addition, an increased level of oxidative stress was found by determining different oxidative stress markers. Treatment with astaxanthin significantly (p<0.05) improved the behavioral disorder and reduced the oxidative stress in brain and liver. In conclusion, prenatal exposure to valproic day in pregnant mice leads to the development of autism-like features. Astaxanthin improves the impaired behavior in animal model of autism presumably by its antioxidant activity.

  1. Oral Administration of Linoleic Acid Induces New Vessel Formation and Improves Skin Wound Healing in Diabetic Rats

    PubMed Central

    Rodrigues, Hosana G.; Vinolo, Marco A. R.; Sato, Fabio T.; Magdalon, Juliana; Kuhl, Carolina M. C.; Yamagata, Ana S.; Pessoa, Ana Flávia M.; Malheiros, Gabriella; dos Santos, Marinilce F.; Lima, Camila; Farsky, Sandra H.; Camara, Niels O. S.; Williner, Maria R.; Bernal, Claudio A.; Calder, Philip C.; Curi, Rui

    2016-01-01

    Introduction Impaired wound healing has been widely reported in diabetes. Linoleic acid (LA) accelerates the skin wound healing process in non-diabetic rats. However, LA has not been tested in diabetic animals. Objectives We investigated whether oral administration of pure LA improves wound healing in streptozotocin-induced diabetic rats. Methods Dorsal wounds were induced in streptozotocin-induced type-1 diabetic rats treated or not with LA (0.22 g/kg b.w.) for 10 days. Wound closure was daily assessed for two weeks. Wound tissues were collected at specific time-points and used to measure fatty acid composition, and contents of cytokines, growth factors and eicosanoids. Histological and qPCR analyses were employed to examine the dynamics of cell migration during the healing process. Results LA reduced the wound area 14 days after wound induction. LA also increased the concentrations of cytokine-induced neutrophil chemotaxis (CINC-2αβ), tumor necrosis factor-α (TNF-α) and leukotriene B4 (LTB4), and reduced the expression of macrophage chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1 (MIP-1). These results together with the histological analysis, which showed accumulation of leukocytes in the wound early in the healing process, indicate that LA brought forward the inflammatory phase and improved wound healing in diabetic rats. Angiogenesis was induced by LA through elevation in tissue content of key mediators of this process: vascular-endothelial growth factor (VEGF) and angiopoietin-2 (ANGPT-2). Conclusions Oral administration of LA hastened wound closure in diabetic rats by improving the inflammatory phase and angiogenesis. PMID:27764229

  2. Astaxanthin improves behavioral disorder and oxidative stress in prenatal valproic acid-induced mice model of autism.

    PubMed

    Al-Amin, Md Mamun; Rahman, Md Mahbubur; Khan, Fazlur Rahman; Zaman, Fahmida; Mahmud Reza, Hasan

    2015-06-01

    Prenatal exposure to valproic acid on gestational day 12.5 may lead to the impaired behavior in the offspring, which is similar to the human autistic symptoms. To the contrary, astaxanthin shows neuroprotective effect by its antioxidant mechanism. We aimed to (i) develop mice model of autism and (ii) investigate the effect of astaxanthin on such model animals. Valproic acid (600 mg/kg) was administered intraperitoneally to the pregnant mice on gestational day 12.5. Prenatal valproic acid-exposed mice were divided into 2 groups on postnatal day 25 and astaxanthin (2mg/kg) was given to the experimental group (VPA_AST, n=10) while saline was given to the control group (VPA, n=10) for 4 weeks. Behavioral test including social interaction, open field and hot-plate were conducted on postnatal day 25 and oxidative stress markers such as lipid peroxidation, advanced protein oxidation product, nitric oxide, glutathione, and activity of superoxide dismutase and catalase were estimated on postnatal day 26 to confirm mice model of autism and on postnatal day 56 to assess the effect of astaxanthin. On postnatal day 25, prenatal valproic acid-exposed mice exhibited (i) delayed eye opening (ii) longer latency to respond painful stimuli, (iii) poor sociability and social novelty and (iv) high level of anxiety. In addition, an increased level of oxidative stress was found by determining different oxidative stress markers. Treatment with astaxanthin significantly (p<0.05) improved the behavioral disorder and reduced the oxidative stress in brain and liver. In conclusion, prenatal exposure to valproic day in pregnant mice leads to the development of autism-like features. Astaxanthin improves the impaired behavior in animal model of autism presumably by its antioxidant activity. PMID:25732953

  3. Potential of protease inhibitor in 3-nitropropionic acid induced Huntington's disease like symptoms: mitochondrial dysfunction and neurodegeneration.

    PubMed

    Hariharan, Ashwini; Shetty, Shruthi; Shirole, Trupti; Jagtap, Aarti G

    2014-12-01

    Huntington's disease (HD) is a genetic, neurodegenerative disorder mainly characterized by motor dysfunction, cognitive decline and psychiatric disturbances. 3-Nitropropionic acid (3-NP) is an inhibitor of succinate dehydrogenase (Complex II) of the mitochondrial respiratory chain, which thereby reduces production of ATP. It induces neurotoxicity by causing striatal degeneration, energy deficit and oxidative stress. Angiotensin converting enzyme (ACE) is an important protease in the renin angiotensin system (RAS) responsible for the conversion of Angiotensin I to Angiotensin II. Angiotensin-II stimulates mitochondrial oxidant release leading to depression of energy metabolism. ACE inhibitors have shown promise in disorders like stress, anxiety, and depression in addition to showing beneficial effects in cognitive disorders like Alzheimer's. Angiotensin-II inhibition enhances energy production by lowering mitochondrial oxidant production, and hence protects mitochondrial structure. Trandolapril is a centrally active ACE inhibitor. 3-NP administered systematically (20mg/kg, i.p) for 4 days consecutively induced HD like symptoms - loss of body weight, neurobehavioral alterations like memory dysfunction (elevated plus maze, Morris water maze performance), Hind-limb impairment (Narrow beam test), motor incoordination (locomotor activity). Biochemical studies on brain tissue showed increased lipid peroxidation, nitrite levels and acetylcholinesterase activity along with decreased levels of reduced glutathione, catalase activity. Mitochondrial enzyme complex activities (I, II, IV and MTT assay) were found to be significantly lowered in brain mitochondria. Administration of Trandolapril (4 and 6 mg/kg, p.o) daily for 12 days showed significant improvement in body weight, neurobehavioral parameters, oxidative stress and mitochondrial enzyme activities in rat brain. These findings were further confirmed by histopathological studies which showed improvement in 3-NP induced

  4. Suberoyl bishydroxamic acid-induced apoptosis in HeLa cells via ROS-independent, GSH-dependent manner.

    PubMed

    You, Bo Ra; Park, Woo Hyun

    2013-05-01

    Suberoyl bishydroxamic acid (SBHA) is a HDAC inhibitor that can regulate many biological functions including apoptosis and proliferation in various cancer cells. Here, we evaluated the effect of SBHA on the growth of HeLa cervical cancer cells in relation to apoptosis, reactive oxygen species (ROS) and glutathione (GSH) levels. Dose-dependent inhibition of cell growth was observed in HeLa cells with an IC50 of approximately 15 μM at 72 h. SBHA also induced apoptosis in HeLa cells, as evidenced by sub-G1 cells, annexin V-FITC staining cells, activations of caspase 3 and 8, and the loss of mitochondrial membrane potential (ΔΨm). In addition, all of the tested caspase inhibitors rescued some cells from SBHA-induced HeLa cell death. SBHA increased ROS levels including O2(•-) and induced GSH depletion in HeLa cells. Generally, caspase inhibitors did not affect ROS levels in SBHA-treated HeLa cells, but they significantly prevented GSH depletion in these cells. Furthermore, while the well-known antioxidants, N-acetyl cysteine and vitamin C, did not affect cell death, ROS level or GSH depletion in SBHA-treated HeLa cells, L-buthionine sulfoximine, a GSH synthesis inhibitor, enhanced cell death and GSH depletion in these cells. In conclusion, SBHA inhibits the growth of HeLa cervical cancer cells via caspase-dependent apoptosis, and the inhibition is independent of ROS level changes, but dependent on GSH level changes.

  5. Suberoylanilide hydroxamic acid-induced HeLa cell death is closely correlated with oxidative stress and thioredoxin 1 levels.

    PubMed

    You, Bo Ra; Park, Woo Hyun

    2014-05-01

    Suberoylanilide hydroxamic acid (SAHA) is a histone deacetylase (HDAC) inhibitor which has anticancer effects. We evaluated the growth inhibitory effects of SAHA on HeLa cervical cancer cells in relation to reactive oxygen species (ROS) levels. SAHA inhibited the growth of HeLa cells with an IC(50) of approximately 10 µM at 24 h, and induced apoptosis which was accompanied by the cleavage of PARP, caspase-3 activation and loss of mitochondrial membrane potential (MMP; ∆ψ(m)). All the tested caspase inhibitors prevented HeLa cell death induced by SAHA whereas TNF-α intensified apoptotic cell death in SAHA-treated HeLa cells. With respect to ROS and glutathione (GSH) levels, SAHA increased ROS levels, especially mitochondrial O(2)•- in HeLa cells and also induced GSH depletion. Caspase inhibitors reduced the levels of ROS and GSH depletion in SAHA-treated HeLa cells whereas TNF-α enhanced the levels in these cells. The well-known antioxidant N-acetyl cysteine (NAC) attenuated cell death and an increase in ROS levels was caused by SAHA. Moreover, SAHA decreased the levels of thioredoxin 1 (Trx1) in HeLa cells. While the downregulation of Trx1 enhanced cell death and ROS levels in SAHA-treated HeLa cells, the overexpression of Trx1 attenuated the levels in these cells. In conclusion, SAHA inhibited the growth of HeLa cell via caspase-dependent apoptosis, which was influenced by the mitochondrial O(2)•- and Trx1 levels.

  6. Pharmacologic suppression of oxidative damage and dendritic degeneration following kainic acid-induced excitotoxicity in mouse cerebrum.

    PubMed

    Zaja-Milatovic, Snjezana; Gupta, Ramesh C; Aschner, Michael; Montine, Thomas J; Milatovic, Dejan

    2008-07-01

    Intense seizure activity associated with status epilepticus and excitatory amino acid (EAA) imbalance initiates oxidative damage and neuronal injury in CA1 of the ventral hippocampus. We tested the hypothesis that dendritic degeneration of pyramidal neurons in the CA1 hippocampal area resulting from seizure-induced neurotoxicity is modulated by cerebral oxidative damage. Kainic acid (KA, 1 nmol/5 microl) was injected intracerebroventricularly to C57Bl/6 mice. F2-isoprostanes (F2-IsoPs) and F4-neuroprostanes (F4-NeuroPs) were used as surrogate measures of in vivo oxidative stress and biomarkers of lipid peroxidation. Nitric oxide synthase (NOS) activity was quantified by evaluating citrulline level and pyramidal neuron dendrites and spines were evaluated using rapid Golgi stains and a Neurolucida system. KA produced severe seizures in mice immediately after its administration and a significant (p<0.001) increase in F2-IsoPs, F4-NeuroPs and citrulline levels were seen 30 min following treatment. At the same time, hippocampal pyramidal neurons showed significant (p<0.001) reduction in dendritic length and spine density. In contrast, no significant change in neuronal dendrite and spine density or F2-IsoP, F4-NeuroPs and citrulline levels were found in mice pretreated with vitamin E (alpha-tocopherol, 100mg/kg, i.p.) for 3 days, or with N-tert-butyl-alpha-phenylnitrone (PBN, 200mg/kg, i.p.) or ibuprofen (inhibitors of cyclooxygenase, COX, 14 microg/ml of drinking water) for 2 weeks prior to KA treatment. These findings indicate novel interactions among free radical-induced generation of F2-IsoPs and F4-NeuroPs, nitric oxide and dendritic degeneration, closely associate oxidative damage to neuronal membranes with degeneration of the dendritic system, and point to possible interventions to limit severe damage in acute neurological disorders.

  7. Adenoviral expression of 15-lipoxygenase-1 in rabbit aortic endothelium: role in arachidonic acid-induced relaxation.

    PubMed

    Aggarwal, Nitin T; Holmes, Blythe B; Cui, Lijie; Viita, Helena; Yla-Herttuala, Seppo; Campbell, William B

    2007-02-01

    Endothelium-dependent vasorelaxation of the rabbit aorta is mediated by either nitric oxide (NO) or arachidonic acid (AA) metabolites from cyclooxygenase (COX) and 15-lipoxygenase (15-LO) pathways. 15-LO-1 metabolites of AA, 11,12,15-trihydroxyeicosatrienoic acid (THETA), and 15-hydroxy-11,12-epoxyeicosatrienoic acid (HEETA) cause concentration-dependent relaxation. We tested the hypothesis that in the 15-LO pathway of AA metabolism, 15-LO-1 is sufficient and is the rate-limiting step in inducing relaxations in rabbit aorta. Aorta and rabbit aortic endothelial cells were treated with adenoviruses containing human 15-LO-1 cDNA (Ad-15-LO-1) or beta-galactosidase (Ad-beta-Gal). Ad-15-LO-1-transduction increased the expression of a 75-kDa protein corresponding to 15-LO-1, detected by immunoblotting with an anti-human15-LO-1 antibody, and increased the production of HEETA and THETA from [(14)C]AA. Immunohistochemical studies on Ad-15-LO-1-transduced rabbit aorta showed the presence of 15-LO-1 in endothelial cells. Ad-15-LO-1-treated aortic rings showed enhanced relaxation to AA (max 31.7 +/- 3.2%) compared with Ad-beta-Gal-treated (max 12.7 +/- 3.2%) or control nontreated rings (max 13.1 +/- 1.6%) (P < 0.01). The relaxations in Ad-15-LO-1-treated aorta were blocked by the 15-LO inhibitor cinnamyl-3,4-dihydroxy-a-cyanocinnamate. Overexpression of 15-LO-1 in the rabbit aortic endothelium is sufficient to increase the production of the vasodilatory HEETA and THETA and enhance the relaxations to AA. This confirms the role of HEETA and THETA as endothelium-derived relaxing factors.

  8. Potential of protease inhibitor in 3-nitropropionic acid induced Huntington's disease like symptoms: mitochondrial dysfunction and neurodegeneration.

    PubMed

    Hariharan, Ashwini; Shetty, Shruthi; Shirole, Trupti; Jagtap, Aarti G

    2014-12-01

    Huntington's disease (HD) is a genetic, neurodegenerative disorder mainly characterized by motor dysfunction, cognitive decline and psychiatric disturbances. 3-Nitropropionic acid (3-NP) is an inhibitor of succinate dehydrogenase (Complex II) of the mitochondrial respiratory chain, which thereby reduces production of ATP. It induces neurotoxicity by causing striatal degeneration, energy deficit and oxidative stress. Angiotensin converting enzyme (ACE) is an important protease in the renin angiotensin system (RAS) responsible for the conversion of Angiotensin I to Angiotensin II. Angiotensin-II stimulates mitochondrial oxidant release leading to depression of energy metabolism. ACE inhibitors have shown promise in disorders like stress, anxiety, and depression in addition to showing beneficial effects in cognitive disorders like Alzheimer's. Angiotensin-II inhibition enhances energy production by lowering mitochondrial oxidant production, and hence protects mitochondrial structure. Trandolapril is a centrally active ACE inhibitor. 3-NP administered systematically (20mg/kg, i.p) for 4 days consecutively induced HD like symptoms - loss of body weight, neurobehavioral alterations like memory dysfunction (elevated plus maze, Morris water maze performance), Hind-limb impairment (Narrow beam test), motor incoordination (locomotor activity). Biochemical studies on brain tissue showed increased lipid peroxidation, nitrite levels and acetylcholinesterase activity along with decreased levels of reduced glutathione, catalase activity. Mitochondrial enzyme complex activities (I, II, IV and MTT assay) were found to be significantly lowered in brain mitochondria. Administration of Trandolapril (4 and 6 mg/kg, p.o) daily for 12 days showed significant improvement in body weight, neurobehavioral parameters, oxidative stress and mitochondrial enzyme activities in rat brain. These findings were further confirmed by histopathological studies which showed improvement in 3-NP induced

  9. Inhibitors of cyclooxygenase-2, but not cyclooxygenase-1 provide structural and functional protection against quinolinic acid-induced neurodegeneration.

    PubMed

    Salzberg-Brenhouse, Heather C; Chen, Er-Yun; Emerich, Dwaine F; Baldwin, Sam; Hogeland, Ken; Ranelli, Sharon; Lafreniere, Denise; Perdomo, Brigido; Novak, Leah; Kladis, Theodora; Fu, Karen; Basile, Anthony S; Kordower, Jeffrey H; Bartus, Raymond T

    2003-07-01

    Cyclooxygenases (COXs) are implicated in neurodegenerative processes associated with acute and chronic neurological diseases. Given the potential utility of COX inhibitors in treating these disorders, we examined the nonselective COX inhibitor flurbiprofen, the specific COX-1 inhibitor valeryl salicylate (VS), and the COX-2 inhibitor N-[2-(cyclohexyloxy)-4-nitrophenyl]methanesulfonamide (NS-398) for their abilities to protect striatal neurons against a quinolinic acid (QA)-induced excitotoxic lesion. Rats were administered COX inhibitors 10 min before a unilateral QA lesion of the striatum, and then tested 2 to 3 weeks later in a battery of motor tasks (bracing, placing, akinesia, and apomorphine-induced rotations). Lesion volume was assessed using immunohistochemical methods 1 month after lesioning. Orally administered flurbiprofen (50 mg) was highly neuroprotective, preserving 84 to 99% of motor performance (ED50 = 8.6-9.7 mg) while reducing lesion volume 75% (ED50 = 3.2 mg). The identities of the COX isoforms associated with QA-induced neurodegeneration were determined using VS and NS-398. Oral VS was ineffective in virtually all indices of functional neuroprotection. In contrast, oral NS-398 was highly effective, preserving approximately 83% of motor performance at2mg(ED50 = 0.1-0.4 mg), and reducing lesion volume 100% (ED50 = 0.4 mg). Similar results were obtained using inhaled flurbiprofen (2 mg), which preserved 88 to 100% of motor performance while reducing striatal lesion size 92%. These results demonstrate that COX-2 inhibition protects neurons from acute, excitotoxic neurodegeneration. Moreover, formulating a nonselective COX inhibitor into an inhalable preparation dramatically improves its potency in treating acute neuronal damage, a situation where the rapidity of drug delivery and onset of action is critical to clinical efficacy.

  10. Benefits of agomelatine in behavioral, neurochemical and blood brain barrier alterations in prenatal valproic acid induced autism spectrum disorder.

    PubMed

    Kumar, Hariom; Sharma, B M; Sharma, Bhupesh

    2015-12-01

    Valproic acid administration during gestational period causes behavior and biochemical deficits similar to those observed in humans with autism spectrum disorder. Although worldwide prevalence of autism spectrum disorder has been increased continuously, therapeutic agents to ameliorate the social impairment are very limited. The present study has been structured to investigate the therapeutic potential of melatonin receptor agonist, agomelatine in prenatal valproic acid (Pre-VPA) induced autism spectrum disorder in animals. Pre-VPA has produced reduction in social interaction (three chamber social behavior apparatus), spontaneous alteration (Y-Maze), exploratory activity (Hole board test), intestinal motility, serotonin levels (prefrontal cortex and ileum) and prefrontal cortex mitochondrial complex activity (complex I, II, IV). Furthermore, Pre-VPA has increased locomotor activity (actophotometer), anxiety, brain oxidative stress (thiobarbituric acid reactive species, glutathione, and catalase), nitrosative stress (nitrite/nitrate), inflammation (brain and ileum myeloperoxidase activity), calcium levels and blood brain barrier leakage in animals. Treatment with agomelatine has significantly attenuated Pre-VPA induced reduction in social interaction, spontaneous alteration, exploratory activity intestinal motility, serotonin levels and prefrontal cortex mitochondrial complex activity. Furthermore, agomelatine also attenuated Pre-VPA induced increase in locomotion, anxiety, brain oxidative stress, nitrosative stress, inflammation, calcium levels and blood brain barrier leakage. It is concluded that, Pre-VPA has induced autism spectrum disorder, which was attenuated by agomelatine. Agomelatine has shown ameliorative effect on behavioral, neurochemical and blood brain barrier alteration in Pre-VPA exposed animals. Thus melatonin receptor agonists may provide beneficial therapeutic strategy for managing autism spectrum disorder. PMID:26498253

  11. Agathisflavone enhances retinoic acid-induced neurogenesis and its receptors α and β in pluripotent stem cells.

    PubMed

    Paulsen, Bruna S; Souza, Cleide S; Chicaybam, Leonardo; Bonamino, Martin Hernán; Bahia, Marcus; Costa, Silvia Lima; Borges, Helena L; Rehen, Stevens K

    2011-10-01

    Flavonoids have key functions in the regulation of multiple cellular processes; however, their effects have been poorly examined in pluripotent stem cells. Here, we tested the hypothesis that neurogenesis induced by all-trans retinoic acid (RA) is enhanced by agathisflavone (FAB, Caesalpinia pyramidalis Tull). Mouse embryonic stem (mES) cells and induced pluripotent stem (miPS) cells growing as embryoid bodies (EBs) for 4 days were treated with FAB (60 μM) and/or RA (2 μM) for additional 4 days. FAB did not interfere with the EB mitotic rate of mES cells, as evidenced by similar percentages of mitotic figures labeled by phospho-histone H3 in control (3.4% ± 0.4%) and FAB-treated groups (3.5% ± 1.1%). Nevertheless, the biflavonoid reduced cell death in both control and RA-treated EBs from mES cells by almost 2-fold compared with untreated EBs. FAB was unable, by itself, to induce neuronal differentiation in EBs after 4 days of treatment. On the other hand, FAB enhanced neuronal differentiation induced by RA in both EBs of mES and miPS. FAB increased the percentage of nestin-labeled cells by 2.7-fold (mES) and 2.4 (miPS) and β-tubulin III-positive cells by 2-fold (mES) and 2.7 (miPS) in comparison to RA-treated EBs only. FAB increased the expression of RA receptors α and β in mES EBs, suggesting that the availability of RA receptors is limiting RA-induced neurogenesis in pluripotent stem cells. This is the first report to describe that naturally occurring biflavonoids regulate apoptosis and neuronal differentiation in pluripotent stem cells.

  12. Visceral Hypersensitivity Is Provoked by 2,4,6-Trinitrobenzene Sulfonic Acid-Induced Ileitis in Rats

    PubMed Central

    Shah, Manoj K.; Wan, Juan; Janyaro, Habibullah; Tahir, Adnan H.; Cui, Luying; Ding, Ming-Xing

    2016-01-01

    Background and Aims: Crohn’s Disease (CD), a chronic Inflammatory Bowel Disease, can occur in any part of the gastrointestinal tract, but most frequently in the ileum. Visceral hypersensitivity contributes for development of chronic abdominal pain in this disease. Currently, the understanding of the mechanism underlying hypersensitivity of Crohn’s ileitis has been hindered by a lack of specific animal model. The present study is undertaken to investigate the visceral hypersensitivity provoked by 2,4,6-trinitrobenzene sulfonic (TNBS)-induced ileitis rats. Methods: Male Sprague-Dawley rats were anaesthetized and laparotomized for intraileal injection of TNBS (0.6 ml, 80 mg/kg body weight in 30% ethanol, n = 48), an equal volume of 30% Ethanol (n = 24), and Saline (n = 24), respectively. Visceral hypersensitivity was assessed by visceromotor responses (VMR) to 20, 40, 60, 80, and 100 mmHg colorectal distension pressure (CRD) at day 1, 3, 7, 14, 21, and 28. Immediately after CRD test, the rats were euthanized for collecting the terminal ileal segment for histopathological examinations and ELISA of myleoperoxidase and cytokines (TNF-α, IL-1β, IL-6), and dorsal root ganglia (T11) for determination of calcitonin gene-related peptide by immunohistochemistry, respectively. Results: Among all groups, TNBS-treatment showed transmural inflammation initially at 3 days, reached maximum at 7 days and persisted up to 21 days. The rats with ileitis exhibited (P < 0.05) VMR to CRD at day 7 to day 21. The calcitonin gene-related peptide-immunoreactive positive cells increased (P < 0.05) in dorsal root ganglia at day 7 to 21, which was persistently consistent with visceral hypersensitivity in TNBS-treated rats. Conclusion: TNBS injection into the ileum induced transmural ileitis including granuloma and visceral hypersensitivity. As this model mimics clinical manifestations of CD, it may provide a road map to probe the pathogenesis of gut inflammation and visceral

  13. The interaction of induction and repression mechanisms in the regulation of galacturonic acid-induced genes in Aspergillus niger.

    PubMed

    Niu, Jing; Homan, Tim G; Arentshorst, Mark; de Vries, Ronald P; Visser, Jaap; Ram, Arthur F J

    2015-09-01

    Aspergillus niger is an important industrial fungus expressing a broad spectrum of pectinolytic genes. The main constituent of pectin, polygalacturonic acid (PGA), is degraded into galacturonic acid (GA) by the combined activity of endo- and exo-polygalacturonases some of which are specifically induced by GA. The regulatory mechanisms that control the expression of genes encoding PGA-degrading enzymes are not well understood. Based on available genome-wide expression profiles from literature, we selected five genes that were specifically induced by GA. These genes include three exo-polygalacturonases (pgaX, pgxB and pgxC), a GA transporter (gatA), and an intracellular enzyme involved in GA metabolism (gaaB). These five genes contain a conserved motif (5'-TCCNCCAAT-3') in their promoter regions, which we named GARE (galacturonic acid-responsive element). Promoter deletion studies and site-directed mutagenesis of the conserved motif of the pgaX gene showed that the conserved element is required for GA-mediated induction. A set of promoter reporter strains was constructed by fusing the promoter region of the five above-mentioned genes to the amdS reporter gene. Expression of the amdS gene is quantitatively correlated with ability to utilise acetamide as an N-source, hence higher expression of amdS improves growth of the strain on acetamide and therefore can be used as an in vivo reporter for gene expression. Growth analysis of the reporter strains indicated that four genes (pgaX, pgxB, pgxC, and gatA) are specifically induced by GA. The in vivo promoter reporter strains were also used to monitor carbon catabolite repression control. Except for gaaB, all promoter-reporter genes analysed were repressed by glucose in a glucose concentration-dependent way. Interestingly, the strength of glucose repression was different for the tested promoters. CreA is important in mediating carbon catabolite repression as deletion of the creA gene in the reporter strains abolished carbon

  14. Low Na intake suppresses expression of CYP2C23 and arachidonic acid-induced inhibition of ENaC.

    PubMed

    Sun, Peng; Lin, Dao-Hong; Wang, Tong; Babilonia, Elisa; Wang, Zhijian; Jin, Yan; Kemp, Rowena; Nasjletti, Alberto; Wang, Wen-Hui

    2006-12-01

    We previously demonstrated that arachidonic acid (AA) inhibits epithelial Na channels (ENaC) through the cytochrome P-450 (CYP) epoxygenase-dependent pathway (34). In the present study, we tested the hypothesis that low Na intake suppresses the expression of CYP2C23, which is mainly responsible for converting AA to epoxyeicosatrienoic acid (EET) in the kidney (11) and attenuates the AA-induced inhibition of ENaC. Immunostaining showed that CYP2C23 is expressed in the Tamm-Horsfall protein (THP)-positive and aquaporin 2 (AQP2)-positive tubules. This suggests that CYP2C23 is expressed in the thick ascending limb (TAL) and collecting duct (CD). Na restriction significantly suppressed the expression of CYP2C23 in the TAL and CD. Western blot also demonstrated that the expression of CYP2C23 in renal cortex and outer medulla diminished in rats on Na-deficient diet (Na-D) but increased in those on high-Na diet (4%). Moreover, the content of 11,12-epoxyeicosatrienoic acid (EET) decreased in the isolated cortical CD from rats on Na-D compared with those on a normal-Na diet (0.5%). Patch-clamp study showed that application of 15 microM AA inhibited the activity of ENaC by 77% in the CCD of rats on a Na-D for 3 days. However, the inhibitory effect of AA on ENaC was significantly attenuated in rats on Na-D for 14 days. Furthermore, inhibition of CYP epoxygenase with MS-PPOH increased the ENaC activity in the CCD of rats on a control Na diet. We also used microperfusion technique to examine the effect of MS-PPOH on Na transport in the distal nephron. Application of MS-PPOH significantly increased Na absorption in the distal nephron of control rats but had no significant effect on Na absorption in rats on Na-D for 14 days. We conclude that low Na intake downregulates the activity and expression of CYP2C23 and attenuates the inhibitory effect of AA on Na transport. PMID:16849695

  15. Altered vasoactive intestinal peptides expression in irritable bowel syndrome patients and rats with trinitrobenzene sulfonic acid-induced colitis

    PubMed Central

    Del Valle-Pinero, Arseima Y; Sherwin, LeeAnne B; Anderson, Ethan M; Caudle, Robert M; Henderson, Wendy A

    2015-01-01

    AIM: To investigate the vasoactive intestinal peptides (VIP) expression in irritable bowel syndrome (IBS) and trinitrobenzene sulfonic acid (TNBS) induced colitis. METHODS: The VIP gene expression and protein plasma levels were measured in adult participants (45.8% male) who met Rome III criteria for IBS for longer than 6 mo and in a rat model of colitis as induced by TNBS. Plasma and colons were collected from naïve and inflamed rats. Markers assessing inflammation (i.e., weight changes and myeloperoxidase levels) were assessed on days 2, 7, 14 and 28 and compared to controls. Visceral hypersensitivity of the rats was assessed with colo-rectal distension and mechanical threshold testing on hind paws. IBS patients (n = 12) were age, gender, race, and BMI-matched with healthy controls (n = 12). Peripheral whole blood and plasma from fasting participants was collected and VIP plasma levels were assayed using a VIP peptide-enzyme immunoassay. Human gene expression of VIP was analyzed using a custom PCR array. RESULTS: TNBS induced colitis in the rats was confirmed with weight loss (13.7 ± 3.2 g) and increased myeloperoxidase activity. Visceral hypersensitivity to colo-rectal distension was increased in TNBS treated rats up to 21 d and resolved by day 28. Somatic hypersensitivity was also increased up to 14 d post TNBS induction of colitis. The expression of an inflammatory marker myeloperoxidase was significantly elevated in the intracellular granules of neutrophils in rat models following TNBS treatment compared to naïve rats. This confirmed the induction of inflammation in rats following TNBS treatment. VIP plasma concentration was significantly increased in rats following TNBS treatment as compared to naïve animals (P < 0.05). Likewise, the VIP gene expression from peripheral whole blood was significantly upregulated by 2.91-fold in IBS patients when compared to controls (P < 0.00001; 95%CI). VIP plasma protein was not significantly different when compared with

  16. Evidence for genetic regulation of mRNA expression of the dosage-sensitive gene retinoic acid induced-1 (RAI1) in human brain

    PubMed Central

    Chen, Li; Tao, Yu; Song, Fan; Yuan, Xi; Wang, Jian; Saffen, David

    2016-01-01

    RAI1 (retinoic acid induced-1) is a dosage-sensitive gene that causes Smith-Magenis syndrome (SMS) when mutated or deleted and Potocki-Lupski Syndrome (PTLS) when duplicated, with psychiatric features commonly observed in both syndromes. How common genetic variants regulate this gene, however, is unknown. In this study, we found that RAI1 mRNA expression in Chinese prefrontal and temporal cortex correlate with genotypes of common single nucleotide polymorphisms (SNPs) located in the RAI1 5′-upstream region. Using genotype imputation, “R2-Δ2” analysis, and data from the RegulomeDB database, we identified SNPs rs4925102 and rs9907986 as possible regulatory variants, accounting for approximately 30–40% of the variance in RAI1 mRNA expression in both brain regions. Specifically, rs4925102 and rs9907986 are predicted to disrupt the binding of retinoic acid RXR-RAR receptors and the transcription factor DEAF1 (Deformed epidermal autoregulatory factor-1), respectively. Consistent with these predictions, we observed binding of RXRα and RARα to the predicted RAI1 target in chromatin immunoprecipitation assays. Retinoic acid is crucial for early development of the central neural system, and DEAF1 is associated with intellectual disability. The observation that a significant portion of RAI1 mRNA expression is genetically controlled raises the possibility that common RAI1 5′-region regulatory variants contribute more generally to psychiatric disorders. PMID:26743651

  17. Receptor for advanced glycation end products plays a more important role in cellular survival than in neurite outgrowth during retinoic acid-induced differentiation of neuroblastoma cells.

    PubMed

    Sajithlal, Gangadharan; Huttunen, Henri; Rauvala, Heikki; Munch, Gerald

    2002-03-01

    The receptor for advanced glycation end products (RAGE), a member of the immunoglobulin superfamily, is known to interact with amphoterin. This interaction has been proposed to play a role in neurite outgrowth and process elongation during neurodifferentiation. However, there is as yet no direct evidence of the relevance of this pathway to neurodifferentiation under physiological conditions. In this study we have investigated a possible role of RAGE and amphoterin in the retinoic acid-induced differentiation of neuroblastoma cells. The functional inactivation of RAGE by dominant negative and antisense strategies showed that RAGE is not required for process outgrowth or differentiation, although overexpression of RAGE accelerates the elongation of neuritic processes. Using the antisense strategy, amphoterin was shown to be essential for process outgrowth and differentiation, suggesting that amphoterin may interact with other molecules to exert its effect in this context. Interestingly, the survival of the neuroblastoma cells treated with retinoic acid was partly dependent on the expression of RAGE, and inhibition of RAGE function partially blocked the increase in anti-apoptotic protein Bcl-2 following retinoic acid treatment. Based on these results we propose that a combination therapy using RAGE blockers and retinoic acid may prove as a useful approach for chemotherapy for the treatment of neuroblastoma.

  18. The protective effect of myo-inositol on hippocamal cell loss and structural alterations in neurons and synapses triggered by kainic acid-induced status epilepticus.

    PubMed

    Kotaria, Nato; Kiladze, Maia; Zhvania, Mzia G; Japaridze, Nadezhda J; Bikashvili, Tamar; Solomonia, Revaz O; Bolkvadze, Tamar

    2013-07-01

    It is known that myo-inositol pretreatment attenuates the seizure severity and several biochemical changes provoked by experimentally induced status epilepticus. However, it remains unidentified whether such properties of myo-inositol influence the structure of epileptic brain. In the present light and electron microscopic research we elucidate if pretreatment with myo-inositol has positive effect on hippocampal cell loss, and cell and synapses damage provoked by kainic acid-induced status epilepticus. Adult male Wistar rats were treated with (i) saline, (ii) saline + kainic acid, (iii) myo-inositol + kainic acid. Assessment of cell loss at 2, 14, and 30 days after treatment demonstrate cytoprotective effect of myo-inositol in CA1 and CA3 areas. It was strongly expressed in pyramidal layer of CA1, radial and oriental layers of CA3 and in less degree-in other layers of both fields. Ultrastructural alterations were described in CA1, 14 days after treatment. The structure of neurons, synapses, and porosomes are well preserved in the rats pretreated with myo-inositol in comparing with rats treated with only kainic acid.

  19. Retinoic acid-inducible gene-I-like receptor (RLR)-mediated antiviral innate immune responses in the lower respiratory tract: Roles of TRAF3 and TRAF5.

    PubMed

    Chiba, Yuki; Matsumiya, Tomoh; Satoh, Tsugumi; Hayakari, Ryo; Furudate, Ken; Xing, Fei; Yoshida, Hidemi; Tanji, Kunikazu; Mizukami, Hiroki; Imaizumi, Tadaatsu; Ito, Etsuro

    2015-11-13

    Upon viral infection, the cytoplasmic viral sensor retinoic acid-inducible gene-I (RIG-I) recognizes viral RNA to activate antiviral signaling to induce type I interferon (IFN). RIG-I-like receptors (RLRs) activate antiviral signaling in a tissue-specific manner. The molecular mechanism underlying antiviral signaling in the respiratory system remains unclear. We studied antiviral signaling in the lower respiratory tract (LRT), which is the site of many harmful viral infections. Epithelial cells of the LRT can be roughly divided into two groups: bronchial epithelial cells (BECs) and pulmonary alveolar epithelial cells (AECs). These two cell types exhibit different phenotypes; therefore, we hypothesized that these cells may play different roles in antiviral innate immunity. We found that BECs exhibited higher antiviral activity than AECs. TNF receptor-associated factor 3 (TRAF3) has been shown to be a crucial molecule in RLR signaling. The expression levels of TRAF3 and TRAF5, which have conserved domains that are nearly identical, in the LRT were examined. We found that the bronchus exhibited the highest expression levels of TRAF3 and TRAF5 in the LRT. These findings suggest the importance of the bronchus in antiviral innate immunity in the LRT and indicate that TRAF3 and TRAF5 may contribute to RLR signaling. PMID:26454171

  20. Equilibrium titrations of acid-induced unfolding-refolding and salt-induced molten globule of cytochrome c by FT-IR spectroscopy.

    PubMed

    Dong, Aichun; Lam, Troy

    2005-04-01

    Despite extensive investigations on the acid-unfolded and acid/salt-induced molten globule(-like) states of cytochrome c using variety of techniques, structural features of the acid-unfolded state in terms of residual secondary structures and the structural transition between the acid-unfolded and acid/salt-refolded states have not been fully characterized beyond the circular dichroism (CD) spectroscopy. It is unusual that secondary structure(s) of the unfolded state leading to the molten globule state, an important protein folding intermediate, as determined by CD was not fully corroborated by independent experimental method(s). In this study, we carried out an equilibrium titration of acid-induced unfolding and subsequent acid- and salt-induced refolding of cytochrome c using Fourier transform infrared spectroscopy. The spectral profiles of the equilibrium titration reveal new structural details about the acid-unfolded state and the structural transition associated with the acid/salt-refolded molten globule(-like) states of cytochrome c.

  1. Antiviral activity of human oligoadenylate synthetases-like (OASL) is mediated by enhancing retinoic acid-inducible gene I (RIG-I) signaling

    PubMed Central

    Zhu, Jianzhong; Zhang, Yugen; Ghosh, Arundhati; Cuevas, Rolando A.; Forero, Adriana; Dhar, Jayeeta; Ibsen, Mikkel Søes; Schmid-Burgk, Jonathan Leo; Schmidt, Tobias; Ganapathiraju, Madhavi K.; Fujita, Takashi; Hartmann, Rune; Barik, Sailen; Hornung, Veit; Coyne, Carolyn B.; Sarkar, Saumendra N.

    2014-01-01

    SUMMARY Virus infection is sensed in the cytoplasm by retinoic acid-inducible gene I (RIG-I, also known as DDX58), which requires RNA and polyubiquitin binding to induce type I interferon (IFN), and activate cellular innate immunity. We show that the human IFN-inducible oligoadenylate synthetases-like (OASL) protein had antiviral activity and mediated RIG-I activation by mimicking polyubiquitin. Loss of OASL expression reduced RIG-I signaling and enhanced virus replication in human cells. Conversely, OASL expression suppressed replication of a number of viruses in a RIG-I-dependent manner and enhanced RIG-I-mediated IFN induction. OASL interacted and colocalized with RIG-I, and through its C-terminal ubiquitin-like domain specifically enhanced RIG-I signaling. Bone marrow derived macrophages from mice deficient for Oasl2 showed that among the two mouse orthologs of human OASL; Oasl2 is functionally similar to human OASL. Our findings show a mechanism by which human OASL contributes to host antiviral responses by enhancing RIG-I activation. PMID:24931123

  2. Gallic Acid Induces a Reactive Oxygen Species-Provoked c-Jun NH2-Terminal Kinase-Dependent Apoptosis in Lung Fibroblasts

    PubMed Central

    Chen, Chiu-Yuan; Chen, Kun-Chieh; Yang, Tsung-Ying; Liu, Hsiang-Chun; Hsu, Shih-Lan

    2013-01-01

    Idiopathic pulmonary fibrosis is a chronic lung disorder characterized by fibroblasts proliferation and extracellular matrix accumulation. Induction of fibroblast apoptosis therefore plays a crucial role in the resolution of this disease. Gallic acid (3,4,5-trihydroxybenzoic acid), a common botanic phenolic compound, has been reported to induce apoptosis in tumor cell lines and renal fibroblasts. The present study was undertaken to examine the role of mitogen-activated protein kinases (MAPKs) in lung fibroblasts apoptosis induced by gallic acid. We found that treatment with gallic acid resulted in activation of c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and protein kinase B (PKB, Akt), but not p38MAPK, in mouse lung fibroblasts. Inhibition of JNK using pharmacologic inhibitor (SP600125) and genetic knockdown (JNK specific siRNA) significantly inhibited p53 accumulation, reduced PUMA and Fas expression, and abolished apoptosis induced by gallic acid. Moreover, treatment with antioxidants (vitamin C, N-acetyl cysteine, and catalase) effectively diminished gallic acid-induced hydrogen peroxide production, JNK and p53 activation, and cell death. These observations imply that gallic acid-mediated hydrogen peroxide formation acts as an initiator of JNK signaling pathways, leading to p53 activation and apoptosis in mouse lung fibroblasts. PMID:23533505

  3. Elucidation of Acid-induced Unfolding and Aggregation of Human Immunoglobulin IgG1 and IgG2 Fc

    PubMed Central

    Latypov, Ramil F.; Hogan, Sabine; Lau, Hollis; Gadgil, Himanshu; Liu, Dingjiang

    2012-01-01

    Understanding the underlying mechanisms of Fc aggregation is an important prerequisite for developing stable and efficacious antibody-based therapeutics. In our study, high resolution two-dimensional nuclear magnetic resonance (NMR) was employed to probe structural changes in the IgG1 Fc. A series of 1H-15N heteronuclear single-quantum correlation NMR spectra were collected between pH 2.5 and 4.7 to assess whether unfolding of CH2 domains precedes that of CH3 domains. The same pH range was subsequently screened in Fc aggregation experiments that utilized molecules of IgG1 and IgG2 subclasses with varying levels of CH2 glycosylation. In addition, differential scanning calorimetry data were collected over a pH range of 3–7 to assess changes in CH2 and CH3 thermostability. As a result, compelling evidence was gathered that emphasizes the importance of CH2 stability in determining the rate and extent of Fc aggregation. In particular, we found that Fc domains of the IgG1 subclass have a lower propensity to aggregate compared with those of the IgG2 subclass. Our data for glycosylated, partially deglycosylated, and fully deglycosylated molecules further revealed the criticality of CH2 glycans in modulating Fc aggregation. These findings provide important insights into the stability of Fc-based therapeutics and promote better understanding of their acid-induced aggregation process. PMID:22084250

  4. Protective effect of hesperidin and naringin against 3-nitropropionic acid induced Huntington's like symptoms in rats: possible role of nitric oxide.

    PubMed

    Kumar, Puneet; Kumar, Anil

    2010-01-01

    3-Nitropropionic acid (3-NP) is a well known experimental model to study Huntington's disease (HD) and associated neuropsychiatric problems. Present study has been designed to explore the protective effects of hesperidin, naringin, and their nitric oxide mechanism (if any) against 3-nitropropionic acid induced neurotoxicity in rats. Systemic 3-nitropropionic acid (10 mg/kg) treatment for 14 days in rats significantly induced HD like symptoms in rats as indicated by reduced locomotor activity, body weight, grip strength, oxidative defense and mitochondrial complex enzymes (complex-I, -II, and -IV) activities in striatum. Naringin and hesperidin pretreatment significantly attenuated behavioral alterations, oxidative stress and mitochondrial enzymes complex dysfunction in 3-NP treated group. L-Arginine (50 mg/kg) pretreatment with lower dose of hesperidin (50 mg/kg) and naringin (50 mg/kg) significantly attenuated the protective effect of hesperidin and naringin respectively. Whereas L-NAME (10 mg/kg), a non-selective NOS inhibitor pretreatment with hesperidin (50 mg/kg) and naringin (50 mg/kg) significantly potentiated their protective effect which was significant as compared to their effect per se. Study highlights the therapeutic potential of hesperidin and naringin against Huntington's like conditions and further indicates that these drugs might act through nitric oxide mechanism. PMID:19716383

  5. Uric acid induces oxidative stress and growth inhibition by activating adenosine monophosphate-activated protein kinase and extracellular signal-regulated kinase signal pathways in pancreatic β cells.

    PubMed

    Zhang, Yongneng; Yamamoto, Tetsuya; Hisatome, Ichiro; Li, Youfeng; Cheng, Weijie; Sun, Ning; Cai, Bozhi; Huang, Tianliang; Zhu, Yuzhang; Li, Zhi; Jing, Xubin; Zhou, Rui; Cheng, Jidong

    2013-08-15

    Hyperuricaemia is a disorder of purine metabolism, and is strongly associated with insulin resistance and abnormal glucose metabolism. As the producer of insulin, pancreatic β cells might be affected by elevated serum uric acid levels and contribute to the disregulated glucose metabolism. In this study, we investigated the effect of high uric acid on rat pancreatic β cell function. Under high uric acid condition, proliferation of pancreatic β cells was inhibited, production of reactive oxygen species increased, and glucose stimulated insulin secretion was also compromised. Further examination on signal transduction pathways revealed that uric acid-induced ROS is involved in the activation of adenosine monophosphate-activated protein kinase (AMPK), and extracellular signal-regulated kinase (ERK). Pharmacological inhibition of ERK activation rescued β cells from growth inhibition. More importantly, activation of ERK induced by uric acid is significantly diminished by AMPK inhibitor, indicating ERK as a downstream target of AMPK in response to high uric acid condition. We also investigated the transportation channel for uric acid into pancreatic β cells. While major urate transporter URAT1 is not expressed in β cells, organic anion transporter (OAT) inhibitor successfully blocked the activation of ERK by uric acid. Our data indicate that high uric acid levels induce oxidative damage and inhibit growth of rat pancreatic β cells by activating the AMPK and ERK signal pathways. Hyperuricemia may contribute to abnormal glucose metabolism by causing oxidative damage and function inhibition of pancreatic β cells.

  6. Alkali- or acid-induced changes in structure, moisture absorption ability and deacetylating reaction of β-chitin extracted from jumbo squid (Dosidicus gigas) pens.

    PubMed

    Jung, Jooyeoun; Zhao, Yanyun

    2014-01-01

    Alkali- or acid-induced structural modifications in β-chitin from squid (Dosidicus gigas, d'Orbigny, 1835) pens and their moisture absorption ability (MAA) and deacetylating reaction were investigated and compared with α-chitin from shrimp shells. β-Chitin was converted into the α-form after 3h in 40% NaOH or 1-3 h in 40% HCl solution, and α-chitin obtained from NaOH treatment had higher MAA than had native α-chitin, due to polymorphic destructions. In contrast, induced α-chitin from acid treatment of β-chitin had few polymorphic modifications, showing no significant change (P>0.05) in MAA. β-Chitin was more susceptible to alkali deacetylation than was α-chitin, and required a lower concentration of NaOH and shorter reaction time. These results demonstrate that alkali- or acid-treated β-chitin retained high susceptibility toward solvents, which in turn resulted in good biological activity of β-chitosan for use as a natural antioxidant and antimicrobial substance or application as edible coatings and films for various food applications.

  7. Neurotropic components from star anise (Illicium verum Hook. fil.)

    PubMed

    Nakamura, T; Okuyama, E; Yamazaki, M

    1996-10-01

    Three new neurotropic sesquiterpenoids, veranisatins A, B and C, were isolated from star anise (Illicium verum Hook. fil., Illiciaceae). Veranisatins showed convulsion and lethal toxicity in mice at a dose of 3 mg/kg (p.o.), and at lower doses they caused hypothermia. Veranisatin A and the related compound, anisatin, were tested for the other pharmacological activities such as locomotor activity and analgesic effect. Both compounds decreased the locomotion enhanced by methamphetamine at oral doses of 0.1 and 0.03 mg/kg, respectively, and demonstrated the analgesia on acetic acid-induced writhing and tail pressure pain at almost similar doses.

  8. Antinociceptive Grayanoids from the Roots of Rhododendron molle.

    PubMed

    Li, Yong; Liu, Yun-Bao; Zhang, Jian-Jun; Liu, Yang; Ma, Shuang-Gang; Qu, Jing; Lv, Hai-Ning; Yu, Shi-Shan

    2015-12-24

    Nine new grayanoids (1-9), together with 11 known compounds, were isolated from the roots of Rhododendron molle. The structures of the new compounds (1-9) were determined on the basis of spectroscopic analysis, including HRESIMS, and 1D and 2D NMR data. Compounds 4, 6, 12, and 14-20 showed significant antinociceptive activities in an acetic acid-induced writhing test. In particular, 14 and 15 were found to be more potent than morphine for both acute and inflammatory pain models and 100-fold more potent than gabapentin in a diabetic neuropathic pain model. PMID:26599832

  9. Critical Role of IRF-3 in the Direct Regulation of dsRNA-Induced Retinoic Acid-Inducible Gene-I (RIG-I) Expression

    PubMed Central

    Hayakari, Ryo; Matsumiya, Tomoh; Xing, Fei; Yoshida, Hidemi; Hayakari, Makoto; Imaizumi, Tadaatsu

    2016-01-01

    The cytoplasmic viral sensor retinoic acid-inducible gene-I (RIG-I), which is also known as an IFN-stimulated gene (ISG), senses viral RNA to activate antiviral signaling. It is therefore thought that RIG-I is regulated in a STAT1-dependent manner. Although RIG-I-mediated antiviral signaling is indispensable for the induction of an appropriate adaptive immune response, the mechanism underlying the regulation of RIG-I expression remains elusive. Here, we examined the direct regulation of RIG-I expression by interferon regulatory factor 3 (IRF-3), which is an essential molecule for antiviral innate immunity. We initially found that RIG-I can be induced by dsRNA in both IFN-independent and IRF-3-dependent manners. A sequence analysis revealed that the RIG-I gene has putative IRF-3-binding sites in its promoter region. Using a combination of cellular, molecular biological, and mutational approaches, we first showed that IRF-3 can directly regulate the expression of RIG-I via a single IRF-element (IRF-E) site in the proximal promoter region of the RIG-I gene in response to dsRNA. IRF-3 is considered a master regulator in antiviral signaling for the generation of type I interferons (IFNs). Thus, our findings demonstrate that RIG-I expression induced by the IRF-3-mediated pathway may serve as a crucial antiviral factor for reinforcing a surveillance system against viral invasion through the regulation of the cytoplasmic viral sensor RIG-I. PMID:27662626

  10. Hepatitis C Virus Frameshift/Alternate Reading Frame Protein Suppresses Interferon Responses Mediated by Pattern Recognition Receptor Retinoic-Acid-Inducible Gene-I

    PubMed Central

    Park, Seung Bum; Seronello, Scott; Mayer, Wasima; Ojcius, David M.

    2016-01-01

    Hepatitis C virus (HCV) actively evades host interferon (IFN) responses but the mechanisms of how it does so are not completely understood. In this study, we present evidence for an HCV factor that contributes to the suppression of retinoic-acid-inducible gene-I (RIG-I)-mediated IFN induction. Expression of frameshift/alternate reading frame protein (F/ARFP) from HCV -2/+1 frame in Huh7 hepatoma cells suppressed type I IFN responses stimulated by HCV RNA pathogen-associated molecular pattern (PAMP) and poly(IC). The suppression occurred independently of other HCV factors; and activation of interferon stimulated genes, TNFα, IFN-λ1, and IFN-λ2/3 was likewise suppressed by HCV F/ARFP. Point mutations in the full-length HCV sequence (JFH1 genotype 2a strain) were made to introduce premature termination codons in the -2/+1 reading frame coding for F/ARFP while preserving the original reading frame, which enhanced IFNα and IFNβ induction by HCV. The potentiation of IFN response by the F/ARFP mutations was diminished in Huh7.5 cells, which already have a defective RIG-I, and by decreasing RIG-I expression in Huh7 cells. Furthermore, adding F/ARFP back via trans-complementation suppressed IFN induction in the F/ARFP mutant. The F/ARFP mutants, on the other hand, were not resistant to exogenous IFNα. Finally, HCV-infected human liver samples showed significant F/ARFP antibody reactivity, compared to HCV-uninfected control livers. Therefore, HCV F/ARFP likely cooperates with other viral factors to suppress type I and III IFN induction occurring through the RIG-I signaling pathway. This study identifies a novel mechanism of pattern recognition receptor modulation by HCV and suggests a biological function of the HCV alternate reading frame in the modulation of host innate immunity. PMID:27404108

  11. Music application alleviates short-term memory impairments through increasing cell proliferation in the hippocampus of valproic acid-induced autistic rat pups.

    PubMed

    Lee, Sung-Min; Kim, Bo-Kyun; Kim, Tae-Woon; Ji, Eun-Sang; Choi, Hyun-Hee

    2016-06-01

    Autism is a neurodevelopmental disorder and this disorder shows impairment in reciprocal social interactions, deficits in communication, and restrictive and repetitive patterns of behaviors and interests. The effect of music on short-term memory in the view of cell proliferation in the hippocampus was evaluated using valproic acid-induced autistic rat pups. Animal model of autism was made by subcutaneous injection of 400-mg/kg valproic acid into the rat pups on the postnatal day 14. The rat pups in the music-applied groups were exposed to the 65-dB comfortable classic music for 1 hr once a day, starting postnatal day 15 and continued until postnatal day 28. In the present results, short-term memory was deteriorated by autism induction. The numbers of 5-bromo-2'-deoxyridine (BrdU)-positive, Ki-67-positive, and doublecortin (DCX)-positive cells in the hippocampal dentate gyrus were decreased by autism induction. Brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) expressions in the hippocampus were also suppressed in the autistic rat pups. Music application alleviated short-term memory deficits with enhancing the numbers of BrdU-positive, Ki-67-positive, and DCX-positive cells in the autistic rat pups. Music application also enhanced BDNF and TrkB expressions in the autistic rat pups. The present study show that application of music enhanced hippocampal cell proliferation and alleviated short-term memory impairment through stimulating BDNF-TrkB signaling in the autistic rat pups. Music can be suggested as the therapeutic strategy to overcome the autism-induced memory deficits. PMID:27419108

  12. Music application alleviates short-term memory impairments through increasing cell proliferation in the hippocampus of valproic acid-induced autistic rat pups

    PubMed Central

    Lee, Sung-Min; Kim, Bo-Kyun; Kim, Tae-Woon; Ji, Eun-Sang; Choi, Hyun-Hee

    2016-01-01

    Autism is a neurodevelopmental disorder and this disorder shows impairment in reciprocal social interactions, deficits in communication, and restrictive and repetitive patterns of behaviors and interests. The effect of music on short-term memory in the view of cell proliferation in the hippocampus was evaluated using valproic acid-induced autistic rat pups. Animal model of autism was made by subcutaneous injection of 400-mg/kg valproic acid into the rat pups on the postnatal day 14. The rat pups in the music-applied groups were exposed to the 65-dB comfortable classic music for 1 hr once a day, starting postnatal day 15 and continued until postnatal day 28. In the present results, short-term memory was deteriorated by autism induction. The numbers of 5-bromo-2′-deoxyridine (BrdU)-positive, Ki-67-positive, and doublecortin (DCX)-positive cells in the hippocampal dentate gyrus were decreased by autism induction. Brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) expressions in the hippocampus were also suppressed in the autistic rat pups. Music application alleviated short-term memory deficits with enhancing the numbers of BrdU-positive, Ki-67-positive, and DCX-positive cells in the autistic rat pups. Music application also enhanced BDNF and TrkB expressions in the autistic rat pups. The present study show that application of music enhanced hippocampal cell proliferation and alleviated short-term memory impairment through stimulating BDNF-TrkB signaling in the autistic rat pups. Music can be suggested as the therapeutic strategy to overcome the autism-induced memory deficits. PMID:27419108

  13. Purple sweet potato color attenuates domoic acid-induced cognitive deficits by promoting estrogen receptor-α-mediated mitochondrial biogenesis signaling in mice.

    PubMed

    Lu, Jun; Wu, Dong-mei; Zheng, Yuan-lin; Hu, Bin; Cheng, Wei; Zhang, Zi-feng

    2012-02-01

    Recent findings suggest that endoplasmic reticulum stress may be involved in the pathogenesis of domoic acid-induced neurodegeneration. Purple sweet potato color, a class of naturally occurring anthocyanins, has beneficial health and biological effects. Recent studies have also shown that anthocyanins have estrogenic activity and can enhance estrogen receptor-α expression. In this study, we evaluated the effect of purple sweet potato color on cognitive deficits induced by hippocampal mitochondrial dysfunction in domoic acid-treated mice and explored the potential mechanisms underlying this effect. Our results showed that the oral administration of purple sweet potato color to domoic acid-treated mice significantly improved their behavioral performance in a step-through passive avoidance task and a Morris water maze task. These improvements were mediated, at least in part, by a stimulation of estrogen receptor-α-mediated mitochondrial biogenesis signaling and by decreases in the expression of p47phox and gp91phox. Decreases in reactive oxygen species and protein carbonylation were also observed, along with a blockade of the endoplasmic reticulum stress pathway. Furthermore, purple sweet potato color significantly suppressed endoplasmic reticulum stress-induced apoptosis, which prevented neuron loss and restored the expression of memory-related proteins. However, knockdown of estrogen receptor-α using short hairpin RNA only partially blocked the neuroprotective effects of purple sweet potato color in the hippocampus of mice cotreated with purple sweet potato color and domoic acid, indicating that purple sweet potato color acts through multiple pathways. These results suggest that purple sweet potato color could be a possible candidate for the prevention and treatment of cognitive deficits in excitotoxic and other brain disorders.

  14. Muscovy duck retinoic acid-induced gene I (MdRIG-I) functions in innate immunity against H9N2 avian influenza viruses (AIV) infections.

    PubMed

    Cheng, Yuqiang; Huang, Qingqing; Ji, Wenhui; Du, Bin; Fu, Qiang; An, Huiting; Li, Jing; Wang, Hengan; Yan, Yaxian; Ding, Chan; Sun, Jianhe

    2015-02-15

    Retinoic acid inducible gene I (RIG-I) is a cytosolic pattern recognition receptor that senses pathogen-associated molecular patterns (PAMPs). Muscovy duck (Cairina moschata) is a large duck different from other species of ducks, and is more susceptible to some microbial pathogens. In this study, the Muscovy duck RIG-I gene (MdRIG-I) was identified. Quantitative RT-PCR showed that MdRIG-I mRNA was widely expressed in different tissues, especially in those with mucosa. RIG-I null DF-1 cells transfected with DNA constructs encoding MdRIG-I or CARDs domain can activate IRF-3 and NF-κB to up-regulated activity of IFN-β promoter. The components of the signaling pathway downstream of RIG-I in mammalian cells including IRF-3, NF-κB, IFN-β and the IFN-stimulated genes Mx-1, PKR and MDA5 were significantly up-regulated in CARDs-overexpressing-DF-1 cells. Implicating RIG-I in the antiviral response to an infection in vivo, we found that RIG-I expression in brain, spleen, lung and bursa were up-regulated in ducks challenged with H9N2 avian influenza virus (AIV), whose six internal genes were closely related to the H7N9 and H10N8 AIV. In vitro, DF-1 cells transfected with MdRIG-I plasmid can respond significantly to H9N2 AIV, evident through enhancement of IFN-β promoter activity and decreased virus titer. Altogether, these results indicated that MdRIG-I is a novel member of RLR gene family, engaging in the early stage of antiviral innate immunity.

  15. The histone deacetylase inhibitor suberoylanilide hydroxamic acid induces apoptosis, down-regulates the CXCR4 chemokine receptor and impairs migration of chronic lymphocytic leukemia cells

    PubMed Central

    Stamatopoulos, Basile; Meuleman, Nathalie; De Bruyn, Cécile; Delforge, Alain; Bron, Dominique; Lagneaux, Laurence

    2010-01-01

    Background Chronic lymphocytic leukemia is a neoplastic disorder that arises largely as a result of defective apoptosis leading to chemoresistance. Stromal cell-derived factor-1 and its receptor, CXCR4, have been shown to play an important role in chronic lymphocytic leukemia cell trafficking and survival. Design and Methods Since histone acetylation is involved in the modulation of gene expression, we evaluated the effects of suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, on chronic lymphocytic leukemia cells and in particular on cell survival, CXCR4 expression, migration, and drug sensitization. Results Here, we showed that treatment with suberoylanilide hydroxamic acid (20 μM) for 48 hours induced a decrease in chronic lymphocytic leukemia cell viability via apoptosis (n=20, P=0.0032). Using specific caspase inhibitors, we demonstrated the participation of caspases-3, -6 and -8, suggesting an activation of the extrinsic pathway. Additionally, suberoylanilide hydroxamic acid significantly decreased CXCR4 mRNA (n=10, P=0.0010) and protein expression (n=40, P<0.0001). As a result, chronic lymphocytic leukemia cell migration in response to stromal cell-derived factor-1 (n=23, P<0.0001) or through bone marrow stromal cells was dramatically impaired. Consequently, suberoylanilide hydroxamic acid reduced the protective effect of the microenvironment and thus sensitized chronic lymphocytic leukemia cells to chemotherapy such as fludarabine. Conclusions In conclusion, suberoylanilide hydroxamic acid induces apoptosis in chronic lymphocytic leukemia cells via the extrinsic pathway and down-regulates CXCR4 expression leading to decreased cell migration. Suberoylanilide hydroxamic acid in combination with other drugs represents a promising therapeutic approach to inhibiting migration, chronic lymphocytic leukemia cell survival and potentially overcoming drug resistance. PMID:20145270

  16. Gibberellic Acid-Induced Aleurone Layers Responding to Heat Shock or Tunicamycin Provide Insight into the N-Glycoproteome, Protein Secretion, and Endoplasmic Reticulum Stress1[W

    PubMed Central

    Barba-Espín, Gregorio; Dedvisitsakul, Plaipol; Hägglund, Per; Svensson, Birte; Finnie, Christine

    2014-01-01

    The growing relevance of plants for the production of recombinant proteins makes understanding the secretory machinery, including the identification of glycosylation sites in secreted proteins, an important goal of plant proteomics. Barley (Hordeum vulgare) aleurone layers maintained in vitro respond to gibberellic acid by secreting an array of proteins and provide a unique system for the analysis of plant protein secretion. Perturbation of protein secretion in gibberellic acid-induced aleurone layers by two independent mechanisms, heat shock and tunicamycin treatment, demonstrated overlapping effects on both the intracellular and secreted proteomes. Proteins in a total of 22 and 178 two-dimensional gel spots changing in intensity in extracellular and intracellular fractions, respectively, were identified by mass spectrometry. Among these are proteins with key roles in protein processing and secretion, such as calreticulin, protein disulfide isomerase, proteasome subunits, and isopentenyl diphosphate isomerase. Sixteen heat shock proteins in 29 spots showed diverse responses to the treatments, with only a minority increasing in response to heat shock. The majority, all of which were small heat shock proteins, decreased in heat-shocked aleurone layers. Additionally, glycopeptide enrichment and N-glycosylation analysis identified 73 glycosylation sites in 65 aleurone layer proteins, with 53 of the glycoproteins found in extracellular fractions and 36 found in intracellular fractions. This represents major progress in characterization of the barley N-glycoproteome, since only four of these sites were previously described. Overall, these findings considerably advance knowledge of the plant protein secretion system in general and emphasize the versatility of the aleurone layer as a model system for studying plant protein secretion. PMID:24344171

  17. Gambogic Acid Induces Apoptosis in Imatinib-Resistant Chronic Myeloid Leukemia Cells via Inducing Proteasome Inhibition and Caspase-Dependent Bcr-Abl Downregulation

    PubMed Central

    Shi, Xianping; Chen, Xin; Li, Xiaofen; Lan, Xiaoying; Zhao, Chong; Liu, Shouting; Huang, Hongbiao; Liu, Ningning; Liao, Siyan; Song, Wenbin; Zhou, Ping; Wang, Shunqing; Xu, Li; Wang, Xuejun; Dou, Q. Ping; Liu, Jinbao

    2014-01-01

    Purpose Chronic myelogenous leukemia (CML) is characterized by the constitutive activation of Bcr-Abl tyrosine kinase. Bcr-Abl-T315I is the predominant mutation that causes resistance to imatinib, cytotoxic drugs, and the second-generation tyrosine kinase inhibitors. The emergence of imatinib resistance in patients with CML leads to searching for novel approaches to the treatment of CML. Gambogic acid, a small molecule derived from Chinese herb gamboges, has been approved for phase II clinical trial for cancer therapy by the Chinese Food and Drug Administration (FDA). In this study, we investigated the effect of gambogic acid on cell survival or apoptosis in CML cells bearing Bcr-Abl-T315I or wild-type Bcr-Abl. Experimental Design CML cell lines (KBM5, KBM5-T315I, and K562), primary cells from patients with CML with clinical resistance to imatinib, and normal monocytes from healthy volunteers were treated with gambogic acid, imatinib, or their combination, followed by measuring the effects on cell growth, apoptosis, and signal pathways. The in vivo antitumor activity of gambogic acid and its combination with imatinib was also assessed with nude xenografts. Results Gambogic acid induced apoptosis and cell proliferation inhibition in CML cells and inhibited the growth of imatinib-resistant Bcr-Abl-T315I xenografts in nude mice. Our data suggest that GA-induced proteasome inhibition is required for caspase activation in both imatinib-resistant and -sensitive CML cells, and caspase activation is required for gambogic acid–induced Bcr-Abl downregulation and apoptotic cell death. Conclusions These findings suggest an alternative strategy to overcome imatinib resistance by enhancing Bcr-Abl downregulation with the medicinal compound gambogic acid, which may have great clinical significance in imatinib-resistant cancer therapy. PMID:24334603

  18. Effects of Abscisic Acid and Ethylene on the Gibberellic Acid-Induced Synthesis of α-Amylase by Isolated Wheat Aleurone Layers 1

    PubMed Central

    Varty, Keith; Arreguín, Barbarín L.; Gómez, Miguel T.; López, Pablo Jaime T.; Gómez, Miguel Angel L.

    1983-01-01

    Gibberellic acid-induced α-amylase synthesis in wheat aleurone layers (Triticum aestivum L. var Potam S-70) escaped from transcriptional control 30 h after addition of the hormone, as evidenced by the tissue's loss of susceptibility to cordycepin. Abscisic acid inhibited the accumulation of α-amylase activity when added to the tissue during this cordycepin-insensitive phase of enzyme induction. α-Amylase synthesis was not restored by the addition of cordycepin, indicating that the response to abscisic acid was not dependent upon the continuous synthesis of a short lived RNA. When ethylene was added simultaneously or some time after abscisic acid, the accumulation of α-amylase activity was sustained or quickly restored. The loss of susceptibility to cordycepin was completely prevented when aleurone layers were incubated with a combination of gibberellic and abscisic acids from the start of the induction period. This effect of abscisic acid was not reversed by ethylene. On the basis of these observations, it is suggested that abscisic acid inhibits both the transcription and translation of α-amylase mRNA, and that only the latter site of action is susceptible to reversal by ethylene. The rate of incorporation of [methyl-14C]choline into phospholipids was also inhibited by abscisic acid. Ethylene reversed this effect. The effects of abscisic acid and ethylene on phospholipid synthesis were not dependent upon the presence of gibberellic acid. No direct relationship was found between the control of α-amylase synthesis and membrane formation by abscisic acid and ethylene. PMID:16663284

  19. Calcium-dependent nitric oxide production is involved in the cytoprotective properties of n-acetylcysteine in glycochenodeoxycholic acid-induced cell death in hepatocytes

    SciTech Connect

    Gonzalez-Rubio, Sandra; Linares, Clara I.; Bello, Rosario I.; Gonzalez, Raul; Ferrin, Gustavo; Hidalgo, Ana B.; Munoz-Gomariz, Elisa; Rodriguez, Blanca A.; Barrera, Pilar; Ranchal, Isidora; Duran-Prado, Mario; De la Mata, Manuel; Muntane, Jordi

    2010-01-15

    The intracellular oxidative stress has been involved in bile acid-induced cell death in hepatocytes. Nitric oxide (NO) exerts cytoprotective properties in glycochenodeoxycholic acid (GCDCA)-treated hepatocytes. The study evaluated the involvement of Ca{sup 2+} on the regulation of NO synthase (NOS)-3 expression during N-acetylcysteine (NAC) cytoprotection against GCDCA-induced cell death in hepatocytes. The regulation of Ca{sup 2+} pools (EGTA or BAPTA-AM) and NO (L-NAME or NO donor) production was assessed during NAC cytoprotection in GCDCA-treated HepG2 cells. The stimulation of Ca{sup 2+} entrance was induced by A23187 in HepG2. Cell death, Ca{sup 2+} mobilization, NOS-1, -2 and -3 expression, AP-1 activation, and NO production were evaluated. GCDCA reduced intracellular Ca{sup 2+} concentration and NOS-3 expression, and enhanced cell death in HepG2. NO donor prevented, and L-NAME enhanced, GCDCA-induced cell death. The reduction of Ca{sup 2+} entry by EGTA, but not its release from intracellular stores by BAPTA-AM, enhanced cell death in GCDCA-treated cells. The stimulation of Ca{sup 2+} entrance by A23187 reduced cell death and enhanced NOS-3 expression in GCDCA-treated HepG2 cells. The cytoprotective properties of NAC were related to the recovery of intracellular Ca{sup 2+} concentration, NOS-3 expression and NO production induced by GCDCA-treated HepG2 cells. The increase of NO production by Ca{sup 2+}-dependent NOS-3 expression during NAC administration reduces cell death in GCDCA-treated hepatocytes.

  20. Comparative analysis of transcriptional profiles of retinoic-acid-induced gene I-like receptors and interferons in seven tissues from ducks infected with avian Tembusu virus.

    PubMed

    Fu, Guanghua; Chen, Cuiteng; Huang, Yu; Cheng, Longfei; Fu, Qiuling; Wan, Chunhe; Shi, Shaohua; Chen, Hongmei; Liu, Wei

    2016-01-01

    Avian Tembusu virus (ATV), an emerging virus that mainly infects laying and breeding ducks in China, has caused severe economic loss in duck industry. However, there have been no reports about host innate immune responses during ATV infection and its correlation with clinical signs or pathology. To identify the roles of these immune factors in the innate host response to ATV infection, quantitative real-time PCR (qPCR) was used to analyze the transcriptional profiles on the genes encoding two retinoic-acid-induced gene I (RIG-I)-like receptors (RLRs) and two interferons (INF-α and INF-γ) in seven tissues of an ATV-infected shelduck. After infection with ATV, both RLR genes were significantly upregulated (P < 0.05) in all seven tissues. The peak expression levels of the two RLR genes were observed at 24 hours postinfection (hpi) and were higher in non-lymphoid tissues (liver, lung, kidney, and ovary) than in lymphoid tissues (thymus, spleen and bursa). Although the transcription levels of both IFN genes were also upregulated, they showed different time-dependent expression patterns compared with those of the RLR genes. In addition, the highest mRNA expression of the two IFN genes was observed in the ovary at 6 hpi. This observation suggests that the ovary is the primary target tissue in ATV infection and explains the clinical characteristics of the primary pathological changes in the ovaries of ATV-infected ducks. Our results, for the first time, elucidate the differential and coordinated expression profiles of two RLRs and two IFNs in an ATV-infected shelduck.

  1. Identification of a retinoic acid-inducible gene I from Japanese eel (Anguilla japonica) and expression analysis in vivo and in vitro.

    PubMed

    Feng, Jianjun; Guo, Songlin; Lin, Peng; Wang, Yilei; Zhang, Ziping; Zhang, Zaipeng; Yu, Lili

    2016-08-01

    RIG-I (retinoic acid inducible gene-I) is one of the key cytosolic pattern recognition receptors (PRRs) for the recognition of cytosolic viral nucleic acids and the production of type I interferons (IFNs). The full-length cDNA sequence of RIG-I (AjRIG-I) in Japanese eel (Anguilla japonica) was identified and characterized in this article. The full-length cDNA of AjRIG-I was 3468 bp, including a 5'-untranslated region (UTR) of 52 bp, a 3'-UTR of 617 bp and an open reading frame (ORF) of 2799 bp encoding a polypeptide of 933 amino acid residues with a calculated molecular mass of 106.2 kDa. NCBI CDD analysis showed that the AjRIG-I protein had the typical conserved domains, including two adjacent caspase activation and recruitment domains (CARDs), a DEXDc domain, a HELICc domain and a C-terminal regulatory domain (RD). Quantitative real-time polymerase chain reaction (qRT-PCR) analysis revealed a broad expression for AjRIG-I in a wide range of tissues, with the predominant expression in liver, followed by the gills, spleen, kidney, intestine, skin, and the very low expression in muscle and heart. The AjRIG-I expressions in liver, spleen and kidney were significantly induced following injection with LPS, the viral mimic poly I:C, and Aeromonas hydrophila infection. In vitro, the AjRIG-I transcripts of Japanese eel liver cells were significantly enhanced by poly I:C and PGN stimulation, down-regulated with CpG-DNA treatment whereas no change of the expression level was found post LPS challenge. These results collectively suggested AjRIG-I transcripts expression possibly play an important role in fish defense against viral and bacterial infection.

  2. Citric acid induces cell-cycle arrest and apoptosis of human immortalized keratinocyte cell line (HaCaT) via caspase- and mitochondrial-dependent signaling pathways.

    PubMed

    Ying, Tsung-Ho; Chen, Chia-Wei; Hsiao, Yu-Ping; Hung, Sung-Jen; Chung, Jing-Gung; Yang, Jen-Hung

    2013-10-01

    Citric acid is an alpha-hydroxyacid (AHA) widely used in cosmetic dermatology and skincare products. However, there is concern regarding its safety for the skin. In this study, we investigated the cytotoxic effects of citric acid on the human keratinocyte cell line HaCaT. HaCaT cells were treated with citric acid at 2.5-12.5 mM for different time periods. Cell-cycle arrest and apoptosis were investigated by 4,6-diamidino-2-phenylindole dihydrochloride (DAPI) staining, flow cytometry, western blot and confocal microscopy. Citric acid not only inhibited proliferation of HaCaT cells in a dose-dependent manner, but also induced apoptosis and cell cycle-arrest at the G2/M phase (before 24 h) and S phase (after 24 h). Citric acid increased the level of Bcl-2-associated X protein (BAX) and reduced the levels of B-cell lymphoma-2 (BCL-2), B-cell lymphoma-extra large (BCL-XL) and activated caspase-9 and caspase-3, which subsequently induced apoptosis via caspase-dependent and caspase-independent pathways. Citric acid also activated death receptors and increased the levels of caspase-8, activated BH3 interacting-domain death agonist (BID) protein, Apoptosis-inducing factor (AIF), and Endonuclease G (EndoG). Therefore, citric acid induces apoptosis through the mitochondrial pathway in the human keratinocyte cell line HaCaT. The study results suggest that citric acid is cytotoxic to HaCaT cells via induction of apoptosis and cell-cycle arrest in vitro.

  3. Increased expression of retinoic acid-induced gene 1 in the dorsolateral prefrontal cortex in schizophrenia, bipolar disorder, and major depression

    PubMed Central

    Haybaeck, Johannes; Postruznik, Magdalena; Miller, Christine L; Dulay, Jeannette R; Llenos, Ida C; Weis, Serge

    2015-01-01

    Background Retinoids regulate gene expression in different cells and tissues at the transcriptional level. Retinoic acid transcriptionally regulates downstream regulatory molecules, including enzymes, transcription factors, cytokines, and cytokine receptors. Animal models indicate an involvement of retinoid signaling pathways in the regulation of synaptic plasticity and learning, especially in the hippocampus. Retinoic acid-inducible or induced gene 1 (RAI-1) is induced during neuronal differentiation, and was associated with the severity of the phenotype and response to medication in schizophrenic patients. Methods In the present study, we used immunohistochemistry to investigate the expression of RAI-1 in 60 brains from the Stanley Neuropathology Consortium (15 cases each from controls and from patients with schizophrenia, bipolar disorder, and major depression). Rating scores for density and intensity were determined in the dorsolateral prefrontal cortex. Results All four groups showed high interindividual variation. RAI-1-positive cells were identified as neurons and astrocytes. Significantly increased intensities in cortical neurons were noted in all three major psychiatric groups compared with controls. The density of RAI-1-positive neurons was increased (P=0.06) in schizophrenia and bipolar disorder. In bipolar disorder, RAI-1-positive astrocytes in gray matter showed a significantly increased intensity and compound value. Thus, a significant increase in the parameters measured was found in schizophrenia, bipolar disorder, and major depression. Conclusion Our study shows a significant increase in expression of RAI-1 in the brains from patients with schizophrenia, bipolar disorder, or major depression. The increased expression might reflect altered signaling pathways, like that for retinoic acid. The underlying mechanisms leading to the increased expression and its functional consequences are so far unknown, and remain to be investigated in future studies

  4. Identification of a retinoic acid-inducible gene I from Japanese eel (Anguilla japonica) and expression analysis in vivo and in vitro.

    PubMed

    Feng, Jianjun; Guo, Songlin; Lin, Peng; Wang, Yilei; Zhang, Ziping; Zhang, Zaipeng; Yu, Lili

    2016-08-01

    RIG-I (retinoic acid inducible gene-I) is one of the key cytosolic pattern recognition receptors (PRRs) for the recognition of cytosolic viral nucleic acids and the production of type I interferons (IFNs). The full-length cDNA sequence of RIG-I (AjRIG-I) in Japanese eel (Anguilla japonica) was identified and characterized in this article. The full-length cDNA of AjRIG-I was 3468 bp, including a 5'-untranslated region (UTR) of 52 bp, a 3'-UTR of 617 bp and an open reading frame (ORF) of 2799 bp encoding a polypeptide of 933 amino acid residues with a calculated molecular mass of 106.2 kDa. NCBI CDD analysis showed that the AjRIG-I protein had the typical conserved domains, including two adjacent caspase activation and recruitment domains (CARDs), a DEXDc domain, a HELICc domain and a C-terminal regulatory domain (RD). Quantitative real-time polymerase chain reaction (qRT-PCR) analysis revealed a broad expression for AjRIG-I in a wide range of tissues, with the predominant expression in liver, followed by the gills, spleen, kidney, intestine, skin, and the very low expression in muscle and heart. The AjRIG-I expressions in liver, spleen and kidney were significantly induced following injection with LPS, the viral mimic poly I:C, and Aeromonas hydrophila infection. In vitro, the AjRIG-I transcripts of Japanese eel liver cells were significantly enhanced by poly I:C and PGN stimulation, down-regulated with CpG-DNA treatment whereas no change of the expression level was found post LPS challenge. These results collectively suggested AjRIG-I transcripts expression possibly play an important role in fish defense against viral and bacterial infection. PMID:27238428

  5. Hepatitis C Virus Frameshift/Alternate Reading Frame Protein Suppresses Interferon Responses Mediated by Pattern Recognition Receptor Retinoic-Acid-Inducible Gene-I.

    PubMed

    Park, Seung Bum; Seronello, Scott; Mayer, Wasima; Ojcius, David M

    2016-01-01

    Hepatitis C virus (HCV) actively evades host interferon (IFN) responses but the mechanisms of how it does so are not completely understood. In this study, we present evidence for an HCV factor that contributes to the suppression of retinoic-acid-inducible gene-I (RIG-I)-mediated IFN induction. Expression of frameshift/alternate reading frame protein (F/ARFP) from HCV -2/+1 frame in Huh7 hepatoma cells suppressed type I IFN responses stimulated by HCV RNA pathogen-associated molecular pattern (PAMP) and poly(IC). The suppression occurred independently of other HCV factors; and activation of interferon stimulated genes, TNFα, IFN-λ1, and IFN-λ2/3 was likewise suppressed by HCV F/ARFP. Point mutations in the full-length HCV sequence (JFH1 genotype 2a strain) were made to introduce premature termination codons in the -2/+1 reading frame coding for F/ARFP while preserving the original reading frame, which enhanced IFNα and IFNβ induction by HCV. The potentiation of IFN response by the F/ARFP mutations was diminished in Huh7.5 cells, which already have a defective RIG-I, and by decreasing RIG-I expression in Huh7 cells. Furthermore, adding F/ARFP back via trans-complementation suppressed IFN induction in the F/ARFP mutant. The F/ARFP mutants, on the other hand, were not resistant to exogenous IFNα. Finally, HCV-infected human liver samples showed significant F/ARFP antibody reactivity, compared to HCV-uninfected control livers. Therefore, HCV F/ARFP likely cooperates with other viral factors to suppress type I and III IFN induction occurring through the RIG-I signaling pathway. This study identifies a novel mechanism of pattern recognition receptor modulation by HCV and suggests a biological function of the HCV alternate reading frame in the modulation of host innate immunity. PMID:27404108

  6. Molecular Analysis of the Retinoic Acid Induced 1 Gene (RAI1) in Patients with Suspected Smith-Magenis Syndrome without the 17p11.2 Deletion

    PubMed Central

    Vilboux, Thierry; Ciccone, Carla; Blancato, Jan K.; Cox, Gerald F.; Deshpande, Charu; Introne, Wendy J.; Gahl, William A.; Smith, Ann C. M.; Huizing, Marjan

    2011-01-01

    Smith-Magenis syndrome (SMS) is a complex neurobehavioral disorder characterized by multiple congenital anomalies. The syndrome is primarily ascribed to a ∼3.7 Mb de novo deletion on chromosome 17p11.2. Haploinsufficiency of multiple genes likely underlies the complex clinical phenotype. RAI1 (Retinoic Acid Induced 1) is recognized as a major gene involved in the SMS phenotype. Extensive genetic and clinical analyses of 36 patients with SMS-like features, but without the 17p11.2 microdeletion, yielded 10 patients with RAI1 variants, including 4 with de novo deleterious mutations, and 6 with novel missense variants, 5 of which were familial. Haplotype analysis showed two major RAI1 haplotypes in our primarily Caucasian cohort; the novel RAI1 variants did not occur in a preferred haplotype. RNA analysis revealed that RAI1 mRNA expression was significantly decreased in cells of patients with the common 17p11.2 deletion, as well as in those with de novo RAI1 variants. Expression levels varied in patients with familial RAI1 variants and in non-17p11.2 deleted patients without identified RAI1 defects. No correlation between SNP haplotype and RAI1 expression was found. Two clinical features, ocular abnormalities and polyembolokoilomania (object insertion), were significantly correlated with decreased RAI1 expression. While not significantly correlated, the presence of hearing loss, seizures, hoarse voice, childhood onset of obesity and specific behavioral aspects and the absence of immunologic abnormalities and cardiovascular or renal structural anomalies, appeared to be specific for the de novo RAI1 subgroup. Recognition of the combination of these features will assist in referral for RAI1 analysis of patients with SMS-like features without detectable microdeletion of 17p11.2. Moreover, RAI1 expression emerged as a genetic target for development of therapeutic interventions for SMS. PMID:21857958

  7. Gibberellic acid-induced aleurone layers responding to heat shock or tunicamycin provide insight into the N-glycoproteome, protein secretion, and endoplasmic reticulum stress.

    PubMed

    Barba-Espín, Gregorio; Dedvisitsakul, Plaipol; Hägglund, Per; Svensson, Birte; Finnie, Christine

    2014-02-01

    The growing relevance of plants for the production of recombinant proteins makes understanding the secretory machinery, including the identification of glycosylation sites in secreted proteins, an important goal of plant proteomics. Barley (Hordeum vulgare) aleurone layers maintained in vitro respond to gibberellic acid by secreting an array of proteins and provide a unique system for the analysis of plant protein secretion. Perturbation of protein secretion in gibberellic acid-induced aleurone layers by two independent mechanisms, heat shock and tunicamycin treatment, demonstrated overlapping effects on both the intracellular and secreted proteomes. Proteins in a total of 22 and 178 two-dimensional gel spots changing in intensity in extracellular and intracellular fractions, respectively, were identified by mass spectrometry. Among these are proteins with key roles in protein processing and secretion, such as calreticulin, protein disulfide isomerase, proteasome subunits, and isopentenyl diphosphate isomerase. Sixteen heat shock proteins in 29 spots showed diverse responses to the treatments, with only a minority increasing in response to heat shock. The majority, all of which were small heat shock proteins, decreased in heat-shocked aleurone layers. Additionally, glycopeptide enrichment and N-glycosylation analysis identified 73 glycosylation sites in 65 aleurone layer proteins, with 53 of the glycoproteins found in extracellular fractions and 36 found in intracellular fractions. This represents major progress in characterization of the barley N-glycoproteome, since only four of these sites were previously described. Overall, these findings considerably advance knowledge of the plant protein secretion system in general and emphasize the versatility of the aleurone layer as a model system for studying plant protein secretion.

  8. Molecular analysis of the Retinoic Acid Induced 1 gene (RAI1) in patients with suspected Smith-Magenis syndrome without the 17p11.2 deletion.

    PubMed

    Vilboux, Thierry; Ciccone, Carla; Blancato, Jan K; Cox, Gerald F; Deshpande, Charu; Introne, Wendy J; Gahl, William A; Smith, Ann C M; Huizing, Marjan

    2011-01-01

    Smith-Magenis syndrome (SMS) is a complex neurobehavioral disorder characterized by multiple congenital anomalies. The syndrome is primarily ascribed to a ∼3.7 Mb de novo deletion on chromosome 17p11.2. Haploinsufficiency of multiple genes likely underlies the complex clinical phenotype. RAI1 (Retinoic Acid Induced 1) is recognized as a major gene involved in the SMS phenotype. Extensive genetic and clinical analyses of 36 patients with SMS-like features, but without the 17p11.2 microdeletion, yielded 10 patients with RAI1 variants, including 4 with de novo deleterious mutations, and 6 with novel missense variants, 5 of which were familial. Haplotype analysis showed two major RAI1 haplotypes in our primarily Caucasian cohort; the novel RAI1 variants did not occur in a preferred haplotype. RNA analysis revealed that RAI1 mRNA expression was significantly decreased in cells of patients with the common 17p11.2 deletion, as well as in those with de novo RAI1 variants. Expression levels varied in patients with familial RAI1 variants and in non-17p11.2 deleted patients without identified RAI1 defects. No correlation between SNP haplotype and RAI1 expression was found. Two clinical features, ocular abnormalities and polyembolokoilomania (object insertion), were significantly correlated with decreased RAI1 expression. While not significantly correlated, the presence of hearing loss, seizures, hoarse voice, childhood onset of obesity and specific behavioral aspects and the absence of immunologic abnormalities and cardiovascular or renal structural anomalies, appeared to be specific for the de novo RAI1 subgroup. Recognition of the combination of these features will assist in referral for RAI1 analysis of patients with SMS-like features without detectable microdeletion of 17p11.2. Moreover, RAI1 expression emerged as a genetic target for development of therapeutic interventions for SMS.

  9. Dose Dependent Activation of Retinoic Acid-Inducible Gene-I Promotes Both Proliferation and Apoptosis Signals in Human Head and Neck Squamous Cell Carcinoma

    PubMed Central

    Yan, Ming; Zhu, Chao; Ye, Weimin; Zhu, Hanguang; Chen, Wantao; Zhang, Chenping; Zhang, Zhiyuan

    2013-01-01

    The retinoic-acid-inducible gene (RIG)-like receptor (RLR) family proteins are major pathogen reorganization receptors (PRR) responsible for detection of viral RNA, which initiates antiviral response. Here, we evaluated the functional role of one RLR family member, RIG-I, in human head and neck squamous cell carcinoma (HNSCC). RIG-I is abundantly expressed both in poorly-differentiated primary cancer and lymph node metastasis, but not in normal adjacent tissues. Activation of RIG-I by transfection with low dose of 5′-triphosphate RNA (3p-RNA) induces low levels of interferon and proinflammatory cytokines and promotes NF-κB- and Akt-dependent cell proliferation, migration and invasion. In contrast, activation of RIG-I by a high dose of 3p-RNA induces robust mitochondria-derived apoptosis accompanied by decreased activation of Akt, which is independent of the interferon and TNFα receptor, but can be rescued by over-expression of constitutively active Akt. Furthermore, co-immunoprecipitation experiments indicate that the CARD domain of RIG-I is essential for inducing apoptosis by interacting with caspase-9. Together, our results reveal a dual role of RIG-I in HNSCC through regulating activation of Akt, in which RIG-I activation by low-dose viral dsRNA increases host cell surviral, whereas higher level of RIG-I activation leads to apopotosis. These findings highlight the therapeutic potential of dsRNA mediated RIG-I activation in the treatment of HNSCC. PMID:23484008

  10. Acid-induced off-response of PKD2L1 channel in Xenopus oocytes and its regulation by Ca(2.).

    PubMed

    Hussein, Shaimaa; Zheng, Wang; Dyte, Chris; Wang, Qian; Yang, JungWoo; Zhang, Fan; Tang, Jingfeng; Cao, Ying; Chen, Xing-Zhen

    2015-01-01

    Polycystic kidney disease (PKD) protein 2 Like 1 (PKD2L1), also called transient receptor potential polycystin-3 (TRPP3), regulates Ca(2+)-dependent hedgehog signalling in primary cilia, intestinal development and sour tasting but with an unclear mechanism. PKD2L1 is a Ca(2+)-permeable cation channel that is activated by extracellular Ca(2+) (on-response) in Xenopus oocytes. PKD2L1 co-expressed with PKD protein 1 Like 3 (PKD1L3) exhibits extracellular acid-induced activation (off-response, i.e., activation following acid removal) but whether PKD1L3 participates in acid sensing remains unclear. Here we used the two-microelectrode voltage-clamp, site directed mutagenesis, Western blotting, reverse transcriptase-polymerase chain reaction (RT-PCR) and immunofluorescence, and showed that PKD2L1 expressed in oocytes exhibits sustained off-response currents in the absence of PKD1L3. PKD1L3 co-expression augmented the PKD2L1 plasma membrane localization but did not alter the observed properties of the off-response. PKD2L1 off-response was inhibited by an increase in intracellular Ca(2+). We also identified two intra-membrane residues aspartic acid 349 (D349) and glutamic acid 356 (E356) in the third transmembrane domain that are critical for PKD2L1 channel function. Our study suggests that PKD2L1 may itself sense acids and defines off-response properties in the absence of PKD1L3. PMID:26502994

  11. Retinoic acid inducible gene-I and melanoma differentiation-associated gene 5 are induced but not essential for dengue virus induced type I interferon response.

    PubMed

    Qin, Cheng-Feng; Zhao, Hui; Liu, Zhong-Yu; Jiang, Tao; Deng, Yong-Qiang; Yu, Xu-Dong; Yu, Man; Qin, E-De

    2011-08-01

    Dengue viruses (DENVs) are important human pathogens that cause mild dengue fever, and severe dengue hemorrhagic fever/dengue shock syndrome, and no vaccine or antiviral therapy are currently available. At the initial stage of DENV infection, host pattern recognition receptors are responsible for sensing viral proteins or nucleic acids and initiating innate antiviral responses, including the activation of type I interferon (IFN) and proinflammatory cytokines. Two RNA helicases, retinoic acid inducible gene-I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5), are recently identified as cytoplasmic PPRs for virus infection. Here, in this study the involvement of RIG-I and MDA5 in DENV-induced IFN-β response A549 cells were investigated. DENV infection readily up-regulated RIG-I expression, activated IRF-3 and RIG-I mRNA transcription, and induced the production of IFN-β in A549 cells in a strain- and serotype-independent manner. While gene silencing of RIG-I by small interfering RNAs failed to significantly inhibit IFN-β production induced by DENV infection. Further experiments demonstrated that MDA5 was also induced by DENV infection, and MDA5 knockout did not block DENV induced IFN-β production in A549 cells. Our results demonstrated that both RIG-I and MDA5 were induced but neither of the two was essential for DENV induced IFN IFN-β response in A549 cells. These findings suggest that innate immune pathway are involved in the recognition of DENV by human non-immune cells, and provide insights for the understanding of the molecular mechanism for DENV-induced antiviral response.

  12. Music application alleviates short-term memory impairments through increasing cell proliferation in the hippocampus of valproic acid-induced autistic rat pups.

    PubMed

    Lee, Sung-Min; Kim, Bo-Kyun; Kim, Tae-Woon; Ji, Eun-Sang; Choi, Hyun-Hee

    2016-06-01

    Autism is a neurodevelopmental disorder and this disorder shows impairment in reciprocal social interactions, deficits in communication, and restrictive and repetitive patterns of behaviors and interests. The effect of music on short-term memory in the view of cell proliferation in the hippocampus was evaluated using valproic acid-induced autistic rat pups. Animal model of autism was made by subcutaneous injection of 400-mg/kg valproic acid into the rat pups on the postnatal day 14. The rat pups in the music-applied groups were exposed to the 65-dB comfortable classic music for 1 hr once a day, starting postnatal day 15 and continued until postnatal day 28. In the present results, short-term memory was deteriorated by autism induction. The numbers of 5-bromo-2'-deoxyridine (BrdU)-positive, Ki-67-positive, and doublecortin (DCX)-positive cells in the hippocampal dentate gyrus were decreased by autism induction. Brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) expressions in the hippocampus were also suppressed in the autistic rat pups. Music application alleviated short-term memory deficits with enhancing the numbers of BrdU-positive, Ki-67-positive, and DCX-positive cells in the autistic rat pups. Music application also enhanced BDNF and TrkB expressions in the autistic rat pups. The present study show that application of music enhanced hippocampal cell proliferation and alleviated short-term memory impairment through stimulating BDNF-TrkB signaling in the autistic rat pups. Music can be suggested as the therapeutic strategy to overcome the autism-induced memory deficits.

  13. A combined physiological and proteomic approach to reveal lactic-acid-induced alterations in Lactobacillus casei Zhang and its mutant with enhanced lactic acid tolerance.

    PubMed

    Wu, Chongde; Zhang, Juan; Chen, Wei; Wang, Miao; Du, Guocheng; Chen, Jian

    2012-01-01

    Lactobacillus casei has traditionally been recognized as a probiotic and frequently used as an adjunct culture in fermented dairy products, where acid stress is an environmental condition commonly encountered. In the present study, we carried out a comparative physiological and proteomic study to investigate lactic-acid-induced alterations in Lactobacillus casei Zhang (WT) and its acid-resistant mutant. Analysis of the physiological data showed that the mutant exhibited 33.8% higher glucose phosphoenolpyruvate:sugar phosphotransferase system activity and lower glycolytic pH compared with the WT under acidic conditions. In addition, significant differences were detected in both cells during acid stress between intracellular physiological state, including intracellular pH, H(+)-ATPase activity, and intracellular ATP pool. Comparison of the proteomic data based on 2D-DIGE and i-TRAQ indicated that acid stress invoked a global change in both strains. The mutant protected the cells against acid damage by regulating the expression of key proteins involved in cellular metabolism, DNA replication, RNA synthesis, translation, and some chaperones. Proteome results were validated by Lactobacillus casei displaying higher intracellular aspartate and arginine levels, and the survival at pH 3.3 was improved 1.36- and 2.10-fold by the addition of 50-mM aspartate and arginine, respectively. To our knowledge, this is the first demonstration that aspartate may be involved in acid tolerance in Lactobacillus casei. Results presented here may help us understand acid resistance mechanisms and help formulate new strategies to enhance the industrial applications of this species. PMID:22159611

  14. Acid-induced sweetness of neoculin is ascribed to its pH-dependent agonistic-antagonistic interaction with human sweet taste receptor.

    PubMed

    Nakajima, Ken-ichiro; Morita, Yuji; Koizumi, Ayako; Asakura, Tomiko; Terada, Tohru; Ito, Keisuke; Shimizu-Ibuka, Akiko; Maruyama, Jun-ichi; Kitamoto, Katsuhiko; Misaka, Takumi; Abe, Keiko

    2008-07-01

    Neoculin (NCL) is a sweet protein that also has taste-modifying activity to convert sourness to sweetness. However, it has been unclear how NCL induces this unique sensation. Here we quantitatively evaluated the pH-dependent acid-induced sweetness of NCL using a cell-based assay system. The human sweet taste receptor, hT1R2-hT1R3, was functionally expressed in HEK293T cells together with G alpha protein. When NCL was applied to the cells under different pH conditions, it activated hT1R2-hT1R3 in a pH-dependent manner as the condition changed from pH 8 to 5. The pH-response sigmoidal curve resembled the imidazole titration curve, suggesting that His residues were involved in the taste-modifying activity. We then constructed an NCL variant in which all His residues were replaced with Ala and found that the variant elicited strong sweetness at neutral pH as well as at acidic pH. Since NCL and the variant elicited weak and strong sweetness at the same neutral pH, respectively, we applied different proportions of NCL-variant mixtures to the cells at this pH. As a result, NCL competitively inhibits the variant-induced receptor activation. All these data suggest that NCL acts as an hT1R2-hT1R3 agonist at acidic pH but functionally changes into its antagonist at neutral pH.

  15. Preliminary pharmacological activity of the methanolic extract of Premna integrifolia barks in rats

    PubMed Central

    Khatun, Hajera; Majumder, Rajib; Al Mamun; Alam, Efte Kharul; Jami, Safkath Ibne; Alam, Badrul

    2014-01-01

    Objective: Premna integrifolia Linn (Family: Verbenaceae) synonym of Premna serratifolia has tremendous medicinal value. Preliminary pharmacological studies were performed on the methanolic extract of Premna integrifolia (MEPI) bark to investigate neuropharmacological, analgesic, and anti-inflammatory activities. Materials and methods: Neuropharmacology study was done by open field and hole cross test whereas acetic acid writhing test and formalin induced pain was done for analgesic activity of MEPI. Carrageenan induced inflammatory model was considered for anti-inflammatory activity evaluation. Results: A statistically significant (p0.05) decrease in locomotor activity was observed at all doses in the open-field and hole-cross tests. The extract significantly (p0.05) and dose dependently reduced the writhing reflex in the acetic acid-induced writhing test as well as licking response in the formalin induced inflammatory pain. At 200 mg/kg body weight dose, MEPI showed 71.16% inhibition in carrageenan induced anti-inflammatory activity. Conclusion: The finding of this study suggests that MEPI will provide scientific support for the use of this species in traditional medicine. PMID:25050319

  16. Acid-induced type VI secretion system is regulated by ExoR-ChvG/ChvI signaling cascade in Agrobacterium tumefaciens.

    PubMed

    Wu, Chih-Feng; Lin, Jer-Sheng; Shaw, Gwo-Chyuan; Lai, Erh-Min

    2012-09-01

    The type VI secretion system (T6SS) is a widespread, versatile protein secretion system in pathogenic Proteobacteria. Several T6SSs are tightly regulated by various regulatory systems at multiple levels. However, the signals and/or regulatory mechanisms of many T6SSs remain unexplored. Here, we report on an acid-induced regulatory mechanism activating T6SS in Agrobacterium tumefaciens, a plant pathogenic bacterium causing crown gall disease in a wide range of plants. We monitored the secretion of the T6SS hallmark protein hemolysin-coregulated protein (Hcp) from A. tumefaciens and found that acidity is a T6SS-inducible signal. Expression analysis of the T6SS gene cluster comprising the imp and hcp operons revealed that imp expression and Hcp secretion are barely detected in A. tumefaciens grown in neutral minimal medium but are highly induced with acidic medium. Loss- and gain-of-function analysis revealed that the A. tumefaciens T6SS is positively regulated by a chvG/chvI two-component system and negatively regulated by exoR. Further epistasis analysis revealed that exoR functions upstream of the chvG sensor kinase in regulating T6SS. ChvG protein levels are greatly increased in the exoR deletion mutant and the periplasmic form of overexpressed ExoR is rapidly degraded under acidic conditions. Importantly, ExoR represses ChvG by direct physical interaction, but disruption of the physical interaction allows ChvG to activate T6SS. The phospho-mimic but not wild-type ChvI response regulator can bind to the T6SS promoter region in vitro and activate T6SS with growth in neutral minimal medium. We present the first evidence of T6SS activation by an ExoR-ChvG/ChvI cascade and propose that acidity triggers ExoR degradation, thereby derepressing ChvG/ChvI to activate T6SS in A. tumefaciens. PMID:23028331

  17. Acid-Induced Type VI Secretion System Is Regulated by ExoR-ChvG/ChvI Signaling Cascade in Agrobacterium tumefaciens

    PubMed Central

    Shaw, Gwo-Chyuan; Lai, Erh-Min

    2012-01-01

    The type VI secretion system (T6SS) is a widespread, versatile protein secretion system in pathogenic Proteobacteria. Several T6SSs are tightly regulated by various regulatory systems at multiple levels. However, the signals and/or regulatory mechanisms of many T6SSs remain unexplored. Here, we report on an acid-induced regulatory mechanism activating T6SS in Agrobacterium tumefaciens, a plant pathogenic bacterium causing crown gall disease in a wide range of plants. We monitored the secretion of the T6SS hallmark protein hemolysin-coregulated protein (Hcp) from A. tumefaciens and found that acidity is a T6SS-inducible signal. Expression analysis of the T6SS gene cluster comprising the imp and hcp operons revealed that imp expression and Hcp secretion are barely detected in A. tumefaciens grown in neutral minimal medium but are highly induced with acidic medium. Loss- and gain-of-function analysis revealed that the A. tumefaciens T6SS is positively regulated by a chvG/chvI two-component system and negatively regulated by exoR. Further epistasis analysis revealed that exoR functions upstream of the chvG sensor kinase in regulating T6SS. ChvG protein levels are greatly increased in the exoR deletion mutant and the periplasmic form of overexpressed ExoR is rapidly degraded under acidic conditions. Importantly, ExoR represses ChvG by direct physical interaction, but disruption of the physical interaction allows ChvG to activate T6SS. The phospho-mimic but not wild-type ChvI response regulator can bind to the T6SS promoter region in vitro and activate T6SS with growth in neutral minimal medium. We present the first evidence of T6SS activation by an ExoR-ChvG/ChvI cascade and propose that acidity triggers ExoR degradation, thereby derepressing ChvG/ChvI to activate T6SS in A. tumefaciens. PMID:23028331

  18. Anti-nociceptive and anti-inflammatory activities of the extracts of Stauntonia chinensis.

    PubMed

    Ying, Chen; Ning, Wu; Ying, Liu; Hao, Gao; Hua-Jin, Dong; Rui-Bin, Su; Xin-Sheng, Yao; Jin, Li

    2014-09-01

    The aim of this investigation was to study the anti-nociceptive and anti-inflammatory activities of Stauntonia chinensis (S. chinensis) and the possible action mechanisms of effective fractions. The anti-nociceptive and anti-inflammatory activities of S. chinensis extracts, including the 60% EtOH extract (YMG), the n-BuOH extract (YMGB) and the aqueous residue (YMGW) of YMG, and the fractions from YMGB (YMGB1~YMGB7) were investigated by using the mouse acetic acid-induced writhing test and the rat formalin test. The effect of these extracts on the PGE2 production was tested as well. In the mouse acetic acid-induced writhing test and the rat formalin test, YMGW and YMGB displayed anti-nociceptive and anti-inflammatory activities, suggesting that they were the active ingredients of YMG. Among the fractions isolated from YMGB, YMGB1, YMGB3, YMGB4 and YMGB6 were the main active ingredients producing anti-nociceptive activity and YMGB3, YMGB5, YMGB6 and YMGB7 were the main active ingredients producing anti-inflammatory activity. Additionally, YMGW, YMGB and its separations reduced the production of PGE2, which might be the mechanism of them producing anti-inflammatory activity. These results demonstrated the active ingredients of S. chinensis producing anti-nociceptive and anti-inflammatory activities, which is valuable to validate the substance basis of S. chinensis's pharmacological actions.

  19. Analgesic and Antipyretic Activities of Methanol Extract and Its Fraction from the Root of Schoenoplectus grossus

    PubMed Central

    Subedi, Nirmal Kumar; Rahman, S. M. Abdur; Akbar, Mohammad Ahsanul

    2016-01-01

    The study aims to evaluate analgesic and antipyretic activities of the methanol extract and its different fractions from root of Schoenoplectus grossus using acetic acid induced writhing and radiant heat tail flick method of pain models in mice and yeast induced pyrexia in rats at the doses of 400 and 200 mg/kg. In acetic acid writhing test, the methanol extract, petroleum ether, and carbon tetrachloride fractions produced significant (P < 0.001 and P < 0.05) inhibition of writhing responses in dose dependent manner. The methanol extract at 400 and 200 mg/kg being more protective with 54% and 45.45% of inhibition compared to diclofenac sodium of 56% followed by petroleum ether fractions of 49.69% and 39.39% at the same doses. The extracts did not produce any significant antinociceptive activity in tail flick test except standard morphine. When studied on yeast induced pyrexia, methanol and petroleum ether fractions significantly lowered the rectal temperature time dependently in a manner similar to standard drug paracetamol and distinctly more significant (P < 0.001) after second hour. These findings suggest that the root extracts of S. grossus possess significant peripherally acting analgesic potential and antipyretic property. The phytochemical screening showed the presence of flavonoids, alkaloids, and tannins. PMID:26977173

  20. Phytochemical Screening and Anti-nociceptive Properties of the Ethanolic Leaf Extract of Trema Cannabina Lour

    PubMed Central

    Hossain, Hemayet; Jahan, Ismet Ara; Islam, Howlader Sariful; Kanti, Dey Shubhra; Arpona, Hira; Arif, Ahmed

    2013-01-01

    Purpose: The present study was designed to investigate the anti-nociceptive activity of ethanolic leaf extract of Trema cannabina Lour (family: Cannabaceae) in experimental animal models. Methods: The anti-nociceptive action was carried out against two types of noxious stimuli, thermal (hot plate and tail immersion tests) and chemical (acetic acid-induced writhing) in mice. Results: Phytochemical analysis of crude extract indicated the presence of reducing sugar, tannins, steroid and alkaloid types of secondary metabolites. Crude extract of T. cannabina (500 mg/kg dose) showed maximum time needed for the response against thermal stimuli (6.79±0.15 seconds) which is comparable to diclofenac sodium (8.26±0.14 seconds) in the hot plate test. Hot tail immersion test also showed similar results as in hot plate test. At the dose of 250 and 500 mg/kg body weight, the extract showed significantly and in a dose-dependent (p<0.001) reduction in acetic acid induced writhing in mice with a maximum effect of 47.56% reduction at 500 mg/kg dose comparable to that of diclofenac sodium (67.07%) at 25 mg/kg. Conclusion: The obtained results tend to suggest the Anti-nociceptive activity of ethanolic leaf extract of Trema cannabina and thus provide the scientific basis for the traditional uses of this plant part as a remedy for pain. PMID:24312820

  1. The antinociceptive effect of some Egyptian medicinal plant extracts.

    PubMed

    Atta, A H; Abo EL-Sooud, K

    2004-12-01

    The antinociceptive effect of methanolic extracts (200 and 400 mg kg(-1)) of eight Egyptian medicinal plants was studied using acetic acid-induced writhing and tail-flick test in mice. Oral administration of 400 mg kg(-1) methanolic extracts of Convolvulus fatmensis, Alhagi maurorum, Plantago major seeds, Conyza dioscaridis significantly (P < 0.05) inhibited the nociception to acetic acid-induced writhes with a protection of 85.5-61.3%. Schouwia thebaica, Diplotaxis acris, Plantago major leaves and Mentha microphylla, in the large dose, showed a protection of 50.8-45.8%, which were significantly different as compared to control. The smaller dose of the tested plant extracts did not protect animals from painful acetic acid stimulation with the exception of Alhagi maurorum. In the tail-flick test, methanolic extracts of Mentha microphylla, Conyza dioscaridis, Alhagi maurorum, Plantago major leaves, Diplotaxis acris and Convolvulus fatmensis in a dose of 400 mg kg(-1) produced significant increase in the latency to response of tail to thermal stimulation. Mild or no effect was observed by the small dose with the exception of Diplotaxis acris that had significant antinociceptive effect at the dose of 200 mg kg(-1). The extracts of all tested plants in doses up to 2 g kg(-1) b.wt. did not cause any deaths or major signs of acute toxicity. Phytochemical screening indicated the presence of unsaturated sterols, triterpenes, tannins, flavonoids and carbohydrates and/or glycosides as major constituents. PMID:15507342

  2. Antinociceptive effects of dehydrocorydaline in mouse models of inflammatory pain involve the opioid receptor and inflammatory cytokines

    PubMed Central

    Yin, Zhi-Yu; Li, Lu; Chu, Shuai-Shuai; Sun, Qing; Ma, Zheng-Liang; Gu, Xiao-Ping

    2016-01-01

    Dehydrocorydaline (DHC) is an alkaloidal component isolated from Rhizoma corydalis. Previous studies have shown that DHC has anti-inflammatory and anti-tumor effects and that it can protect the cardiovascular system. However, there are few studies of the antinociceptive effects of DHC in vivo. This study explored the antinociceptive effects and possible mechanisms of DHC in mice using two inflammatory pain models: the acetic acid-induced writhing test and the formalin paw test. The intraperitoneal administration of DHC (3.6, 6 or 10 mg/kg) showed a dose-dependent antinociceptive effect in the acetic acid-induced writhing test and significantly attenuated the formalin-induced pain responses in mice. The antinociceptive effects of DHC were not associated with changes in the locomotor activity or motor responses of animals, and no obvious acute or chronic toxic effects were observed in the mice. Furthermore, the use of naloxone confirmed the involvement of the opioid receptor in the central antinociceptive effects of DHC. DHC reduced formalin-induced paw edema, which indicated that DHC may produce an anti-inflammatory effect in the periphery. In the formalin test, DHC decreased the expression of caspase 6 (CASP6), TNF-α, IL-1β and IL-6 proteins in the spinal cord. These findings confirm that DHC has antinociceptive effects in mice. PMID:27272194

  3. Antinociceptive effect of Encholirium spectabile: A Bromeliaceae from the Brazilian caatinga biome

    PubMed Central

    de Lima-Saraiva, Sarah Raquel Gomes; Silva, Juliane Cabral; Branco, Carla Rodrigues Cardoso; Branco, Alexsandro; Cavalcanti Amorim, Elba Lúcia; da Silva Almeida, Jackson Roberto Guedes

    2014-01-01

    Background: Encholirium spectabile is a species found in outcrops rocky throughout the Brazilian Caatinga. Objective: This study was carried out to evaluate the antinociceptive effects of ethanolic extract of the leaves from E. spectabile (Es-EtOH) in mice using chemical and thermal models of nociception. Material and Methods: HPLC was used to determine the fingerprint chromatogram. The Es-EtOH was examined for its antinociceptive activity at the doses of 100, 200 and 400 mg/kg intraperitoneal (i.p.). The evaluation of antinociceptive activity was carried out by the acetic acid-induced writhing, formalin and hot plate tests in mice. Rota-rod test was used for the evaluation of motor coordination. Results: In the acetic acid-induced writhing test, the Es-EtOH (100, 200 and 400 mg/kg, i.p.) reduced the number of writhings by 68.59, 79.33 and 65.28%, respectively. Additionally, Es-EtOH (100, 200 and 400 mg/kg, i.p.) decreased by 34.14, 52.61 and 60.97% the paw licking time in the first phase, as well as 89.56, 79.90 and 96.71% in the second phase of the formalin test, respectively. Es-EtOH also showed effect in the hot plate test, since increased the latency time at dose of 100 mg/kg after 60 minutes. In addition, Es-EtOH did not impair motor coordination. The presence of phenolic compounds in the extract was confirmed using HPLC. These results indicate that Es-EtOH has antinociceptive activity, probably of peripheral origin. The mechanism involved is not completely understood but, at least in part there is the participation of opioid receptors. PMID:25298687

  4. Involvement of opioid receptors in the systemic and peripheral antinociceptive actions of montelukast in the animal models of pain.

    PubMed

    Ghorbanzadeh, Behnam; Mansouri, Mohammad Taghi; Sahraei, Hedayat; Alboghobeish, Soheila

    2016-05-15

    This study aimed to investigate the involvement of opioid receptors in the systemic and peripheral antinociceptive activities of montelukast in different animal models of pain. Rats and mice were injected with montelukast to produce analgesia. The formalin and acetic acid-induced writhing tests were used to assess the nociceptive activity. The results showed that i.p. administration of montelukast (0.3-10mg/kg) dose-dependently reduced flinching behavior in both the first and second phases of formalin test with mean ED50 of 0.55 and 5.31mg/kg, respectively. Also, intraplantar administration of montelukast (3-30μg/paw) produced antinociception against the two phases of formalin assay in a dose-dependent way with mean ED30 of 2.92 and 8.11μg/paw, respectively. Furthermore, pre-treatment with naloxone (a non-selective opioid receptor antagonist) significantly inhibited both the systemic and also peripheral antinociceptive actions of montelukast in formalin test. In writhing test, the results showed that intraperitoneal administration of montelukast (3-10mg/kg) significantly reduced the writhe number induced by acetic acid in mice. Moreover, co-administration of non-effective doses of montelukast (0.3 and 1mg/kg; i.p.) and morphine (0.25mg/kg; i.p.) significantly decreased the writhes number induced by acetic acid. Also, this effect was naloxone-reversible. These findings suggest that the systemic and peripheral antinociception produced by montelukast were mediated through the opioid receptors in central and peripheral nervous systems. Moreover, combination of montelukast and morphine could be noted as a new strategy for pain relief. PMID:26948314

  5. Analgesic, Anti-Inflammatory and Anticancer Activities of Extra Virgin Olive Oil

    PubMed Central

    Senovilla, Laura; Jemaà, Mohamed; Ben-Attia, Mossadok

    2013-01-01

    Background. In folk medicine, extra virgin olive oil (EVOO) is used as a remedy for a variety of diseases. This study investigates the in vivo antinociceptive, anti-inflammatory, and anti-cancer effects of EVOO on mice and rats. Materials and Methods. In this experimental study, using the acetic acid-induced writhing and formalin tests in mice, the analgesic effect of EVOO was evaluated. Acetylsalicylic acid and morphine were used as standard drugs, respectively. The anti-inflammatory activity was investigated by means of the carrageenan-induced paw edema model in rats using acetylsalicylic acid and dexamethasone as standard drugs. Last, the xenograft model in athymic mice was used to evaluate the anticancer effect in vivo. Results. EVOO significantly decreased acetic acid-induced abdominal writhes and reduces acute and inflammatory pain in the two phases of the formalin test. It has also a better effect than Dexamethasone in the anti-inflammatory test. Finally, the intraperitoneal administration of EVOO affects the growth of HCT 116 tumours xenografted in athymic mice. Conclusion. EVOO has a significant analgesic, anti-inflammatory, and anticancer properties. However, further detailed studies are required to determine the active component responsible for these effects and mechanism pathway. PMID:24455277

  6. Anti-hyperalgesic activity of crude extract and 7-methyljuglone of Diospyros lotus roots.

    PubMed

    Rauf, Abdur; Uddin, Ghias; Khan, Haroon; Siddiqui, Bina S; Arfan, Mohammad

    2015-01-01

    This study was designed to evaluate the antihyperalgesic effect of crude extract of Diospyros lotus followed by the isolation and characterisation of 7-methyljuglone in acetic acid and formalin tests. The pretreatment of crude extract evoked dose-dependent inhibition of noxious stimulation with maximum effect of 56.78% in acetic acid-induced writhing test, which were 51.89% and 60.69% in first and second phases, respectively, at 100 mg/kg i.p. The structure of 7-methyljuglone was confirmed by spectroscopic analysis. 7-Methyljuglone evoked profound increase in pain threshhold dose dependently; when it was studied in acetic acid-induced writhing test with 63.73% pain attenuation while 51.22% and 65.44% pain amelioration in first and second phases, respectively, at 100 mg/kg i.p. In conclusion, crude extract and 7-methyljuglone of D. lotus roots possessed both peripheral and central antinociceptive potential and thus could be a useful new therapeutic agent. PMID:25604725

  7. Screening of Ficus religiosa leaves fractions for analgesic and anti-inflammatory activities

    PubMed Central

    Gulecha, Vishal; Sivakumar, T; Upaganlawar, Aman; Mahajan, Manoj; Upasani, Chandrashekhar

    2011-01-01

    Objective: To evaluate the different fractions of dried leaves of Ficus religiosa Linn for analgesic and anti-inflammatory activity using different models of pain and inflammation Materials and Methods: The analgesic activity of F. religiosa carried out using acetic acid-induced writhing in mice and tail flick test in rats. The anti-inflammatory activity was evaluated using carrageenan-induced rat paw edema and cotton pellet-granuloma formation in rats. Five different fractions (FRI, FRII, FRIII, FRIV and FRV) of F. religiosa at the dose level of 20 and 40 mg/kg, p.o were tested. Results: The fraction FRI (40 mg/kg, p.o.) and FRIII (40 mg/kg, p.o) were found to be more effective (P<0.01) in preventing carrageenan induced rat paw edema, cotton pellet granuloma formation, and acetic acid induced writhing compared to the other fractions. FRI (20 mg/kg, p.o.) and FRIII (20 mg/kg, p.o.) were also found to be more effective in increasing latency period in tail flick method. Conclusion: Out of five different fractions of F. religiosa leaves tested, FRI and FRIII possess potent analgesic and anti-inflammatory activities against different models of inflammation and pain. PMID:22144770

  8. Antinociceptive, antioxidant and phytochemical studies of Pakistani medicinal plants.

    PubMed

    Uddin, Ghias; Rauf, Abdur; Siddiqui, Bina Shaheen; Khan, Haroon; Barkatullah; Ullah, Rooh

    2016-05-01

    The aim of the current study was to evaluate the antinociceptive activity of the selected Pakistani medicinal plants (Chenopodium botrys, Micromeria biflora and Teucrium stocksianum) in-vivo followed by their antioxidant potential against 1,1-diphenyl-2-picrylhidrazyl (DPPH) in-vitro. The results demonstrated profound antinociceptive effect of both the crude methanolic extract of Chenopodium botrys (CBM) and subsequent aqueous fraction (CBW) of C. botrys with 80.76% and 84% pain relief in acetic acid induced writhing test at 100 mg/kg i.p respectively. Similarly the crude methanolic extract of Micromeria biflora (MBM) and its subsequent aqueous fraction (MBW) with 66.46% 78.08% pain reversal in acetic acid induced writhing test respectively at 100mg/kg i.p. However, the crude methanolic extract and isolated water fraction of Teucrium stocksianum (TS) did not show any significant effect at test doses. Both the crude extracts and aqueous fractions of selected medicinal plants exhibited marked scavenging effects on DPPH and therefore strongly support the antinociceptive activity. Phytochemical analysis indicated the presence of various classes of natural products (alkaloids, terpenoids, flavonoids etc.) and thus the current finding can be attributed to the presence of these compounds. In short, our findings provide a strong scientific background to the folk uses C. botrys and M. biflora in the management of various painful conditions. PMID:27166536

  9. Anti-hyperalgesic activity of crude extract and 7-methyljuglone of Diospyros lotus roots.

    PubMed

    Rauf, Abdur; Uddin, Ghias; Khan, Haroon; Siddiqui, Bina S; Arfan, Mohammad

    2015-01-01

    This study was designed to evaluate the antihyperalgesic effect of crude extract of Diospyros lotus followed by the isolation and characterisation of 7-methyljuglone in acetic acid and formalin tests. The pretreatment of crude extract evoked dose-dependent inhibition of noxious stimulation with maximum effect of 56.78% in acetic acid-induced writhing test, which were 51.89% and 60.69% in first and second phases, respectively, at 100 mg/kg i.p. The structure of 7-methyljuglone was confirmed by spectroscopic analysis. 7-Methyljuglone evoked profound increase in pain threshhold dose dependently; when it was studied in acetic acid-induced writhing test with 63.73% pain attenuation while 51.22% and 65.44% pain amelioration in first and second phases, respectively, at 100 mg/kg i.p. In conclusion, crude extract and 7-methyljuglone of D. lotus roots possessed both peripheral and central antinociceptive potential and thus could be a useful new therapeutic agent.

  10. Inhibition of neuronal and inducible nitric oxide synthase does not affect the analgesic effects of NMDA antagonists in visceral inflammatory pain.

    PubMed

    Srebro, Dragana; Vučković, Sonja; Prostran, Milica

    2016-01-01

    Previously we described the antinociceptive effect of magnesium sulfate and dizocilpine (MK-801) in the visceral and somatic rat models of pain. In the somatic model of pain, we established the influence of selective inhibitors of neuronal and inducible nitric oxide synthase on the antihyperalgesic effects of magnesium sulfate and dizocilpine. Therefore, the objective of the present study was to determine in the rat model of visceral pain whether same mechanisms are involved in the antinociceptive action of magnesium sulfate and dizocilpine. Analgesic activity was assessed using the acetic acid-induced writhing test in rats. Subcutaneous injection of either magnesium sulfate (15 mg/kg) or dizocilpine (0.01 mg/kg) decreased the number of writhes by about 60 and 70%, respectively. The role of nitric oxide on the effects of magnesium sulfate and dizocilpine was evaluated using selective inhibitor of neuronal (N-ω-Propyl-L-arginine hydrochloride (L-NPA)) and inducible (S-methylisothiourea (SMT)) nitric oxide synthase, which per se did not affect the number of writhes. We observed that the antinociceptive effect of magnesium sulfate or dizocilpine did not change in the presence of L-NPA (2 and 10 mg/kg, i.p.) and SMT (0.015 and 10 mg/kg, i.p.). We conclude that, nitric oxide produced by neuronal and inducible nitric oxide synthase does not modulate the effects of magnesium sulfate and dizocilpine in the visceral inflammatory model of pain in the rat. PMID:27373948

  11. Phytochemistry, anti-inflammatory and analgesic activities of the aqueous leaf extract of Lagenaria breviflora (Cucurbitaceae) in laboratory animals.

    PubMed

    Adedapo, Adeolu; Adewuyi, Temitayo; Sofidiya, Margaret

    2013-03-01

    The plant, and especially the fruit of Lagenaria breviflora is widely used in folklore medicine in West Africa as a herbal remedy for the treatment of human measles, digestive disorders, and as wound antiseptics (e.g. umbilical incision wound), while livestock farmers use it for Newcastle disease and coccidiosis treatment in various animal species, especially poultry. The purpose of this study was to contribute with new information on this plant leaves extract effect, as few studies have considered their effects. We collected fresh leaves of Lagenaria breviflora from the school farm of the University of Ibadan, Nigeria in May 2011. Dried leaves were ground and a 200g sample was used to prepare the extract. The grounded leaves material was allowed to shake in 1000mL distilled water for 48h, in an orbital shaker at room temperature of 24 degreeC. The obtained extract was filtered and concentrated to dryness under reduced pressure at 40 degreeC, and the thick solution was lyophilized, for a final extract yield of 12.6%. Standard phytochemical methods were used to test the presence of saponins, alkaloids, tannins, anthraquinones, cardiac glycosides, cyanogenetic glycosides and flavonoids. The anti-inflammatory activity of the aqueous leaf extract of the plant was assessed using carrageenan-induced paw edema and histamine-induced paw edema in rats. The analgesic effect was determined using the acetic acid writhing method as well as formalin test in mice. Our results showed that the extract at 100 and 200mg/ kg body weight significantly reduced the formation of the oedema induced by carrageenan and histamine. In the acetic acid-induced writhing model, the extract showed a good analgesic effect characterized by reduction in the number of writhes when compared to the control. The extract caused dose-dependent decrease of licking time and licking frequency in rats injected with 2.5% formalin, signifying its analgesic effect. These results were however less than those of

  12. Phytochemistry, anti-inflammatory and analgesic activities of the aqueous leaf extract of Lagenaria breviflora (Cucurbitaceae) in laboratory animals.

    PubMed

    Adedapo, Adeolu; Adewuyi, Temitayo; Sofidiya, Margaret

    2013-03-01

    The plant, and especially the fruit of Lagenaria breviflora is widely used in folklore medicine in West Africa as a herbal remedy for the treatment of human measles, digestive disorders, and as wound antiseptics (e.g. umbilical incision wound), while livestock farmers use it for Newcastle disease and coccidiosis treatment in various animal species, especially poultry. The purpose of this study was to contribute with new information on this plant leaves extract effect, as few studies have considered their effects. We collected fresh leaves of Lagenaria breviflora from the school farm of the University of Ibadan, Nigeria in May 2011. Dried leaves were ground and a 200g sample was used to prepare the extract. The grounded leaves material was allowed to shake in 1000mL distilled water for 48h, in an orbital shaker at room temperature of 24 degreeC. The obtained extract was filtered and concentrated to dryness under reduced pressure at 40 degreeC, and the thick solution was lyophilized, for a final extract yield of 12.6%. Standard phytochemical methods were used to test the presence of saponins, alkaloids, tannins, anthraquinones, cardiac glycosides, cyanogenetic glycosides and flavonoids. The anti-inflammatory activity of the aqueous leaf extract of the plant was assessed using carrageenan-induced paw edema and histamine-induced paw edema in rats. The analgesic effect was determined using the acetic acid writhing method as well as formalin test in mice. Our results showed that the extract at 100 and 200mg/ kg body weight significantly reduced the formation of the oedema induced by carrageenan and histamine. In the acetic acid-induced writhing model, the extract showed a good analgesic effect characterized by reduction in the number of writhes when compared to the control. The extract caused dose-dependent decrease of licking time and licking frequency in rats injected with 2.5% formalin, signifying its analgesic effect. These results were however less than those of

  13. Effect of Jyotishmati (Celastrus paniculatus) seeds in animal models of pain and inflammation

    PubMed Central

    Kulkarni, Yogesh A.; Agarwal, Sneha; Garud, Mayuresh S.

    2015-01-01

    Background: Jyotishmati, scientifically known as Celastrus paniculatus Wild (Celastraceae) is one of the most important medicinal plants in Ayurveda. The plant has shown significant pharmacological activities like anti-arthritic, wound healing, hypolipidemic, and antioxidant. Objective: To study possible effects of alcoholic extract of Celastrus paniculatus seeds (AlcE) in experimentally induced pain and inflammation in mice. Materials and Methods: The antinociceptive activity was evaluated in Swiss albino mice by tail immersion, hot plate, and acetic-acid-induced writhing tests at doses of 250, 500, and 1,000 mg/kg. Anti-inflammatory activity was evaluated in model of carrageenan-induced acute plantar inflammation in Wistar rats. Results: In tail immersion test, AlcE showed significant (P < 0.05) increase in tail withdrawal response at dose of 250 mg/kg with maximum possible effect of 15.71%. The maximum possible effect of 23.32% and 30.16% (P < 0.001) was seen at dose of 500 and 1000 mg/kg at 3 hours after administration of extract, respectively. In hot plate test, increase in paw licking time was reported at dose of 500 and 1000 mg/kg. AlcE (1,000 mg/kg) showed maximum response (6.23 ± 0.46) when compared with control (3.20 ± 0.18) at 90 min. In acetic acid induced writhings, AlcE at dose of 250, 500, and 1,000 mg/kg body weight showed 32.35%, 49.01%, and 58.82% inhibition in writhings, respectively. AlcE treated animals (500 and 1,000 mg/kg) showed significant decrease in paw edema at 3 hours and 4 hours, when compared with control animals. Conclusion: Jyotishmati seed extract possesses significant antinociceptive and anti-inflammatory activity. PMID:26166997

  14. Analgesic, Anti-Inflammatory, and GC-MS Studies on Castanospermum australe A. Cunn. & C. Fraser ex Hook.

    PubMed Central

    Sajeesh, Thankarajan; Parimelazhagan, Thangaraj

    2014-01-01

    The present study was aimed to evaluate the analgesic and anti-inflammatory properties of Castanospermum australe and to profile phytochemicals by GC-MS. The ethanolic extracts were prepared by successive solvent extraction using Soxhlet apparatus. The analgesic activity was analyzed by hot plate method and acetic acid-induced writhing test whereas anti-inflammatory study was done by carrageenan induced paw oedema model. The acute toxicity study revealed that ethanol extracts of leaf and bark of C. australe were safe even at a higher dose of 2000 mg/kg whereas ethanol extract of seed was toxic at the same dose. In both hot plate method (5.85 s) and acetic acid-induced writhing test (57%), the leaf ethanol extract exhibited significant analgesic activity (P < 0.001) at a dose of 400 mg/kg. The anti-inflammatory activity of leaf extract was exhibited by the reduction in paw linear diameter by 64.76% at 400 mg/kg in carrageenan induced paw oedema. The GC-MS analysis of the ethanol extract of leaf revealed sixteen major compounds of which 1,7-dimethyl-4,10-dioxa-1,7-diazacyclododecane, (+)-N-methylephedrine, and permethylspermine were found to be pharmaceutically and the most important. These findings justify that C. australe can be a valuable natural analgesic and anti-inflammatory source which seemed to provide potential phytotherapeutics against various ailments. PMID:24672339

  15. Anti-inflammatory, antinociceptive activity of an essential oil recipe consisting of the supercritical fluid CO2 extract of white pepper, long pepper, cinnamon, saffron and myrrh in vivo.

    PubMed

    Zhang, Yuanbin; Wang, Xinfang; Ma, Ling; Dong, Lin; Zhang, Xinhui; Chen, Jing; Fu, Xueyan

    2014-01-01

    This study was designed to investigate the anti-inflammatory and antinociceptive activities of essential oil recipe (OR) in rodents. The anti-inflammatory activity was evaluated by inflammatory models of dimethylbenzene (DMB)-induced ear vasodilatation and acetic acid-induced capillary permeability enhancement in mice whereas the antinociceptive activity was evaluated using acetic acid-induced writhes and hot plate test methods in mice. Additionally, the chemical composition of OR has been also analyzed by gas chromatography and mass spectrometry (GC/MS). 37 compounds, representing 74.42% of the total oil content, were identified. β-Selinene (7.38%), aromadendrene (5.30%), β-elemene (5.22%), cis-piperitol (5.21%), cis-β-guaiene (4.67%), ylangene (3.70%), 3-heptadecene (3.55%), δ-cadinene (3%) and β-cadinene (2.87%) were found to be the major constituents of the oil. Oral pretreatment with OR (62.5-1000 mg/kg) not only decreased the DMB-induced ear vasodilatation but also attenuated capillary permeability under acetic acid challenge in mice. OR significantly reduced the writhing number evoked by acetic acid injection. All test samples showed no significant analgesic activity on the hot plate pain threshold in mice. These data demonstrated that the OR inhibits inflammatory and peripheral inflammatory pain. These results may support the fact that the essential oil of traditional Hui prescription played a role in the inflammation of stroke. PMID:25263165

  16. Anti-inflammatory, antinociceptive activity of an essential oil recipe consisting of the supercritical fluid CO2 extract of white pepper, long pepper, cinnamon, saffron and myrrh in vivo.

    PubMed

    Zhang, Yuanbin; Wang, Xinfang; Ma, Ling; Dong, Lin; Zhang, Xinhui; Chen, Jing; Fu, Xueyan

    2014-01-01

    This study was designed to investigate the anti-inflammatory and antinociceptive activities of essential oil recipe (OR) in rodents. The anti-inflammatory activity was evaluated by inflammatory models of dimethylbenzene (DMB)-induced ear vasodilatation and acetic acid-induced capillary permeability enhancement in mice whereas the antinociceptive activity was evaluated using acetic acid-induced writhes and hot plate test methods in mice. Additionally, the chemical composition of OR has been also analyzed by gas chromatography and mass spectrometry (GC/MS). 37 compounds, representing 74.42% of the total oil content, were identified. β-Selinene (7.38%), aromadendrene (5.30%), β-elemene (5.22%), cis-piperitol (5.21%), cis-β-guaiene (4.67%), ylangene (3.70%), 3-heptadecene (3.55%), δ-cadinene (3%) and β-cadinene (2.87%) were found to be the major constituents of the oil. Oral pretreatment with OR (62.5-1000 mg/kg) not only decreased the DMB-induced ear vasodilatation but also attenuated capillary permeability under acetic acid challenge in mice. OR significantly reduced the writhing number evoked by acetic acid injection. All test samples showed no significant analgesic activity on the hot plate pain threshold in mice. These data demonstrated that the OR inhibits inflammatory and peripheral inflammatory pain. These results may support the fact that the essential oil of traditional Hui prescription played a role in the inflammation of stroke.

  17. Guava pomace: a new source of anti-inflammatory and analgesic bioactives

    PubMed Central

    2013-01-01

    Background Guava pomace is an example of the processing waste generated after the manufacturing process from the juice industry that could be a source of bioactives. Thus, the present investigation was carried out in order to evaluate the anti-inflammatory and antinociceptive potential and determinate the main phenolic compounds of a guava pomace extract (GPE). Methods The anti-inflammatory activity was evaluated by carrageenan, dextran, serotonin, histamine-induced paw edema and neutrophils migration in the peritoneal cavity models. Acetic acid-induced abdominal writhing and formalin test were performed to investigate the antinociceptive effects. In addition, the content of total phenolic and of individual phenolic compounds was determined by GC/MS. Results GPE showed anti-inflammatory activity by carrageenan, dextran, serotonin, histamine-induced paw edema and neutrophils migration in the peritoneal cavity models (p < 0.05). GPE also demonstrated antinociceptive activity by acetic acid-induced abdominal writhing and formalin test (p < 0.05). The total phenolic value was 3.40 ± 0.09 mg GAE/g and epicatechin, quercetin, myricetin, isovanilic and gallic acids were identified by GC/MS analysis. Conclusions The presence of bioactive phenolic compounds as well as important effects demonstrated in animal models suggest that guava pomace could be an interesting source of anti-inflammatory and analgesic substances. PMID:24063346

  18. Antinociceptive, Immunomodulatory and Antipyretic Activity of Nymphayol Isolated from Nymphaea stellata (Willd.) Flowers

    PubMed Central

    Pandurangan, Subash-Babu; Paul, Antony Samy; Savarimuthu, Ignacimuthu; Ali, Alshatwi A

    2013-01-01

    In the present study, we aimed to analyze the antinociceptive, immunomodulatory and antipyretic activities of nymphayol were investigated in wistar rats and mice. Antinociceptive effect was evaluated by acetic acid induced writhing, formalin induced paw licking and hot-plate tests. Immunomodulatory activity was assessed by neutrophil adhesion test, humoral response to sheep red blood cells, delayed-type hypersensitivity, phagocytic activity and cyclophosphamide induced myelosuppression. Antipyretic activity was evaluated by yeast induced hyperthermia in rats. Nymphayol produced signifi cant (p<0.05) antinociceptive activity in acetic acid induced writhing response and late phase of the formalin induced paw licking response. Pre-treatment with nymphayol (50 mg/kg, oral) evoked a signifi cant increase in neutrophil adhesion to nylon fi bres. The augmentation of humoral immune response to sheep red blood cells by nymphayol (50 mg/kg) was evidenced by increase in antibody titres in rats. Oral administration of nymphayol (50 mg/kg) to rats potentiated the delayed-type hypersensitivity reaction induced by sheep red blood cells. Treatment with nymphayol showed a signifi cant (p<0.05) reduction in pyrexia in rats. The results suggest that nymphayol possesses potent anti-nociceptive, immunomodulatory and antipyretic activities. PMID:24244827

  19. Analgesic and Anti-Inflammatory Activities of Leaf Extract of Mallotus repandus (Willd.) Muell. Arg.

    PubMed Central

    Hasan, Md. Mahadi; Uddin, Nizam; Hasan, Md. Rakib; Islam, A. F. M. Mahmudul; Hossain, Md. Monir; Rahman, Akib Bin; Hossain, Md. Sazzad; Chowdhury, Ishtiaque Ahmed; Rana, Md. Sohel

    2014-01-01

    In folk medicine Mallotus repandus (Willd.) Muell. Arg. is used to treat muscle pain, itching, fever, rheumatic arthritis, snake bite, hepatitis, and liver cirrhosis. This study aimed to evaluate the antinociceptive as well as the anti-inflammatory activities of the methanol extract of leaf. The leaves were extracted with methanol following hot extraction and tested for the presence of phytochemical constituents. Analgesic and anti-inflammatory activities were evaluated using acetic acid induced writhing test, xylene induced ear edema, cotton pellet induced granuloma, and tail immersion methods at doses of 500, 1000, and 2000 mg/kg body weight. The presence of flavonoids, saponins, and tannins was identified in the extract. The extract exhibited considerable antinociceptive and anti-inflammatory activities against four classical models of pain. In acetic acid induced writhing, xylene induced ear edema, and cotton pellet granuloma models, the extract revealed dose dependent activity. Additionally, it increased latency time in tail immersion model. It can be concluded that M. repandus possesses significant antinociceptive potential. These findings suggest that this plant can be used as a potential source of new antinociceptive and anti-inflammatory candidates. The activity of methanol extract is most likely mediated through central and peripheral inhibitory mechanisms. This study justified the traditional use of leaf part of this plant. PMID:25629031

  20. Domain-confined catalytic soot combustion over Co3O4 anchored on a TiO2 nanotube array catalyst prepared by mercaptoacetic acid induced surface-grafting

    NASA Astrophysics Data System (ADS)

    Ren, Jiale; Yu, Yifu; Dai, Fangfang; Meng, Ming; Zhang, Jing; Zheng, Lirong; Hu, Tiandou

    2013-11-01

    Herein, we introduce a specially designed domain-confined macroporous catalyst, namely, the Co3O4 nanocrystals anchored on a TiO2 nanotube array catalyst, which was synthesized by using the mercaptoacetic acid induced surface-grafting method. This catalyst exhibits much better performance for catalytic soot combustion than the conventional TiO2 powder supported one in gravitational contact mode (GMC).Herein, we introduce a specially designed domain-confined macroporous catalyst, namely, the Co3O4 nanocrystals anchored on a TiO2 nanotube array catalyst, which was synthesized by using the mercaptoacetic acid induced surface-grafting method. This catalyst exhibits much better performance for catalytic soot combustion than the conventional TiO2 powder supported one in gravitational contact mode (GMC). Electronic supplementary information (ESI) available: The images of XRD, UV-vis, EDX and soot-TPR. The table providing information on Co/Ti-NA catalysts. See DOI: 10.1039/c3nr03757f

  1. Aqueous Methanol Extracts of Cochlospermum tinctorium (A. Rich) Possess Analgesic and Anti-inflammatory Activities

    PubMed Central

    Ahmed, TS; Magaji, MG; Yaro, AH; Musa, AM; Adamu, AK

    2011-01-01

    Cochlopermum tinctorium A. Rich. (Cochlospermaceae) is a commonly used medicinal plant in the West Africa sub-region for the management of various conditions including pain and inflammatory conditions. In the present study, we report the analgesic and anti-inflammatory activities of the aqueous methanol leaf (20–80 mg/kg), root (7.5–30 mg/kg), and root bark (20–80 mg/kg) extracts of the plant. The analgesic potentials of the extracts were studied using acetic acid induced writhing and hot plate tests in mice while the anti-inflammatory activity was investigated using carrageenan-induced paw edema in rats.The extracts significantly and dose dependently inhibited the acetic acid-induced writhing in mice. However, the highest protection against writhing was produced by aqueous methanol leaf extract at the dose of 80 mg/kg (96.65%) which even was greater than that of the standard agent, ketoprofen (82.30%). The extracts did not significantly increase mean latency of response in the hot plate test. However, aqueous methanol root bark extract at the dose of 20 mg/kg significantly (P < 0.05) increased the mean latency of pain response. While the extracts of the root and root bark extracts of the plant afforded non dose-dependent protection against carrageenan-induced edema, the aqueous methanol leaf extract significantly and dose-dependently inhibited carrageenan-induced hind paw edema at the end of the third hour.The present study suggests that the aqueous methanol leaf, root, and root bark extracts of Cochlopermum tinctorium possess analgesic and anti-inflammatory activities which lend some credence to the ethnomedical claim of the use of the plant in the management of pain and inflammatory conditions. PMID:21897665

  2. Inhibition of NO2, PGE2, TNF-α, and iNOS EXpression by Shorea robusta L.: An Ethnomedicine Used for Anti-Inflammatory and Analgesic Activity

    PubMed Central

    Debprasad, Chattopadhyay; Hemanta, Mukherjee; Paromita, Bag; Durbadal, Ojha; Kumar, Konreddy Ananda; Shanta, Dutta; Kumar, Haldar Pallab; Tapan, Chatterjee; Ashoke, Sharon; Sekhar, Chakraborti

    2012-01-01

    This paper is an attempt to evaluate the anti-inflammatory and analgesic activities and the possible mechanism of action of tender leaf extracts of Shorea robusta, traditionally used in ailments related to inflammation. The acetic-acid-induced writhing and tail flick tests were carried out for analgesic activity, while the anti-inflammatory activity was evaluated in carrageenan-and dextran- induced paw edema and cotton-pellet-induced granuloma model. The acetic-acid-induced vascular permeability, erythrocyte membrane stabilization, release of proinflammatory mediators (nitric oxide and prostaglandin E2), and cytokines (tumor necrosis factor-α, and interleukins-1β and -6) from lipopolysaccharide-stimulated human monocytic cell lines were assessed to understand the mechanism of action. The results revealed that both aqueous and methanol extract (400 mg/kg) caused significant reduction of writhing and tail flick, paw edema, granuloma tissue formation (P < 0.01), vascular permeability, and membrane stabilization. Interestingly, the aqueous extract at 40 μg/mL significantly inhibited the production of NO and release of PGE2, TNF-α, IL-1β, and IL-6. Chemically the extract contains flavonoids and triterpenes and toxicity study showed that the extract is safe. Thus, our study validated the scientific rationale of ethnomedicinal use of S. robusta and unveils its mechanism of action. However, chronic toxicological studies with active constituents are needed before its use. PMID:22649472

  3. Antinociceptive and anti-inflammatory effects of ethanolic extracts of Glycine max (L.) Merr and Rhynchosia nulubilis seeds.

    PubMed

    Yim, Joo Hyuk; Lee, Ok-Hwan; Choi, Ung-Kyu; Kim, Young-Chan

    2009-11-01

    The aim of this study was to assess the in vivo potential of ethanolic extracts of Glycine max (L.) Merr. (SoRiTae) and Rhynchosia nulubilis (Yak-Kong) seeds as natural anti-nociceptive and anti-inflammatory agents. To assess the anti-nociceptive and anti-inflammatory potential, the ethanolic extracts of SoRiTae and Yak-Kong seeds were tested in arachidonic acid-induced ear edema, carrageenan induced paw edema, formalin-induced licking time, acetic acid induced writhing and hot plate-induced thermal stimulation in mice. The administration of ethanolic extracts of SoRiTae and Yak-Kong seeds evoked a significant effect of anti-nociceptive and anti-inflammatory activities as compared to standards aminopyrine and indomethacin. The ear edema, paw edema, paw licking time, pain and writhes in mice were significantly reduced (p < 0.05) as compared to the control. The results obtained in this study indicate that both SoRiTae and Yak-Kong soybeans possesses potential anti-nociceptive and anti-inflammatory activities.

  4. Antinociceptive and Anti-Inflammatory Effects of Ethanolic Extracts of Glycine max (L.) Merr and Rhynchosia nulubilis Seeds

    PubMed Central

    Yim, Joo Hyuk; Lee, Ok-Hwan; Choi, Ung-Kyu; Kim, Young-Chan

    2009-01-01

    The aim of this study was to assess the in vivo potential of ethanolic extracts of Glycine max (L.) Merr. (SoRiTae) and Rhynchosia nulubilis (Yak-Kong) seeds as natural anti-nociceptive and anti-inflammatory agents. To assess the anti-nociceptive and anti-inflammatory potential, the ethanolic extracts of SoRiTae and Yak-Kong seeds were tested in arachidonic acid-induced ear edema, carrageenan induced paw edema, formalin-induced licking time, acetic acid induced writhing and hot plate-induced thermal stimulation in mice. The administration of ethanolic extracts of SoRiTae and Yak-Kong seeds evoked a significant effect of anti-nociceptive and anti-inflammatory activities as compared to standards aminopyrine and indomethacin. The ear edema, paw edema, paw licking time, pain and writhes in mice were significantly reduced (p < 0.05) as compared to the control. The results obtained in this study indicate that both SoRiTae and Yak-Kong soybeans possesses potential anti-nociceptive and anti-inflammatory activities. PMID:20087462

  5. Anti-inflammatory, analgesic and antipyretic properties of Clitoria ternatea root.

    PubMed

    Devi, B Parimala; Boominathan, R; Mandal, Subhash C

    2003-06-01

    Clitoria ternatea roots methanol extract when given by oral route to rats was found to inhibit both the rat paw oedema caused by carrageenin and vascular permeability induced by acetic acid in rats. Moreover, the extract exhibited a significant inhibition in yeast-induced pyrexia in rats. In the acetic acid-induced writhing response, the extract markedly reduced the number of writhings at doses of 200 and 400 mg/kg (p.o.) in mice. PMID:12781804

  6. Anti-Inflammatory and Antinociceptive Activities of a Hydroethanolic Extract of Tamarindus indica Leaves.

    PubMed

    Bhadoriya, Santosh Singh; Mishra, Vijay; Raut, Sushil; Ganeshpurkar, Aditya; Jain, Sunil K

    2012-01-01

    The present study aimed to investigate the anti-inflammatory and anti-nociceptive potential of a hydroethanolic extract of Tamarindus indica L. leaves (HTI) along with its possible mode of action. The anti-inflammatory activity of HTI was estimated by carrageenan-induced hind paw oedema in male Wistar albino rats. Furthermore, HTI was assessed to determine its effects on membrane stabilization. The antinociceptive action was determined by acetic acid-induced writhing, tail-flick, and the hot plate model. Oral administration of HTI at the dose of 500, 750, and 1000 mg/kg body weight produced significant (P< 0.01) anti-inflammatory as well as antinociceptive actions in a dose-dependent manner. Among all tested doses, 1000 mg/kg, p. o. reduced carrageenan-induced rat paw oedema at 1, 2, 3, and 4 h. Moreover, the 1000 mg/kg dose exhibited maximum percentage inhibition of acetic acid-induced writhing (48.9%), whereas standard drug diclofenac (25 mg/kg, p. o.) showed maximum inhibition (50.9%) of writhing. In the hot plate model, HTI (1000 mg/kg, orally) increased mean basal reaction time after 120 min (7.12±0.05 sec). In the tail flick model, HTI increased the maximum percentage of latency (36.06%), whereas the standard drug pethidine (4 mg/kg, intraperitoneally) showed maximum percentage of latency (43.85%) after 60 min. The findings of the present study supported anti-inflammatory and antinociceptive claims of T. indica as were mentioned in Indian traditional and folklore practices.

  7. Ameliorative Effects of a Polyphenolic Fraction of Cinnamomum zeylanicum L. Bark in Animal Models of Inflammation and Arthritis.

    PubMed

    Rathi, Badal; Bodhankar, Subhash; Mohan, V; Thakurdesai, Prasad

    2013-01-01

    Cinnamon bark (Cinnamomum zeylanicum Syn C. verum, family: Lauraceae) is one of the oldest traditional medicines for inflammatory- and pain-related disorders. The objective of the present study was to evaluate the efficacy of the polyphenol fraction from Cinnamomum zeylanicum bark (CPP) in animal models of inflammation and rheumatoid arthritis. Dose-response studies of CPP (50, 100, and 200 mg/kg) used in a separate set of in vivo experiments were conducted in acute (carrageenan-induced rat paw edema), subacute (cotton pellet-induced granuloma), and sub-chronic (AIA, adjuvant-induced established polyarthrtis) models of inflammation in rats and the acetic acid-induced writhing model of pain in mice. Effects of CPP on cytokine (IL-2, IL-4, and IFNγ) release from Concanavalin (ConA)-stimulated lymphocytes were also evaluated in vitro. CPP showed a strong and dose-dependent reduction in paw volume, weight loss reversal effects against carrageenan-induced paw edema, and cotton pellet-induced granuloma models in rats. CPP (200 mg/kg p.o. for 10 days) showed a significant reduction in elevated serum TNF-α concentration without causing gastric ulcerogenicity in the AIA model in rats. CPP also demonstrated mild analgesic effects during acute treatment as evidenced by the reduction in the writhing and paw withdrawal threshold of the inflamed rat paw during the acetic acid-induced writhing model and Randall-Selitto test. CPP was found to inhibit cytokine (IL-2, IL-4, and IFNγ) release from ConA-stimulated lymphocytes in vitro. In conclusion, CPP demonstrated prominent action in animal models of inflammation and arthritis and therefore can be considered as a potential anti-rheumatic agent with disease-modifying action.

  8. Antinociceptive and Anti-Inflammatory Activities of Crude Methanolic Extract of Red Alga Bryothamnion triquetrum

    PubMed Central

    Cavalcante-Silva, Luiz Henrique Agra; da Matta, Carolina Barbosa Brito; de Araújo, Morgana Vital; Barbosa-Filho, José Maria; de Lira, Daysianne Pereira; de Oliveira Santos, Bárbara Viviana; de Miranda, George Emmanuel C.; Alexandre-Moreira, Magna Suzana

    2012-01-01

    The marine environment is an extraordinary reservoir of bioactive natural products, many of which exhibit chemical and structural features not found in terrestrial natural products. In this regard, the aim of this study was to investigate the possible antinociceptive and anti-inflammatory activities of a crude methanolic extract of the red alga Bryothamnion triquetrum (BT-MeOH) in murine models. Groups of Swiss mice of both sexes (25–30 g) were used throughout the experiments. The potential antinociceptive of BT-MeOH was evaluated by means of the following tests: acetic acid-induced writhing, hot-plate test and glutamate- and formalin-induced nociception. The anti-inflammatory activity of BT-MeOH was investigated using the zymosan A-induced peritonitis test. The tests were conducted using 100 mg/kg (p.o.) BT-MeOH, 33.3 mg/kg (p.o.) dipyrone, 35.7 mg/kg (p.o.) indomethacin and 5.7 mg/kg (s.c.) morphine. The extract and all standard drugs were administered 40 min before the nociceptive/inflammatory stimulus. In the acetic acid-induced writhing test, BT-MeOH and dipyrone inhibited the nociceptive response by 55.9% (22.2 ± 2.0 writhings; p < 0.01) and 80.9% (9.6 ± 2.1 writhings; p < 0.01). In the hot-plate test, BT-MeOH did not increase the latency time of the animals in the time evaluated. In addition, BT-MeOH inhibited glutamate-induced nociception by 50.1%. While BT-MeOH did not inhibit the neurogenic phase in formalin-induced nociception, the inflammatory phase was inhibited by 53.1% (66.8 ± 14.2 s; p < 0.01). Indomethacin inhibited the inflammatory phase by 60.2% (56.8 ± 8.7 s; p < 0.01). In the zymosan-induced peritonitis test, BT-MeOH inhibited 55.6% (6.6 ± 0.2 × 106 leukocytes/mL; p < 0.01) of leukocyte migration, while indomethacin inhibited 78.1% (3.2 ± 0.1 × 106 leukocytes/mL; p < 0.01). Based on the results obtained in this study, we conclude that BT-MeOH has peripheral antinociceptive and anti-inflammatory activities. However, more studies need

  9. Co-administration of α-lipoic acid and cyclosporine aggravates colon ulceration of acetic acid-induced ulcerative colitis via facilitation of NO/COX-2/miR-210 cascade.

    PubMed

    El-Gowelli, Hanan M; Saad, Evan I; Abdel-Galil, Abdel-Galil A; Ibrahim, Einas R

    2015-11-01

    In this work, α-lipoic acid and cyclosporine demonstrated significant protection against acetic acid-induced ulcerative colitis in rats. We proposed that α-lipoic acid and cyclosporine co-administration might modulate their individual effects. Induction of ulcerative colitis in rats was performed by intra-rectal acetic acid (5% v/v) administration for 3 consecutive days. Effects of individual or combined used of α-lipoic acid (35 mg/kg ip) or cyclosporine (5mg/kg sc) for 6 days starting 2 days prior to acetic acid were assessed. Acetic acid caused colon ulceration, bloody diarrhea and weight loss. Histologically, there was mucosal atrophy and inflammatory cells infiltration in submucosa, associated with depletion of colon reduced glutathione, superoxide dismutase and catalase activities and elevated colon malondialdehyde, serum C-reactive protein (C-RP) and tumor necrosis factor-α (TNF-α). Colon gene expression of cyclooxygenase-2 and miR-210 was also elevated. These devastating effects of acetic acid were abolished upon concurrent administration of α-lipoic acid. Alternatively, cyclosporine caused partial protection against acetic acid-induced ulcerative colitis. Cyclosporine did not restore colon reduced glutathione, catalase activity, serum C-RP or TNF-α. Unexpectedly, co-administration of α-lipoic acid and cyclosporine aggravated colon ulceration. Concomitant use of α-lipoic acid and cyclosporine significantly increased nitric oxide production, cyclooxygenase-2 and miR-210 gene expression compared to all other studied groups. The current findings suggest that facilitation of nitric oxide/cyclooxygenase-2/miR-210 cascade constitutes, at least partially, the cellular mechanism by which concurrent use of α-lipoic acid and cyclosporine aggravates colon damage. Collectively, the present work highlights the probable risk of using α-lipoic acid/cyclosporine combination in ulcerative colitis patients.

  10. Phytochemical Screening and Antinociceptive and Antidiarrheal Activities of Hydromethanol and Petroleum Benzene Extract of Microcos paniculata Barks

    PubMed Central

    Moushome, Rafath Ara; Akter, Mst. Irin

    2016-01-01

    Introduction. Microcos paniculata is traditionally used for treating diarrhea, wounds, cold, fever, hepatitis, dyspepsia, and heat stroke. Objective. To investigate the qualitative phytochemical constituents of hydromethanol (HMPB) and petroleum benzene extract of Microcos paniculata barks (PBMPB) and to evaluate their antinociceptive and antidiarrheal activities. Methods. Phytochemical constituents and antinociceptive and antidiarrheal activities were determined and evaluated by different tests such as Molisch's, Fehling's, Mayer's, Wagner's, Dragendorff's, frothing, FeCl3, alkali, Pew's, and Salkowski's test, general test of glycosides, Baljet and NH4OH test, formalin-induced paw licking, acetic acid-induced writhing, tail immersion, and hot plate tests, and castor oil and MgSO4 induced diarrheal tests. Results. These extracts revealed the presence of saponins, flavonoids, and triterpenoids and significantly (⁎P < 0.05, versus control) reduced paw licking and abdominal writhing of mice. At 30 min after their administration, PBMPB revealed significant increase in latency (⁎P < 0.05, versus control) in tail immersion test. In hot plate test, HMPB and PBMPB 200 mg/kg showed significant increase in response latency (⁎P < 0.05, versus control) at 30 min after their administration. Moreover, both extracts significantly (⁎P < 0.05, versus control) inhibited percentage of diarrhea in antidiarrheal models. Conclusion. Study results indicate that M. paniculata may provide a source of plant compounds with antinociceptive and antidiarrheal activities. PMID:27777944

  11. The effect of duration of exposure on sulfuric acid-induced pulmonary function changes in asthmatic adolescent subjects: A dose-response study

    SciTech Connect

    Koenig, J.Q.; Covert, D.S.; Larson, T.V.; Pierson, W.E. )

    1992-09-01

    To evaluate the pulmonary effects of varying doses of sulfuric acid, adolescent subjects with asthma were exposed to 35 or 70 micrograms/m3 sulfuric acid for 45 or 90 min. Exposure was carried out during intermittent moderate exercise. The pulmonary functions measured before and after exposure were FEV1, FVC, and total respiratory resistance. The 45 min exposures were associated with larger decreases in FEV1 (-6% or -3%) than the 90 min exposures (-1% or +2%). Analysis of variance of the change in FEV1 among the exposures revealed that the 45 min exposure to 35 micrograms/m3 was significant (p = 0.03). The p value for 45 min exposure to 70 micrograms/m3 was not significant (p = 0.08). Using analysis of variance, neither of the 90 min exposures was associated with a significant decrease in FEV1 compared to air exposure. Also, none of the changes in FVC or RT was significant. When baseline to post-exposure changes were compared for each of the five test atmospheres using paired t tests, both of the 45 min exposures were associated with statistical significance (p < 0.001 for 35 micrograms/m3 and p < 0.005 for 70 micrograms/m3). This baseline to post exposure change was not statistically significant for the 90 min exposures. The reason for the lesser effect on pulmonary function at increased exposure duration is not known; it may be due to changes in either varying deposition patterns or changes in buffering capacity of the cells lining the airways. With respect to individual sensitivities to H2SO4, the data showed a significant consistency across test atmospheres.

  12. Stability-indicating methods for the analysis of ciprofloxacin in the presence of its acid induced degradation product: A comparative study

    NASA Astrophysics Data System (ADS)

    Attia, Khalid A. M.; Nassar, Mohammed W. I.; El-Zeiny, Mohamed B.; Serag, Ahmed

    2016-04-01

    Four rapid, simple, accurate and precise spectrophotometric methods were used for the determination of ciprofloxacin in the presence of its acidic degradation product. The methods under study are ratio derivative, ratio difference, mean centering and dual wavelength. All the methods were validated according to the ICH guidelines and the obtained accuracy, precision and repeatability were found to be within the acceptable limits. The selectivity of the proposed methods was tested using laboratory prepared mixtures and assessed by applying the standard addition technique. So, they can be used for the routine analysis of ciprofloxacin in quality-control laboratories.

  13. Ortho-eugenol exhibits anti-nociceptive and anti-inflammatory activities.

    PubMed

    Fonsêca, Diogo V; Salgado, Paula R R; Aragão Neto, Humberto de C; Golzio, Adriana M F O; Caldas Filho, Marcelo R D; Melo, Cynthia G F; Leite, Fagner C; Piuvezam, Marcia R; Pordeus, Liana Clébia de Morais; Barbosa Filho, José M; Almeida, Reinaldo N

    2016-09-01

    Ortho-eugenol is a much used phenylpropanoid whose ability to reduce pain and inflammation has never been studied. Researching ortho-eugenol's antinociceptive and anti-inflammatory activity, and its possible mechanisms of action is therefore of interest. The administration of vehicle, ortho-eugenol (50, 75 and 100mg/kg i.p.), morphine (6mg/kg, i.p.) or dexamethasone (2mg/kg, s.c.) occurred 30min before the completion of pharmacological tests. Pretreatment with ortho-eugenol did not change motor coordination test results, but reduced the number of writhes and licking times in the writhing test and glutamate test, respectively. The reaction time from thermal stimulus was significantly increased in the hot plate test after administration of ortho-eugenol. Treatment with yohimbine reversed the antinociceptive effect of ortho-eugenol, suggesting involvement of the adrenergic system. In anti-inflammatory tests, ortho-eugenol inhibited acetic acid induced vascular permeability and leukocyte migration, reducing TNF-α and IL-1β by virtue of its suppression of NF-κB and p38 phosphorylated forms in the peritonitis test. From these results, ortho-eugenol antinociceptive effects mediated by the adrenergic system and anti-inflammatory activity through regulation of proinflammatory cytokines and phosphorylation of NF-kB and p38 become evident for the first time. PMID:27355133

  14. Ortho-eugenol exhibits anti-nociceptive and anti-inflammatory activities.

    PubMed

    Fonsêca, Diogo V; Salgado, Paula R R; Aragão Neto, Humberto de C; Golzio, Adriana M F O; Caldas Filho, Marcelo R D; Melo, Cynthia G F; Leite, Fagner C; Piuvezam, Marcia R; Pordeus, Liana Clébia de Morais; Barbosa Filho, José M; Almeida, Reinaldo N

    2016-09-01

    Ortho-eugenol is a much used phenylpropanoid whose ability to reduce pain and inflammation has never been studied. Researching ortho-eugenol's antinociceptive and anti-inflammatory activity, and its possible mechanisms of action is therefore of interest. The administration of vehicle, ortho-eugenol (50, 75 and 100mg/kg i.p.), morphine (6mg/kg, i.p.) or dexamethasone (2mg/kg, s.c.) occurred 30min before the completion of pharmacological tests. Pretreatment with ortho-eugenol did not change motor coordination test results, but reduced the number of writhes and licking times in the writhing test and glutamate test, respectively. The reaction time from thermal stimulus was significantly increased in the hot plate test after administration of ortho-eugenol. Treatment with yohimbine reversed the antinociceptive effect of ortho-eugenol, suggesting involvement of the adrenergic system. In anti-inflammatory tests, ortho-eugenol inhibited acetic acid induced vascular permeability and leukocyte migration, reducing TNF-α and IL-1β by virtue of its suppression of NF-κB and p38 phosphorylated forms in the peritonitis test. From these results, ortho-eugenol antinociceptive effects mediated by the adrenergic system and anti-inflammatory activity through regulation of proinflammatory cytokines and phosphorylation of NF-kB and p38 become evident for the first time.

  15. Analgesic effects of stem bark extracts of Trichilia monadelpha (Thonn.) JJ De Wilde

    PubMed Central

    Woode, Eric; Amoh-Barimah, Ama Kyeraa; Abotsi, Wonder Kofi Mensah; Ainooson, George Kwaw; Owusu, George

    2012-01-01

    Objectives: Various parts of Trichilia monadelpha (Thonn) JJ De Wilde (Fam. Meliaceae) are used in Ghanaian traditional medicine for the treatment of painful and inflammatory conditions. The present study examined the analgesic properties of the petroleum ether (PEE), ethyl acetate (EAE), and the hydro-ethanolic (HAE) extract of the stem bark of the plant in murine models. Materials and Methods: PEE, EAE, and HAE were assessed in chemical (acetic acid-induced abdominal writhing and formalin tests), thermal (hot plate test), and mechanical (Randall-Selitto paw pressure test) pain models. The possible mechanisms of the antinociceptive action were also examined with various antagonists in the formalin test. Results: HAE, EAE, and PEE, each at doses of 10–100 mg/kg orally, and the positive controls (morphine and diclofenac) elicited significant dose-dependent antinociceptive activity in the chemical (acetic acid abdominal writhing and formalin tests), thermal (hot plate test), and mechanical (Randall-Selitto paw pressure test) pain models in rodents. The antinociceptive effect of HAE was partly or wholly reversed by systemic administration of atropine, naloxone, and glibenclamide. The antinociceptive effects of EAE and PEE were inhibited by atropine. Conclusion: The extracts HAE, EAE, and PEE caused dose-related antinociception in chemical, thermal, and mechanical models of pain in animals. The mechanism of action of HAE involves an interaction with muscarinic cholinergic, adenosinergic, opioidergic pathways, and ATP-sensitive K+ channels while that of EAE and PEE involve the muscarinic cholinergic system. PMID:23248409

  16. Neuroprotective Effect of Uncaria rhynchophylla in Kainic Acid-Induced Epileptic Seizures by Modulating Hippocampal Mossy Fiber Sprouting, Neuron Survival, Astrocyte Proliferation, and S100B Expression

    PubMed Central

    Liu, Chung-Hsiang; Lin, Yi-Wen; Tang, Nou-Ying; Liu, Hsu-Jan; Hsieh, Ching-Liang

    2012-01-01

    Uncaria rhynchophylla (UR), which is a traditional Chinese medicine, has anticonvulsive effect in our previous studies, and the cellular mechanisms behind this are still little known. Because of this, we wanted to determine the importance of the role of UR on kainic acid- (KA-) induced epilepsy. Oral UR for 6 weeks can successfully attenuate the onset of epileptic seizure in animal tests. Hippocampal mossy fiber sprouting dramatically decreased, while neuronal survival increased with UR treatment in hippocampal CA1 and CA3 areas. Furthermore, oral UR for 6 weeks significantly attenuated the overexpression of astrocyte proliferation and S100B proteins but not γ-aminobutyric acid A (GABAA) receptors. These results indicate that oral UR for 6 weeks can successfully attenuate mossy fiber sprouting, astrocyte proliferation, and S100B protein overexpression and increase neuronal survival in KA-induced epileptic rat hippocampus PMID:21837247

  17. Domains of the cucumber mosaic virus 2b silencing suppressor protein affecting inhibition of salicylic acid-induced resistance and priming of salicylic acid accumulation during infection

    PubMed Central

    Zhou, Tao; Murphy, Alex M.; Lewsey, Mathew G.; Westwood, Jack H.; Zhang, Heng-Mu; González, Inmaculada; Canto, Tomás

    2014-01-01

    The cucumber mosaic virus (CMV) 2b silencing suppressor protein allows the virus to overcome resistance to replication and local movement in inoculated leaves of plants treated with salicylic acid (SA), a resistance-inducing plant hormone. In Arabidopsis thaliana plants systemically infected with CMV, the 2b protein also primes the induction of SA biosynthesis during this compatible interaction. We found that CMV infection of susceptible tobacco (Nicotiana tabacum) also induced SA accumulation. Utilization of mutant 2b proteins expressed during infection of tobacco showed that the N- and C-terminal domains, which had previously been implicated in regulation of symptom induction, were both required for subversion of SA-induced resistance, while all mutants tested except those affecting the putative phosphorylation domain had lost the ability to prime SA accumulation and expression of the SA-induced marker gene PR-1. PMID:24633701

  18. Folic acid induces cell type-specific changes in the transcriptome of breast cancer cell lines: a proof-of-concept study.

    PubMed

    Price, R Jordan; Lillycrop, Karen A; Burdge, Graham C

    2016-01-01

    The effect of folic acid (FA) on breast cancer (BC) risk is uncertain. We hypothesised that this uncertainty may be due, in part, to differential effects of FA between BC cells with different phenotypes. To test this we investigated the effect of treatment with FA concentrations within the range of unmetabolised FA reported in humans on the expression of the transcriptome of non-transformed (MCF10A) and cancerous (MCF7 and Hs578T) BC cells. The total number of transcripts altered was: MCF10A, seventy-five (seventy up-regulated); MCF7, twenty-four (fourteen up-regulated); and Hs578T, 328 (156 up-regulated). Only the cancer-associated gene TAGLN was altered by FA in all three cell lines. In MCF10A and Hs578T cells, FA treatment decreased pathways associated with apoptosis, cell death and senescence, but increased those associated with cell proliferation. The folate transporters SLC19A1, SLC46A1 and FOLR1 were differentially expressed between cell lines tested. However, the level of expression was not altered by FA treatment. These findings suggest that physiological concentrations of FA can induce cell type-specific changes in gene regulation in a manner that is consistent with proliferative phenotype. This has implications for understanding the role of FA in BC risk. In addition, these findings support the suggestion that differences in gene expression induced by FA may involve differential activities of folate transporters. Together these findings indicate the need for further studies of the effect of FA on BC.

  19. Antinociceptive and Anti-inflammatory Activities of the Methanolic Extract from the Stem Bark of Lophanthera lactescens.

    PubMed

    dos Santos, Gabriela Carmelinda Martins; Fernandes, Renata Duarte; Barros, Tarcila Rocha; Abreu, Heber dos Santos; Suzart, Luciano Ramos; de Carvalho, Mário Geraldo; Braz Filho, Raimundo; Marinho, Bruno Guimarães

    2015-12-01

    Lophanthera lactescens is a medicinal plant commonly used in traditional medicine to relieve fever and pain in inflammatory processes. In the present study, the in vivo antinociceptive and anti-inflammatory effects of the methanolic extract from L. lactescens have been investigated. Antinociceptive activity was evaluated through writhing, formalin, and tail flick tests, while the anti-inflammatory activity was evaluated through paw oedema and air pouch tests in mice. A phytochemical analysis was performed. The extract produced significant inhibition on nociception induced by acetic acid-induced abdominal writhing, formalin, and tail flick tests, and on inflammation induced by oedema and air pouch tests. The previous administration of atropine and glibenclamide reduced the antinociceptive effect produced by the methanolic extract from L. lactescens on the tail flick test in 89% and 66%, respectively. The methanolic extract had no significant effect in the open field test. No intoxication symptoms were observed in the animals administered orally at increasing doses up to 2000 mg/kg. The methanolic extract from the stem bark of L. lactescens possesses antinociceptive properties on models of acute pain induced by chemical and thermal stimuli as well as in models of inflammation and further suggests that this anti-inflammatory activity might involve inhibition of the proinflammatory cytokines, and the antinociceptive activity might involve participation of the cholinergic system and adenosine triphosphate-dependent K+ channel.

  20. Preliminary pharmacological screening of Bixa orellana L. leaves.

    PubMed

    Shilpi, Jamil Ahmad; Taufiq-Ur-Rahman, Md; Uddin, Shaikh Jamal; Alam, Md Shahanur; Sadhu, Samir Kumar; Seidel, Véronique

    2006-11-24

    Preliminary pharmacological studies were performed on the methanol extract of Bixa orellana L. (Bixaceae) leaves to investigate neuropharmacological, anticonvulsant, analgesic, antidiarrhoeal activity and effect on gastrointestinal motility. All studies were conducted in mice using doses of 125, 250 and 500 mg/kg of body weight. In the pentobarbitone-induced hypnosis test, the extract statistically reduced the time for the onset of sleep at 500 mg/kg dose and (dose-dependently) increased the total sleeping time at 250 and 500 mg/kg dose. A statistically significant decrease in locomotor activity was observed at all doses in the open-field and hole-cross tests. In the strychnine-induced anticonvulsant test, the extract increased the average survival time of the test animals (statistically significant at 250 and 500 mg/kg). The extract significantly and dose-dependently reduced the writhing reflex in the acetic acid-induced writhing test. Antidiarrhoeal activity was supported by a statistically significant decrease in the total number of stools (including wet stools) in castor oil-induced diarrhoea model. A statistically significant delay in the passage of charcoal meal was observed at 500 mg/kg in the gastrointestinal motility test. The extract was further evaluated in vitro for antioxidant and antibacterial activity. It revealed radical scavenging properties in the DPPH assay (IC(50)=22.36 microg/ml) and antibacterial activity against selected causative agents of diarrhoea and dysentery, including Shigella dysenteriae. PMID:16963211

  1. Wavelength-dependent in-vitro and in-vivo photodynamic effects after sensitization with 5-aminolevulinic acid induced protoporphyrin IX

    NASA Astrophysics Data System (ADS)

    Szeimies, Rolf-Markus; Abels, Christoph; Fritsch, Clemens; Steinbach, Pia; Baeumler, Wolfgang; Messmann, Helmut; Goetz, Alwin E.; Goerz, Guenter; Landthaler, Michael

    1996-01-01

    Photodynamic therapy (PDT) with topically applied 5-aminolevulinic acid (ALA) is of growing interest, in particular in dermatology. Due to the fact that PDT with intravenously administered Photofrin is the only clinically approved sensitizer so far and is performed at a wavelength of 630 nm, this wavelength is also used in most experimental and clinical trials with ALA. In this study influence of irradiation with coherent light from a tunable dye laser at different wavelengths ranging from 625 to 649 nm was investigated. In in vitro experiments HaCaT immortalized human keratinocytes were sensitized with 30 (mu) g/ml ALA for 24 hrs. By determination of cell viability with the MTT test, best cell-killing effects were observed following irradiation at 635 nm. In an in vivo setting using an amelanotic melanoma (A-Mel-3) grown subcutaneously in Syrian Golden hamsters, these results were confirmed: tumor growth determined by measuring tumor volume increase after 28 days was less pronounced in animals treated with 100 mg/kg ALA i.v. and irradiated 2.5 hrs. later at 635 nm, as compared to animals receiving an equal dose and irradiated at 630 nm. This observation in vitro is probably due to large amounts of photosensitizing protoporphyrin IX (PP) localized in cell membranes which is visualized by confocal laser scanning microscopy (CLSM) and determined by HPLC analysis. These results suggest that in ALA-PDT when a coherent light source is used probably better results are achieved irradiating at 635 nm.

  2. Jasmonic acid-induced volatiles of Brassica oleracea attract parasitoids: effects of time and dose, and comparison with induction by herbivores

    PubMed Central

    Bruinsma, Maaike; Posthumus, Maarten A.; Mumm, Roland; Mueller, Martin J.; van Loon, Joop J. A.; Dicke, Marcel

    2009-01-01

    Caterpillar feeding induces direct and indirect defences in brassicaceous plants. This study focused on the role of the octadecanoid pathway in induced indirect defence in Brassica oleracea. The effect of induction by exogenous application of jasmonic acid (JA) on the responses of Brussels sprouts plants and on host-location behaviour of associated parasitoid wasps was studied. Feeding by the biting–chewing herbivores Pieris rapae and Plutella xylostella resulted in significantly increased endogenous levels of JA, a central component in the octadecanoid signalling pathway that mediates induced plant defence. The levels of the intermediate 12-oxophyto-dienoic acid (OPDA) were significantly induced only after P. rapae feeding. Three species of parasitoid wasps, Cotesia glomerata, C. rubecula, and Diadegma semiclausum, differing in host range and host specificity, were tested for their behavioural responses to volatiles from herbivore-induced, JA-induced, and non-induced plants. All three species were attracted to volatiles from JA-induced plants compared with control plants; however, they preferred volatiles from herbivore-induced plants over volatiles from JA-induced plants. Attraction of C. glomerata depended on both timing and dose of JA application. JA-induced plants produced larger quantities of volatiles than herbivore-induced and control plants, indicating that not only quantity, but also quality of the volatile blend is important in the host-location behaviour of the wasps. PMID:19451186

  3. Inhibition of 13-cis retinoic acid-induced gene expression of reactive-resistance genes by thalidomide in glioblastoma tumours in vivo.

    PubMed

    Milanovic, Dusan; Sticht, Carsten; Röhrich, Manuel; Maier, Patrick; Grosu, Anca-L; Herskind, Carsten

    2015-10-01

    The cell differentiation potential of 13-cis retinoic acid (RA) has not succeeded in the clinical treatment of glioblastoma (GBM) so far. However, RA may also induce the expression of resistance genes such as HOXB7 which can be suppressed by Thalidomide (THAL). Therefore, we tested if combined treatment with RA+THAL may inhibit growth of glioblastoma in vivo. Treatment with RA+THAL but not RA or THAL alone significantly inhibited tumour growth. The synergistic effect of RA and THAL was corroborated by the effect on proliferation of glioblastoma cell lines in vitro. HOXB7 was not upregulated but microarray analysis validated by real-time PCR identified four potential resistance genes (IL-8, HILDPA, IGFBPA, and ANGPTL4) whose upregulation by RA was suppressed by THAL. Furthermore, genes coding for small nucleolar RNAs (snoRNA) were identified as a target for RA for the first time, and their upregulation was maintained after combined treatment. Pathway analysis showed upregulation of the Ribosome pathway and downregulation of pathways associated with proliferation and inflammation. In conclusion, combined treatment with RA + THAL delayed growth of GBM xenografts and suppressed putative resistance genes associated with hypoxia and angiogenesis. This encourages further pre-clinical and clinical studies of this drug combination in GBM.

  4. Targeting neuro-inflammatory cytokines and oxidative stress by minocycline attenuates quinolinic-acid-induced Huntington's disease-like symptoms in rats.

    PubMed

    Kalonia, Harikesh; Mishra, Jitendriya; Kumar, Anil

    2012-11-01

    Recent experimental and clinical reports support the fact that the minocycline exhibits significant neuroprotective activity in neurodegenerative diseases. However, its mechanism of neuroprotection is still far from our understanding. Besides, minocycline does not always produce neuroprotective effect. Therefore, this study has been designed to explore the possible mechanism of minocycline in experimental model of HD in rats. Intrastriatal administration of quinolinic acid caused a significant reduction in body weight, motor dysfunction (impaired locomotor activity, rotarod performance, and beam walk test), oxidative damage (as evidenced by increase in lipid peroxidation, nitrite concentration, and depletion of super oxide dismutase and catalase), increased TNF-α and IL-6 levels as compared to the sham-treated animals. Minocycline (25, 50, and 100 mg/kg) treatment (for 21 days) significantly improved body weight, locomotor activity, rotarod performance, balance beam walk performance, oxidative defense, attenuated TNF-α and IL-6 levels as compared to quinolinic-acid (QA)-treated animals. This study provides evidence that minocycline might have neuroprotective effect against QA-induced Huntington-like behavioral, biochemical alterations, and neuroinflammation in rats. PMID:22392362

  5. Analgesic, neuropharmacological, anti-diarrheal, and cytotoxic activities of the extract of Solanum sisymbriifolium (Lam.) leaves

    PubMed Central

    Apu, Apurba Sarker; Bhuyan, Shakhawat Hossan; Matin, Maima; Hossain, Faruq; Khatun, Farjana; Taiab, Abu; Jamaluddin

    2013-01-01

    Objective: The present study was undertaken to evaluate the possible analgesic, neuropharmacological, anti-diarrheal, and cytotoxic activities of the ethanol extract of leaves of Solanum sisymbriifolium Lam. (Family: Solanaceae). Materials and Methods: The analgesic activity was measured by acetic acid-induced writhing inhibition test. The neuropharmacological activities were evaluated using hole cross, hole board, and elevated plus-maze test and the anti-diarrheal activity was assessed using castor oil-induced diarrhea inhibition method. Brine shrimp lethality bioassay was carried out for assessing the cytotoxicity of the ethanol extract of the leaves. Except cytotoxic activity, all the tests were conducted on mice. Results: The extract at oral doses of 200 and 400 mg/kg body weight showed highly significant (p<0.001) decrease in number of writhing, 52.1±0.66 and 4.4±0.64 compared with the control (78.6±0.29) with the percentage of inhibitions of writhing response were found to be 33.72% and 94.40%, respectively. Compare with the control, the extract at both doses showed significant sedative effect in hole cross test. In hole board test, the extract exhibited highly significant (p<0.001) anxiolytic activity at dose of (200 mg/kg), while the same activity was observed at dose of 400 mg/kg in elevated plus-maze test. The extract showed highly significant (p<0.001) anti-diarrheal activity in a dose-dependent manner. With the extract, significant lethality to brine shrimp was found with LC50 value of 61.66±0.9 μg/ml, which was comparable with the positive control (LC50: 11.89±0.8 µg/ml). Conclusion: The results from the present studies support the traditional uses of this plant part and could form the basis of further investigation including compound isolation. PMID:25050287

  6. Antinociceptive and Toxicological Effects of Dioclea grandiflora Seed Pod in Mice

    PubMed Central

    Sá, Rita de Cássia da Silveira e; de Oliveira, Leandra Eugênia Gomes; de Farias Nóbrega, Franklin Ferreira; Bhattacharyya, Jnanabrata; de Almeida, Reinaldo Nóbrega

    2010-01-01

    The acute treatment of mice with an ethanolic extract from the seed pod of Dioclea grandiflora (EDgP) at doses of 75, 150 and 300 mg/kg by intraperitoneal administration produced a significant antinociceptive effect as displayed by the acetic acid-induced writhing test and the formalin test. The antinociception was observed through the first (neurogenic pain) and second (inflammatory pain) phases in the formalin test. The hot plate test did not show an increase in the antinociceptive latency whereas the motor performance was affected by the administration at 300 mg/kg at the beginning (30 minutes) of the observation period but not at later periods (60 and 120 minutes). These results suggest that EDgP has a central antinociceptive action and a possible anti-inflammatory activity in mice. PMID:20368784

  7. Ursolic acid plays a role in Nepeta sibthorpii Bentham CNS depressing effects.

    PubMed

    Taviano, M F; Miceli, N; Monforte, M T; Tzakou, O; Galati, E M

    2007-04-01

    The sedative, anticonvulsant and analgesic activity of ursolic acid, a terpenoid bioassay-isolated from Nepeta sibthorpii Bentham, was evaluated in mice. The oral administration of ursolic acid (2.3 mg/kg) produced a significant depressant effect on CNS by reducing spontaneous motor activity and the number and lethality of pentylenetetrazol (PTZ)-induced seizures. Two models of nociception, the writhing test and the hot plate test, were also used to examine the analgesic effect of ursolic acid. At a dose of 2.3 mg/kg, ursolic acid caused an inhibition of acetic acid-induced abdominal constriction, but was inactive in the hot plate test. Treatment at a higher dose (20 mg/kg) significantly increased the reaction time in the hot plate test. This effect, reversed by naloxone, evidently involves opioid receptors, but the analgesic activity of ursolic acid may be related also to the antiinflammatory and antioxidant properties of this compound.

  8. Palmitic acid induces osteoblastic differentiation in vascular smooth muscle cells through ACSL3 and NF-κB, novel targets of eicosapentaenoic acid.

    PubMed

    Kageyama, Aiko; Matsui, Hiroki; Ohta, Masahiko; Sambuichi, Keisuke; Kawano, Hiroyuki; Notsu, Tatsuto; Imada, Kazunori; Yokoyama, Tomoyuki; Kurabayashi, Masahiko

    2013-01-01

    Free fatty acids (FFAs), elevated in metabolic syndrome and diabetes, play a crucial role in the development of atherosclerotic cardiovascular disease, and eicosapentaenoic acid (EPA) counteracts many aspects of FFA-induced vascular pathology. Although vascular calcification is invariably associated with atherosclerosis, the mechanisms involved are not completely elucidated. In this study, we tested the hypothesis that EPA prevents the osteoblastic differentiation and mineralization of vascular smooth muscle cells (VSMC) induced by palmitic acid (PA), the most abundant long-chain saturated fatty acid in plasma. PA increased and EPA abolished the expression of the genes for bone-related proteins, including bone morphogenetic protein (BMP)-2, Msx2 and osteopontin in human aortic smooth muscle cells (HASMC). Among the long-chain acyl-CoA synthetase (ACSL) subfamily, ACSL3 expression was predominant in HASMC, and PA robustly increased and EPA efficiently inhibited ACSL3 expression. Importantly, PA-induced osteoblastic differentiation was mediated, at least in part, by ACSL3 activation because acyl-CoA synthetase (ACS) inhibitor or siRNA targeted to ACSL3 completely prevented the PA induction of both BMP-2 and Msx2. Conversely, adenovirus-mediated ACSL3 overexpression enhanced PA-induced BMP-2 and Msx2 expression. In addition, EPA, ACSL3 siRNA and ACS inhibitor attenuated calcium deposition and caspase activation induced by PA. Notably, PA induced activation of NF-κB, and NF-κB inhibitor prevented PA-induction of osteoblastic gene expression and calcium deposition. Immunohistochemistry revealed the prominent expression of ACSL3 in VSMC and macrophages in human non-calcifying and calcifying atherosclerotic plaques from the carotid arteries. These results identify ACSL3 and NF-κB as mediators of PA-induced osteoblastic differentiation and calcium deposition in VSMC and suggest that EPA prevents vascular calcification by inhibiting such a new molecular pathway elicited

  9. Green tea constituents (-)-epigallocatechin-3-gallate (EGCG) and gallic acid induce topoisomerase I- and topoisomerase II-DNA complexes in cells mediated by pyrogallol-induced hydrogen peroxide.

    PubMed

    López-Lázaro, Miguel; Calderón-Montaño, José Manuel; Burgos-Morón, Estefanía; Austin, Caroline A

    2011-07-01

    Green tea and its major active constituent, (-)-epigallocatechin-3-gallate (EGCG), are in clinical trials for the prevention and treatment of several diseases such as cancer. DNA topoisomerase (topo) poisons are commonly prescribed anticancer drugs that kill cancer cells by inducing topo-DNA complexes. Using purified topoisomerases, previous in vitro studies have shown that EGCG induces the formation of topo-DNA complexes. Because the activity of a drug on purified topoisomerases does not always represent the activity in a cell, we have used an immunofluorescence technique that allows the visualisation of topo I- and topo II-DNA complexes produced in individual cells to evaluate the activity of EGCG on both enzymes. High levels of topo I- and topo II-DNA complexes were observed in K562 leukaemia cells exposed to EGCG. Similar levels of topo I- and topo II-DNA complexes were visualised in cells treated with gallic acid (GA) (the acid part of the EGCG ester). Pyrogallol (PG) also induced topo-DNA complexes with both enzymes, therefore suggesting that the activity of EGCG and GA is mediated by their PG moieties. Catalase prevented both the cytotoxicity and the formation of topo I- and topo II-DNA complexes induced by EGCG, GA, PG and myricetin (a PG-containing flavonoid recently shown to induce topo I- and topo II-DNA complexes in cells), indicating that hydrogen peroxide mediates these activities. Hydrogen peroxide induced topo I- and topo II (α and β)-DNA complexes in a time- and dose-dependent manner. The formation of topo I- and topo II-DNA complexes in cells exposed to hydrogen peroxide correlated well with the induction of apoptosis, suggesting that the topo-DNA complexes induced at long exposure times by the compounds tested in our study may be apoptotic topo-DNA complexes. Finally, we report results suggesting that PG-containing drugs may selectively kill tumour cells by generating hydrogen peroxide.

  10. Diphenylarsinic Acid Induced Activation of Cultured Rat Cerebellar Astrocytes: Phosphorylation of Mitogen-Activated Protein Kinases, Upregulation of Transcription Factors, and Release of Brain-Active Cytokines.

    PubMed

    Negishi, Takayuki; Matsumoto, Mami; Kojima, Mikiya; Asai, Ryota; Kanehira, Tomoko; Sakaguchi, Fumika; Takahata, Kazuaki; Arakaki, Rina; Aoyama, Yohei; Yoshida, Hikari; Yoshida, Kenji; Yukawa, Kazunori; Tashiro, Tomoko; Hirano, Seishiro

    2016-03-01

    Diphenylarsinic acid (DPAA) was detected as the primary compound responsible for the arsenic poisoning that occurred in Kamisu, Ibaraki, Japan, where people using water from a well that was contaminated with a high level of arsenic developed neurological (mostly cerebellar) symptoms and dysregulation of regional cerebral blood flow. To understand the underlying molecular mechanism of DPAA-induced cerebellar symptoms, we focused on astrocytes, which have a brain-protective function. Incubation with 10 µM DPAA for 96 h promoted cell proliferation, increased the expression of antioxidative stress proteins (heme oxygenase-1 and heat shock protein 70), and induced the release of cytokines (MCP-1, adrenomedullin, FGF2, CXCL1, and IL-6). Furthermore, DPAA overpoweringly increased the phosphorylation of three major mitogen-activated protein kinases (MAPKs) (ERK1/2, p38MAPK, and SAPK/JNK), which indicated MAPK activation, and subsequently induced expression and/or phosphorylation of transcription factors (Nrf2, CREB, c-Jun, and c-Fos) in cultured rat cerebellar astrocytes. Structure-activity relationship analyses of DPAA and other related pentavalent organic arsenicals revealed that DPAA at 10 µM activated astrocytes most effective among organic arsenicals tested at the same dose. These results suggest that in a cerebellum exposed to DPAA, abnormal activation of the MAPK-transcription factor pathway and irregular secretion of these neuroactive, glioactive, and/or vasoactive cytokines in astrocytes can be the direct/indirect cause of functional abnormalities in surrounding neurons, glial cells, and vascular cells: This in turn might lead to the onset of cerebellar symptoms and disruption of cerebral blood flow. PMID:26645585

  11. Decreased striatal dopamine release underlies increased expression of long-term synaptic potentiation at corticostriatal synapses 24 hours after 3-nitropropionic acid induced chemical hypoxia

    PubMed Central

    Akopian, Garnik; Crawford, Cynthia; Beal, M. Flint; Cappelletti, Maurand; Jakowec, Michael W.; Petzinger, Giselle M.; Zheng, Ling; Gheorghe, Stacey L.; Reichel, Carmela M.; Chow, Robert; Walsh, John P

    2008-01-01

    The striatum is particularly sensitive to the irreversible inhibitor of succinate dehyrdrogenase 3-nitropropionic acid (3-NP). In the present study we examined early changes in behavior and dopamine and glutamate synaptic physiology created by a single systemic injection of 3-NP in Fischer 344 rats. Hind limb dystonia was seen 2 hours after 3-NP injections and rats performed poorly on balance beam and rota-rod motor tests 24 hours later. Systemic 3-NP increased NMDA receptor-dependent long-term potentiation (LTP) at corticostriatal synapses over the same time period. The 3-NP induced corticostriatal LTP was not due to increased NMDA receptor number or function, since 3-NP did not change MK-801 binding or NMDA/AMPA receptor current ratios. The LTP seen 24 hours after 3-NP was D1 receptor-dependent and reversed by exogenous addition of dopamine or a D2 receptor agonist to brain slices. High performance liquid chromatography and fast scan cyclic voltammetry revealed a decrease in dopamine content and release in rats injected 24 hours earlier with 3-NP, and much like the enhanced LTP, dopamine changes were reversed by 48 hours. Tyrosine hydroxylase expression was not changed and there was no evidence of striatal cell loss at 24–48 hours after 3-NP exposure. Sprague-Dawley rats showed similar physiological responses to systemic 3-NP, albeit with reduced sensitivity. Thus, 3-NP causes significant changes in motor behavior marked by parallel changes in striatal dopamine release and corticostriatal synaptic plasticity. PMID:18799690

  12. Combination of 13 cis-retinoic acid and tolfenamic acid induces apoptosis and effectively inhibits high-risk neuroblastoma cell proliferation.

    PubMed

    Shelake, Sagar; Eslin, Don; Sutphin, Robert M; Sankpal, Umesh T; Wadwani, Anmol; Kenyon, Laura E; Tabor-Simecka, Leslie; Bowman, W Paul; Vishwanatha, Jamboor K; Basha, Riyaz

    2015-11-01

    Chemotherapeutic regimens used for the treatment of Neuroblastoma (NB) cause long-term side effects in pediatric patients. NB arises in immature sympathetic nerve cells and primarily affects infants and children. A high rate of relapse in high-risk neuroblastoma (HRNB) necessitates the development of alternative strategies for effective treatment. This study investigated the efficacy of a small molecule, tolfenamic acid (TA), for enhancing the anti-proliferative effect of 13 cis-retinoic acid (RA) in HRNB cell lines. LA1-55n and SH-SY5Y cells were treated with TA (30μM) or RA (20μM) or both (optimized doses, derived from dose curves) for 48h and tested the effect on cell viability, apoptosis and selected molecular markers (Sp1, survivin, AKT and ERK1/2). Cell viability and caspase activity were measured using the CellTiter-Glo and Caspase-Glo kits. The apoptotic cell population was determined by flow cytometry with Annexin-V staining. The expression of Sp1, survivin, AKT, ERK1/2 and c-PARP was evaluated by Western blots. The combination therapy of TA and RA resulted in significant inhibition of cell viability (p<0.0001) when compared to individual agents. The anti-proliferative effect is accompanied by a decrease in Sp1 and survivin expression and an increase in apoptotic markers, Annexin-V positive cells, caspase 3/7 activity and c-PARP levels. Notably, TA+RA combination also caused down regulation of AKT and ERK1/2 suggesting a distinct impact on survival and proliferation pathways via signaling cascades. This study demonstrates that the TA mediated inhibition of Sp1 in combination with RA provides a novel therapeutic strategy for the effective treatment of HRNB in children.

  13. Caprylic acid-induced impurity precipitation from protein A capture column elution pool to enable a two-chromatography-step process for monoclonal antibody purification.

    PubMed

    Zheng, Ji; Wang, Lu; Twarowska, Barbara; Laino, Sarah; Sparks, Colleen; Smith, Timothy; Russell, Reb; Wang, Michelle

    2015-01-01

    This article presents the use of caprylic acid (CA) to precipitate impurities from the protein A capture column elution pool for the purification of monoclonal antibodies (mAbs) with the objective of developing a two chromatography step antibody purification process. A CA-induced impurity precipitation in the protein A column elution pool was evaluated as an alternative method to polishing chromatography techniques for use in the purification of mAbs. Parameters including pH, CA concentrations, mixing time, mAb concentrations, buffer systems, and incubation temperatures were evaluated on their impacts on the impurity removal, high-molecular weight (HMW) formation and precipitation step yield. Both pH and CA concentration, but not mAb concentrations and buffer systems, are key parameters that can affect host-cell proteins (HCPs) clearance, HMW species, and yield. CA precipitation removes HCPs and some HMW species to the acceptable levels under the optimal conditions. The CA precipitation process is robust at 15-25°C. For all five mAbs tested in this study, the optimal CA concentration range is 0.5-1.0%, while the pH range is from 5.0 to 6.0. A purification process using two chromatography steps (protein A capture column and ion exchange polishing column) in combination with CA-based impurity precipitation step can be used as a robust downstream process for mAb molecules with a broad range of isoelectric points. Residual CA can be effectively removed by the subsequent polishing cation exchange chromatography.

  14. Global analysis of gene expression changes during retinoic acid-induced growth arrest and differentiation of melanoma: comparison to differentially expressed genes in melanocytes vs melanoma

    PubMed Central

    Estler, Mary; Boskovic, Goran; Denvir, James; Miles, Sarah; Primerano, Donald A; Niles, Richard M

    2008-01-01

    Background The incidence of malignant melanoma has significantly increased over the last decade. Some of these malignancies are susceptible to the growth inhibitory and pro-differentiating effects of all-trans-retinoic acid (RA). The molecular changes responsible for the biological activity of RA in melanoma are not well understood. Results In an analysis of sequential global gene expression changes during a 4–48 h RA treatment of B16 mouse melanoma cells, we found that RA increased the expression of 757 genes and decreased the expression of 737 genes. We also compared the gene expression profile (no RA treatment) between non-malignant melan-a mouse melanocytes and B16 melanoma cells. Using the same statistical test, we found 1495 genes whose expression was significantly higher in melan-a than in B16 cells and 2054 genes whose expression was significantly lower in melan-a than in B16 cells. By intersecting these two gene sets, we discovered a common set of 233 genes whose RNA levels were significantly different between B16 and melan-a cells and whose expression was altered by RA treatment. Within this set, RA treatment altered the expression of 203 (87%) genes toward the melan-a expression level. In addition, hierarchical clustering showed that after 48 h of RA treatment expression of the 203 genes was more closely related to the melan-a gene set than any other RA treatment time point. Functional analysis of the 203 gene set indicated that RA decreased expression of mRNAs that encode proteins involved in cell division/cell cycle, DNA replication, recombination and repair, and transcription regulation. Conversely, it stimulated genes involved in cell-cell signaling, cell adhesion and cell differentiation/embryonic development. Pathway analysis of the 203 gene set revealed four major hubs of connectivity: CDC2, CHEK1, CDC45L and MCM6. Conclusion Our analysis of common genes in the 48 h RA-treatment of B16 melanoma cells and untreated B16 vs. melan-a data set show

  15. Chlamydia Testing

    MedlinePlus

    ... Amplification Test (NAAT); Chlamydia trachomatis Culture; Chlamydia trachomatis DNA Probe Related tests: Gonorrhea Testing , HIV Antibody and HIV Antigen , Syphilis Tests , Herpes Testing , HPV Test , Trichomonas Testing All content on Lab Tests Online has ...

  16. What State Tests Test.

    ERIC Educational Resources Information Center

    McGee, Glenn W.

    What the Illinois Goal Assessment Program (IGAP) test actually tests and the consequences of these tests for funding decisions were studied with a random sample of 100 school districts in the Cook County suburbs of Chicago. Eighth-grade IGAP scores for reading were obtained from the state report card, a document prepared by each school district…

  17. c-Jun N-terminal Kinase-Dependent Endoplasmic Reticulum Stress Pathway is Critically Involved in Arjunic Acid Induced Apoptosis in Non-Small Cell Lung Cancer Cells.

    PubMed

    Joo, HyeEun; Lee, Hyun Joo; Shin, Eun Ah; Kim, Hangil; Seo, Kyeong-Hwa; Baek, Nam-In; Kim, Bonglee; Kim, Sung-Hoon

    2016-04-01

    Though arjunic acid, a triterpene isolated from Terminalia arjuna, was known to have antioxidant, antiinflammatory, and cytotoxic effects, its underlying antitumor mechanism still remains unclear so far. Thus, in the present study, the molecular antitumor mechanism of arjunic acid was examined in A549 and H460 non-small cell lung cancer (NSCLC) cells. Arjunic acid exerted cytotoxicity by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide (MTT) assay and significantly increased sub-G1 population in A549 and H460 cells by cell cycle analysis. Consistently, arjunic acid cleaved poly (ADP-ribose) polymerase (PARP), activated Bax, and phosphorylation of c-Jun N-terminal kinases (JNK), and also attenuated the expression of pro-caspase-3 and Bcl-2 in A549 and H460 cells. Furthermore, arjunic acid upregulated the expression of endoplasmic reticulum (ER) stress proteins such as IRE1 α, ATF4, p-eIF2α, and C/EBP homologous protein (CHOP) in A549 and H460 cells. Conversely, CHOP depletion attenuated the increase of sub-G1 population by arjunic acid, and also JNK inhibitor SP600125 blocked the cytotoxicity and upregulation of IRE1 α and CHOP induced by arjunic acid in A549 and H460 cells. Overall, our findings suggest that arjunic acid induces apoptosis in NSCLC cells via JNK mediated ER stress pathway as a potent chemotherapeutic agent for NSCLC. PMID:26787261

  18. Comparison of anti-inflammatory and anti-nociceptive activities of Curcuma wenyujin Y.H. Chen et C. Ling and Scutellaria baicalensis Georgi.

    PubMed

    Zhou, Jue; Qu, Fan; Zhang, Hang-Jun; Zhuge, Xiao-Hong; Cheng, Liang-Zhong

    2010-01-01

    The study aimed to compare the anti-inflammatory and anti-nociceptive activities of Curcuma wenyujin Y.H. Chen et C. Ling (Curcuma wenyujin) and Scutellaria baicalensis Georgi (Scutellaria baicalensis). This study used three parts to compare the two herbs. Firstly, animals were randomly divided into a Scutellaria baicalensis group, a Curcuma wenyujin group, an indomethacin group, and a model-control group to perform an ear edema test, a carrageenin-induced paw edema test, a cotton pellet-induced granuloma formation test, and an acetic acid-induced writhing test. Secondly, model rats with pelvic inflammation were established, and the serum levels of TNF-α and IL-6 in each group was detected with the Enzyme-Linked Immunosorbent Assay (ELISA). Thirdly, pharmacokinetics analysis of Scutellaria baicalensis and Curcuma wenyujin was conducted on the model rats. The ear edema test, carrageenin-induced paw edema test, cotton pellet-induced granuloma formation test, and acetic acid-induced writhing test all showed that Curcuma wenyujin had stronger anti-inflammatory and anti-nociceptive effects than Scutellaria baicalensis. There is significant difference between the effects of Curcuma wenyujin and Scutellaria baicalensis on the levels of TNF-α and IL-6 for the model rats. Curcuma wenyujin decreased the levels of TNF-α and IL-6 more than Scutellaria baicalensis. The pharmacokinetics analysis showed that curcumol's Tmax, Cmax, and the area under the curve (AUC) were all higher than baicalin's. This study indicated that for pelvic inflammation, Curcuma wenyujin had better anti-inflammatory and anti-nociceptive effects than Scutellaria baicalensis.

  19. Antinociceptive Activity of Ethanol Extract from Duguetia chrysocarpa Maas (Annonaceae)

    PubMed Central

    Almeida, Jackson Roberto Guedes da Silva; Araújo, Edigênia Cavalcante da Cruz; Ribeiro, Luciano Augusto de Araújo; de Lima, Julianeli Tolentino; Nunes, Xirley Pereira; Lúcio, Ana Sílvia Suassuna Carneiro; Agra, Maria de Fátima; Barbosa Filho, José Maria

    2012-01-01

    The ethanol extract from the fruits of Duguetia chrysocarpa was evaluated for its antinociceptive activity in chemical and thermal models of nociception in mice. The intraperitoneal administration of the ethanol extract (100, 200, and 400 mg/kg body weight) showed a dose-dependent inhibition of acetic-acid-induced abdominal writhes. The extract also produced a significant inhibition of both phases of the formalin test in all doses tested and increased the reaction time in hot-plate test at dose of 200 mg/kg. The data obtained suggest that the antinociceptive effect of the extract may be mediated via both peripheral and central mechanisms. The phytochemical investigation yielded the isolation of the benzenoid derivative 3-methoxy-4-ethoxy benzoic acid which is being reported for the first time in this genus. PMID:22645460

  20. Pharmacological Evaluation of Naproxen Metal Complexes on Antinociceptive, Anxiolytic, CNS Depressant, and Hypoglycemic Properties.

    PubMed

    Hasan, Md Sharif; Das, Narhari; Al Mahmud, Zobaer; Abdur Rahman, S M

    2016-01-01

    Purpose. The present study was designed to investigate the antinociceptive, anxiolytic, CNS depressant, and hypoglycemic effects of the naproxen metal complexes. Methods. The antinociceptive activity was evaluated by acetic acid-induced writhing method and radiant heat tail-flick method while anxiolytic activity was evaluated by elevated plus maze model. The CNS depressant activity of naproxen metal complexes was assessed using phenobarbitone-induced sleeping time test and the hypoglycemic test was performed using oral glucose tolerance test. Results. Metal complexes significantly (P < 0.001) reduced the number of abdominal muscle contractions induced by 0.7% acetic acid solution in a dose dependent manner. At the dose of 25 mg/kg body weight p.o. copper, cobalt, and zinc complexes exhibited higher antinociceptive activity having 59.15%, 60.56%, and 57.75% of writhing inhibition, respectively, than the parent ligand naproxen (54.93%). In tail-flick test, at both doses of 25 and 50 mg/kg, the copper, cobalt, silver, and zinc complexes showed higher antinociceptive activity after 90 minutes than the parent drug naproxen. In elevated plus maze (EPM) model the cobalt and zinc complexes of naproxen showed significant anxiolytic effects in dose dependent manner, while the copper, cobalt, and zinc complexes showed significant CNS depressant and hypoglycemic activity. Conclusion. The present study demonstrated that copper, cobalt, and zinc complexes possess higher antinociceptive, anxiolytic, CNS depressant, and hypoglycemic properties than the parent ligand. PMID:27478435

  1. Pharmacological Evaluation of Naproxen Metal Complexes on Antinociceptive, Anxiolytic, CNS Depressant, and Hypoglycemic Properties

    PubMed Central

    Das, Narhari; Abdur Rahman, S. M.

    2016-01-01

    Purpose. The present study was designed to investigate the antinociceptive, anxiolytic, CNS depressant, and hypoglycemic effects of the naproxen metal complexes. Methods. The antinociceptive activity was evaluated by acetic acid-induced writhing method and radiant heat tail-flick method while anxiolytic activity was evaluated by elevated plus maze model. The CNS depressant activity of naproxen metal complexes was assessed using phenobarbitone-induced sleeping time test and the hypoglycemic test was performed using oral glucose tolerance test. Results. Metal complexes significantly (P < 0.001) reduced the number of abdominal muscle contractions induced by 0.7% acetic acid solution in a dose dependent manner. At the dose of 25 mg/kg body weight p.o. copper, cobalt, and zinc complexes exhibited higher antinociceptive activity having 59.15%, 60.56%, and 57.75% of writhing inhibition, respectively, than the parent ligand naproxen (54.93%). In tail-flick test, at both doses of 25 and 50 mg/kg, the copper, cobalt, silver, and zinc complexes showed higher antinociceptive activity after 90 minutes than the parent drug naproxen. In elevated plus maze (EPM) model the cobalt and zinc complexes of naproxen showed significant anxiolytic effects in dose dependent manner, while the copper, cobalt, and zinc complexes showed significant CNS depressant and hypoglycemic activity. Conclusion. The present study demonstrated that copper, cobalt, and zinc complexes possess higher antinociceptive, anxiolytic, CNS depressant, and hypoglycemic properties than the parent ligand. PMID:27478435

  2. Gonorrhea Test

    MedlinePlus

    ... gonorrhoeae Culture; Neisseria gonorrhoeae Gram Stain; Neisseria gonorrhoeae DNA Probe Related tests: Chlamydia Testing , HIV Antibody and HIV Antigen , Syphilis Tests , Herpes Testing , HPV Test , Trichomonas Testing All content on Lab Tests Online has ...

  3. Antinociceptive Effect of 3-(2,3-Dimethoxyphenyl)-1-(5-methylfuran-2-yl)prop-2-en-1-one in Mice Models of Induced Nociception.

    PubMed

    Ismail, Nur Izzati; Ming-Tatt, Lee; Lajis, Nordin; Akhtar, Muhammad Nadeem; Akira, Ahmad; Perimal, Enoch Kumar; Israf, Daud Ahmad; Sulaiman, Mohd Roslan

    2016-08-22

    The antinociceptive effects produced by intraperitoneal administration of a novel synthetic chalcone, 3-(2,3-dimethoxyphenyl)-1-(5-methylfuran-2-yl)prop-2-en-1-one (DMFP), were investigated in several mouse models of induced nociception. The administration of DMFP (0.1, 0.5, 1.0 and 5.0 mg/kg) produced significant attenuation on the acetic acid-induced abdominal-writhing test. It also produced a significant increase in response latency time in the hot-plate test and a marked reduction in time spent licking the injected paw in both phases of the formalin-induced paw-licking test. In addition, it was also demonstrated that DMFP exhibited significant inhibition of the neurogenic nociceptive response induced by intraplantar injections of capsaicin and glutamate. Moreover, the antinociceptive effect of DMFP in the acetic acid-induced abdominal-writhing test and the hot-plate test was not antagonized by pretreatment with a non-selective opioid receptor antagonist, naloxone. Finally, DMFP did not show any toxic effects and/or mortality in a study of acute toxicity and did not interfere with motor coordination during the Rota-rod test. Our present results show that DMFP exhibits both peripheral and central antinociceptive effects. It was suggested that its peripheral antinociceptive activity is associated with attenuated production and/or release of NO and various pro-inflammatory mediators, while central antinociceptive activity seems to be unrelated to the opioidergic system, but could involve, at least in part, an interaction with the inhibition of capsaicin-sensitive fibers and the glutamatergic system.

  4. Antinociceptive Effect of 3-(2,3-Dimethoxyphenyl)-1-(5-methylfuran-2-yl)prop-2-en-1-one in Mice Models of Induced Nociception.

    PubMed

    Ismail, Nur Izzati; Ming-Tatt, Lee; Lajis, Nordin; Akhtar, Muhammad Nadeem; Akira, Ahmad; Perimal, Enoch Kumar; Israf, Daud Ahmad; Sulaiman, Mohd Roslan

    2016-01-01

    The antinociceptive effects produced by intraperitoneal administration of a novel synthetic chalcone, 3-(2,3-dimethoxyphenyl)-1-(5-methylfuran-2-yl)prop-2-en-1-one (DMFP), were investigated in several mouse models of induced nociception. The administration of DMFP (0.1, 0.5, 1.0 and 5.0 mg/kg) produced significant attenuation on the acetic acid-induced abdominal-writhing test. It also produced a significant increase in response latency time in the hot-plate test and a marked reduction in time spent licking the injected paw in both phases of the formalin-induced paw-licking test. In addition, it was also demonstrated that DMFP exhibited significant inhibition of the neurogenic nociceptive response induced by intraplantar injections of capsaicin and glutamate. Moreover, the antinociceptive effect of DMFP in the acetic acid-induced abdominal-writhing test and the hot-plate test was not antagonized by pretreatment with a non-selective opioid receptor antagonist, naloxone. Finally, DMFP did not show any toxic effects and/or mortality in a study of acute toxicity and did not interfere with motor coordination during the Rota-rod test. Our present results show that DMFP exhibits both peripheral and central antinociceptive effects. It was suggested that its peripheral antinociceptive activity is associated with attenuated production and/or release of NO and various pro-inflammatory mediators, while central antinociceptive activity seems to be unrelated to the opioidergic system, but could involve, at least in part, an interaction with the inhibition of capsaicin-sensitive fibers and the glutamatergic system. PMID:27556438

  5. Lysophosphatidic acid induces osteocyte dendrite outgrowth

    SciTech Connect

    Karagiosis, Sue A.; Karin, Norm J.

    2007-05-25

    A method was developed to measure dendrite formation in bone cells. Lysophosphatidic acid (LPA) was found to stimulate dendrite outgrowth. It is postulated that LPA plays a role in regulating the osteocyte network in vivo.

  6. Ursodeoxycholic acid induced generalized fixed drug eruption.

    PubMed

    Ozkol, Hatice Uce; Calka, Omer; Dulger, Ahmet Cumhur; Bulut, Gulay

    2014-09-01

    Fixed drug eruption (FDE) is a rare form of drug allergies that recur at the same cutaneous or mucosal site in every usage of drug. Single or multiple round, sharply demarcated and dusky red plaques appear soon after drug exposure. Ursodeoxycholic acid (UDCA: 3α,7β-dihydroxy-5β-cholanic acid) is used for the treatment of cholestatic liver diseases. Some side effects may be observed, such as diarrhea, dyspepsia, pruritus and headaches. We encountered only three cases of lichenoid reaction regarding the use of UDCA among previous studies. In this article, we reported a generalized FDE case related to UDCA intake in a 59-year-old male patient with cholestasis for the first time in the literature. PMID:24147950

  7. Analgesic and anti-inflammatory activities of the ethanol extract of Taxillus tsaii Chiu in mice.

    PubMed

    Liu, Chia-Yu; Chiu, Yung-Jia; Kuo, Chao-Lin; Chien, Tzu-Mei; Wu, Lung-Yuan; Peng, Wen-Huang

    2015-06-01

    Preclinical Research This study was conducted to investigate the analgesic activities and mechanism of anti-inflammatory activities of a 50% ethanol extract of Taxillus tsaii (ETT) in vivo using the acetic acid induced writhing test and formalin induced paw licking in mice. The anti-inflammatory effect of ETT was evaluated using a mouse model of λ-carrageenan (Carr)-induced paw edema. ETT reduced the writhing in the acetic acid assay test at a dose 1.0 g/kg po and reduced the licking time in the late phase of the formalin test at doses of 0.5 and 1.0 g/kg po). Carr-induced paw edema was reduced when ETT (0.5 and 1.0 g/kg po) was administered 3-5 h after Carr injection. ETT (1.0 g/kg po) reduced the level of malondialdehyde in the edemic paw by increasing the activity of antioxidant enzymes, e.g., superoxide dismutase and glutathione reductase, in the liver and reducing TNF-α, IL-1β, and IL-6 activity in the edemic paw. This study demonstrates the analgesic and anti-inflammatory effects of ETT, thus verifying its application in traditional Chinese medicine.

  8. Antinociceptive and anti-inflammatory effects of flavonoids PMT1 and PMT2 isolated from Piper montealegreanum Yuncker (Piperaceae) in mice.

    PubMed

    de Queiroz, Aline Cavalcanti; Alves, Harley da Silva; Cavalcante-Silva, Luiz Henrique Agra; Dias, Thays de Lima Matos Freire; Santos, Mariana da Silva; Melo, Gabriela Muniz de Albuquerque; Campesatto, Eliane Aparecida; Chaves, Maria Célia de Oliveira; Alexandre-Moreira, Magna Suzana

    2014-01-01

    In this study, we identified the antinociceptive and anti-inflammatory effects of two flavonoids (PMT1 and PMT2) from Piper montealegreanum. The antinociceptive effect was evaluated using the classical tests: acetic acid-induced writhing, formalin and hot plate test. PMT1 and PMT2 (0.1, 1, 30 and 100 μmol/kg, i.p.) reduced the writhings, with an ID50 of 0.58 and 0.44 μmol/kg, respectively. Moreover, these flavonoids (100 μmol/kg, i.p.) inhibited paw-licking time in the neurogenic phase of the formalin test, but only PMT2 was active in the inflammatory phase. However, PMT1 and PMT2 (100 μmol/kg, i.p.) did not increase the latency time of the animals in the hot plate. In order to evaluate the anti-inflammatory effect of these flavonoids, capsaicin-induced ear oedema was carried out. Both flavonoids (100 μmol/kg, i.p.) were active in this model. These results suggest that PMT1 and PMT2 have antinociceptive and anti-inflammatory activities.

  9. Isolation of a dihydrobenzofuran lignan, icariside E4, with an antinociceptive effect from Tabebuia roseo-alba (Ridley) Sandwith (Bignoniaceae) bark.

    PubMed

    Ferreira-Júnior, Jesu C; Conserva, Lucia M; Lyra Lemos, Rosangela P; de Omena-Neta, Genilda C; Cavalcante-Neto, Araken; Barreto, Emiliano

    2015-06-01

    The antinociceptive activity of icariside E4, a dihydrobenzofuran-type lignan isolated from Tabebuia roseo-alba (Ridley) Sandwith (Bignoniaceae) bark, was evaluated in mice by using chemical and thermal models of nociception. Intraperitoneal (i.p.) administration of crude T. roseo-alba bark extract and its methanol fraction inhibited acetic acid-induced abdominal constriction in mice. Furthermore, i.p. administration of 0.1, 1, and 10 mg/kg of icariside E4 reduced the number of writhes evoked by acetic acid injection by 46.9, 82.3, and 66.6%, respectively. Icariside E4 administration had no effect in the first phase of the formalin test, but it reduced nociceptive behavior in the second phase as indicated by a reduction in the licking time. Icariside E4 did not modify thermal nociception in the hot-plate test model, suggesting that it had a peripheral antinociceptive action. The antinociceptive effect of icariside E4 in the writhing test was reversed by pre-administration of glibenclamide, but not of naloxone, atropine, yohimbine, or haloperidol. Together, these results indicated that the antinociceptive activity of icariside E4 from T. roseo-alba in models of chemical pain occurred through ATP-sensitive K(+) channel-dependent mechanisms.

  10. Synthesis and Evaluation of New 1,3,4-Thiadiazole Derivatives as Antinociceptive Agents.

    PubMed

    Altıntop, Mehlika Dilek; Can, Özgür Devrim; Demir Özkay, Ümide; Kaplancıklı, Zafer Asım

    2016-01-01

    In the current work, new 1,3,4-thiadiazole derivatives were synthesized and investigated for their antinociceptive effects on nociceptive pathways of nervous system. The effects of these compounds against mechanical, thermal and chemical stimuli were evaluated by tail-clip, hot-plate and acetic acid-induced writhing tests, respectively. In addition, activity cage was performed to assess the locomotor activity of animals. The obtained data indicated that compounds 3b, 3c, 3d, 3e, 3g and 3h increased the reaction times of mice both in the hot-plate and tail-clip tests, indicating the centrally mediated antinociceptive activity of these compounds. Additionally, the number of writhing behavior was significantly decreased by the administration of compounds 3a, 3c, 3e and 3f, which pointed out the peripherally mediated antinociceptive activity induced by these four compounds. According to the activity cage tests, compounds 3a, 3c and 3f significantly decreased both horizontal and vertical locomotor activity of mice. Antinociceptive behavior of these three compounds may be non-specific and caused by possible sedative effect or motor impairments. PMID:27490523

  11. Enhanced Analgesic Properties and Reduced Ulcerogenic Effect of a Mononuclear Copper(II) Complex with Fenoprofen in Comparison to the Parent Drug: Promising Insights in the Treatment of Chronic Inflammatory Diseases

    PubMed Central

    Gumilar, Fernanda; Boeris, Mónica; Toso, Ricardo; Minetti, Alejandra

    2014-01-01

    Analgesic and ulcerogenic properties have been studied for the copper(II) coordination complex of the nonsteroidal anti-inflammatory drug Fenoprofen and imidazole [Cu(fen)2(im)2] (Cu: copper(II) ion; fen: fenoprofenate anion from Fenoprofen, im: imidazole). A therapeutic dose of 28 mg/kg was tested for [Cu(fen)2(im)2] and 21 mg/kg was employed for Fenoprofen calcium, administered by oral gavage in female mice to compare the therapeutic properties of the new entity. The acetic acid induced writhing test was employed to study visceral pain. The percentage of inhibition in writhing and stretching was 78.9% and 46.2% for the [Cu(fen)2(im)2] and Fenoprofen calcium, respectively. This result indicates that the complex could be more effective in diminishing visceral pain. The formalin test was evaluated to study the impact of the drugs over nociceptive and inflammatory pain. The complex is a more potent analgesic on inflammatory pain than the parent drug. Ulcerogenic effects were evaluated using a model of gastric lesions induced by hypothermic-restraint stress. Fenoprofen calcium salt caused an ulcer index of about 79 mm2 while the one caused by [Cu(fen)2(im)2] was 22 mm2. The complex diminished the development of gastric mucosal ulcers in comparison to the uncomplexed drug. Possible mechanisms of action related to both therapeutic properties have been discussed. PMID:25050353

  12. Evaluation of Antinociceptive Activity of Ethanol Extract of Leaves of Adenanthera pavonina

    PubMed Central

    Moniruzzaman, Md.; Khatun, Ambia; Imam, Mohammad Zafar

    2015-01-01

    Adenanthera pavonina is a deciduous tree commonly used in the traditional medicine to treat inflammation and rheumatism. The aim of this study was to evaluate the antinociceptive activity of ethanol extract of leaves of A. pavonina (EEAP). EEAP was investigated using various nociceptive models induced thermally or chemically in mice including hot plate and tail immersion test, acetic acid-induced writhing, and glutamate- and formalin-induced licking tests at the doses of 50, 100, and 200 mg/kg body weight (p.o.). In addition, to assess the possible mechanisms, involvement of opioid system was verified using naloxone (2 mg/kg) and cyclic guanosine monophosphate (cGMP) signaling pathway by methylene blue (MB; 20 mg/kg). The results have demonstrated that EEAP produced a significant and dose-dependent increment in the hot plate latency and tail withdrawal time. It also reduced the number of abdominal constrictions and paw lickings induced by acetic acid and glutamate respectively. EEAP inhibited the nociceptive responses in both phases of formalin test. Besides, the reversal effects of naloxone indicated the association of opioid receptors on the exertion of EEAP action centrally. Moreover, the enhancement of writhing inhibitory activity by MB suggests the possible involvement of cGMP pathway in EEAP-mediated antinociception. These results prove the antinociceptive activity of the leaves of A. pavonina and support the traditional use of this plant. PMID:26346723

  13. Purification, physicochemical properties, thermal analysis and antinociceptive effect of atranorin extracted from Cladina kalbii.

    PubMed

    Melo, Marcélia Garcez Dória; Araújo, Adriano Antunes Souza; Rocha, Carla Paula Leite; Almeida, Emyle Mayra Santana Alves; Siqueira, Rosana de Souza; Bonjardim, Leonardo Rigoldi; Quintans, Lucindo José

    2008-10-01

    Lichens and their secondary metabolites have attracted the interest of many researchers. Some species have been shown to contain substances with remarkable biologic activity, as antimicrobial, mainly against Gram positive bacteria; antineoplasic acting on solid and ascetic tumors, or in culture cells; antiviral; hypotensive; and spasmolytic effects. The aim of this study was to isolate and characterize atranorin, one of the major constituents which presents in Cladina kalbii (DES ABB.) AHTI., and analyze its antinociceptive effect. The antinociceptive activity was verified in acetic acid-induced writhing test and formalin test with mice. In this work it was observed that atranorin was effective in significant reducing (p<0.05) abdominal writhing at doses of 200 and 400 mg/kg (p.o.) by 52.6 and 61.3%, respectively, when compared to control group (vehicle). The formalin test showed in 200 and 400 mg/kg (p.o.) that atranorin injection was able to inhibit the inflammatory processes (second phase) dose dependently. PMID:18827367

  14. Anti-inflammatory effect of the ethanolic extract from Bowdichia virgilioides H.B.K stem bark.

    PubMed

    Barros, Wander M; Rao, Vietla S N; Silva, Regilane M; Lima, Joaquim C S; Martins, Domingos T O

    2010-09-01

    Bowdichia virgilioides H.B.K stem bark (Fabaceae), locally known as "sucupira-preta", is a reputed folk-remedy to treat some inflammatory disorders. To validate its traditional claim, the ethanolic extract from B. virgilioides was evaluated in several animal models of inflammation and nociception. The extract at oral doses of 100 to 1000 mg/kg body weight caused a significant inhibition of carrageenan-induced hind paw oedema, suppression of exudate volume and leukocyte immigration in rat pleurisy induced by carrageenan, and reduction of granuloma weights in the model of subcutaneous granulomas promoted by cotton pellets. In addition, the plant extract significantly inhibited the vascular permeability increase induced by intraperitoneal acetic acid. It also showed marked antinociceptive effect in acetic acid-induced writhing test and in the second phase of formalin test in mice. These findings evidence the anti-inflammatory potential of Bowdichia virgilioides bark and supports its traditional use in inflammatory conditions.

  15. Analgesic activity of gold preparations used in Ayurveda & Unani-Tibb.

    PubMed

    Bajaj, S; Vohora, S B

    1998-09-01

    Calcined gold preparations, Ayurvedic Swarna Bhasma (SB) and Unani Kushta Tila Kalan (KTK) were investigated for analgesic effects in rats and mice using four types of noxious stimuli. Auranofin (AN) used in modern medicine was also studied for comparisons. The test drugs SB and KTK (25-50 mg/kg, p.o.) and AN (2.5-5.0 mg/kg, p.o.) exhibited analgesic activity against chemical (acetic acid induced writhing), electrical (pododolorimeter), thermal (Eddy's hot plate and analgesiometer) and mechanical (tail clip) test. While the analgesic effects of SB and KTK could be partly blocked by pretreatment with naloxone (1-5 mg/kg, i.p.,--15 min), such antagonism was not discernible with AN at the doses used. Involvement of opioidergic mechanism is suggested for the observed analgesic activity.

  16. Evaluation of anti-pyretic and analgesic activity of Emblica officinalis Gaertn.

    PubMed

    Perianayagam, James B; Sharma, S K; Joseph, Aney; Christina, A J M

    2004-11-01

    The present study was designed to investigate the anti-pyretic and analgesic activity of ethanol (EEO) and aqueous (AEO) extracts of Emblica officinalis fruits in several experimental models. A single oral dose of EEO and AEO (500 mg/kg, i.p.) showed significant reduction in brewer's yeast induced hyperthermia in rats. EEO and AEO also elicited pronounced inhibitory effect on acetic acid-induced writhing response in mice in the analgesic test. Both, EEO and AEO did not show any significant analgesic activity in the tail-immersion test. These findings suggest that extracts of Emblica officinalis fruits possessed potent anti-pyretic and analgesic activity. Preliminary phytochemical screening of the extracts showed the presence of alkaloids, tannins, phenolic compounds, carbohydrates and amino acids, which may be responsible for anti-pyretic and analgesic activities. PMID:15374611

  17. Uric acid attenuates nitric oxide production by decreasing the interaction between endothelial nitric oxide synthase and calmodulin in human umbilical vein endothelial cells: a mechanism for uric acid-induced cardiovascular disease development.

    PubMed

    Park, Jung-Hyun; Jin, Yoon Mi; Hwang, Soojin; Cho, Du-Hyong; Kang, Duk-Hee; Jo, Inho

    2013-08-01

    The elevated level of uric acid in the body is associated with increased risk of cardiovascular diseases, which is mediated by endothelial dysfunction. However, its underlying mechanism is not fully understood, although dysregulation of endothelial nitric oxide (NO) production is likely to be involved. Using human umbilical vascular endothelial cells (HUVEC), we explored the molecular mechanism of uric acid on endothelial NO synthase (eNOS) activity and NO production. Although high dose of uric acid (12mg/dl for 24h treatment) significantly decreased eNOS activity and NO production, it did not alter eNOS expression and phosphorylations at eNOS-Ser(1177), eNOS-Thr(495) and eNOS-Ser(114). Under this condition, we also found no alterations in the dimerization and acetylation of eNOS, compared with the control. Furthermore, uric acid did not change the activity of arginase II, an enzyme degrading l-arginine, a substrate of eNOS, and intracellular level of calcium, a cofactor for eNOS activation. We also found that uric acid did not alter xanthine oxidase activity, suggesting no involvement of xanthine oxidase-derived O2(-) production in the observed inhibitory effects. In vitro and in cell coimmunoprecipitation studies, however, revealed that uric acid significantly decreased the interaction between eNOS and calmodulin (CaM), an eNOS activator, although it did not change the intracellular CaM level. Like in HUVEC, uric acid also decreased eNOS-CaM interaction in bovine aortic EC. Finally, uric acid attenuated ionomycin-induced increase in the interaction between eNOS and CaM. This study suggests firstly that uric acid decreased eNOS activity and NO production through reducing the binding between eNOS and CaM in EC. Our result may provide molecular mechanism by which uric acid induces endothelial dysfunction.

  18. Expression Analysis of SOX14 during Retinoic Acid Induced Neural Differentiation of Embryonal Carcinoma Cells and Assessment of the Effect of Its Ectopic Expression on SOXB Members in HeLa Cells

    PubMed Central

    Popovic, Jelena; Stanisavljevic, Danijela; Schwirtlich, Marija; Klajn, Andrijana; Marjanovic, Jelena; Stevanovic, Milena

    2014-01-01

    SOX14 is a member of the SOXB2 subgroup of transcription factors implicated in neural development. Although the first SOX14 gene in vertebrates was cloned and characterized more than a decade ago and its expression profile during development was revealed in various animal model systems, the role of this gene during neural development is largely unknown. In the present study we analyzed the expression of SOX14 in human NT2/D1 and mouse P19 pluripotent embryonal carcinoma cells. We demonstrated that it is expressed in both cell lines and upregulated during retinoic acid induced neural differentiation. We showed that SOX14 was expressed in both neuronal and non-neuronal differentiated derivatives, as revealed by immunocytochemistry. Since it was previously proposed that increased SOXB2 proteins level interfere with the activity of SOXB1 counteracting partners, we compared expression patterns of SOXB members during retinoic acid induction of embryonal carcinoma cells. We revealed that upregulation of SOX14 expression is accompanied by alterations in the expression patterns of SOXB1 members. In order to analyze the potential cross-talk between them, we generated SOX14 expression construct. The ectopic expression of SOX14 was demonstrated at the mRNA level in NT2/D1, P19 and HeLa cells, while an increased level of SOX14 protein was detected in HeLa cells only. By transient transfection experiments in HeLa cells we showed for the first time that ectopic expression of SOX14 repressed SOX1 expression, whereas no significant effect on SOX2, SOX3 and SOX21 was observed. Data presented here provide an insight into SOX14 expression during in vitro neural differentiation of embryonal carcinoma cells and demonstrate the effect of its ectopic expression on protein levels of SOXB members in HeLa cells. Obtained results contribute to better understanding the role of one of the most conserved SOX proteins. PMID:24637840

  19. Anti-nociceptive Activity of Ethnomedicinally Important Analgesic Plant Isodon rugosus Wall. ex Benth: Mechanistic Study and Identifications of Bioactive Compounds

    PubMed Central

    Zeb, Anwar; Ahmad, Sajjad; Ullah, Farhat; Ayaz, Muhammad; Sadiq, Abdul

    2016-01-01

    Isodon rugosus Wall. ex Benth. is extensively used as traditional medicine for the management of various types of pain including tooth ache, gastric pain, abdominal pain, ear ache, and generalized body pain. The current study is designed to scientifically verify the purported uses of I. rugosus as analgesic agent and to figure out its possible mechanism of action. Bioactive compounds responsible for analgesic activity were identified using GC and GC-MS analysis. Analgesic potentials were evaluated using acetic acid induced writhing, hot plate test, and formalin induced paw licking test. In acetic acid induced writhing chloroform fraction (Ir.Chf) exhibited 53% analgesia while formalin test displayed 61% inhibition at phase-I and 45% at phase-II respectively at a dose of 100 mg/kg. Similarly, in hot plate test Ir.Chf displayed average reaction time of 7 min at 15, 30, 45, and 60 min intervals. The possible mechanism of action was found to be the central pathway via opioidergic receptors as the mice showed morphine like analgesic activity at pre-administration of naloxone (opioid antagonist) in hot plate and formalin tests. In GC-MS analysis, 83 compounds were identified among which eight compounds including benzyl alcohol, sebacic acid, myristic acid, phytol, sugiol, Tocopherol, α-Amyrin, and stigmasterol were sorted out as previously reported analgesic compounds. Current study revealed that analgesic potential of I. rugosus can attributed to the presence of analgesic compounds. It may also be concluded that opioids receptors are involved in the analgesic mechanism of I. rugosus due to effective antagonism of nalaxone. PMID:27458379

  20. Anti-nociceptive Activity of Ethnomedicinally Important Analgesic Plant Isodon rugosus Wall. ex Benth: Mechanistic Study and Identifications of Bioactive Compounds.

    PubMed

    Zeb, Anwar; Ahmad, Sajjad; Ullah, Farhat; Ayaz, Muhammad; Sadiq, Abdul

    2016-01-01

    Isodon rugosus Wall. ex Benth. is extensively used as traditional medicine for the management of various types of pain including tooth ache, gastric pain, abdominal pain, ear ache, and generalized body pain. The current study is designed to scientifically verify the purported uses of I. rugosus as analgesic agent and to figure out its possible mechanism of action. Bioactive compounds responsible for analgesic activity were identified using GC and GC-MS analysis. Analgesic potentials were evaluated using acetic acid induced writhing, hot plate test, and formalin induced paw licking test. In acetic acid induced writhing chloroform fraction (Ir.Chf) exhibited 53% analgesia while formalin test displayed 61% inhibition at phase-I and 45% at phase-II respectively at a dose of 100 mg/kg. Similarly, in hot plate test Ir.Chf displayed average reaction time of 7 min at 15, 30, 45, and 60 min intervals. The possible mechanism of action was found to be the central pathway via opioidergic receptors as the mice showed morphine like analgesic activity at pre-administration of naloxone (opioid antagonist) in hot plate and formalin tests. In GC-MS analysis, 83 compounds were identified among which eight compounds including benzyl alcohol, sebacic acid, myristic acid, phytol, sugiol, Tocopherol, α-Amyrin, and stigmasterol were sorted out as previously reported analgesic compounds. Current study revealed that analgesic potential of I. rugosus can attributed to the presence of analgesic compounds. It may also be concluded that opioids receptors are involved in the analgesic mechanism of I. rugosus due to effective antagonism of nalaxone. PMID:27458379

  1. Antinociceptive and anti-inflammatory effects of essential oil extracted from Chamaecyparis obtusa in mice.

    PubMed

    Park, Yujin; Jung, Seung Min; Yoo, Seung-Ah; Kim, Wan-Uk; Cho, Chul-Soo; Park, Bum-Jin; Woo, Jong-Min; Yoon, Chong-Hyeon

    2015-12-01

    Essential oil extracted from Chamaecyparis obtusa (EOCO) consists of several monoterpenes with anti-inflammatory effects. Monoterpenes are expected to have an analgesic effect through inhibition of pro-inflammatory mediators. The present study investigated the anti-nociceptive and anti-inflammatory effects of EOCO in animal models of pain. Intraperitoneal injection with EOCO (5 or 10mg/kg), aspirin (positive control, 300mg/kg), or DMSO (negative control) was performed 1h before the nociception tests: acetic acid-induced writhing response, formalin test, and hot plate test in mice, and acidic saline-induced allodynia in rats. The expression of pro-inflammatory cytokines and pro-inflammatory enzymes in formalin-injected paws was determined by ELISA and western blotting, respectively. Treatment with EOCO significantly reduced acetic acid-induced writhing and paw-licking time in late response of the formalin tests. The anti-nociceptive effect was comparable with aspirin. However, EOCO did not affect the reaction time of licking of the hind paws or jumping in hot plate test and the mechanical withdrawal thresholds in acidic saline-induced allodynia model. Formalin-injected paws of mice treated with EOCO revealed the down-regulated expression of tumor necrosis factor-α, interleukin-1β, inducible nitric oxide synthase, and cyclooxygenase-2, as compared with those of control mice. These data showed the anti-nociceptive and anti-inflammatory effects of EOCO. The pain-relieving effect might be attributed to inhibition of peripheral pain in association with inflammatory response. EOCO could be a useful therapeutic strategy to manage pain and inflammatory diseases.

  2. Susceptibility Testing

    MedlinePlus

    ... page helpful? Also known as: Sensitivity Testing; Drug Resistance Testing; Culture and Sensitivity; C & S; Antimicrobial Susceptibility Formal name: Bacterial and Fungal Susceptibility Testing Related tests: Urine Culture ; ...

  3. A preliminary evaluation of antihyperglycemic and analgesic activity of Alternanthera sessilis aerial parts

    PubMed Central

    2014-01-01

    Background Alternanthera sessilis is used by folk medicinal practitioners of Bangladesh for alleviation of severe pain. The objective of this study was to scientifically analyze the analgesic (non-narcotic) property of aerial parts of the plant along with antihyperglycemic activity. Methods Antihyperglycemic activity was measured by oral glucose tolerance tests. Analgesic (non-narcotic) activity was determined by observed decreases in abdominal writhings in intraperitoneally administered acetic acid-induced pain model in mice. Results Administration of methanol extract of aerial parts led to dose-dependent and significant reductions in blood glucose levels in glucose-loaded mice. At doses of 50, 100, 200 and 400 mg per kg body weight, the extract reduced blood sugar levels by 22.9, 30.7, 45.4 and 46.1%, respectively compared to control animals. By comparison, a standard antihyperglycemic drug, glibenclamide, when administered at a dose of 10 mg per kg body weight, reduced blood glucose level by 48.9%. In analgesic activity tests, the extract at the above four doses reduced the number of abdominal writhings by 27.6, 37.9, 41.4, and 44.8%, respectively. A standard analgesic drug, aspirin, reduced the number of writhings by 31.0 and 51.7%, respectively, when administered at doses of 200 and 400 mg per kg body weight. Conclusion The results validate the folk medicinal use of the plant to alleviate pain. At the same time, the antihyperglycemic activity result suggests that the plant may be a potential source for blood sugar lowering drug(s). PMID:24885344

  4. Antinociceptive effect of Ferula assa-foetida oleo-gum-resin in mice

    PubMed Central

    Bagheri, S.M.; Dashti-R, M.H.; Morshedi, A.

    2014-01-01

    Ferula assa-foetida L. is distributed throughout central Asia and Mediterranean area and grows wildly in Iran and Afghanistan. Asafoetida is an oleo-gum-resin that is the exudates of the roots of Ferula assa-foetida and some other Ferula species. In Iranian traditional medicine, asafoetida is considered to be sedative, analgesic, carminative, antispasmodic, diuretic, antihelmintic, emmenagogue and expectorant. The aim of this study was to evaluate the antinociceptive effect of asafoetida in mice. The analgesic activity of asafoetida (25, 50 and 100 mg/kg) was compared with that of sodium diclofenac (30 mg/kg) or morphine sulfate (8 mg/kg) by using hot plate and acetic acid induced writhing tests. In hot plate test, the percentage of maximum possible effect (%MPE) against the thermal stimulus at 15 min post treatment time point for all doses of asafoetida was significantly greater than the control group. The number of writhes in all three doses of asafoetida was significantly less than the control group. GraphPad Prism 5 software was used to analyze the behavioral responses. Data were analyzed using repeated measure one-way ANOVA and P<0.05 was considered as the significant level. According to our findings, asafoetida exhibited a significant antinociceptive effect on chronic and acute pain in mice. These effects probably involve central opioid pathways and peripheral anti-inflammatory action. PMID:25657791

  5. Analgesic and anti-inflammatory activity of root bark of Grewia asiatica Linn. in rodents

    PubMed Central

    Paviaya, Udaybhan Singh; Kumar, Parveen; Wanjari, Manish M.; Thenmozhi, S.; Balakrishnan, B. R.

    2013-01-01

    Background: Grewia asiatica Linn. (Family: Tiliaceae), called Phalsa in Hindi is an Indian medicinal plant used for a variety of therapeutic and nutritional uses. The root bark of the plant is traditionally used in rheumatism (painful chronic inflammatory condition). Aims: The present study demonstrates the analgesic and anti-inflammatory activity of root bark of G. asiatica in rodents. Settings and Design: The methanolic extract of Grewia asiatica (MEGA) and aqueous extract of Grewia asiatica (AEGA) of the bark were prepared and subjected to phytochemical tests and pharmacological screening for analgesic and anti-inflammatory effect in rodents. Materials and Methods: Analgesic effect was studied using acetic acid-induced writhing in mice and hot plate analgesia in rats while anti-inflammatory activity was investigated using carrageenan-induced paw oedema in rats. The MEGA or AEGA was administered orally in doses of 200 and 400 mg/kg/day of body weight. Statistical Analysis: Data were analysed by one-way analysis of variance followed by Dunnett's test. Results: The extracts showed a significant inhibition of writhing response and increase in hot plate reaction time and also caused a decrease in paw oedema. The effects were comparable with the standard drugs used. Conclusions: The present study indicates that root bark of G. asiatica exhibits peripheral and central analgesic effect and anti-inflammatory activity, which may be attributed to the various phytochemicals present in root bark of G. asiatica. PMID:24501443

  6. Antinociceptive and antioxidant activity of Zanthoxylum budrunga wall (Rutaceae) seeds.

    PubMed

    Islam, Md Khirul; Biswas, Nripendra Nath; Saha, Sanjib; Hossain, Hemayet; Jahan, Ismet Ara; Khan, Tanzir Ahmed; Awang, Khalijah; Shilpi, Jamil A

    2014-01-01

    Different parts of the medicinal plant Zanthoxylum budrunga Wall enjoy a variety of uses in ethnobotanical practice in Bangladesh. In the present study, a number of phytochemical and pharmacological investigations were done on the ethanol extract of Z. budrunga seeds (ZBSE) to evaluate its antinociceptive and antioxidant potential. ZBSE was also subjected to HPLC analysis to detect the presence of some common antioxidants. In acetic acid induced writhing test in mice, ZBSE showed 65.28 and 74.30% inhibition of writhing at the doses of 250 and 500 mg/kg and the results were statistically significant (P < 0.001). In hot-plate test, ZBSE raised the pain threshold significantly (P < 0.001) throughout the entire observation period. In DPPH scavenging assay, the IC50 of ZBSE was observed at 82.60 μg/mL. The phenolic content was found to be 338.77 mg GAE/100 g of dried plant material. In reducing power assay, ZBSE showed a concentration dependent reducing ability. HPLC analysis indicated the presence of caffeic acid with a concentration of 75.45 mg/100 g ZBSE. Present investigation supported the use of Zanthoxylum budrunga seed in traditional medicine for pain management. Constituents including caffeic acid and other phenolics might have some role in the observed activity. PMID:24707219

  7. Bioactivities of the ethanol extract from Ageratum fastigiatum branches: antioxidant, antinociceptive and anti-inflammatory.

    PubMed

    Del-Vechio-Vieira, Glauciemar; Santos, Bruna C S; Alves, Maria Silvana; Araújo, Aílson L A; Yamamoto, Célia H; Pinto, Míriam A O; Kaplan, Maria Auxiliadora C; Sousa, Orlando V

    2016-07-11

    The present study was designed to investigate the antioxidant, antinociceptive and anti-inflammatory activities of the ethanol extract from Ageratum fastigiatum branches. Phytochemical screening and total phenol and flavonoid contents were determined. The antioxidant activity was assessed by 2,2-diphenyl-1-pycrilhydrazin (DPPH) and iron reducing power methods. The antinociceptive effect was evaluated using the acetic acid-induced writhing, formalin, hot plate and tail immersion assays; while the carrageenan-induced paw edema and pleurisy tests were performed to examine the anti-inflammatory activity against acute inflammation. The extract revealed the presence of flavonoids, tannins, coumarins, terpenes, sterols and saponins. Expressive levels of total phenols and flavonoids and a promising antioxidant effect were quantified. At the doses of 50, 100 and 200 mg/kg, the extract inhibited the writhing, reduced both phases of paw licking time and increased the reaction time on the hot plate. In the tail immersion test, the extract (50, 100 and 200 mg/kg) caused a significant inhibition of pain. In these doses, the paw edema, exudate volume and leucocyte mobilization were significantly reduced. These results suggest that A. fastigiatum can be an active source of substances with antioxidant, antinociceptive and anti-inflammatory activities, adding scientific support to the appropriate use in the Brazilian folk medicine. PMID:27411067

  8. Antinociceptive activity of (-)-carvone: evidence of association with decreased peripheral nerve excitability.

    PubMed

    Gonçalves, Juan Carlos Ramos; Oliveira, Fernando de Sousa; Benedito, Rubens Batista; de Sousa, Damião Pergentino; de Almeida, Reinaldo Nóbrega; de Araújo, Demetrius Antônio Machado

    2008-05-01

    (-)-Carvone is a monoterpene ketone that is the main active component of Mentha plant species like Mentha spicata. This study aimed to investigate the antinociceptive activity of (-)-carvone using different experimental models of pain and to investigate whether such effects might be involved in the nervous excitability elicited by others monoterpenes. In the acetic acid-induced writhing test, we observed that (-)-carvone-treated mice exhibited a significant decrease in the number of writhes when 100 and 200 mg/kg was administered. It was also demonstrated that (-)-carvone inhibited the licking response of the injected paw when 100 and 200 mg/kg was administered (i.p.) to mice in the first and second phases of the formalin test. Since naloxone (5 mg/kg, s.c.), an opioid antagonist, showed no influence on the antinociceptive action of (-)-carvone (100 mg/kg), this suggested nonparticipation of the opioid system in the modulation of pain induced by (-)-carvone. Such results were unlikely to be provoked by motor abnormality, since (-)-carvone-treated mice did not exhibit any performance alteration on the Rota-rod apparatus. Because the antinociceptive effects could be associated with neuronal excitability inhibition, we performed the single sucrose gap technique and observed that (-)-carvone (10 mM) was able to reduce the excitability of the isolated sciatic nerve through a diminution of the compound action potential amplitude by about 50% from control recordings. We conclude that (-)-carvone has antinociceptive activity associated with decreased peripheral nerve excitability.

  9. Test plan :

    SciTech Connect

    Dwyer, Stephen F.

    2013-05-01

    This test plan is a document that provides a systematic approach to the planned testing of rooftop structures to determine their actual load carrying capacity. This document identifies typical tests to be performed, the responsible parties for testing, the general feature of the tests, the testing approach, test deliverables, testing schedule, monitoring requirements, and environmental and safety compliance.

  10. Analgesic and anti-inflammatory activity of Leonurus sibiricus.

    PubMed

    Islam, M Amirul; Ahmed, Firoj; Das, A K; Bachar, S C

    2005-06-01

    The methanolic extract of Leonurus sibiricus aerial parts injected intraperitoneally at dose of 250 and 500 mg/kg showed a significant analgesic effect in acetic acid-induced writhing in mice. Moreover, when given orally to rats at dose of 200 and 400 mg/kg, it showed a significant anti-inflammatory activity against carrageenin induced rat paw edema in rats.

  11. Prenatal Tests

    MedlinePlus

    ... X Home > Pregnancy > Prenatal care > Prenatal tests Prenatal tests E-mail to a friend Please fill in ... if you’re feeling fine. What are prenatal tests? Prenatal tests are medical tests you get during ...

  12. Thyroid Tests

    MedlinePlus

    ... calories and how fast your heart beats. Thyroid tests check how well your thyroid is working. They ... thyroid diseases such as hyperthyroidism and hypothyroidism. Thyroid tests include blood tests and imaging tests. Blood tests ...

  13. Pinworm test

    MedlinePlus

    Oxyuriasis test; Enterobiasis test; Tape test ... diagnose this infection is to do a tape test. The best time to do this is in ... to determine if there are eggs. The tape test may need to be done on 3 separate ...

  14. Testing? Testing? In Literature?

    ERIC Educational Resources Information Center

    Purves, Alan C.

    The assumptions behind secondary school literature course tests--whether asking students to recall aspects of literary works, to relate literary works to each other, or to analyze unfamiliar literary works--are open to question. They fail to acknowledge some of the most important aspects of literature which, if properly taught, should provide a…

  15. Testing "Compatibility Testing."

    ERIC Educational Resources Information Center

    Robins, Elliot; Huston, Ted L.

    Most models of marital choice are attempts to explain choices within the field of available eligibles. The essence of compatibility testing is that people select their mates by evaluating the match between psychological characteristics after sorting the available field on the basis of social characteristics. A compatibility model seems to require…

  16. Antinociceptive, anti-inflammatory, antimicrobial and central nervous system depressant activities of ethanolic extract of leaves and roots of Gomphostemma parviflorum var. parviflorum wall

    PubMed Central

    Shams-Ud-Doha, KM; Al Mahmud, Zobaer; Bachar, Sitesh C.; Qais, Nazmul

    2013-01-01

    Background: Gomphostemma parviflorum (Lamiaceae) is a medicinal plant of Bangladesh which has been used traditionally in the treatment of painful and inflammatory conditions such as asthma, headache, fever, etc. Objective: To investigate the antinociceptive, anti-inflammatory, central nervous system (CNS) depressant and antimicrobial activities of ethanolic extracts of leaves (GPLE) and roots (GPRE) of the plant. Materials and Methods: The antinociceptive potentials of the extracts were studied using acetic acid-induced writhing test in mice, anti-inflammatory activity was investigated using carrageenan-induced paw edema in rats, CNS depressant activities were evaluated using pentobarbitone-induced sleeping time, Hole cross and Open field tests in mice while the anti-microbial activity was studied by in vitro disc diffusion method. Results: The extracts GPLE and GPRE significantly (P < 0.001) and dose dependently inhibited the acetic acid-induced writhing in mice with 73.15% and 53.69% inhibition, respectively at the dose of 200 mg/kg. At the same dose GPLE and GPRE significantly inhibited carrageenan-induced rats paw edema at the end of 4 hour with 35.54% and 28.17% inhibition, respectively. The extracts significantly prolonged the pentobarbitone-induced sleeping time and decreased the locomotory activities in open field and Hole cross tests in mice. The GPLE showed strong antimicrobial activity against Gram-positive and Gram-negative bacteria with zones of inhibition ranging from 8 to 20 mm at a concentration of 400 μg/disc. Conclusion: The findings of the study indicate that the leaves and roots of G. parviflorum possess antinociceptive, anti-inflammatory and CNS depressant activity and revealed the antimicrobial activities of leaves extract of the plant. The results justify the traditional use of the plant in the treatment of painful and inflammatory disorders. PMID:24174815

  17. Analgesic and antipyretic activities of Momordica charantia Linn. fruits

    PubMed Central

    Patel, Roshan; Mahobia, Naveen; Upwar, Nitin; Waseem, Naheed; Talaviya, Hetal; Patel, Zalak

    2010-01-01

    Plant Momordica charantia Linn. belongs to family Cucurbitaceae. It is known as bitter gourd in English and karela in Hindi. Earlier claims show that the plant is used in stomachic ailments as a carminative tonic; as an antipyretic and antidiabetic agent; and in rheumatoid arthritis and gout. The fruit has been claimed to contain charantin, steroidal saponin, momordium, carbohydrates, mineral matters, ascorbic acid, alkaloids, glucosides, etc. The ethanolic extract of the fruit showed the presence of alkaloids, tannins, glycosides, steroids, proteins, and carbohydrates. The present study was carried out using acetic acid-induced writhing and tail-immersion tests in mice, while yeast-induced pyrexia in rats. The ethanolic extracts (250 and 500 mg/kg, po.) showed an analgesic and antipyretic effect, which was significantly higher than that in the control rats. The observed pharmacological activities provide the scientific basis to support traditional claims as well as explore some new and promising leads. PMID:22247882

  18. Non-carboxylic analogues of aryl propionic acid: synthesis, anti-inflammatory, analgesic, antipyretic and ulcerogenic potential.

    PubMed

    Eissa, S I; Farrag, A M; Galeel, A A A

    2014-09-01

    As a part of ongoing studies in developing new potent anti-inflammatory and analgesic agents, a series of novel 6-methoxy naphthalene derivatives was efficiently synthesized and characterized by spectral and elemental analyses. The newly synthesized compounds were evaluated for their anti-inflammatory activities using carrageenin-induced rat paw edema model, analgesic activities using acetic acid induced writhing model in mice and anti-pyretic activity using yeast induced hyperpyrexia method as well as ulcerogenic effects. Among the synthesized compounds, thiourea derivative (6a, e) exhibited higher anti-inflammatory activity than the standard drug naproxen in reduction of the rat paw edema (88.71, 89.77%) respectively. All of the non-carboxylic tested compounds were found to have promising anti-inflammatory, analgesic and antipyretic activity, while were devoid of any ulcerogenic effects. PMID:24446206

  19. Evaluation of Analgesic and Anti-Inflammatory Activity of Extract of Holoptelea Integrifolia and Argyreia Speciosa in Animal Models

    PubMed Central

    Hiray, R. S.; Ghongane, B. B.

    2015-01-01

    Background Long term use of NSAIDs, opioids and corticosteroids was associated with serious adverse effects. Hence, the search for a safer analgesic and anti-inflammatory agent was always going on. It was considered worthwhile to evaluate analgesic and anti-inflammatory activities of Holoptelea integrifolia and Argyreia speciosa. Aim To evaluate analgesic and anti-inflammatory activities of aqueous extract of leaves of Holoptelea Integrifolia and methanolic extract of Argyreia Speciosa root powder in mice and rats. Materials and Methods After obtaining permission from animal ethics committee, the animals were divided into 7 groups of 6 animals each {control, standard – ibuprofen 100mg/kg, Holoptelea integrifolia (250 and 500 mg/kg), Argyreia speciosa (100 and 300 mg/kg) and combination of Holoptelea integrifolia (250 mg/kg) and Argyreia speciosa (100 mg/kg)}. The analgesic activity of the extracts was evaluated using tail-flick with radiant heat and acetic acid induced writhing method and the anti-inflammatory activity was evaluated using carrageenan induced paw oedema method. Statistical Analysis One-way ANOVA followed by post-hoc test. p < 0.05 was considered to be significant. Results In tail-flick method, both Holoptelea integrifolia and Argyreia speciosa produced significant (p<0.05) increase in latency as compared to control, their combination showed a significant increase in latency as compared to control as well as to the standard – ibuprofen. In writhing method, Holoptelea integrifolia and Argyreia speciosa, alone and in combination, significantly decreased the number of writhes as compared to control. In paw oedema method, both Holoptelea integrifolia and Argyreia speciosa showed significant inhibition of paw oedema as compared to control and the activity was comparable to ibuprofen. Conclusion Extracts of Holoptelea integrifolia and Argyreia speciosa exhibits significant central and peripheral analgesic and anti-inflammatory activity. PMID:26393140

  20. Antinociceptive effect of ethanolic extract of Selaginella convoluta in mice

    PubMed Central

    2012-01-01

    Background Selaginella convoluta (Arn.) Spring (Selaginellaceae), commonly known as “jericó”, is a medicinal plant found in northeastern Brazil. S. convoluta is used in folk medicine as an antidepressant, aphrodisiac, diuretic, analgesic, anti-inflammatory and it is used to combat amenorrhea, coughing and bleeding. This study was performed to evaluate the antinociceptive effects of ethanolic extract from S. convoluta in mice exposed to chemical and thermal models of nociception. Methods Preliminary phytochemical analysis of the ethanolic extract was performed. The ethanolic extract from Selaginella convoluta (Sc-EtOH) was examined for its intraperitoneal (i.p.) antinociceptive activity at the doses of 100, 200 and 400 mg/kg body weight. Acetic acid-induced writhing, formalin injection and hot plate tests were used to evaluate the antinociceptive activity of Sc-EtOH extract. The rota-rod test was used to evaluate motor coordination. Results A preliminary analysis of Sc-EtOH revealed that it contained phenols, steroids, terpenoids and flavonoids. In the acetic acid-induced writhing test, mice treated with Sc-EtOH (100, 200 and 400 mg/kg, i.p.) exhibited reduced writhing (58.46, 75.63 and 82.23%, respectively). Secondly, Sc-EtOH treatment (100, 200 and 400 mg/kg, i.p.) decreased the paw licking time in mice during the first phase of the formalin test (by 44.90, 33.33 and 34.16%, respectively), as well as during the second phase of the test (by 86.44, 56.20 and 94.95%, respectively). Additionally, Sc-EtOH treatment at doses of 200 and 400 mg/kg increased the latency time in the hot plate test after 60 and 90 minutes, respectively. In addition, Sc-EtOH did not impair motor coordination. Conclusion Overall, these results indicate that Sc-EtOH is effective as an analgesic agent in various pain models. The activity of Sc-EtOH is most likely mediated via the inhibition of peripheral mediators and central inhibitory mechanisms. This study supports previous claims of

  1. Antinociceptive profiles of crude extract from roots of Angelica gigas NAKAI in various pain models.

    PubMed

    Choi, Seong-Soo; Han, Ki-Jung; Lee, Han-Kyu; Han, Eun-Jung; Suh, Hong-Won

    2003-09-01

    To characterize the antinociceptive profiles of Angelica gigas NAKAI (ANG; Korean angelica), methanol extract from the dried roots of ANG was made and mice were administered orally at the various doses (from 0.25 to 3 g/kg). ANG produced the increased latencies of the tail-flick and hot-plate paw-licking responses in a dose-dependent manner. In acetic acid-induced writhing test, ANG dose-dependently decreased writhing numbers. Moreover, the cumulative response time of nociceptive behaviors induced by intraplantar formalin injection was reduced during both the 1st and the 2nd phases in a dose-dependent manner in ANG-treated mice. Furthermore, oral administration of ANG did not cause licking, scratching and biting responses induced by TNF-alpha (100 pg), IFN-gamma (100 pg) or IL-1beta (100 pg) injected intrathecally (i.t.), especially at higher dose (3 g/kg). Additionally, in ANG treated mice, the cumulative nociceptive response time for i.t. administration of substance P or capsaicin was dose-dependently diminished. Finally, nociceptive responses elicited by i.t. injection of glutamate (20 microg), N-methyl-D-aspartic acid (60 ng), alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (13 ng) or kainic acid (12 ng) were decreased by oral administration of ANG. Our results suggest that ANG produces antinociception via acting on the central nervous system and shows antinociceptive profiles in various pain models, especially inflammatory pain.

  2. Evaluation of anti-inflammatory, analgesic, and antipyretic effects of ethanolic extract of Pedalium murex Linn. fruits.

    PubMed

    Patel, Mahendra K; Mandavia, Divyesh R; Patel, Tejas K; Barvaliya, Manish J; Tripathi, C B

    2013-01-01

    This study investigated the possible anti-inflammatory, analgesic, and antipyretic effects of ethanolic extract of Pedalium murex Linn. fruits in selected experimental animal models. Anti-inflammatory activity of Pedalium murex Linn., with doses of 200 mg/kg and 400 mg/kg, p.o., was evaluated by Lambda-carrageenan induced paw oedema in Wistar albino rats; analgesic activity with doses of 280 mg/kg and 560 mg/kg, p.o., was evaluated by hot plate method and acetic acid induced writhing method in Swiss albino mice; and antipyretic activity with doses of 110 mg/kg and 220 mg/kg, p.o., was evaluated in New Zealand white rabbits by injecting gram -ve lipopolysaccharide obtained from E. coli. Results were analysed by one way ANOVA followed by Dunnet's multiple comparison test. Pedalium murex Linn. showed significant anti-inflammatory activity from 15 min to 180 min as compared to vehicle treated animals. It was comparable to diclofenac sodium at 180 min. The extract did not prolong the reaction time on hot plate method but significantly reduced the number of writhing after acetic acid administration. Also the extract did not show any antipyretic activity on lipopolysaccharide induced pyrexia. It is therefore concluded that the ethanolic extract of Pedalium murex Linn. fruits has an anti-inflammatory and peripheral analgesic effects.

  3. Analgesic and Anti-Inflammatory Activities of Methanol Extract of Cissus repens in Mice

    PubMed Central

    Chang, Ching-Wen; Chang, Wen-Te; Liao, Jung-Chun; Chiu, Yung-Jia; Hsieh, Ming-Tsuen; Peng, Wen-Huang; Lin, Yu-Chin

    2012-01-01

    The aim of this study was to investigate possible analgesic and anti-inflammatory mechanisms of the CRMeOH. Analgesic effect was evaluated in two models including acetic acid-induced writhing response and formalin-induced paw licking. The anti-inflammatory effect was evaluated by λ-carrageenan-induced mouse paw edema and histopathologic analyses. The results showed that CRMeOH (500 mg/kg) decreased writhing response in the acetic acid assay and licking time in the formalin test. CRMeOH (100 and 500 mg/kg) significantly decreased edema paw volume at 4th to 5th hours after λ-carrageenan had been injected. Histopathologically, CRMeOH abated the level of tissue destruction and swelling of the edema paws. These results were indicated that anti-inflammatory mechanism of CRMeOH may be due to declined levels of NO and MDA in the edema paw through increasing the activities of SOD, GPx, and GRd in the liver. Additionally, CRMeOH also decreased IL-1β, IL-6, NFκB, TNF-α, COX-2, and iNOS levels. The contents of two active ingredients, ursolic acid and lupeol, were quantitatively determined. This paper demonstrated possible mechanisms for the analgesic and anti-inflammatory effects of CRMeOH and provided evidence for the classical treatment of Cissus repens in inflammatory diseases. PMID:22991570

  4. Analgesic and Anti-Inflammatory Activities of the Methanol Extract from Pogostemon cablin

    PubMed Central

    Lu, Tsung-Chun; Liao, Jung-Chun; Huang, Tai-Hung; Lin, Ying-Chih; Liu, Chia-Yu; Chiu, Yung-jia; Peng, Wen-Huang

    2011-01-01

    Pogostemon cablin (PC) is a herbal medicine traditionally applied to treat not only common cold, nausea and diarrhea but also headache and fever. The aim of this study was to investigate the analgesic and anti-inflammatory properties of standardized PC methanol extract (PCMeOH) in vivo. Investigations were performed in mice with two analgesic models. One was acetic acid-induced writhing response and the other formalin-induced paw licking. The anti-inflammatory effect was tested by λ-carrageenan (Carr)-induced mice paw edema. These analgesic experimental results indicated that PCMeOH (1.0 g/kg) decreased the acetic acid-induced writhing responses and PCMeOH (0.5 and 1.0 g/kg) decreased the licking time in the second phase of the formalin test. Moreover, Carr-induced paw edema inflammation was significantly reduced in a dose-dependent manner when PCMeOH (0.5 and 1.0 g/kg) was administered 3 and 4 h after the Carr injection. Mechanistic studies showed that PCMeOH decreased the levels of malondialdehyde in the edema paw by increasing the activities of anti-oxidant enzymes, such as superoxide dismutase, glutathione peroxidase and glutathione reductase, in the liver and decreasing the cyclooxygenase 2 and tumor necrosis factor-α activities in the edema paw. This study has demonstrated the analgesic and anti-inflammatory effects of PCMeOH, thus verifying its popular use in traditional medicine. PMID:19933324

  5. Pharmacological evaluation of Mallotus philippinensis (Lam.) Muell.-Arg. fruit hair extract for anti-inflammatory, analgesic and hypnotic activity

    PubMed Central

    Gangwar, Mayank; Gautam, Manish Kumar; Ghildiyal, Shivani; Nath, Gopal; Goel, Raj Kumar

    2016-01-01

    Objective: Recently, we observed wound healing activity of 50% ethanol extract of Mallotus philippinensis Muell. Arg (MP) fruit hairs extract (MPE). In several intestinal infections, localized inflammation is of common occurrence and hence we evaluated the anti-inflammatory, analgesic and hypnotic activity of MPE in different rat experimental models. Materials and Methods: Anti-inflammatory activity was evaluated by carrageenan (acute) and turpentine oil induced formalin (subacute) induced paw edema and while granuloma pouch (subacute) in rats. Analgesic and hypnotic activity of MPE was undertaken by tail-flick, hot-plate, and acetic acid-induced writhing tests while pentobarbitone-induced hypnotic potentiation in rats. Results: MPE at a dose of 200 mg/kg at 3 h after their administration showed inhibition of formalin-induced paw edema by 41.60% (P < 0.001) and carrageenan-induced paw edema by 55.30% (P < 0.001). After 7 days of treatments, MPE showed 38.0% (P < 0.001) inhibition against formalin-induced paw edema and reduced weight of turpentine-induced granuloma pouch by 29.6% (P < 0.01) and volume of exudates by 26.1% (P < 0.01), respectively. MPE (200 mg/kg) showed dose-dependent elevation in pain threshold and peak analgesic effect at 120 min as evidenced by increased latency period in tail flick method and increased reaction time in the hot-plate test while the reduction in the number of acetic acid-induced writhes by 45.7% (P < 0.001). The pentobarbitone-induced hypnosis model showed potentiation, as defined by increased duration of sleep in treated group rats as compared to control. Conclusion: Thus, the study revealed MPE is effective in reducing acute and subacute inflammation and showed effective and similar analgesic activity. This seemed to be safe in the treatment of pain and inflammation. PMID:27069718

  6. Ham test

    MedlinePlus

    Acid hemolysin test; Paroxysmal nocturnal hemoglobinuria - Ham test; PNH - Ham test ... BJ. In: Chernecky CC, Berger BJ, eds. Laboratory Tests and Diagnostic Procedures . 6th ed. Philadelphia, PA: Elsevier ...

  7. Coombs test

    MedlinePlus

    Direct antiglobulin test; Indirect antiglobulin test; Anemia - hemolytic ... No special preparation is necessary for this test. ... There are 2 types of the Coombs test: Direct Indirect The direct ... that are stuck to the surface of red blood cells. Many diseases ...

  8. Trichomonas Testing

    MedlinePlus

    ... vaginalis by Amplified Detection; Trichomonas vaginalis by Direct Fluorescent Antibody (DFA) Related tests: Pap Smear , Chlamydia Testing , ... and men. Other methods. These include the direct fluorescent antibody (DFA) test and a test that detects ...

  9. Antinociceptive and anti-inflammatory effects of compounds isolated from Scaphyglottis livida and Maxillaria densa.

    PubMed

    Déciga-Campos, Myrna; Palacios-Espinosa, Juan Francisco; Reyes-Ramírez, Adelfo; Mata, Rachel

    2007-11-01

    Oral administration of a CH(2)Cl(2)-MeOH (1:1) extract of Scaphyglottis livida produced dose-dependent antinociceptive and anti-inflammatory effects when tested in mice and rats using the hot-plate (150-600 mg/kg) and carrageenan-induced inflammation (150-600 mg/kg) models, respectively. Morphine (1.5-6 mg/kg, p.o.) and indomethacin (10-40 mg/kg, p.o.) were used as positive controls, respectively. Four compounds were isolated from the active extract of Scaphyglottis livida, namely 5alpha-lanosta-24,24-dimethyl-9(11),25-dien-3beta-ol (LDD), 24,24,dimethyl-9,19-cyclolanosta-9(11),25-dien-3-one (cyclobalanone), gigantol and 3,4'-dihydroxy-3',4,5-trimethoxybibenzyl (DTB). LDD and gigantol (25-100 mg/kg, p.o.) significantly increased the hot-plate latency in comparison to vehicle-treated mice and decreased carrageenan-induced inflammation in rats. The antinociception provoked by LDD and gigantol was partially blocked by naloxone (1mg/kg, i.p.). However, pretreatment with L-NAME (100 mg/kg, i.p.) and glibenclamide (10 mg/kg, i.p.) did not affect the antinociceptive response induced by LDD or gigantol suggesting that their pharmacological effect could be partially due to activation of opioid receptors. Moreover, a CH(2)Cl(2)-MeOH (1:1) extract of Maxillaria densa reduced acetic acid-induced abdominal writhes but was not able to produce antinociception in the hot-plate assay. Two compounds were isolated from the active extract of Maxillaria densa, namely fimbriol A and erianthridin. Both compounds partially reduced acetic acid-induced writhes. The results tend to support the popular use of this species in folk medicine for treatment of painful complaints.

  10. Analgesic and Anti-Inflammatory Activities of Rosa taiwanensis Nakai in Mice.

    PubMed

    Tsai, Der-Shiang; Huang, Mei-Hsuen; Tsai, Jen-Chieh; Chang, Yuan-Shuang; Chiu, Yung-Jia; Lin, Yen-Chang; Wu, Lung-Yuan; Peng, Wen-Huang

    2015-05-01

    In this study, we evaluated the analgesic and anti-inflammatory activities of a 70% ethanol extract from Rosa taiwanensis Nakai (RTEtOH). The analgesic effect was determined using acetic acid-induced writhing response and formalin test. The anti-inflammatory activity was evaluated by λ-carrageenan-induced paw edema in mice. The anti-inflammatory mechanism of RTEtOH was examined by measuring the levels of cyclooxygenase-2 (COX-2), nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and malondialdehyde (MDA) in the paw edema tissue and the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GRd) in the liver tissue. The betulinic acid and oleanolic acid contents of RTEtOH were assayed by HPLC. The results showed that RTEtOH decreased the acetic acid-induced writhing responses (1.0 g/kg) and the late phase of the formalin-induced licking time (0.5 and 1.0 g/kg). In the anti-inflammatory models, RTEtOH (0.5 and 1.0 g/kg) reduced the paw edema at 3, 4, and 5 h after λ-carrageenan administration. Moreover, the anti-inflammatory mechanisms might be due to the decreased levels of COX-2, TNF-α, IL-1β, and IL-6, as well as the inhibition of NO and MDA levels through increasing the activities of SOD, GPx, and GRd. The contents of two active compounds, betulinic acid and oleanolic acid, were quantitatively determined. This study demonstrated the analgesic and anti-inflammatory activities of RTEtOH and provided evidence to support its therapeutic use in inflammatory diseases.

  11. Analgesic and Anti-Inflammatory Activities of Rosa taiwanensis Nakai in Mice

    PubMed Central

    Tsai, Der-Shiang; Huang, Mei-Hsuen; Tsai, Jen-Chieh; Chang, Yuan-Shuang; Chiu, Yung-Jia; Lin, Yen-Chang

    2015-01-01

    Abstract In this study, we evaluated the analgesic and anti-inflammatory activities of a 70% ethanol extract from Rosa taiwanensis Nakai (RTEtOH). The analgesic effect was determined using acetic acid-induced writhing response and formalin test. The anti-inflammatory activity was evaluated by λ-carrageenan-induced paw edema in mice. The anti-inflammatory mechanism of RTEtOH was examined by measuring the levels of cyclooxygenase-2 (COX-2), nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and malondialdehyde (MDA) in the paw edema tissue and the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GRd) in the liver tissue. The betulinic acid and oleanolic acid contents of RTEtOH were assayed by HPLC. The results showed that RTEtOH decreased the acetic acid-induced writhing responses (1.0 g/kg) and the late phase of the formalin-induced licking time (0.5 and 1.0 g/kg). In the anti-inflammatory models, RTEtOH (0.5 and 1.0 g/kg) reduced the paw edema at 3, 4, and 5 h after λ-carrageenan administration. Moreover, the anti-inflammatory mechanisms might be due to the decreased levels of COX-2, TNF-α, IL-1β, and IL-6, as well as the inhibition of NO and MDA levels through increasing the activities of SOD, GPx, and GRd. The contents of two active compounds, betulinic acid and oleanolic acid, were quantitatively determined. This study demonstrated the analgesic and anti-inflammatory activities of RTEtOH and provided evidence to support its therapeutic use in inflammatory diseases. PMID:25494361

  12. [Anti-inflammatory, analgesic and anti-pyretic activities of a non-steroidal anti-inflammatory drug, etofenamate, in experimental animals].

    PubMed

    Nakamura, H; Motoyoshi, S; Imazu, C; Ishii, K; Yokoyama, Y; Seto, Y; Kadokawa, T; Shimizu, M

    1982-08-01

    Anti-inflammatory, analgesic, and anti-pyretic activities of orally administered etofenamate, the diethylene glycol ester of flufenamic acid, were investigated in experimental animals. Against acetic acid-induced vascular permeability in mice and ultra-violet light-induced erythema in guinea pigs, etofenamate produced a dose related inhibition at doses of 40--320 mg/kg and 5--20 mg/kg, respectively. In rats, felt-pellet-induced granuloma formation and adjuvant-induced arthritis were significantly inhibited by repeated administration of etofenamate at doses of 20 mg/kg/day for 5 days and 40 mg/kg/day for 21 days, respectively. Etofenamate showed an inhibitory activity on the squeak response caused by flexing and extending the silver nitrate-induced arthritic joint in rats; and it produced a dose related anti-writhing activity at doses of 50--300 mg/kg and 10--80 mg/kg in mice and rats, respectively, in the acetic acid-induced writhing test. Etofenamate showed a significant anti-pyretic activity at doses of 0.2 mg/kg or more. These potencies of etofenamate were 0.5 to 1.6 times those of flufenamic acid. In particular, the anti-erythema, anti-arthritis, and anti-pyretic activities of etofenamate were approximately equivalent to or superior to those of flufenamic acid. From these results, it was suggested that etofenamate given orally, like other non-steroidal anti-inflammatory drugs, showed anti-inflammatory, analgesic, and anti-pyretic activities in experimental animals. PMID:6983482

  13. Prenatal Testing

    MedlinePlus

    ... tests are suggested for all women, such as screenings for gestational diabetes, Down syndrome, and HIV. Other tests might be offered based on your: Age Personal or family health history Ethnic background Results of routine tests Some tests are screening tests. They detect risks for or signs of ...

  14. Thyroid Tests

    MedlinePlus

    ... Organizations (PDF, 269 KB). Alternate Language URL Thyroid Tests Page Content On this page: What is the ... Top ] Why do health care providers perform thyroid tests? Health care providers perform thyroid tests to assess ...

  15. Laboratory Tests

    MedlinePlus

    Laboratory tests check a sample of your blood, urine, or body tissues. A technician or your doctor ... compare your results to results from previous tests. Laboratory tests are often part of a routine checkup ...

  16. Laboratory Tests

    MedlinePlus

    ... Home Medical Devices Products and Medical Procedures In Vitro Diagnostics Lab Tests Laboratory Tests Share Tweet Linkedin ... Approved Home and Lab Tests Find All In Vitro Diagnostic Products and Decision Summaries Since November 2003 ...

  17. IQ testing

    MedlinePlus

    Many IQ tests are used today. Whether they measure actual intelligence or simply certain abilities is controversial. IQ tests measure a specific functioning ability and may not accurately ... any intelligence test may be culturally biased. The more widely ...

  18. Test Madness

    ERIC Educational Resources Information Center

    Hedrick, Wanda B., Ed.

    2007-01-01

    There's accountability and then there's the testing craze an iatrogenic practice that undermines real learning. Hedrick documents the negative effects of testing, giving teachers another weapon in their arsenal against mindless preparation for high-stakes tests.

  19. String test

    MedlinePlus

    Duodenal parasites test; Giardia - string test ... To have this test, you swallow a string with a weighted gelatin capsule on the end. The string is pulled out 4 hours later. Any bile , blood, or mucus attached to ...

  20. Anti-nociceptive effects of Carpolobia lutea G. Don (Polygalaceae) leaf fractions in animal models.

    PubMed

    Nwidu, Lucky Lebgosi; Nwafor, Paul Alozie; da Silva, Viviane Cândida; Rodrigues, Clenilson Martins; dos Santos, Lourdes Campaner; Vilegas, Wagner; Nunes-de-Souza, Ricardo Luiz

    2011-08-01

    Leaves from Carpolobia lutea (Polygalaceae) were screened to establish the antiulcer ethnomedicinal claim and to quantitatively isolate, elucidate the active compounds by semi-preparative HPLC. The anti-nociceptive effects of Carpolobia lutea (CL) G. Don (Polygalaceae) organic leaf extracts were tested in experimental models in mice. The anti-nociceptive mechanism was determined using tail-flick test, acetic acid-induced abdominal constrictions, formalin-induced hind paw licking and the hot plate test. The fractions (ethanol, ethyl acetate, chloroform, n-hexane) and crude ethyl acetate extract of CL (770 mg/kg, i.p.) produced significant inhibitions of both phases of the formalin-induced pain in mice, a reduction in acetic acid-induced writhing as well as and an elevation of the pain threshold in the hot plate test in mice. The inhibitions were greater to those produced by indomethacin (5 mg/kg, i.p.). Ethyl acetate fraction revealed cinnamic and coumaric acids derivatives, which are described for the first time in literature. These cinnamalglucosides polyphenols characterised from CL may in part account for the pharmacological activities. These findings confirm its ethnomedical use in anti-inflammatory pain and in pains from gastric ulcer-associated symptoms. PMID:21347744

  1. Testing Services

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Trace Laboratories is an independent testing laboratory specializing in testing printed circuit boards, automotive products and military hardware. Technical information from NASA Tech Briefs and two subsequent JPL Technical Support packages have assisted Trace in testing surface insulation resistance on printed circuit board materials. Testing time was reduced and customer service was improved because of Jet Propulsion Laboratory technical support packages.

  2. Analysis of chemical constituents and antinociceptive potential of essential oil of Teucrium Stocksianum bioss collected from the North West of Pakistan

    PubMed Central

    2012-01-01

    Background Medicinal plants are used for the treatment of different diseases in almost all cultures. Teucrium species grow wildly at different geographical locations around the world. Teucrium stocksianum is used in folk medicine for the treatment of diarrhea, cough, jaundice and abdominal pain. Scientific study on Teucrium stocksianum shows that it possesses anthelmintic, cytotoxic and antispasmodic activity. The aim of our present study is to identify the chemical composition and antinociceptive potential of the essential oil extracted from Teucrium stocksianum bioss. Method Essential oil (EO) from the aerial parts of Teucrium stocksianum were extracted by hydrodistillation process. The qualitative and quantitative composition of essential oil was determined with Gas chromatography/Mass spectrometer. Antinociceptive activity was determined by acetic acid induced writhing method. Percent inhibition of writhes of the test concentration was determined by comparing it with that of control. Tween-80 emulsion 2.5% (5 ml/kg b.w) was used as a control while Diclofenic sodium 50 mg/kg (b.w) was used as a standard drug. Results The chromatogram of the essential oil of Teucrium stocksianum shows differences both qualitatively and quantatively from essential oil composition reported in other countries. Hydrodistillation of Teucrium stocksianum yielded 0.4% (v/w), pale yellowish oil on dry basis. A total of 26 chemicals were identified by GC-MS accounting for 90.28% of the oil. The major components of essential oil were δ-cadinene (12.92%), α-pinene (10.3%), myrcene (8.64%), β-caryophyllene (8.23%), germacrene D (5.18%) and limonene (2.36%). Essential oil of Teucrium stocksianum has shown outstanding antinociceptive activity. It has been observed that increase in percent writhe inhibition (PWI) occurred from 20-80 mg/kg (b.w) and maximum writhe inhibition has been noted at a concentration of 80 mg/kg (b.w), but PWI decreased at 160 mg/kg, which may be due to some

  3. Workplace Testing: Who's Testing Whom?

    ERIC Educational Resources Information Center

    Greenberg, Eric Rolfe

    1989-01-01

    A survey conducted by the American Management Association on workplace-testing policies included questions about drug testing, polygraphs, and testing for the human immunodeficiency virus. The survey found that testing increased from 21 percent in 1986 to 37 percent in 1987 and 48 percent in the 1988 survey. (JOW)

  4. Net Test

    2001-09-01

    Nettest is a secure, real-time network utility. The nettest framework is designed to incorporate existing and new network tests, and be run as a daemon or an interactive process. Requests for network tests are received via a SSL connection or the user interface and are authorized using a ACL list (in the future authorization using Akenti will also be supported). For tests that require coordination between the two ends of the test, Nettest establishes anmore » SSL connection to accomplish this coordination. A test between two remote computers can be requested via the user interlace if the Nettest daemon is running on both remote machines and the user is authorized. Authorization for the test is through a chain of trust estabtished by the nettest daemons. Nettest is responsible for determining if the test request is authorized, but it does nothing further to secure the test once the test is running. Currently the Nettest framework incorporates lperf-vl.2, a simple ping type test, and a tuned TCP test that uses a given required throughput and ping results to determine the round trip time to set a buffer size (based on the delay bandwidth product) and then performs an iperf TCP throughput test. Additional network test tools can be integrated into the Nettest framework in the future.« less

  5. Pertussis Tests

    MedlinePlus

    ... as: Whooping Cough Tests Formal name: Bordetella pertussis Culture; Bordetella pertussis by PCR; Bordetella pertussis Antibodies (IgA, ... outbreak, at least one case be confirmed using culture. Culture – this test was the "gold standard" for ...

  6. Electrolytes Test

    MedlinePlus

    ... include other tests such as BUN , creatinine , and glucose . Electrolyte measurements may be used to help investigate conditions that cause electrolyte imbalances such as dehydration , kidney disease , lung diseases , or heart conditions . Repeat testing may then ...

  7. Sweat Test

    MedlinePlus

    ... insipidus , and hypothyroidism . Edema can result in a false-negative result. The sweat chloride test should only ... kind of testing. Otherwise, problems in accuracy, including false negatives due to poor collection technique, can arise. ^ ...

  8. Malnutrition Tests

    MedlinePlus

    ... be limited. Home Visit Global Sites Search Help? Malnutrition Share this page: Was this page helpful? Overview | Symptoms | Tests | Treatment | Related Pages Tests Malnutrition will often be noticeable to the doctor's trained ...

  9. Kidney Tests

    MedlinePlus

    ... taking out waste products and making urine. Kidney tests check to see how well your kidneys are working. They include blood, urine, and imaging tests. Early kidney disease usually does not have signs ...

  10. Procalcitonin Test

    MedlinePlus

    ... tests: C-Reactive Protein , Complete Blood Count , Blood Culture , CSF Analysis ... test is relatively new, but its utilization is increasing. Recent studies have shown that it has promise in helping ...

  11. Bilirubin Test

    MedlinePlus

    ... test in conjunction with other laboratory tests ( alkaline phosphatase , aspartate aminotransferase , alanine aminotransferase ) when someone shows signs ... Gilbert syndrome, due to low levels of the enzyme that produces conjugated bilirubin If conjugated (direct) bilirubin ...

  12. Tensilon test

    MedlinePlus

    Myasthenia gravis-tensilon ... Tensilon tests to help tell the difference between myasthenia gravis and other conditions. ... The test helps: Diagnose myasthenia gravis Tell the difference ... conditions Monitor treatment with oral anticholinesterase drugs ...

  13. HPV Test

    MedlinePlus

    ... test for wider range of HPV types. 2009 Mar 13. US Food and Drug Administration. Available online ... approves two DNA tests to detect HPV. 2009 Mar 17. Infectious Disease News. Available online at http:// ...

  14. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1988-01-01

    Describes three flame test demonstrations including "Student-Presented Demonstrations on the Colors of Transition Metal Complexes,""A Flame Test Demonstration Device," and "Vivid Flame Tests." Preparation and procedures are discussed. Included in the first demonstration is an evaluation scheme for grading student demonstrations. (CW)

  15. Schilling test

    MedlinePlus

    Vitamin B12 absorption test ... This test may be done in four different stages to find the cause of a low vitamin B12 level. ... can absorb vitamin B12. Stage II of the test can tell whether a low vitamin B12 level ...

  16. Allergy Testing.

    PubMed

    Tourlas, Konstantinos; Burman, Deepa

    2016-09-01

    Allergic diseases are common in outpatient primary care. Allergy testing can guide management to determine allergy as a cause of symptoms and target therapeutic interventions. This article provides a review of common methods of allergy testing available so that physicians may counsel and refer patients appropriately. Immediate-type hypersensitivity skin tests can be used for airborne allergens, foods, insect stings, and penicillin. Radioallergosorbent testing can be used to evaluate immediate-type hypersensitivity. Delayed-type hypersensitivity or patch-type skin tests are used in patients with suspected contact dermatitis. PMID:27545728

  17. Analytical testing

    NASA Technical Reports Server (NTRS)

    Flannelly, W. G.; Fabunmi, J. A.; Nagy, E. J.

    1981-01-01

    Analytical methods for combining flight acceleration and strain data with shake test mobility data to predict the effects of structural changes on flight vibrations and strains are presented. This integration of structural dynamic analysis with flight performance is referred to as analytical testing. The objective of this methodology is to analytically estimate the results of flight testing contemplated structural changes with minimum flying and change trials. The category of changes to the aircraft includes mass, stiffness, absorbers, isolators, and active suppressors. Examples of applying the analytical testing methodology using flight test and shake test data measured on an AH-1G helicopter are included. The techniques and procedures for vibration testing and modal analysis are also described.

  18. Evaluation of antinociceptive activity of nanoliposome-encapsulated and free-form diclofenac in rats and mice

    PubMed Central

    Goh, Jun Zheng; Tang, Sook Nai; Chiong, Hoe Siong; Yong, Yoke Keong; Zuraini, Ahmad; Hakim, Muhammad Nazrul

    2015-01-01

    Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) that exhibits anti-inflammatory, antinociceptive, and antipyretic activities. Liposomes have been shown to improve the therapeutic efficacy of encapsulated drugs. The present study was conducted to compare the antinociceptive properties between liposome-encapsulated and free-form diclofenac in vivo via different nociceptive assay models. Liposome-encapsulated diclofenac was prepared using the commercialized proliposome method. Antinociceptive effects of liposome-encapsulated and free-form diclofenac were evaluated using formalin test, acetic acid-induced abdominal writhing test, Randall–Selitto paw pressure test, and plantar test. The results of the writhing test showed a significant reduction of abdominal constriction in all treatment groups in a dose-dependent manner. The 20 mg/kg liposome-encapsulated diclofenac demonstrated the highest antinociceptive effect at 78.97% compared with 55.89% in the free-form group at equivalent dosage. Both liposome-encapsulated and free-form diclofenac produced significant results in the late phase of formalin assay at a dose of 20 mg/kg, with antinociception percentages of 78.84% and 60.71%, respectively. Significant results of antinociception were also observed in both hyperalgesia assays. For Randall–Sellito assay, the highest antinociception effect of 71.38% was achieved with 20 mg/kg liposome-encapsulated diclofenac, while the lowest antinociceptive effect of 17.32% was recorded with 0 mg/kg liposome formulation, whereas in the plantar test, the highest antinociceptive effect was achieved at 56.7% with 20 mg/kg liposome-encapsulated diclofenac, and the lowest effect was shown with 0 mg/kg liposome formulation of 8.89%. The present study suggests that liposome-encapsulated diclofenac exhibits higher antinociceptive efficacy in a dose-dependent manner in comparison with free-form diclofenac. PMID:25678786

  19. Evaluation of antinociceptive activity of nanoliposome-encapsulated and free-form diclofenac in rats and mice.

    PubMed

    Goh, Jun Zheng; Tang, Sook Nai; Chiong, Hoe Siong; Yong, Yoke Keong; Zuraini, Ahmad; Hakim, Muhammad Nazrul

    2015-01-01

    Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) that exhibits anti-inflammatory, antinociceptive, and antipyretic activities. Liposomes have been shown to improve the therapeutic efficacy of encapsulated drugs. The present study was conducted to compare the antinociceptive properties between liposome-encapsulated and free-form diclofenac in vivo via different nociceptive assay models. Liposome-encapsulated diclofenac was prepared using the commercialized proliposome method. Antinociceptive effects of liposome-encapsulated and free-form diclofenac were evaluated using formalin test, acetic acid-induced abdominal writhing test, Randall-Selitto paw pressure test, and plantar test. The results of the writhing test showed a significant reduction of abdominal constriction in all treatment groups in a dose-dependent manner. The 20 mg/kg liposome-encapsulated diclofenac demonstrated the highest antinociceptive effect at 78.97% compared with 55.89% in the free-form group at equivalent dosage. Both liposome-encapsulated and free-form diclofenac produced significant results in the late phase of formalin assay at a dose of 20 mg/kg, with antinociception percentages of 78.84% and 60.71%, respectively. Significant results of antinociception were also observed in both hyperalgesia assays. For Randall-Sellito assay, the highest antinociception effect of 71.38% was achieved with 20 mg/kg liposome-encapsulated diclofenac, while the lowest antinociceptive effect of 17.32% was recorded with 0 mg/kg liposome formulation, whereas in the plantar test, the highest antinociceptive effect was achieved at 56.7% with 20 mg/kg liposome-encapsulated diclofenac, and the lowest effect was shown with 0 mg/kg liposome formulation of 8.89%. The present study suggests that liposome-encapsulated diclofenac exhibits higher antinociceptive efficacy in a dose-dependent manner in comparison with free-form diclofenac.

  20. Rubella Test

    MedlinePlus

    Advertisement Proceeds from website advertising help sustain Lab Tests Online. AACC is a not-for-profit organization ... for trustworthy health information. Verify Compliance . Produced by Advertisement

  1. Glucose Tests

    MedlinePlus

    Advertisement Proceeds from website advertising help sustain Lab Tests Online. AACC is a not-for-profit organization ... for trustworthy health information. Verify Compliance . Produced by Advertisement

  2. Cholesterol Test

    MedlinePlus

    Advertisement Proceeds from website advertising help sustain Lab Tests Online. AACC is a not-for-profit organization ... for trustworthy health information. Verify Compliance . Produced by Advertisement

  3. Performance tests.

    PubMed Central

    Wetherell, A

    1996-01-01

    This paper discusses the use of psychological performance tests to assess the effects of environmental stressors. The large number and the variety of performance tests are illustrated, and the differences between performance tests and other psychological tests are described in terms of their design, construction, use, and purpose. The stressor emphasis is on the effects of drugs since that is where most performance tests have found their main application, although other stressors, e.g., fatigue, toxic chemicals, are mentioned where appropriate. Diazepam is used as an example. There is no particular performance emphasis since the tests are intended to have wide applicability. However, vehicle-driving performance is discussed because it has been the subject of a great deal of research and is probably one of the most important areas of application. Performance tests are discussed in terms of the four main underlying models--factor analysis, general information processing, multiple resource and strategy models, and processing-stage models--and in terms of their psychometric properties--sensitivity, reliability, and content, criterion, construct, and face validity. Some test taxonomies are presented. Standardization is also discussed with reference to the reaction time, mathematical processing, memory search, spatial processing, unstable tracking, verbal processing, and dual task tests used in the AGARD STRES battery. Some comments on measurement strengths and appropriate study designs and methods are included. PMID:9182033

  4. Serotonin Test

    MedlinePlus

    Advertisement Proceeds from website advertising help sustain Lab Tests Online. AACC is a not-for-profit organization ... for trustworthy health information. Verify Compliance . Produced by Advertisement

  5. Software testing

    NASA Astrophysics Data System (ADS)

    Price-Whelan, Adrian M.

    2016-01-01

    Now more than ever, scientific results are dependent on sophisticated software and analysis. Why should we trust code written by others? How do you ensure your own code produces sensible results? How do you make sure it continues to do so as you update, modify, and add functionality? Software testing is an integral part of code validation and writing tests should be a requirement for any software project. I will talk about Python-based tools that make managing and running tests much easier and explore some statistics for projects hosted on GitHub that contain tests.

  6. Ammonia Test

    MedlinePlus

    ... be ordered, along with other tests such as glucose , electrolytes , and kidney and liver function tests , to help diagnose the cause of ... Pages tab.) An increased ammonia level and decreased glucose ... may indicate that severe liver or kidney damage has impacted the body's ability ...

  7. Pharmacogenomic Testing

    MedlinePlus

    ... with pharmacogenomic testing. Visit the Food and Drug Administration (FDA) website for a list of drugs with pharmacogenomic information in their labeling. Did You Know? One size does not fit all. In the future, pharmacogenomic tests will be able to help many ...

  8. Erythropoietin test

    MedlinePlus

    ... kidney. These cells release more EPO when blood oxygen level is low. How the Test is Performed A blood sample is needed. How ... your doctor about the meaning of your specific test result. What ... in response to an event such as low blood oxygen level. The condition may occur at high altitudes ...

  9. Strength Testing.

    ERIC Educational Resources Information Center

    Londeree, Ben R.

    1981-01-01

    Postural deviations resulting from strength and flexibility imbalances include swayback, scoliosis, and rounded shoulders. Screening tests are one method for identifying strength problems. Tests for the evaluation of postural problems are described, and exercises are presented for the strengthening of muscles. (JN)

  10. Genetic Testing

    MedlinePlus

    ... genetic tests for several reasons. These include Finding genetic diseases in unborn babies Finding out if people carry a gene for a disease and might pass it on to their children Screening embryos for disease Testing for genetic diseases in adults before they cause ...

  11. Antinociceptive and anti-inflammatory activity of the siaresinolic acid, a triterpene isolated from the leaves of Sabicea grisea Cham. & Schltdl. var. grisea.

    PubMed

    de Oliveira, Anderson Marques; de Araújo, Almair Ferreira; Lyra Lemos, Rosangela P; Conserva, Lucia M; de Souza Ferro, Jamylle Nunes; Barreto, Emiliano

    2015-04-01

    In the present study, siaresinolic acid (siaresinol, SA) was isolated from the leaves of Sabicea grisea and studied to evaluate its antinociceptive and anti-inflammatory activity. The antinociceptive effect of SA was investigated in mice using different animal models to study pain. In the acetic acid-induced writhing test, intraperitoneal (i.p.) injection of SA (0.1, 1, and 10 mg/kg, i.p.) 1 h before a pain stimulus significantly reduced the nociceptive response (by 42.3, 68.2, and 70.9 %, respectively). Pretreatment with glibenclamide, but not with yohimbine, metoclopramide, ketanserin, or naloxone, restored the antinociceptive effect induced by SA in the writhing test, suggesting that the K(+)ATP channel pathway might be involved in its mechanism of action. In the formalin test, SA (1 mg/kg, i.p.) decreased licking time in the second phase only, thereby indicating an anti-inflammatory effect. In the hot plate test, there was no significant difference in nociceptive behavior. In the rota-rod test, it was verified that a high dose of SA (10 mg/kg, i.p.) did not affect the locomotor activity of mice. In the pleurisy model, induced by carrageenan, treatment with SA inhibited important events involved in inflammatory responses, namely leukocyte influx, plasma leakage, and increased inflammatory mediators (TNF-α, IL-1β, and chemokine CXCL1), in the pleural exudate. Additionally, SA itself was not cytotoxic when evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in macrophages cultured for 24 h at concentrations ranging from 1 to 200 μg/mL. These results suggest, for the first time, that SA attenuates nociceptive behavior through mechanisms involving receptors for ATP-dependent potassium channels, in addition to suppressing acute inflammatory responses.

  12. Optical testing

    NASA Technical Reports Server (NTRS)

    Wyant, James; Hochberg, Eric; Breault, Robert; Greivenkamp, John; Hunt, Gary; Mason, Pete; Mcguire, James; Meinel, Aden; Morris, Mike; Scherr, Larry

    1992-01-01

    Optical testing is one of the most vital elements in the process of preparing an optical instrument for launch. Without well understood, well controlled, and well documented test procedures, current and future mission goals will be jeopardized. We should keep in mind that the reason we test is to provide an opportunity to catch errors, oversights, and problems on the ground, where solutions are possible and difficulties can be rectified. Consequently, it is necessary to create tractable test procedures that truly provide a measure of the performance of all optical elements and systems under conditions which are close to those expected in space. Where testing is not feasible, accurate experiments are required in order to perfect models that can exactly predict the optical performance. As we stretch the boundaries of technology to perform more complex space and planetary investigations, we must expand the technology required to test the optical components and systems which we send into space. As we expand the observational wavelength ranges, so must we expand our range of optical sources and detectors. As we increase resolution and sensitivity, our understanding of optical surfaces to accommodate more stringent figure and scatter requirements must expand. Only with research and development in these areas can we hope to achieve success in the ever increasing demands made on optical testing by the highly sophisticated missions anticipated over the next two decades. Technology assessment and development plan for surface figure, surface roughness, alignment, image quality, radiometric quantities, and stray light measurement are presented.

  13. Point-of-care platelet function tests: detection of platelet inhibition induced by nonopioid analgesic drugs.

    PubMed

    Scharbert, Gisela; Gebhardt, Kristina; Sow, Zacharia; Duris, Monika; Deusch, Engelbert; Kozek-Langenecker, Sibylle

    2007-12-01

    Detection of platelet inhibition is of clinical relevance in the preinterventional risk-benefit assessment in chronic low-back-pain patients scheduled for invasive pain therapy. We evaluated the sensitivity of various point-of-care platelet function tests for the detection of platelet inhibition induced by nonopioid analgesic drugs. After Institutional Review Board approval and informed consent, citrated whole blood from 40 patients with chronic unspecific low back pain was investigated before and 30 min after intravenous infusion of the study medication consisting of diclofenac 75 mg (plus orphenadrin 30 mg; Neodolpasse; Fresenius Kabi Austria GmbH, Austria), parecoxib 40 mg (Dynastat; Pharmacia Europe EEIG, UK), paracetamol 1 g (Perfalgan; Bieffe Medital S.P.A., Italy), or normal saline in a randomized, cross-over, double-blinded, placebo-controlled study. Platelet function was assessed using the PFA-100 platelet function analyzer and thromboelastometry, as well as impedance aggregometry (in the last 17 patients recruited after it became commercially available). Sensitivity for detecting diclofenac-induced platelet inhibition was 85% for the PFA-100 using epinephrine as agonist and 94% for arachidonic acid-induced impedance aggregometry. ADP-induced platelet function tests, as well as cytochalasin D-modified thromboelastometry were unreliable. All tests had a low incidence of false-positive test results after normal saline. Paracetamol and parecoxib had no significant platelet inhibiting effect. The PFA-100 using epinephrine as agonist and arachidonic acid-induced impedance aggregometry are recommended for the detection of cyclooxygenase-I-inhibiting effects of nonsteroidal anti-inflammatory drugs such as diclofenac. Our findings confirm that a single rescue dose of paracetamol and parecoxib has no antiplatelet effect. PMID:17982319

  14. Patch tests*

    PubMed Central

    Lazzarini, Rosana; Duarte, Ida; Ferreira, Alessandra Lindmayer

    2013-01-01

    Patch tests were introduced as a diagnostic tool in the late nineteenth century. Since then, they have improved considerably becoming what they are today. Patch tests are used in the diagnostic investigation of contact dermatitis worldwide. Batteries or series previously studied and standardized should be used in patch testing. The methodology is simple, but it requires adequate training for the results to be correctly interpreted and used. Despite having been used for over a century, it needs improvement like all other diagnostic techniques in the medical field. PMID:24474094

  15. Phytopharmacological evaluation of ethanol extract of Sida cordifolia L. roots

    PubMed Central

    Momin, Mohammad Abdul Motalib; Bellah, Sm Faysal; Rahman, Sarder Mohammad Raussel; Rahman, Ahmed Ayedur; Murshid, Gazi Mohammad Monjur; Emran, Talha Bin

    2014-01-01

    Objective To investigate the phytochemical screening (group determination) and selected pharmacological activities (antioxidant, antimicrobial and analgesic activity) of the plant Sida cordifolia Linn (S. cordifolia). Methods Eighty percent concentrated ethanol extract of the roots was used. To identify the chemical constituents of plant extract standard procedures were followed. In phytochemical screening the crude extract was tested for the presence of different chemical groups like reducing sugar, tannins, saponins, steroids, flavonoids, gums, alkaloids and glycosides. The antioxidant property of ethanolic extract of S. cordifolia was assessed by DPPH free radical scavenging activity. Analgesic activity of the extract was tested using the model of acetic acid induced writhing in mice. Diclofenac sodium is used as reference standard drug for the analgesic activity test. Antibacterial activity of plant extract was carried out using disc diffusion method with five pathogenic bacteria comparison with kanamycin as a standard. Results Phytochemical analysis of the ethanolic extract of the roots of S. cordifolia indicated the presence of reducing sugar, alkaloids, steroids and saponins. In DPPH scavenging assay the IC50 value was found to be 50 µg/mL which was not comparable to the standard ascorbic acid. The crude extract produced 44.30% inhibition of writhing at the dose of 500 mg/kg body weight which is statistically significant (P>0.001). The in vitro antimicrobial activity of the ethanol extract of the roots of S. cordifolia showed no antimicrobial activity against five types of microorganisms. The experiment was conducted only with five species of bacteria as test species, which do not at all indicate the total inactivity against micro-organisms. Conclusions The obtained results provide a support for the use of this plant in traditional medicine but further pharmacological studies are required. PMID:24144125

  16. AMA Test

    MedlinePlus

    ... Smooth muscle antibodies (SMA) Antinuclear antibodies (ANA) Alkaline phosphatase (ALP) IgM level Bilirubin Albumin Prothrombin time (PT) ... a liver panel (elevated liver enzymes), especially alkaline phosphatase (ALP) . An AMA or AMA-M2 test may ...

  17. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L.

    1990-01-01

    Included are three demonstrations that include the phase change of ice when under pressure, viscoelasticity and colloid systems, and flame tests for metal ions. The materials, procedures, probable results, and applications to real life situations are included. (KR)

  18. Genetic Testing

    MedlinePlus

    ... diagnose celiac disease, but have been on the gluten-free diet for a significant period of time, ... antibody test, measure the autoimmune response triggered by gluten that occurs at a point in time. (Think ...

  19. Troponins Test

    MedlinePlus

    ... significantly elevated troponin levels and, in particular, a rise in the results from a series of tests ... do not affect cardiac troponin levels. Troponin may rise following strenuous exercise, although in the absence of ...

  20. Cortisol Test

    MedlinePlus

    ... is produced and secreted by the adrenal glands . Production of the hormone is regulated by the hypothalamus ... help determine its cause: Testing for Excess Cortisol Production If a person has a high blood cortisol ...

  1. Pregnancy Tests

    MedlinePlus

    ... the hCG. hCG is made when a fertilized egg implants in the uterus. This usually happens about ... conception (when the man's sperm fertilizes the woman's egg). 1 Some home pregnancy tests are more sensitive ...

  2. Lead Test

    MedlinePlus

    ... to determine lead sources, educating family members about lead poisoning , and instituting follow-up testing to monitor the ... high levels of lead, see the article on Lead Poisoning . The Occupational Safety and Health Administration (OSHA) has ...

  3. Test report :

    SciTech Connect

    Rose, David Martin; Schenkman, Benjamin L.; Borneo, Daniel R.

    2013-10-01

    The Department of Energy Office of Electricity (DOE/OE), Sandia National Laboratories (SNL) and the Base Camp Integration Lab (BCIL) partnered together to incorporate an energy storage system into a microgrid configured Forward Operating Base to reduce the fossil fuel consumption and to ultimately save lives. Energy storage vendors will be sending their systems to SNL Energy Storage Test Pad (ESTP) for functional testing and then to the BCIL for performance evaluation. The technologies that will be tested are electro-chemical energy storage systems comprising of lead acid, lithium-ion or zinc-bromide. Raytheon/KTech has developed an energy storage system that utilizes zinc-bromide flow batteries to save fuel on a military microgrid. This report contains the testing results and some limited analysis of performance of the Raytheon/KTech Zinc-Bromide Energy Storage System.

  4. Test report :

    SciTech Connect

    Rose, David Martin; Schenkman, Benjamin L.; Borneo, Daniel R.

    2013-08-01

    The Department of Energy Office of Electricity (DOE/OE), Sandia National Laboratory (SNL) and the Base Camp Integration Lab (BCIL) partnered together to incorporate an energy storage system into a microgrid configured Forward Operating Base to reduce the fossil fuel consumption and to ultimately save lives. Energy storage vendors will be sending their systems to SNL Energy Storage Test Pad (ESTP) for functional testing and then to the BCIL for performance evaluation. The technologies that will be tested are electro-chemical energy storage systems comprised of lead acid, lithium-ion or zinc-bromide. Princeton Power Systems has developed an energy storage system that utilizes lithium ion phosphate batteries to save fuel on a military microgrid. This report contains the testing results and some limited analysis of performance of the Princeton Power Systems Prototype Energy Storage System.

  5. Test report :

    SciTech Connect

    Rose, David Martin; Schenkman, Benjamin L.; Borneo, Daniel R.

    2013-08-01

    The Department of Energy Office of Electricity (DOE/OE), Sandia National Laboratory (SNL) and the Base Camp Integration Lab (BCIL) partnered together to incorporate an energy storage system into a microgrid configured Forward Operating Base to reduce the fossil fuel consumption and to ultimately save lives. Energy storage vendors have supplied their systems to SNL Energy Storage Test Pad (ESTP) for functional testing and a subset of these systems were selected for performance evaluation at the BCIL. The technologies tested were electro-chemical energy storage systems comprised of lead acid, lithium-ion or zinc-bromide. MILSPRAY Military Technologies has developed an energy storage system that utilizes lead acid batteries to save fuel on a military microgrid. This report contains the testing results and some limited assessment of the Milspray Scorpion Energy Storage Device.

  6. Test Report :

    SciTech Connect

    Rose, David Martin; Schenkman, Benjamin L.; Borneo, Daniel R.

    2013-10-01

    The Department of Energy Office of Electricity (DOE/OE), Sandia National Laboratories (SNL) and the Base Camp Integration Lab (BCIL) partnered together to incorporate an energy storage system into a microgrid configured Forward Operating Base to reduce the fossil fuel consumption and to ultimately save lives. Energy storage vendors will be sending their systems to SNL Energy Storage Test Pad (ESTP) for functional testing and then to the BCIL for performance evaluation. The technologies that will be tested are electro-chemical energy storage systems comprising of lead acid, lithium-ion or zinc-bromide. GS Battery and EPC Power have developed an energy storage system that utilizes zinc-bromide flow batteries to save fuel on a military microgrid. This report contains the testing results and some limited analysis of performance of the GS Battery, EPC Power HES RESCU.

  7. Neuropathy Tests

    MedlinePlus

    ... be limited. Home Visit Global Sites Search Help? Neuropathy Share this page: Was this page helpful? Overview | ... of testing are: To diagnose the presence of neuropathy and distinguish it from other conditions that may ...

  8. Lipase test

    MedlinePlus

    ... the bowel (bowel obstruction) Celiac disease Duodenal ulcer Cancer of the pancreas Infection or swelling of the pancreas This test may also be done for familial lipoprotein lipase deficiency . Risks ... Update Date 2/4/2015 Updated ...

  9. VMA Test

    MedlinePlus

    ... is primarily used to detect and rule out neuroblastomas in children with an abdominal mass or other ... homovanillic acid (HVA) test to help diagnose a neuroblastoma, to monitor the effectiveness of treatment, and to ...

  10. Iron Test

    MedlinePlus

    ... detect and help diagnose iron deficiency or iron overload. In people with anemia , these tests can help ... also be ordered when iron deficiency or iron overload is suspected. Early iron deficiency often goes unnoticed. ...

  11. Test Anxiety

    MedlinePlus

    ... for Parents for Kids for Teens Teens Home Body Mind Sexual Health Food & Fitness Diseases & Conditions Infections Q& ... Like other anxiety reactions, test anxiety affects the body and the mind. When you're under stress, your body releases ...

  12. VDRL test

    MedlinePlus

    ... conditions may cause a false-positive test, including: HIV Lyme disease Certain types of pneumonia Malaria Systemic lupus erythematosus The body does not always produce antibodies specifically in response to the syphilis bacteria, so ...

  13. RPR test

    MedlinePlus

    ... infections and is routinely used to screen pregnant women for the disease. Several states also require that couples be screened for syphilis before getting a marriage license. The test is also used to see ...

  14. Prealbumin Test

    MedlinePlus

    ... used to help detect and diagnose protein-calorie malnutrition as well as to monitor people receiving total ... be used to assess nutritional status or diagnose malnutrition. However, others believe that the test can be ...

  15. Calcium Test

    MedlinePlus

    ... as thyroid disease , parathyroid disorder , malabsorption , cancer, or malnutrition An ionized calcium test may be ordered when ... albumin , which can result from liver disease or malnutrition , both of which may result from alcoholism or ...

  16. Genomic Testing

    MedlinePlus

    ... Working Group Independent Web site Informing the effective integration of genomics into health practice—Lynch syndrome ACCE Model for Evaluating Genetic Tests Recommendations by the EGAPP Working Group Top of ... ...

  17. Phosphorus Test

    MedlinePlus

    ... be limited. Home Visit Global Sites Search Help? Phosphorus Share this page: Was this page helpful? Also ... else I should know? How is it used? Phosphorus tests are most often ordered along with other ...

  18. Triglycerides Test

    MedlinePlus

    ... be limited. Home Visit Global Sites Search Help? Triglycerides Share this page: Was this page helpful? Also known as: TG; TRIG Formal name: Triglycerides Related tests: Cholesterol ; HDL Cholesterol ; LDL Cholesterol ; Direct ...

  19. ACT Test

    MedlinePlus

    ... this page helpful? Also known as: ACT; Activated Coagulation Time Formal name: Activated Clotting Time Related tests: ... in the blood called platelets and proteins called coagulation factors are activated in a sequence of steps ...

  20. Fibrinogen Test

    MedlinePlus

    ... Related tests: PT and INR , PTT , D-dimer , Coagulation Factors , Thrombin Time , hs-CRP At a Glance ... and D-dimer to help diagnose disseminated intravascular coagulation (DIC) or abnormal fibrinolysis Occasionally to help monitor ...

  1. Sodium Test

    MedlinePlus

    ... be limited. Home Visit Global Sites Search Help? Sodium Share this page: Was this page helpful? Also known as: Na Formal name: Sodium Related tests: Chloride , Bicarbonate , Potassium , Electrolytes , Osmolality , Basic ...

  2. Toxoplasmosis Testing

    MedlinePlus

    ... Toxoplasma gondii Molecular Detection by PCR Related tests: TORCH ; CSF Analysis ; Amniotic Fluid Analysis At a Glance ... may sometimes be performed as part of a TORCH panel . TORCH is an acronym for several infections ...

  3. Testosterone Test

    MedlinePlus

    ... of other conditions, such as polycystic ovarian syndrome (PCOS) . ^ Back to top What does the test result ... are normally low. Increased testosterone levels can indicate: PCOS Ovarian or adrenal gland tumor Congenital adrenal hyperplasia ^ ...

  4. Insulin Test

    MedlinePlus

    ... people with type 2 diabetes , polycystic ovarian syndrome (PCOS) , prediabetes or heart disease , or metabolic syndrome . A ... resistance), especially in obese individuals and those with PCOS . This test involves an IV-infusion of insulin, ...

  5. Testing Composites

    NASA Technical Reports Server (NTRS)

    1981-01-01

    A device for testing composites for strength characteristics has been developed by Acoustic Emission Technology Corporation. Called the Model 206AU, the system is lightweight and portable. It is comprised of three sections. The "pulser" section injects ultrasonic waves into the material under test. A receiver picks up the simulated stress waves as they pass through the material and relays the signals to the acoustic emission section, where they are electronically analyzed.

  6. Synthesis, Anti-Inflammatory and Anti- Nociceptive Activities and Cytotoxic Effect of Novel Thiazolidin-4-ones Derivatives as Selective Cyclooxygenase (COX-2) Inhibitors

    PubMed Central

    Moallem, Seyed Adel; Imenshahidi, Mohsen; Shahini, Narges; Javan, Ahmad Reza; Karimi, Mohsen; Alibolandi, Mona; Ghandadi, Morteza; Etemad, Leila; Motamedshariaty, Vahidehsadat; Hosseini, Toktam; Hadizadeh, Farzin

    2013-01-01

    Objective(s): Nowadays, COX-2 inhibitors such as valdecoxib are removed from the market because of their cardiovascular toxicity and their potential to increase the risk of strokes. In response to this, medicinal chemists have attempted to synthesize new classes of COX-2 Inhibitors. Materials and Methods: In this study, three novel analogues of thiazolidin-4-ones derivatives 2a-c were synthesized. The ability of these compounds to inhibit ovine COX-1 and COX-2 (0.2- 0.8 µM) was determined using a colorimetric method. The cytotoxic effect of the synthesized compounds (25-100 M) was also investigated by measuring their cytotoxicity against Caco-2 and MCF-7 cell lines using MTT assay. Cell apoptosis was determined by flow cytometry. Writhing test (7.5-75 mg/kg) was used to examine the antinociceptive effects in mice. The effect of the analogues against acute inflammation (7.5-75 mg/kg) was also studied using xylene-induced ear edema test in mice. Results: The synthesized compounds showed a weak capacity to inhibit the proliferation of Caco-2 and MCF-7 cell lines. The COX-2 inhibition potency and selectivity index for test compounds 2a–b were as follows; celecoxib > 2b > 2a. On the other hand, all three analogues exhibited strong antinociceptive activity against acetic acid-induced writhing. The anti-inflammatory and antinociceptive effects of the analogues were markedly more than positive control, celecoxib. Conclusion: This study demonstrates that the antinociceptive and anti-inflammatory activity profiles exhibited by the novel synthesized compounds are independent from their COX-2 inhibitory potencies. The found antinociceptive and anti-inflammatory effects can be caused by interaction with other target; independent from COX-2. Accordingly, the compounds 2a-c could serve as lead compounds to develop novel anti-inflammation and antinociceptive drugs. PMID:24570829

  7. Antinociceptive activity of NK1 receptor antagonists: non-specific effects of racemic RP67580.

    PubMed Central

    Rupniak, N. M.; Boyce, S.; Williams, A. R.; Cook, G.; Longmore, J.; Seabrook, G. R.; Caeser, M.; Iversen, S. D.; Hill, R. G.

    1993-01-01

    1. Release of substance P in the dorsal horn is considered a primary event in the perception of pain. The profile of racemic RP67580, a non-peptide antagonist at the NK1 (substance P) receptor, was examined in a range of antinociception tests on rodents. 2. At doses up to 30 mg kg-1, s.c. racemic RP67580 exhibited antinociceptive activity in writhing and formalin paw tests in mice and gerbils. Acetic acid induced writhing and the licking response to formalin were reduced to 40-50% of the level observed in vehicle-treated animals (P < 0.05). However, this agent was not active in mouse tail flick, rat paw pressure or rat and guinea-pig formalin paw tests. 3. Like racemic RP67580, the calcium channel blockers nifedipine (30 mg kg-1, i.p.) and verapamil (10 or 20 mg kg-1, s.c.) inhibited the response to formalin by approximately 60% in gerbils (P < 0.05 compared with vehicle-treated animals). 4. Evidence for calcium channel antagonist activity of RP67580 was obtained in vitro. Racemic RP67580 inhibited calcium entry into depolarized strips of guinea-pig ileum longitudinal muscle myenteric plexus (apparent KB = 587 +/- 115 nM), inhibited [3H]-diltiazem binding to rabbit skeletal membranes (IC50 = 298 nM) and depressed high threshold calcium currents in neurones cultured from rat cortex (10% inhibition at 10 microM). 5. These findings indicate that the acute antinociceptive effects of RP67580 may not be attributable to a specific interaction with NK1 receptors and may be mediated via calcium channel blockade. PMID:8306108

  8. Testing technology

    SciTech Connect

    Not Available

    1993-10-01

    This bulletin from Sandia National Laboratories presents current research highlights in testing technology. Ion microscopy offers new nondestructive testing technique that detects high resolution invisible defects. An inexpensive thin-film gauge checks detonators on centrifuge. Laser trackers ride the range and track helicopters at low-level flights that could not be detected by radar. Radiation transport software predicts electron/photon effects via cascade simulation. Acoustic research in noise abatement will lead to quieter travelling for Bay Area Rapid Transport (BART) commuters.

  9. Rotational testing.

    PubMed

    Furman, J M

    2016-01-01

    The natural stimulus for the semicircular canals is rotation of the head, which also might stimulate the otolith organs. Vestibular stimulation usually induces eye movements via the vestibulo-ocular reflex (VOR). The orientation of the subject with respect to the axis of rotation and the orientation of the axis of rotation with respect to gravity together determine which labyrinthine receptors are stimulated for particular motion trajectories. Rotational testing usually includes the measurement of eye movements via a video system but might use a subject's perception of motion. The most common types of rotational testing are whole-body computer-controlled sinusoidal or trapezoidal stimuli during earth-vertical axis rotation (EVAR), which stimulates primarily the horizontal semicircular canals bilaterally. Recently, manual impulsive rotations, known as head impulse testing (HIT), have been developed to assess individual horizontal semicircular canals. Most types of rotational stimuli are not used routinely in the clinical setting but may be used in selected research environments. This chapter will discuss clinically relevant rotational stimuli and several types of rotational testing that are used primarily in research settings. PMID:27638070

  10. Amylase Test

    MedlinePlus

    ... tests are sometimes used to monitor treatment of cancers involving the pancreas and after the removal of gallstones that have ... in people with pancreatic duct obstruction and pancreatic cancers . In ... cells in the pancreas. Decreased levels can also be due to kidney ...

  11. Microgrid Testing

    SciTech Connect

    Shirazi, M.; Kroposki, B.

    2012-01-01

    With the publication of IEEE 1574.4 Guide for Design, Operation, and Integration of Distributed Resource Island Systems with Electric Power Systems, there is an increasing amount of attention on not only the design and operations of microgrids, but also on the proper operation and testing of these systems. This standard provides alternative approaches and good practices for the design, operation, and integration of microgrids. This includes the ability to separate from and reconnect to part of the utility grid while providing power to the islanded power system. This presentation addresses the industry need to develop standardized testing and evaluation procedures for microgrids in order to assure quality operation in the grid connected and islanded modes of operation.

  12. Earthquake Testing

    NASA Technical Reports Server (NTRS)

    1979-01-01

    During NASA's Apollo program, it was necessary to subject the mammoth Saturn V launch vehicle to extremely forceful vibrations to assure the moonbooster's structural integrity in flight. Marshall Space Flight Center assigned vibration testing to a contractor, the Scientific Services and Systems Group of Wyle Laboratories, Norco, California. Wyle-3S, as the group is known, built a large facility at Huntsville, Alabama, and equipped it with an enormously forceful shock and vibration system to simulate the liftoff stresses the Saturn V would encounter. Saturn V is no longer in service, but Wyle-3S has found spinoff utility for its vibration facility. It is now being used to simulate earthquake effects on various kinds of equipment, principally equipment intended for use in nuclear power generation. Government regulations require that such equipment demonstrate its ability to survive earthquake conditions. In upper left photo, Wyle3S is preparing to conduct an earthquake test on a 25ton diesel generator built by Atlas Polar Company, Ltd., Toronto, Canada, for emergency use in a Canadian nuclear power plant. Being readied for test in the lower left photo is a large circuit breaker to be used by Duke Power Company, Charlotte, North Carolina. Electro-hydraulic and electro-dynamic shakers in and around the pit simulate earthquake forces.

  13. Antinociceptive and neuropharmacological activities of methanol extract of Phoenix sylvestris fruit pulp

    PubMed Central

    Shajib, Md. Shafiullah; Akter, Saleha; Ahmed, Tajnin; Imam, Mohammad Zafar

    2015-01-01

    Fruits of Phoenix sylvestris Roxb. (Arecaceae) are used to treat back pain, toothache, headache, arthritis, nervous debility and as sedative. The aim of this study was to evaluate the antinociceptive and neuropharmacological activities of methanol extract of P. sylvestris fruit pulp (MEPS). The antinociceptive activity of MEPS was evaluated by heat-induced (hot plate, tail immersion test) and chemical-induced pain models (acetic acid-induced writhing, formalin-induced nociception, glutamate-induced nociception and paw edema test). The effect of MEPS on central nervous system (CNS) was studied using hole cross test, open field test, sodium thiopental-induced sleeping time and elevated plus maze test. MEPS showed strong, significant and dose-dependent antinociceptive activity in all heat-induced and chemical-induced pain models at all experimental doses. Involvement of opioid receptor mediated analgesia was evident from the reversal of analgesic effect by naloxone. MEPS also showed reduced locomotor activity in both hole cross and open field tests. The increase in sleeping time in sodium thiopental-induced sleeping test and anxiolytic activity in elevated plus maze test were also significant. So, it is evident that MEPS possesses strong central and peripheral antinociceptive activity as well as CNS depressant, sedative and anxiolytic activity. The results justify the ethnomedicinal use of P. sylvestris fruit in different painful conditions and CNS disorders. PMID:26483687

  14. Dietary supplementation with ethyl ester concentrates of fish oil (n-3) and borage oil (n-6) polyunsaturated fatty acids induces epidermal generation of local putative anti-inflammatory metabolites.

    PubMed

    Miller, C C; Tang, W; Ziboh, V A; Fletcher, M P

    1991-01-01

    Clinical reports have attributed the amelioration of chronic inflammatory skin disorders to the presence of certain polyunsaturated fatty acids (PUFA) in dietary oils. To test the hypothesis of a local modulatory effect of these PUFA in the epidermis, the basal diet of normal guinea pigs was supplemented with ethyl esters of either fish oil [rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] or borage oil [rich in gamma-linolenic acid (GLA)]. Our data demonstrated that dietary oils influence the distribution of PUFA in epidermal phospholipids and the epidermal levels of PUFA-derived hydroxy fatty acids. Specifically, animals supplemented with ethyl esters of fish oil markedly incorporated EPA and DHA into epidermal phospholipids, which paralleled the epidermal accumulation of 15-hydroxyeicosapentaenoic acid (15-HEPE) and 17-hydroxydocosahexaenoic acid (17-HDoHE). Similarly, animals supplemented with esters of borage oil preferentially incorporated dihomogammalinolenic acid (DGLA), the epidermal elongase product of GLA, into the epidermal phospholipids, which also was accompanied by epidermal accumulation of 15-hydroxyeicosatrienoic acid (15-HETrE). By factoring the epidermal levels of the 15-lipoxygenase products and their relative inhibitory potencies, we evolved a measure of the overall potential of dietary oils to exert local anti-inflammatory effect. For example, the leukotriene inhibition potentials (LIP) of both fish oil and borage oil were greatly enhanced when compared to controls. Thus, the altered profiles of epidermal 15-lipoxygenase products generated from particular dietary oils may be responsible, at least in part, for reported ameliorative effects of oils on chronic inflammatory skin disorders.

  15. Airlock Testing

    NASA Technical Reports Server (NTRS)

    1966-01-01

    National Aeronautics and Space Adminstration's Langley Research Center scientists use this plexiglass space station airlock test model to determine astronauts' ability to move in and out through an airlock with the restraint of a pressurized suit. Operations in space that call for crew transfer between spacecraft require airlocks of some kind. Mobility and performance in airlock systems must be determined to establish geometry and associated hardware for equipment suitable for manned space vehicle use. The airlock prevents artificial atmosphere loss when an astronaut transfers from one spacecraft to another or from the interior to the exterior in the performance of duties.

  16. Performance Testing

    NASA Technical Reports Server (NTRS)

    1991-01-01

    Systems Technology, Inc., Hawthorne, CA, developed an electronic Critical Tracking Task (CTT) system that analyzes and rates a subject's visual/motor responses for Ames Research Center. Originally applied to measuring the effects of long term confinement in the mid 1960's, the CTT system is now marketed as FACTOR 1000 by Performance Factors, Inc. Alameda, CA, under a licensing agreement with Systems Technology. The system is a non-invasive, self-administered test that takes less than a minute and detects impairment from a broad range of causes, including stress, fatigue, illness, drugs, or alcohol. It is used daily by Old Town Trolley Tours, San Diego, CA, to assess each driver's physical coordination skills prior to the start of each shift. FACTOR 1000 reduces liabilities and costs related to accidents, and costs less than one dollar per day per employee. Performance Factors is now BioFactors, Inc.

  17. Nerolidol exhibits antinociceptive and anti-inflammatory activity: involvement of the GABAergic system and proinflammatory cytokines.

    PubMed

    Fonsêca, Diogo V; Salgado, Paula R R; de Carvalho, Fabíola L; Salvadori, Mirian Graciela S S; Penha, Antônia Rosângela S; Leite, Fagner C; Borges, Clóvis José S; Piuvezam, Marcia R; Pordeus, Liana Clébia de Morais; Sousa, Damião P; Almeida, Reinaldo N

    2016-02-01

    Nerolidol, an acyclic sesquiterpene found as a major constituent of several essential oils, has several pharmacological activities, but its action in pain processes has never been studied. The purpose of our research was to evaluate the antinociceptive and anti-inflammatory activities of nerolidol, as well as possible mechanisms of action, in experimental mouse models of pain. Antinociceptive activity was evaluated using the acetic acid-induced writhing test, the formalin test, and the hot-plate test. The nerolidol-treated group showed lesser acetic acid-induced abdominal contractions than the control group in all of the three doses tested (200, 300, and 400 mg/kg, p.o.). The formalin test doses of 300 and 400 mg/kg p.o. inhibited licking time, in both the first phase and the second phase. In the hot-plate test, nerolidol did not alter latency at any of the observed time points. Motor coordination, evaluated through the rotarod test, was not hindered in animals treated with nerolidol. Regarding the mechanism of action, the antinociceptive activity of nerolidol is related to the GABAergic system, and not to the opioidergic or ATP-sensitive K(+) channels. Treatment with nerolidol reduced carrageenan-induced paw edema. In the model of carrageenan-induced peritonitis, nerolidol decreased the influx of polymorphonuclear cells and also reduced levels of tumor necrosis factor (TNF-α) in peritoneal lavage. Nerolidol reduced production of interleukin 1 beta (IL-1β) in LPS-stimulated, peritoneal macrophages. Thus, these results showed that nerolidol has antinociceptive activity with possible involvement of the GABAergic system, and anti-inflammatory activity, attributed to the suppression of TNF-α and IL-1β proinflammatory cytokines.

  18. Evaluation of antinociceptive and antidiarrhoeal properties of Manilkara zapota leaves in Swiss albino mice.

    PubMed

    Ganguly, Amlan; Al Mahmud, Zobaer; Kumar Saha, Sajal; Abdur Rahman, S M

    2016-08-01

    Context Manilkara zapota (L.). P. Royen. (Sapotaceae) has been used in folk medicine to treat pain, diarrhoea, inflammation, arthralgia, and other disorders. Objective Screening of Manilkara zapota leaves ethanol extract and its different solvent soluble fractions for possible antinociceptive and antidiarrhoeal activities in Swiss albino mice. Materials and methods The extract and various fractions (200 and 400 mg/kg body weight; p.o.) were tested for peripheral and central antinociceptive activity by acetic acid-induced writhing and radiant heat tail-flick method, respectively; castor oil-induced diarrhoeal model was used to evaluate antidiarrhoeal activity at both doses. All the samples were administered once in a day and the duration of study was approximately 5 h. Results Ethanol extract (400 mg/kg), petroleum ether fraction (400 mg/kg), and ethyl acetate fraction (400 mg/kg) showed significant peripheral antinociceptive activity having 59.89, 58.24, and 46.7% (p < 0.001) of writhing inhibition, respectively, which is comparable with that of standard diclofenac (59.34% inhibition). The ethanol extract (400 mg/kg) and petroleum ether fraction (400 mg/kg) also showed promising central analgesic activity having 74.15 and 82.15% (p < 0.001) elongation of reaction time, respectively, at 90 min after administration of sample which is also similar to that obtained by morphine (85.84% elongation). In antidiarrhoeal activity screening, ethanol extract (200 and 400 mg/kg) showed significant inhibition of defecation by 53.57 and 60.71%, respectively (p < 0.001) compared with that of loperamide (71.42%). Discussion and conclusion The findings of the studies demonstrated antinociceptive and antidiarrhoeal activities of M. zapota leaves which could be the therapeutic option against pain and diarrhoeal disease. PMID:26799747

  19. Bioactivity studies on Musa seminifera Lour

    PubMed Central

    Saha, Sanjib; Shilpi, Jamil A.; Mondal, Himangsu; Gofur, Royhan; Billah, Morsaline; Nahar, Lutfun; Sarker, Satyajit D.

    2013-01-01

    Background: Musa seminifera Lour is a tree-like perennial herb that has been used in folk medicine in Bangladesh to heal a number of ailments. Objective: To evaluate the antioxidant, analgesic, antidiarrheal, anthelmintic activities, and general toxicity of the ethanol extract of the roots. Materials and Methods: The extract was assessed for free-radical-scavenging activity by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, total phenolic content (TPC) by the Folin Ciocalteu reagent, antioxidant activity by the ferric reducing power assay, analgesic activity by the acetic acid-induced writhing and hot-plate tests, antidiarrheal activity by the castor oil-induced diarrhea model in mice, anthelmintic activity on Paramphistomum cervi and Haemonchus contortus, and general toxicity by the brine shrimp lethality assay. Results: The extract showed free-radical-scavenging activity with an IC50 value of 44.86 μg/mL. TPC was 537.89 mg gallic acid equivalent/100 g of dried plant material. It showed concentration-dependent reducing power, and displayed 42.11 and 69.32% writhing inhibition at doses of 250 and 500 mg/kg body weight, respectively. The extract also significantly raised the pain threshold at the above-mentioned dose levels. In vivo antidiarrheal property was substantiated by significant prolongation of latent period and decrease in total number of stools compared with the control. The LC50 against brine shrimp nauplii was 36.21 μg/mL. The extract exhibited dose-dependent decrease in paralysis and death time of the helminths. Conclusion: The above results demonstrated that the plant possesses notable bioactivities and somewhat supports its use in folk medicine. PMID:24124283

  20. Comparison of analgesic and anti-inflammatory activity of meloxicam gel with diclofenac and piroxicam gels in animal models: pharmacokinetic parameters after topical application.

    PubMed

    Gupta, S K; Bansal, P; Bhardwaj, R K; Jaiswal, J; Velpandian, T

    2002-01-01

    Meloxicam, a non-steroidal anti-inflammatory drug, is a preferential inhibitor of cyclooxygenase-2 and has demonstrated potent analgesic and anti-inflammatory activity after oral administration. The present work was carried out to elucidate the anti-inflammatory and analgesic activity of a newer topical gel formulation of meloxicam (1% w/w gel) and compare it with 0.5% w/w piroxicam and 1% w/w diclofenac gels in experimental animal models. The study was also extended to determine the pharmacokinetic profile of a newer formulation of meloxicam gel after topical application on depilated skin of rats. The anti-inflammatory activities of meloxicam, piroxicam and diclofenac gels were compared using carrageenan-induced acute paw oedema and complete Freund's adjuvant-induced chronic paw oedema in rats. Meloxicam gel showed increased protection against inflammation as compared to piroxicam and diclofenac gels. Acetic acid-induced writhing and formalin-induced phase I and phase II pain models were used to compare their analgesic activity. Meloxicam gel showed significant protection in formalin-induced phase II pain whereas its analgesic activity was less as compared to diclofenac and piroxicam gels in writhing test and formalin-induced phase I pain. The pharmacokinetic studies showed peak plasma drug concentration (C(max)) of 48.48 +/- 6.57 microg/ml at 2 h (T(max)) after topical application of 500 mg of meloxicam gel formulation. The area under the curve as calculated from 0 to 6 h was found to be 114.18 +/- 4.23 and 194.13 +/- 3.78 microg x h/ml for 0 to infinity. The results indicate that topical preparation of meloxicam could be an effective alternative to diclofenac and piroxicam gels in inflammatory conditions and its associated pain with the possibility of less systemic side-effects.

  1. PPD skin test

    MedlinePlus

    Chernecky CC, Berger BJ. Mantoux skin test (PPD test, purified protein derivative test, Tb test, tuberculin skin test, TST, tuberculosis test) - diagnostic. In: Chernecky CC, Berger BJ, eds. Laboratory Tests and Diagnostic Procedures . ...

  2. APU diaphragm testing. Test plan

    NASA Technical Reports Server (NTRS)

    Shelley, Richard

    1992-01-01

    Auxiliary Power Unit (APU) fuel (hydrazine) tanks have had to be removed from the Columbia Shuttle (OV-102) because they have been in service for 11 years, which is the limit of their useful life. As part of an effort to determine whether the useful life of the fuel tanks can be extended, examination of the ethylene propylene rubber (EPR) diaphragm and the metal from one of the APU tanks is required. The JSC Propulsion and Power Division has requested White Sands Test Facility (WSTF) to examine the EPR diaphragm thoroughly and the metal casing generally from one tank. The objective is to examine the EPR diaphragm for signs of degradation that may limit the life of its function in the APU propellant tank. The metal casing will also be examined for signs of surface corrosion.

  3. Antinociceptive activity of atranorin in mice orofacial nociception tests.

    PubMed

    Siqueira, Rosana S; Bonjardim, Leonardo R; Araújo, Adriano A S; Araújo, Bruno E S; Melo, Marcélia G D; Oliveira, Marília G B; Gelain, Daniel P; Silva, Francilene A; DeSantana, Josimari M; Albuquerque-Júnior, Ricardo L C; Rocha, Ricardo F; Moreira, José C F; Antoniolli, Angelo R; Quintans-Júnior, Lucindo J

    2010-01-01

    Physicochemical characterization and antinociceptive and anti-inflammatory activities of atranorin (AT) extracted from Cladina kalbii Ahti in formalin- and capsaicin-induced orofacial pain and anti-inflammatory tests in rodents were studied. Physicochemical characterization showed that AT has the general formula C19H18O8. Male Swiss mice were pretreated with AT (100, 200, and 400 mg/kg, i.p.), morphine (3 mg/kg, i.p.), or vehicle (0.9% saline with two drops of 0.2% Tween 80) before formalin (20 microl, 2%) or capsaicin (20 microl, 2.5 microg) were injected into the right vibrissa. Our results showed that i.p. treatment with AT displayed marked inhibitory effects in different orofacial pain tests in mice. AT (400 mg/kg, i.p.) was effective in reducing the nociceptive face-rubbing behavioural response in both phases of the formalin test, which was also naloxone-sensitive. Additionally, AT produced a significant antinociceptive effect at all doses in the capsaicin test. Such results were unlikely to be provoked by motor abnormality, since AT-treated mice exhibited no performance alteration on the rota rod apparatus. AT exhibited significant anti-inflammatory activity in the acute model of inflammation (leukocyte migration to the peritoneal cavity), carrageenan- and arachidonic acid-induced hind paw edema in rats. Additionally, AT exhibited a dose-dependent antioxidant activity in vitro, as assessed by total radical-trapping antioxidant parameter and total antioxidant reactivity assays. All these findings suggest that AT might represent an important tool for the management of orofacial pain and/or inflammatory disorders. PMID:21138055

  4. Formic-acid-induced depolymerization of oxidized lignin to aromatics.

    PubMed

    Rahimi, Alireza; Ulbrich, Arne; Coon, Joshua J; Stahl, Shannon S

    2014-11-13

    Lignin is a heterogeneous aromatic biopolymer that accounts for nearly 30% of the organic carbon on Earth and is one of the few renewable sources of aromatic chemicals. As the most recalcitrant of the three components of lignocellulosic biomass (cellulose, hemicellulose and lignin), lignin has been treated as a waste product in the pulp and paper industry, where it is burned to supply energy and recover pulping chemicals in the operation of paper mills. Extraction of higher value from lignin is increasingly recognized as being crucial to the economic viability of integrated biorefineries. Depolymerization is an important starting point for many lignin valorization strategies, because it could generate valuable aromatic chemicals and/or provide a source of low-molecular-mass feedstocks suitable for downstream processing. Commercial precedents show that certain types of lignin (lignosulphonates) may be converted into vanillin and other marketable products, but new technologies are needed to enhance the lignin value chain. The complex, irregular structure of lignin complicates chemical conversion efforts, and known depolymerization methods typically afford ill-defined products in low yields (that is, less than 10-20wt%). Here we describe a method for the depolymerization of oxidized lignin under mild conditions in aqueous formic acid that results in more than 60wt% yield of low-molecular-mass aromatics. We present the discovery of this facile C-O cleavage method, its application to aspen lignin depolymerization, and mechanistic insights into the reaction. The broader implications of these results for lignin conversion and biomass refining are also considered.

  5. Pyroglutamic acid-induced metabolic acidosis: a case report.

    PubMed

    Luyasu, S; Wamelink, M M C; Galanti, L; Dive, A

    2014-06-01

    High anion gap metabolic acidosis due to pyroglutamic acid (5-oxoproline) is a rare complication of acetaminophen treatment (which depletes glutathione stores) and is often associated with clinically moderate to severe encephalopathy. Acquired 5-oxoprolinase deficiency (penicillins) or the presence of other risk factors of glutathione depletion such as malnutrition or sepsis seems to be necessary for symptoms development. We report the case of a 55-year-old women who developed a symptomatic overproduction of 5-oxoproline during flucloxacillin treatment for severe sepsis while receiving acetaminophen for fever control. Hemodialysis accelerated the clearance of the accumulated organic acid, and was followed by a sustained clinical improvement.

  6. ERK, synaptic plasticity and acid-induced muscle pain

    PubMed Central

    Yang, Hsiu-Wen; Yen, Chen-Tung; Chen, Chien-Chang; Chen, Chih-Cheng; Cheng, Sin-Jhong

    2011-01-01

    Chronic pain is characterized by post-injury pain hypersensitivity. Current evidence suggests that it might result from altered neuronal excitability and/or synaptic functions in pain-related pathways and brain areas, an effect known as central sensitization. Increased activity of extracellular signal-regulated kinase (ERK) has been well-demonstrated in the dorsal horn of the spinal cord in chronic pain animal models. Recently, increased ERK activity has also been identified in two supraspinal areas, the central amygdala and the paraventricular thalamic nucleus anterior. Our recent work on the capsular central amygdala has shown that this increased ERK activity can enhance synaptic transmission, which might account for central sensitization and behavior hypersensitivity in animals receiving noxious stimuli. PMID:21966555

  7. Benzoic Acid-Inducible Gene Expression in Mycobacteria

    PubMed Central

    Dragset, Marte S.; Barczak, Amy K.; Kannan, Nisha; Mærk, Mali; Flo, Trude H.; Valla, Svein; Rubin, Eric J.; Steigedal, Magnus

    2015-01-01

    Conditional expression is a powerful tool to investigate the role of bacterial genes. Here, we adapt the Pseudomonas putida-derived positively regulated XylS/Pm expression system to control inducible gene expression in Mycobacterium smegmatis and Mycobacterium tuberculosis, the causative agent of human tuberculosis. By making simple changes to a Gram-negative broad-host-range XylS/Pm-regulated gene expression vector, we prove that it is possible to adapt this well-studied expression system to non-Gram-negative species. With the benzoic acid-derived inducer m-toluate, we achieve a robust, time- and dose-dependent reversible induction of Pm-mediated expression in mycobacteria, with low background expression levels. XylS/Pm is thus an important addition to existing mycobacterial expression tools, especially when low basal expression is of particular importance. PMID:26348349

  8. Valproic Acid Induces Antimicrobial Compound Production in Doratomyces microspores.

    PubMed

    Zutz, Christoph; Bacher, Markus; Parich, Alexandra; Kluger, Bernhard; Gacek-Matthews, Agnieszka; Schuhmacher, Rainer; Wagner, Martin; Rychli, Kathrin; Strauss, Joseph

    2016-01-01

    One of the biggest challenges in public health is the rising number of antibiotic resistant pathogens and the lack of novel antibiotics. In recent years there is a rising focus on fungi as sources of antimicrobial compounds due to their ability to produce a large variety of bioactive compounds and the observation that virtually every fungus may still contain yet unknown so called "cryptic," often silenced, compounds. These putative metabolites could include novel bioactive compounds. Considerable effort is spent on methods to induce production of these "cryptic" metabolites. One approach is the use of small molecule effectors, potentially influencing chromatin landscape in fungi. We observed that the supernatant of the fungus Doratomyces (D.) microsporus treated with valproic acid (VPA) displayed antimicrobial activity against Staphylococcus (S.) aureus and two methicillin resistant clinical S. aureus isolates. VPA treatment resulted in enhanced production of seven antimicrobial compounds: cyclo-(L-proline-L-methionine) (cPM), p-hydroxybenzaldehyde, cyclo-(phenylalanine-proline) (cFP), indole-3-carboxylic acid, phenylacetic acid (PAA) and indole-3-acetic acid. The production of the antimicrobial compound phenyllactic acid was exclusively detectable after VPA treatment. Furthermore three compounds, cPM, cFP, and PAA, were able to boost the antimicrobial activity of other antimicrobial compounds. cPM, for the first time isolated from fungi, and to a lesser extent PAA, are even able to decrease the minimal inhibitory concentration of ampicillin in MRSA strains. In conclusion we could show in this study that VPA treatment is a potent tool for induction of "cryptic" antimicrobial compound production in fungi, and that the induced compounds are not exclusively linked to the secondary metabolism. Furthermore this is the first discovery of the rare diketopiperazine cPM in fungi. Additionally we could demonstrate that cPM and PAA boost antibiotic activity against antibiotic resistant strains, suggesting a possible application in combinatorial antibiotic treatment against resistant pathogens.

  9. Acetylsalicylic acid induces programmed cell death in Arabidopsis cell cultures.

    PubMed

    García-Heredia, José M; Hervás, Manuel; De la Rosa, Miguel A; Navarro, José A

    2008-06-01

    Acetylsalicylic acid (ASA), a derivative from the plant hormone salicylic acid (SA), is a commonly used drug that has a dual role in animal organisms as an anti-inflammatory and anticancer agent. It acts as an inhibitor of cyclooxygenases (COXs), which catalyze prostaglandins production. It is known that ASA serves as an apoptotic agent on cancer cells through the inhibition of the COX-2 enzyme. Here, we provide evidences that ASA also behaves as an agent inducing programmed cell death (PCD) in cell cultures of the model plant Arabidopsis thaliana, in a similar way than the well-established PCD-inducing agent H(2)O(2), although the induction of PCD by ASA requires much lower inducer concentrations. Moreover, ASA is herein shown to be a more efficient PCD-inducing agent than salicylic acid. ASA treatment of Arabidopsis cells induces typical PCD-linked morphological and biochemical changes, namely cell shrinkage, nuclear DNA degradation, loss of mitochondrial membrane potential, cytochrome c release from mitochondria and induction of caspase-like activity. However, the ASA effect can be partially reverted by jasmonic acid. Taking together, these results reveal the existence of common features in ASA-induced animal apoptosis and plant PCD, and also suggest that there are similarities between the pathways of synthesis and function of prostanoid-like lipid mediators in animal and plant organisms.

  10. Lysophosphatidic acid induces necrosis and apoptosis in hippocampal neurons.

    PubMed

    Holtsberg, F W; Steiner, M R; Keller, J N; Mark, R J; Mattson, M P; Steiner, S M

    1998-01-01

    A diverse body of evidence indicates a role for the lipid biomediator lysophosphatidic acid (LPA) in the CNS. This study identifies and characterizes the induction of neuronal death by LPA. Treatment of cultured hippocampal neurons from embryonic rat brains with 50 microM LPA resulted in neuronal necrosis, as determined morphologically and by the release of lactate dehydrogenase. A concentration of LPA as low as 10 microM led to the release of lactate dehydrogenase. In contrast, treatment of neurons with 0.1 or 1.0 microM LPA resulted in apoptosis, as determined by chromatin condensation. In addition, neuronal death induced by 1 microM LPA was characterized as apoptotic on the basis of terminal dUTP nick end-labeling (TUNEL) staining, externalization of phosphatidylserine, and protection against chromatin condensation, TUNEL staining, and phosphatidylserine externalization by treatment with N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone, a broad-spectrum inhibitor of caspases, i.e., members of the interleukin-1beta converting enzyme family. Studies with antagonists of ionotropic glutamate receptors did not indicate a significant role for these receptors in apoptosis induced by 1 microM LPA. LPA (1 microM) also induced a decrease in mitochondrial membrane potential. Moreover, pretreatment of neurons with cyclosporin A protected against the LPA-induced decrease in mitochondrial membrane potential and neuronal apoptosis. Thus, LPA, at pathophysiological levels, can induce neuronal apoptosis and could thereby participate in neurodegenerative disorders. PMID:9422348

  11. Acid-induced secretory cell metaplasia in hamster bronchi

    SciTech Connect

    Christensen, T.G.; Lucey, E.C.; Breuer, R.; Snider, G.L.

    1988-02-01

    Hamsters were exposed to an intratracheal instillation of 0.5 ml of 0.08 N nitric, hydrochloric, or sulfuric acid to determine their airway epithelial response. Three weeks after exposure, the left intrapulmonary bronchi in Alcian blue/PAS-strained paraffin sections were evaluated for the amount of secretory product in the airway epithelium as a measure of secretory cell metaplasia (SCM). Compared to saline-treated control animals, all three acids caused statistically significant SCM. In addition to the bronchial lesion, all three acids caused similar interstitial fibrosis, bronchiolectasis, and bronchiolization of alveoli that varied in individual animals from mild to severe. In a separate experiment to study the persistence of the SCM, hamsters treated with a single instillation of 0.1 N nitric acid showed significant SCM 3, 7, and 17 weeks after exposure. There was a high correlation (r = 0.96) between a subjective assessment of SCM and objective assessment using a digital image-analysis system. We conclude that protons induce SCM independently of the associated anion; the SCM persists at least 17 weeks. Sulfuric acid is an atmospheric pollutant and nitric acid may form locally on the mucosa of lungs exposed to nitrogen dioxide. These acids may contribute to the development of maintenance of the SCM seen in the conducting airways of humans with chronic obstructive pulmonary disease.

  12. Excessive dietary linoleic acid induces proinflammatory markers in rats.

    PubMed

    Marchix, Justine; Choque, Benjamin; Kouba, Maryline; Fautrel, Alain; Catheline, Daniel; Legrand, Philippe

    2015-12-01

    Following the historical dietary recommendations, the substitution of polyunsaturated fatty acids (PUFAs) for saturated fatty acids (SFAs) resulted in a dramatic increase of linoleic acid (LA) in the Western diet. While proatherogenic properties of SFAs have been described, the involvement of LA on the inflammatory process remains controversial. Herein, we evaluated the effects of an excessive LA intake on the cytokine-induced expression of endothelial adhesion molecules vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1), through the nuclear factor (NF)-κB pathway, in comparison with a control diet and regarding a "positive" SFA diet. Wistar rats were fed experimental diets - a control diet or diets enriched with LA or SFA - for 11 weeks. Plasma lipid parameters and proinflammatory cytokine production such as interleukin-1β and tumor necrosis factor (TNF)-α were analyzed. Expression of endothelial adhesion molecules and NF-κB was determined by immunohistochemical analysis. No difference was observed in body weight. The enriched diets did not affect triglyceride and total cholesterol levels in plasma. Our results demonstrated that excessive dietary LA intake increased TNF-α levels (P<.05) in plasma. Rats fed the LA-enriched diet showed a significantly higher expression of VCAM-1, ICAM-1 and NF-κB in aortas. In addition, our results demonstrated that an excess of LA is more efficient to activate endothelial molecular process than an excess of SFA. The present study provides further support for the proinflammatory properties of LA and suggests an LA-derivatives pathway involved in the inflammatory process.

  13. Glycyrrhetinic acid-induced permeability transition in rat liver mitochondria.

    PubMed

    Salvi, Mauro; Fiore, Cristina; Armanini, Decio; Toninello, Antonio

    2003-12-15

    Glycyrrhetinic acid, a hydrolysis product of one of the main constituents of licorice, the triterpene glycoside of glycyrrhizic acid, when added to rat liver mitochondria at micromolar concentrations induces swelling, loss of membrane potential, pyridine nucleotide oxidation, and release of cytochrome c and apoptosis inducing factor. These changes are Ca(2+) dependent and are prevented by cyclosporin A, bongkrekic acid, and N-ethylmaleimide. All these observations indicate that glycyrrhetinic acid is a potent inducer of mitochondrial permeability transition and can trigger the pro-apoptotic pathway. PMID:14637195

  14. Perflurooctanoic Acid Induces Developmental Cardiotoxicity in Chicken Embryos and Hatchlings

    EPA Science Inventory

    Perfluorooctanoic acid (PFOA) is a widespread environmental contaminant that is detectable in serum of the general U.S. population. PFOA is a known developmental toxicant that induces mortality in mammalian embryos and is thought to induce toxicity via interaction with the peroxi...

  15. Bile-acid-induced cell injury and protection

    PubMed Central

    Perez, Maria J; Briz, Oscar

    2009-01-01

    Several studies have characterized the cellular and molecular mechanisms of hepatocyte injury caused by the retention of hydrophobic bile acids (BAs) in cholestatic diseases. BAs may disrupt cell membranes through their detergent action on lipid components and can promote the generation of reactive oxygen species that, in turn, oxidatively modify lipids, proteins, and nucleic acids, and eventually cause hepatocyte necrosis and apoptosis. Several pathways are involved in triggering hepatocyte apoptosis. Toxic BAs can activate hepatocyte death receptors directly and induce oxidative damage, thereby causing mitochondrial dysfunction, and induce endoplasmic reticulum stress. When these compounds are taken up and accumulate inside biliary cells, they can also cause apoptosis. Regarding extrahepatic tissues, the accumulation of BAs in the systemic circulation may contribute to endothelial injury in the kidney and lungs. In gastrointestinal cells, BAs may behave as cancer promoters through an indirect mechanism involving oxidative stress and DNA damage, as well as acting as selection agents for apoptosis-resistant cells. The accumulation of BAs may have also deleterious effects on placental and fetal cells. However, other BAs, such as ursodeoxycholic acid, have been shown to modulate BA-induced injury in hepatocytes. The major beneficial effects of treatment with ursodeoxycholic acid are protection against cytotoxicity due to more toxic BAs; the stimulation of hepatobiliary secretion; antioxidant activity, due in part to an enhancement in glutathione levels; and the inhibition of liver cell apoptosis. Other natural BAs or their derivatives, such as cholyl-N-methylglycine or cholylsarcosine, have also aroused pharmacological interest owing to their protective properties. PMID:19360911

  16. [Elucidation of mechanisms underlying docosahexaenoic acid-induced antinociception].

    PubMed

    Nishinaka, Takashi; Matsumoto, Kengo; Nakamoto, Kazuo; Anbo, Akihiro; Mankura, Mitsumasa; Koyama, Yutaka; Tokuyama, Shogo

    2013-01-01

    Docosahexaenoic acid (DHA), a predominant of n-3 polyunsaturated fatty acids (n-3 PUFA), has numerous beneficial physiological effects, including neuroprotection and cardiovascular protection. Recently, a possible involvement of n-3 PUFA in pain control has gathered considerable attention because numerous studies have reported a regulatory role of n-3 PUFAs. However, the mechanisms underlying how DHA exerts antinociceptive effect remain unknown. Here, we performed elucidation of mechanisms underlying DHA-induced antinociception. DHA administration dose-dependently exerted an antinociceptive effect. This effect was abolished by pretreated with the β-funaltrexamine (β-FNA), a μ-opioid receptor antagonist, and the nartrindole (NTI), a δ-opioid receptor antagonist, but not by the nor-binaltorphimine (nor-BNI), a κ-opioid receptor antagonist. In the radioligand binding assay, DHA itself did not have the affinity for μ-, δ- and κ- opioid receptor. Furthermore, the pretreatment of anti β-endorphin antiserum inhibited DHA-induced antinociception. The plasma levels of β-endorphin increased 30 min after DHA administration. The β-endorphin immunoreactivity in the brain increased at 30 min after DHA treatment. Expression of GPR40 protein was widely observed in the brain as well as the spinal cord. The intracerebroventricular but not intrathecal injection of DHA and GW9508, a GPR40/GPR120 agonist, significantly reduced formalin-induced pain behavior. The β-endorphin immunoreactivity in the brain increased at 10 and 20 min after intracerebroventricular injection of DHA and GW9508. These findings suggest that DHA-induced antinociception via β-endorphin release may be mediated through GPR40 signaling in the supraspinal area. PMID:23649389

  17. Formic-acid-induced depolymerization of oxidized lignin to aromatics

    NASA Astrophysics Data System (ADS)

    Rahimi, Alireza; Ulbrich, Arne; Coon, Joshua J.; Stahl, Shannon S.

    2014-11-01

    Lignin is a heterogeneous aromatic biopolymer that accounts for nearly 30% of the organic carbon on Earth and is one of the few renewable sources of aromatic chemicals. As the most recalcitrant of the three components of lignocellulosic biomass (cellulose, hemicellulose and lignin), lignin has been treated as a waste product in the pulp and paper industry, where it is burned to supply energy and recover pulping chemicals in the operation of paper mills. Extraction of higher value from lignin is increasingly recognized as being crucial to the economic viability of integrated biorefineries. Depolymerization is an important starting point for many lignin valorization strategies, because it could generate valuable aromatic chemicals and/or provide a source of low-molecular-mass feedstocks suitable for downstream processing. Commercial precedents show that certain types of lignin (lignosulphonates) may be converted into vanillin and other marketable products, but new technologies are needed to enhance the lignin value chain. The complex, irregular structure of lignin complicates chemical conversion efforts, and known depolymerization methods typically afford ill-defined products in low yields (that is, less than 10-20wt%). Here we describe a method for the depolymerization of oxidized lignin under mild conditions in aqueous formic acid that results in more than 60wt% yield of low-molecular-mass aromatics. We present the discovery of this facile C-O cleavage method, its application to aspen lignin depolymerization, and mechanistic insights into the reaction. The broader implications of these results for lignin conversion and biomass refining are also considered.

  18. Valproic Acid Induces Antimicrobial Compound Production in Doratomyces microspores

    PubMed Central

    Zutz, Christoph; Bacher, Markus; Parich, Alexandra; Kluger, Bernhard; Gacek-Matthews, Agnieszka; Schuhmacher, Rainer; Wagner, Martin; Rychli, Kathrin; Strauss, Joseph

    2016-01-01

    One of the biggest challenges in public health is the rising number of antibiotic resistant pathogens and the lack of novel antibiotics. In recent years there is a rising focus on fungi as sources of antimicrobial compounds due to their ability to produce a large variety of bioactive compounds and the observation that virtually every fungus may still contain yet unknown so called “cryptic,” often silenced, compounds. These putative metabolites could include novel bioactive compounds. Considerable effort is spent on methods to induce production of these “cryptic” metabolites. One approach is the use of small molecule effectors, potentially influencing chromatin landscape in fungi. We observed that the supernatant of the fungus Doratomyces (D.) microsporus treated with valproic acid (VPA) displayed antimicrobial activity against Staphylococcus (S.) aureus and two methicillin resistant clinical S. aureus isolates. VPA treatment resulted in enhanced production of seven antimicrobial compounds: cyclo-(L-proline-L-methionine) (cPM), p-hydroxybenzaldehyde, cyclo-(phenylalanine-proline) (cFP), indole-3-carboxylic acid, phenylacetic acid (PAA) and indole-3-acetic acid. The production of the antimicrobial compound phenyllactic acid was exclusively detectable after VPA treatment. Furthermore three compounds, cPM, cFP, and PAA, were able to boost the antimicrobial activity of other antimicrobial compounds. cPM, for the first time isolated from fungi, and to a lesser extent PAA, are even able to decrease the minimal inhibitory concentration of ampicillin in MRSA strains. In conclusion we could show in this study that VPA treatment is a potent tool for induction of “cryptic” antimicrobial compound production in fungi, and that the induced compounds are not exclusively linked to the secondary metabolism. Furthermore this is the first discovery of the rare diketopiperazine cPM in fungi. Additionally we could demonstrate that cPM and PAA boost antibiotic activity against antibiotic resistant strains, suggesting a possible application in combinatorial antibiotic treatment against resistant pathogens. PMID:27148199

  19. Retinoic acid-induced neural differentiation of embryonal carcinoma cells.

    PubMed Central

    Jones-Villeneuve, E M; Rudnicki, M A; Harris, J F; McBurney, M W

    1983-01-01

    We have previously shown that the P19 line of embryonal carcinoma cells develops into neurons, astroglia, and fibroblasts after aggregation and exposure to retinoic acid. The neurons were initially identified by their morphology and by the presence of neurofilaments within their cytoplasm. We have more fully documented the neuronal nature of these cells by showing that their cell surfaces display tetanus toxin receptors, a neuronal cell marker, and that choline acetyl-transferase and acetyl cholinesterase activities appear coordinately in neuron-containing cultures. Several days before the appearance of neurons, there is a marked decrease in the amount of an embryonal carcinoma surface antigen, and at the same time there is a substantial decrease in the volumes of individual cells. Various retinoids were able to induce the development of neurons in cultures of aggregated P19 cells, but it did not appear that polyamine metabolism was involved in the effect. We have isolated a mutant clone which does not differentiate in the presence of any of the drugs which are normally effective in inducing differentiation of P19 cells. This mutant and others may help to elucidate the chain of events triggered by retinoic acid and other differentiation-inducing drugs. Images PMID:6656766

  20. Epigenetic modifications in valproic acid-induced teratogenesis

    SciTech Connect

    Tung, Emily W.Y.; Winn, Louise M.

    2010-11-01

    Exposure to the anticonvulsant drug valproic acid (VPA) in utero is associated with a 1-2% increase in neural tube defects (NTDs), however the molecular mechanisms by which VPA induces teratogenesis are unknown. Previous studies demonstrated that VPA, a direct inhibitor of histone deacetylase, can induce histone hyperacetylation and other epigenetic changes such as histone methylation and DNA demethylation. The objective of this study was to determine if maternal exposure to VPA in mice has the ability to cause these epigenetic alterations in the embryo and thus contribute to its mechanism of teratogenesis. Pregnant CD-1 mice (GD 9.0) were administered a teratogenic dose of VPA (400 mg/kg, s.c.) and embryos extracted 1, 3, 6, and 24 h after injection. To assess embryonic histone acetylation and histone methylation, Western blotting was performed on whole embryo homogenates, as well as immunohistochemical staining on embryonic sections. To measure DNA methylation changes, the cytosine extension assay was performed. Results demonstrated that a significant increase in histone acetylation that peaked 3 h after VPA exposure was accompanied by an increase in histone methylation at histone H3 lysine 4 (H3K4) and a decrease in histone methylation at histone H3 lysine 9 (H3K9). Immunohistochemical staining revealed increased histone acetylation in the neuroepithelium, heart, and somites. A decrease in methylated histone H3K9 staining was observed in the neuroepithelium and somites, METHYLATED histone H3K4 staining was observed in the neuroepithelium. No significant differences in global or CpG island DNA methylation were observed in embryo homogenates. These results support the possibility that epigenetic modifications caused by VPA during early mouse organogenesis results in congenital malformations.