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Sample records for kainic acid colchicine

  1. Subtype selective kainic acid receptor agonists

    DEFF Research Database (Denmark)

    Bunch, Lennart; Krogsgaard-Larsen, Povl

    2009-01-01

    (S)-Glutamic acid (Glu) is the major excitatory neurotransmitter in the mammalian central nervous system, activating the plethora of glutamate receptors (GluRs). In broad lines, the GluRs are divided into two major classes: the ionotropic Glu receptors (iGluRs) and the metabotropic Glu receptors (m......GluRs). Within the iGluRs, five subtypes (KA1, KA2, iGluR5-7) show high affinity and express full agonist activity upon binding of the naturally occurring amino acid kainic acid (KA). Thus these receptors have been named the KA receptors. This review describes all-to our knowledge-published KA receptor agonists...

  2. Colchicine

    Science.gov (United States)

    ... your doctor right away if you experience a gout attack during your treatment. Your doctor may tell you to take an extra dose of colchicine, followed by a smaller dose one hour later. If you take extra doses of colchicine to treat a gout attack, you should not take your next scheduled ...

  3. EFFECTS OF KAINIC ACID ON GLUTATIONE AND NITRITE IN RAT HIPPOCAMPUS

    OpenAIRE

    2011-01-01

    Epileptiformic activity could result in apoptotic neuronal death, in which oxidative stress could play an important role. In case of decreased antioxidant brain status cellular death could be facilitated. Kainic acid is often used in a model of epilepsy in rats. Up to now there is not enough data evaluating levels of glutathione and nitric oxide in kainic acid-induced epilepsy acutely and several days after the kainic acid exposure. This information will be useful for assessing long term pro...

  4. EFFECTS OF KAINIC ACID ON GLUTATIONE AND NITRITE IN RAT HIPPOCAMPUS

    Directory of Open Access Journals (Sweden)

    Nadka I. Boyadjieva

    2011-09-01

    Full Text Available Epileptiformic activity could result in apoptotic neuronal death, in which oxidative stress could play an important role. In case of decreased antioxidant brain status cellular death could be facilitated. Kainic acid is often used in a model of epilepsy in rats. Up to now there is not enough data evaluating levels of glutathione and nitric oxide in kainic acid-induced epilepsy acutely and several days after the kainic acid exposure. This information will be useful for assessing long term prognosis on a risk of further brain damage.We studied hippocampal levels of glutathione and nitric oxide at the 3th hour (acute group and after 7 days of kainic (chronic group acid exposure. We found that glutathione level is statistically significantly lower in the hippocampus 7 days after kainic acid exposure, as compared with values measured in the acute group. For both kainic acid treated groups glutathione levels were significantly lower than controls.Levels of nitric oxide were found to be significantly higher 7 days after kainic acid exposure as compared with acute group. For both kainic acid treated groups nitric oxyde levels were significantly lower than controls.We conclude that in kainic acid treated rats oxidative stress could be present even after a single treatment. This could be a potentially pathogenic factor for further brain damages.

  5. Chronic exercise dampens hippocampal glutamate overflow induced by kainic acid in rats.

    Science.gov (United States)

    Holmes, Philip V; Reiss, Jenny I; Murray, Patrick S; Dishman, Rod K; Spradley, Jessica M

    2015-05-01

    Our laboratory has previously reported that chronic, voluntary exercise diminishes seizure-related behaviors induced by convulsant doses of kainic acid. The present experiments tested the hypothesis that exercise exerts this protective effect through a mechanism involving suppression of glutamate release in the hippocampal formation. Following three weeks of voluntary wheel running or sedentary conditions, rats were injected with 10 mg/kg of kainic acid, and hippocampal glutamate was measured in real time using a telemetric, in vivo voltammetry system. A separate experiment measured electroencephalographic (EEG) activity following kainic acid treatment. Results of the voltammetry experiment revealed that the rise in hippocampal glutamate induced by kainic acid is attenuated in exercising rats compared to sedentary controls, indicating that the exercise-induced protection against seizures involves regulation of hippocampal glutamate release. The findings reveal the potential benefit of regular exercise in the treatment and prevention of seizure disorders and suggest a possible neurobiological mechanism underlying this effect.

  6. Increased susceptibility to hippocampal and amygdala kindling following intrahippocampal kainic acid.

    Science.gov (United States)

    Feldblum, S; Ackermann, R F

    1987-08-01

    The effects of unilateral intrahippocampal injection of kainic acid, a potent neuroexcitant and neurotoxin, on subsequent susceptibility to kindling of the contralateral hippocampus or contralateral amygdala were investigated in albino rats. At the chosen doses (0.20 to 1.25 micrograms dissolved in physiologic saline), the kainic acid-induced lesion was confined to the injected hippocampus and in two cases the ipsilateral entorhinal cortex; never were there contralateral lesions. Approximately 2 to 6 weeks post-injection, each animal received daily afterdischarge-producing electrical stimulations until stage 5 kindled limbic seizures occurred. Kindling in pretreated animals was significantly accelerated compared with controls; the hippocampal kindling rate decreased from 13.2 stimulations to 3.7, the amygdala kindling rate from 7.8 stimulations to 3.0. Many treated animals had first-stimulation stage 5 seizures, compared with none for controls. Importantly, this facilitation of kindling was not reversed by suppression of the acute, induced seizures with the anticonvulsants, diazepam and phenobarbital, which have repeatedly been demonstrated to effectively suppress limbic kindling. Such results, considered together with findings from the literature, suggest that partial kindling does not occur during kainic acid-induced seizures, and that the observed susceptibility to kindling and other epileptogenic agents subsequent to kainic acid treatment may in fact be related to neurophysiologic and neurochemical consequences of kainic acid-induced lesions.

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

    Science.gov (United States)

    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.

  8. Phylogenetic distribution of [3H]kainic acid receptor binding sites in neuronal tissue.

    Science.gov (United States)

    London, E D; Klemm, N; Coyle, J T

    1980-06-23

    The phylogenetic distribution of specific binding sites for kainic acid was determined in 14 species including invertebrates and vertebrates. The highest level of binding was observed in brains of the frog (Xenopus laevis), followed by the spiny dogfish (Heterodontus francisci), the goldfish (Carasius auratus) and the chick (Gallus domesticus). Although significant specific binding was noted in some of the lowest forms tested (e.g. Hydra littoralis), this was not a consistent observation in the invertebrates. In most cases, specific binding to both high and low affinity sites was detected; notable exceptions were the cockroach brain (Periplaneta americana), which had negligible high affinity binding, and the crayfish brain (Procambarus) which had negligible low affinity binding. In the spiny dogfish, the smooth dogfish and the chick, the highest level of binding occurred in cerebellum with less in the forebrain and the least in the medulla; in the mammalian species, the highest level of binding occurred in the forebrain structures with less in the cerebellum and least in the medulla. Eadie plots of the saturation isotherms for [3H]kainic acid revealed similar kinetics of binding for frog whole brain, rat forebrain and human parietal cortex with two apparent populations of binding sites: KD1 = 25--50 nM and KD2 = 3--14 nM. While binding in the spiny dogfish forebrain and human caudate nucleus occurred exclusively at a high affinity component, the cerebella of chick, rat and man exhibited only a low affinity binding site. In the 3 species studied most extensively, frog, rat and man, unlabeled kainic acid was the most potent inhibitor of the specific binding of [3H]-kainic acid. L-Glutamic acid was 20--20-fold less potent than kainic acid, and D-glutamic acid was 4--2500-fold less potent than its L-isomer. Reduction of the isopropylene side chain of kainic acid to form dihydrokainic acid decreased the affinity of the derivative 115--30,000-fold. Hill coefficients

  9. Protective effects of gastrodine on dendritic spines in kainic acid-injured neurons

    Institute of Scientific and Technical Information of China (English)

    Yangfei Ji; Boai Zhang; Yanjie Jia; Guifang Sun; Yu Liu; Tao Peng; Yanru Liu; Xingrong Ma

    2011-01-01

    EphB2 affects neuronal cells by altering the dendritic spines. The present study analyzed the neuroprotective effects of gastrodine by measuring EphB2 expression in rat neural cells cultured in vitro and injured by kainic acid. Gastrodine (12.5, 25, and 50 mg/L) improved morphology in kainic acid-injured neurons, reduced lactate dehydrogenase leakage, decreased neuronal apoptosis, and increased EphB2 expression in neuronal cells. A moderate dose of 25 mg/L gastrodine resulted in the most significant effects. These results suggested that gastrodine suppressed the neurotoxic effects of excitatory amino acids and provided neuroprotection by remodeling neuronal dendritic spines.

  10. A role for sodium and chloride in kainic acid-induced beading of inhibitory interneuron dendrites.

    Science.gov (United States)

    Al-Noori, S; Swann, J W

    2000-01-01

    Excitotoxic injury of the dendrites of inhibitory interneurons could lead to decreases in their synaptic activation and explain subsequent local circuit hyperexcitability and epilepsy. A hallmark of dendrotoxicity, at least in principal neurons of the hippocampus and cortex, is focal or varicose swellings of dendritic arbors. In experiments reported here, transient (1h) exposure of hippocampal explant cultures to kainic acid produced marked focal swellings of the dendrites of parvalbumin-immunoreactive pyramidal basket cells in a highly reproducible and dose-dependent manner. At 5mM kainic acid, more than half of the immunopositive apical dendrites in area CA(1) had a beaded appearance. However, the somal volumes of these cells were unaltered by the same treatment. The presence of focal swellings was reversible with kainate washout and was not accompanied by interneuronal cell death. In contrast, exposure to much higher concentrations (300mM) of kainic acid resulted in the total loss of parvalbumin-positive interneurons from explants. Surprisingly, kainic acid-induced dendritic beading does not appear to be mediated by extracellular calcium. Beading was unaltered in the presence of N-methyl-D-aspartate receptor antagonists, the L-type calcium channel antagonist, nimodipine, cadmium, or by removing extracellular calcium. However, blockade of voltage-gated sodium channels by either tetrodotoxin or lidocaine abolished dendritic beading, while the activation of existing voltage-gated sodium channels by veratridine mimicked the kainic acid-induced dendritic beading. Finally, the removal of extracellular chloride prevented the kainic acid-induced dendritic beading.Thus, we suggest that the movement of Na(+) and Cl(-), rather than Ca(2+), into cells underlies the focal swellings of interneuron dendrites in hippocampus.

  11. Blood-brain barrier permeability and brain uptake mechanism of kainic Acid and dihydrokainic Acid

    DEFF Research Database (Denmark)

    Gynther, Mikko; Petsalo, Aleksanteri; Hansen, Steen Honoré;

    2015-01-01

    The glutamatergic neurotransmitter system is involved in important neurophysiological processes and thus constitutes a promising target for the treatment of neurological diseases. The two ionotropic glutamate receptor agonists kainic acid (KA) and dihydrokainic acid (DHK) have been used as research...... volume of distribution in brain is also low. Therefore, even though the total KA and DHK concentrations in the brain are low after systemic dosing, the concentrations in the vicinity of the glutamate receptors are sufficient for their activation and thus the observed efficacy....

  12. Alteration of kainic acid and quinolinic acid toxicity by neostriatal transplants in vitro.

    Science.gov (United States)

    Whetsell, W O; Allen, G S; Tulipan, N B

    1989-01-02

    Mature (greater than 21 days in vitro) organotypic corticostriatal cultures prepared from newborn rat brain were incubated in either kainic acid (KA) 10(-3) M or quinolinic acid (QUIN) 10(-3) M for up to 48 h. Other identical cultures were similarly incubated immediately after they had received one or two additional explants of neonatal striatal tissue placed beside each corticostriatal culture. The cultures incubated with either KA or QUIN in the presence of the neonatal striatal tissue showed better preservation than cultures incubated with KA or QUIN alone. Results suggest that the neonatal striatal explants or 'transplants' afford some protective effect against the toxicity or either KA or QUIN.

  13. Systemic injection of kainic acid differently affects LTP magnitude depending on its epileptogenic efficiency.

    Directory of Open Access Journals (Sweden)

    Luz M Suárez

    Full Text Available Seizures have profound impact on synaptic function and plasticity. While kainic acid is a popular method to induce seizures and to potentially affect synaptic plasticity, it can also produce physiological-like oscillations and trigger some forms of long-term potentiation (LTP. Here, we examine whether induction of LTP is altered in hippocampal slices prepared from rats with different sensitivity to develop status epilepticus (SE by systemic injection of kainic acid. Rats were treated with multiple low doses of kainic acid (5 mg/kg; i.p. to develop SE in a majority of animals (72-85% rats. A group of rats were resistant to develop SE (15-28% after several accumulated doses. Animals were subsequently tested using chronic recordings and object recognition tasks before brain slices were prepared for histological studies and to examine basic features of hippocampal synaptic function and plasticity, including input/output curves, paired-pulse facilitation and theta-burst induced LTP. Consistent with previous reports in kindling and pilocapine models, LTP was reduced in rats that developed SE after kainic acid injection. These animals exhibited signs of hippocampal sclerosis and developed spontaneous seizures. In contrast, resistant rats did not become epileptic and had no signs of cell loss and mossy fiber sprouting. In slices from resistant rats, theta-burst stimulation induced LTP of higher magnitude when compared with control and epileptic rats. Variations on LTP magnitude correlate with animals' performance in a hippocampal-dependent spatial memory task. Our results suggest dissociable long-term effects of treatment with kainic acid on synaptic function and plasticity depending on its epileptogenic efficiency.

  14. Interleukin-6 deficiency reduces the brain inflammatory response and increases oxidative stress and neurodegeneration after kainic acid-induced seizures

    DEFF Research Database (Denmark)

    Penkowa, M; Molinero, A; Carrasco, J

    2001-01-01

    , the immunoreactivity for inducible nitric oxide synthase, peroxynitrite-induced nitration of proteins and byproducts of fatty acid peroxidation were dramatically increased, as was that for metallothionein I+II, Mn-superoxide dismutase and Cu/Zn-superoxide dismutase. In accordance, a significant neuronal apoptosis...... was caused by kainic acid, as revealed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling and interleukin-1beta converting enzyme/Caspase-1 stainings. In kainic acid-injected interleukin-6 null mice, reactive astrogliosis and microgliosis were reduced, while......The role of interleukin-6 in hippocampal tissue damage after injection with kainic acid, a rigid glutamate analogue inducing epileptic seizures, has been studied by means of interleukin-6 null mice. At 35mg/kg, kainic acid induced convulsions in both control (75%) and interleukin-6 null (100%) mice...

  15. Pu-Erh tea and GABA attenuates oxidative stress in kainic acid-induced status epilepticus

    OpenAIRE

    2011-01-01

    Abstract Background Pu-Erh tea is one of the most-consumed beverages due to its taste and the anti-anxiety-producing effect of the gamma-aminobutyric acid (GABA) if contains. However the protective effects of Pu-Erh tea and its constituent, GABA to kainic acid (KA)-induced seizure have not been fully investigated. Methods We analyzed the effect of Pu-Erh tea leaf (PETL) and GABA on KA-induced neuronal injury in vivo and in vitro. Results PETL and GABA reduced the maximal seizure classes, pred...

  16. Cysteinyl-leukotriene production during limbic seizures triggered by kainic acid.

    Science.gov (United States)

    Simmet, T; Tippler, B

    1990-05-07

    In rats kainic acid-induced seizures were accompanied by time-dependent cerebral cysteinyl-leukotriene (LT) and prostaglandin (PG) F2 alpha formation. Cysteinyl-LT were identified in the rat brain tissue extracts by their immunoreactive properties and their retention times upon reversed phase HPLC profiling. In perfused blood-free brain tissue contents of LTC4-like material were significantly elevated in cortex, hippocampus, midbrain and hypothalamus at 3 h after kainic acid injection. PGF2 alpha tissue contents were significantly elevated in all brain areas studied with very large amounts in the hippocampus and smaller amounts in the cortex. The cyclooxygenase inhibitor indomethacin significantly inhibited formation of PGF2 alpha in whole brain tissue while leaving unaffected the production of cysteinyl-LT. A dose of indomethacin which nearly completely inhibited cyclooxygenase activity as monitored by cerebral PGF2 alpha contents also tended to aggravate behavioral changes and significantly increased the mortality. Phenidone, a lipoxygenase inhibitor, significantly and dose-dependently inhibited formation of cysteinyl-LT but did not significantly affect PGF2 alpha formation. Seizure activity tended to be attenuated by a higher dose of this compound. Dexamethasone which supposedly inhibits phospholipase A2 activity by induction of lipocortins, did not significantly reduce either cysteinyl-LT or PGF2 alpha biosynthesis. Flunarizine, trifluoperazine and diazepines protected a certain percentage of animals from kainic acid-induced seizures. In rats in which seizures occurred in spite of pretreatment with these compounds, the eicosanoid formation was not inhibited but in the case of flunarizine was even found to be somewhat enhanced.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Effect of nootropic Solcoseryl on kainic acid-induced excitotoxic brain injury.

    Science.gov (United States)

    Mintz, M; Knowlton, B; Myslobodsky, M S

    1993-05-01

    Solcoseryl (S) has been shown to provide significant cytoprotection in a variety of models of cerebral hypoxia. In the present study, we quantified the epileptiform effects caused by kainic acid administered into the pontine reticular formation of rats and their response to S pretreatment. Compared to saline, the agent appeared to significantly reduce the mortality of rats in the course of status epilepticus. However, S-pretreated rats manifested an increased incidence of behavioral seizures. This untoward effect is attributed to the fact that S improves the functional potential of injured tissue and retards the period of metabolic exhaustion at a time when neuronal activity should be minimized.

  18. Neonatal striatal grafts prevent lethal syndrome produced by bilateral intrastriatal injection of kainic acid.

    Science.gov (United States)

    Tulipan, N; Huang, S; Whetsell, W O; Allen, G S

    1986-07-02

    It is reported that unilateral grafts of neonatal striatal tissue protect the recipient from the lethal aphagia and adipsia produced by bilateral intrastriatal injection of 10 nmol of kainic acid in rats. It is shown that neither adult striatum nor neonatal tissue from other sites have the same lifesaving effect and that the salutary effect of the graft is dependent upon graft survival. Grafts from a histoincompatible donor are apparently rejected, leading to the death of the recipient. Cyclosporine inhibits rejection thereby enabling recipient survival. It is postulated that the graft exerts a neurohumoral influence that protects the striatum from the toxic effect of kainate.

  19. Striatal grafts provide sustained protection from kainic and quinolinic acid-induced damage.

    Science.gov (United States)

    Tulipan, N; Luo, S Q; Allen, G S; Whetsell, W O

    1988-12-01

    Grafts of neonatal striatal tissue were placed into the striata of adult rats. When challenged immediately with intrastriatal injections of either kainic or quinolinic acid, excitotoxic damage was prevented. Thirty days later these same graft recipients received another injection of excitotoxin. The intrastriatal grafts continued to mitigate toxin-induced damage. It is hypothesized that the grafted cells not only survive, but that they may continue to elaborate some substance or substances that prevent excitotoxin-induced injury for at least 30 days. Previous investigations indicated that grafts of neonatal striatal tissue can protect the recipient striatum from kainic acid toxicity. In the following study it is demonstrated that such grafts also protect the striatum from quinolinic acid, an endogenous excitotoxin which induces kainate-like neuronal degeneration and has been implicated in the pathogenesis of Huntington's disease. It is postulated that the salutary effect of striatal grafting may be sufficiently long lasting to mitigate a chronic toxic insult. Such grafting may therefore represent a therapy for Huntington's disease and other neurodegenerative disorders in which an endogenous or exogenous toxin has been implicated as the pathogenetic agent.

  20. Blood-brain barrier permeability and brain uptake mechanism of kainic acid and dihydrokainic acid.

    Science.gov (United States)

    Gynther, Mikko; Petsalo, Aleksanteri; Hansen, Steen H; Bunch, Lennart; Pickering, Darryl S

    2015-03-01

    The glutamatergic neurotransmitter system is involved in important neurophysiological processes and thus constitutes a promising target for the treatment of neurological diseases. The two ionotropic glutamate receptor agonists kainic acid (KA) and dihydrokainic acid (DHK) have been used as research tools in various in vivo central nervous system disease models in rodents, as well as being templates in the design of novel ligands affecting the glutamatergic system. Both molecules are highly polar but yet capable of crossing the blood-brain barrier (BBB). We used an in situ rat brain perfusion technique to determine the brain uptake mechanism and permeability across the BBB. To determine KA and DHK concentrations in the rat brain, simple and rapid sample preparation and liquid chromatography mass spectrometer methods were developed. According to our results the BBB permeability of KA and DHK is low, 0.25 × 10(-6) and 0.28 × 10(-6) cm/s for KA and DHK, respectively. In addition, the brain uptake is mediated by passive diffusion, and not by active transport. Furthermore, the non-specific plasma and brain protein binding of KA and DHK was determined to be low, which means that the unbound drug volume of distribution in brain is also low. Therefore, even though the total KA and DHK concentrations in the brain are low after systemic dosing, the concentrations in the vicinity of the glutamate receptors are sufficient for their activation and thus the observed efficacy.

  1. Acupuncture suppresses kainic acid-induced neuronal death and inflammatory events in mouse hippocampus.

    Science.gov (United States)

    Kim, Seung-Tae; Doo, Ah-Reum; Kim, Seung-Nam; Kim, Song-Yi; Kim, Yoon Young; Kim, Jang-Hyun; Lee, Hyejung; Yin, Chang Shik; Park, Hi-Joon

    2012-09-01

    The administration of kainic acid (KA) causes seizures and produces neurodegeneration in hippocampal CA3 pyramidal cells. The present study investigated a possible role of acupuncture in reducing hippocampal cell death and inflammatory events, using a mouse model of kainic acid-induced epilepsy. Male C57BL/6 mice received acupuncture treatments at acupoint HT8 or in the tail area bilaterally once a day for 2 days and again immediately after an intraperitoneal injection of KA (30 mg/kg). HT8 is located on the palmar surface of the forelimbs, between the fourth and fifth metacarpal bones. Twenty-four hours after the KA injection, neuronal cell survival, the activations of microglia and astrocytes, and mRNA expression of two proinflammatory cytokines, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), were measured in the hippocampus. Acupuncture stimulation at HT8, but not in the tail area, significantly reduced the KA-induced seizure, neuron death, microglial and astrocyte activations, and IL-1β mRNA expression in the hippocampus. The acupuncture stimulation also decreased the mRNA expression of TNF-α, but it was not significant. These results indicate that acupuncture at HT8 can inhibit hippocampal cell death and suppress KA-induced inflammatory events, suggesting a possible role for acupuncture in the treatment of epilepsy.

  2. Hippocampal corticosterone receptors and novelty-induced behavioral activity : effect of kainic acid lesion in the hippocampus

    NARCIS (Netherlands)

    Nyakas, C; De Kloet, E R; Veldhuis, H D; Bohus, B

    1983-01-01

    Rats were injected bilaterally in the dorsal and ventral hippocampus with kainic acid (KA) or with artificial CSF and their behavior and brain corticosterone (B) receptor systems were studied. The hippocampal KA injection destroyed part of the pyramidal neurons and of the dentate gyrus neurons. Thes

  3. Seizures in the intrahippocampal kainic acid epilepsy model: Characterization using long-term video-EEG monitoring in the rat

    NARCIS (Netherlands)

    R. Raedt; A. Van Dycke; D. Van Melkebeke; T. De Smedt; P. Claeys; T. Wyckhuys; K. Vonck; W. Wadman; P. Boon

    2009-01-01

    Objective - Intrahippocampal injection of kainic acid (KA) in rats evokes a status epilepticus (SE) and leads to spontaneous seizures. However to date, precise electroencephalographic (EEG) and clinical characterization of spontaneous seizures in this epilepsy model using long-term video-EEG monitor

  4. Chronic activity wheel running reduces the severity of kainic acid-induced seizures in the rat: possible role of galanin.

    Science.gov (United States)

    Reiss, J I; Dishman, R K; Boyd, H E; Robinson, J K; Holmes, P V

    2009-04-17

    Studies in both humans and rodents suggest that exercise can be neuroprotective, but the mechanisms by which this occurs are still poorly understood. Three weeks of voluntary, physical activity in rats upregulates prepro-galanin messenger RNA levels in the locus coeruleus. Galanin is a neuropeptide extensively coexisting with norepinephrine that decreases neuronal hyperexcitability both in vivo and in vitro. Thus, exercise may diminish neural hyperexcitability through a galaninergic mechanism. The current experiments tested whether voluntary activity wheel running would protect against kainic acid-evoked seizures and whether galaninergic signaling is a necessary factor in this protection. In experiment 1, rats were given access to running wheels or remained sedentary for three weeks. After this period, rats received an intraperitoneal (i.p.) injection of 0, 7, 10 or 14 mg/kg kainic acid. Exercise decreased the severity of or eliminated seizure behaviors and hippocampal c-fos expression induced by kainic acid. In experiment 2, exercising or sedentary rats were injected intracerebroventricularly (i.c.v.) with 0.2 or 0.4 microg of kainic acid following either an injection of M-40 (a galanin receptor antagonist) or saline. Exercise decreased kainic acid-induced seizures at the 0.2 microg dose, and M-40 (6 nmol) decreased this effect. In contrast, there were no detectable differences between exercising and sedentary rats in behavior at the 0.4 microg dose. The results suggest that the protective effects of exercise against seizures are at least partially mediated by regulation of neural excitability through a process involving galanin.

  5. Protective effects of C-phycocyanin against kainic acid-induced neuronal damage in rat hippocampus.

    Science.gov (United States)

    Rimbau, V; Camins, A; Romay, C; González, R; Pallàs, M

    1999-12-03

    The neuroprotective role of C-phycocyanin was examined in kainate-injured brains of rats. The effect of three different treatments with C-phycocyanin was studied. The incidence of neurobehavioral changes was significantly lower in animals receiving C-phycocyanin. These animals also gained significantly more weight than the animals only receiving kainic acid, whereas their weight gain did not differed significantly from controls. Equivalent results were found when the neuronal damage in the hippocampus was evaluated through changes in peripheral benzodiazepine receptors (microglial marker) and heat shock protein 27 kD expression (astroglial marker). Our results are consistent with the oxygen radical scavenging properties of C-phycocyanin described elsewhere. Our findings and the virtual lack of toxicity of C-phycocyanin suggest this drug could be used to treat oxidative stress-induced neuronal injury in neurodegenerative diseases, such as Alzheimer's and Parkinson's.

  6. Neuroprotective and anti-inflammatory effects of lidocaine in kainic acid-injected rats.

    Science.gov (United States)

    Chiu, Kuan Ming; Lu, Cheng Wei; Lee, Ming Yi; Wang, Ming Jiuh; Lin, Tzu Yu; Wang, Su Jane

    2016-05-04

    Lidocaine, the most commonly used local anesthetic, inhibits glutamate release from nerve terminals. Given the involvement of glutamate neurotoxicity in the pathogenesis of various neurological disorders, this study investigated the role of lidocaine in hippocampal neuronal death and inflammatory events induced by an i.p. injection of kainic acid (KA) (15 mg/kg), a glutamate analog. The results showed that KA significantly led to neuronal death in the CA3 pyramidal layers of the hippocampus and this effect was attenuated by the systemic administration of lidocaine (0.8 or 4 mg/kg, i.p.) 30 min before KA injection. Moreover, KA-induced microglia activation and gene expression of proinflammatory cytokines, namely, interleukin-1β, interleukin-6, and tumor necrosis factor-α, in the hippocampus were reduced by the lidocaine pretreatment. Altogether, the results suggest that lidocaine can effectively treat glutamate excitotoxicity-related brain disorders.

  7. Transient changes in the limbic histaminergic system after systemic kainic acid-induced seizures.

    Science.gov (United States)

    Lintunen, Minnamaija; Sallmen, Tina; Karlstedt, Kaj; Panula, Pertti

    2005-10-01

    Increased brain histamine is reported to protect against convulsions. We used systemic kainic acid (KA) administration to study possible changes of the histaminergic system in rat brain in status epilepticus (SE). Robust increases in brain histamine concentrations and numbers of histamine-immunoreactive nerve fibers were detected in the piriform cortex (Pir) and amygdala after KA injection, suggesting a reactive increase, which is opposite to other published aminergic transmitter responses. These changes, lasting several weeks, might be coupled to a mechanism unrelated to the anticonvulsive function of histamine. Transient increases in mRNA expression of H(3) receptor isoforms with a full-length third intracellular loop, coupled to mitogen-activated protein kinase pathway, were detected first in the hippocampal CA3c area, followed by the Pir and amygdala and then the hippocampal CA1 area. These results suggest that histamine and H3 receptors, which also control the release of GABA and glutamate, might be involved in convulsive SE.

  8. Effects of topiramate on hippocampal neuronal apoptosis in rats after kainic acid-evoked seizures

    Institute of Scientific and Technical Information of China (English)

    Yuan Wu; Jiarong Pang; Jinou Zheng; Xiaoqing Deng; Xiulin Liang; Jiaquan Li; Zhiying Chen

    2008-01-01

    BACKGROUND:Apoptosis plays an important role in brain injury after seizures and the formation of chronic epilepsy.It is important to investigate whether topiramate exhibits either antiepileptic and/or anti-apoptotic effects on hippocampal neurons.OBJECTIVE:To observe euronal apoptosis in hippocampus of rat seizure models,and to investigate the antagonizing effect of topiramate on neuronal apoptosis after seizures.DESIGN:An animal experiment of comparative observation.SETTING:First Affiliated Hospital of Guangxi Medical University.MATERIALS:Sixty healthy male Sprague Dawley(SD)rats,4-6 weeks old and weighing 160-220 g,were provided by the Experimental Animal Center of Guangxi Medical University.Main apparatus and reagents were as follows:Rat brain solid positioner(SR-6N,made in Japan); kainic acid by Sigma(USA);pathological image analyzer(DMR+550)by Leica(Germany); in situ apoptosis detection kit by Wuhan Boster Biological Technology Co.,Ltd; topiramate by Xi'an-Janssen Pharmaceutical,Ltd.The treatment on animals in the experiment was in accordance with the standards of animal ethics.METHODS:The experiments were performed at the Scientific Experimental Center of Guangxi Medical University from June to December 2006.The rats were randomly divided into a topiramate-treated group(n=30)and a model group(n=30).① After anesthesia,all rats were administered a kainic acid injection(0.2 μ L,2 g/L)into the right lateral ventricle.Grade Ⅲ and greater Racine standards were considered to be a successful model establishment.Thirty minutes after seizure ,rats in the topiramate-treated group were treated with an intraperitoneal(i.p.)injection of topiramate every day(40 mg/kg/d)for 2 weeks.The rats in the model group were treated with an equal volume of saline for 2 weeks.③Six rats in the topiramate-treated group were sacrificed at 1 day,and 1,2,3,and 4 weeks after treatment,respectively.The model group animals were sacrificed at corresponding time points.The brain

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

    Science.gov (United States)

    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.

  10. Does kainic acid induce partial brain lesion in an invertebrate model: sepia officinalis? Comparison with electrolytic lesion.

    Science.gov (United States)

    Graindorge, Nicolas; Jozet-Alves, Christelle; Chichery, Raymond; Dickel, Ludovic; Bellanger, Cécile

    2008-10-31

    The present study investigates the feasibility of excitotoxic lesions in the cuttlefish in the mapping of brain functions in Cephalopods. Adult animals were injected locally with a neurotoxin, kainic acid. The brain region receiving the neurotoxin was the vertical lobe, a key brain structure for learning and memory processes. Brain damage induced by these injections was evaluated using different histological stainings: hematoxilin-eosin, Fink-Heimer and DAPI. The results were compared with histological changes after electrolytic lesion of the vertical lobe. Neurodegeneration was revealed in and around the injection site: an intense area of proliferative cells, degenerating terminal axon ramifications and cell death. In comparison with electrolytic lesion, excitotoxic lesion displays important advantages, since fibres of passage are not destroyed by kainic acid injection, which induces only a restricted lesion and so is an appropriate method of investigating the role of the vertical lobe or other brain regions in a Cephalopod model, Sepia officinalis.

  11. Blood-brain barrier changes with kainic acid-induced limbic seizures

    Energy Technology Data Exchange (ETDEWEB)

    Zucker, D.K.; Wooten, G.F.; Lothman, E.W.

    1983-02-01

    Rats were treated with kainic acid (KA) i.v. to produce increasingly severe limbic seizures that were monitored with a behavioral rating scale. At various times after the induction of seizures, the animals; blood-brain barriers (B-BB) were studied with alpha-(/sup 14/C)aminoisobutyric acid ((/sup 14/C)AIBA) autoradiography. Using optical density ratios, a coefficient was devised to assess the functional integrity of the B-BB in discrete anatomic regions and to quantitatively compare these measurements among different groups of experimental animals. In animals that exhibited only mild seizures, the B-BB was not different from controls. Animals with severe limbic seizures, however, showed alterations. For as long as 2 h after delivery of KA, the B-BB appeared normal; from 2 to 24 h, the permeability to (/sup 14/C)AIBA was markedly increased throughout the brain, especially in limbic regions; from 24 h to 7 days the B-BB returned to normal except for a small residual change in limbic structures. These findings were confirmed with Evans blue dye studies of the B-BB. A correlation between focal accentuation of B-BB alterations and neuropathologic changes was found. These experiments indicted that recurrent limbic seizures may lead to a breakdown in the B-BB independent of systemic metabolic derangements. Marked focal metabolic and electrical changes, however, occurred in several limbic structures several hours before the blood-brain barrier was altered.

  12. Intracerebroventricular kainic acid administration to neonatal rats alters interneuron development in the hippocampus.

    Science.gov (United States)

    Dong, Hongxin; Csernansky, Cynthia A; Chu, Yunxiang; Csernansky, John G

    2003-10-10

    The effects of neonatal exposure to excitotoxins on the development of interneurons have not been well characterized, but may be relevant to the pathogenesis of neuropsychiatric disorders. In this study, the excitotoxin, kainic acid (KA) was administered to rats at postnatal day 7 (P7) by intracerebroventricular (i.c.v.) infusion. At P14, P25, P40 and P60, Nissl staining and immunohistochemical studies with the interneuron markers, glutamic acid decarboxylase (GAD-67), calbindin-D28k (CB) and parvalbumin (PV) were performed in the hippocampus. In control animals, the total number of interneurons, as well as the number of interneurons stained with GAD-67, CB and PV, was nearly constant from P14 through P60. In KA-treated rats, Nissl staining, GAD-67 staining, and CB staining revealed a progressive decline in the overall number of interneurons in the CA1 and CA3 subfields from P14 to P60. In contrast, PV staining in KA-treated rats showed initial decreases in the number of interneurons in the CA1 and CA3 subfields at P14 followed by increases that approached control levels by P60. These results suggest that, in general, early exposure to the excitotoxin KA decreases the number of hippocampal interneurons, but has a more variable effect on the specific population of interneurons labeled by PV. The functional impact of these changes may be relevant to the pathogenesis of neuropsychiatric disorders, such as schizophrenia.

  13. Kainic Acid-Induced Excitotoxicity Experimental Model: Protective Merits of Natural Products and Plant Extracts

    Directory of Open Access Journals (Sweden)

    Nur Shafika Mohd Sairazi

    2015-01-01

    Full Text Available Excitotoxicity is well recognized as a major pathological process of neuronal death in neurodegenerative diseases involving the central nervous system (CNS. In the animal models of neurodegeneration, excitotoxicity is commonly induced experimentally by chemical convulsants, particularly kainic acid (KA. KA-induced excitotoxicity in rodent models has been shown to result in seizures, behavioral changes, oxidative stress, glial activation, inflammatory mediator production, endoplasmic reticulum stress, mitochondrial dysfunction, and selective neurodegeneration in the brain upon KA administration. Recently, there is an emerging trend to search for natural sources to combat against excitotoxicity-associated neurodegenerative diseases. Natural products and plant extracts had attracted a considerable amount of attention because of their reported beneficial effects on the CNS, particularly their neuroprotective effect against excitotoxicity. They provide significant reduction and/or protection against the development and progression of acute and chronic neurodegeneration. This indicates that natural products and plants extracts may be useful in protecting against excitotoxicity-associated neurodegeneration. Thus, targeting of multiple pathways simultaneously may be the strategy to maximize the neuroprotection effect. This review summarizes the mechanisms involved in KA-induced excitotoxicity and attempts to collate the various researches related to the protective effect of natural products and plant extracts in the KA model of neurodegeneration.

  14. Naringin Attenuates Autophagic Stress and Neuroinflammation in Kainic Acid-Treated Hippocampus In Vivo

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    Kyoung Hoon Jeong

    2015-01-01

    Full Text Available Kainic acid (KA is well known as a chemical compound to study epileptic seizures and neuronal excitotoxicity. KA-induced excitotoxicity causes neuronal death by induction of autophagic stress and microglia-derived neuroinflammation, suggesting that the control of KA-induced effects may be important to inhibit epileptic seizures with neuroprotection. Naringin, a flavonoid in grapefruit and citrus fruits, has anti-inflammatory and antioxidative activities, resulting in neuroprotection in animal models from neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease. In the present study, we examined its beneficial effects involved in antiautophagic stress and antineuroinflammation in the KA-treated hippocampus. Our results showed that naringin treatment delayed the onset of KA-induced seizures and decreased the occurrence of chronic spontaneous recurrent seizures (SRS in KA-treated mice. Moreover, naringin treatment protected hippocampal CA1 neurons in the KA-treated hippocampus, ameliorated KA-induced autophagic stress, confirmed by the expression of microtubule-associated protein light chain 3 (LC3, and attenuated an increase in tumor necrosis factor-α (TNFα in activated microglia. These results suggest that naringin may have beneficial effects of preventing epileptic events and neuronal death through antiautophagic stress and antineuroinflammation in the hippocampus in vivo.

  15. Conditioned Medium Reconditions Hippocampal Neurons against Kainic Acid Induced Excitotoxicity: An In Vitro Study

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    Pradeep Kumar K. Bevinahal

    2014-01-01

    Full Text Available Stem cell therapy is gaining attention as a promising treatment option for neurodegenerative diseases. The functional efficacy of grafted cells is a matter of debate and the recent consensus is that the cellular and functional recoveries might be due to “by-stander” effects of grafted cells. In the present study, we investigated the neuroprotective effect of conditioned medium (CM derived from human embryonic kidney (HEK cells in a kainic acid (KA induced hippocampal degeneration model system in in vitro condition. Hippocampal cell line was exposed to KA (200 µM for 24 hrs (lesion group whereas, in the treatment group, hippocampal cell line was exposed to KA in combination with HEK-CM (KA + HEK-CM. We observed that KA exposure to cells resulted in significant neuronal loss. Interestingly, HEK-CM cotreatment completely attenuated the excitotoxic effects of KA. In HEK-CM cotreatment group, the cell viability was ~85–95% as opposed to 47% in KA alone group. Further investigation demonstrated that treatment with HEK-CM stimulated the endogenous cell survival factors like brain derived neurotrophic factors (BDNF and antiapoptotic factor Bcl-2, revealing the possible mechanism of neuroprotection. Our results suggest that HEK-CM protects hippocampal neurons against excitotoxicity by stimulating the host’s endogenous cell survival mechanisms.

  16. Alterations of taurine in the brain of chronic kainic acid epilepsy model.

    Science.gov (United States)

    Baran, H

    2006-10-01

    The aim of the study was to investigate the changes of taurine in the kainic acid (KA, 10 mg/kg, s.c.) chronic model of epilepsy, six months after KA application. The KA-rats used were divided into a group of animals showing weak behavioural response to KA (WDS, rare focal convulsion; rating scale 3 up to 3 h after KA injection). The brain regions investigated were caudate nucleus, substantia nigra, septum, hippocampus, amygdala/piriform cortex, and frontal, parietal, temporal and occipital cortices. KA-rats with rating rats with rating >3 developed spontaneous recurrent seizures and six months after injection increased taurine levels were found in the caudate nucleus (162.5% of control) and hippocampus (126.6% of control), while reduced taurine levels were seen in the septum (78.2% of control). In summary, increased taurine levels in the hippocampus may involve processes for membrane stabilisation, thus favouring recovery after neuronal hyperactivity. The increased taurine levels in the caudate nucleus could be involved in the modulation of spontaneous recurrent seizure activity.

  17. Soman- or kainic acid-induced convulsions decrease muscarinic receptors but not benzodiazepine receptors

    Energy Technology Data Exchange (ETDEWEB)

    Churchill, L.; Pazdernik, T.L.; Cross, R.S.; Nelson, S.R.; Samson, F.E. (Univ. of Kansas Medical Center, Kansas City (USA))

    (3H)Quinuclidinyl benzilate (QNB) binding to muscarinic receptors decreased in the rat forebrain after convulsions induced by a single dose of either soman, a potent inhibitor of acetylcholinesterase, or kainic acid, an excitotoxin. A Rosenthal plot revealed that the receptors decreased in number rather than affinity. When the soman-induced convulsions were blocked, the decrease in muscarinic receptors at 3 days was less extensive than when convulsions occurred and at 10 days they approached control levels in most of the brain areas. The most prominent decrements in QNB binding were in the piriform cortex where the decline in QNB binding is probably related to the extensive convulsion-associated neuropathology. The decrements in QNB binding after convulsions suggest that the convulsive state leads to a down-regulation of muscarinic receptors in some brain areas. In contrast to the decrease in QNB binding after convulsions, (3H)flunitrazepam binding to benzodiazepine receptors did not change even in the piriform cortex where the loss in muscarinic receptors was most prominent. Thus, it appears that those neuronal processes that bear muscarinic receptors are more vulnerable to convulsion-induced change than those with benzodiazepine receptors.

  18. Resting state functional network disruptions in a kainic acid model of temporal lobe epilepsy

    Directory of Open Access Journals (Sweden)

    Ravnoor Singh Gill

    2017-01-01

    Full Text Available We studied the graph topological properties of brain networks derived from resting-state functional magnetic resonance imaging in a kainic acid induced model of temporal lobe epilepsy (TLE in rats. Functional connectivity was determined by temporal correlation of the resting-state Blood Oxygen Level Dependent (BOLD signals between two brain regions during 1.5% and 2% isoflurane, and analyzed as networks in epileptic and control rats. Graph theoretical analysis revealed a significant increase in functional connectivity between brain areas in epileptic than control rats, and the connected brain areas could be categorized as a limbic network and a default mode network (DMN. The limbic network includes the hippocampus, amygdala, piriform cortex, nucleus accumbens, and mediodorsal thalamus, whereas DMN involves the medial prefrontal cortex, anterior and posterior cingulate cortex, auditory and temporal association cortex, and posterior parietal cortex. The TLE model manifested a higher clustering coefficient, increased global and local efficiency, and increased small-worldness as compared to controls, despite having a similar characteristic path length. These results suggest extensive disruptions in the functional brain networks, which may be the basis of altered cognitive, emotional and psychiatric symptoms in TLE.

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

    Science.gov (United States)

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

    2016-04-01

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

  20. Selective stimulation of excitatory amino acid receptor subtypes and the survival of cerebellar granule cells in culture: effect of kainic acid

    DEFF Research Database (Denmark)

    Balázs, R; Hack, N; Jørgensen, Ole Steen

    1990-01-01

    Our previous studies showed that the survival of cerebellar granule cells in culture is promoted by treatment with N-methyl-D-aspartate. Here we report on the influence of another glutamate analogue, kainic acid, which, in contrast to N-methyl-D-aspartate, is believed to stimulate transmitter rec...

  1. The Ketogenic Diet Suppresses the Cathepsin E Expression Induced by Kainic Acid in the Rat Brain

    Science.gov (United States)

    Jeong, Hyun Jeong; Kim, Hojeong; Kim, Yoon-Kyoung; Park, Sang-Kyu; Kang, Dong-Won

    2010-01-01

    Purpose The ketogenic diet has long been used to treat epilepsy, but its mechanism is not yet clearly understood. To explore the potential mechanism, we analyzed the changes in gene expression induced by the ketogenic diet in the rat kainic acid (KA) epilepsy model. Materials and Methods KA-administered rats were fed the ketogenic diet or a normal diet for 4 weeks, and microarray analysis was performed with their brain tissues. The effects of the ketogenic diet on cathepsin E messenger ribonucleic acid (mRNA) expression were analyzed in KA-administered and normal saline-administered groups with semi-quantitative and real-time reverse transcription polymerase chain reaction (RT-PCR). Brain tissues were dissected into 8 regions to compare differential effects of the ketogenic diet on cathepsin E mRNA expression. Immunohistochemistry with an anti-cathepsin E antibody was performed on slides of hippocampus obtained from whole brain paraffin blocks. Results The microarray data and subsequent RT-PCR experiments showed that KA increased the mRNA expression of cathepsin E, known to be related to neuronal cell death, in most brain areas except the brain stem, and these increases of cathepsin E mRNA expression were suppressed by the ketogenic diet. The expression of cathepsin E mRNA in the control group, however, was not significantly affected by the ketogenic diet. The change in cathepsin E mRNA expression was greatest in the hippocampus. The protein level of cathepsin E in the hippocampus of KA-administered rat was elevated in immunohistochemistry and the ketogenic diet suppressed this increase. Conclusion Our results showed that KA administration increased cathepsin E expression in the rat brain and its increase was suppressed by the ketogenic diet. PMID:20635438

  2. A macaque model of mesial temporal lobe epilepsy induced by unilateral intrahippocampal injection of kainic Acid.

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    Ning Chen

    Full Text Available OBJECTIVE: In order to better investigate the cause/effect relationships of human mesial temporal lobe epilepsy (mTLE, we hereby describe a new non-human primate model of mTLE. METHODS: Ten macaques were studied and divided into 2 groups: saline control group (n = 4 and kainic acid (KA injection group (n = 6. All macaques were implanted bilaterally with subdural electrodes over temporal cortex and depth electrodes in CA3 hippocampal region. KA was stereotaxically injected into the right hippocampus of macaques. All animals were monitored by video and electrocorticography (ECoG to assess status epilepticus (SE and subsequent spontaneous recurrent seizures (SRS. Additionally, in order to evaluate brain injury produced by SE or SRS, we used both neuroimaging, including magnetic resonance image (MRI & magnetic resonance spectroscopy (MRS, and histological pathology, including Nissl stainning and glial fibrillary acid protein (GFAP immunostaining. RESULTS: The typical seizures were observed in the KA-injected animal model. Hippocampal sclerosis could be found by MRI & MRS. Hematoxylin and eosin (H&E staining and GFAP immunostaining showed neuronal loss, proliferation of glial cells, formation of glial scars, and hippocampal atrophy. Electron microscopic analysis of hippocampal tissues revealed neuronal pyknosis, partial ribosome depolymerization, an abnormal reduction in rough endoplasmic reticulum size, expansion of Golgi vesicles and swollen star-shaped cells. Furthermore, we reported that KA was able to induce SE followed by SRS after a variable period of time. Similar to human mTLE, brain damage is confined to the hippocampus. Accordingly, hippocampal volume is in positive correlations with the neuronal cells count in the CA3, especially the ratio of neuron/glial cell. CONCLUSIONS: The results suggest that a model of mTLE can be developed in macaques by intra-hippocampal injection of KA. Brain damage is confined to the hippocampus which

  3. Acacetin inhibits glutamate release and prevents kainic acid-induced neurotoxicity in rats.

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    Tzu-Yu Lin

    Full Text Available An excessive release of glutamate is considered to be a molecular mechanism associated with several neurological diseases that causes neuronal damage. Therefore, searching for compounds that reduce glutamate neurotoxicity is necessary. In this study, the possibility that the natural flavone acacetin derived from the traditional Chinese medicine Clerodendrum inerme (L. Gaertn is a neuroprotective agent was investigated. The effect of acacetin on endogenous glutamate release in rat hippocampal nerve terminals (synaptosomes was also investigated. The results indicated that acacetin inhibited depolarization-evoked glutamate release and cytosolic free Ca(2+ concentration ([Ca(2+]C in the hippocampal nerve terminals. However, acacetin did not alter synaptosomal membrane potential. Furthermore, the inhibitory effect of acacetin on evoked glutamate release was prevented by the Cav2.2 (N-type and Cav2.1 (P/Q-type channel blocker known as ω-conotoxin MVIIC. In a kainic acid (KA rat model, an animal model used for excitotoxic neurodegeneration experiments, acacetin (10 or 50 mg/kg was administrated intraperitoneally to the rats 30 min before the KA (15 mg/kg intraperitoneal injection, and subsequently induced the attenuation of KA-induced neuronal cell death and microglia activation in the CA3 region of the hippocampus. The present study demonstrates that the natural compound, acacetin, inhibits glutamate release from hippocampal synaptosomes by attenuating voltage-dependent Ca(2+ entry and effectively prevents KA-induced in vivo excitotoxicity. Collectively, these data suggest that acacetin has the therapeutic potential for treating neurological diseases associated with excitotoxicity.

  4. Downregulation of 14-3-3 Proteins in a Kainic Acid-Induced Neurotoxicity Model.

    Science.gov (United States)

    Smani, Danyal; Sarkar, Sumit; Raymick, James; Kanungo, Jyotshna; Paule, Merle G; Gu, Qiang

    2017-08-24

    The 14-3-3 proteins are among the most abundant proteins expressed in the brain, comprising about 1% of the total amount of soluble brain proteins. Through phosphoserine- and phosphothreonine-binding motifs, 14-3-3 proteins regulate many signaling proteins and cellular processes including cell death. In the present study, we utilized a well-known kainic acid (KA)-induced excitotoxicity rat model and examined the expression of 14-3-3 and its isoforms in the frontal cortex of KA-treated and control animals. Among the different 14-3-3 isoforms, abundant levels of eta and tau were detected in the frontal cortex, followed by sigma, epsilon, and gamma, while the expression levels of alpha/beta and zeta/delta isoforms were low. Compared to the control animals, KA treatment induced a significant downregulation of the overall 14-3-3 protein level as well as the levels of the abundant isoforms eta, tau, epsilon, and gamma. We also investigated two 14-3-3-interacting proteins that are involved in the cell death process: Bcl-2-associated X (BAX) and extracellular signal-regulated kinase (ERK). Both BAX and phosphorylated ERK showed increased levels following KA treatment. Together, these findings demonstrate an abundance of several 14-3-3 isoforms in the frontal cortex and that KA treatment can cause a downregulation of 14-3-3 expression and an upregulation of 14-3-3-interacting proteins BAX and phospho-ERK. Thus, downregulation of 14-3-3 proteins could be one of the early molecular events associated with excitotoxicity. This could lead to subsequent upregulation of 14-3-3-binding proteins such as BAX and phospho-ERK that contribute to further downstream apoptosis processes, eventually leading to cell death. Maintaining sufficient levels of 14-3-3 expression and function may become a target of therapeutic intervention for excitotoxicity-induced neurodegeneration.

  5. Histamine H3 receptor antagonism by ABT-239 attenuates kainic acid induced excitotoxicity in mice.

    Science.gov (United States)

    Bhowmik, Malay; Saini, Neeru; Vohora, Divya

    2014-09-18

    The multifaceted pathogenesis of temporal lobe epilepsy (TLE) offers a number of adjunctive therapeutic prospects. One such therapeutic strategy could be targeting H3 receptor (H3R) by selective H3R antagonists which are perceived to have antiepileptic and neuroprotective potential. Kainic acid (KA) induced seizure, a reliable model of TLE, triggers epileptogenic events resulting from initial neuronal death and ensuing recurring seizures. The present study aimed to determine whether pre-treatment with ABT-239, a novel H3R antagonist, and its combinations with sodium valproate (SVP) and TDZD-8 (glycogen synthase kinase-3β (GSK3β) inhibitor) can prevent the excitotoxic events in mice exposed to KA (10 mg/kg i.p.). ABT-239 (1 and 3 mg/kg i.p.) significantly attenuated KA-mediated behavioural and excitotoxic anomalies and restored altered expression of Bax, cleaved caspase-3, phospho-Akt (Ser473) and cAMP response element binding protein (CREB). Surprisingly, restoration of Bcl2 and phospho-GSK3β (Ser9) by ABT-239 did not reach the level of statistical significance. Co-administration of ABT-239 (1 and 3 mg/kg) with a sub-effective dose of SVP (150 mg/kg i.p.) yielded improved efficacy than when given alone. Similarly, low and high dose combinations of ABT-239 (1 and 3 mg/kg) with TDZD-8 (5 and 10 mg/kg i.p.) produced greater neuroprotection than any other treatment group. Our findings suggests a neuroprotective potential of ABT-239 and its combinations with SVP and TDZD-8 against KA-induced neurotoxicity, possibly mediated through in part each by modulating Akt/GSK3β and CREB pathways. The use of H3R antagonists as adjuvant in the treatment of human TLE might find potential utility, and can be pursued further.

  6. Neuroprotective effect of Arthrospira (Spirulina) platensis against kainic acid-neuronal death.

    Science.gov (United States)

    Pérez-Juárez, Angélica; Chamorro, Germán; Alva-Sánchez, Claudia; Paniagua-Castro, Norma; Pacheco-Rosado, Jorge

    2016-08-01

    Context Arthrospira (Spirulina) platensis (SP) is a cyanobacterium which has attracted attention because of its nutritional value and pharmacological properties. It was previously reported that SP reduces oxidative stress in the hippocampus and protects against damaging neurobehavioural effects of systemic kainic acid (KA). It is widely known that the systemic administration of KA induces neuronal damage, specifically in the CA3 hippocampal region. Objective The present study determines if the SP sub-chronic treatment has neuroprotective properties against KA. Materials and methods Male SW mice were treated with SP during 24 d, at doses of 0, 200, and 800 mg/kg, once daily, and with KA (35 mg/kg, ip) as a single dose on day 14. After the treatment, a histological analysis was performed and the number of atrophic neuronal cells in CA3 hippocampal region was quantified. Results Pretreatment with SP does not protect against seizures induced by KA. However, mortality in the SP 200 and the SP 800 groups was of 20%, while for the KA group, it was of 60%. A single KA ip administration produced a considerable neuronal damage, whereas both doses of SP sub-chronic treatment reduced the number of atrophic neurons in CA3 hippocampal region with respect to the KA group. Discussion The SP neurobehaviour improvement after KA systemic administration correlates with the capacity of SP to reduce KA-neuronal death in CA3 hippocampal cells. This neuroprotection may be related to the antioxidant properties of SP. Conclusion SP reduces KA-neuronal death in CA3 hippocampal cells.

  7. Phenolic antioxidants attenuate hippocampal neuronal cell damage against kainic acid induced excitotoxicity

    Indian Academy of Sciences (India)

    M S Parihar; Taruna Hemnani

    2003-02-01

    Increasing evidence supports the role of excitotoxicity in neuronal cell injury. Thus, it is extremely important to explore methods to retard or reverse excitotoxic neuronal injury. In this regard, certain dietary compounds are begining to receive increased attention, in particular those involving phytochemicals found in medicinal plants in alleviating neuronal injury. In the present study, we examined whether medicinal plant extracts protect neurons against excitotoxic lesions induced by kainic acid (KA) in female Swiss albino mice. Mice were anesthetized with ketamine and xylazine (200 mg and 2 mg/kg body wt. respectively) and KA (0.25 g in a volume of 0.5 l) was administered to mice by intra hippocampal injections. The results showed an impairment of the hippocampus region of brain after KA injection. The lipid peroxidation and protein carbonyl content were significantly ( < 0.05) increased in comparison to controls. Glutathione peroxidase (GPx) activity (EC 1.11.1.9) and reduced glutathione (GSH) content declined after appearance of excitotoxic lesions. As GPx and GSH represent a major pathway in the cell for metabolizing hydrogen peroxide (H2O2), their depletion would be expected to allow H2O2 to accumulate to toxic levels. Dried ethanolic plant extracts of Withania somnifera (WS), Convolvulus pleuricauas (CP) and Aloe vera (AV) dissolved in distilled water were tested for their total antioxidant activity. The diet was prepared in terms of total antioxidant activity of plant extracts. The iron (Fe3+) reducing activity of plant extracts was also tested and it was found that WS and AV were potent reductants of Fe3+ at pH 5.5. CP had lower Fe3+ reducing activity in comparison to WS and AV. Plant extracts given singly and in combination 3 weeks prior to KA injections resulted in a decrease in neurotoxicity. Measures of lipid peroxidation and protein carbonyl declined. GPx activity and GSH content were elevated in hippocampus supplemented with WS and combination of

  8. Endogenous BDNF protein is increased in adult rat hippocampus after a kainic acid induced excitotoxic insult but exogenous BDNF is not neuroprotective.

    Science.gov (United States)

    Rudge, J S; Mather, P E; Pasnikowski, E M; Cai, N; Corcoran, T; Acheson, A; Anderson, K; Lindsay, R M; Wiegand, S J

    1998-02-01

    Systemic administration of the excitotoxin kainic acid to adult rats results in a well defined pattern of loss of the CA1 and CA3 pyramidal neurons of the hippocampus. Prior to this neuronal loss, brain-derived neurotrophic factor (BDNF) mRNA is substantially increased. We show here that BDNF protein is increased after excitotoxic insult in specific areas of the hippocampus, reaching maximal levels 24 h after the insult. BDNF protein levels in the hippocampus increase in direct relation to the severity of seizure. Up to 7 days after injection of kainic acid, levels of full-length TrkB protein were unchanged, whereas levels of truncated TrkB protein were significantly increased by 12 h. To determine whether elevations in BDNF protein levels are potentially beneficial to hippocampal neurons exposed to an excitotoxic stress, we infused exogenous BDNF prior to and during the period of neuronal death caused by kainic acid. We find that administration of high levels of exogenous BDNF does not affect severity of seizure, but does in fact, exacerbate the injury caused by kainic acid, specifically to CA3 pyramidal neurons. Although there was a trend toward sparing of CA1 pyramidal neurons on the side infused with BDNF, this was not significant. In the same paradigm, infusion of exogenous NT-3 had no effect.

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

    Science.gov (United States)

    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.

  10. Gene expression analysis of the emergence of epileptiform activity after focal injection of kainic acid into mouse hippocampus

    DEFF Research Database (Denmark)

    Motti, Dario; Le Duigou, Caroline; Eugène, Emmanuel

    2010-01-01

    We report gene profiling data on genomic processes underlying the progression towards recurrent seizures after injection of kainic acid (KA) into the mouse hippocampus. Focal injection enabled us to separate the effects of proepileptic stimuli initiated by KA injection. Both the injected...... and contralateral hippocampus participated in the status epilepticus. However, neuronal death induced by KA treatment was restricted to the injected hippocampus, although there was some contralateral axonal degeneration. We profiled gene expression changes in dorsal and ventral regions of both the injected......-temporal changes revealed an early transcriptional response, strong immune, cell death and growth responses at 2 weeks and an activation of immune and extracellular matrix genes persisting at 6 months. Immunostaining for proteins coded by genes identified from array studies provided evidence for gliogenesis...

  11. Midkine, heparin-binding growth factor, blocks kainic acid-induced seizure and neuronal cell death in mouse hippocampus

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    Lim In J

    2010-03-01

    Full Text Available Abstract Background Midkine (MK, a member of the heparin-binding growth factor family, which includes MK and pleiotrophin, is known to possess neurotrophic and neuroprotective properties in the central nervous system. Previous studies have shown that MK is an effective neuroprotective agent in reducing retinal degeneration caused by excessive light and decreasing hippocampal neuronal death in ischemic gerbil brain. The present study was undertaken to investigate whether MK acts as an anticonvulsant in kainic acid (KA-induced seizure in mouse and blocks KA-mediated neuronal cell death in hippocampus. Results Increased expression of MK was found in hippocampus of mouse following seizures induced by intracerebroventricular injection of KA, and MK expression was found in glial fibrillary acidic protein (GFAP-positive astrocytes. Concurrent injection of MK and KA attenuated KA-induced seizure activity and cell death of hippocampal neurons including pyramidal cells and glutamic acid decarboxylase 67 (GAD67-positive GABAergic interneurons in the CA3 and hilar area. Conclusion The results of the present study indicate that MK functions as an anticonvulsant and neuroprotective agent in hippocampus during KA-induced seizures.

  12. Melatonin Mediates Protective Effects against Kainic Acid-Induced Neuronal Death through Safeguarding ER Stress and Mitochondrial Disturbance

    Science.gov (United States)

    Xue, Feixiao; Shi, Cai; Chen, Qingjie; Hang, Weijian; Xia, Liangtao; Wu, Yue; Tao, Sophia Z.; Zhou, Jie; Shi, Anbing; Chen, Juan

    2017-01-01

    Kainic acid (KA)-induced neuronal death is linked to mitochondrial dysfunction and ER stress. Melatonin is known to protect hippocampal neurons from KA-induced apoptosis, but the exact mechanisms underlying melatonin protective effects against neuronal mitochondria disorder and ER stress remain uncertain. In this study, we investigated the sheltering roles of melatonin during KA-induced apoptosis by focusing on mitochondrial dysfunction and ER stress mediated signal pathways. KA causes mitochondrial dynamic disorder and dysfunction through calpain activation, leading to neuronal apoptosis. Ca2+ chelator BAPTA-AM and calpain inhibitor calpeptin can significantly restore mitochondrial morphology and function. ER stress can also be induced by KA treatment. ER stress inhibitor 4-phenylbutyric acid (PBA) attenuates ER stress-mediated apoptosis and mitochondrial disorder. It is worth noting that calpain activation was also inhibited under PBA administration. Thus, we concluded that melatonin effectively inhibits KA-induced calpain upregulation/activation and mitochondrial deterioration by alleviating Ca2+ overload and ER stress. PMID:28293167

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

    Science.gov (United States)

    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.

  14. Involvement of the neuronal phosphotyrosine signal adaptor N-Shc in kainic acid-induced epileptiform activity.

    Science.gov (United States)

    Baba, Shiro; Onga, Kazuko; Kakizawa, Sho; Ohyama, Kyoji; Yasuda, Kunihiko; Otsubo, Hiroshi; Scott, Brian W; Burnham, W McIntyre; Matsuo, Takayuki; Nagata, Izumi; Mori, Nozomu

    2016-06-08

    BDNF-TrkB signaling is implicated in experimental seizures and epilepsy. However, the downstream signaling involved in the epileptiform activity caused by TrkB receptor activation is still unknown. The aim of the present study was to determine whether TrkB-mediated N-Shc signal transduction was involved in kainic acid (KA)-induced epileptiform activity. We investigated KA-induced behavioral seizures, epileptiform activities and neuronal cell loss in hippocampus between N-Shc deficient and control mice. There was a significant reduction in seizure severity and the frequency of epileptiform discharges in N-Shc deficient mice, as compared with wild-type and C57BL/6 mice. KA-induced neuronal cell loss in the CA3 of hippocampus was also inhibited in N-Shc deficient mice. This study demonstrates that the activation of N-Shc signaling pathway contributes to an acute KA-induced epileptiform activity and neuronal cell loss in the hippocampus. We propose that the N-Shc-mediated signaling pathway could provide a potential target for the novel therapeutic approaches of epilepsy.

  15. Occurrence of complement protein C3 in dying pyramidal neurons in rat hippocampus after systemic administration of kainic acid.

    Science.gov (United States)

    Morita, Hiroyuki; Suzuki, Katsuaki; Mori, Norio; Yasuhara, Osamu

    2006-11-27

    To evaluate the roles of complement in kainic acid (KA)-induced neuronal damages, the immunohistochemical localization of the complement protein C3 was examined in rat hippocampus after systemic KA injection. The immunoreactivity for C3 was found in glial cells in control rats, and such glial cells were increased in number after KA injection. Our confocal study showed that C3-positive glial cells were microglia. Three to seven days after KA, C3 immunoreactivity appeared in CA1 and CA3 pyramidal neurons. Double staining for C3 combined with the terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling showed that occurrence of C3 immunoreactivity in neurons coincided well with that of DNA fragmentation. Western blot analysis and RT-PCR experiments suggested local synthesis of C3 by brain cells. Our results suggest that C3 contributes greatly to neuronal death after systemic KA administration, and that microglia and neurons are the local source of C3 in KA-induced brain injury.

  16. Naringenin ameliorates kainic acid-induced morphological alterations in the dentate gyrus in a mouse model of temporal lobe epilepsy.

    Science.gov (United States)

    Park, Jungha; Jeong, Kyoung Hoon; Shin, Won-Ho; Bae, Young-Seuk; Jung, Un Ju; Kim, Sang Ryong

    2016-10-19

    Granule cell dispersion (GCD) in the dentate gyrus (DG) of the hippocampus is a morphological alteration characteristic of temporal lobe epilepsy. Recently, we reported that treatment with naringin, a flavonoid found in grapefruit and citrus fruits, reduced spontaneous recurrent seizures by inhibiting kainic acid (KA)-induced GCD and neuronal cell death in mouse hippocampus, suggesting that naringin might have beneficial effects for preventing epileptic events in the adult brain. However, it is still unclear whether the beneficial effects of naringin treatment are mediated by the metabolism of naringin into naringenin in the KA-treated hippocampus. To investigate this possibility, we evaluated whether intraperitoneal injections of naringenin could mimic naringin-induced effects against GCD caused by intrahippocampal KA injections in mice. Our results showed that treatment with naringenin delayed the onset of KA-induced seizures and attenuated KA-induced GCD by inhibiting activation of the mammalian target of rapamycin complex 1 in both neurons and reactive astrocytes in the DG. In addition, its administration attenuated the production of proinflammatory cytokines such as tumor necrosis tumor necrosis factor-α (TNFα) and interleukin-1β (IL-1β) from microglial activation in the DG following KA treatment. These results suggest that naringenin may be an active metabolite of naringin and help prevent the progression of epileptic insults in the hippocampus in vivo; therefore, naringenin may be a beneficial metabolite of naringin for the treatment of epilepsy.

  17. Key Proteins of Activating Cell Death Can Be Predicted through a Kainic Acid-Induced Excitotoxic Stress

    Directory of Open Access Journals (Sweden)

    Hsiu-Ling Tsai

    2015-01-01

    Full Text Available Epilepsy is a major neurological disorder characterized by spontaneous seizures accompanied by neurophysiological changes. Repeated seizures can damage the brain as neuronal death occurs. A better understanding of the mechanisms of brain cell death could facilitate the discovery of novel treatments for neurological disorders such as epilepsy. In this study, a model of kainic acid- (KA- induced neuronal death was established to investigate the early protein markers associated with apoptotic cell death due to excitotoxic damage in the rat cortex. The results indicated that KA induces both apoptotic and necrotic cell death in the cortex. Incubation with high concentrations (5 and 500 μM, >75% and low concentrations (0.5 pM: 95% and 50 nM: 8% of KA for 180 min led to necrotic and apoptotic cell death, respectively. Moreover, proteomic analysis using two-dimensional gel electrophoresis and mass spectrometry demonstrated that antiapoptotic proteins, including heat shock protein 70, 3-mercaptopyruvate sulfurtransferase, tubulin-B-5, and pyruvate dehydrogenase E1 component subunit beta, were significantly higher in apoptosis than in necrosis induced by KA. Our findings provide direct evidence that several proteins are associated with apoptotic and necrotic cell death in excitotoxicity model. The results indicate that these proteins can be apoptotic biomarkers from the early stages of cell death.

  18. Overexpression of γ-aminobutyric acid transporter subtype I leads to susceptibility to kainic acid-induced seizure in transgenic mice

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    γ-aminobutyric acid (GABA) is the principal inhibitory neurotransmitter,and the GABAergic synaptic transmission is normally terminated by the rapid uptake through GABA transporters.With transgenic mice ubiquitously overexpressing GABA transporter subtype I (GAT1),the present study explored the pathophysiological role of GAT1 in epileptogenesis.Though displaying no spontaneous seizure activity,these mice exhibit altered electroencephalographic patterns and increased susceptibility to seizure induced by kainic acid.In addition,the GABAA receptor and glutamate transporters are up-regulated in transgenic mice,which perhaps reflects a compensatory or corrective change to the elevated level of GAT1.These preliminary findings support the hypothesis that excitatory and inhibitory neurotransmission,and seizure susceptibility can be altered by neurotransmitter transporters.

  19. Glia activation and cytokine increase in rat hippocampus by kainic acid-induced status epilepticus during postnatal development.

    Science.gov (United States)

    Rizzi, Massimo; Perego, Carlo; Aliprandi, Marisa; Richichi, Cristina; Ravizza, Teresa; Colella, Daniele; Velískŏvá, Jana; Moshé, Solomon L; De Simoni, M Grazia; Vezzani, Annamaria

    2003-12-01

    In adult rats, status epilepticus (SE) induces cytokine production by glia especially when seizures are associated with neuronal injury. This suggests that cytokines may play a role in seizure-induced neuronal damage. As SE-induced injury is age-specific, we used rats of different ages (with distinct susceptibilities to seizure-induced neuronal injury) to elucidate the role of cytokines in this process. Thus, we investigated the activation of microglia and astrocytes, induction of cytokines, and hippocampal neuronal injury 4 and 24 h following kainic acid-induced SE in postnatal day (PN) 9, 15, and 21 rats. At PN9, there was little activation of microglia and astrocytes at any time point studied. Interleukin-1beta (IL), tumor necrosis factor-alpha (TNF), and IL-6 or the naturally occurring IL-1 receptor antagonist (Ra) mRNA expression did not increase. No evidence of cell injury has been detected. At PN15, immunostaining of microglia and astrocytes was enhanced, but only IL-1beta mRNA expression was increased. These changes were observed 4 h after SE. Scattered injured neurons in CA3 and subiculum, but not in any other region, were present 24 h following SE. At PN21, immunostaining of microglia and astrocytes and the mRNA expression of all cytokines studied was significantly increased already 4 h after SE. At 24 h, many injured neurons were present in CA1 and CA3 regions and in 40% of rats in other forebrain areas. These data show that (i) the pattern of glia activation and cytokine gene transcription induced by SE is age-dependent and (ii) neuronal injury in the hippocampus occurs only when cytokines are induced and their synthesis precedes the appearance of neuronal damage. Thus, cytokine expression in immature brain is associated specifically with cell injury rather than with seizures per se, suggesting that proinflammatory cytokines may contribute to the occurence of SE-induced hippocampal damage.

  20. Early induction of secretoneurin expression following kainic acid administration at convulsant doses in the rat and gerbil hippocampus.

    Science.gov (United States)

    Marti, E; Blasi, J; Ferrer, I

    2002-01-01

    The expression of secretogranin-II and its major proteolytic product secretoneurin (SN) is under the control of neuronal excitation, as demonstrated by treating rats with the excitotoxic kainic acid (KA). Differences in the structure and function of the hippocampus in rats and gerbils have been described; these suggest possible differential reactive responses to KA. In the present study, the SN immunostaining pattern in relation with cell damage is analyzed from 6 h to 4 days following KA administration in rats and gerbils. Dramatic differences in the expression of SN were found in the hippocampal complex following KA administration in gerbils and rats. A robust increase in SN immunoreactivity was detected in the pyramidal cell layer of the rat hippocampus, especially in the CA1 area. In the gerbil, however, a strong increase in SN immunostaining was detected in interneurons of the hippocampal formation, as shown by double-labeling immunohistochemistry to SN and the calcium-binding proteins parvalbumin, calbindin, and calretinin. In addition, no damage (in the hippocampal formation) or moderate damage (in the entorhinal cortex) was observed in the gerbil, in contrast to the rat. The administration of KA and the GABA-B receptor inhibitors (CGP56999A or CGP36742) to the gerbil resulted in a strong rise in SN immunoreactitivty in the CA1 pyramidal cell layer of the hippocampus, as in the rat. However, no increased cell damage was observed under these conditions. The present data provide evidence of a species-differential reactive response to KA that might be based, in part, on distinct inhibitory intrahippocampal circuitry.

  1. In vivo microdialysis studies on the effects of decortication and excitotoxic lesions on kainic acid-induced calcium fluxes, and endogenous amino acid release, in the rat striatum

    Energy Technology Data Exchange (ETDEWEB)

    Butcher, S.P.; Lazarewicz, J.W.; Hamberger, A.

    1987-11-01

    The in vivo effects of kainate (1 mM) on fluxes of /sup 45/Ca2+, and endogenous amino acids, were examined in the rat striatum using the brain microdialysis technique. Kainate evoked a rapid decrease in dialysate /sup 45/Ca2+, and an increase in the concentration of amino acids in dialysates in Ca2+-free dialysates. Taurine was elevated six- to 10-fold, glutamate two- to threefold, and aspartate 1.5- to twofold. There was also a delayed increase in phosphoethanolamine, whereas nonneuroactive amino acids were increased only slightly. The kainic acid-evoked reduction in dialysate /sup 45/Ca2+ activity was attenuated in striata lesioned previously with kainate, suggesting the involvement of intrinsic striatal neurons in this response. The increase in taurine concentration induced by kainate was slightly smaller under these conditions. Decortication did not affect the kainate-evoked alterations in either dialysate /sup 45/Ca2+ or amino acids. These data suggest that kainate does not release acidic amino acids from their transmitter pools located in corticostriatal terminals.

  2. Altered mRNA editing and expression of ionotropic glutamate receptors after kainic acid exposure in cyclooxygenase-2 deficient mice.

    Directory of Open Access Journals (Sweden)

    Luca Caracciolo

    Full Text Available Kainic acid (KA binds to the AMPA/KA receptors and induces seizures that result in inflammation, oxidative damage and neuronal death. We previously showed that cyclooxygenase-2 deficient (COX-2(-/- mice are more vulnerable to KA-induced excitotoxicity. Here, we investigated whether the increased susceptibility of COX-2(-/- mice to KA is associated with altered mRNA expression and editing of glutamate receptors. The expression of AMPA GluR2, GluR3 and KA GluR6 was increased in vehicle-injected COX-2(-/- mice compared to wild type (WT mice in hippocampus and cortex, whereas gene expression of NMDA receptors was decreased. KA treatment decreased the expression of AMPA, KA and NMDA receptors in the hippocampus, with a significant effect in COX-2(-/- mice. Furthermore, we analyzed RNA editing levels and found that the level of GluR3 R/G editing site was selectively increased in the hippocampus and decreased in the cortex in COX-2(-/- compared with WT mice. After KA, GluR4 R/G editing site, flip form, was increased in the hippocampus of COX-2(-/- mice. Treatment of WT mice with the COX-2 inhibitor celecoxib for two weeks decreased the expression of AMPA/KA and NMDAR subunits after KA, as observed in COX-2(-/- mice. After KA exposure, COX-2(-/- mice showed increased mRNA expression of markers of inflammation and oxidative stress, such as cytokines (TNF-α, IL-1β and IL-6, inducible nitric oxide synthase (iNOS, microglia (CD11b and astrocyte (GFAP. Thus, COX-2 gene deletion can exacerbate the inflammatory response to KA. We suggest that COX-2 plays a role in attenuating glutamate excitotoxicity by modulating RNA editing of AMPA/KA and mRNA expression of all ionotropic glutamate receptor subunits and, in turn, neuronal excitability. These changes may contribute to the increased vulnerability of COX-2(-/- mice to KA. The overstimulation of glutamate receptors as a consequence of COX-2 gene deletion suggests a functional coupling between COX-2 and the

  3. Administration of simvastatin after kainic acid-induced status epilepticus restrains chronic temporal lobe epilepsy.

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    Chuncheng Xie

    Full Text Available In this study, we examined the effect of chronic administration of simvastatin immediately after status epilepticus (SE on rat brain with temporal lobe epilepsy (TLE. First, we evaluated cytokines expression at 3 days post KA-lesion in hippocampus and found that simvastatin-treatment suppressed lesion-induced expression of interleukin (IL-1β and tumor necrosis factor-α (TNF-α. Further, we quantified reactive astrocytosis using glial fibrillary acidic protein (GFAP staining and neuron loss using Nissl staining in hippocampus at 4-6 months after KA-lesion. We found that simvastatin suppressed reactive astrocytosis demonstrated by a significant decrease in GFAP-positive cells, and attenuated loss of pyramidal neurons in CA3 and interneurons in dentate hilar (DH. We next assessed aberrant mossy fiber sprouting (MFS that is known to contribute to recurrence of spontaneous seizure in epileptic brain. In contrast to the robust MFS observed in saline-treated animals, the extent of MFS was restrained by simvastatin in epileptic rats. Attenuated MFS was related to decreased neuronal loss in CA3 and DH, which is possibly a mechanism underlying decreased hippocampal susceptibility in animal treated with simvastatin. Electronic encephalography (EEG was recorded during 4 to 6 months after KA-lesion. The frequency of abnormal spikes in rats with simvastatin-treatment decreased significantly compared to the saline group. In summary, simvastatin treatment suppressed cytokines expression and reactive astrocytosis and decreased the frequency of discharges of epileptic brain, which might be due to the inhibition of MFS in DH. Our study suggests that simvastatin administration might be a possible intervention and promising strategy for preventing SE exacerbating to chronic epilepsy.

  4. Kainic acid-induced endoplasmic reticulum stress model%红藻氨酸诱导内质网应激模型的途径

    Institute of Scientific and Technical Information of China (English)

    袁磊; 张海霞; 钱诗蕾; 徐斌; 龚济钦; 刘湘华; 唐园; 禹华旭

    2014-01-01

    背景:前期研究表明,海马内注射红藻氨酸海可诱发兴奋性红藻氨酸受体KA1亚受体在海马神经元的表达明显上调,内质网应激标志物磷酸化真核翻译起始因子2α表达增加并伴随细胞死亡。目的:探讨红藻氨酸海马内注射后内质网应激发生的机制。方法:取昆明小鼠32只,将0.15 nmol 红藻氨酸注入海马CA1区域,注射时间为60 s。分别于红藻氨酸注射后第1,2,3,4,5,6,8,12小时灌注取脑,灌注取脑前进行Bederson体征评分,然后行全脑切片FJB染色分析与免疫荧光双标记观察。结果与结论:①红藻氨酸注射后第3,4,5,6,8小时,Bederson 体征评分表明中枢神经功能出现明显损伤,FJB染色示小鼠海马内神经元死亡明显;注射后第1,2,12小时,Bederson体征评分中枢神经功能未见明显损伤,FJB染色小鼠海马神经元死亡结果不明显。②根据FJB结果,取第3,8小时的脑片做免疫组化。海马内注射红藻氨酸后导致海马神经元中KA1和磷酸化真核翻译起始因子2α在相同的时间点表达明显上调,将KA1与磷酸化真核翻译起始因子2α图片结果进行叠加处理,两者完全重合,表明KA1的表达和内质网应激发生在同一个神经细胞内。结果表明红藻氨酸首先诱导了兴奋性膜上受体KA1表达的上调,其KA1的表达上调可能引起细胞内质网功能紊乱,导致内质网应激反应,并进一步促进了神经细胞的死亡。%BACKGROUND:Previous studies have shown that kainic acid injected into hippocampus can significantly upregulate the expression of excitatory KA1 subunit of the kainate receptor in the hippocampus, and endoplasmic reticulum stress markers, phosphorylation of the alpha subunit of eukaryotic initiation factor 2, accompanied by celldeath. OBJECTIVE:To explore the mechanism of endoplasmic reticulum stress after kainic acid is injected into the

  5. Neuroprotective Effect of Uncaria rhynchophylla in Kainic Acid-Induced Epileptic Seizures by Modulating Hippocampal Mossy Fiber Sprouting, Neuron Survival, Astrocyte Proliferation, and S100B Expression

    Directory of Open Access Journals (Sweden)

    Chung-Hsiang Liu

    2012-01-01

    Full Text Available 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

  6. [The microglial activation and the expression of heat shock protein 27 through the propagation pathway of kainic acid-induced hippocampal seizure in the rat].

    Science.gov (United States)

    Taniwaki, Y

    2001-02-01

    We studied activation of microglia and expression of the 27 kDa heat shock protein (HSP27) in the brain during kainic acid-induced acute hippocampal seizures in rats. The microglial activation was observed at 6 hrs after seizure induction, but the expression of HSP27 was delayed until 3 days after seizure induction. The gross anatomical distributions of the two phenomena in the brain structures were almost identical, being localized not only in the primary focus at the dorsal hippocampus ipsilateral to the kainic acid injection, but also in selected remote brain structures that was highly consistent with the propagation pathways of the hippocampal seizure as detected previously by metabolic mapping. These structures included the hippocampus, amygdala, entorhinal cortex, piriform cortex, sensorimotor cortex, hypothalamus and thalamus. A close observation, however, revealed a difference in distribution of the two phenomena in the layers of the contralateral hippocampus: The HSP27 expression showed a layer-specific distribution, being localized selectively in the molecular layer and hilus of the dentate gyrus, and the radiatum and molecular layers of the CA-3 subfield suggesting the expression in the neuropil. On the other hand, the distribution of the microglial activation was non-specific to the layers, being scattered in the whole regions of the dorsal hippocampus. There were no apparent morphological changes in the neurons in these structures except for the ipsilateral dorsal hippocampus, by light microscopic examinations with hematoxylin-eosin staining. These findings thus indicate that activation of microglial cells and expression of HSP27 occur transsynaptically by epileptic activities through the propagation pathways of hippocampal seizure and suggest that these phenomena may reflect a part of early microenvironmental alterations in epileptic brain.

  7. Glutamic acid decarboxylase-67-positive hippocampal interneurons undergo a permanent reduction in number following kainic acid-induced degeneration of ca3 pyramidal neurons.

    Science.gov (United States)

    Shetty, A K; Turner, D A

    2001-06-01

    Kainic acid (KA)-induced degeneration of CA3 pyramidal neurons leads to synaptic reorganization and hyperexcitability in both dentate gyrus and CA1 region of the hippocampus. We hypothesize that the substrate for hippocampal inhibitory circuitry incurs significant and permanent alterations following degeneration of CA3 pyramidal neurons. We quantified changes in interneuron density (N(v)) in all strata of the dentate gyrus and the CA1 and CA3 subfields of adult rats at 1, 4, and 6 months following intracerebroventricular (icv) KA administration, using glutamic acid decarboxylase-67 (GAD-67) immunocytochemistry. At 1 month postlesion, GAD-67-positive interneuron density was significantly reduced in all strata of every hippocampal region except stratum pyramidale of CA1. The reduction in GAD-67-positive interneuron density either persisted or exacerbated at 4 and 6 months postlesion in every stratum of all hippocampal regions. Further, the soma of remaining GAD-67-positive interneurons in dentate gyrus and CA3 subfield showed significant hypertrophy. Thus, both permanent reductions in the density of GAD-67-positive interneurons in all hippocampal regions and somatic hypertrophy of remaining GAD-67-positive interneurons in dentate gyrus and CA3 subfield occur following icv KA. In contrast, the density of interneurons visualized with Nissl in CA1 and CA3 regions was nearly equivalent to that in the intact hippocampus at all postlesion time points. Collectively, these results suggest that persistent reductions in GAD-67-positive interneuron density observed throughout the hippocampus following CA3 lesion are largely due to a permanent loss of GAD-67 expression in a significant fraction of interneurons, rather than widespread degeneration of interneurons. Nevertheless, a persistent decrease in interneuron activity, as evidenced by permanent down-regulation of GAD-67 in a major fraction of interneurons, would likely enhance the degree of hyperexcitability in the CA3

  8. Parvalbumin interneurons and calretinin fibers arising from the thalamic nucleus reuniens degenerate in the subiculum after kainic acid-induced seizures.

    Science.gov (United States)

    Drexel, M; Preidt, A P; Kirchmair, E; Sperk, G

    2011-08-25

    The subiculum is the major output area of the hippocampus. It is closely interconnected with the entorhinal cortex and other parahippocampal areas. In animal models of temporal lobe epilepsy (TLE) and in TLE patients it exerts increased network excitability and may crucially contribute to the propagation of limbic seizures. Using immunohistochemistry and in situ-hybridization we now investigated neuropathological changes affecting parvalbumin and calretinin containing neurons in the subiculum and other parahippocampal areas after kainic acid-induced status epilepticus. We observed prominent losses in parvalbumin containing interneurons in the subiculum and entorhinal cortex, and in the principal cell layers of the pre- and parasubiculum. Degeneration of parvalbumin-positive neurons was associated with significant precipitation of parvalbumin-immunoreactive debris 24 h after kainic acid injection. In the subiculum the superficial portion of the pyramidal cell layer was more severely affected than its deep part. In the entorhinal cortex, the deep layers were more severely affected than the superficial ones. The decrease in number of parvalbumin-positive neurons in the subiculum and entorhinal cortex correlated with the number of spontaneous seizures subsequently experienced by the rats. The loss of parvalbumin neurons thus may contribute to the development of spontaneous seizures. On the other hand, surviving parvalbumin neurons revealed markedly increased expression of parvalbumin mRNA notably in the pyramidal cell layer of the subiculum and in all layers of the entorhinal cortex. This indicates increased activity of these neurons aiming to compensate for the partial loss of this functionally important neuron population. Furthermore, calretinin-positive fibers terminating in the molecular layer of the subiculum, in sector CA1 of the hippocampus proper and in the entorhinal cortex degenerated together with their presumed perikarya in the thalamic nucleus reuniens. In

  9. Regionally specific induction of BDNF and truncated trkB.T1 receptors in the hippocampal formation after intraseptal injection of kainic acid.

    Science.gov (United States)

    Venero, J L; Hefti, F

    1998-04-20

    The septo-hippocampal cholinergic and GABAergic systems were lesioned with single unilateral injections of kainic acid (KA) into the septum to further characterize the role of these afferents in the regulation of hippocampal brain-derived neurotrophic factor (BDNF) expression. Nearly all cells expressing choline acetyltransferase, trkA or glutamic acid decarboxylase mRNA disappeared in the medial septum 7 days after the neurotoxin administration. The lesion resulted in a complete loss of CA3 pyramidal cells, and robust increases in BDNF mRNA levels in hippocampal granular dentate cells and in the amygdala. There were rapid transient increases of BDNF mRNA levels in the hippocampal formation and cortex. In addition, we found a strong induction of truncated trkB.T1 mRNA receptors in the stratum radiatum and stratum oriens of the CA3 subfield. The prolonged induction of BDNF mRNA levels suggests an important role of this neurotrophin, possibly mediated by truncated trkB receptors, in the regulation of hippocampal plasticity following injury.

  10. Evidence for increased cellular uptake of glutamate and aspartate in the rat hippocampus during kainic acid seizures. A microdialysis study using the "indicator diffusion' method

    DEFF Research Database (Denmark)

    Bruhn, T; Christensen, Thomas; Diemer, Nils Henrik

    1997-01-01

    Using a newly developed technique, based on microdialysis, which allows cellular uptake of glutamate and aspartate to be studied in awake animals, we investigated uptake of glutamate and aspartate in the hippocampal formation of rats during limbic seizures induced by systemical administration of ....... The results indicate that during KA-induced seizures, uptake of glutamate and aspartate is increased, possibly aimed at maintaining the extracellular homeostasis of these two excitatory amino acids.......Using a newly developed technique, based on microdialysis, which allows cellular uptake of glutamate and aspartate to be studied in awake animals, we investigated uptake of glutamate and aspartate in the hippocampal formation of rats during limbic seizures induced by systemical administration...... of kainic acid (KA). With [14C]mannitol as an extracellular reference substance, the cellular extraction of the test substance [3H]D-aspartate was measured at different stages of seizure-activity. The results were compared to those obtained in a sham operated control group. During severe generalized clonic...

  11. Increase in α-tubulin modifications in the neuronal processes of hippocampal neurons in both kainic acid-induced epileptic seizure and Alzheimer’s disease

    Science.gov (United States)

    Vu, Hang Thi; Akatsu, Hiroyasu; Hashizume, Yoshio; Setou, Mitsutoshi; Ikegami, Koji

    2017-01-01

    Neurodegeneration includes acute changes and slow-developing alterations, both of which partly involve common cellular machinery. During neurodegeneration, neuronal processes are impaired along with dysregulated post-translational modifications (PTMs) of cytoskeletal proteins. In neuronal processes, tubulin undergoes unique PTMs including a branched form of modification called glutamylation and loss of the C-terminal tyrosine residue and the penultimate glutamic acid residue forming Δ2-tubulin. Here, we investigated the state of two PTMs, glutamylation and Δ2 form, in both acute and slow-developing neurodegenerations, using a newly generated monoclonal antibody, DTE41, which had 2-fold higher affinity to glutamylated Δ2-tubulin, than to unmodified Δ2-tubulin. DTE41 recognised glutamylated Δ2-tubulin preferentially in immunostaining than in enzyme-linked immunosorbent assay and immunoblotting. In normal mouse brain, DTE41 stained molecular layer of the cerebellum as well as synapse-rich regions in pyramidal neurons of the cerebral cortex. In kainic acid-induced epileptic seizure, DTE41-labelled signals were increased in the hippocampal CA3 region, especially in the stratum lucidum. In the hippocampi of post-mortem patients with Alzheimer’s disease, intensities of DTE41 staining were increased in mossy fibres in the CA3 region as well as in apical dendrites of the pyramidal neurons. Our findings indicate that glutamylation on Δ2-tubulin is increased in both acute and slow-developing neurodegeneration. PMID:28067280

  12. Long-Term Intake of Uncaria rhynchophylla Reduces S100B and RAGE Protein Levels in Kainic Acid-Induced Epileptic Seizures Rats

    Directory of Open Access Journals (Sweden)

    Nou-Ying Tang

    2017-01-01

    Full Text Available Epileptic seizures are crucial clinical manifestations of recurrent neuronal discharges in the brain. An imbalance between the excitatory and inhibitory neuronal discharges causes brain damage and cell loss. Herbal medicines offer alternative treatment options for epilepsy because of their low cost and few side effects. We established a rat epilepsy model by injecting kainic acid (KA, 12 mg/kg, i.p. and subsequently investigated the effect of Uncaria rhynchophylla (UR and its underlying mechanisms. Electroencephalogram and epileptic behaviors revealed that the KA injection induced epileptic seizures. Following KA injection, S100B levels increased in the hippocampus. This phenomenon was attenuated by the oral administration of UR and valproic acid (VA, 250 mg/kg. Both drugs significantly reversed receptor potentiation for advanced glycation end product proteins. Rats with KA-induced epilepsy exhibited no increase in the expression of metabotropic glutamate receptor 3, monocyte chemoattractant protein 1, and chemokine receptor type 2, which play a role in inflammation. Our results provide novel and detailed mechanisms, explaining the role of UR in KA-induced epileptic seizures in hippocampal CA1 neurons.

  13. Radiation-induced apoptosis in developing rats and kainic acid-induced excitotoxicity in adult rats are associated with distinctive morphological and biochemical c-Jun/AP-1 (N) expression

    Energy Technology Data Exchange (ETDEWEB)

    Pozas, E. [Unitat de Neuropatologia, Servei d' Anatomia Patologica, Hospital Princeps d' Espanya, Universitat de Barcelona, 08907 Hospitalet de Llobregat (Spain); Planas, A.M. [Departament de Farmacologia i Toxicologia, IIBB, CSIC Barcelona (Spain); Ferrer, I. [Unitat de Neuropatologia, Servei d' Anatomia Patologica, Hospital Princeps d' Espanya, Universitat de Barcelona, 08907 Hospitalet de Llobregat (Spain)

    1997-07-14

    Ionizing radiation produces apoptosis in the developing rat brain. Strong c-Jun immunoreactivity, as revealed with the antibody c-Jun/AP-1 (N) which is raised against the amino acids 91-105 mapping with the amino terminal domain of mouse c-Jun p39, is simultaneously observed in the nucleus and cytoplasm of apoptotic cells. Western blotting of total brain homogenates, using the same antibody, shows a p39 band in control rats which is accompanied by a strong, phosphorylated p62 double-band in irradiated animals. In addition, increased c-Jun N-terminal kinase 1 expression, as found on western blots, is found in irradiated rats when compared with controls. Intraperitoneal injection of kainic acid at convulsant doses to the adult rat produces cell death with morphological features of necrosis, together with the appearance of cells with fine granular chromatin degeneration and small numbers of apoptotic-like cells, in the entorhinal and piriform cortices, basal amygdala, certain thalamic nuclei, and CA1 region of the hippocampus. c-Jun expression in kainic acid-treated rats, as revealed with the c-Jun/AP-1 (N) antibody, is found in the nuclei of a minority of cells in the same areas. The vast majority of c-Jun-immunoreactive cells have normal nuclear morphology, whereas necrotic cells are negative and only a few cells with fine granular chromatin condensation and apoptotic cells following kainic acid injection are stained with c-Jun antibodies. Western blotting, using the same antibody, shows a p39 band in control rats, which is accompanied by a band at about p26 from 6 h onwards following kainic acid injection. Decreased c-Jun N-terminal kinase 1 expression, as revealed on western blots, is observed in kainic acid-treated rats.These results show that the antibody c-Jun/AP-1 (N) recognizes three different forms of c-Jun-related immunoreactivity in normal and pathological states, which are associated with the different outcome of cells. These results stress the necessity

  14. Kindling epilepsy models with kainic acid in different parts of rat brain%大鼠脑内不同部位海人酸点燃模型的比较

    Institute of Scientific and Technical Information of China (English)

    刘诤; 王峰; 夏鹤春; 齐江华; 宋子木; 孙涛

    2011-01-01

    Objective To discussion the methods of simpler production and better effect in the kainic acid induced epilepsy model. Methods By stereotactic operation,injection the kainic acid 1.0 μl to the insular, the amygdala and the lateral ventricle of the rats, observing the changes of the behavior, the EEG and the pathology and comparing the ignition characteristic in epileptic rats. Results The change of the behavior, the EEG and the pathology in epileptic rats confirmed that the rats of injection the kainic acid to insular can be successfully established experimental animal models. Compared to the traditional position (injection the kainic acid to amygdala and lateral ventricle) ,the insular ignite group primary seizure time is (59. 96 ±4. 36) min,static duration is(11. 90 ±0. 54) d,significantly faster than the amygdala group and the lateral ventricle group ( P < 0. 05 ). Conclusion The insular has the seizure potency, the kainic acid injection the rat' s insular has the advantages in shortened test cycle and reduced the cost of experiments.%目的 探讨制作简便、效果良好的海人酸(KA)点燃致痫模型方法。方法 立体定向操作下于岛叶、杏仁核和侧脑室局部注射海人酸1.0μl,观察致痫大鼠的行为学和脑电图改变,检测其病理学变化,比较其点燃特征。结果 行为学、脑电图和病理学证实岛叶点燃组与传统致痫(杏仁核、侧脑室)点燃组比较,具有相同的致痫特征;同时,岛叶点燃组初次发作时间为(59.96±4.36)min,静止持续时间为(11.90±0.54)d,明显快于杏仁核组和侧脑室组(P<0.05)。结论 岛叶本身具备致痫潜能,大鼠岛叶海人酸致痫模型具有缩短实验周期、降低实验成本的优势。

  15. Extracellular HMGB1 Modulates Glutamate Metabolism Associated with Kainic Acid-Induced Epilepsy-Like Hyperactivity in Primary Rat Neural Cells

    Directory of Open Access Journals (Sweden)

    Yuji Kaneko

    2017-02-01

    Full Text Available Background/Aims: Neuroinflammatory processes have been implicated in the pathophysiology of seizure/epilepsy. High mobility group box 1 (HMGB1, a non-histone DNA binding protein, behaves like an inflammatory cytokine in response to epileptogenic insults. Kainic acid (KA is an excitotoxic reagent commonly used to induce epilepsy in rodents. However, the molecular mechanism by which KA-induced HMGB1 affords the initiation of epilepsy, especially the role of extracellular HMGB1 in neurotransmitter expression, remains to be elucidated. Methods: Experimental early stage of epilepsy-related hyperexcitability was induced in primary rat neural cells (PRNCs by KA administration. We measured the localization of HMGB1, cell viability, mitochondrial activity, and expression level of glutamate metabolism-associated enzymes. Results: KA induced the translocation of HMGB1 from nucleus to cytosol, and its release from the neural cells. The translocation is associated with post-translational modifications. An increase in extracellular HMGB1 decreased PRNC cell viability and mitochondrial activity, downregulated expression of glutamate decarboxylase67 (GAD67 and glutamate dehydrogenase (GLUD1/2, and increased intracellular glutamate concentration and major histocompatibility complex II (MHC II level. Conclusions: That a surge in extracellular HMGB1 approximated seizure initiation suggests a key pathophysiological contribution of HMGB1 to the onset of epilepsy-related hyperexcitability.

  16. Neuronal degeneration and a decrease in laminin-like immunoreactivity is associated with elevated tissue-type plasminogen activator in the rat hippocampus after kainic acid injection.

    Science.gov (United States)

    Nagai, N; Urano, T; Endo, A; Takahashi, H; Takada, Y; Takada, A

    1999-02-01

    Tissue-type plasminogen activator (tPA) is a serine protease that converts the inactive precursor plasminogen to the active protease plasmin. In the central nervous system, tPA has been suggested to participate in plasticity, memory and the neuronal degeneration caused by excitotoxins, but its precise functions during these processes are still unclear. We show in this report that tPA antigen level and extracellular tPA activity increased in the hippocampus during the early stages of neuronal degeneration in the CA3 region following the injection of kainic acid (KA) into the lateral cerebral ventricles. The increase in tPA antigen level was transient and its peak was at 4 h after the injection. tPA activity was also increased 4 h after the injection, but it remained at a high level for more than 8 h. Histological zymography showed that the increase in tPA activity was mainly localized in the CA3 region. In the same region, the disappearance of interneuronal laminin-like immunoreactivity and atrophic changes in pyramidal neurons were observed 4 h after the injection of KA. These results suggested that such focal and transient increases in tPA synthesis and release, which result in the proteolysis of laminin through plasminogen activation, could be involved in the neuronal degeneration in the CA3 region after the injection of KA.

  17. Nuclear Factor-Kappa B Activity Regulates Brain Expression of P-Glycoprotein in the Kainic Acid-Induced Seizure Rats

    Directory of Open Access Journals (Sweden)

    Nian Yu

    2011-01-01

    Full Text Available This study was aimed to investigate the effect of NF-κB activity on the seizure susceptibility, brain damage, and P-gp expression in kainic acid- (KA- induced seizure rats. Male SD rats were divided into saline control group (NS group, KA induced epilepsy group (EP group, and epilepsy group intervened with NF-κB inhibitor-pyrrolidine dithiocarbamate salt (PDTC group or with dexamethasone (DEX group. No seizures were observed in the rats of NS group. Compared with NS group, increased P-gp expression and NF-κB activation in the rat brain of the EP group were observed after KA micro-injection. Both PDTC and DEX pre-treatment significantly increased the latency to grade III or V seizure onset compared to EP group but failed to show neuron-protective effect as the number of survival neurons didn't significantly differ from that in EP group. Furthermore, PDTC pre-treatment significantly decreased P-gp expression along with NF-κB activation in the hippocampus CA3 area and amygdala complex of rats compared with the EP group, implying that NF-κB activation involved in the seizure susceptibility and seizure induced brain P-gp over-expression. Additionally, DEX pre-treatment only decreased P-gp expression level without inhibition of NF-κB activation, suggesting NF-κB independent pathway may also participate in regulating seizure induced P-gp over-expression.

  18. Mitochondrial and nuclear damages and caspase-3 expression in the hippicampal CA3 region of rats with kainic acid induced status epilepticus

    Institute of Scientific and Technical Information of China (English)

    Shuhai Tang; Jianying Sun; Xiaojun Pan; Li Zhang

    2006-01-01

    BACKGROUND: Some scholars believed that the neuronal injury after status epilepticus is apoptosis,the main evidence is the changes of expressions of various apoptosis releted genes,such as immediate-early gene,p53 gene and genes of bcl-2 family,etc.But there is still no ultrastructural evidence for apoptosis.OBJECTIVE: To observe the ultrastructural damages of mitochondrion and nucleus and the changes of caspase expression in neurons of hippocampal CA3 region in rats with status epilepticus induced by kainic acid.DESIGN: A randomized controlled study.SETTING: Department of Anesthesiology and Department of Neurology,Qilu Hospital of Shandong University.MATERIALS: Seventy-five adult male Wistar rats of 250-300 g.clean degree,were provided by the experimental animal center of Shandong University.Kainic acid was purchased from Sigma Company (USA);rabbit anti-rat polyclonal antibody caspase-3 from Santa Cruz Company(USA).METHODS:The experiments were carried out in the Department of Anesthesiology,Qilu Hospital of Shandong University from October 2005 to February 2006.①The 75 rats were randomly divided into experimental group (n=45)and control group(n=30).②Model establishment,convulsion grading and the judging standards for status epilepticus:Rats in the experimental group were given intraperitoneal injection of kainic acid(10 mg/kg),and those in the control group were injected with saline of the same volume.The time of seizure was recorded and their behavioral manifestations were observed,and the seizure was terminated by intraperitoneal injection of diazepam(10 mg/kg).③Observation under electron microscope:At 3, 12 and 24 hours after status epilepticus respectively,bilateral hippocampal tissues were taken out,semithin sections of about 75 nm were prepared after fixation,dehydration and embedding,and then observed under H-800 transmission electron microscope.④Immunohistochemical detection:Bilateral hippocampi were removed at 3,12 and 24 hours after status

  19. Acute reduction of neuronal RNA binding Elavl2 protein and Gap43 mRNA in mouse hippocampus after kainic acid treatment.

    Science.gov (United States)

    Ohtsuka, Takafumi; Yano, Masato; Okano, Hideyuki

    2015-10-09

    Activity-dependent gene regulation in neurons has been hypothesized to be under transcriptional control and to include dramatic increases in immediate early genes (IEGs) after neuronal activity. In addition, several reports have focused on post-transcriptional regulation, which could be mediated by neuronal post-transcriptional regulators, including RNA binding proteins (RNABPs). One such protein family is the neuronal Elavls (nElavls; Elavl2, Elavl3, and Elavl4), whose members are widely expressed in peripheral and central nervous system. Previous reports showed that Elavl3 and 4 are up-regulated following repeated stimulation such as during cocaine administration, a seizure, or a spatial discrimination task. In this study, we focused on Elavl2, a candidate gene for schizophrenia and studied its role in neuronal activity. First we found that Elavl2 has a cell-type specific expression pattern that is highly expressed in hippocampal CA3 pyramidal neurons and hilar interneurons using Elavl2 specific antibody. Second, unexpectedly, we discovered that the Elavl2 protein level in the hippocampus was acutely down-regulated for 3 h after a kainic acid (KA)-induced seizure in the hippocampal CA3 region. In addition, level of Gap43 mRNA, a target mRNA of Elavl2 is decreased 12 h after KA treatment, thus suggesting the involvement of Elavl2 in activity-dependent RNA regulation.

  20. Exercise, but not environmental enrichment, improves learning after kainic acid-induced hippocampal neurodegeneration in association with an increase in brain-derived neurotrophic factor.

    Science.gov (United States)

    Gobbo, O L; O'Mara, S M

    2005-04-15

    Previous studies have suggested that exercise in a running wheel can be neuroprotective, perhaps due to, among others, gene-expression changes after exercise, increases in trophic proteins and/or enhanced cardiovascular responsivity. Here we ask whether physical exercise or environmental enrichment provide protection after brain damage, especially in terms of recovery of cognitive function. To evaluate the neuroprotective effect of these conditions, we used the kainic acid (KA) model of neuronal injury. Systemically-administered KA induces excitotoxicity by overstimulation of glutamate receptors, resulting in neuronal death by necrosis and apoptosis. Our results show that exercise, but not enriched environment, prior to KA-induced brain damage, improved behavioural performance in both Morris watermaze and object exploration tasks. However, prior exercise did not decrease to control levels the hyperactivity normally seen in KA-treated animals, as measured by ambulation in the open field. Furthermore, both exercise and enriched environment did not protect against neuron loss in CA1, CA2 and CA3 areas of the hippocampus, despite a substantial increase in brain-derived neutrophic factor (BDNF) levels in dentate gyrus of the exercise and KA-treated animals.

  1. Role of gamma-aminobutyricacidB(GABA(B)) receptors in the regulation of kainic acid-induced cell death in mouse hippocampus.

    Science.gov (United States)

    Lee, Han Kyu; Seo, Young Jun; Choi, Seong Soo; Kwon, Min Soo; Shim, Eon Jeong; Lee, Jin Young; Suh, Hong Won

    2005-12-31

    Kainic acid (KA) is well-known as an excitatory, neurotoxic substance. In mice, KA administered intracerebroventricularly (i.c.v.) lead to morphological damage of hippocampus expecially concentrated on the CA3 pyramidal neurons. In the present study, the possible role of gamma-aminobutyric acid B (GABA(B)) receptors in hippocampal cell death induced by KA (0.1 microg) administered i.c.v. was examined. 5-Aminovaleric acid (5-AV; GABA(B) receptors antagonist, 20 mug) reduced KA-induced CA3 pyramidal cell death. KA increased the phosphorylated extracellular signal-regulated kinase (p-ERK) and Ca(2+)/calmodulin-dependent protein kinase II (p-CaMK II) immunoreactivities (IRs) 30 min after KA treatment, and c-Fos, c-Jun IR 2 h, and glial fibrillary acidic protein (GFAP), complement receptor type 3 (OX-42) IR 1 day in hippocampal area in KA-injected mice. 5-AV attenuated KA-induced p-CaMK II, GFAP and OX-42 IR in the hippocampal CA3 region. These results suggest that p-CaMK II may play as an important regulator on hippocampal cell death induced by KA administered i.c.v. in mice. Activated astrocytes, which was presented by GFAP IR, and activated microglia, which was presented by the OX-42 IR, may be a good indicator for measuring the cell death in hippocampal regions by KA excitotoxicity. Furthermore, it showed that GABA(B) receptors appear to be involved in hippocampal CA3 pyramidal cell death induced by KA administered i.c.v. in mice.

  2. Systemic injection of kainic acid: Gliosis in olfactory and limbic brain regions quantified with ( sup 3 H)PK 11195 binding autoradiography

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    Altar, C.A.; Baudry, M. (Genentech, Inc., South San Francisco, CA (USA))

    1990-09-01

    Neurodegenerative diseases may result from excessive stimulation of excitatory amino acid receptors by endogenous ligands. Because neuronal degeneration is associated with glial proliferation and hypertrophy, the degenerative changes throughout rat brain following the systemic administration of kainic acid (12 mg/kg) were mapped with quantitative autoradiography of (3H)PK 11195. This radioligand binds to a mitochondrial benzodiazepine binding site (MBBS) on microglia and astrocytes. Analysis of eight horizontal and four coronal brain levels revealed up to 16-fold increases in (3H)PK 11195 binding from 1 to 5 weeks but not 1 day after kainate injection. Increases in (3H)PK 11195 binding were predominantly in ventral limbic brain regions and olfactory projections to neocortical areas, with the olfactory cortex greater than subiculum/CA1 greater than anterior olfactory nucleus, medial thalamic nucleus, and piriform cortex greater than cingulate cortex and rostral hippocampus greater than dentate gyrus, septum, and amygdala greater than entorhinal cortex and temporal cortex. Little or no enhancement of (3H)PK 11195 binding was observed in numerous regions including the caudate-putamen, substantia nigra, nucleus accumbens, olfactory tubercle, cerebellum, thalamic nuclei, choroid plexus, medulla, parietal or occipital cortex, or pons. A 2-fold greater extent of neurodegeneration was obtained in ventral portions of the olfactory bulb, entorhinal cortex, temporal cortex, and dentate gyrus compared with the dorsal portions of these structures. The pattern of increase in (3H)PK 11195 binding closely matched the patterns of neuronal degeneration reported following parenteral kainate injection. These findings strengthen the notion that quantitative autoradiography of (3H)PK 11195 is a valuable tool to quantify the extent of neuronal degeneration.

  3. Alleviation of Kainic Acid-Induced Brain Barrier Dysfunction by 4-O-Methylhonokiol in In Vitro and In Vivo Models

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    Jin-Yi Han

    2015-01-01

    Full Text Available This experiment was designed to investigate whether 4-O-methylhonokiol (MH, a principal ingredient of Magnolia (M. officinalis bark, alleviated acute intraperitoneal (i.p. kainic acid- (KA- induced brain blood barrier dysfunction (BBBD via pathological examination and cytological analyses of the brain tissues of mice. KA (10–30 mg/kg time- and dose-dependently increased the water content of brain tissues and induced edema and encephalopathy. However, pretreatment with MH (5 and 20 mg/kg, i.p. significantly reduced the water content of the brain compared to that observed in the KA control group. Furthermore, MH significantly and dose-dependently reversed the remarkable variations in evan’s blue dye (EBD staining and malondialdehyde (MDA levels that were induced by KA (10 mg/kg, i.p.. MH also decreased the elevated seizure scores that were induced by KA (10 mg/kg, i.p. in mice in a manner similar to scavengers such as DMTU and trolox. Additionally, MH significantly scavenged intracellular ROS and Ca2+ within hippocampal cells. The tight junction seals mediated by claudin (Cld-5 were also found to be modulated by MH. MH efficiently reduced 1,1-diphenyl-2-picrylhydrazyl (DPPH (IC50, 52.4 mM and •OH with an electron spin resonance (ESR signal rate constant of 4×109 M-1·S-1, which is close to the reactivity of the vitamin E analog trolox. Taken together, these results suggest that MH may enhance radical scavenging in lipid and hydrophobic environments, which may be important for the physiological activity of the barrier.

  4. Kainic acid-induced neurodegeneration and activation of inflammatory processes in organotypic hippocampal slice cultures: treatment with cyclooxygenase-2 inhibitor does not prevent neuronal death.

    Science.gov (United States)

    Järvelä, Juha T; Ruohonen, Saku; Kukko-Lukjanov, Tiina-Kaisa; Plysjuk, Anna; Lopez-Picon, Francisco R; Holopainen, Irma E

    2011-06-01

    In the postnatal rodent hippocampus status epilepticus (SE) leads to age- and region-specific excitotoxic neuronal damage, the precise mechanisms of which are still incompletely known. Recent studies suggest that the activation of inflammatory responses together with glial cell reactivity highly contribute to excitotoxic neuronal damage. However, pharmacological tools to attenuate their activation in the postnatal brain are still poorly elucidated. In this study, we investigated the role of inflammatory mediators in kainic acid (KA)-induced neuronal damage in organotypic hippocampal slice cultures (OHCs). A specific cyclooxygenase-2 (COX-2) inhibitor N-[2-(cyclohexyloxy)-4-nitrophenyl]-methanesulfonamide (NS-398) was used to study whether or not it could ameliorate neuronal death. Our results show that KA treatment (24 h) resulted in a dose-dependent degeneration of CA3a/b pyramidal neurons. Furthermore, COX-2 immunoreactivity was pronouncedly enhanced particularly in CA3c pyramidal neurons, microglial and astrocyte morphology changed from a resting to active appearance, the expression of the microglial specific protein, Iba1, increased, and prostaglandin E₂ (PGE₂) production increased. These indicated the activation of inflammatory processes. However, the expression of neither proinflammatory cytokines, i.e. tumour necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β), nor the anti-inflammatory cytokine IL-10 mRNA was significantly altered by KA treatment as studied by real-time PCR. Despite activation of an array of inflammatory processes, neuronal damage could not be rescued either with the combined pre- and co-treatment with a specific COX-2 inhibitor, NS-398. Our results suggest that KA induces activation of a repertoire of inflammatory processes in immature OHCs, and that the timing of anti-inflammatory treatment to achieve neuroprotection is a challenge due to developmental properties and the complexity of inflammatory processes activated by

  5. Sesamin ameliorates oxidative stress and mortality in kainic acid-induced status epilepticus by inhibition of MAPK and COX-2 activation

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    Lin Ching-Huei

    2011-05-01

    Full Text Available Abstract Background Kainic acid (KA-induced status epilepticus (SE was involved with release of free radicals. Sesamin is a well-known antioxidant from sesame seeds and it scavenges free radicals in several brain injury models. However the neuroprotective mechanism of sesamin to KA-induced seizure has not been studied. Methods Rodents (male FVB mice and Sprague-Dawley rats were fed with sesamin extract (90% of sesamin and 10% sesamolin, 15 mg/kg or 30 mg/kg, for 3 days before KA subcutaneous injection. The effect of sesamin on KA-induced cell injury was also investigated on several cellular pathways including neuronal plasticity (RhoA, neurodegeneration (Caspase-3, and inflammation (COX-2 in PC12 cells and microglial BV-2 cells. Results Treatment with sesamin extract (30 mg/kg significantly increased plasma α-tocopherol level 50% and 55.8% from rats without and with KA treatment, respectively. It also decreased malondialdehyde (MDA from 145% to 117% (p = 0.017 and preserved superoxide dismutase from 55% of the vehicle control mice to 81% of sesamin-treated mice, respectively to the normal levels (p = 0.013. The treatment significantly decreased the mortality from 22% to 0% in rats. Sesamin was effective to protect PC12 cells and BV-2 cells from KA-injury in a dose-dependent manner. It decreased the release of Ca2+, reactive oxygen species, and MDA from PC12 cells. Western blot analysis revealed that sesamin significantly reduced ERK1/2, p38 mitogen-activated protein kinases, Caspase-3, and COX-2 expression in both cells and RhoA expression in BV-2 cells. Furthermore, Sesamin was able to reduce PGE2 production from both cells under KA-stimulation. Conclusions Taken together, it suggests that sesamin could protect KA-induced brain injury through anti-inflammatory and partially antioxidative mechanisms.

  6. Intracisternal delivery of NFkappaB-inducible scAAV2/9 reveals locoregional neuroinflammation induced by systemic kainic acid treatment.

    Directory of Open Access Journals (Sweden)

    Olivier eBockstael

    2014-12-01

    Full Text Available We have previously demonstrated disease-dependent gene delivery in the brain using an AAV vector responding to NFB activation as a probe for inflammatory responses. This vector, injected focally in the parenchyma prior to a systemic kainic acid (KA injection mediated inducible transgene expression in the hippocampus but not in the cerebellum, regions respectively known to be affected or not by the pathology. However, such a focal approach relies on previous knowledge of the model parameters and does not allow to predict the whole brain response to the disease. Global brain gene delivery would allow to predict the regional distribution of the pathology as well as to deliver therapeutic factors in all affected brain regions.We show that self-complementary AAV2/9 (scAAV2/9 delivery in the adult rat cisterna magna allows a widespread but not homogenous transduction of the brain. Indeed, superficial regions, i.e. cortex, hippocampus and cerebellum were more efficiently transduced than deeper regions, such as striatum, and substantia nigra. These data suggest that viral particles penetration from the cerebrospinal fluid (CSF into the brain is a limiting factor. Interestingly, AAV2/9-2YF a rationally-designed capsid mutant (affecting surface tyrosines increased gene transfer efficiency approx. 5-fold. Neurons, astrocytes and oligodendrocytes, but not microglia, were transduced in varying proportions depending on the brain region and the type of capsid.Finally, after a single intracisternal injection of scAAV2/9-2YF using the NFB-inducible promoter, KA treatment induced transgene expression in the hippocampus and cortex but not in the cerebellum, corresponding to the expression of the CD11b marker of microglial activation.These data support the use of disease-inducible vectors administered in the cisterna magna as a tool to characterize the brain pathology in systemic drug-induced or transgenic disease models. However, further improvements are

  7. Comparison of short-term effects of midazolam and lorazepam in the intra-amygdala kainic acid model of status epilepticus in mice.

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    Diviney, Mairead; Reynolds, James P; Henshall, David C

    2015-10-01

    Benzodiazepines remain as the first-line treatment for status epilepticus (SE), but debate continues as to the choice and delivery route of pharmacotherapy. Lorazepam is currently the preferred anticonvulsant for clinical use, but midazolam has become a popular alternative, particularly as it can be given by nonintravenous routes. Anticonvulsants are also commonly used to terminate SE in animal models. Here, we aimed to compare the efficacy of midazolam with that of lorazepam in an experimental model of focal-onset SE. Status epilepticus was induced by intra-amygdala microinjection of kainic acid in 8week old C57Bl/6 mice. Forty minutes later, mice were treated with an intraperitoneal injection of either lorazepam or midazolam (8mg/kg). Electroencephalogram (EEG) activity, histology, and behavioral tests assessing recovery of function were evaluated and compared between groups. Intraperitoneal injection of either lorazepam or midazolam resulted in similar patterns of reduced EEG epileptiform activity during 1-hour recordings. Damage to the hippocampus and presentation of postinsult anxiety-related behavior did not significantly differ between treatment groups at 72h. However, return of normal behaviors such as grooming, levels of activity, and the evaluation of overall recovery of SE mice were all superior at 24h in animals given midazolam compared with lorazepam. Our results indicate that midazolam is as effective as lorazepam as an anticonvulsant in this model while also providing improved animal recovery after SE. These data suggest that midazolam might be considered by researchers as an anticonvulsant in animal models of SE, particularly as it appears to satisfy the requirements of refining procedures involving experimental animals at early time-points after SE.

  8. Protein tyrosine kinase inhibitors modify kainic acid-induced epileptiform activity and mossy fiber sprouting but do not protect against limbic cell death

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    C.M. Queiroz

    2008-05-01

    Full Text Available Intrahippocampal administration of kainic acid (KA induces synaptic release of neurotrophins, mainly brain-derived neurotrophic factor, which contributes to the acute neuronal excitation produced by the toxin. Two protein tyrosine kinase inhibitors, herbimycin A and K252a, were administered intracerebroventricularly, in a single dose, to attenuate neurotrophin signaling during the acute effects of KA, and their role in epileptogenesis was evaluated in adult, male Wistar rats weighing 250-300 g. The latency for the first Racine stage V seizure was 90 ± 8 min in saline controls (N = 4 which increased to 369 ± 71 and 322 ± 63 min in animals receiving herbimycin A (1.74 nmol, N = 4 and K252a (10 pmol, N = 4, respectively. Behavioral alterations were accompanied by diminished duration of EEG paroxysms in herbimycin A- and K252a-treated animals. Notwithstanding the reduction in seizure severity, cell death (60-90% of cell loss in KA-treated animals in limbic regions was unchanged by herbimycin A and K252a. However, aberrant mossy fiber sprouting was significantly reduced in the ipsilateral dorsal hippocampus of K252a-treated animals. In this model of temporal lobe epilepsy, both protein kinase inhibitors diminished the acute epileptic activity triggered by KA and the ensuing morphological alterations in the dentate gyrus without diminishing cell loss. Our current data indicating that K252a, but not herbimycin, has an influence over KA-induced mossy fiber sprouting further suggest that protein tyrosine kinase receptors are not the only factors which control this plasticity. Further experiments are necessary to elucidate the exact signaling systems associated with this K252a effect.

  9. Changes in brain glucose use and extracellular ions associated with kainic acid-induced seizures: (/sup 14/C)-2-deoxyglucose and intracranial

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    Chastain, J.E Jr.

    1986-01-01

    The effect of kainic acid (KA) on brain glucose use with coadministration of diazepam, and the effect of KA on brain extracellular (K/sup +/), Ca/sup 2 +/), and (Na/sup +/) was investigated in rats by means of (/sup 14/C)-2-deoxyglucose (2-DG) and intracranial microdialysis, respectively. Also, the impact of intracranial microdialysis on brain regional metabolic function was studied. Co-treatment with KA and diazepam attenuated KA-induced 3 hr increases and prevented 48 hr decreases in glucose use within all structures measured, particularly the piriform cortex and amygdala. Hippocampal CA/sub 3/, CA/sub 4/, and CA/sub 1/-ventral were least affected by diazepam. The results suggest that diazepam suppresses KA seizure spread from its focus, proposed to be CA/sub 3/. KA-induced ions changes were studied by intracranial microdialysis. Dialysis fibers were implanted within the hippocampus or piriform cortex and perfused 24 hr later. Samples, collected before and after KA, were analyzed for (K/sup +/), (Ca/sup 2 +/), and (Na/sup +/). KA caused an early and prolonged increase in extracellular (K/sup +/) and a negligible decrease in (Ca/sup 2 +/) within the hippocampus. In the piriform cortex, both (K/sup +/) and (Na/sup +/) increase during a period of early seizure signs. The results indicate that ion homostatic control of ion levels is better maintained during parenteral KA-induced seizures than when the brain is activated locally or during ischemia/hypoxia. The effect of intracranial microdialysis was studied by means of 2-DG in control state and KA-induced seizure state. The results indicate that intracranial microdialysis alters brain metabolic function during KA-induced seizures, but not in the control state. At 3 hr post KA, seizure metabolic activity was enhanced within the piriform cortex, and attenuated within the hippocampus.

  10. Changes in /sup 3/H-substance P receptor binding in the rat brain after kainic acid lesion of the corpus striatum

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    Mantyh, P.W.; Hunt, S.P.

    1986-06-01

    Previous studies have indicated that the substantia nigra contains the highest concentration of substance P-like immunoreactivity (SPLI) in the brain. Paradoxically, it also appears to contain one of the lowest concentrations of substance P receptors in the brain. One possibility is that the massive amount of SPLI blocks the binding of the radioligand to the substance P receptor and/or down-regulates the number of substance P receptors present in this structure. Since greater than 95% of the SPLI within the substantia nigra originates from the corpus striatum, we have lesioned this area and measured the changes in substance P receptor concentration in the substantia nigra and other corpus striatal projection areas. A semiquantitative autoradiographic technique for measuring the binding of /sup 3/H-substance P to substance P receptors was used in conjunction with tritium-sensitive film. 3H-substance P binding was measured in both the corpus striatum and its projection areas after kainic acid lesion of the corpus striatum. At either 4 or 21 d after the lesion there was approximately a 90% loss of substance P receptors in the rostral striatum, a 74% loss in the globus pallidus, a 57% increase in receptor number in lamina I and II of the ipsilateral somatosensory cortex, and no apparent change in the number of receptors in the substantia nigra pars reticulata, superior colliculus, and central gray. These findings suggest that the low concentration of substance P receptors found within the substantia nigra is not due the massive SPLI innervation, since removal of greater than 95% of the SPLI had no measurable effect on the concentration of substance P receptors.

  11. Changes and overlapping distribution in the expression of CB1/OX1-GPCRs in rat hippocampus by kainic acid-induced status epilepticus.

    Science.gov (United States)

    Zhu, Fei; Wang, Xiang-Qing; Chen, Ya-Nan; Yang, Nan; Lang, Sen-Yang; Zuo, Ping-Ping; Zhang, Jia-Tang; Li, Rui-Sheng

    2015-02-09

    Status epilepticus (SE) is a life-threatening neurological disorder. It is important to discover new drugs to control SE without the development of pharmacoresistance. Focus on the cannabinoid receptor and cannabinoid-related compounds might be a good option. Cannabinoid receptor 1 (CB1) and orexin receptor 1 (OX1) both belong to the GPCR superfamily and display "cross-talk" interactions, however, there has been no study of the effect of OX1/CB1 in epilepsy. Therefore, we investigated the potential long-term effects of SE on CB1 and OX1 expression in rat hippocampus, aiming to elucidate whether they are involved in the causative mechanism of epilepsy and whether they might form a heterodimer. In this study, SE was induced with kainic acid, and results of immunohistochemistry and RT-PCR both showed that the expression of CB1 in the hippocampus increased after SE and was significantly higher compared to controls especially 1 week post-SE. However we did not find any significant difference in the expression of OX1 between the SE group and the controls at any time. Under immunofluorescence staining, we observed an overlapping distribution of CB1 and OX1 in the hippocampus. The increased expression of CB1 in the hippocampus indicates that CB1 may play an important role in the underlying mechanism of SE, but the effect of OX1 was not obvious. The overlapping distribution of CB1 and OX1 in the hippocampus indicates that they may form a heterodimer to exert their effect in epilepsy.

  12. Neuronal deletion of caspase 8 protects against brain injury in mouse models of controlled cortical impact and kainic acid-induced excitotoxicity.

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    Maryla Krajewska

    Full Text Available Acute brain injury is an important health problem. Given the critical position of caspase 8 at the crossroads of cell death pathways, we generated a new viable mouse line (Ncasp8(-/-, in which the gene encoding caspase 8 was selectively deleted in neurons by cre-lox system.Caspase 8 deletion reduced rates of neuronal cell death in primary neuronal cultures and in whole brain organotypic coronal slice cultures prepared from 4 and 8 month old mice and cultivated up to 14 days in vitro. Treatments of cultures with recombinant murine TNFα (100 ng/ml or TRAIL (250 ng/mL plus cyclohexamide significantly protected neurons against cell death induced by these apoptosis-inducing ligands. A protective role of caspase 8 deletion in vivo was also demonstrated using a controlled cortical impact (CCI model of traumatic brain injury (TBI and seizure-induced brain injury caused by kainic acid (KA. Morphometric analyses were performed using digital imaging in conjunction with image analysis algorithms. By employing virtual images of hundreds of brain sections, we were able to perform quantitative morphometry of histological and immunohistochemical staining data in an unbiased manner. In the TBI model, homozygous deletion of caspase 8 resulted in reduced lesion volumes, improved post-injury motor performance, superior learning and memory retention, decreased apoptosis, diminished proteolytic processing of caspases and caspase substrates, and less neuronal degeneration, compared to wild type, homozygous cre, and caspase 8-floxed control mice. In the KA model, Ncasp8(-/- mice demonstrated superior survival, reduced seizure severity, less apoptosis, and reduced caspase 3 processing. Uninjured aged knockout mice showed improved learning and memory, implicating a possible role for caspase 8 in cognitive decline with aging.Neuron-specific deletion of caspase 8 reduces brain damage and improves post-traumatic functional outcomes, suggesting an important role for this

  13. Asymmetric aza-[2,3]-Wittig sigmatropic rearrangements: chiral auxiliary control and formal asymmetric synthesis of (2S, 3R, 4R)-4-hydroxy-3-methylproline and (-)-kainic acid.

    Science.gov (United States)

    Anderson, James C; O'Loughlin, Julian M A; Tornos, James A

    2005-08-07

    A survey of 16 different chiral auxiliaries and a variety of strategies found that an (-)-8-phenylmenthol ester of a glycine derived migrating group can control the absolute stereochemistry of aza-[2,3]-Wittig sigmatropic rearrangements with diastereoselectivities of ca. 3 : 1 with respect to the auxiliary. In two specific examples, ca. 50% yields of enantiomerically pure products were obtained after chromatographic purification. These were synthetically manipulated with no erosion of stereochemistry into intermediates that completed formal asymmetric syntheses of (+)-HyMePro and (-)-kainic acid.

  14. Management of familial Mediterranean fever by colchicine does not normalize the altered profile of microbial long chain fatty acids in the human metabolome

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    Zhanna eKtsoyan

    2013-01-01

    Full Text Available In our previous works we established that in an autoinflammatory condition, familial Mediterranean fever, the gut microbial diversity is specifically restructured, which also results in the altered profiles of microbial long chain fatty acids (LCFAs present in the systemic metabolome. The mainstream management of the disease is based on oral administration of colchicine to suppress clinical signs and extend remission periods and our aim was to determine whether this therapy normalizes the microbial LCFA profiles in the metabolome as well. Unexpectedly, the treatment does not normalize these profiles. Moreover, it results in the formation of new distinct microbial LCFA clusters, which are well separated from the corresponding values in healthy controls and FMF patients without the therapy. We hypothesize that the therapy alters the proinflammatory network specific for the disease, with the concomitant changes in gut microbiota and the corresponding microbial LCFAs in the metabolome.

  15. Management of familial Mediterranean fever by colchicine does not normalize the altered profile of microbial long chain fatty acids in the human metabolome.

    Science.gov (United States)

    Ktsoyan, Zhanna A; Beloborodova, Natalia V; Sedrakyan, Anahit M; Osipov, George A; Khachatryan, Zaruhi A; Manukyan, Gayane P; Arakelova, Karine A; Hovhannisyan, Alvard I; Arakelyan, Arsen A; Ghazaryan, Karine A; Zakaryan, Magdalina K; Aminov, Rustam I

    2013-01-01

    In our previous works we established that in an autoinflammatory condition, familial Mediterranean fever (FMF), the gut microbial diversity is specifically restructured, which also results in the altered profiles of microbial long chain fatty acids (LCFAs) present in the systemic metabolome. The mainstream management of the disease is based on oral administration of colchicine to suppress clinical signs and extend remission periods and our aim was to determine whether this therapy normalizes the microbial LCFA profiles in the metabolome as well. Unexpectedly, the treatment does not normalize these profiles. Moreover, it results in the formation of new distinct microbial LCFA clusters, which are well separated from the corresponding values in healthy controls and FMF patients without the therapy. We hypothesize that the therapy alters the proinflammatory network specific for the disease, with the concomitant changes in gut microbiota and the corresponding microbial LCFAs in the metabolome.

  16. An electron spin resonance study for real-time detection of ascorbyl free radicals after addition of dimethyl sulfoxide in murine hippocampus or plasma during kainic acid-induced seizures.

    Science.gov (United States)

    Matsumoto, Shigekiyo; Shingu, Chihiro; Koga, Hironori; Hagiwara, Satoshi; Iwasaka, Hideo; Noguchi, Takayuki; Yokoi, Isao

    2010-07-01

    Electron spin resonance (ESR)-silent ascorbate solutions generate a detectable, likely concentration-dependent signal of ascorbyl free radicals (AFR) immediately upon addition of a molar excess of dimethyl sulfoxide (DMSO). We aimed to perform quantitative ESR analysis of AFR in real time after addition of DMSO (AFR/DMSO) to evaluate ascorbate concentrations in fresh hippocampus or plasma following systemic administration of kainate in mice. Use of a special tissue-type quartz cell allowed immediate detection of AFR/DMSO ESR spectra in fresh tissues from mice. AFR/DMSO content was increased significantly in fresh hippocampus or plasma obtained during kainate-induced seizures of mice, reaching maximum levels at 90 min after intraperitoneal administration of 50 mg/kg kainic acid. This suggests that oxidative injury of the hippocampus resulted from the accumulation of large amounts of ascorbic acid in the brain after kainic acid administration. AFR/DMSO content measured on an ESR spectrometer can be used for real-time evaluation of ascorbate content in fresh tissue. Due to the simplicity, good performance, low cost and real-time monitoring of ascorbate, this method may be applied to clinical research and treatment in the future.

  17. The neuroprotective efficacy of cell-penetrating peptides TAT, penetratin, Arg-9, and Pep-1 in glutamic acid, kainic acid, and in vitro ischemia injury models using primary cortical neuronal cultures.

    Science.gov (United States)

    Meloni, Bruno P; Craig, Amanda J; Milech, Nadia; Hopkins, Richard M; Watt, Paul M; Knuckey, Neville W

    2014-03-01

    Cell-penetrating peptides (CPPs) are small peptides (typically 5-25 amino acids), which are used to facilitate the delivery of normally non-permeable cargos such as other peptides, proteins, nucleic acids, or drugs into cells. However, several recent studies have demonstrated that the TAT CPP has neuroprotective properties. Therefore, in this study, we assessed the TAT and three other CPPs (penetratin, Arg-9, Pep-1) for their neuroprotective properties in cortical neuronal cultures following exposure to glutamic acid, kainic acid, or in vitro ischemia (oxygen-glucose deprivation). Arg-9, penetratin, and TAT-D displayed consistent and high level neuroprotective activity in both the glutamic acid (IC50: 0.78, 3.4, 13.9 μM) and kainic acid (IC50: 0.81, 2.0, 6.2 μM) injury models, while Pep-1 was ineffective. The TAT-D isoform displayed similar efficacy to the TAT-L isoform in the glutamic acid model. Interestingly, Arg-9 was the only CPP that displayed efficacy when washed-out prior to glutamic acid exposure. Neuroprotection following in vitro ischemia was more variable with all peptides providing some level of neuroprotection (IC50; Arg-9: 6.0 μM, TAT-D: 7.1 μM, penetratin/Pep-1: >10 μM). The positive control peptides JNKI-1D-TAT (JNK inhibitory peptide) and/or PYC36L-TAT (AP-1 inhibitory peptide) were neuroprotective in all models. Finally, in a post-glutamic acid treatment experiment, Arg-9 was highly effective when added immediately after, and mildly effective when added 15 min post-insult, while the JNKI-1D-TAT control peptide was ineffective when added post-insult. These findings demonstrate that different CPPs have the ability to inhibit neurodamaging events/pathways associated with excitotoxic and ischemic injuries. More importantly, they highlight the need to interpret neuroprotection studies when using CPPs as delivery agents with caution. On a positive note, the cytoprotective properties of CPPs suggests they are ideal carrier molecules to

  18. Pregnane X Receptor Not Nuclear Factor-kappa B Up-regulates P-glycoprotein Expression in the Brain of Chronic Epileptic Rats Induced by Kainic Acid.

    Science.gov (United States)

    Yu, Nian; Zhang, Yan-Fang; Zhang, Kang; Cheng, Yong-Fei; Ma, Hai-Yan; Di, Qing

    2017-03-16

    Drug-resistance epilepsy (DRE) is attributed to the brain P-glycoprotein (P-gp) overexpression. We previously reported that nuclear factor-kappa B (NF-κB) played a critical role in regulating P-gp expression at the brain of the acute seizure rats. This study was extended further to investigate the interaction effect of NF-κB and pregnane X receptor (PXR) on P-gp expression at the brain of chronic epileptic rats treated with carbamazepine (CBZ). The chronic epileptic models were induced by the micro-injection of kainic acid (KA) into rats' hippocampus. Subsequently, the successful models were treated with different intervention agents of CBZ; PMA(a non-specific PXR activity inhibitor) or PDTC(a specific NF-κB activity inhibitor) respectively. The expression levels of P-gp and its encoded gene mdr1a/b were significantly up-regulated on the brain of KA-induced chronic epilepsy rats or the epilepsy rats treated with CBZ for 1 week, meanwhile with a high expression of PXR. The treatment of PMA dramatically reduced both PXR and P-gp expressions at the protein and mRNA levels in the chronic epilepsy brain. By compared to the epilepsy model group, the P-gp expression was not markedly attenuated by the inhibition of NF-κB activity with PDTC treatment, nevertheless with a decrease of NF-κB expression in this intervention group. Higher levels of proinflammatory cytokines(IL-1β, IL-6, TNF-α) were found both in the brain tissue and the serum in the epilepsy rats of each group. There was a declined trend of the pro-inflammatory cytokines expression of the PDTC treatment group but with no statistical significance. This study demonstrates for the first time that P-gp up-regulation is due to increase PXR expression in the chronic phase of epilepsy, differently from that NF-κB signaling may induce the P-gp expression in the acute seizure phase. Our results offer insights into the mechanism underlying the development of DRE using or not using CBZ treatment.

  19. 海人酸大鼠癫痫模型的建立%Establishment of epilepsy models in rat by stereotactic injection of kainic acid

    Institute of Scientific and Technical Information of China (English)

    孟凡刚; 孙异临; 张建国; 王忠诚; 刘阿力; 初君盛; 张凯; 马羽; 张斌; 张颖

    2008-01-01

    Objective To investigate the biological characteristic of temporal lobe epilepsy models in rat models established by injection of kainic acid(KA).Methods KA was injected into hippocampus of rat by stereotactic operation.Behavior changes,electrophysiological changes and ultrastructural examination were recorded.Results Typical seizure such as wet-dog shakes,convulsion of forelimb,stumble,and clonic-tonic seizure occurred and was recorded by video recording.Electrocorticography(ECoG)showed multiple epileptic waves and extracellular spike recordings of signal neuron showed extensive spikes with irregular shape.Ultrastructural changes of the hippocampus include denaturalization and pyknosis of neuron,swelling of astrocyte and neurite,mitochondria swell,disintegrate with cristal twist,vascular endothelial cells swell and destruction of blood-brain barrier were displayed with electron microscope.Conclusion Epilepsy model in rats established by stereotactic injection of KA can be regarded as one of the ideal models.%目的 应用海人酸注射建立海人酸大鼠癫痫模型,评价其生物学特性.方法 通过立体定位手术,大鼠海马组织微量注射海人酸,术后观察大鼠行为学表现、电生理改变及海马超微形态结构变化.结果 海人酸注射后实验大鼠出现典型的颞叶癫痫发作过程,表现为湿狗样抖动、前肢抽搐、跌倒以及全身强直-阵挛性发作等,皮层脑电图出现多种形式的痫性放电,单神经元放电细胞外记录显示癫痫模型大鼠放电杂乱,形态不规整.电镜显示神经细胞固缩,星形细胞突起肿胀,神经突触水肿,可见兴奋性递质小泡,线粒体水肿崩解,嵴排列紊乱,血管内皮细胞水肿,血脑屏障破坏.结论 大鼠立体定向海人酸药物注射是一种较理想的癫痫模型.

  20. Expression of sodium channel α subunits 1.1, 1.2 and 1.6 in rat hippocampus after kainic acid-induced epilepsy.

    Science.gov (United States)

    Qiao, Xin; Werkman, Taco R; Gorter, Jan A; Wadman, Wytse J; van Vliet, Erwin A

    2013-09-01

    Voltage-gated Na(+) channels control neuronal excitability and are the primary target for the majority of anti-epileptic drugs. This study investigates the (sub)cellular expression patterns of three important brain-associated Na(+) channel α subunits: NaV1.1, NaV1.2 and NaV1.6 during epileptogenesis (induced by kainic acid) using time points that cover the period from induction to the chronic phase of epilepsy. NaV1.1 immunoreactivity was persistently reduced at 1 day, 3 weeks and 2 months after SE in CA1 and CA3. About 50% of the NaV1.1-positive interneurons was lost at one day after SE in all regions investigated. In the hilus a similar reduction in NeuN-positive neurons was found, while in the CA1 and CA3 region the loss in NeuN-positive neurons only reached 15% in the chronic phase of epilepsy. This implies a stronger shift in the balance between excitation and inhibition toward excitation in the CA1 and CA3 region than in the hilus. NaV1.2 immunoreactivity in the inner molecular layer of the dentate gyrus was lower than control at 1 day after SE. It increased at 3 weeks and 2 months after SE in the inner molecular layer and overlapped with sprouted mossy fibers. NaV1.6 immunoreactivity in the dendritic region of CA1 and CA3 was persistently reduced at all time-points during epileptogenesis. Some astrocytes expressed NaV1.1 and NaV1.6 at 3 weeks after SE. Expression data alone are not sufficient to explain changes in network stability, or infer causality in epileptogenesis. These results demonstrate that hippocampal sub-regional expression of NaV1.1, NaV1.2 and NaV1.6 Na(+) channel α subunits is altered during epileptogenesis in a time and location specific way. This implies that understanding epileptogenesis has to take into account several distinct and type-specific changes in sodium channel expression.

  1. Different duration of Colchicine for preventing recurrence of Gouty arthritis

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    H Karimzadeh

    2006-05-01

    Full Text Available Background: Gout is a Common recurrent clinical syndrome characterized by increased serum uric acid and recurrent attacks of acute arthritis. Colchicine is used for Prophylaxis against recurrence of arthritis, but the duration of its administration has mentioned variable. In this study, optimal duration of prophylactic colchicine for prevention of gouty arthritis was assessed. Methods : In a clinical trial 190 patients with gouty arthritis divided randomly to group 1,2and 3 and received colchicine for 3 to 6, 7 to 9 and 10 to 12 months then colchicine discontinued and the patients followed one year for recurrence of arthritis. Result assessed by survival analysis with Kaplan –Meier method. Results: The probability of recurrence of arthritis (in order of duration of colchicine prophylaxis was 54%, 27.5% and 23%, respectively. The difference between group one and others was statistically significant, but between group 2 and 3 was not statistically significant. Conclusion: The most suitable duration of colchicine prophylaxis that accompanied with lower recurrence rate was 7-9 months, which seems more cost -effective than 10-12 months regimen. Key words: Gout, Colchicine, Arthritis, Recurrence

  2. Compound list: colchicine [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available colchicine COL 00113 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/colchicine....Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/colchicine....Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single/colchicine...ive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/colchicine.Rat.in_vivo.Liver.Repeat.zip ...

  3. 神经干细胞在海人酸毁损大鼠海马中的迁移和分化%MIGRATION AND DIFFERENTIATION OF NSCs TRANSPLANTED INTO ADULT RAT HIPPOCAMPUS DAMAGED BY KAINIC ACID

    Institute of Scientific and Technical Information of China (English)

    吴星; 张沛云; 罗莉; 徐昌芬

    2006-01-01

    本研究旨在观察胎鼠神经干细胞移植入海人酸毁损成年大鼠海马中的迁移和分化情况.立体定位注射海人酸毁损大鼠海马CA1区锥体细胞,毁损一周后,将Hoechst33342标记的神经干细胞移植毁损区,分别于术后1、2、4、8周取材,利用荧光技术和免疫组织化学方法,追踪移植的神经干细胞在毁损侧海马中的存活、迁移和分化情况.结果显示,移植的神经干细胞在海马锥体层呈链状迁移,并分化为MAP2阳性细胞和GFAP阳性细胞.这些结果提示移植的神经干细胞在海马锥体层呈链状迁移,大部分分化为胶质细胞,部分分化为神经元.%The present study aims to investigate the survival, migration and differentiation of the neural stem cells (NSCs) transplanted into the hippocampus of adult rat damaged by kainic acid. Hippocampal CA1 pyramid neurons were degenerated by stereotaxical injection of kainic acid, one week later, NSCs labeled by Hoechst33342 were transplanted into the damaged hippocampus. The rats were sacrificed at 1,2,4 and 8 weeks, and the brains were examined by immunohistochemical analysis to observe the survival, migration and differentiation of the NSCs in the lesioned hippocampus. The results showed that transplanted neural stem cells migrate in the mode of chain in pyramid layer of hippocampus and most of them express the astrocytic marker of GFAP, others express the neuronal marker of MAP2. These results suggest that transplanted neural stem cells migrate in the mode of chain in pyramid layer of hippocampus. Most of them differentiate intoastrocytes, others differentiate into neurons.

  4. Antiepileptic Effect of Uncaria rhynchophylla and Rhynchophylline Involved in the Initiation of c-Jun N-Terminal Kinase Phosphorylation of MAPK Signal Pathways in Acute Seizures of Kainic Acid-Treated Rats

    Directory of Open Access Journals (Sweden)

    Hsin-Cheng Hsu

    2013-01-01

    Full Text Available Seizures cause inflammation of the central nervous system. The extent of the inflammation is related to the severity and recurrence of the seizures. Cell surface receptors are stimulated by stimulators such as kainic acid (KA, which causes intracellular mitogen-activated protein kinase (MAPK signal pathway transmission to coordinate a response. It is known that Uncaria rhynchophylla (UR and rhynchophylline (RP have anticonvulsive effects, although the mechanisms remain unclear. Therefore, the purpose of this study is to develop a novel strategy for treating epilepsy by investigating how UR and RP initiate their anticonvulsive mechanisms. Sprague-Dawley rats were administered KA (12 mg/kg, i.p. to induce seizure before being sacrificed. The brain was removed 3 h after KA administration. The results indicate that pretreatment with UR (1.0 g/kg, RP (0.25 mg/kg, and valproic acid (VA, 250 mg/kg for 3 d could reduce epileptic seizures and could also reduce the expression of c-Jun aminoterminal kinase phosphorylation (JNKp of MAPK signal pathways in the cerebral cortex and hippocampus brain tissues. Proinflammatory cytokines interleukin (IL-1β, IL-6, and tumor necrosis factor-α remain unchanged, indicating that the anticonvulsive effect of UR and RP is initially involved in the JNKp MAPK signal pathway during the KA-induced acute seizure period.

  5. Auricular Electroacupuncture Reduced Inflammation-Related Epilepsy Accompanied by Altered TRPA1, pPKCα, pPKCε, and pERk1/2 Signaling Pathways in Kainic Acid-Treated Rats

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    Yi-Wen Lin

    2014-01-01

    Full Text Available Background. Inflammation is often considered to play a crucial role in epilepsy by affecting iron status and metabolism. In this study, we investigated the curative effect of auricular acupuncture and somatic acupuncture on kainic acid- (KA- induced epilepsy in rats. Methods. We established an epileptic seizure model in rats by KA (12 mg, ip. The 2 Hz electroacupuncture (EA was applied at auricular and applied at Zusanli and Shangjuxu (ST36-ST37 acupoints for 20 min for 3 days/week for 6 weeks beginning on the day following the KA injection. Results. The electrophysiological results indicated that neuron overexcitation occurred in the KA-treated rats. This phenomenon could be reversed among either the auricular EA or ST36-ST37 EA treatment, but not in the sham-control rats. The Western blot results revealed that TRPA1, but not TRPV4, was upregulated by injecting KA and could be attenuated by administering auricular or ST36-ST37 EA, but not in the sham group. In addition, potentiation of TRPA1 was accompanied by increased PKCα and reduced PKCε. Furthermore, pERK1/2, which is indicated in inflammation, was also increased by KA. Furthermore, the aforementioned mechanisms could be reversed by administering auricular EA and could be partially reversed by ST36-ST37 EA. Conclusions. These results indicate a novel mechanism for treating inflammation-associated epilepsy and can be translated into clinical therapy.

  6. Long-term electrical stimulation at ear and electro-acupuncture at ST36-ST37 attenuated COX-2 in the CA1 of hippocampus in kainic acid-induced epileptic seizure rats.

    Science.gov (United States)

    Liao, En-Tzu; Tang, Nou-Ying; Lin, Yi-Wen; Liang Hsieh, Ching

    2017-03-28

    Seizures produce brain inflammation, which in turn enhances neuronal excitability. Therefore, anti-inflammation has become a therapeutic strategy for antiepileptic treatment. Cycloxygenase-2 (COX-2) plays a critical role in postseizure brain inflammation and neuronal hyperexcitability. Our previous studies have shown that both electrical stimulation (ES) at the ear and electro-acupuncture (EA) at the Zusanli and Shangjuxu acupoints (ST36-ST37) for 6 weeks can reduce mossy fiber sprouting, spike population, and high-frequency hippocampal oscillations in kainic acid (KA)-induced epileptic seizure rats. This study further investigated the effect of long-term ear ES and EA at ST36-ST37 on the inflammatory response in KA-induced epileptic seizure rats. Both the COX-2 levels in the hippocampus and the number of COX-2 immunoreactive cells in the hippocampal CA1 region were increased after KA-induced epileptic seizures, and these were reduced through the 6-week application of ear ES or EA at ST36-ST37. Thus, long-term ear ES or long-term EA at ST36-ST37 have an anti-inflammatory effect, suggesting that they are beneficial for the treatment of epileptic seizures.

  7. 红藻氨酸诱导PC12细胞凋亡及阿魏酸对神经元的保护作用%Ferulic acid protects against apoptosis of PC12 cells induced by kainic acid

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    陈勤; 叶海燕; 陈逸青; 余嗣明

    2013-01-01

    AIM:To investigate the effect of ferulic acid (FA) on the apoptosis of PC12 cells induced by kainic acid (KA) in vitro.METHODS:In order to establish an Alzheimer disease neuronal cell model,the rat pheochromocytoma cell line PC12 was treated with KA at a concentration of 50 μmol/L.These model neurons were divided into KA model group and3 groups treated with FA at doses of 25,50 and 100 μmol/L,respectively.At the same time,normal group was established without KA pretreatment.The viability of the PC12 cells was detected by MTT assay.The expression of Bcl-2,Bax and cytochrome C (Cyt C) was determined by immunocytochemical method.Apoptotic rate of the PC12 cells was measured by flow cytometry with annexin V/PI double staining.The protein levels of Bcl-2,Bax and Cyt C were analyzed by Western blotting.RESULTS:The cell survival rate,the expression of Bcl-2 and the ratio of Bcl-2 to Bax in KA model group were significantly decreased (P <0.01),while the expression of Bax and Cyt C was obviously increased com pared with normal control group (P <0.01).The apoptotie rate in KA model group was obviously increased compared with normal control group (P <0.01) After the intervention of FA,the cell survival rates were increased and the apoptotic rates were decreased.Furthermore,the positive rate and expression of Bcl-2,and the ratio of Bcl-2 to Bax in each dose of FA treatment group were significantly increased,while the expression of Bax and Cyt C in each dose group was significantly reduced as compared with KA model group (P < 0.05 or P < 0.01).CONCLUSION:KA obviously induces apoptosis of PC12 cells.FA had obvious protective effect on PC12 cells against the toxicity of KA.FA blocks endogenous apoptic pathway through inhibiting the expression of Bax and Cyt C and increasing the expression of Bcl-2 and the ratio of Bcl-2/Bax,thus improving the survival rate of PC12 cells.%目的:探讨阿魏酸(ferulic acid,FA)对红藻氨酸(kainic acid,KA)诱导的PC12细胞凋亡

  8. The effects of different doses of topiramate on rats' cognitive function in rat epilepsy models induced by kainic acid%不同剂量托吡酯对癫痫大鼠认知功能的影响

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    孙素真; 李海花; 冯宗怀

    2011-01-01

    To investigate the effect of different doses of topiramate on rats' cognitive function in rats with epilepsy induced by Kainic acid. Methods 48 health male Sprague - Dawley rats,weighted ( 100 ±10g) ,were randomly divided into 5 groups:normal control group ( n =8) ,epilepsy model group ( n = 10) ,lowdose topiramate (20mg/kg) treatment group ( n = 10) ,medium-dose topiramate (40mg/kg) treatment group ( n = 10) ,high -dose topiramate (80mg/kg) treatment group( n = 10). The rat epilepsy models were established by using stereotaxic apparatus to inject kainic acid into CA3 zone of right-side hippocampus,after 6-week gavage, the Morris water maze test was conducted to evaluate the rats' memory function. Results During the 4-day trainning,the average time of looking for the platform everyday in epilepsy model group was significantly longer than that of normal control group, however, the number of times of looking for the platform in epilepsy model group was significantly fewer than that in normal control group ( P < 0.05 ). The average time of looking for the platform everyday in medium-dose and high-dose topiramate treatment groups was significantly longer than that of epilepsy model group, however, the number of times of looking for the platform in the two groups was significantly fewer than that of epilepsy model group, and there was a significant difference between medium-dose topiramate treatment group and epilepsy model group, and between high-dose topiramate treatment group and epilepsy model group ( P < 0.05 ). However there was no significant differennce between low-dose topiramate treatment group and epilepsy model group (P > 0. 05 ). Conclusion The effects of topiramate on rats' cognitive functions are dose-dependment. The low-dose topiramate has no obvious effect on the rats ' cognitive function, but medium-dose and high-doae topiramate can reduce the rats' cognitive function.%目的 探讨不同剂量托吡酯对颞叶癫痫大鼠学习、记

  9. Systemic administration of kainic acid induces selective time dependent decrease in [{sup 125}I]insulin-like growth factor I, [{sup 125}I]insulin-like growth factor II and [{sup 125}I]insulin receptor binding sites in adult rat hippocampal formation

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    Quirion, R. [Department of Pharmacology and Therapeutics, McGill University, Montreal (Canada); Chabot, J.-G.; Dore, S. [Douglas Hospital Research Center, Department of Psychiatry, McGill University, Montreal (Canada); Seto, D. [Department of Pharmacology and Therapeutics, McGill University, Montreal (Canada); Kar, S. [Douglas Hospital Research Center, Department of Psychiatry, McGill University, Montreal (Canada)

    1997-08-11

    Administration of kainic acid evokes acute seizure in hippocampal pathways that results in a complex sequence of functional and structural alterations resembling human temporal lobe epilepsy. The structural alterations induced by kainic acid include selective loss of neurones in CA1-CA3 subfields and the hilar region of the dentate gyrus followed by sprouting and permanent reorganization of the synaptic connections of the mossy fibre pathways. Although the neuronal degeneration and process of reactive synaptogenesis have been extensively studied, at present little is known about means to prevent pathological conditions leading to kainate-induced cell death. In the present study, to address the role of insulin-like growth factors I and II, and insulin in neuronal survival as well as synaptic reorganization following kainate-induced seizure, the time course alterations of the corresponding receptors were evaluated. Additionally, using histological preparations, the temporal profile of neuronal degeneration and hypertrophy of resident astroglial cells were also studied. [{sup 125}I]Insulin-like growth factor I binding was found to be decreased transiently in almost all regions of the hippocampal formation at 12 h following treatment with kainic acid. The dentate hilar region however, exhibited protracted decreases in [{sup 125}I]insulin-like growth factor I receptor sites throughout (i.e. 30 days) the study. [{sup 125}I]Insulin-like growth factor II receptor binding sites in the hippocampal formation were found to be differentially altered following systemic administration of kainic acid. A significant decrease in [{sup 125}I]insulin-like growth factor II receptor sites was observed in CA1 subfield and the pyramidal cell layer of the Ammon's horn at all time points studied whereas the hilar region and the stratum radiatum did not exhibit alteration at any time. A kainate-induced decrease in [{sup 125}I]insulin receptor binding was noted at all time points in the

  10. Electrophysiological effects of kainic acid on vasopressin-enhanced green fluorescent protein and oxytocin-monomeric red fluorescent protein 1 neurones isolated from the supraoptic nucleus in transgenic rats.

    Science.gov (United States)

    Ohkubo, J; Ohbuchi, T; Yoshimura, M; Maruyama, T; Ishikura, T; Matsuura, T; Suzuki, H; Ueta, Y

    2014-01-01

    The supraoptic nucleus (SON) contains two types of magnocellular neurosecretory cells: arginine vasopressin (AVP)-producing and oxytocin (OXT)-producing cells. We recently generated and characterised two transgenic rat lines: one expressing an AVP-enhanced green fluorescent protein (eGFP) and the other expressing an OXT-monomeric red fluorescent protein 1 (mRFP1). These transgenic rats enable the visualisation of AVP or OXT neurones in the SON. In the present study, we compared the electrophysiological responses of AVP-eGFP and OXT-mRFP1 neurones to glutamic acid in SON primary cultures. Glutamate mediates fast synaptic transmission through three classes of ionotrophic receptors: the NMDA, AMPA and kainate receptors. We investigated the contributions of the three classes of ionotrophic receptors in glutamate-induced currents. Three different antagonists were used, each predominantly selective for one of the classes of ionotrophic receptor. Next, we focused on the kainate receptors (KARs). We examined the electrophysiological effects of kainic acid (KA) on AVP-eGFP and OXT-mRFP1 neurones. In current clamp mode, KA induced depolarisation and increased firing rates. These KA-induced responses were inhibited by the non-NMDA ionotrophic receptor antagonist 6-cyano-7-nitroquinoxaline-2,3(1H4H)-dione in both AVP-eGFP and OXT-mRFP1 neurones. In voltage clamp mode, the application of KA evoked inward currents in a dose-dependent manner. The KA-induced currents were significantly larger in OXT-mRFP1 neurones than in AVP-eGFP neurones. This significant difference in KA-induced currents was abolished by the GluK1-containing KAR antagonist UBP302. At high concentrations (250-500 μm), the specific GluK1-containing KAR agonist (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid (ATPA) induced significantly larger currents in OXT-mRFP1 neurones than in AVP-eGFP neurones. Furthermore, the difference between the AVP-eGFP and OXT-mRFP1 neurones in the ATPA currents

  11. Colchicine Poisoning in Children: 7 Case Reports

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    Mehmet Karacan

    2009-09-01

    Full Text Available Colchicine is a drug that has been used primarily in several diseases. Colchicine poisoning is an infrequent but potentially life-threatening problem characterized by multiorgan involvement. We present seven children with colchicine poisoning. Their ages ranged between 1 and 9 years. In six children, the amount of colchicine consumed was between 0.16 and 0.39 mg/kg; the most frequent findings were diarrhea and vomiting. In one patient, the ingested amount was unknown. One of the patients died and all others recovered without sequelae. The severity of colchicine poisoning tends to be related to the dosage of ingested drug and the time of admission to hospital. Symptomatic treatment should be started as soon as possible in colchicine poisoning. (Journal of Current Pediatrics 2009; 7: 96-100

  12. Review: Colchicine, current advances and future prospects

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    MAHENDRA KUMAR RAI

    2010-07-01

    Full Text Available Ade R, Rai MK. 2010. Colchicine, current advances and future prospects. Nusantara Bioscience 2: 90-96. Colchicine is a toxic natural compound and secondary metabolite commonly produced by plants like Colchicum autumnale and Gloriosa superba. It is originally used to treat rheumatic complaints, especially gout, and still finds its uses for these purposes today despite dosing issues concerning its toxicity. It is also prescribed for its cathartic and emetic effects. Initially oral colchicine has not been approved as a drug by U.S. Food and Drug Administration (FDA. But now FDA approved colchicine as a drug for some disorders. Colchicine's present medicinal use is in the treatment of gout and familial mediterranean fever. It is also being investigated for its use as an anticancer drug. In neurons, axoplasmic transport is disrupted by colchicine. Due to all the pharmacological application of colchicine, there is urgent need to enhance the properties and increase the production of colchicine with the help of in vitro technologies. The present review is mainly focused on the chemistry of colchicine, its medicinal uses and toxicity.

  13. Effects of colchicine on the intestinal transport of endogenous lipid. Ultrastructural, biochemical, and radiochemical studies in fasting rats

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    Pavelka, M.; Gangl, A.

    1983-03-01

    The involvement of microtubules in the transepithelial transport of exogenous lipid in intestinal absorptive cells has been suggested. Using electronmicroscopic, biochemical, and radiochemical methods, researchers have studied the effects of the antimicrotubular agent colchicine on the intestinal mucosa and on the intestinal transport of endogenous lipid of rats in the fasting state. After colchicine treatment, the concentration of triglycerides in intestinal mucosa of rats fasted for 24 h doubled, and electron microscopic studies showed a striking accumulation of lipid particles in absorptive epithelial cells of the tips of jejunal villi. These findings suggest that colchicine interferes with the intestinal transepithelial transport of endogenous lipoproteins. Additional studies, using an intraduodenal pulse injection of (/sup 14/C)linoleic acid, showed that colchicine does not affect the uptake of fatty acids by intestinal mucosa. However, it had divergent effects on fatty acid esterification, enhancing their incorporation into triglycerides relative to phospholipids, and caused a significant accumulation of endogenous diglycerides, triglycerides, and cholesterol esters within the absorptive intestinal epithelium. Detailed ultrastructural and morphometric studies revealed a decrease of visible microtubules, and a displacement of the smooth and rough endoplasmic reticulum and Golgi apparatus. Furthermore, it is shown that after colchicine treatment, microvilli appear at the lateral plasma membrane of intestinal absorptive cells, a change not previously reported to our knowledge. Thus, our study shows that colchicine causes significant changes in enterocyte ultrastructure and colchicine perturbs the reesterification of absorbed endogenous fatty acids and their secretion in the form of triglyceride-rich lipoproteins from the enterocyte.

  14. Ulcerative necrobiosis lipoidica responsive to colchicine.

    Science.gov (United States)

    Schofield, Clare; Sladden, Michael J

    2012-08-01

    Necrobiosis lipoidica is an uncommon granulomatous disease of unknown aetiology. Few treatments have emerged with consistent efficacy and the ulcerated form of necrobiosis lipoidica can be particularly difficult to treat. A 56-year-old non-diabetic woman with chronic ulcerative necrobiosis lipoidica unresponsive to other therapies was commenced on colchicine treatment. Complete resolution of the ulcers was observed after 2 months' therapy with colchicine 500 µg twice daily.

  15. Comparative Analyses of the β-Tubulin Gene and Molecular Modeling Reveal Molecular Insight into the Colchicine Resistance in Kinetoplastids Organisms

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    Luis Luis

    2013-01-01

    Full Text Available Differential susceptibility to microtubule agents has been demonstrated between mammalian cells and kinetoplastid organisms such as Leishmania spp. and Trypanosoma spp. The aims of this study were to identify and characterize the architecture of the putative colchicine binding site of Leishmania spp. and investigate the molecular basis of colchicine resistance. We cloned and sequenced the β-tubulin gene of Leishmania (Viannia guyanensis and established the theoretical 3D model of the protein, using the crystallographic structure of the bovine protein as template. We identified mutations on the Leishmania  β-tubulin gene sequences on regions related to the putative colchicine-binding pocket, which generate amino acid substitutions and changes in the topology of this region, blocking the access of colchicine. The same mutations were found in the β-tubulin sequence of kinetoplastid organisms such as Trypanosoma cruzi, T. brucei, and T. evansi. Using molecular modelling approaches, we demonstrated that conformational changes include an elongation and torsion of an α-helix structure and displacement to the inside of the pocket of one β-sheet that hinders access of colchicine. We propose that kinetoplastid organisms show resistance to colchicine due to amino acids substitutions that generate structural changes in the putative colchicine-binding domain, which prevent colchicine access.

  16. COLCHICINE DECREASES AIRWAY HYPERACTIVITY AFTER PHOSGENE EXPOSURE

    Science.gov (United States)

    Phosgene (COCl(2)) exposure affects an influx of inflammatory cells into the lung, which can be reduced in an animal model by pretreatment with colchicine. Inflammation in the respiratory tract can be associated with an increase in airway hyperreactivity. We tested the hypotheses...

  17. Anion-induced increases in the rate of colchicine binding to tubulin.

    Science.gov (United States)

    Bhattacharyya, B; Wolff, J

    1976-06-01

    The rate of binding of colchicine to tubulin to tubulin is enhanced by certain anions. Among the inorganic anions tested, only sulfate was effective. The organic anions include mostly dicarboxylic acids, among which tartrate was the most effective. This effect occurs onlt at low concentrations of colchicine (less than 0.6 X 10(-5) M). The rate increase dor sulfate and L-(+)-tartrate is ca. 2.5-fold at 1.0 mM and plateaus at a limiting value of ca. 4-fold at 100mM. The overall dissociation rate of the colchicine from the complex, which includes both the true rate of dissociation and the rate of irreversible denaturation of tubulin, is not influenced by 1.0 mM tartrate. The affinity constants for colchicine determined from the rate constants are 8.7 X 10(6) and 2.1 X 10(7) M-1 in the absence and the presence of 1.0 mM L-(+)-tartrate. The limiting value is 3.2 X 10(7) M-1. The affinity constant calculated from steady-state measurements is 3.2 X 10(6) M-1 with or without anions. The binding of other ligands like podophyllotoxin, vinblastine, and 1 -anilino-8-naphthalenesulfonate to tubulin is not affected by tartrate. No major conformational changes resulting from anion treatment could be detected by circular dichroism or intrinsic fluorescence. However, the ability of tubulin to polymerize is inhibited by L-(+)-tartrate at concentrations that increase the rate of colchicine binding. We conclude that anions must have a local effect at or near the binding site which enhances the binding rate of colchicine and which may be related to inhibition of polymerization.

  18. Mechanism of action of colchicine in the treatment of gout.

    Science.gov (United States)

    Dalbeth, Nicola; Lauterio, Thomas J; Wolfe, Henry R

    2014-10-01

    The aims of this article were to systematically review the literature about the mechanism of action of colchicine in the multimodal pathology of acute inflammation associated with gout and to consider the clinical utility of colchicine in other chronic inflammatory diseases. The English-language literature on PubMed was searched for articles published between 1990 and October 2013, with a cross-reference to citations across all years. Relevant articles pertaining to the mechanism of action of colchicine and the clinical applications of colchicine in gout and other inflammatory conditions were identified and reviewed. The molecular pathology of acute inflammation associated with gouty arthritis involves several concurrent pathways triggered by a variety of interactions between monosodium urate crystals and the surface of cells. Colchicine modulates multiple pro- and antiinflammatory pathways associated with gouty arthritis. Colchicine prevents microtubule assembly and thereby disrupts inflammasome activation, microtubule-based inflammatory cell chemotaxis, generation of leukotrienes and cytokines, and phagocytosis. Many of these cellular processes can be found in other diseases involving chronic inflammation. The multimodal mechanism of action of colchicine suggests potential efficacy of colchicine in other comorbid conditions associated with gout, such as osteoarthritis and cardiovascular disease. Colchicine has multiple mechanisms of action that affect inflammatory processes and result in its utility for treating and preventing acute gout flare. Other chronic inflammatory diseases that invoke these molecular pathways may represent new therapeutic applications for colchicine. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Colchicine use in isolated renal AA amyloidosis.

    Science.gov (United States)

    Meneses, Carlos F; Egües, César A; Uriarte, Miren; Belzunegui, Joaquín; Rezola, Marta

    2015-01-01

    We present the case of a 45-year-old woman, with two-year history of chronic renal insufficiency and proteinuria. A kidney biopsy showed the presence of AA amyloidosis (positive Congo red staining and immunohistochemistry). There was no evidence of amyloid deposits in other organs and there was no underlying disease. AA amyloidosis normally is secondary to chronic inflammatory or infectious diseases. High levels of IL-1, IL-6 and TNF-α play a role in the pathogenesis of amyloidosis and induce the synthesis of serum amyloid A protein (SAA), a precursor of tissue amyloid deposits. We empirically treated the patient with a low dose colchicine. The patient responded well. Colchicine has been used for the treatment of Familiar Mediterranean Fever and related auto-inflammatory diseases. To monitor treatment responses, we measured SAA finding low titers. Soon after treatment onset there were signs of improvement pertaining to proteinuria and stabilization of renal function.

  20. Gastric changes following colchicine therapy in patients with FMF.

    Science.gov (United States)

    Al-Daraji, Wael Ismail; Al-Mahmoud, Riham M W; Ilyas, Mohammed

    2008-08-01

    Familial Mediterranean fever (FMF) is also called recurrent polyserositis. The salient features of this disease include brief recurrent episodes of peritonitis, pleuritis, and arthritis, which are usually associated with fever. Colchicine is highly effective in the treatment of FMF and in preventing the development of recurrent attacks and amyloidosis, and it is essential to make the correct diagnosis and institute daily therapy with colchicine (0.5-0.6 mg bid). Colchicine is used to treat a variety of conditions but it is known to have gastrointestinal (GI) side effects. In this study, effects of colchicines on the gastrointestinal tract were evaluated in patients with FMF treated with colchicine. Biopsies were reviewed from 43 patients attending Ain Shams University Hospital (Egypt) who were diagnosed with FMF and treated with colchicine. One-hundred and twelve GI biopsies, obtained over a 14-year period, were reviewed. This included biopsies from stomach body (38), stomach antrum (50), and colon (24). In addition, gastric biopsies were reviewed from 17 control patients who did not have FMF and were not on colchicine. Three patients known to have FMF and on colchicine therapy showed typical histological features of colchicine (metaphase mitoses, epithelial pseudoproliferation, mucin depletion, and frequent apoptosis). These features were seen only in gastric antral biopsies and not in colonic biopsies. None of the control group showed the characteristic morphological features of colchicine toxicity. This is the first report of histological changes seen in the stomach following colchicine therapy. In contrast with previous reports, we did not find any definitive change in the large intestine. Our data show that gastric changes can be encountered in symptomatic patients who have recently had colchicine. If these finding are seen histologically, they merit correlation with the clinical impression and should not be interpreted as toxicity in isolation.

  1. Lichenoid drug eruption induced by colchicine: case report.

    Science.gov (United States)

    An, Isa; Demir, Vasfiye; Akdeniz, Sedat

    2016-07-15

    Lichenoid drug eruption (LDE) is a common cutaneous side effect of drugs including antimalarials, antihypertensives, nonsteroids, anti-inflammatory drugs and diuretics. The physiopathologic relationship between colchicine treatment and LDE is unclear. There is very little documentation of LDE induced by colchicine in the literature. In this report, we present a case that developed LDE on the abdomen and the legs during the colchicine treatment.

  2. Cerebral hippocampal neuronal apoptosis following kainic acid-induced epilepsy and the intervention of antagonists of dopamine D1 and D2 receptors%红藻氨酸致痫后脑海马神经元凋亡与黑质多巴胺受体D1及D2拮抗剂的干预作用

    Institute of Scientific and Technical Information of China (English)

    王松青; 陈海棠; 柯以铨; 徐如祥; 姜晓丹; 张怡然; 陈利锋

    2005-01-01

    BACKGROUND: Dopamine is closely associated with occurrence of epilepsy and transmission in central nerval system, and its various functions are determined by specific receptors.OBJECTIVE: To establish temporal epilepsy model so as to probe into the influences of SCH23390, the antagonist of dopamine D1 receptors and haloperidol, the antagonist of dopamine D2 receptors injected in substantia nigra on temporal epileptic seizure induced by kainic acid and on electroencephalic activityDESIGN: Randomized controlled verified experiment.SETTING: Neurology Medicine Institute of Zhujiang Hospital Affiliated to Southern Medical University.MATERIALS: The experiment was performed in General Military Neurology Medicine Institute of Zhujiang Hospital Affiliated to First Military University of Chinese PLA from August to December 2004, in which, 30SD adult male rats were employed, massed varied from 250 to 300 g.METHODS: ① 30 rats were randomized into physiological saline (control) group (6 rats), kainic acid (KA) group (6 rats) and experimental group (18 rats). The experimental group was divided into 3 subgroups, named the antagonist of dopamine D1 receptors, SCH23390 + kainic acid group (D1 +KA group), the antagonist of dopamine D2 receptors,haloperidol + kainic acid group (D2+KA group) and physiological saline + kainic acid group (PS + KA group), 6 rats in each. In the control, physi ological saline 2 μL was injected in the right cerebral ventricle unilaterally. In KA group, kainic acid 2 μL was injected in the right ventricle. In each of experimental group, SCH23390, the antagonist of dopamine D1 re ceptors, haloperidol, the antagonist of dopamine D2 receptors and physio logical saline 1 μL for each was injected in substantia nigra on the right side successively and simultaneously, kainic acid 2 μL was injected in the right ventricle. ② Observed items: alters of EEG on the 0.5th 1st, 2nd, 6th and 24th hours after medication in each experimental group (compared with EEG

  3. Current trends in colchicine treatment in familial Mediterranean fever.

    Science.gov (United States)

    La Regina, Micaela; Ben-Chetrit, Eldad; Gasparyan, Armen Yuri; Livneh, Avi; Ozdogan, Huri; Manna, Raffaele

    2013-01-01

    Since the publication of the first reports on the efficiency of colchicine in familial Mediterranean fever (FMF), very few randomised studies have investigated issues related to its long-term use. Thus, different approaches taken by physicians involved in FMF care, are exclusively empiric, emulative, and based on case-reports or case-series. Problems such as colchicine intolerance and colchicine resistance have not been solved yet. This paper aims to evaluate trends in colchicine therapy among physicians taking care of FMF patients around the world. We conducted a survey by sending questionnaires to FMF research and treatment centres in Europe and Asia. Many issues (such as dosages, schedules, side effects, interactions, efficacy and toxicity monitoring, definition of colchicine intolerance, colchicine resistance and responsiveness, etc) have been investigated. When more than 70% of physicians responded giving similar answers to an item, the response was considered as a 'trend'. A comparison between answers of physicians from FMF-prevalent and non-prevalent countries was also made. Thirty-five physicians from 11 countries filled the questionnaires, taking care of a total of more than 15000 FMF patients (pts). Different approaches were evident among the various physicians. Statistically significant different approaches between physicians from FMF-prevalent countries with respect to those from non-prevalent countries were found in items like colchicine during pregnancy, severity score and blood tests for disease monitoring. No consensus was found regarding the definition of colchicine resistance. The current study demonstrated significant variations in the strategy of colchicine therapy for FMF around the world and re-emphasised the need for standardised definitions of colchicine resistance and colchicine intolerance.

  4. Therapeutic efficacy of small doses of colchicine combined with glucocorticoid for acute gouty arthritis

    Directory of Open Access Journals (Sweden)

    Ying LIU

    2015-10-01

    Full Text Available Objective To observe the clinical effect of small dose of colchicine combined with glucocorticoid for acute gouty arthritis. Methods Ninety-two patients with acute gouty arthritis were equally and randomly divided into small doses of colchicine combined with dexamethasone treatment group (treatment group and conventional large dose colchicine treatment group (control group between January 2009 and December 2013. The articular lesion scoring and clinical efficacy evaluation were performed at 3, 6, 12, 24, 48, and 72h after treatment. Erythrocyte sedimentation rate (ESR, white blood cells, hepatorenal function and glomerular filtration rate (GFR were determined before and 72h after treatment respectively. The gastrointestinal adverse events and recurrence rate were observed within one month after treatment. Results The articular lesion scores were significantly decreased at 6, 12, 48, and 72h after treatment in treatment group compared with control group (P0.05. Serum uric acid, glutamic-pyruvic transaminase in serum (SGPT, and GFR did not show any change before and 72h after the treatment, and there was also no significant difference between groups (P>0.05. The incidence of gastrointestinal adverse events were obviously higher in control group (76.1% compared with that of the treatment group (P<0.05, and the differences was statistically significant. There was no statistical difference in recurrence rate between the control group and treatment group after a follow-up of one month. Conclusions Compared with conventional large dose colchicine, small dose of colchicine combined with dexamethasone can more rapidly and effectively control acute gouty arthritis, with good tolerability and safety, thus being worthy of popularization clinically. DOI: 10.11855/j.issn.0577-7402.2015.08.10

  5. Colchicine in the treatment of type 2 lepra reaction.

    Science.gov (United States)

    Sharma, V K; Kumar, B; Kaur, I; Singh, M; Kaur, S

    1986-01-01

    Fifteen patients of lepromatous leprosy having type 2 lepra reaction were treated with colchicine. Seven had moderate, five mild and three had severe E.N.L., colchicine was found effective in all mild, six moderate and one case of pustular E.N.L.

  6. Early ripening mutants induced by colchicine in rice

    Institute of Scientific and Technical Information of China (English)

    CAIGuohai; YANWanchao; CAOXin

    1993-01-01

    In 1981-1983, the frequency and range of the mutants induced by colchicine were investigated in M2 and M3 of two indica-rice cultivars.Seedlings of M2 and M3 were treated with 0.05% colchicine solution at 4-5 leaf stage.

  7. Colchicine induces apoptosis in organotypic hippocampal slice cultures

    DEFF Research Database (Denmark)

    Kristensen, Bjarne W; Noer, Helle; Gramsbergen, Jan Bert;

    2003-01-01

    with the colchicine-induced apoptosis in 1-week-old cultures showed that colchicine-induced PI uptake and formation of apoptotic nuclei were temporarily prevented by coapplication of the protein synthesis inhibitor cycloheximide. Application of the pancaspase inhibitor z-VAD-fmk almost completely abolished...

  8. Treatment of Colchicine-Resistant Familial Mediterranean Fever With Anakinra

    OpenAIRE

    Javadi Parvaneh; Shiari

    2015-01-01

    Introduction Familial Mediterranean Fever (FMF) is an auto-inflammatory disease presenting with periodic fever and various clinical manifestations. Almost 10% of the patients with FMF do not respond to colchicine therapy. Case Presentation Herein was reported a colchicine non-responsive patient with accurate diagnosis and early treatment of FMF. She had presented with recurrent and persistent acute abdominal pain attacks and sever...

  9. Evaluation of N-benzyl-N-[11C]methyl-2- (7-methyl-8-oxo-2-phenyl-7,8-dihydro-9H-purin-9-yl)acetamide ([11C]DAC) as a novel translocator protein (18 kDa) radioligand in kainic acid-lesioned rat.

    Science.gov (United States)

    Yanamoto, Kazuhiko; Yamasaki, Tomoteru; Kumata, Katsushi; Yui, Joji; Odawara, Chika; Kawamura, Kazunori; Hatori, Akiko; Inoue, Osamu; Yamaguchi, Masatoshi; Suzuki, Kazutoshi; Zhang, Ming-Rong

    2009-11-01

    The aim of this study was to evaluate N-benzyl-N-[11C]methyl-2-(7-methyl-8-oxo-2-phenyl-7,8-dihydro-9H-purin-9-yl)acetamide ([11C]DAC) as a new translocator protein (18 kDa) [TSPO, formerly known as the peripheral-type benzodiazepine receptor (PBR)] positron emission tomography (PET) ligand in normal mice and unilateral kainic acid (KA)-lesioned rats. DAC is a derivative of AC-5216, which is a potent and selective PET ligand for the clinical investigation of TSPO. The binding affinity and selectivity of DAC for TSPO were similar to those of AC-5216, and DAC was less lipophilic than AC-5216. The distribution pattern of [11C]DAC was in agreement with TSPO distribution in rodents. No radioactive metabolite of [11C]DAC was found in the mouse brain, although it was metabolized rapidly in mouse plasma. Using small-animal PET, we examined the in vivo binding of [11C]DAC for TSPO in KA-lesioned rats. [11C]DAC and [11C]AC-5216 exhibited similar brain uptake in the lesioned and nonlesioned striatum, respectively. The binding of [11C]DAC to TSPO was increased significantly in the lesioned striatum, and [(11)C]DAC showed good contrast between the lesioned and nonlesioned striatum (the maximum ratio was about threefold). In displacement experiments, the uptake of [11C]DAC in the lesioned striatum was eventually blocked using an excess of either unlabeled DAC or PK11195 injected. [11C]DAC had high in vivo specific binding to TSPO in the injured rat brain. Therefore, [11C]DAC is a useful PET ligand for TSPO imaging, and its specific binding to TSPO is suitable as a new biomarker for brain injury.

  10. Colchicine induces apoptosis in organotypic hippocampal slice cultures

    DEFF Research Database (Denmark)

    Kristensen, Bjarne W; Noer, Helle; Gramsbergen, Jan Bert

    2003-01-01

    The microtubule-disrupting agent colchicine is known to be particular toxic for certain types of neurons, including the granule cells of the dentate gyrus. In this study we investigated whether colchicine could induce such neuron-specific degeneration in developing (1 week in vitro) and mature (3...... weeks in vitro) organotypic hippocampal slice cultures and whether the induced cell death was apoptotic and/or necrotic. When applied to 1-week-old cultures for 48 h, colchicine induced primarily apoptotic, but also a minor degree of necrotic cell death in the dentate granule cells, as investigated...... the formation of active caspase 3 protein and apoptotic nuclei induced by colchicine, but the formation of necrotic nuclei increased correspondingly and the PI uptake was unaffected. We conclude that colchicine induces caspase 3-dependent apoptotic cell death of dentate granule cells in hippocampal brain slice...

  11. Effect of GDNF against kainic acid excitotoxicity on cultured neonatal rats doral root ganlian neurons%胶质源性神经营养因子对损伤的培养大鼠背根神经节的作用

    Institute of Scientific and Technical Information of China (English)

    毕辉; 杨浩; 杜亮; 胡三觉

    2001-01-01

    目的 应用体外培养海人藻酸(KA)兴奋性毒素损伤的细胞模型,研究GDNF对损伤的背根节神经元的不同作用,为进一步研究GDNF对神经元作用机制,表达产生及检测方法提供思路.方法 采用原代培养的方法,用N1无血清分离培养背根节神经元,再用5μmol.L-1KA作用6~8h,加上含有GDNF的无血清培养基,继续培养24h,然后用MTT法检测反映细胞的活性,胎盘蓝染色记数、细胞总蛋白测定以及形态学观察突起的生长状况.结果 ①细胞活性A值:GDNF+KA(0.0328±0.006),KA(0.0285±0.0075),GDNF(0.0398±0.002),Blank(0.041±0.002)(P<0.05);②活细胞数相应为GDNF+KA(60±4.4),KA(35.7±2.2),GDNF(59.3±3.6),Blank(57.7±2.9);③细胞的总蛋白分别为GDNF+KA(70.3±9.2)(P<0.01),KA(49.0±3.7),GDNF(75.0±7.3),Blank(68.0±5.5)(P<0.01);④突起长度:实验组与对照组不明显,GDNF组与空白对照组不明显.结论 在正常无血清体外培养情况下GDNF对DRG神经元作用不明显,在KA兴奋性毒素损伤后,对细胞的活性、存活及总蛋白合成有明显的保护作用,但对突起的生长则没有明显的促进作用.%AIM To study the different effects of glial-de-rived neurotrophicfactor( GDNF) on injured dosal root ganglion(DRG) neurons using injurious model of neurons induced by kainic acid in vitro, so as to provide new thoughts for studying functional mechanism, expression pattern, and bioassay methods of GDNF. METHODS Primarily cultured DRG neurons were dissected from neonatal rats in N1 serum-free medium,and then kainic acid medium was added into cultures at the final concentration of 5 μmol.L-1 and incubated for 6~8 h . The next step was performed to culture in DF12 serum-free medium supplemented with GDNF for 24 h. Eventually, MTT was used to test viability of cells by value. Trypan blue staining cell count and total protein of neurons were determined. DRG neurons were observed to detect the

  12. Interleukin-8 enhances the effect of colchicine on cell death.

    Science.gov (United States)

    Yokoyama, Chikako; Yajima, Chika; Machida, Tetsuro; Kawahito, Yuji; Uchida, Marie; Hisatomi, Hisashi

    2017-03-25

    Pro-inflammatory cytokines are known to be generated in tumors and play important roles in angiogenesis, mitosis, and tumor progression. However, few studies have investigated the synergistic effects of pro-inflammatory cytokines and anticancer drugs on cell death. In the present study, we examined the combined effects of pro-inflammatory cytokines and colchicine on cell death of cancer cells. Colchicine induces G2/M arrest in the cell cycle by binding to tubulin, one of the main constituents of microtubules. SUIT-2 human pancreatic cancer cell line cells overexpressing pro-inflammatory cytokines, including interleukin (IL)-1β, IL-8, and tumor necrosis factor (TNF)-α, were treated with colchicine. The effect of colchicine on cell death was enhanced in cells overexpressing IL-8. Moreover, the effect of colchicine on cell death was enhanced in cells overexpressing two IL-8 up-regulators, NF-κB and IL-6, but not in cells overexpressing an IL-8 down-regulator, splicing factor proline/glutamine-rich (SFPQ). Synergistic effects of IL-8 and colchicine were also observed in cells overexpressing IL-8 isoforms lacking the signal peptide. Therefore, IL-8 appeared to function as an enhancer of cell death in cancer cells treated with colchicine. The present results suggest a new role for IL-8 related to cell death of cancer cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Colchicine-responsive protracted gouty arthritis with systemic inflammatory reactions.

    Science.gov (United States)

    Nonaka, Fumiaki; Migita, Kiyoshi; Haramura, Tomoko; Sumiyoshi, Remi; Kawakami, Atsushi; Eguchi, Katsumi

    2014-05-01

    Acute gouty arthritis is a severe but self-limiting arthritis caused by inflammatory responses to urate crystals. Oral colchicines are effective for initial stages or prophylaxis, but generally, colchicines are ineffective for established gouty arthritis. We describe an unusual case of gouty arthritis with systemic inflammatory reactions, including high fever and polymyalgia. Refractory polyarthritis and high fever were eradicated by colchicine treatment. Genetic analysis revealed a heterozygous mutation in exon 2 of the MEFV gene (E148Q). This case underscores the possibility that MEFV gene mutations may modify the phenotype of gouty arthritis.

  14. Synthesis, antiproliferative activity and molecular docking of Colchicine derivatives.

    Science.gov (United States)

    Huczyński, Adam; Majcher, Urszula; Maj, Ewa; Wietrzyk, Joanna; Janczak, Jan; Moshari, Mahshad; Tuszynski, Jack A; Bartl, Franz

    2016-02-01

    In order to create more potent anticancer agents, a series of five structurally different derivatives of Colchicine have been synthesised. These compounds were characterised spectroscopically and structurally and their antiproliferative activity against four human tumour cell lines (HL-60, HL-60/vinc, LoVo, LoVo/DX) was evaluated. Additionally the activity of the studied compounds was calculated using computational methods involving molecular docking of the Colchicine derivatives to β-tubulin. The experimental and computational results are in very good agreement indicating that the antimitotic activity of Colchicine derivatives can be readily predicted using computational modeling methods.

  15. Sobrevivência e diferenciação de protocormos de Oncidium flexuosum submetidos a tratamento com ácido peracético e colchicina = Survival and differentiation of Oncidium flexuosum protocorm submitted to peracetic acid and colchicine treatment

    Directory of Open Access Journals (Sweden)

    Lilian Keiko Unemoto

    2009-07-01

    Full Text Available O objetivo deste trabalho foi verificar o efeito do ácido peracético e da colchicina na diferenciação de protocormos de Oncidium flexuosum. O ácido peracético foi testado previamente nas concentrações de 0, 3, 6 e 9 mL L-1, durante dez dias, para verificara eficácia na esterilização do meio de cultura e os possíveis efeitos fitotóxicos nos protocormos. Após determinação da concentração, foram adicionados 6 mL L-1 de ácido peracético em meio MS com 0,05% de colchicina e DMSO 1%. Os protocormos foram mantidos em agitação pelos períodos: 0, 24, 48, 72, 96 e 120h. O experimento foi inteiramente casualizado com seis tratamentos, dez repetições e cinco protocormos por repetição. Após 30 dias, foi avaliada a sobrevivência dos protocormos e, após 180 dias, foram avaliados: número de brotos, altura da parte aérea, número de raízes, comprimento da maiorraiz e massa fresca das plântulas regeneradas. Os dados foram submetidos à análise de regressão. A concentração de 6 mL L-1 de ácido peracético a 0,25% pode ser utilizada em substituição ao processo de filtração da solução de colchicina. O aumento do tempo deexposição à colchicina causou aumento no número de protocormos mortos.The objective of this work was to evaluate the effect of colchicine, when applied at different times on O. flexuosum protocorm differentiation. Peracetic acid was previously tested at 0, 3, 6 and 9 mL L-1 concentrations for 10 days, in order to verify the efficacy on the culture medium sterilization and the possible phytotoxic effects on protocorms. After determining the concentration, 6 mL L-1 of peracetic acid were added in MS medium with 0.05% colchicineand DMSO 1%. The protocorms were agitated during 0, 24, 48, 72, 96 and 120 hours. The experimental delineation used was the completely randomized blocks, with 6 treatments, 10 repetitions and 5 protocorms per repetition. Thirty days after the treatment began, protocorm survival

  16. Is colchicine therapy effective in all patients with secondary amyloidosis?

    Science.gov (United States)

    Unverdi, Selman; Inal, Salih; Ceri, Mevlut; Unverdi, Hatice; Batgi, Hikmetullah; Tuna, Rana; Ozturk, Mehmet Akif; Guz, Galip; Duranay, Murat

    2013-09-01

    Although colchicine is effective on prevention and regression of amyloidosis in many cases, rate of unresponsiveness to colchicine therapy is not too low. However, there is no sufficient data about which factors effect to response of colchicine therapy on regression of amyloidosis. 24 patients with renal amyloidosis were enrolled into the study. The patients were divided in two groups according to urinary protein excretions: non-nephrotic stage (14/24) and nephrotic stage (10/24). The patients were also categorized according to the etiology of amyloidosis; familial Mediterranean fever (FMF)-associated amyloidosis (15/24) versus rheumatoid disorders (RD)-associated amyloidosis (9/24). The changes of amount of proteinuria and estimated glomerular filtration rates were investigated after colchicine treatment started in these groups. The mean follow-up period was 27.7 ± 19.2 months. After initiating colchicine therapy, the degree of proteinuria was decreased higher than 50% in 11/14 (78%) of non-nephrotic patients and elevated only in three (22%) patients. In nephrotic group, proteinuria was increased in 5/10 (50%) of patients. Glomerular filtration rates were stable in nephrotic and non-nephrotic groups. Presenting with nephrotic syndrome was higher in RD-associated amyloidosis (RD_A) group (5/9) than FMF-associated amyloidosis (FMF_A) group (5/15) without statistical significance (p > 0.05). After colchicine treatment, proteinuria was decreased in 12/15 patients in FMF_A group, however, the significant decreasing of proteinuria was not observed in RD_A group (p = 0.05 vs. p > 0.05). Colchicine therapy was found more effective in low proteinuric stage of amyloidosis. The beneficial effect of colchicine therapy was not observed in patients with RD- associated amyloidosis.

  17. Beyond Gout: Colchicine Use in the Cardiovascular Patient

    Science.gov (United States)

    Cicci, Teresa A.; Vora, Alyssa K.; Burgess, Lindsey D.

    2015-01-01

    Colchicine is one of the oldest medications still in use today and is commonly used for the treatment of gout and familial Mediterranean fever. Its anti-inflammatory properties have raised the question of its utility in managing several cardiovascular diseases, including postoperative atrial fibrillation and pericarditis. This article will review the evidence for colchicine in these conditions and provide recommendations for use. PMID:27729672

  18. Induction of Tetraploids from Petiole Explants through Colchicine Treatments in Echinacea purpurea L.

    Directory of Open Access Journals (Sweden)

    Dahanayake Nilanthi

    2009-01-01

    Full Text Available Petiole explants were obtained from in vitro grown diploid (2x=22 Echinacea purpurea plantlets. Shoots were regenerated by culturing the explants on MS basal medium containing 0.3 mg/L benzyladenine (BA, 0.01 mg/L naphthaleneacetic acid (NAA and four concentrations (30, 60, 120, and 240 mg/L of colchicine for 30 days, or 120 mg/L of colchicine for various durations (7, 14, 21, and 28 days. The regenerated shoots were induced to root on MS basal medium with 0.01 mg/L NAA, and then the root-tips of the regenerated shoots were sampled for count of chromosome number. It was found that a treatment duration of >7 days was necessary for induction of tetraploid (4x=44 shoots, and treatment with 120 mg/L colchicine for 28 days was the most efficient for induction of tetraploids, yielding 23.5% of tetraploids among all the regenerated shoots. Chimeras were observed in almost all the treatments. However, the ratio of tetraploid to diploid cells in a chimeric plant was usually low. In comparison with diploid plants, tetraploid plants in vitro had larger stomata and thicker roots with more root branches, and had prominently shorter inflorescence stalk when mature.

  19. Induction of tetraploids from petiole explants through colchicine treatments in Echinacea purpurea L.

    Science.gov (United States)

    Nilanthi, Dahanayake; Chen, Xiao-Lu; Zhao, Fu-Cheng; Yang, Yue-Sheng; Wu, Hong

    2009-01-01

    Petiole explants were obtained from in vitro grown diploid (2x = 22) Echinacea purpurea plantlets. Shoots were regenerated by culturing the explants on MS basal medium containing 0.3 mg/L benzyladenine (BA), 0.01 mg/L naphthaleneacetic acid (NAA) and four concentrations (30, 60, 120, and 240 mg/L) of colchicine for 30 days, or 120 mg/L of colchicine for various durations (7, 14, 21, and 28 days). The regenerated shoots were induced to root on MS basal medium with 0.01 mg/L NAA, and then the root-tips of the regenerated shoots were sampled for count of chromosome number. It was found that a treatment duration of >7 days was necessary for induction of tetraploid (4x = 44) shoots, and treatment with 120 mg/L colchicine for 28 days was the most efficient for induction of tetraploids, yielding 23.5% of tetraploids among all the regenerated shoots. Chimeras were observed in almost all the treatments. However, the ratio of tetraploid to diploid cells in a chimeric plant was usually low. In comparison with diploid plants, tetraploid plants in vitro had larger stomata and thicker roots with more root branches, and had prominently shorter inflorescence stalk when mature.

  20. Effect of ketogenic diet on spatial learning ability and GluR5 expression in young rats with epilepsy induced by kainic acid%生酮饮食对海藻酸致癎大鼠空间学习记忆能力和GluR5表达的影响

    Institute of Scientific and Technical Information of China (English)

    徐向平; 孙若鹏; 石秀玉; 金瑞峰

    2006-01-01

    目的 探讨生酮饮食对大鼠空间学习记忆能力的影响和其可能的抗癫癎机制.方法 以海藻酸(kainic acid,KA)致癎幼鼠为研究对象,按是否经KA致癎和饮食处理不同分为海藻酸+正常饮食组(KA+ND)、海藻酸+生酮饮食组(KA+KD)、生理盐水+正常饮食组(NS+ND)和生理盐水+生酮饮食组(NS+KD).观察各组动物癫癎行为的变化;经Morris水迷宫对大鼠的空间学习和记忆能力及对已存储信息的再摄取能力进行评价并用Western Blot法检测海马海藻酸受体(CluR5)的表达.结果 KA+KD组动物自发性反复惊厥的次数(1.40±1.03)明显少于KA+ND组(7.36±3.75),四组动物找到平台的潜伏期随实验进行呈缩短趋势(F=30.86,P<0.001),各组动物间潜伏期比较差异无统计学意义(F=1.04,P>0.05).KA+KD组大鼠海马CluR5的表达(189.38±40.03)明显高于KA+ND组(128.79±46.51,t=2.79,P<0.05).结论 酮食疗法对KA致癎大鼠确有抗癫癎作用,其抗癫癎机制可能与增加幼年大鼠CA1区中间神经元CluR5的表达,使海马内抑制性突触传递增强,进而阻止癫癎活动扩散有关.生酮饮食对大鼠的空间学习和记忆能力无明显影响.

  1. 生酮饮食对海藻酸致痫大鼠海马突触重建和GluR5、GluR6 Mrna的影响%Effect of ketogenic diet on hippocampus synaptic reorganization and GluR5, GluR6 mRNA in kainic acid induced model

    Institute of Scientific and Technical Information of China (English)

    徐向平; 孙若鹏; 金瑞峰

    2005-01-01

    目的生酮饮食是一种高脂、低蛋白和低糖饮食. 它的抗痫作用早已明确,但其抗痫机制至今不明.本研究试图从海马突触重建和GluR5、GluR6 mRNA表达两方面初步探讨生酮饮食的可能抗痫机制.方法以海藻酸(Kainic acid,KA)点燃的雄性SD大鼠(P28)为研究对象,经正常饮食和生酮饮食喂养8周.通过行为学检测、Timm's 染色和尼氏染色,观察经不同饮食处理的动物海马苔藓纤维发芽(MFS)和神经元损伤情况,及其癫痫行为和空间学习、记忆功能的变化;经 RT-PCR法检测海马GluR5、 GluR6 mRNA的表达.结果 KA致痫后生酮饮食组动物自发性反复惊厥的次数为(1.40±1.03)次明显少于正常饮食组(7.36±3.7)次.在水迷宫检测中,各组动物找到平台的潜伏期随着测试进行明显缩短(F=33.93 , P0.05). Conclusion KD had prominent antiepileptic effect on KA-induced rats and it had no significant impairment on spatial learning and memory for the developing brain. KD can not prevent the MFS in young KA-induced rats, but it may play its antiepileptic role by keeping the high level expression of GluR6 mRNA in the hippocampus, due to its specific neuroprotective action, to inhibit the excitatory transmission at the MF pathway.

  2. Colchicine Significantly Reduces Incident Cancer in Gout Male Patients

    Science.gov (United States)

    Kuo, Ming-Chun; Chang, Shun-Jen; Hsieh, Ming-Chia

    2015-01-01

    Abstract Patients with gout are more likely to develop most cancers than subjects without gout. Colchicine has been used for the treatment and prevention of gouty arthritis and has been reported to have an anticancer effect in vitro. However, to date no study has evaluated the relationship between colchicine use and incident cancers in patients with gout. This study enrolled male patients with gout identified in Taiwan's National Health Insurance Database for the years 1998 to 2011. Each gout patient was matched with 4 male controls by age and by month and year of first diagnosis, and was followed up until 2011. The study excluded those who were diagnosed with diabetes or any type of cancer within the year following enrollment. We calculated hazard ratio (HR), aged-adjusted standardized incidence ratio, and incidence of 1000 person-years analyses to evaluate cancer risk. A total of 24,050 male patients with gout and 76,129 male nongout controls were included. Patients with gout had a higher rate of incident all-cause cancers than controls (6.68% vs 6.43%, P = 0.006). A total of 13,679 patients with gout were defined as having been ever-users of colchicine and 10,371 patients with gout were defined as being never-users of colchicine. Ever-users of colchicine had a significantly lower HR of incident all-cause cancers than never-users of colchicine after adjustment for age (HR = 0.85, 95% CI = 0.77–0.94; P = 0.001). In conclusion, colchicine use was associated with a decreased risk of incident all-cause cancers in male Taiwanese patients with gout. PMID:26683907

  3. Colchicine-induced myoneuropathy in a cyclosporine-treated renal transplant recipient

    Directory of Open Access Journals (Sweden)

    Kyungmin Huh

    2013-06-01

    Full Text Available Colchicine is a relatively safe medication that is widely used for both prevention and treatment of gout attack. However, serious adverse events, including myoneuropathy and multiorgan failure, have been reported. We report a case of colchicine-induced myoneuropathy in a female kidney transplant recipient who had been taking cyclosporine. She developed gastrointestinal discomfort and paresthesia 5 days after the initiation of colchicine. She showed signs of myoneuropathy, and hepatic and renal injury. Colchicine toxicity was suspected, and colchicine was discontinued. Her symptoms and laboratory findings improved gradually. Literature was reviewed for previous reports of colchicine-induced myoneuropathy in solid organ transplant recipients.

  4. Biotherapeutic potential and mechanisms of action of colchicine.

    Science.gov (United States)

    Dubey, Kashyap Kumar; Kumar, Punit; Labrou, Nikolaos E; Shukla, Pratyoosh

    2017-12-01

    Cancer is a clinical situation caused by uncontrolled cell division and is responsible for a large number of deaths worldwide. Colchicine is a classical antimitotic, tubulin-binding agent (TBA) which is being explored for its antitumor activities, although its tubulin-binding ability leads to some toxicity toward normal cells proliferation. Colchicine derivatives are considered as potent antitumor compounds with less toxicity compared to colchicine. Derivatives with substituted functional groups at A-ring (methoxy), B-ring (acetamide) or C-ring (methoxy) have been synthesized via chemical and microbial routes and show modified bioactivities and altered tropolonic functionality. Earlier reports, in combination with our group's research findings, suggest that microbial biotransformation is an efficient choice for the production of bioactive colchicine derivatives. This route has gained significant interest in the mass production of regio-specific, cost-effective, safe and eco-friendly derivatives. The present review paper critically analyzes and discusses the development and application of colchicine derivatives as a potent antitumor molecule and their production through a microbial transformation process. The information provided in this review might assist in the stimulation of new ideas regarding the development of alternative therapeutic agent(s) for cancer treatment.

  5. Diploidization of cucumber (Cucumis sativus L. haploids by colchicine treatment

    Directory of Open Access Journals (Sweden)

    Vesselina Nikolova

    2014-02-01

    Full Text Available Haploid cucumber plants are totally infertile and do not undergo spontaneous diploidization. The use of haploids depends on the possibility of doubling the chromosome number and the obtaining of stable doubled haploids (DH. Four haploids of different genotypes propagated vegetatively were treated with colchicine in order to obtain DH. The following procedures were used: 1 apical shoot meristem treatment, 2 soaking of shoot explants, 3 placing of shoot explants on medium with colchicine. Plants of the C1 generation were evaluated in respect to morphological and cytological characters and fertility. The best result of 20.9% DH was obtained after repeated treatment of the meristem with colchicine. A large group of chimeras (28.5% was also distinguished as were haploids and tetraploids. DH plants were fertile and gave uniform progeny. Chimeras had a decreased fertility and showed disturbances in meiotic divisions.

  6. Synthesis of both epimeric triacid ananlogs of kainic acid

    Institute of Scientific and Technical Information of China (English)

    Hai Ling Hao; Pi Sun; Guang Xing Wang; Kyoji Fruta; Masaaki Suzuki

    2008-01-01

    Axially substituted tin phthalocyanines, namely dichloride-tetra-(α-pentyloxy) tin (IV) phthalocyanine 2, dihydroxy-tetra-(α-pentyloxy) tin (IV) phthalocyanine 3 and its dimmer di-μ-oxo-tetra-(α-pentyloxy) tin(IV) phthalocyanine 4 were synthesized. The catalytic effect of H2O-free CaCl2 in quinoline was used for condensation of dihydroxy tin phthalocyanine 3 to the cofacially array dimmer 4. Their structures were characterized by UV-vis, IR, elemental analysis, MS, as well as 1HNMR spectroscopy.

  7. Tandem Wittig-ene reaction approach to kainic acid

    Digital Repository Service at National Institute of Oceanography (India)

    Majik, M.S.; Parameswaran, P.S.; Tilve, S.G.

    ), 5.11-5.16 (m, 1H), 7.16-7.39 (m, 5H). 13 C NMR (CDCl 3 ,75 MHz): δ 17.8, 25.6, 26.3 [26.5], 45.7 [43.5], 48.3 [50.8], 119.3 [118.5], 126.3 [127.3], 127.7 [127.9], 128.5 [128.9], 136.8 [136.2], 137.2, 166.8. HRMS: m/z [M + Na] + calcd for C 14 H 18....10-5.15] (m, 1H), 7.10-7.51 (m, 20H). 13 C NMR (CDCl 3 , 75 MHz): δ 17.8, 25.6, 29.6, 45.6 [42.6], 50.8 [47.7], 119.6, 126.2, 128.3, 128.5, 131.8, 132.0, 132.8, 137.5, 170.5. HRMS: m/z [M + H] + calcd for C 32 H 33 NOP, 478.2300; found, 478.2313. N...

  8. Hemophagocytic lymphohistiocytosis and Pelger-Huët anomaly associated with colchicine intoxication

    Directory of Open Access Journals (Sweden)

    Baris Malbora

    2014-06-01

    Full Text Available Colchicine is frequently used in the treatment of familial Mediterranean fever (FMF. First symptoms of colchicine intoxication are gastrointestinal disturbances, such as abdominal cramps, diarrhea, pancytopenia and so on. Herein, we report a female FMF patient with pancytopenia and hemophagocytic lymphohitiocytosis (HLH, following colchicine intoxication for committing suicide. To our knowledge, this is the first reported case of a patient with HLH associated with colchicine intoxication.

  9. Polyploid induction of Allium ascalonicum L. by colchicine

    Directory of Open Access Journals (Sweden)

    SUMINAH

    2002-01-01

    Full Text Available The low production rate of shallot (Allium ascalonicum L. in Indonesia could be caused by rarely excellent cultivars. Colchicine was one of the mutation agents frequently used in plant breeding in order to get polyploidy of cultivars. The aim of this research was to find out the differentiation of morphometric evidences and ploidy of shallot chromosomes induced by colchicines 1%. Preparation was made by squash method and stained by acetocarmine. The results indicated that the amount, length and shape of chromosomes altered by the application of the agent. The polyploids produced could be grouped into tetraploids, pentaploids, hexaploids, octaploids, and nonaploids.

  10. 胶质细胞源性神经营养因子在大鼠 急性痫性发作中的表达%Time course expression of GDNF protein in rat hippocampus after intrahippocampal kainic acid injection induced acute seizure

    Institute of Scientific and Technical Information of China (English)

    张贺; 肖波; 王蓉

    2001-01-01

    目的动态观察胶质细胞源性神经营养因子(GDNF)蛋白在红藻氨酸(KA)诱导的大鼠急性痫性发作中的表达水平,探讨GDNF在急性癫痫发作中的作用。方法成年SD大鼠随机分为NS对照组和KA处理组。急性痫性发作经单侧海马内注入KA (0.6μg/0.3μl) 诱导。两组大鼠分别在注射后第3、6、24h和第4、7d,采用免疫细胞化学方法检测GDNF蛋白在海马中的表达水平。结果 NS组海马GDNF表达极微量,各时间点均在基线水平。KA组在注射后3h GDNF少量增高,6h达高峰,并持续至第4d,均高于各时间点 NS组(P0.05)。双侧GDNF表达在各时间点无显著差异。结论单侧海马内注射KA诱导的大鼠急性痫性发作可导致双侧海马齿状回和门区GDNF蛋白表达增高,GDNF可能参与拮抗KA神经兴奋性毒性作用,对海马齿状回颗粒细胞起保护效应。%Objective  To examine the expression of glial cell line-derived neurotrophic factor(GDNF)protein in hippocampus of acute epileptic SD rats. Method  Forty Sprague-Dawley rats were randomly divided into two groups: normal control (Group NS) and kainic acid-treated (Group KA). The models were induced by unilateral intrahippocampal injection of KA(0.6μg/0.3μl). GDNF were examined with immunocolloidal-gold-silver staining (IGSS) dynamically at post-injection hours 3, 6 and 24; and post-injection days 4 and 7 in both groups. The density of IGSS staining were analyzed using an imaging analysis system. Results In group NS, GDNF immunoreactivity was very weak, and remained at the normal level at each time point. In group KA, GDNF protein began to increase bilaterally in the dentate gyri and hilar area within 3h after KA injection, reached its maximum level at 6h, then decreased at 24h and PID 4, these were higher than the corresponding control(P<0.05), and returned to the control level by PID 7. No significant difference was found in GDNF between

  11. UPTAKE OF [3H]-COLCHICINE INTO BRAIN AND LIVER OF MOUSE, RAT, AND CHICK

    Energy Technology Data Exchange (ETDEWEB)

    Bennett, Edward L.; Alberti, Marie Hebert; Flood, James F.

    1980-07-01

    The uptake of [ring A-4-{sup 3}H] colchicine and [ring C-methoxy-{sup 3}H]colchicine has been compared in mice from 1 to 24 hr after administration. Less radioactivity was found in brain after administration of ring-labeled colchicine than after administration of the methoxy-labeled colchicine. Three hr after administration of ring-labeled colchicine, 5% of the label was in liver and about 0.01% of the label was present in brain. Forty percent of the brain radioactivity was bound to tubulin as determined by vinblastine precipitation. After 3 hr, an average of 8% of the radioactivity from methoxy-labeled colchicine was found in the liver and 0.16% in brain. However, less than 5% of the activity in brain was precipitated by vinblastine, and the colchicine equivalent was comparable to that found after administration of the ring-labeled colchicine. The amount of colchicine entering mouse brain after subcutaneous injection is comparable to the minimum behaviorally effective dose when administered to the caudate. The metabolism of [ring C-methoxy-{sup 3}H] and [ring A-{sup 3}H]colchicine was also studied in rats. the general pattern was similar to mice; less radioactivity was found in brain after administration of the ring-labeled alkoloid than after administration of methoxy-labeled colchicine. Again, 40-50% of ring-labeled colchicine was precipitated by vinblastine. A much smaller percentage of the methoxy-labeled drug was precipitated by vinblastine than of the ring A-labeled colchicine. These experiments, together with behavioral experiments [7], support the hypotheses that structural alteration in synapses by recently synthesized proteins which are transported down the axons and dendrites may be an essential process for long-term memory formation.

  12. Polyploid induction of Lespedeza formosa by colchicine treatment

    Institute of Scientific and Technical Information of China (English)

    Li Wei; Hu Dong-nan; Li Hui; Chen Xiao-yang

    2007-01-01

    Polyploid induction has been conducted by different colchicines concentrations with seed. hypocotyl and apices of Lespedeza formosa. Morphological variation and amounts of chromosome about the polyploidy have also been analyzed. Results show that the best material for polyploid induction of L. formosa is the new apices from seed germination, with an induction rate of 44. 4% at 0. 1% colchicines concentration and 36 hours of treatment time. Compared with normal diploid plants. the polyploidy plants of L. formosa inducted in our experiments have short stature and stems with thick and wide leaves. Cytological studies show that the changed seedlings,whose morphology has changed dramatically, are tetraploid, with 44 (2n=4x=44)chromosomes in the somatic cells.

  13. Colchicine for alcoholic and non-alcoholic liver fibrosis or cirrhosis

    DEFF Research Database (Denmark)

    Rambaldi, A; Gluud, C

    2001-01-01

    Colchicine is an anti-inflammatory and anti-fibrotic drug. Several randomized clinical trials have addressed the question whether colchicine has any efficacy in patients with alcoholic as well as non-alcoholic fibrosis and cirrhosis. The objectives were to assess the efficacy of colchicine...... evaluated in randomized trials on mortality, liver related mortality, liver related complications, liver fibrosis markers, liver histology, alcohol consumption, quality of life, and health economics in patients with alcoholic and non-alcoholic fibrosis or cirrhosis....

  14. Canakinumab treatment in four children with colchicine resistant familial mediterranean fever.

    Science.gov (United States)

    Ozkan, Solmaz; Atas, Bulent

    2017-06-01

    Familial Mediterranean Fever (FMF) is an autosomal recessive and autoinflammatory disease, characterized with inflammation of serous membranes such as peritoneum, pleura, synovium with fever and pain. Colchicine is the main treatment of FMF, but 5-10 % of patients are unresponsive to colchicine. We report using anti-interleukin-1 agents anakinra and canakinumab in four colchicine-resistant patients who were successfully treated. Three of the patients were siblings.

  15. Tolerance of nestin+ cholinergic neurons in the basal forebrain against colchicine-induced cytotoxicity

    Institute of Scientific and Technical Information of China (English)

    Jing Yu; Kaihua Guo; Dongpei Li; Jinhai Duan; Juntao Zou; Junhua Yang; Zhibin Yao

    2011-01-01

    In the present study we injected colchicine into the lateral ventricle of Sprague-Dawley rats to investigate the effects of colchicine on the number of different-type neurons in the basal forebrain and to search for neurons resistant to injury. After colchicine injection, the number of nestin+ cholinergic neurons was decreased at 1 day, but increased at 3 days and peaked at 14-28 days. The quantity of nestin- cholinergic neurons, parvalbumin-positive neurons and choline acetyl transferase-positive neurons decreased gradually. Our results indicate that nestin+ cholinergic neurons possess better tolerance to colchicine-induced neurotoxicity.

  16. Outstanding inhibitive effect of colchicine on aluminium alloy 6061 corrosion

    Directory of Open Access Journals (Sweden)

    Mudigere Krishnegowda Pavithra

    2015-12-01

    Full Text Available The corrosion protection ability of colchicine (CC on Aluminium alloy 6061 (AA6061 in 3.5% NaCl medium was examined by potentiodynamic polarization, electrochemical impedance, and chronoamperometric techniques. About 99 % of protection efficiency was achieved by 2 mM concentration of CC in 3.5% NaCl solution.The adsorption of CC on AA6061 surface obeys Langmuir isotherm by following both physisorption and chemisorption mechanism. Variation in the surface morphology of inhibited and uninhibited metal samples was examined by scanning electron microscopy. 

  17. Sarcoidosis and chronic hepatitis C: treatment with prednisone and colchicine*

    Science.gov (United States)

    Pereira, Eduardo Guimarães; Guimarães, Tais Ferreira; Bottino, Caroline Bertolini; D’Acri, Antonio Macedo; Lima, Ricardo Barbosa; Martins, Carlos José

    2016-01-01

    Sarcoidosis is a disease which still has uncertain etiology. Possible environmental causes are cited in the literature, like organic and inorganic particles and infectious agents. Recent studies have demonstrated the occurrence of sarcoidosis in patients with chronic C hepatitis; however, this association remains without statistical or causal evidence. In this report a case of sarcoidosis associated with chronic hepatitis C will be described, with subcutaneous lesions, considered rare, and good response to treatment with colchicine and prednisone. The hepatitis C virus was isolated in sarcoid tissue and the association between the two diseases will be discussed. PMID:27192527

  18. Colchicine for alcoholic and non-alcoholic liver fibrosis and cirrhosis

    DEFF Research Database (Denmark)

    Rambaldi, A; Gluud, C

    2005-01-01

    Alcohol and hepatotropic viruses cause the majority of liver cirrhosis cases in the Western World. Colchicine is an anti-inflammatory and anti-fibrotic medication. Several randomised clinical trials have addressed the question whether colchicine has any efficacy in patients with alcoholic or non-alcoholic...

  19. Colchicine for alcoholic and non-alcoholic liver fibrosis and cirrhosis

    DEFF Research Database (Denmark)

    Rambaldi, A; Gluud, C

    2001-01-01

    The majority of liver fibrosis and liver cirrhosis cases in the Western World is caused by alcohol and hepatotoxic viruses. Colchicine is an anti-inflammatory and anti-fibrotic medication. Several randomised clinical trials have addressed the question whether colchicine has any efficacy in patients...... with alcoholic as well as non-alcoholic fibrosis and cirrhosis....

  20. High-throughput drug library screening identifies colchicine as a thyroid cancer inhibitor

    Science.gov (United States)

    Zhang, Le; Yang, Zhaoying; Granieri, Letizia; Pasculescu, Adrian; Datti, Alessandro; Asa, Sylvia L.; Xu, Zheli; Ezzat, Shereen

    2016-01-01

    We employed a high-throughput drug library screening platform to identify novel agents affecting thyroid cancer cells. We used human thyroid cancer cell lines to screen a collection of approximately 5200 small molecules with biological and/or pharmacologial properties. Parallel primary screens yielded a number of hits differentially active between thyroid and melanoma cells. Amongst compounds specifically targeting thyroid cancer cells, colchicine emerged as an effective candidate. Colchicine inhibited cell growth which correlated with G2 cell cycle arrest and apoptosis. These effects were hampered through inhibition of MEK1/2 and JNK. In contrast, inhibition of p38-MAPK had little effect, and AKT had no impact on colchicine action. Systemic colchicine inhibited thyroid cancer progression in xenografted mice. These findings demonstrate that our screening platform is an effective vehicle for drug reposition and show that colchicine warrants further attention in well-defined clinical niches such as thyroid cancer. PMID:26942566

  1. High-throughput drug library screening identifies colchicine as a thyroid cancer inhibitor.

    Science.gov (United States)

    Zhang, Le; Yang, Zhaoying; Granieri, Letizia; Pasculescu, Adrian; Datti, Alessandro; Asa, Sylvia L; Xu, Zheli; Ezzat, Shereen

    2016-04-12

    We employed a high-throughput drug library screening platform to identify novel agents affecting thyroid cancer cells. We used human thyroid cancer cell lines to screen a collection of approximately 5200 small molecules with biological and/or pharmacologial properties. Parallel primary screens yielded a number of hits differentially active between thyroid and melanoma cells. Amongst compounds specifically targeting thyroid cancer cells, colchicine emerged as an effective candidate. Colchicine inhibited cell growth which correlated with G2 cell cycle arrest and apoptosis. These effects were hampered through inhibition of MEK1/2 and JNK. In contrast, inhibition of p38-MAPK had little effect, and AKT had no impact on colchicine action. Systemic colchicine inhibited thyroid cancer progression in xenografted mice. These findings demonstrate that our screening platform is an effective vehicle for drug reposition and show that colchicine warrants further attention in well-defined clinical niches such as thyroid cancer.

  2. 获得性免疫反应与海人藻酸引起的C57BL/6小鼠海马损伤的关系%Adaptive immune response is involved in kainic acid-induced hippocampal injury in C57BL/6 mice

    Institute of Scientific and Technical Information of China (English)

    祝威; 崔香艳; 祝捷

    2007-01-01

    BACKGROUND: Kainic acid (KA)-induced hippocampal injury in rodents is a good model for studying human neurodegenerative diseases. Although many studies have evidenced that inflammatory molecules and responses participate in and accelerated the process of disease, it is still unclear whether adaptive immune response, especially immune competent cells, such as T and B cells, is involved in the pathogenesis of neurodegenerative diseases.OBJECTIVE: To observe the roles of B and T cell subsets in KA-induced hippocampal neurodegeneration.DESIGN: Randomized controlled animal trial.5ETTING: Department of Otolaryngology and Head, and Department of Neurology, First Hospital, Jilin University; Division of Geriatrics, Department of Neurotec, Huddinge Hospital, Karolinska Institute.MATERrALS: This trial was conducted in the Department of Neurotec, Huddinge Hospital, Karolinska Institute during June to September 2000. Twenty male C57 BL/6 mice (wide-type), and knockout mice CD4(-/-) (n =17), CD8(-/-)(n =19), CD4/CD8(-/-) (n =15) and Igh-6(-/-) (n =14) of C57BL/6 background were involved in this trial. They were aged 5 to 6 weeks,weighing 18 to 20 g. Three age- and body mass-matched C57BL/6 mice received water as controls. Reagent and instruments: KA (Sigma, USA). Bicolor flow cytometer and CellQuest (Becton Dickinson, CA, USA).METHODS: ① Eighty-five anesthetized mice were slowly administrated with 7.69 g/L KA by micropipette which was connected to nose of mouse at the dose of 48 mg/kg. Three control C57BL/6 mice received the same amount of water intranasally. ②Clinical symptoms of mice were monitored. Seizures were graded using a 6-point scale, 0: normal; 6: death.③After 4 to 5 hours of administration of KA, surface immunofluorescence staining of spleen cells was measured with flow cytometer. ④After 7 days of administration of KA, all the mice were anesthetized, and their brains were harvested,then fixed and embedded. For assessment of the severity and extent of

  3. [Use of colchicine in studying the proliferative activity of chicken embryos].

    Science.gov (United States)

    Efremov, V I; El Zajat, M

    1977-07-01

    Manifestation of mitotic activity of colchicin in 4- and 5-day-old chick embryos was studied under different modes of colchicin injection into the eggs. Three methods were tested: colchicin solution was injected into the serous-amniotic cavity (1) and into the yolk sac (2) and also by dripping on the serous membrane over the enbryo (3). Perfect metastatic effect was observed only when colchicin was used in concentration of 1 X 10(-4) g/ml and injected by the third mehtod. Increase in the solution volume over 0.1 ml resulted in a greater percentage of embryo death. Lack of a definite inhibitory action after colchicin injection into the serous-amniotic cavity might be explained by decrease of the substance concentration as a result of its dilution by the cavity fluid. A complete lack of blocked mitoses in the embryo tissues after colchicin injection into the yolk sac can be explained, according to the authors, by the presence, in the yolk, of a great number of ovoflavins capable to inhibit mitotic activity of colchicin.

  4. Acute pancreatitis related to therapeutic dosing with colchicine: a case report

    Directory of Open Access Journals (Sweden)

    Ting Joseph

    2007-08-01

    Full Text Available Abstract Background Colchicine is used in the treatment and prophylaxis of gout. It possesses a narrow therapeutic window, frequently resulting in dose-limiting gastrointestinal side-effects such as diarrhoea and emesis. As colchicine is a cellular anti-mitotic agent, the most serious effects include myelosuppression, myoneuropathy and multiple organ failure. This occurs with intentional overdose or with therapeutic dosing in patients with reduced clearance of colchicine due to pre-existing renal or hepatic impairment. Acute pancreatitis has rarely been reported, and only in association with severe colchicine overdose accompanied by multi-organ failure. Case presentation We report a case of acute pancreatitis without other organ toxicity related to recent commencement of colchicine for acute gout, occurring in an elderly male with pre-existing renal impairment. Conclusion 1 Colchicine should be used with care in elderly patients or patients with impaired renal function. 2 Aside from myelosuppression, myoneuropathy and multiple organ failure, colchicine may now be associated with acute pancreatitis even with therapeutic dosing; this has not previously being reported.

  5. Normal arterial stiffness in familial Mediterranean fever: evidence for a possible cardiovascular protective role of colchicine.

    Science.gov (United States)

    Kukuy, Olga; Livneh, Avi; Mendel, Liran; Benor, Ariel; Giat, Eitan; Perski, Oleg; Feld, Olga; Kassel, Yonatan; Ben-Zvi, Ilan; Lidar, Merav; Holtzman, Eliezer J; Leiba, Adi

    2017-02-09

    Familial Mediterranean fever (FMF) is an autoinflammatory disorder with episodic and persistent inflammation, which is only partially suppressed by continuous colchicine treatment. While chronic inflammation is considered an important cardiovascular risk factor in many inflammatory disorders, its impact in FMF is still disputed. We measured arterial stiffness, a marker of atherosclerotic cardiovascular disease, in a group of FMF patients, in order to evaluate the cardiovascular consequences of inflammation in FMF and the role of colchicine in their development. Eighty colchicine treated FMF patients, without known traditional cardiovascular risk factors, were randomly enrolled in the study. Demographic, genetic, clinical and laboratory data were retrieved from patient files and examinations. Arterial stiffness was measured using pulse wave velocity (PWV). The recorded values of PWV were compared with those of an age and blood pressure adjusted normal population, using internationally endorsed values. FMF patients displayed normal PWV values, with an even smaller than expected proportion of patients deviating from the 90th percentile of the reference population (5% vs. 10%, p=0.02). The lowest PWV values were recorded in patients receiving the highest dose of colchicine (≥2 mg vs. 0-1 mg, p=0.038), and in patients of North African Jewish origin, whose disease was typically more severe than that of patients of other ethnicities; both observations supporting an ameliorating colchicine effect (p=0.043). Though subjected to chronic inflammation, colchicine treated FMF patients have normal PWV. Our findings provide direct evidence for a cardiovascular protective role of colchicine in FMF.

  6. Neuroprotective Effects of Centella asiatica against Intracerebroventricular Colchicine-Induced Cognitive Impairment and Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Anil Kumar

    2009-01-01

    Full Text Available Oxidative stress appears to be an early event involved in the pathogenesis of Alzheimer's disease. The present study was designed to investigate the neuroprotective effects of Centella asiatica against colchicine-induced memory impairment and oxidative damage in rats. Colchicine (15 μg/5 μL was administered intracerebroventricularly in the lateral ventricle of male wistar rats. Morris water maze and plus-maze performance tests were used to assess memory performance tasks. Various biochemical parameters such as lipid peroxidation, nitrite, reduced glutathione, glutathione-S-transferase, superoxide dismutase, acetylcholinesterase were also assessed. ICV colchicine resulted marked memory impairment and oxidative damage. Chronic treatment with Centella asiatica extract (150 and 300 mg/kg, p.o. for a period of 25 days, beginning 4 days prior to colchicine administration, significantly attenuated colchicine-induced memory impairment and oxidative damage. Besides, Centella asiatica significantly reversed colchicines administered increase in acetylcholinesterase activity. Thus, present study indicates protective effect of Centella asiatica against colchicine-induced cognitive impairment and associated oxidative damage.

  7. A survey of resistance to colchicine treatment for French patients with familial Mediterranean fever.

    Science.gov (United States)

    Corsia, Alice; Georgin-Lavialle, Sophie; Hentgen, Véronique; Hachulla, Eric; Grateau, Gilles; Faye, Albert; Quartier, Pierre; Rossi-Semerano, Linda; Koné-Paut, Isabelle

    2017-03-16

    Colchicine is the standard treatment for familial Mediterranean fever (FMF), preventing attacks and inflammatory complications. True resistance is rare and yet not clearly defined. We evaluated physicians' definition of colchicine resistance and report how they manage it. We recruited patients with a clinical diagnosis of FMF, one exon-10 Mediterranean fever (MEFV) gene mutation and considered resistant to colchicine, via networks of expert physicians. Clinical, biological characteristics and information about colchicine treatment (dose adjustment, compliance) were collected. The severity of FMF was assessed by the Tel Hashomer criteria. We included 51 patients, most females (55%), mean age 34 ± 23.1 years years (range 4.7-86.3). Overall, 58% (27/47) patients had homozygous M694 MEFV gene mutations. Seventeen of 42 patients (40%) declared full adherence to colchicine treatment, greater for children (48%) than adults (22%). Physicians considered colchicine resistance with > 6 attacks/year (n = 21/51, 42%), > 4 attacks in the last 6 months (n = 13/51, 26%), persistent inflammation (n = 23/51, 45%), renal amyloidosis in (n = 6/28, 22%) of adult patients and intolerance to an increase in colchicine dose (n = 10/51, 19%), and other reasons (n = 13/51, 23%), including chronic arthralgia (n = 6/51, 12%). Interleukin 1-targeting drugs represented the only alternative treatments in addition to daily colchicine. Resistance to colchicine is rare (treatment is a key component of resistance.

  8. Colchicine modulates calcium homeostasis and electrical property of HL-1 cells.

    Science.gov (United States)

    Lu, Yen-Yu; Chen, Yao-Chang; Kao, Yu-Hsun; Lin, Yung-Kuo; Yeh, Yung-Hsin; Chen, Shih-Ann; Chen, Yi-Jen

    2016-06-01

    Colchicine is a microtubule disruptor that reduces the occurrence of atrial fibrillation (AF) after an operation or ablation. However, knowledge of the effects of colchicine on atrial myocytes is limited. The aim of this study was to determine if colchicine can regulate calcium (Ca(2+) ) homeostasis and attenuate the electrical effects of the extracellular matrix on atrial myocytes. Whole-cell clamp, confocal microscopy with fluorescence, and western blotting were used to evaluate the action potential and ionic currents of HL-1 cells treated with and without (control) colchicine (3 nM) for 24 hrs. Compared with control cells, colchicine-treated HL-1 cells had a longer action potential duration with smaller intracellular Ca(2+) transients and sarcoplasmic reticulum (SR) Ca(2+) content by 10% and 47%, respectively. Colchicine-treated HL-1 cells showed a smaller L-type Ca(2+) current, reverse mode sodium-calcium exchanger (NCX) current and transient outward potassium current than control cells, but had a similar ultra-rapid activating outward potassium current and apamin-sensitive small-conductance Ca(2+) -activated potassium current compared with control cells. Colchicine-treated HL-1 cells expressed less SERCA2a, total, Thr17-phosphorylated phospholamban, Cav1.2, CaMKII, NCX, Kv1.4 and Kv1.5, but they expressed similar levels of the ryanodine receptor, Ser16-phosphorylated phospholamban and Kv4.2. Colchicine attenuated the shortening of the collagen-induced action potential duration in HL-1 cells. These findings suggest that colchicine modulates the atrial electrical activity and Ca(2+) regulation and attenuates the electrical effects of collagen, which may contribute to its anti-AF activity.

  9. Design and Synthesis of a Series of L-trans-4-Substituted Prolines as Selective Antagonists for the Ionotropic Glutamate Receptors Including Functional and X-ray Crystallographic Studies of New Subtype Selective Kainic Acid Receptor Subtype 1 (GluK1) Antagonist (2S,4R)-4-(2-Carboxyphenoxy)pyrrolidine-2-carboxylic Acid

    DEFF Research Database (Denmark)

    Krogsgaard-Larsen, Niels; Delgar, Claudia; Koch, Karina;

    2017-01-01

    Ionotropic glutamate receptor antagonists are valuable tool compounds for studies of neurological pathways in the central nervous system. On the basis of rational ligand design, a new class of selective antagonists, represented by (2S,4R)-4-(2-carboxy-phenoxy)pyrrolidine-2-carboxylic acid (1b), f...

  10. Intradentate colchicine retards the development of amygdala kindling.

    Science.gov (United States)

    Dasheiff, R M; McNamara, J O

    1982-04-01

    The mechanisms underlying the kindling model of epilepsy are unknown. Presumably, an altered network of neural circuits underlie amygdala kindling. Biochemical and radiohistochemical studies have pointed to the dentate granule cells (DGC) of the hippocampal formation as a member of this altered circuit. To test the role of these cells, colchicine, a neurotoxin of DGC, was directly injected into the dentate gyrus. Prior destruction of DGC retarded the development of amygdala kindling. Destruction of DGC after kindling was completed did not reverse the kindling effect. We conclude that DGC play a key role in the development, but not the permanence, of amygdala kindling. We propose a model whereby the greater the input to the hippocampal formation, the faster limbic kindling will proceed.

  11. Efficacy of anakinra treatment in a patient with colchicine-resistant familial Mediterranean fever.

    Science.gov (United States)

    Alpay, Nilüfer; Sumnu, Abdullah; Calışkan, Yaşar; Yazıcı, Halil; Türkmen, Aydın; Gül, Ahmet

    2012-10-01

    Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by self-limited recurrent attacks of fever and serositis. The serious complication of FMF is AA-type amyloidosis, which can result in end-stage renal disease. Although colchicine is effective in the majority of patients, there is no established treatment for those who are resistant or intolerant to colchicine. We herein report the efficacy of anakinra in a 52-year-old Turkish patient with FMF, secondary amyloidosis and renal transplant, who was resistant to colchicine treatment.

  12. Non-response to colchicine in familial Mediterranean fever should be identified accurately.

    Science.gov (United States)

    Melikoglu, Meltem A; Senel, Kazim

    2014-04-07

    Colchicine prophylaxis is the single most important factor in ameliorating familial Mediterranean fever (FMF) for the prevention of both attacks and secondary amyloidosis. The aim of the present study was to evaluate the exact proportion of those patients who do not respond to colchicine and to characterize their demographic, sociodemographic and clinical aspects. One hundred and eight patients with FMF were included in our study. The demographic (age, gender), socioeconomic (education level, employment status, economic income level) and clinical features (age at onset of FMF, age at FMF diagnosis, family history of FMF, mean duration of colchicine use and mean daily colchicine dose) of the patients were evaluated. The patients unresponsive to colchicine therapy, according to their statements, were recorded. Also with another question, patients' routine colchicine-consuming habits were elucidated in a self-answering format. 'Non-responders' were defined as patients who experienced FMF attacks at a frequency greater than once every 3 months despite treatment with 2 mg colchicine daily. Data were analyzed with the chi-square test and Fisher's exact test. There were 50 female and 58 male patients with a mean age of 42.4 ± 11.3 years. The mean age at FMF onset and at FMF diagnosis were 14.3 ± 10.5 and 19.1 ± 12.9 years, respectively. Sixteen percent of the patients defined themselves as 'suffering from attacks in spite of regular colchicine'. Irregular colchicine usage was determined in 11% of the patients who were considered as 'unresponsive to colchicine therapy' according to their statements. In spite of regular colchicine regimen, attacks were present in 5% of the patients in our study. Although there was no difference in demographic and clinical aspects, patients with irregular colchicine usage were found to be from lower socioeconomic backgrounds, had less education and more unemployment (P FMF before claiming its failure. © 2014 Asia Pacific

  13. Effect of colchicine on mammalian liver nuclear envelope and on nucleo-cytoplasmic RNA transport.

    Science.gov (United States)

    Agutter, P S; Suckling, K E

    1982-09-27

    The binding of colchicine to nuclear envelopes was studied in order to elucidate the mechanism whereby this compound inhibits nucleocytoplasmic RNA transport. The results suggest that a single class of colchicine-binding site (dissociation constant=approx. 0.7 mM, concentration=approx. 330 nmol colchicine/mg protein) is localised in the nuclear periphery (pore-lamina) and that binding to these sites effects a constriction of the pore-complexes with concomitant inhibition of RNA egress and disordering of the nuclear membrane phospholipid bilayers.

  14. The Effect of Colchicine on Thyroid Eye Disease: A Case Report

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    Ali Saklamaz

    2015-12-01

    Full Text Available Thyroid eye disease (TED is the most common extrathyroidal manifestation of Graves’ disease (GD. Corticosteroids are mostly used drug for this complication. Can colchicine be used for the treatment of Graves’ ophthalmopathy (GO? A 49-year-old female, who suffered hyperthyroidism for 5 years, was admitted to our clinic for GO. Although the euthyroidism was achieved, there was no improvement in orbitopathy. Because of the patient’s condition, we could not prescribe corticosteroids to our patient. TED improved after 3 months of colchicine treatment and the patient was found to be satisfied with her new appearance. No side effects related with colchicine treatment were observed. Colchicine can be used as an effective and safe drug in GO.

  15. Toxicokinetics of colchicine in humans: analysis of tissue, plasma and urine data in ten cases.

    Science.gov (United States)

    Rochdi, M; Sabouraud, A; Baud, F J; Bismuth, C; Scherrmann, J M

    1992-11-01

    1. A specific and sensitive radioimmunoassay was used to study the toxicokinetics of colchicine in seven cases of acute human poisoning. Post-mortem tissue concentrations of colchicine were measured in three further cases. Depending on the time of patient admission, two disposition processes could be observed. The first, in three patients, admitted early, showed a bi-exponential plasma colchicine decrease, with distribution half-lives of 30, 45 and 90 min. The second, in four patients, admitted late, showed a mono-exponential decrease. Plasma terminal half-lives ranged from 10.6 to 31.7 h for both groups. 2. Pharmacokinetic analysis of urine colchicine data was performed for two patients. The fraction of unchanged colchicine excreted in urine was about 30%, renal clearance was about 13 l h-1 and three-fold less than total body clearance (39 l h-1). The apparent volume of distribution was 21 l kg-1. 3. Post-mortem tissue analysis showed an ubiquitous colchicine distribution. Colchicine accumulated at high concentrations in the bone marrow (more than 600 ng g-1), testicle (400 ng g-1), spleen (250 ng g-1), kidney (200 ng g-1), lung (200 ng g-1) and heart (95 ng g-1); it was also found in the brain (125 ng g-1). 4. This toxicokinetic study shows that after massive ingestion, the disposition parameters and kinetics of colchicine are not markedly modified from those occurring in healthy volunteers. The absorption process was not delayed and the distribution and elimination half-lives were in the range known to occur with therapeutic doses.

  16. In vivo Induction of Tetraploid in Tangerine Citrus Plants (Citrus reticulata Blanco) with the Use of Colchicine.

    Science.gov (United States)

    Surson, Suntaree; Sitthaphanit, Suphasit; Wongma, Nattapong

    2015-01-01

    This in vivo experiment was carried out at Sakhon Nakhon Rajabhat University, Sakhon Nakhon Province, Thailand during March-October 2013. The study aims to search for some possibilities in inducing a large number of tetraploid sets of chromosomes in tangerine citrus seedlings with the use of colchicine chemical. A Randomized Complete Block Design (RCBD) with four replications was used. Seeds of tangerine citrus were treated with colchicine solutions. The experiment consisted of seven treatments, i.e., T1 with 0.0% colchicine (control), T2 with 0.2% colchicine solution and submerged for 12 h, T3 with 0.2% colchicine solution and submerged for 24 h, T4 with 0.4% colchicine solution and submerged for 12 h, T5 with 0.4% colchicine solution and submerged for 24 h, T6 with 0.8% colchicine solution and submerged for 12 h, T7 with 0.8% colchicine solution and submerged for 24 h. The experiment was conducted for 91 days. The results showed that colchicine compound severely and significantly affected germination of tangerine citrus seeds. Colchicine of 0.2% in the solution with seeds submerged for 24 h gave the highest percentages of tetraploid chromosomes in seedlings of tangerine citrus (63.64%). Colchicine significantly affected seed germination, plant height, stomata density and leaf index of the tangerine citrus seeds and seedlings. Colchicine had no significant effect on poly-embryos, mono-embryos, leaf number, leaf area, leaf weight, leaf length and stomata length of the tangerine citrus seedlings.

  17. Colchicine treatment in children with familial Mediterranean fever: is it a risk factor for neuromyopathy?

    Science.gov (United States)

    Işıkay, Sedat; Yılmaz, Kutluhan; Yiğiter, Remzi; Balat, Ayşe; Büyükçelik, Mithat

    2013-12-01

    We cared for a 17-year-old adolescent with familial Mediterranean fever under colchicine treatment. Because of the increased creatinine kinase level (3937 U/L) observed in this individual, we planned to assess all pediatric patients with familial Mediterranean fever under colchicine treatment to detect any resultant neuromyopathy. The study included 88 children with familial Mediterranean fever who were receiving colchicine. The patient with myopathy was not included in the study. Serum creatinine kinase levels were measured and nerve conduction studies were carried out in all patients. The study included 88 patients (47 female, 53.4%) with an average age of 10.1 ± 3.35 years. The average period of colchicine use was 28.25 ± 17.66 months. Side effects of colchicine were detected in 10 patients (11%)--as diarrhea in eight patients, leukopenia in one patient, and hair loss in one patient. Nerve conduction studies determined incidental carpal tunnel syndrome in only one patient. Our study did not suggest an elevated risk of neuromyopathy associated with the use of colchicine for familial Mediterranean fever. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

  18. Association between colchicine resistance and vitamin D in familial Mediterranean fever.

    Science.gov (United States)

    Ozer, Ismail; Mete, Turkan; Turkeli Sezer, Ozlem; Kolbasi Ozgen, Guyem; Kucuk, Gultekin Ozan; Kaya, Coskun; Kilic Kan, Elif; Duman, Gulhan; Ozturk Kurt, Hacer Pinar

    2015-08-01

    Although colchicines are the only effective treatment of familial Mediterranean fever (FMF), resistance to colchicines (CR) which is observed in up to 30% of the patients is still a problem. Clinically, resistance to colchicine is defined as three or more attacks within the last 6 months period while using ≥2 mg/day colchicine. Previous studies have shown decreased vitamin D levels in FMF patients compared with healthy controls. The aim of this study is to evaluate whether vitamin D levels differ between CR and non-CR FMF patients. This study included 64 FMF patients who were being followed in Nephrology Clinic of Samsun Research and Education Hospital for at least 1 year. FMF was diagnosed according to the criteria defined by Livneh et al. Serum 25-hydroxy vitamin D (25-OHD) concentration (ng/mL) was detected in all FMF patients who were not in an acute attack period. From 64 patients 29 were accepted as CR. Mean 25-OHD level was 9.39 ± 1.00 ng/mL in CR patients and 18.48 ± 1.09 ng/mL in colchicine responsive patients (p < 0.001). Plasma vitamin D levels were significantly lower in colchicine resistant patients. Vitamin D deficiency may be a factor in etiopathogenesis of CR. Studies in larger patient samples that particularly evaluate the response to vitamin D replacement in CR FMF patients are needed.

  19. Effects of colchicine on pericardial diseases: a review of the literature and current evidence

    Directory of Open Access Journals (Sweden)

    Syed Raza Shah

    2016-07-01

    Full Text Available Colchicine, extracted from the colchicum autumnale plant, used by the ancient Greeks more than 20 centuries ago, is one of the most ancient drugs still prescribed even today. The major mechanism of action is binding to microtubules thereby interfering with mitosis and subsequent modulation of polymorphonuclear leukocyte function. Colchicine has long been of interest in the treatment of cardiovascular disease; however, its efficacy and safety profile for specific conditions have been variably established in the literature. In the subset of pericardial diseases, colchicine has been shown to be effective in recurrent pericarditis and post-pericardiotomy syndrome (PPS. The future course of treatment and management will therefore highly depend on the results of the ongoing large randomized placebo-controlled clinical trial to evaluate the efficacy and safety of colchicine for the primary prevention of several postoperative complications and in the perioperative period. Also, given the positive preliminary outcomes of colchicine usage in pericardial effusions, the future therapeutical use of colchicine looks promising. Further study is needed to clarify its role in these disease states, as well as explore other its role in other cardiovascular conditions.

  20. Effects of colchicine on pericardial diseases: a review of the literature and current evidence

    Science.gov (United States)

    Shah, Syed Raza; Alweis, Richard; Shah, Syed Arbab; Arshad, Mohammad Hussham; Manji, Adil Al-Karim; Arfeen, Arham Amir; Javed, Maheen; Shujauddin, Syed Muhammad; Irfan, Rida; Shabbir, Sakina; Shaikh, Shehryar

    2016-01-01

    Colchicine, extracted from the colchicum autumnale plant, used by the ancient Greeks more than 20 centuries ago, is one of the most ancient drugs still prescribed even today. The major mechanism of action is binding to microtubules thereby interfering with mitosis and subsequent modulation of polymorphonuclear leukocyte function. Colchicine has long been of interest in the treatment of cardiovascular disease; however, its efficacy and safety profile for specific conditions have been variably established in the literature. In the subset of pericardial diseases, colchicine has been shown to be effective in recurrent pericarditis and post-pericardiotomy syndrome (PPS). The future course of treatment and management will therefore highly depend on the results of the ongoing large randomized placebo-controlled clinical trial to evaluate the efficacy and safety of colchicine for the primary prevention of several postoperative complications and in the perioperative period. Also, given the positive preliminary outcomes of colchicine usage in pericardial effusions, the future therapeutical use of colchicine looks promising. Further study is needed to clarify its role in these disease states, as well as explore other its role in other cardiovascular conditions. PMID:27406462

  1. Colchicine Inhibited the Expression of Tissue Inhibitor of Metalloprotenase-1 and Interleukin-6 in Cultured Activated Hepatic Stellate Cells

    Institute of Scientific and Technical Information of China (English)

    LI Zesong; CAI Shaoxi; JIANG Yuan; GUO RuiJun; ZHANG Wen

    2006-01-01

    Cultured HSCs were treated colchicine with different concentrations for 12 h, respectively. The effects of colchicine on HSCs growth were measured by MTT assay. Effects of colchicine on gene expression of HSCs were analysed by using a self-made oligonucleotide microarray. Colchicine inhibited HSCs growth in a dose-dependent manner. After 12 h of treatment with 6.25 mg/L of colchicine, the expression of tissue inhibitor of metalloprotenase1 (TIMP-1) and the expression of interleukin-6 (IL-6) in HSCs were downregulated by 2.3 folds and 2.1 folds, respectively. These results suggest that colchicine's beneficial effects may, at least in part, owe to the inhibitory to the proliferation of HSCs and down-regulation of the expression of both TIMP1 and IL-6 in HSCs.

  2. To Investigate the Effect of Colchicine in Prevention of Adhesions Caused by Serosal Damage in Rats

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    İhsan Yıldız

    2015-01-01

    Full Text Available Introduction and Aim. Adhesion formation is a process which starts with an inflammation caused by a number of factors and eventually results in fibrosis. Colchicine prevents adhesion formation which is antifibrous process. The effectivity of colchicine in the prevention of adhesions was investigated. Materials and Methods. A total of 36 rats were equally divided into three groups: (I control group 1 (n=12, (II abrasion group 2 (n=12, and (III abrasion + colchicine group 3 (n=12. Group 1 underwent laparotomy and was orally given physiological serum 2 cc/day for 10 days. In Group 2, injury was created in the cecum serosa following laparotomy and they were orally given physiological serum 2 cc/day for 10 days. In Group 3, injury was created in the cecum serosa following laparotomy and the rats were orally given colchicine 50 mcg kg/day mixed with physiological serum 2 cc/day for 10 days. Laparotomy was performed and adhesions were examined both macroscopically and microscopically. Both macroscopic and microscopic examinations were performed using Zühlke’s score. Results. A significant difference was observed among the adhesion scores of the groups both macroscopically and microscopically. Macroscopic score was lower in group 3 than group 2. Microscopic score was lower in group 3 than group 2. Conclusion. Oral administration of colchicine is effective in the prevention of adhesions.

  3. Colchicine may assist in reducing granulation tissue in junctional epidermolysis bullosa

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    Minhee Kim, MBBS

    2016-06-01

    Full Text Available Epidermolysis bullosa (EB is a rare, inherited blistering genodermatosis. Patients with junctional EB (JEB due to LAMB3 mutations have widespread blisters and erosions of skin, mucosae, and nails, creating significant physical, emotional, and psychosocial burdens. Here we report the use of colchicine for ameliorating hypergranulating wounds in a 41-year-old female with JEB generalized intermediate. Her skin wounds and granulation tissue gradually exacerbated under silicone dressings such that she became profoundly anemic. Subsequently, she was commenced on colchicine 500 μg daily on the basis that it may inhibit cell proliferation and be anti-inflammatory. After a 6-month trial of colchicine, she had an objective and subjective improvement in her validated EB Disease Activity and Scarring Index activity and damage scores and Quality Of Life in EB score with less skin erosions, granulation tissue, and erythema. In addition, her anemia resolved. She denied any gastrointestinal side effects. The exact mechanism of colchicine in assisting reduction of the blistering, erosions, and granulation in JEB is unclear, but the anti-inflammatory and antimitotic properties of colchicine may be partially responsible for this process.

  4. Risk of Colchicine-Associated Myopathy in Gout: Influence of Concomitant Use of Statin.

    Science.gov (United States)

    Kwon, Oh Chan; Hong, Seokchan; Ghang, Byeongzu; Kim, Yong-Gil; Lee, Chang-Keun; Yoo, Bin

    2017-05-01

    The purpose of this study was to investigate the risk of myopathy when statins are coadministered with colchicine in patients with gout. In gout patients who received colchicine with or without statin, clinical data collected included medications and history of hypertension, chronic kidney disease, and liver cirrhosis. Myopathy was defined as the presence of muscle symptoms with elevated creatine kinase or myoglobin. Multivariate analysis was performed to identify risk factors for myopathy. Inverse probability of treatment weighting (IPTW)-adjusted analysis was used to evaluate the influence of concomitant colchicine and statin use on myopathy. Of 674 patients, 486 received colchicine alone and 188 also received statin. The incidence of myopathy was not significantly higher in those on both drugs than in those on colchicine alone (2.7% vs 1.4%, P = .330). On multivariate analysis, chronic kidney disease (hazard ratio [HR] 29.056; 95% confidence interval [CI], 4.387-192.450; P gout patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Mutagenic influences of colchicine on phenological and molecular diversity of Calendula officinalis L.

    Science.gov (United States)

    El-Nashar, Y I; Ammar, M H

    2016-04-26

    Six different colchicine concentrations: 0, 400, 800, 1200, 1600, and 2000 ppm, in combination with four soaking time treatments (1, 2, 3, and 4 h), were selected to assess the effects on germination, vegetative growth, and flower yield components in calendula plants. The molecular diversity among the treatments was assessed using ten SRAP marker combinations. Seed soaking in colchicine significantly enhanced both the fresh and the dry shoot and root masses, flowering date, number of flowers per plant, and flower diameter. At 1200-ppm colchicine combined with a 4-h soaking time, a superior effect on seed germination was observed, whereas 800 ppm for 4 h produced the highest number of flowers and the largest flower diameter. The earliest flowering time was found at 800 ppm combined with a short soaking time (1 h), while the 4-h soaking time with 800 ppm, is recommended for growing calendula outdoors, since it enhances flower development. At the molecular level, 752 fragments were successfully amplified using the SRAP primers, with 280 genetic loci found throughout the calendula genome. The polymorphism percentage ranged from 79 to 100% and the polymorphic information content (PIC) values ranged between 0.85 and 0.97. The high number of detected loci and PIC values suggests a great power of SRAP markers in detecting mutant molecular diversity. Our results clearly show the existence of genetic variation among colchicine treated calendula plants and the clustering of the studied mutants was concordant with the colchicine concentration used.

  6. A high performance thin layer chromatographic method for the estimation of colchicine in different formulations

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    Mohd Fahim

    2015-01-01

    Full Text Available Background: Colchicine is a main alkaloid present in bitter and sweet variety of colchicum (Colchicum luteum Baker, which have been reported to possess anti-rheumatic, anti-gout, and anticancer potential. Colchicum is an important ingredient of several Unani and Herbal formulations. Quantification of colchicine will play a great role in quality control of these formulations. Hence, a high-performance thin layer chromatographic (TLC method has been developed for the analysis of colchicine in Unani formulations of various dosage forms such as hubb (tablet and capsules. Materials and Methods: The samples were applied on aluminum TLC plates precoated with silica gel 60-F254and developed using mobile phase toluene-dichloromethane-methanol in equal proportions. Quantification was done by densitometric scanning at 350 nm, which showed a linear response in the range of 50–500 ng/spot. The developed method was validated as per the International Conference on Harmonization guidelines for linearity, precision, accuracy, specificity, robustness, limit of detection, and limit of quantification. Results and Conclusion: The developed method was applied for quantitative estimation of colchicine in different Unani and Herbal formulations. The method was found simple, selective, accurate with a wide range of linearity, hence suitable for the quality control of different formulations and varieties of colchicum with respect to colchicine content.

  7. Colchicine-clarithromycin-induced rhabdomyolysis in Familial Mediterranean Fever patients under treatment for Helicobacter pylori.

    Science.gov (United States)

    Cohen, Oren; Locketz, Garrett; Hershko, Alon Y; Gorshtein, Alexander; Levy, Yair

    2015-11-01

    Chronic administration of colchicine remains a mainstay of therapy for patients with Familial Mediterranean Fever (FMF). As this medication is a strong CYP3A4 inhibitor, it has the potential to interact with many routinely used medications. One such medication is clarithromycin, itself a strong inhibitor of the same enzyme, and a typical choice for triple therapy eradication of H. pylori. Various sequelae of colchicine-clarithromycin interaction have been documented and can be expected by prescribing physicians, with rhabdomyolysis, though rare, being among the most serious. Review of cases from a tertiary academic medical center and full PubMed/MEDLINE literature review. Despite the prevalence of diseases treated with clarithromycin and the expected drug interaction with colchicine, only two cases in the literature document clinical rhabdomyolysis due to colchicine-clarithromycin interaction. In neither case, however, were patients undergoing treatment for FMF. Herein, we describe the first two cases in the literature of clinical rhabdomyolysis in FMF patients under colchicine therapy after administration of clarithromycin as part of therapy treating H. pylori infection.

  8. The effect of colchicine and disease severity on physical growth in children with familial Mediterranean fever.

    Science.gov (United States)

    Yoldaş, Tuba Çelen; Çakar, Nilgün; Başaran, Özge; Acar, Banu; Uncu, Nermin; Çaycı, F Şemsa

    2016-06-01

    This study aimed to investigate the effects of colchicine on growth parameters in familial Mediterranean fever (FMF) patients. Fifty-one (29 girls, 22 boys) FMF patients were enrolled in the study. All of the patients were in the prepubertal stage and had not received colchicine treatment before the study. Anthropometric measurements, demographic features, clinical findings at diagnosis and during periods of attacks of FMF, disease activity, frequency of exacerbations, colchicine dosage, and weight and height measurements were recorded at an interval of 6 months. Height, weight, and body mass index standard deviation scores and Z-scores were calculated. The mean height standard deviation score (HSDS) was significantly increased from -0.64 ± 1.20 to -0.26 ± 1.07 (p treatment compared with before initiation of treatment. In patients who had no FMF attacks during colchicine treatment, height and weight were significantly increased at 1 year (HSDS: p < 0.001 WSDS: p = 0.002), but in patients who had recurrent attacks, height and weight did not change (HSDS: p = 0.051, WSDS: p = 0.816). Even when subclinical inflammation is present, preventing attacks of FMF with colchicine allows growth to continue. However, suppression of subclinical inflammation and control of attacks of FMF are required for weight gain.

  9. Rapid onset of muscle weakness (rhabdomyolysis) associated with the combined use of simvastatin and colchicine.

    Science.gov (United States)

    Justiniano, Maria; Dold, Sylvia; Espinoza, Luis R

    2007-10-01

    We report a case of a patient with mild chronic renal insufficiency who had been taking simvastatin for over a year and developed acute weakness within 3 weeks after the start of treatment with colchicine for acute gouty bursitis. Profound muscle weakness of lower extremities with inability to stand up and/or walk was present. Elevated muscle enzymes and findings on electromyography were consistent with myopathy. Rapid improvement in muscle strength accompanied by prompt resolution of abnormal elevation of muscle enzymes followed cessation of both medications. Both colchicine and statin therapy may be associated with myopathy, which usually occurs after several months of therapy. The concomitant use, however, of colchicine and statin has been associated with the rapid onset of muscle weakness. Four patients with similar clinical and laboratory characteristics to our patient's after the combined use of colchicine and statins have been described in the literature. Patients receiving combination therapy with colchicine and simvastatin, particularly in the presence of renal insufficiency, should be monitored for the development of myopathy, including rhabdomyolysis.

  10. Colchicine failure in familial Mediterranean fever and potential alternatives: embarking on the anakinra trial.

    Science.gov (United States)

    Ben-Zvi, Ilan; Livneh, Avi

    2014-05-01

    Familial Mediterranean fever (FMF) is a genetic auto-inflammatory disease characterized by spontaneous short attacks of fever, elevated acute-phase reactants, and serositis. Approximately 5%-10% of FMF patients do not respond to colchicine treatment and another 5% are intolerant to colchicine because of side effects. Recently, following the discovery of the inflammasome and recognition of the importance of interleukin-1beta (IL-1beta) as the major cytokine involved in the pathogenesis of FMF, IL-1beta blockade has been suggested and tried sporadically to treat FMF, with good results. To date, case reports and small case series involving colchicine-resistant FMF patients and showing high efficacy of IL-1beta blockade have been reported. At the Israel Center for FMF at the Sheba Medical Centerthe first double-blind randomized placebo-controlled trial of anakinra in FMF patients who are resistant or intolerant to colchicines is underway. In this report we discuss the mechanism of colchicine resistance in FMF patients, the data in the literature on IL1beta blockade in these patients, and the anakinra trial inclusion criteria and study protocol.

  11. Polygamain, a new microtubule depolymerizing agent that occupies a unique pharmacophore in the colchicine site.

    Science.gov (United States)

    Hartley, R M; Peng, J; Fest, G A; Dakshanamurthy, S; Frantz, D E; Brown, M L; Mooberry, S L

    2012-03-01

    Bioassay-guided fractionation was used to isolate the lignan polygamain as the microtubule-active constituent in the crude extract of the Mountain torchwood, Amyris madrensis. Similar to the effects of the crude plant extract, polygamain caused dose-dependent loss of cellular microtubules and the formation of aberrant mitotic spindles that led to G(2)/M arrest. Polygamain has potent antiproliferative activities against a wide range of cancer cell lines, with an average IC(50) of 52.7 nM. Clonogenic studies indicate that polygamain effectively inhibits PC-3 colony formation and has excellent cellular persistence after washout. In addition, polygamain is able to circumvent two clinically relevant mechanisms of drug resistance, the expression of P-glycoprotein and the βIII isotype of tubulin. Studies with purified tubulin show that polygamain inhibits the rate and extent of purified tubulin assembly and displaces colchicine, indicating a direct interaction of polygamain within the colchicine binding site on tubulin. Polygamain has structural similarities to podophyllotoxin, and molecular modeling simulations were conducted to identify the potential orientations of these compounds within the colchicine binding site. These studies suggest that the benzodioxole group of polygamain occupies space similar to the trimethoxyphenyl group of podophyllotoxin but with distinct interactions within the hydrophobic pocket. Our results identify polygamain as a new microtubule destabilizer that seems to occupy a unique pharmacophore within the colchicine site of tubulin. This new pharmacophore will be used to design new colchicine site compounds that might provide advantages over the current agents.

  12. Effect of colchicine applied to callus of mangosteen on morphological changes of regenerated plants

    Directory of Open Access Journals (Sweden)

    Te-chato, S.

    2000-07-01

    Full Text Available Calli of mangosteen raised on callus induction medium (CIM at 20 days of culture were submerged in various concentrations of colchicine. The cultures were incubated on a rotary shaker and shaken at 80 rpm for 2 hours. In the case of high concentrations of colchicine (500 and 750 mg/l, the calli were cultured directily on the colchicine-containing media for 90 days. The results showed that leaves of regenerated shoots contained more chlorophyll b than those of control. However, shoot size, leaf area and leaf number tended to decrease while number and lenght of roots increased. A high concentration of colchicine, 500 mg/l, produced shoots with brown-callused leaves. However, roots could be induced from these shoots to from complete plantlets. Some of the intact leaves produced a large number of shoots. Colchicine at 750 mg/l gave some morphological abnormalities with 5 roots per shoot. A small shoot could produce a large healthy root. Some shoots produced 3 leaves per whorl.

  13. Interest of Colchicine for the Treatment of Cystic Fibrosis Patients. Preliminary Report

    Directory of Open Access Journals (Sweden)

    I. Sermet-Gaudelus

    1999-01-01

    Full Text Available Cystic fibrosis (CF lung disease is characterized by persistent inflammation. Antiinflammatory drugs, such as corticosteroids and ibuprofene, have proved to slow the decline of pulmonary function although their use is limited because of frequent adverse events. We hypothesized that colchicine could be an alternative treatment because of its antiinflammatory properties and upregulatory effect on cystic fibrosis transmembrane regulator (CFTR closely related proteins. We herein present results obtained in an open study of eight CF children treated with colchicine for at least 6 months. Clinical status was better in all patients and respiratory function tests significantly improved in five. Median duration of antibiotherapy decreased significantly. These preliminary results support our hypothesis of a beneficial effect of colchicine in CF patients and stress the need for a controlled therapeutic trial.

  14. Quinolin-6-Yloxyacetamides Are Microtubule Destabilizing Agents That Bind to the Colchicine Site of Tubulin

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    Ashwani Sharma

    2017-06-01

    Full Text Available Quinolin-6-yloxyacetamides (QAs are a chemical class of tubulin polymerization inhibitors that were initially identified as fungicides. Here, we report that QAs are potent anti-proliferative agents against human cancer cells including ones that are drug-resistant. QAs act by disrupting the microtubule cytoskeleton and by causing severe mitotic defects. We further demonstrate that QAs inhibit tubulin polymerization in vitro. The high resolution crystal structure of the tubulin-QA complex revealed that QAs bind to the colchicine site on tubulin, which is targeted by microtubule-destabilizing agents such as colchicine and nocodazole. Together, our data establish QAs as colchicine-site ligands and explain the molecular mechanism of microtubule destabilization by this class of compounds. They further extend our structural knowledge on antitubulin agents and thus should aid in the development of new strategies for the rational design of ligands against multidrug-resistant cancer cells.

  15. Colchicine to Reduce Atrial Fibrillation in the Postoperative Period of Myocardial Revascularization

    Science.gov (United States)

    Zarpelon, Camila Stuchi; Netto, Miguel Chomiski; Jorge, José Carlos Moura; Fabris, Cátia Carolina; Desengrini, Dieli; Jardim, Mariana da Silva; da Silva, Diego Guedes

    2016-01-01

    Background The high prevalence of atrial fibrillation (AF) in the postoperative period of myocardial revascularization surgery increases morbidity and mortality. Objective To assess the efficacy of colchicine to prevent AF in the postoperative period of myocardial revascularization surgery, the impact of AF on hospital length of stay and death, and to identify its risk factors. Methods Between May 2012 and November 2013, 140 patients submitted to myocardial revascularization surgery were randomized, 69 to the control group and 71 to the colchicine group. Colchicine was used at the dose of 1 mg orally, twice daily, preoperatively, and of 0.5 mg, twice daily, until hospital discharge. A single dose of 1 mg was administered to those admitted 12 hours or less before surgery. Results The primary endpoint was AF rate in the postoperative period of myocardial revascularization surgery. Colchicine group patients showed no reduction in AF incidence as compared to control group patients (7.04% versus 13.04%, respectively; p = 0.271). There was no statistically significant difference between the groups regarding death from any cause rate (5.6% versus 10.1%; p = 0,363) and hospital length of stay (14.5 ± 11.5 versus 13.3 ± 9.4 days; p = 0.490). However, colchicine group patients had a higher infection rate (26.8% versus 8.7%; p = 0.007). Conclusion The use of colchicine to prevent AF after myocardial revascularization surgery was not effective in the present study. Brazilian Registry of Clinical Trials number RBR-556dhr. PMID:27223641

  16. Efficient production of tetraploid barley (Hordeum vulgare L. by colchicine treatment of diploid barley

    Directory of Open Access Journals (Sweden)

    Ayed Sourour

    2014-03-01

    Full Text Available An experiment was conducted to induce tetraploidy in three diploid barley varieties (Martin, Rihane and Manel through different colchicines treatments. Colchicine was added for three different concentrations at three different stages of plant development i.e. on seed (0.05% for 48 hours, on pre-germinated seeds (0.1% for 2 hours and on three leaf stage (0.1% for 16 hours. Colchicine application reduced significantly germination percentage and viability of plants. Seed germination was completely inhibited in Martin, while a reduction of 20% and 30% for germination percentage compared to control was recorded in varieties Manel and Rihane, respectively at 0.1% colchicine concentration. Ploidy evaluation showed no tetraploidy in all the three tested varieties by colchicine application of 0.05% for 48 hours on seeds and 0.1% for 2 hours on pre-germinated seeds. However, tetraploid plants were produced only by treatment with 0.1% for 16 hours of seedlings. The percentages of plants were 40%, 44% and 100% for Rihane, Manel and Martin, respectively. Cytological analyses showed the increase of chromosome numbers from 2n=2x=14 to 2n=4x=28. The increase of ploidy levels caused major changes in some morphological traits. In fact, the induced tetraploids in barley was accompanied by significant (P<0.01 decrease in plant height, tiller height, leaf number and leaf length compared to diploid control plants. colchicine treatment induce successfully the production of tetraploid barley plants and could be used in breeding programs.

  17. Relationship between response to colchicine treatment and MDR1 polymorphism in familial Mediterranean fever patients.

    Science.gov (United States)

    Uludag, Ahmet; Silan, Coskun; Atik, Sinem; Akurut, Cisem; Uludag, Aysegul; Silan, Fatma; Ozdemir, Ozturk

    2014-02-01

    Investigate the relationship between MDR1 C3435T polymorphism and colchicine response in Familial Mediterranean fever (FMF) patients. Patients (n=50) who received colchicine regularly, were willing to participate in the study, and attended control visits were included in the study. MDR1 C3435T genotype was defined by the real-time polymerase chain reaction method. Patients were divided into three groups. Patients, who recovered from episodes with standard colchicine treatment, and had no attack in the last 1 year were accepted as complete; patients whose episode number and intensity were decreased with the ongoing standard treatment as partial; and patients whose episodes were not decreased despite the standard treatment as nonresponders. MDR1 C and T allele frequencies of FMF patients with colchicine responses of complete, partial, and nonresponders were C=0.75 and T=0.25; C=0.56 and T=0.44; and C=0.50 and T=0.50, respectively. When complete responding patients were compared with the partial responding patients, subjects with CT genotype had 6.18 times more increased risk than with CC genotype (OR=6.18; p=0.015). Poor response risk of subjects with the T allele was increased 2.45 times more when compared with the C allele (p=0.03). MDR1 gene C3435T polymorphism enacts an important role on colchicine response in FMF; good response to colchicine treatment was related to the C allele, whereas poor response was related to the T allele in FMF.

  18. Novel therapeutics for the treatment of familial Mediterranean fever: from colchicine to biologics.

    Science.gov (United States)

    Grattagliano, I; Bonfrate, L; Ruggiero, V; Scaccianoce, G; Palasciano, G; Portincasa, P

    2014-01-01

    Familial Mediterranean fever (FMF), an inherited autosomal recessive disorder, is characterized by sporadic, paroxysmal attacks of fever and serosal inflammation, lasting 1-3 days. Patients may develop renal amyloidosis, arthritis, serositis, and skin and oral lesions. Diagnosis is based on clinical features, response to treatment with colchicine, and genetic analysis. Colchicine prevents attacks and renal amyloidosis, in addition to reversing proteinuria. Nonresponders may receive novel therapy, including interleukin (IL)-1 receptor antagonists and IL-1 decoy receptor. Recently, new options have been considered.

  19. Treatment of colchicine-resistant Familial Mediterranean fever in children and adolescents.

    Science.gov (United States)

    Eroglu, Fehime Kara; Beşbaş, Nesrin; Topaloglu, Rezan; Ozen, Seza

    2015-10-01

    Familial Mediterranean fever (FMF) is the most common autoinflammatory disease worldwide. Approximately 5-10 % of patients are unresponsive to colchicine. Aim of this study was to determine the short- and long-term efficacy and safety of anti-interleukin 1 (anti-IL1) and anti-tumor necrosis factor agents in colchicine-resistant FMF cases in Turkish children and adolescents. This is a single-center retrospective case series of colchicine-resistant FMF patients. The included patients were treated with biologics for either colchicine resistance or because of one of the following: (1) amyloidosis, (2) recurrent prolonged febrile myalgia and frequent need of steroid and (3) persistent arthritis. Colchicine resistance was defined as at least one attack per month for three consecutive months and elevated erythrocyte sedimentation rate or C-reactive protein or serum amyloid A in-between attacks despite taking adequate dose of colchicine. Response to biologicals was evaluated by the Autoinflammatory Diseases Activity Index (AIDAI) score sheet, patients/parents'/physicians' global assessment of disease severity and laboratory parameters every 3-6 months. Fourteen patients were included in the study. Three patients were treated with etanercept for median 7 months (range 3-11 months), and all patients had to be switched to anti-IL1 treatment because of adverse effects and/or partial response. Eleven patients were treated with anakinra with a median duration of 8 months (4-60 months). Nine patients responded to treatment at the third month, but four of them switched to canakinumab because of noncompliance, local side effects and active arthritis. Nine patients were treated with canakinumab, all responded. At follow-up, in two patients the dose had to be increased, and on the other hand, in three patients the interval was increased to every 12-16 weeks. In three patients, anti-IL1 treatment could be stopped and they are fine with colchicine. This case series describes the

  20. Successful Colchicine Therapy in a Patient With Follicular Bronchiolitis Presumed to Be Asthma.

    Science.gov (United States)

    Goksel, Ozlem; Nart, Deniz; Ergonul, Ayse Gul; Sever, Fidan; Goksel, Tuncay

    2015-07-01

    Follicular bronchiolitis (FB) is a rare small-airway pathology that is associated mainly with connective tissue diseases. This case report presents a new, diagnosed, different airway disease in a non-smoker with rheumatoid arthritis in remission who was treated for presumed asthma, but was not controlled. She was ultimately diagnosed with FB after video-assisted thoracoscopic surgery. The clinical findings of FB were controlled successfully by colchicine after she did not respond to systemic steroid therapy. This is the first case report of FB associated with rheumatoid arthritis that responded to colchicine.

  1. Incomplete response to colchicine in M694V homozygote FMF patients.

    Science.gov (United States)

    Lidar, Merav; Yonath, Hagith; Shechter, Naama; Sikron, Fabienne; Sadetzki, Siegal; Langevitz, Pnina; Livneh, Avi; Pras, Elon

    2012-11-01

    Previous studies have shown that with prophylactic colchicine 65% of the patients suffering from Familial Mediterranean fever (FMF) will show a complete response, 30% a partial response and about 5% will show minimum or no response. These studies were performed before the isolation of the disease gene. Genotyping enables us to study the response rates according to specific mutations. We have witnessed a large number of M694V homozygotes who do not respond well to colchicine despite being treated with maximal sustained doses. To assess the response rates to colchicine in M694V homozygote FMF patients in comparison to other prevalent genotypes. We conducted a telephonic survey which included 112 FMF patients: 40 M694V homozygotes, and 2 comparison groups of 41 M694V/V726A compound heterozygotes and 31 V726A homozygotes. The questionnaire included demographic, social and clinical features, colchicine dose, response rates and reported side effects. M694 homozygotes showed a more severe disease, and were treated with higher doses of colchicine (average dose 1.98±0.56 compared to 1.47±0.58, p=0.0001 and 1.13±0.41, p<0.001 in the M694V/V726A compound heterozygotes and the V726A homozygotes, respectively); Colchicine related side effects were noted in 40% of the M694V homozygotes. The average rate of attacks in treated M694V homozygotes (0.70±1.06) was higher compared to the two other groups (0.14±0.26, p=0.002 and 0.08±0.20, p=0.0009, respectively) and only 25% of them reported no attacks in the last year. None of the patients who took part in this study had amyloidosis. Side effects limiting the dose of colchicine were noted in 40% of the M694V homozygotes. Despite receiving higher doses of colchicine the prevalence of complete responders among M694V homozygotes is much lower than previously appreciated. The results highlight the need for additional treatment modalities for these patients. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Colchicine inhibits epidermal growth factor degradation in 3T3 cells.

    OpenAIRE

    Brown, K. D.; Friedkin, M; Rozengurt, E

    1980-01-01

    Colchicine (2 microM) did not affect the initial rate of association of 125I-labeled epidermal growth factor (125I-EGF) to Swiss 3T3 cells but continued incubation (up to 24 hr) led to an increase in cell-associated radioactivity. The effect is also produced by Colcemid, vinblastine, and podophyllotoxin but not by lumicolchicine. Disruption of microtubules with colchicine does not alter the rate of "down regulation" of EGF receptors, suggesting the binding and internalization of the factor pr...

  3. Pharmacological and clinical basis of treatment of Familial Mediterranean Fever (FMF) with colchicine or analogues: an update.

    Science.gov (United States)

    Cerquaglia, C; Diaco, M; Nucera, G; La Regina, M; Montalto, M; Manna, R

    2005-02-01

    Familial Mediterranean Fever (FMF), an autosomal recessive disorder, is characterised by recurrent attacks of fever and serositis, lasting 24-72 hours. Since 1972 colchicine has become the drug of choice for prophylaxis against FMF attacks and amyloidosis FMF-associated. Colchicine, an alkaloid neutral, is absorbed in the jejunum and ileum. It metabolised by liver and only small amounts are recovered unchanged in the urine. Really plasma half-life is prolonged in patients with liver or renal failure. Colchicine is able to prevent activation of neutrophils, binding beta-tubulin and making beta-tubulin-colchicine complexes; this way inhibits assembly of microtubules and mitotic spindle formation; moreover its mode of action includes modulation of chemokines, prostanoids production, inhibition of neutrophil and endothelial cell adhesion molecules. The minimal daily dose in adults is 1.0 mg/die, but in children there is not a definite dose. Since in vitro high dosages of colchicine stop mitosis, this drug might interfere with male and female fertility and with children growth, but, according to current guidelines and because of rare side effects of the drug, FMF patients are recommended to take colchicine. Since colchicine treatment is often complicated by frequent gastrointestinal side effects, by our experience, in order to improve colchicine tolerance we recommend: lactose-free diet and treatment of intestinal bacterial overgrowth and/or Hp-infection, assessed by breath tests. Since our data showed that 10-15% of FMF patients seem are non-responders or intolerant to colchicine, today we are working in the design of colchicine analogues which may have lesser toxicities and a larger therapeutic window.

  4. Molecular pharmacology of 4-substituted glutamic acid analogues at ionotropic and metabotropic excitatory amino acid receptors

    DEFF Research Database (Denmark)

    Bräuner-Osborne, Hans; Nielsen, B; Stensbøl, T B;

    1997-01-01

    using rat brain ionotropic glutamate receptors, and in functional assays using cloned metabotropic glutamate (mGlu) receptors. As a notable result of these studies, (2S,4R)-4-methylglutamic acid and (2S,4S)-4-methylglutamic acid were shown to be selective for kainic acid receptors and mGlu receptors......The pharmacology of (2S,4R)-4-methylglutamic acid, (2S,4S)-4-methylglutamic acid and (S)- and (R)-4-methyleneglutamic acids (obtained in high chemical and enantiomeric purity from racemic 4-methyleneglutamic acid by chiral HPLC using a Crownpak CR(+) column), was examined in binding experiments...... (subtypes 1alpha and 2), respectively, whereas (S)-4-methyleneglutamic acid showed high but rather non-selective affinity for the (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA), kainic acid, NMDA and mGlu receptors (subtypes 1alpha and 2). Although none of the compounds were specific...

  5. 75 FR 60768 - Single-Ingredient Oral Colchicine Products; Enforcement Action Dates

    Science.gov (United States)

    2010-10-01

    ..., Mutual Pharmaceutical Co., Inc. (Mutual), of Philadelphia, PA, has received approval for three NDAs for... supporting a potentially lethal interaction between P-glycoprotein (P-gp) inhibitors/strong cytochrome P450 3A4 (CYP3A4) inhibitors (such as clarithromycin) and colchicine. Although these interactions have...

  6. Induced Polyploidy in Diploid Ornamental Ginger (Hedychium muluense) Using Colchicine and Oryzalin

    Science.gov (United States)

    The ploidy level of H. muluense, a diploid (2n = 2x = 34) and dwarf ornamental ginger species, has been determined and is reported for the first time. Oryzalin and colchicine were successfully used to induce polyploidy in Hedychium muluense in vitro. Embryogenic cell lines were treated with oryzalin...

  7. The effects of grape seed and colchicine on carbon tetrachloride induced hepatic damage in rats.

    Science.gov (United States)

    Atasever, Ayhan; Yaman, Duygu

    2014-10-01

    This study aims to determine the effects of grape seed and colchicine on carbon tetrachloride (CCl4) induced hepatic damage and on some serum biochemical parameters. Sixty male Wistar albino rats (200-250 g) were randomly divided into six groups (ten rats/group) and included the control group the group were given isotonic sodium chloride (1 mL/kg b.w) intraperitonealy (i.p.), group 2 the group treated i.p. injection of CCl4 (1.0 mL/kg b.w) in corn oil twice in the first week, Groups 3 and 4 injected with CCl4 as described for group 2 and the rats were orally given (100 mg/kg b.w) GSE and i.p. injected (10 μg/rat) with colchicine for four weeks, respectively and groups 5 and 6 were the grape seed and colchicine control groups in which rats were orally given grape seed (100 mg/kg b.w) and i.p. injected with colchicine (10 μg/rat), respectively. Anorexia, weight loss, motionlessness and hepatic colour variation at necropsy were observed in groups 2, 3, and 4. Hyperemia, focal bleeding, fat degeneration, changes ranging from degenerative to necrotic, increase in connective tissue elements, pronounced in portal sites in particular, and infiltration of lymphoid series cell observed in the livers of the rats in group 2, treated with CCl4. Histological hepatic changes in the rats in group 3 and 4 were similar to those in group 2. The levels of serum total protein, albumin and globulin decreased in groups 2, 3, and 4, compared with groups 1, 5 and 6; aspartate transaminase (ALT) activities increased. The lowest alkaline phosphatase (ALP) activities were in groups 4 and 5. We concluded that GSE and colchicine have not sufficient ameliorative effects to CCl4 induced acute hepatic damage.

  8. 秋水仙碱肝损伤机制探讨%Study of the mechanism of liver injury induced by colchicin

    Institute of Scientific and Technical Information of China (English)

    宋金萍; 王涛; 陈雪梅; 杨洁; 张富春; 尚靖

    2011-01-01

    upregulated , FXR , BSEP . MRP2 were downregulated in 6 mg · kg-1 group. ALP activity and concentration of TBA were not significantly changed , while extent of liver damage in total alkaloid extract of Colchicum autumnale L group ( 20 mg · kg-1 ) was lighter than that of colchicin group ( 6 mg · kg-1 ). Conclusion Compared with total alkaloid extract of Colchicum autumnale L, colchicin induced liver injury more severely. In the condition of liver injury, colchicin was similar in regulating synthesis and transportation of bile acid to 4-Acetamido phenol, inferred mainly colchicine induced liver injury caused by severe intrahepatic cholestasis.

  9. 愈痫灵方对KA致痫大鼠海马及颞叶皮质多药耐药基因MDR1b表达的影响%Effects of Yuxianling Decoction on the Expression of Multiple Drug Resistant Gene MDR1b in Hippocampusand Temporal Lobe Cortex of Epileptic Rats Induced by Kainic Acid

    Institute of Scientific and Technical Information of China (English)

    李振光; 宋祖丽; 王净净; 李智雄; 谢静涛; 左亚杰; 张曦; 肖瑶

    2015-01-01

    〔Abstract〕 Objective To investigate the effects of Yuxianling Decoction (YXLD) on expression of multiple drug resistant gene MDR1b in hippocampus and temporal lobe cortex of epileptic rats induced by kaicic acid (KA). Methods (1) Making models:The Hippocampus in rats located by brain stereotactic apparatus was microinjected 1μg KA (1.0 μg/μL) to kindle seizures models. The rats at above seizure behavior surpass Ⅳ level were intragastric administration interfered by sodium valproate and carbamazepine for 14 days, and rekindled 0.5 μL. The rats second attacked seizure at above Ⅳ level and with persistent state were selected.Moreover, the rats with epileptiform discharge wave were selected to be successful resistant refractory epilepsy model rats. (2) Grouping and treatment: The Successful model rats were randomly divided into YXLD group, lamotrigine control group and model group, rats were also assigned into sham operation group and normal control group, 12 rats in each group. The rats were intragastric administration interfered by the same volume of distilled water, lamotrigine and YXLD respectively for 30 days (2 mL/d). (3) Selecting and detecting specimens: The expression of MDR 1b in hippocampus area and temporal lobe cortex was detected by real-time fluorescent quantitative polymerase chain reaction (RT-PCR) method. Results Compared with sham operation control group and normal blank control group, the expression level of MDR1b in hippocampus area was increased obviously (P0.05); The MDR1b expression in hippocampus area of all model groups was higher than that in temporal lobe cortex, the differences have statistical significance (P0.05); MDR1b expression level intemporal lobe cortex between all groups have no statistical significance (P>0.05). Conclusion The expression of multiple drug resistant gene MDR1b in the hippocampus of KA epileptic rats was increased significantly than that in temporal lobe cortex. One of mechanisms of YXLD on anti

  10. Molecular modeling and competition binding study of Br-noscapine and colchicine provides insight into noscapinoid-tubulin binding site

    OpenAIRE

    Naik, Pradeep K.; Santoshi, Seneha; Rai, Ankit; Joshi, Harish C.

    2011-01-01

    We have previously discovered the tubulin-binding anti-cancer properties of noscapine and its derivatives (noscapinoids). Here, we present three lines of evidence that noscapinoids bind at or near the well studied colchicine binding site of tubulin: 1) In silico molecular docking studies of Br-noscapine and noscapine yield highest docking score with the well characterised colchicine-binding site from the co-crystal structure; 2) the molecular mechanics-generalized Born/surface area (MM-GB/SA)...

  11. Optimization of ultrasound-assisted extraction of colchicine compound from Colchicum haussknechtii by using response surface methodology

    Directory of Open Access Journals (Sweden)

    Saeid Khodadoust

    2017-04-01

    Full Text Available In this research an ultrasound-assisted extraction (UAE method was used for extraction of colchicine in root of Colchicum haussknechtii prior to high-performance liquid chromatography with UV detection. C. haussknechtii is used widely in traditional medicine for the treatment of various diseases. The root of this plant is full of colchicine that is suitable for the treatment of gout and cirrhosis and applicable in plant breeding studies to produce polyploidy. The influence of variables on the extraction method was investigated by response surface methodology (RSM and composite design (CCD to achieve maximum extraction yield of colchicine from the root of C. haussknechtii. The most suitable condition for the extraction of colchicine was found to at 40 °C temperature, 32 min extraction time, and 70:30 v/v ethanol–water mixtures with 45:1 solvent-solid ratio. Obtained results showed that there is 1.2% colchicine in the root of C. haussknechtii, so this plant could be introduced as a rich source of colchicine.

  12. Anakinra for Colchicine-Resistant Familial Mediterranean Fever: A Randomized, Double-Blind, Placebo-Controlled Trial.

    Science.gov (United States)

    Ben-Zvi, Ilan; Kukuy, Olga; Giat, Eitan; Pras, Elon; Feld, Olga; Kivity, Shaye; Perski, Oleg; Bornstein, Gil; Grossman, Chagai; Harari, Gil; Lidar, Merav; Livneh, Avi

    2017-04-01

    Familial Mediterranean fever (FMF) is refractory to colchicine prophylaxis in 10-20% of patients. In a number of patient series, treatment with anakinra, an interleukin-1-blocking agent, prevented FMF attacks in those with colchicine-resistant FMF. This study was undertaken to evaluate the efficacy and safety of anakinra in the treatment of colchicine-resistant FMF, using a randomized controlled trial. Patients with colchicine-resistant FMF receiving colchicine (dosage ≥1.5 to ≤3 mg/day) were recruited and randomly assigned to receive anakinra or placebo (vehicle). The treatment duration was 4 months. Primary efficacy outcomes were the number of attacks per month, and the number of patients with a mean of FMF (14 women) were enrolled, of whom 12 were randomized to receive anakinra and 13 to receive placebo. The mean ± SD number of attacks per patient per month was 1.7 ± 1.7 in those receiving anakinra and 3.5 ± 1.9 in those receiving placebo (P = 0.037). Six patients in the anakinra group, compared to none in the placebo group, had treatment for colchicine-resistant FMF. © 2016, American College of Rheumatology.

  13. Molecular modelling and competition binding study of Br-noscapine and colchicine provide insight into noscapinoid-tubulin binding site.

    Science.gov (United States)

    Naik, Pradeep K; Santoshi, Seneha; Rai, Ankit; Joshi, Harish C

    2011-06-01

    We have previously discovered the tubulin-binding anti-cancer properties of noscapine and its derivatives (noscapinoids). Here, we present three lines of evidence that noscapinoids bind at or near the well studied colchicine binding site of tubulin: (1) in silico molecular docking studies of Br-noscapine and noscapine yield highest docking score with the well characterised colchicine-binding site from the co-crystal structure; (2) the molecular mechanics-generalized Born/surface area (MM-GB/SA) scoring results ΔΔG(bind-cald) for both noscapine and Br-noscapine (3.915 and 3.025 kcal/mol) are in reasonably good agreement with our experimentally determined binding affinity (ΔΔG(bind-Expt) of 3.570 and 2.988 kcal/mol, derived from K(d) values); and (3) Br-noscapine competes with colchicine binding to tubulin. The simplest interpretation of these collective data is that Br-noscapine binds tubulin at a site overlapping with, or very close to colchicine-binding site of tubulin. Although we cannot rule out a formal possibility that Br-noscapine might bind to a site distinct and distant from the colchicine-binding site that might negatively influence the colchicine binding to tubulin.

  14. Normal QT dispersion in colchicine-resistant familial Mediterranean fever (FMF).

    Science.gov (United States)

    Nussinovitch, Udi; Livneh, Avi; Volovitz, Benjamin; Nussinovitch, Moshe; Ben-Zvi, Ilan; Lidar, Merav; Nussinovitch, Naomi

    2012-07-01

    The association between familial Mediterranean fever (FMF) and subclinical cardiac disease remains controversial. The aim of the current study was to evaluate whether FMF patients, who do not respond to colchicine treatment, and thereby endure persistent inflammation, have increased QT dispersion (QTd) values. Twenty-two FMF patients and 22 age- and sex-matched control subjects were included in the study. Repolarization and QT dispersion parameters were computed from 12-lead ECG recording using designated computer software, and results of five beats were subsequently averaged. Both FMF patients and controls had similar comorbidities, similar values of average QT, average corrected QT interval length, average QTd interval, average QT corrected dispersion, QT dispersion ratio, JT dispersion (JTd), and JT corrected dispersion. In conclusion, FMF patients who were unresponsive to colchicine treatment and did not develop amyloidosis had normal QTd and JTd parameters, indicating a non-increased risk for repolarization-associated ventricular arrhythmias.

  15. [The induction of chromosome loss and gain by colchicine (author's transl)].

    Science.gov (United States)

    Traut, H; Sommer, U

    1976-09-03

    The fruit fly Drosophila melanogaster is one of the standard systems used for mutagen screening. The colchicine-containing drugs Colchicum-Dispert and Colchysat Burger were fed at extremely low concentrations (1:300 000 and 1:50 000 respectively) to Drosophila females. Among their offspring a remarkably high frequency of aneuploid individuals (XO and XXY flies) were found. These aneuploids correspond karyotypically to the human Ullrich-Turner (XO) and Klinefelter's (XXY) syndromes and result from chromosome loss (XO) and chromosome gain (XXY). The maximum aneuploidy frequency observed after colchicine feeding was 24 times the control value. Depending on their size the aneuploidy frequencies are as great as those obtained by X-irradiation with some hundred or some thousand R.

  16. [A case of colchicine-responsive Mollaret's meningitis with MEFV gene mutation].

    Science.gov (United States)

    Kinohshita, Tomomi; Matsushima, Akira; Satoh, Shunichi; Hoshi, Kenichi; Kishida, Dai; Yahikozawa, Hiroyuki

    2014-01-01

    A 66-year-old woman was admitted to our hospital with recurrent meningitis. She presented with 10 episodes of meningitis in 10 months. Examination of cerebrospinal fluid demonstrated pleocytosis, with neutrophils dominant at the early stage, and lymphocytes dominant at the late stage. Mollaret cells were found and the level of IL-6 was increased in cerebrospinal fluid. Several antibiotics and antiviral agents failed to prevent relapse. However, colchicine therapy successfully prevented the recurrence of meningitis. Genetic testing for familial Mediterranean fever (FMF) showed a mutation in the MEFV gene. It is difficult to diagnose the cause of Mollaret's meningitis in some patients. FMF, neuro-Behçet's disease, and neuro-Sweet disease should be included in the differential diagnosis of recurrent meningitis. In addition, colchicine therapy can prevent the relapse of meningitis in such cases.

  17. Colchicine therapy in amyloidosis related with plasmacytic castleman disease presenting with nephrotic syndrome

    Directory of Open Access Journals (Sweden)

    Saime Paydas

    2015-01-01

    Full Text Available Castleman disease (CD is a neoplasm that presents with single or multiple lymphadenopathy. The disease is characterized by fever, weight loss, anemia, polyclonal hyperglobulinemia, splenomegaly, thrombocytosis and peripheral lymphadenopathy. In this paper, we report a young man with plasmacytic type CD and amyloid A (AA deposition who presented with intra-abdominal mass and nephrotic syndrome. He was successfully treated with colchicine following surgery.

  18. Efficacy and safety of canakinumab in adolescents and adults with colchicine-resistant familial Mediterranean fever.

    Science.gov (United States)

    Gül, Ahmet; Ozdogan, Huri; Erer, Burak; Ugurlu, Serdal; Kasapcopur, Ozgur; Davis, Nicole; Sevgi, Serhan

    2015-09-04

    This open-label pilot study aimed to investigate the efficacy of canakinumab in colchicine-resistant familial Mediterranean fever (FMF) patients. Patients with one or more attacks in a month in the preceding 3 months despite colchicine were eligible to enter a 30-day run-in period. Patients who had an attack during the first run-in period advanced to a second 30-day period. At the first attack, patients started to receive three canakinumab 150 mg subcutaneous injections at 4-week intervals, and were then followed for an additional 2 months. Primary efficacy outcome measure was the proportion of patients with 50 % or more reduction in attack frequency. Secondary outcome measures included time to next attack following last canakinumab dose and changes in quality of life assessed by SF-36. Thirteen patients were enrolled in the run-in period and 9 advanced to the treatment period. All 9 patients achieved a 50 % or more reduction in attack frequency, and only one patient had an attack during the treatment period. C-reactive protein and serum amyloid A protein levels remained low throughout the treatment period. Significant improvement was observed in both physical and mental component scores of the Short Form-36 at Day 8. Five patients had an attack during the 2-month follow-up, occurring median 71 (range, 31 to 78) days after the last dose. Adverse events were similar to those observed in the previous canakinumab trials. Canakinumab was effective at controlling the attack recurrence in patients with FMF resistant to colchicine. Further investigations are warranted to explore canakinumab's potential in the treatment of patients with colchicine resistant FMF. ClinicalTrials.gov NCT01088880 . Registered 16 March 2010.

  19. Colchicine as a therapeutic option in periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis (PFAPA) syndrome.

    Science.gov (United States)

    Butbul Aviel, Yonatan; Tatour, Sameh; Gershoni Baruch, Ruth; Brik, Riva

    2016-02-01

    To evaluate the efficacy of colchicine in reducing the frequency of attacks in patients with PFAPA. We conducted a 6-month open label, randomized, controlled study among patients with PFAPA who attend the Pediatric Rheumatology Clinic at the Rambam Medical Center in Israel. A total of 18 patients aged4 -11 years (males:females ratio = 11:7) were randomized into a control group (I, 10 children) and a study group (II, 8 children). Group I was followed for 6 months without any intervention, and group II was initially followed for 3 months and was thereafter treated with colchicine for 3 additional months, according to standard regimen. During the 6-month period of the study the patients and their physician recorded all the episodes of PFAPA in a constructed log. DNA analyses for the 5 common FMF mutations in Israel were performed in 17 out of the 18 patients. The number of episodes during the first 3 months was similar in both groups (group I 3.2 ± 1.5, group II 4.9 ± 2.3; p ≤ 0.12). Group II had significantly less PFAPA attacks in the second period while on colchicine therapy (4.9 ± 2.3 vs. 1.6 ± 1.2; p ≤ 0.01), in opposition to group I, where no difference in the number of attacks was noted between the first and second period of follow-up (3.2 ± 1.5 vs. 2.7 ± 1.5; p = 0.33). Of the 17 patients tested, 8 were carriers for FMF mutations (2 in group I and 6 in group II). Colchicine prophylaxis seems to be effective in reducing the number of attacks in PFAPA. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Is colchicine an effective treatment in periodic fever, aphtous stomatitis, pharyngitis, cervical adenitis (PFAPA) syndrome?

    Science.gov (United States)

    Dusser, Perrine; Hentgen, Véronique; Neven, Bénédicte; Koné-Paut, Isabelle

    2016-07-01

    PFAPA syndrome is the most frequent periodic fever syndrome in non-Mediterranean patients. The pathogenesis is unclear and the treatment is purely symptomatic and not standardized. The aim of this study was to assess colchicine's efficacy as prophylactic treatment in PFAPA syndrome and to identify factors able to predict response to treatment. We performed a retrospective, multicentric, cohort study of PFAPA patients under colchicine prophylaxis. PFAPA diagnosis was established according to Feder's criteria. Medical records were reviewed and analyzed for demographic, clinical and laboratory data. We distinguished one responder's group, defined as patients who had no more or twice fewer crises under colchicine and another one of non-responders. Subgroup analyses were performed using non-parametric Mann-Whitney test for quantitative data and calculating odds ratio and confidence interval for qualitative data. Difference between the two groups was considered significant for P-value<0.05 or a confidence interval different from 1. Twenty children, 65% of whom were boys, were analyzed. Their mean age at disease onset was 2.3±1.5 years. Among the nine responder patients, five were MEFV (71%) heterozygotes: M694V mutation in four and V726A once. Heterozygous MEFV gene mutation tended to be more frequent in the responders group (71% versus 43%; OR=0.3 [0.03-2.7]). Non-responder patients had more chronic fatigue (82% versus 33%; OR=9 [1,14-71]) and had more oral aphtosis (82% versus 11%; OR=36 [1,7-141]) than the responders ones. Although not significant, colchicine treatment appeared more effective in patients with less complete PFAPA phenotype and MEFV heterozygosity. Copyright © 2016 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  1. Novel analogue of colchicine induces selective pro-death autophagy and necrosis in human cancer cells.

    Directory of Open Access Journals (Sweden)

    Kristen Larocque

    Full Text Available Colchicine, a natural product of Colchicum autumnae currently used for gout treatment, is a tubulin targeting compound which inhibits microtubule formation by targeting fast dividing cells. This tubulin-targeting property has lead researchers to investigate the potential of colchicine and analogs as possible cancer therapies. One major study conducted on an analogue of allocolchicine, ZD 6126, was halted in phase 2 clinical trials due to severe cardio-toxicity associated with treatment. This study involves the development and testing of novel allocolchicine analogues that hold non-toxic anti-cancer properties. Currently we have synthesized and evaluated the anti-cancer activities of two analogues; N-acetyl-O-methylcolchinol (NSC 51046 or NCME, which is structurally similar to ZD 6126, and (S-3,8,9,10-tetramethoxyallocolchicine (Green 1, which is a novel derivative of allocolchicine that is isomeric in the A ring. NSC 51046 was found to be non-selective as it induced apoptosis in both BxPC-3 and PANC-1 pancreatic cancer cells and in normal human fibroblasts. Interestingly, we found that Green 1 was able to modestly induce pro-death autophagy in these pancreatic cancer cells and E6-1 leukemia cells but not in normal human fibroblasts. Unlike colchicine and NSC 51046, Green 1 does not appear to affect tubulin polymerization indicating that it has a different molecular target. Green 1 also caused increased reactive oxygen species (ROS production in mitochondria isolated from pancreatic cancer cells. Furthermore, in vivo studies revealed that Green 1 was well tolerated in mice. Our findings suggest that a small change in the structure of colchicine has apparently changed the mechanism of action and lead to improved selectivity. This may lead to better selective treatments in cancer therapy.

  2. Binding of dihydroxynaphthyl aryl ketones to tubulin colchicine site inhibits microtubule assembly.

    Science.gov (United States)

    Gutierrez, Eunices; Benites, Julio; Valderrama, Jaime A; Calderon, Pedro Buc; Verrax, Julien; Nova, Esteban; Villanelo, Felipe; Maturana, Daniel; Escobar, Cristian; Lagos, Rosalba; Monasterio, Octavio

    2015-10-23

    Dihydroxynaphthyl aryl ketones 1-5 have been evaluated for their abilities to inhibit microtubule assembly and the binding to tubulin. Compounds 3, 4 and 5 displayed competitive inhibition against colchicine binding, and docking analysis showed that they bind to the tubulin colchicine-binding pocket inducing sheets instead of microtubules. Remarkable differences in biological activity observed among the assayed compounds seem to be related to the structure and position of the aryl substituent bonded to the carbonyl group. Compounds 2, 3 and 4, which contain a heterocyclic ring, presented higher affinity for tubulin compared to the carbocyclic analogue 5. Compound 4 showed the best affinity of the series, with an IC50 value of 2.1 μM for microtubule polymerization inhibition and a tubulin dissociation constant of 1.0 ± 0.2 μM, as determined by thermophoresis. Compound 4 was more efficacious in disrupting microtubule assembly in vitro than compound 5 although it contains the trimethoxyphenyl ring present in colchicine. Hydrogen bonds with Asn101 of α-tubulin seem to be responsible for the higher affinity of compound 4 respects to the others.

  3. Effects of Melatonin on Colchicine-Treated PLBs of Dendrobium sonia-28 Orchid.

    Science.gov (United States)

    Lim, M S; Antony, J J J; Islam, S M Shahinul; Suhana, Z; Sreeramanan, S

    2017-01-01

    Dendrobium hybrid orchid is popular in orchid commercial industry due to its short life cycle and ability to produce various types of flower colours. This study was conducted to identify the morphological, biochemical and scanning electron microscopy (SEM) analysis in the Dendrobium sonia-28 orchid plants. In this study, 0.05 and 0.075 % of colchicine-treated Dendrobium sonia-28 (4-week-old culture) protocorm-like bodies (PLBs) were treated in different concentrations of melatonin (MEL) posttreatments (0, 0.05, 0.1, 0.5, 1, 5 and 10 μM). Morphological parameters such as number of shoots, growth index and number of PLBs were determined. In the 0.05 and 0.075 % of colchicine-treated PLBs which were posttreated with 0.05 μM MEL resulted in the highest value of the morphological parameters tested based on the number of shoots (84.5 and 96.67), growth index (16.94 and 12.15) and number of PLBs (126.5 and 162.33), respectively. SEM analysis of the 0.05 μM MEL posttreatment on both the colchicine-treated regenerated PLBs showed irregular cell lineages, and some damages occurred on the stomata. This condition might be due to the effect of plasmolyzing occurred in the cell causing irregular cell lineages.

  4. Normal Heart Rate Variability in Colchicine-Resistant Familial Mediterranean Fever Patients.

    Science.gov (United States)

    Nussinovitch, Naomi; Esev, Konstantin; Lidar, Merav; Nussinovitch, Udi; Livneh, Avi

    2015-05-01

    The relationship between autonomic nervous system (ANS) dysfunction and familial Mediterranean fever (FMF) is controversial. We recently reported normal heart rate variability (HRV), suggestive of normal ANS, in patients with uncomplicated FMF. To evaluate ANS function in colchicine non-responders by using the HRV tool. The study group comprised 24 FMF patients suffering from recurrent FMF attacks despite treatment with a maximal colchicine dose. Electrocardiogram was measured under strict conditions and HRV parameters were calculated. Results were compared with age- and gender-matched unaffected controls. No statistically significant difference was found between the groups in any of the HRV parameters: maximal RR, minimal RR and average RR intervals, standard deviation of RR interval, square root of the mean squared differences of successive RR intervals, HRV triangular index, NN50, pNN50, and power spectral analysis parameters. Although a small difference in HRV parameters in the current study cannot be entirely excluded, FMF patients in whom colchicine did not provide adequate symptomatic relief and who did not develop amyloidosis appear to have normal HRV parameters suggestive of normal ANS function, compared with healthy adults.

  5. Effects of colchicine or demecolcine on cytoplasmic protrusions and assisted enucleation of golden hamster oocytes.

    Science.gov (United States)

    Wang, Lingyan; Jiang, Han; Su, Li; Tang, Bo; Li, Dexue; Li, Ziyi

    2009-12-01

    To establish experimental protocols for cloning golden hamsters, optimal concentrations of colchicine and demecolcine were determined for inducing cytoplasmic protrusion (containing chromosomes) and assisting enucleation of their oocytes. Denuded oocytes at different ages were treated with 2.5-10 microg/ml of colchicine for 1-4h or 0.02-0.6 microg/ml of demecolcine for 15-60 min. Cytoplasmic protrusions of oocytes were removed with a micromanipulation pipette. The results show that: 1) at 13.5-18h post-hCG injection, approximately 90% of oocytes treated for with 10 microg/ml of colchicine formed cytoplasmic protrusions, and in some oocytes enucleation occurred; 2) when treated with 0.4 microg/ml of demecolcine for 1h, cytoplasmic protrusions 13.5-18h post-hCG treatment were present in almost all oocytes; 3) after the protrusions induced by either treatment had been removed, the assisted enucleation rate was >80%, whereas it was approximately 32% with blind enucleation.

  6. Microglial MHC antigen expression after ischemic and kainic acid lesions of the adult rat hippocampus

    DEFF Research Database (Denmark)

    Finsen, B.R.; Jørgensen, Martin Balslev; Diemer, Nils Henrik

    1993-01-01

    Leukocyte common antigen, macrophages, blood-brain barrier, neural degeneration, fascia dentata, neuropathology......Leukocyte common antigen, macrophages, blood-brain barrier, neural degeneration, fascia dentata, neuropathology...

  7. A metallothionein mimetic peptide protects neurons against kainic acid-induced excitotoxicity

    DEFF Research Database (Denmark)

    Sonn, Katrin; Pankratova, Stanislava; Korshunova, Irina

    2010-01-01

    Metallothioneins I and II (MTI/II) are metal-binding proteins overexpressed in response to brain injury. Recently, we have designed a peptide, termed EmtinB, which is modeled after the beta-domain of MT-II and mimics the biological effects of MTI/II in vitro. Here, we demonstrate the neuroprotect...

  8. Association between ABCB1 (MDR1) gene 3435 C>T polymorphism and colchicine unresponsiveness of FMF patients.

    Science.gov (United States)

    Ozen, Filiz; Silan, Coskun; Uludag, Ahmet; Candan, Ferhan; Silan, Fatma; Ozdemir, Semra; Atik, Sinem; Ozdemir, Ozturk

    2011-01-01

    The multidrug resistance gene-1 (MDR1, adenosine triphosphate-binding cassette transporter: ABCB1, P-glycoprotein) encodes membrane proteins that play a crucial role in protecting cells from xenobiotics, chemicals, and drugs. The TT genotype of 3435 codon in exon 26 of MDR1 gene causes overexpression of gene activity and effluxes many chemically diverse compounds across the plasma membrane. We studied the association between C3435T polymorphisms (single nucleotide polymorphism) of MDR1 gene and colchicine-resistant familial Mediterranean fever (FMF) patients. Total genomic DNA samples from 52 FMF patients of colchicine unresponsiveness were used for FMF (MEFV) and MDR1 genes profile analyses. Target genes were genotyped by multiplex PCR-based reverse-hybridization Strip Assay method. The preliminary current results showed increased T allele frequency (0.596) in colchicine unresponsiveness of FMF patients. The distributions of the CC, CT, and TT genotypes in colchicine nonresponder FMF patients were 17%, 46%, and 37%, respectively. Our results indicate that C3435T polymorphism in exon 26 of MDR1 gene is associated with colchicine resistance in nonresponder FMF patients during the common therapy protocol.

  9. Uniparental disomy of chromosome 16 in offsprings of Familial Mediterranean Fever (FMF) patients treated with colchicine

    Energy Technology Data Exchange (ETDEWEB)

    Korenstein, A.; Avivi, L. [Tel-Avivi University (Israel); Ravia, Y. [Sheba Medical Center, Tel-Hashomer (Israel)

    1994-09-01

    Uniparental disomy (UPD), an altered mode of Mendelian inheritance, may reveal expression of recessive alleles due to the loss of heterozygosity, as well as imprinted genes. The mechanism causing UPD can be best elucidated in offsprings of individuals at high risk for chromosomal non-disjunction. Such individuals are Familial Mediterranean Fever (FMF) patients, who are routinely treated with the antimitotic agent colchicine, and, therefore, are expected to be at an increased risk for aneuploidy. A dominant mode of inheritance was observed in four FMF offsprings having one parent exhibiting the FMF phenotype (homozygote recessive) while the other was free of the mutant allele (as assumed from his ethnic background). Out of these, two exhibited UPD of chromosome 16, which carries the FMF gene, as judged from four different RFLP markers along this chromosome. Since in both case the UPD was of maternal origin, it is suggested that the colchicine-treated FMF mothers contributed two doses of chromosome 16, presumably due to meiotic non-disjunction, followed by a somatic loss of the paternal chromosome 16 in the embryo. The somatic chromosome loss is also assumed to be caused by the antimitotic drug since the mother continued to receive it during pregnancy. Whether the UPD arises from the colchicine treatment, from the high tendency of chromosome 16 to maternal non-disjunction or from both remains to be elucidated. Our results highlighted the importance of taking UPD into account when counseling individuals who are either treated with antimitotic agents or are carriers of recessive mutant alleles which are mapped to chromosomes prone to aneuploidy.

  10. Of liver, whisky and plants: a requiem for colchicine in alcoholic cirrhosis?

    Science.gov (United States)

    Lonardo, Amedeo; Loria, Paola

    2002-04-01

    Colchicine decreases liver fibrosis in experimental and human disease, but a meta-analysis recently concluded that colchicine should not be used for liver fibrosis or cirrhosis irrespective of the aetiology. In this issue, Cortez-Pinto et al. confirm such negative conclusions in their series of 55 outpatients with biopsy-proven alcoholic cirrhosis followed for a median of 3.5 years. Although well tolerated, colchicine did not affect either the annual incidence rate of complications or liver function tests. Current treatment of alcoholic cirrhosis includes correction of nutritional deficiencies, exogenous administration of antioxidants (notably S-adenosylmethionine and polyenylphosphatidylcholine), and liver transplantation. In the future, preventive/therapeutic strategies will include campaigns to decrease alcohol abuse aimed at subjects genetically prone to develop alcoholic liver injury, prevention of liver fibrosis via inhibition of the Na+/H+ exchange, stimulation of apoptosis of stellate cells, antagonism of cytokines involved in liver injury, degradation of extracellular matrix, and reversal of ethanol-induced inflammatory and fibrotic changes via increased nitric oxide levels. On the grounds that it renders the hepatocyte more vulnerable to necrosis, steatosis has a key role in the pathogenesis of alcoholic and non-alcoholic liver disease. Conditions associated with insulin resistance have been recognized as risk factors for chronic liver disease and hepatocellular carcinoma in the alcoholic. This suggests that, through steatosis, insulin resistance could be a co-factor of alcoholic liver disease. Were such a hypothesis confirmed, it would unify our view of the pathogenesis of alcoholic and non-alcoholic liver disease, with all its inherent therapeutic implications.

  11. [Evaluation of frequency and the attacks features of patients with colchicine resistance in FMF].

    Science.gov (United States)

    Cetin, Gozde Yildirim; Balkarli, Ayse; Öksüz, Ali Nuri; Kimyon, Gezmiş; Pehlivan, Yavuz; Orhan, Ozlem; Kisacik, Bunyamin; Cobankara, Veli; Sayarlioglu, Hayriye; Onat, Ahmet Mesut; Sayarlioglu, Mehmet

    2014-01-01

    Colchicine is the mainstay for the treatment of FMF, which is an auto-inflammatory disease mainly with relapsing polyserositis. Despite daily doses of 2mg or more each day, approximately 5% to 10% of the patients continue to suffer from its attacks. In this study, we aimed to investigate the depression and attack features in patients with FMF who have colchicine resistance (CR). CR was defined for FMF patients with 2 or more attacks within the last 6 months period while using 2mg/day colchicine. Eighteen patients (9 Female/9 Male) were enrolled into the CR group and 41 patients were enrolled into the control group (12 Male/29 Female). Demographic, clinical e laboratory findings, treatment adherence, and the Beck Depression Inventory (BDI) scores were evaluated. The age of onset of FMF was significantly lower in the CR group (12.3 yrs vs. 16.9 yrs, P=0.03). Disease duration was longer in the CR group (P=0.01). Abdominal and leg pain due to exercise were significantly more frequent in the CR group versus controls (83% vs. 51%; P=0.02 e 88% vs. 60%; P=0.04, respectively). Patients with BDI scores over 17 points were more frequent in the CR group compared to controls (50% vs. 34.1%; P<0.001). We found that: (1) the age of disease onset was lower and (2) the disease duration was longer in CR group. Pleuritic attacks, hematuria e proteinuria were more frequent in CR patients. We propose that depression is an important factor to consider in the susceptibility to CR. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

  12. Research on the biology of Colchicum autumnale L., germination, flowering and colchicin content

    Directory of Open Access Journals (Sweden)

    Leon Sorin MUNTEAN

    1981-08-01

    Full Text Available Common Autumn Crocus planted in spring of 1979, under the protection of Lolium perenne, has sprouted in 1980. during the first vegetative year the following plant parts had developed: the mezocotyl, root, hypocotyl, a small bulbotuber below the surface of the ground and the leaf, above it. The blooming spreads over a rather long period of time, reaching its peak in autumn, that is in the first half of October. Self fertilization is to be revealed with the plant - this is mostly allogamous. The plant displays a large variability, inas much as the colchicine content is concerned. The chromosome number in the somatic cells is 2n=38.

  13. Colchicine reduces procollagen Ⅲ and increases pseudocholinesterase in chronic liver disease

    Institute of Scientific and Technical Information of China (English)

    Sergio; Muntoni; Marcos; Rojkind; Sandro; Muntoni

    2010-01-01

    AIM:To test whether colchicine would be an effective antif ibrotic agent for treatment of chronic liver diseases in patients who could not be treated with α-interferon.METHODS:Seventy-four patients(46 males,28 females) aged 40-66 years(mean 53±13 years) participated in the study.The patients were affected by chronic liver diseases with cirrhosis which was proven histologically(n=58);by chronic active hepatitis C(n=4),chronic active hepatitis B(n=2),and chronic persistent hepatitis C(n=6).In the four patient...

  14. Rilonacept for colchicine-resistant or -intolerant familial Mediterranean fever: a randomized trial.

    Science.gov (United States)

    Hashkes, Philip J; Spalding, Steven J; Giannini, Edward H; Huang, Bin; Johnson, Anne; Park, Grace; Barron, Karyl S; Weisman, Michael H; Pashinian, Noune; Reiff, Andreas O; Samuels, Jonathan; Wright, Dowain A; Kastner, Daniel L; Lovell, Daniel J

    2012-10-16

    Currently, there is no proven alternative therapy for patients with familial Mediterranean fever (FMF) that is resistant to or intolerant of colchicine. Interleukin-1 is a key proinflammatory cytokine in FMF. To assess the efficacy and safety of rilonacept, an interleukin-1 decoy receptor, in treating patients with colchicine-resistant or -intolerant FMF. Randomized, double-blind, single-participant alternating treatment study. (ClinicalTrials.gov number: NCT00582907). 6 U.S. sites. Patients with FMF aged 4 years or older with 1 or more attacks per month. One of 4 treatment sequences that each included two 3-month courses of rilonacept, 2.2 mg/kg (maximum, 160 mg) by weekly subcutaneous injection, and two 3-month courses of placebo. Differences in the frequency of FMF attacks and adverse events between rilonacept and placebo. 8 males and 6 females with a mean age of 24.4 years (SD, 11.8) were randomly assigned. Among 12 participants who completed 2 or more treatment courses, the rilonacept-placebo attack risk ratio was 0.59 (SD, 0.12) (equal-tail 95% credible interval, 0.39 to 0.85). The median number of attacks per month was 0.77 (0.18 and 1.20 attacks in the first and third quartiles, respectively) with rilonacept versus 2.00 (0.90 and 2.40, respectively) with placebo (median difference, -1.74 [95% CI, -3.4 to -0.1]; P = 0.027). There were more treatment courses of rilonacept without attacks (29% vs. 0%; P = 0.004) and with a decrease in attacks of greater than 50% compared with the baseline rate during screening (75% vs. 35%; P = 0.006) than with placebo. However, the duration of attacks did not differ between placebo and rilonacept (median difference, 1.2 days [-0.5 and 2.4 days in the first and third quartiles, respectively]; P = 0.32). Injection site reactions were more frequent with rilonacept (median difference, 0 events per patient treatment month [medians of -4 and 0 in the first and third quartiles, respectively]; P = 0.047), but no differences were seen

  15. DEVELOPMENT OF UV SPECTROPHOTOMETRIC METHOD FOR ESTIMATION OF COLCHICINE IN PHOSPHATE BUFFER SALINE pH 6.4

    Directory of Open Access Journals (Sweden)

    Arpna patial

    2012-02-01

    Full Text Available The present investigation explores a method to analyze colchicine in phosphate buffer saline pH 6.4. Based on the spectrophotometric characteristics of colchicine, λmax selected was 353.8 nm. Analytical parameters validated were linearity, accuracy, precision, LOD, LOQ and robustness. The developed method demonstrated exemplary linearity in phosphate buffer saline pH6.4 (R2 = 0.995 for concentration of 6-22 µg/ml with linear equation of y=0.037x+0.005. LOD and LOQ obtained were found to be i.e. 0.145µg/ml and 0.483µg/ml respectively. All validation parameters were observed to be within acceptable range, as recommended by ICH guidelines. The above results confirmed the validity of proposed method for routine estimation of colchicine in phosphate buffer saline pH6.4.

  16. Adherence to guidelines and the screening tool of older persons' potentially inappropriate prescriptions criteria for colchicine dosing for gout treatment in beneficiaries of the Nova Scotia Seniors' Pharmacare Program.

    Science.gov (United States)

    Black, Emily; Sketris, Ingrid; Skedgel, Chris; MacLean, Erica; Hanly, John G

    2015-10-01

    Colchicine is commonly used in the management of gout; however, older persons have higher risks of toxicity. Accordingly, the Screening Tool of Older Person's potentially inappropriate Prescriptions (STOPP) criteria for colchicine consider >3 months of treatment as potentially inappropriate in older persons. Recent evidence also suggests lower dosing of colchicine is as effective and results in fewer toxicities than high-dose colchicine. The objectives of this study were to determine the dose, duration, and prescribers of colchicine and to evaluate adherence to the STOPP criteria and international guidelines for colchicine in older persons. A retrospective, observational study was conducted from April 1, 2006 to March 31, 2011 to evaluate colchicine use. Nova Scotia Seniors' Pharmacare Program beneficiaries who met inclusion criteria for an incident case of gout and who filled at least 1 prescription for colchicine during the study period were included. Colchicine dose and duration were reported descriptively. Multivariate logistic regression was used to identify predictors of the study population in making a claim for colchicine >90 and >180 days. A total of 518 persons were dispensed 1327 courses of colchicine during the study period. The mean daily dose of colchicine ranged from 1.39 to 1.50 mg. Colchicine doses >1.2 mg were prescribed in approximately one-third of the study population. Colchicine was prescribed for >90 days in 14.2% of treatment courses and for >180 days in 8.1% of treatment courses. Female sex was the only predictor of treatment duration >90 days. This study is the first to report on colchicine dose and duration using STOPP criteria in a specific cohort of older persons with incident gout. Strategies to improve colchicine prescribing in older persons are needed. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Preparation of colchicine ethosome patches and evaluation of their in vitro transdermal diffusion%秋水仙碱醇质体贴剂的制备及其体外透皮释药

    Institute of Scientific and Technical Information of China (English)

    宋三孔; 宋霞; 魏立明; 杨效宇; 焦海胜

    2012-01-01

    目的:制备秋水仙碱醇质体贴剂并研究其体外透皮释药性能.方法:采用注入法制备秋水仙碱醇质体,以Ⅳ#丙烯酸树脂、柠檬酸三乙酯和琥珀酸压敏胶材料制备压敏胶作为骨架,制成秋水仙碱贴剂;用高效液相色谱(HPLC)法测定贴剂中秋水仙碱的含量,并以改良的Franz扩散池研究贴剂体外透皮释药性能.结果:秋水仙碱经制成醇质体,再用丙烯酸压敏胶制成秋水仙醇质体贴剂,符合Higuchi方程;不含月桂氮革酮与含5%、10%比例月桂氯革酮的醇质体药物透皮释药速率分别为(2.64±0.16),(3.92±0.12)μg·cm-·h-1和(4.26±0.18)μg·cm-2·h-1,明显高于不含醇质体贴剂(P<0.05);不含月桂氮革酮与含5%、10%月桂氮革酮的醇质体皮肤药物滞留量分别为(2.94±0.12),(3.64±0.09)μg·cm-2和(4.03±0.12)μg·cm-2,可改变透皮吸收促进剂的用量控制贴剂的释药速率(P<0.05).结论:所制备的秋水仙碱醇质体贴剂具有明显的缓释作用和较高的透皮吸收促进作用.%OBJECTIVE To prepare the colchicines ethosome patches and to evaluate their in vitro transdermal diffusioa METHODS Colchicine ethosomes were prepared by the injection method. The W polyacrylic resin, triethyl citrate and suc-cinic acid were used to prepare the pressure sensitive adhesive as matrix Then it was used to prepare colchicine ethosome patches. The HPLC was adopted to determine the content of colchicine of colchicine ethosome patches. The reformed Franz diffusion cell was adopted to investigate the in vitro transdermal diffusioa RESULTS The Colchicine ethosome patches, which were prepared by colchicine ethosomes and acrylate pressure-sentitive adhesive, complied with the Higuchi equation. Comparing with the ordinary patches, the colchicine ethosome patches without azone,and with azone of 5% and 10%, which had the release rates of (2. 64±0. 16) ,(3. 92±0. 12)μg·cm-2·h-1 and (4. 26 ± 0. 18)μg·cmZ-2·h-1

  18. Excitatory amino acid neurotoxicity and modulation of glutamate receptor expression in organotypic brain slice cultures

    DEFF Research Database (Denmark)

    Zimmer, J; Kristensen, Bjarne Winther; Jakobsen, B

    2000-01-01

    Using organotypic slice cultures of hippocampus and cortex-striatum from newborn to 7 day old rats, we are currently studying the excitotoxic effects of kainic acid (KA), AMPA and NMDA and the neuroprotective effects of glutamate receptor blockers, like NBQX. For detection and quantitation of the...

  19. Tetrazolyl isoxazole amino acids as ionotropic glutamate receptor antagonists: synthesis, modelling and molecular pharmacology

    DEFF Research Database (Denmark)

    Frølund, Bente; Greenwood, Jeremy R; Holm, Mai Marie

    2005-01-01

    and 1b were pharmacologically characterized in receptor binding assays, and electrophysiologically on homomeric AMPA receptors (GluR1-4), homomeric (GluR5 and GluR6) and heteromeric (GluR6/KA2) kainic acid receptors, using two-electrode voltage-clamped Xenopus laevis oocytes expressing these receptors...

  20. Comparison of rDNA sequences from colchicine treated and untreated sporocysts of Phyllodistomum folium and Bucephalus polymorphus (Digenea).

    Science.gov (United States)

    Stunzenas, Virmantas; Cryan, Jason R; Molloy, Daniel P

    2004-09-01

    The most frequently used antimitotic agent in cytogenetic studies is colchicine. We investigated whether the initial treatment of trematodes for karyological analysis with colchicine would have mutagenic or degradational effect on rDNA sequences. Dreissena polymorpha is the intermediate host of Phyllodistomum folium and Bucephalus polymorphus, and the sporocyst stage of these trematode species develop, respectively, in the gills and gonads of this mussel. Sporocysts of P. folium and B. polymorphus were obtained from D. polymorpha collected from waterbodies in Belarus and in Lithuania. 5.8S and 28S rDNA genes, ITS1 and ITS2 of P folium and B. polymorphus were sequenced and compared, and no nucleotide sequence differences between colchicine treated and untreated trematodes were found. Based on these results, we conclude that colchicine treatment for 3-5 h has no mutagenic or degradational effect on rDNA sequences. During the course of this investigation, two genetically different P. folium samples were noted in Belarus.

  1. Colchicine, Biologic Agents and More for the Treatment of Familial Mediterranean Fever. The Old, the New, and the Rare.

    Science.gov (United States)

    Portincasa, P

    2016-01-01

    Familial Mediterranean Fever (FMF) is a rare autosomal recessive autoinflammatory disorder involving the innate immunity and affecting almost exclusively populations with Mediterranean origin. Clinical features include recurrent episodes of fever, leukocitosis, serositis (peritonitis or pleuritis, arthritis), myalgia or erysipelas-like skin lesions, lasting 12-72 hrs. The MEFV gene mutations on chromosome 16p13.3 encodes the abnormal pyrin (marenostrin), a protein expressed in granulocytes, monocytes, serosal and synovial fibroblasts and involved in the activation of caspase-1 and the processing and release of active pro-inflammatory IL-1β. Since the first report in 1972, maintenance therapy with colchicine, a tricyclic neutral alkaloid, remains the mainstay of treatment in symptomatic FMF patients since it reduces the disease activity and prevents the development of secondary amyloidosis and renal damage. Adjunctive symptomatic therapy to colchicine includes nonsteroideal antinflammatory drugs and corticosteroids. In a small group of colchicine-intolerant or colchicine-resistant FMF patients, alternative treatments must be considered. Evolving experiences have focussed on the potential effectiveness of biologic agents working as TNF-α inhibitors (etanercept, infliximab), IL-1 trap (Rilonacept), IL-1 inhibitors (Anakinra, Canakinumab) and IL-6 receptor antibody (Tocilizumab). Interferon-α and thalidomide have also been employed in FMF patients. Still, clinical trials are mainly uncontrolled and restricted to few cases, thus requiring definitive conclusions. Old, and new treatments are discussed in the rare FMF disease, with the concept that any ideal treatment has to stand the test of time.

  2. Topical Colchicine Gel versus Diclofenac Sodium Gel for the Treatment of Actinic Keratoses: A Randomized, Double-Blind Study

    Science.gov (United States)

    Faghihi, Gita; Iraji, Fariba; Behfar, Shadi; Abtahi-Naeini, Bahareh

    2016-01-01

    Introduction. Actinic keratoses (AKs), a premalignant skin lesion, are a common lesion in fair skin. Although destructive treatment remains the gold standard for AKs, medical therapies may be preferable due to the comfort and reliability .This study aims to compare the effects of topical 1% colchicine gel and 3% diclofenac sodium gel in AKs. Materials and Methods. In this randomized double-blind study, 70 lesions were selected. Patients were randomized before receiving either 1% colchicine gel or 3% diclofenac sodium cream twice a day for 6 weeks. Patients were evaluated in terms of their lesion size, treatment complications, and recurrence at 7, 30, 60, and 120 days after treatment. Results. The mean of changes in the size was significant in both groups both before and after treatment ( 0.05). No case of erythema was seen in the colchicine group, while erythema was seen in 22.9% (eight cases) of patients in the diclofenac sodium group (p = 0.005). Conclusions. 1% colchicine gel was a safe and effective medication with fewer side effects and lack of recurrence of the lesion. PMID:27689135

  3. Quantum-chemical, NMR, FT IR, and ESI MS studies of complexes of colchicine with Zn(II).

    Science.gov (United States)

    Jankowski, Wojciech; Kurek, Joanna; Barczyński, Piotr; Hoffmann, Marcin

    2017-04-01

    Colchicine is a tropolone alkaloid from Colchicinum autumnale. It shows antifibrotic, antimitotic, and anti-inflammatory activities, and is used to treat gout and Mediterranean fever. In this work, complexes of colchicine with zinc(II) nitrate were synthesized and investigated using DFT, (1)H and (13)C NMR, FT IR, and ESI MS. The counterpoise-corrected and uncorrected interaction energies of these complexes were calculated. We also calculated their (1)H, (13)C NMR, and IR spectra and compared them with the corresponding experimentally obtained data. According to the ESI MS mass spectra, colchicine forms stable complexes with zinc(II) nitrate that have various stoichiometries: 2:1, 1:1:1, and 2:1:1 with respect to colchichine, Zn(II), and nitrate ion. All of the complexes were investigated using the quantum theory of atoms in molecules (QTAIM). The calculated and the measured spectra showed differences before and after the complexation process. Calculated electron densities and bond critical points indicated the presence of bonds between the ligands and the central cation in the investigated complexes that satisfied the quantum theory of atoms in molecules. Graphical Abstract DFT, NMR, FT IR, ESI MS, QTAIM and puckering studies of complexes of colchicine with Zn(II).

  4. Quick and Simple Detection Technique to Assess the Binding of Antimicrotubule Agents to the Colchicine-Binding Site

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    Fortin Sébastien

    2010-04-01

    Full Text Available Abstract Development of antimitotic binding to the colchicine-binding site for the treatment of cancer is rapidly expanding. Numerous antimicrotubule agents are prepared every year, and the determination of their binding affinity to tubulin requires the use of purified tubulins and radiolabeled ligands. Such a procedure is costly and time-consuming and therefore is limited to the most promising candidates. Here, we report a quick and inexpensive method that requires only usual laboratory resources to assess the binding of antimicrotubules to colchicine-binding site. The method is based on the ability of N,N'-ethylene-bis(iodoacetamide (EBI to crosslink in living cells the cysteine residues at position 239 and 354 of β-tubulin, residues which are involved in the colchicine-binding site. The β-tubulin adduct formed by EBI is easily detectable by Western blot as a second immunoreacting band of β-tubulin that migrates faster than β-tubulin. The occupancy of colchicine-binding site by pertinent antimitotics inhibits the formation of the EBI: β-tubulin adduct, resulting in an assay that allows the screening of new molecules targeting this binding site.

  5. Quick and Simple Detection Technique to Assess the Binding of Antimicrotubule Agents to the Colchicine-Binding Site

    Directory of Open Access Journals (Sweden)

    Moreau Emmanuel

    2010-01-01

    Full Text Available Abstract Development of antimitotic binding to the colchicine-binding site for the treatment of cancer is rapidly expanding. Numerous antimicrotubule agents are prepared every year, and the determination of their binding affinity to tubulin requires the use of purified tubulins and radiolabeled ligands. Such a procedure is costly and time-consuming and therefore is limited to the most promising candidates. Here, we report a quick and inexpensive method that requires only usual laboratory resources to assess the binding of antimicrotubules to colchicine-binding site. The method is based on the ability of N,N'-ethylene-bis(iodoacetamide (EBI to crosslink in living cells the cysteine residues at position 239 and 354 of β-tubulin, residues which are involved in the colchicine-binding site. The β-tubulin adduct formed by EBI is easily detectable by Western blot as a second immunoreacting band of β-tubulin that migrates faster than β-tubulin. The occupancy of colchicine-binding site by pertinent antimitotics inhibits the formation of the EBI: β-tubulin adduct, resulting in an assay that allows the screening of new molecules targeting this binding site.

  6. Nitric oxide synthase inhibitor, aminoguanidine reduces intracerebroventricular colchicine induced neurodegeneration, memory impairments and changes of systemic immune responses in rats.

    Science.gov (United States)

    Sil, Susmita; Ghosh, Tusharkanti; Ghosh, Rupsa; Gupta, Pritha

    2017-02-15

    Intracerebroventricular (i.c.v.) injection of colchicine induces neurodegeneration, memory impairments and changes of some systemic immune responses in rats. Though the role of cox 2 in these colchicine induced changes have been evaluated, the influence of nitric oxide synthase (NOS) remains to be studied. The present study was designed to assess the role of NOS on the i.c.v. colchicine induced neurodegeneration, memory impairments and changes of some systemic immune responses by inhibiting its activity with aminoguanidine. In the present study the impairments of working and reference memories, neurodegeneration (chromatolysis and plaque formation) and changes of neuroinflammatory markers in the hippocampus (increased TNF α, IL 1β, ROS and nitrite) along with changes of serum inflammatory markers (TNF α, IL 1β, ROS and nitrite) and alteration of systemic immune responses (higher phagocytic activity of blood WBC and splenic PMN, higher cytotoxicity and lower leukocyte adhesion inhibition index of splenic MNC) were measured in the intracerebroventricular colchicine injected rats (ICIR). Administration of aminoguanidine (p.o. 30/50mg/kg body weight) to ICIR resulted in recovery of neuroinflammation and partial prevention of neurodegeneration which could be corroborated with the partial recovery of memory impairments in this model. The recovery of serum inflammatory markers and the systemic immune responses in ICIR was also observed after administration of aminoguanidine. Therefore, the present study shows that aminoguanidine can protect the colchicine induced neurodegeneration, memory impairments, and changes of systemic immune systemic responses in ICIR by inhibiting the iNOS. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Colchicine effect on the DNA content and stomata size of Glycyrrhiza glabra var.glandulifera and Carthamus tinctorius L. cultured in vitro

    Directory of Open Access Journals (Sweden)

    Nahid Moghbel

    2015-06-01

    Full Text Available In vitro induction of polyploids using colchicine causes an increase in DNA content in plants. This is of high importance especially for plants that have medicinal and commercial values. Seeds of two medicinal plants, licorice Glycyrrhiza glabra L. var.glandulifera and safflower Carthamus tinctorius were treated with different concentrations of colchicine, 0%, 0.03%, 0.05%, 0.08%, 0.1% (W/V in vitro for 24 and 48 h. Treated seeds then were cultured on solid Murashige and Skoog (MS media under controlled conditions. After a month, the length of the stomata was measured to study the effect of colchicine on stomata size. Cellular DNA content of the regenerated plants was measured by spectrophotometry. Flow cytometry was used for confirming the results obtained from stomata size measurement and spectrophotometry. Results suggested that treated plants have a fair amount of larger stomata, significantly in licorice plantlets that were treated with 0.1% colchicine for 24 h and safflower plantlets that were treated with 0.03%, 0.05% and 0.1% colchicine. Safflower DNA content in all treatments enhanced significantly, but in licorice only DNA content of plantlets that were treated with 0.05% colchicine for 24 h and 0.1%, 0.03% colchicine for 48 h found to be increased significantly. The morphological features of treated plantlets such as shoot and leaf thickness were found to be increased. Flow cytometry confirmed the previously mentioned results and suggested tetraploids in all treated safflower plantlets and licorice plantlets obtained from treatment with 0.08% of colchicine and mixoploids in licorice plantlets obtained from treatment with 0.1% of colchicine.

  8. [Morphologic indices of the rat heart after colchicine application to the vagus nerve].

    Science.gov (United States)

    Uzbekova, T A; Chervova, I A; Dobrovol'skiĭ, G F

    1985-10-01

    By means of the light optic and electron microscopic methods atrial ganglia, myocytes, vessels of the right cardiac chambers have been studied in rats 2 days--3 weeks after application of 100 mcg of colchicine on the right nervus vagus. Certain changes of the neural fibers have been described at the area of the application. In the myocardium the microcirculatory bed, focal edema and hypoxic alterations of the myocyte ultrastructure have been revealed. In the ventrical ganglia destruction of some terminals of the preganglionar fibers, chromatolysis and vacuolization of single neurocytes, as well as intraganglionar granule-containing cells have been found. The changes described take place for 7 days and they nearly completely disappear in 10 days. A suggestion is made that some phenomena, in particular, destruction of the preganglionar fibers and changes of the cardiac microcirculatory bed are connected with certain disturbances of the quick transport of substances in the nervus vagus fibers.

  9. Interactive effects involving different classes of excitatory amino acid receptors and the survival of cerebellar granule cells in culture

    DEFF Research Database (Denmark)

    Balázs, R; Hack, N; Jørgensen, Ole Steen

    1990-01-01

    Differentiating granule cells develop survival requirements in culture which can be met by treatment with high K+ or N-methyl-D-aspartate (NMDA) and, according to our recent findings, also with low concentrations of kainic acid (KA, 50 microM). We have now attempted to elucidate the mechanism(s) ...

  10. Induction of apomixis and fixation of heterosis in Egyptian rice Hybrid1 line using colchicine mutagenesis

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    Reda M. Gaafar

    2017-06-01

    Full Text Available It is known that hybrid rice yields 15–20% over inbred varieties in first generation because of heterosis. However, heterosis is normally broken due to segregation. Applying apomixis produces plants as a clone of mother plant and overcomes the problem of breaking heterosis. In order to fix heterosis in the Egyptian rice Hybrid1, their seeds were mutagenized in 0.2% colchicine for two time periods 24 and 50 h. After colchicine mutagenesis, rice seedlings were grown in the field till maturation and the resulted M1 seeds were sown in season 2 and plants were selected based on yield and homogeneity. Then, seeds were sown to be evaluated in season 3. Pollen fertility test, esterase isozyme analysis, and flow cytometry seed screening were performed to confirm the results of field selection of populations identical to control. Pollen fertility examination was performed on the populations of the third season. Pollens of populations 304, 298, 292, 284, 281, 154 and 149 were found to be completely sterile. However, these plants had high seed set percentage. The flow cytometry screening of the six yield-based identical populations and the control seeds showed that populations 220, 339, 351 and 298 have higher nuclear DNA content (C2 than untreated hybrid (C2 & C3. Results of flow cytometry clearly showed that population 298 has one peak (C2 and its endosperm was formed autonomously without fertilization. Although its pollen grains were sterile, it showed high seed set percentage. This indicates that heterosis was completely fixed by apomixis in this population.

  11. Inhibitory effect of pironetin analogue/colchicine hybrids on the expression of the VEGF, hTERT and c-Myc genes.

    Science.gov (United States)

    Vilanova, Concepción; Díaz-Oltra, Santiago; Murga, Juan; Falomir, Eva; Carda, Miguel; Marco, J Alberto

    2015-08-15

    A small group of hybrid molecules composed of a colchicine moiety and a pironetin analogue fragment have been investigated for their ability to inhibit the expression of the VEGF, hTERT and c-Myc genes. The VEGF gene is involved in the generation of the vascular endothelial growth factor (VEGF) and thus in the angiogenic process whereas the two latter ones are related to the activation of telomerase. All three genes therefore may be of paramount importance in the cancer generation process. It has been found that colchicine and some of its derivatives display a measurable ability to inhibit the expression of the VEGF and the two other telomerase-related genes. In the case of some of the hybrids, the available data point to the colchicine fragment being responsible for the observed biological activities. It is the first time that the last biological feature has been reported for colchicine or derivatives thereof. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Excitatory amino acid receptor antagonists

    DEFF Research Database (Denmark)

    Johansen, T N; Frydenvang, Karla Andrea; Ebert, B

    1997-01-01

    We have previously shown that (RS)-2-amino-2-(5-tert-butyl-3-hydroxyisoxazol-4-yl)acetic acid (ATAA) is an antagonist at N-methyl-D-aspartic acid (NMDA) and (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) receptors. We have now resolved ATAA via diastereomeric salt formation......)-phenylethylamine salt of N-BOC-(R)-ATAA. Like ATAA, neither (R)- nor (S)-ATAA significantly affected (IC50 > 100 microM) the receptor binding of tritiated AMPA, kainic acid, or (RS)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid, the latter being a competitive NMDA antagonist. Electrophysiological experiments......, using the rat cortical wedge preparation, showed the NMDA antagonist effect as well as the AMPA antagonist effect of ATAA to reside exclusively in the (R)-enantiomer (Ki = 75 +/- 5 microM and 57 +/- 1 microM, respectively). Neither (R)- nor (S)-ATAA significantly reduced kainic acid-induced excitation...

  13. N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)colcemid, a probe for different classes of colchicine-binding site on tubulin.

    Science.gov (United States)

    Sengupta, S; Puri, K D; Surolia, A; Roy, S; Bhattacharyya, B

    1993-03-01

    The nature of binding of 7-nitrobenz-2-oxa-1,3-diazol-4-yl-colcemid (NBD-colcemid), an environment-sensitive fluorescent analogue of colchicine, to tubulin was tested. This article reports the first fluorometric study where two types of binding site of a colchicine analogue on tubulin were detected. Binding of NBD-colcemid to one of these sites equilibrates slowly. NBD-colcemid competes with colchicine for this site. Binding of NBD-colcemid to this site also causes inhibition of tubulin self-assembly. In contrast, NBD-colcemid binding to the other site is characterised by rapid equilibration and lack of competition with colchicine. Nevertheless, binding to this site is highly specific for the colchicine nucleus, as alkyl-NBD analogues have no significant binding activity. Fast-reaction-kinetic studies gave 1.76 x 10(5) M-1 s-1 for the association and 0.79 s-1 for the dissociation rate constants for the binding of NBD-colcemid to the fast site of tubulin. The association rate constants for the two phases of the slow site are 444.4 M-1 s-1 and 11.67 M-1 s-1 [corrected], respectively. These two sites may be related to the two sites of colchicine reported earlier, with binding characteristics altered by the increased hydrophobic nature of NBD-colcemid.

  14. An Unexpected Interaction between Sofosbuvir/Ledipasvir and Atorvastatin and Colchicine Causing Rhabdomyolysis in a Patient with Impaired Renal Function

    Science.gov (United States)

    Andres, Jennifer

    2016-01-01

    Hepatitis C virus (HCV) infection affects roughly 170 million people worldwide. Sofosbuvir/Ledipasvir (Sof/Led) is a new once daily direct acting antiviral combination pill that was approved in October 2014 for use in patients with HCV genotype 1 infection. Coadministration of Sof/Led is studied only with rosuvastatin which shows significantly increased level of drug and is associated with increased risk of myopathy, including rhabdomyolysis. There is no mention of such HMG-CoA reductase inhibitor interaction as a class, as pravastatin did not have any clinically significant interaction with Sof/Led. Other myotoxic drugs, including colchicine are not studied. We present a case of a serious drug interaction between Sof/Led and atorvastatin, in the background of CKD and colchicine use. PMID:27635145

  15. An Unexpected Interaction between Sofosbuvir/Ledipasvir and Atorvastatin and Colchicine Causing Rhabdomyolysis in a Patient with Impaired Renal Function

    Directory of Open Access Journals (Sweden)

    Shyam Patel

    2016-01-01

    Full Text Available Hepatitis C virus (HCV infection affects roughly 170 million people worldwide. Sofosbuvir/Ledipasvir (Sof/Led is a new once daily direct acting antiviral combination pill that was approved in October 2014 for use in patients with HCV genotype 1 infection. Coadministration of Sof/Led is studied only with rosuvastatin which shows significantly increased level of drug and is associated with increased risk of myopathy, including rhabdomyolysis. There is no mention of such HMG-CoA reductase inhibitor interaction as a class, as pravastatin did not have any clinically significant interaction with Sof/Led. Other myotoxic drugs, including colchicine are not studied. We present a case of a serious drug interaction between Sof/Led and atorvastatin, in the background of CKD and colchicine use.

  16. CXI-benzo-84 reversibly binds to tubulin at colchicine site and induces apoptosis in cancer cells.

    Science.gov (United States)

    Rai, Ankit; Gupta, Tilak Kumar; Kini, Sudarshan; Kunwar, Ambarish; Surolia, Avadhesha; Panda, Dulal

    2013-08-01

    Here, we have discovered CXI-benzo-84 as a potential anticancer agent from a library of benzimidazole derivatives using cell based screening strategy. CXI-benzo-84 inhibited cell cycle progression in metaphase stage of mitosis and accumulated spindle assembly checkpoint proteins Mad2 and BubR1 on kinetochores, which subsequently activated apoptotic cell death in cancer cells. CXI-benzo-84 depolymerized both interphase and mitotic microtubules, perturbed EB1 binding to microtubules and inhibited the assembly and GTPase activity of tubulin in vitro. CXI-benzo-84 bound to tubulin at a single binding site with a dissociation constant of 1.2±0.2μM. Competition experiments and molecular docking suggested that CXI-benzo-84 binds to tubulin at the colchicine-site. Further, computational analysis provided a significant insight on the binding site of CXI-benzo-84 on tubulin. In addition to its potential use in cancer chemotherapy, CXI-benzo-84 may also be useful to screen colchicine-site agents and to understand the colchicine binding site on tubulin.

  17. Proteomic analysis of the low mutation rate of diploid male gametes induced by colchicine in Ginkgo biloba L.

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    Nina Yang

    Full Text Available Colchicine treatment of G. biloba microsporocytes results in a low mutation rate in the diploid (2n male gamete. The mutation rate is significantly lower as compared to other tree species and impedes the breeding of new economic varieties. Proteomic analysis was done to identify the proteins that influence the process of 2n gamete formation in G. biloba. The microsporangia of G. biloba were treated with colchicine solution for 48 h and the proteins were analyzed using 2-D gel electrophoresis and compared to protein profiles of untreated microsporangia. A total of 66 proteins showed difference in expression levels. Twenty-seven of these proteins were identified by mass spectrometry. Among the 27 proteins, 14 were found to be up-regulated and the rest 13 were down-regulated. The identified proteins belonged to five different functional classes: ATP generation, transport and carbohydrate metabolism; protein metabolism; ROS scavenging and detoxifying enzymes; cell wall remodeling and metabolism; transcription, cell cycle and signal transduction. The identification of these differentially expressed proteins and their function could help in analysing the mechanism of lower mutation rate of diploid male gamete when the microsporangium of G. biloba was induced by colchicine.

  18. Tetrazolyl isoxazole amino acids as ionotropic glutamate receptor antagonists: synthesis, modelling and molecular pharmacology.

    Science.gov (United States)

    Frølund, Bente; Greenwood, Jeremy R; Holm, Mai M; Egebjerg, Jan; Madsen, Ulf; Nielsen, Birgitte; Bräuner-Osborne, Hans; Stensbøl, Tine B; Krogsgaard-Larsen, Povl

    2005-09-15

    Two 3-(5-tetrazolylmethoxy) analogues, 1a and 1b, of (RS)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA), a selective AMPA receptor agonist, and (RS)-2-amino-3-(5-tert-butyl-3-hydroxy-4-isoxazolyl)propionic acid (ATPA), a GluR5-preferring agonist, were synthesized. Compounds 1a and 1b were pharmacologically characterized in receptor binding assays, and electrophysiologically on homomeric AMPA receptors (GluR1-4), homomeric (GluR5 and GluR6) and heteromeric (GluR6/KA2) kainic acid receptors, using two-electrode voltage-clamped Xenopus laevis oocytes expressing these receptors. Both analogues proved to be antagonists at all AMPA receptor subtypes, showing potencies (Kb=38-161 microM) similar to that of the AMPA receptor antagonist (RS)-2-amino-3-[3-(carboxymethoxy)-5-methyl-4-isoxazolyl]propionic acid (AMOA) (Kb=43-76 microM). Furthermore, the AMOA analogue, 1a, blocked two kainic acid receptor subtypes (GluR5 and GluR6/KA2), showing sevenfold preference for GluR6/KA2 (Kb=19 microM). Unlike the iGluR antagonist (S)-2-amino-3-[5-tert-butyl-3-(phosphonomethoxy)-4-isoxazolyl]propionic acid [(S)-ATPO], the corresponding tetrazolyl analogue, 1b, lacks kainic acid receptor effects. On the basis of docking to a crystal structure of the isolated extracellular ligand-binding core of the AMPA receptor subunit GluR2 and a homology model of the kainic acid receptor subunit GluR5, we were able to rationalize the observed structure-activity relationships.

  19. High Frequency Production of Doubled Haploid Rapeseed Plants by Direct Colchicine Treatment of Isolated Microspores%油菜小孢子秋水仙素直接处理增加纯合两倍体植株频率

    Institute of Scientific and Technical Information of China (English)

    周伟军; Per,H

    2000-01-01

    @@ Techniques for microspore culture of Brassica napus have been improved rapidly, and embryogenesis has been achieved in a wide range of genotypes. Plants regenerated from microspore-derived embryoids can be haploid, diploid or polyploid. From rapeseed microspore culture it is reported that 70%-90% of regenerated plants are haploid. The usual methods of chromosome doubling involve soaking roots (most common) or whole plants in a colchicine solution, or culturing plantlets in colchicine-containing medium in the greenhouse. Other alternatives are injecting colchicine into the secondary buds or applying colchicine-soaked cotton plugs to axillary buds.

  20. The Effects of Colchicine on Risk of Cardiovascular Events and Mortality Among Patients with Gout: A Cohort Study Using Electronic Medical Records Linked with Medicare Claims

    Science.gov (United States)

    Solomon, Daniel H.; Liu, Chih-Chin; Kuo, I-Hsin; Zak, Agnes; Kim, Seoyoung C.

    2016-01-01

    Background Colchicine may have beneficial effects on cardiovascular (CV) disease, but there are sparse data on its CV effect among patients with gout. We examined the potential association between colchicine and CV risk and all-cause mortality in gout. Methods The analyses used data from an electronic medical record (EMR) database linked with Medicare claims (2006–2011). To be eligible for the study cohort, subjects must have had a diagnosis of gout in the EMR and Medicare claims. New users of colchicine were identified and followed-up from the first colchicine dispensing date. Non-users had no evidence of colchicine prescriptions during the study period and were matched to users on the start of follow-up, age, and gender. Both groups were followed for the primary outcome, a composite of myocardial infarction (MI), stroke or transient ischemic attack (TIA). We calculated hazard ratios (HRs) in Cox regression, adjusting for potential confounders. Results We matched 501 users with an equal number of non-users with a median follow-up of 16.5 months. During follow-up, 28 primary CV events were observed among users and 82 among non-users. Incidence rates per 1,000 person-years were 35.6 for users and 81.8 for non-users. After full adjustment, colchicine use was associated with a 49% lower risk (HR 0.51, 95% CI 0.30 – 0.88) in the primary CV outcome as well as a 73% reduction in all-cause mortality (HR 0.27, 95% CI 017 – 0.43). Conclusion Colchicine use was associated with a reduced risk of a CV event among patients with gout. PMID:26582823

  1. Rational Design, Synthesis and Pharmacological Evaluation of the (2R)- and (2S)-Stereoisomers of 3-(2-Carboxypyrrolidinyl)-2-methyl Acetic Acid as Ligands for the Ionotropic Glutamate Receptors

    DEFF Research Database (Denmark)

    Rasmussen, Julie; Storgaard, Morten; Pickering, Darryl S;

    2011-01-01

    In this paper we describe the rational design, synthesis and pharmacological evaluation of two new stereoisomeric (S)-glutamate (Glu) analogues. The rational design was based on hybrid structures of the natural product kainic acid, a synthetic analogue CPAA and the high-affinity Glu analogue SYM...

  2. Poliploidia artificial em seringueira (Hevea Brasiliensis Muell.-Arg. Colchicine induced polyploidy of hevea rubber plants

    Directory of Open Access Journals (Sweden)

    Luiz O. T. Mendes

    1963-01-01

    Full Text Available Tendo em vista verificar se, com a duplicação do número de cromossômios, obter-se-iam seringueiras com vasos laticíferos de maior diâmetro que o observado em plantas normais e, conseqüentemente, de maior produção de látex, os autores, por meio de soluções de colchicina, trataram plantas recém-germinadas, assim obtendo poliplóides artificiais. No decurso dos trabalhos foi desenvolvida uma técnica especial, pela qual, de uma mesma semente de seringueira, eram obtidas duas plantas, uma normal e outra com o número duplo de cromossômios; dessa maneira, a planta normal se constitui em perfeita testemunha da planta poliplóide, podendo-se, assim, atribuir à poliploidia tôda e qualquer alteração que se venha a verificar na planta com o número duplo de cromossômios. Acreditam os autores que êsse mesmo processo poderá ser utilizado com êxito em outras plantas dicotiledôneas. Os resultados mostram que, nas plantas poliplóides, os estornas são maiores e em menor número, por unidade de superfície foliar, que nas plantas normais; observam-se também diferenças morfológicas nessas plantas, que se desenvolvem satisfatòriamente. Ainda não foram feitos estudos para a determinação do diâmetro dos vasos laticíferos. O material foi multiplicado por enxertia e está sendo incluído em experimentos a cargo da Seção de Plantas Tropicais.Based on the assumption that latex production is positively correlated to the diameter of the latex vessels and hoping to obtain rubber plants with larger latex vessels than those observed in normal plants, the authors duplicated the chromosome number of small seedlings, using aqueous solutions of colchicine. Some polyploid plants with 72 chromosomes were obtained. A special technique was developed, ensuring the obtention of twin plants from a single seed, by splitting very young seedlings; one of them remained untreated, while the other was submitted to a colchicine aqueous solution. Any

  3. Endogenous excitatory amino acid neurotransmission regulates thyroid-stimulating hormone and thyroid hormone secretion in conscious freely moving male rats.

    Science.gov (United States)

    Arufe, M C; Durán, R; Perez-Vences, D; Alfonso, M

    2002-04-01

    The role of neurotransmission of endogenous excitatory amino acid (EAA) on serum thyroid hormones and thyroid-stimulating hormone (TSH) levels was examined in conscious and freely moving adult male Sprague-Dawley rats. The rats were cannulated at the third ventricle 2 d before the experiments. Several glutamate receptor agonists, such as kainic acid and domoic acid, and antagonists, such as 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and dizocilpine (MK-801) were administered into the third ventricle. Serum TSH levels were assesed by radioimmunoassay, and serum thyroid hormone levels were assessed by enzyme immunoassay. The results showed that the administration of CNQX and MK-801 produced a decrease in serum levels of TSH and thyroid hormones. The administration of kainic acid and domoic acid increased TSH concentrations, whereas CNQX completely blocked the release of TSH induced by kainic acid and domoic acid. These results suggest the importance of endogenous EAA in the regulation of hormone secretion from the pituitary-thyroid axis, as well as the role of the N-methyl-D-aspartate (NMDA) and non-NMDA receptors in the stimulatory effect of EAAs on the pituitary-thyroid axis.

  4. Neuroprotective Effects of α-Tocotrienol on Kainic Acid-Induced Neurotoxicity in Organotypic Hippocampal Slice Cultures

    Directory of Open Access Journals (Sweden)

    Bae Hwan Lee

    2013-09-01

    Full Text Available Vitamin E, such as alpha-tocopherol (ATPH and alpha-tocotrienol (ATTN, is a chain-breaking antioxidant that prevents the chain propagation step during lipid peroxidation. In the present study, we investigated the effects of ATTN on KA-induced neuronal death using organotypic hippocampal slice culture (OHSC and compared the neuroprotective effects of ATTN and ATPH. After 15 h KA (5 µM treatment, delayed neuronal death was detected in the CA3 region and reactive oxygen species (ROS formation and lipid peroxidation were also increased. Both co-treatment and post-treatment of ATPH (100 µM or ATTN (100 µM significantly increased the cell survival and reduced the number of TUNEL-positive cells in the CA3 region. Increased dichlorofluorescein (DCF fluorescence and levels of thiobarbiturate reactive substances (TBARS were decreased by ATPH and ATTN treatment. These data suggest that ATPH and ATTN treatment have protective effects on KA-induced cell death in OHSC. ATTN treatment tended to be more effective than ATPH treatment, even though there was no significant difference between ATPH and ATTN in co-treatment or post-treatment.

  5. Metallothionein reduces central nervous system inflammation, neurodegeneration, and cell death following kainic acid-induced epileptic seizures

    DEFF Research Database (Denmark)

    Penkowa, Milena; Florit, Sergi; Giralt, Mercedes

    2005-01-01

    , such as oxidative stress (formation of nitrotyrosine, malondialdehyde, and 8-oxoguanine), neurodegeneration (neuronal accumulation of abnormal proteins), and apoptotic cell death (judged by TUNEL and activated caspase-3). This reduced bystander damage in TgMT mice could be due to antiinflammatory and antioxidant...

  6. Sprouty2 and -4 hypomorphism promotes neuronal survival and astrocytosis in a mouse model of kainic acid induced neuronal damage.

    Science.gov (United States)

    Thongrong, Sitthisak; Hausott, Barbara; Marvaldi, Letizia; Agostinho, Alexandra S; Zangrandi, Luca; Burtscher, Johannes; Fogli, Barbara; Schwarzer, Christoph; Klimaschewski, Lars

    2016-05-01

    Sprouty (Spry) proteins play a key role as negative feedback inhibitors of the Ras/Raf/MAPK/ERK pathway downstream of various receptor tyrosine kinases. Among the four Sprouty isoforms, Spry2 and Spry4 are expressed in the hippocampus. In this study, possible effects of Spry2 and Spry4 hypomorphism on neurodegeneration and seizure thresholds in a mouse model of epileptogenesis was analyzed. The Spry2/4 hypomorphs exhibited stronger ERK activation which was limited to the CA3 pyramidal cell layer and to the hilar region. The seizure threshold of Spry2/4(+/-) mice was significantly reduced at naive state but no difference to wildtype mice was observed 1 month following KA treatment. Histomorphological analysis revealed that dentate granule cell dispersion (GCD) was diminished in Spry2/4(+/-) mice in the subchronic phase after KA injection. Neuronal degeneration was reduced in CA1 and CA3 principal neuron layers as well as in scattered neurons of the contralateral CA1 and hilar regions. Moreover, Spry2/4 reduction resulted in enhanced survival of somatostatin and neuropeptide Y expressing interneurons. GFAP staining intensity and number of reactive astrocytes markedly increased in lesioned areas of Spry2/4(+/-) mice as compared with wildtype mice. Taken together, although the seizure threshold is reduced in naive Spry2/4(+/-) mice, neurodegeneration and GCD is mitigated following KA induced hippocampal lesions, identifying Spry proteins as possible pharmacological targets in brain injuries resulting in neurodegeneration. The present data are consistent with the established functions of the ERK pathway in astrocyte proliferation as well as protection from neuronal cell death and suggest a novel role of Spry proteins in the migration of differentiated neurons.

  7. Ultrastructural changes to rat hippocampus in pentylenetetrazol- and kainic acid-induced status epilepticus: A study using electron microscopy.

    Science.gov (United States)

    Zhvania, Mzia G; Ksovreli, Mariam; Japaridze, Nadezhda J; Lordkipanidze, Tamar G

    2015-07-01

    A pentylenetetrazol (PTZ)-induced status epilepticus model in rats was used in the study. The brains were studied one month after treatment. Ultrastructural observations using electron microscopy performed on the neurons, glial cells, and synapses, in the hippocampal CA1 region of epileptic brains, demonstrated the following major changes over normal control brain tissue. (i) There is ultrastructural alterations in some neurons, glial cells and synapses in the hippocampal CA1 region. (ii) The destruction of cellular organelles and peripheral, partial or even total chromatolysis in some pyramidal cells and in interneurons are observed. Several astrocytes are proliferated or activated. Presynaptic terminals with granular vesicles and degenerated presynaptic profiles are rarely observed. (iii) The alterations observed are found to be dependent on the frequency of seizure activities following the PTZ treatment. It was observed that if seizure episodes are frequent and severe, the ultrastructure of hippocampal area is significantly changed. Interestingly, the ultrastructure of CA1 area is found to be only moderately altered if seizure episodes following the status epilepticus are rare and more superficial; (iv) alterations in mitochondria and dendrites are among the most common ultrastructural changes seen, suggesting cell stress and changes to cellular metabolism. These morphological changes, observed in brain neurons in status epilepticus, are a reflection of epileptic pathophysiology. Further studies at the chemical and molecular level of neurotransmitter release, such as at the level of porosomes (secretory portals) at the presynaptic membrane, will further reveal molecular details of these changes.

  8. Enhanced seizures and hippocampal neurodegeneration following kainic acid-induced seizures in metallothionein-I + II-deficient mice

    DEFF Research Database (Denmark)

    Carrasco, J; Penkowa, M; Hadberg, H

    2000-01-01

    ), a potent convulsive agent, to examine the neurobiological importance of these MT isoforms. At 35 mg/kg KA, MT-I + II deficient male mice showed a higher number of convulsions and a longer convulsion time than control mice. Three days later, KA-injected mice showed gliosis and neuronal injury...

  9. Induction and Flow Cytometry Identification of Tetraploids from Seed-Derived Explants through Colchicine Treatments in Catharanthus roseus (L. G. Don

    Directory of Open Access Journals (Sweden)

    Shi-Hai Xing

    2011-01-01

    Full Text Available The tetraploid plants of Catharanthus roseus (L. G. Don was obtained by colchicine induction from seeds explants, and the ploidy of the plants was identified by flow cytometry. The optimal treatment is 0.2% colchicine solution treated for 24 hours, and the induction rate reaches up to 30%. Comparing with morphological characteristics and growth habits between tetraploids and the control, we found that tetraploids of C. roseus had larger stoma and more branches and leaves. HPLC analysis showed tetraploidization could increase the contents of terpenoid indole alkaloids in C. roseus. Thus, tetraploidization could be used to produce higher alkaloids lines for commercial use. QRT-PCR results showed that the expression of enzymes involved in terpenoid indole alkaloids biosynthesis pathway had increased in the tetraploid plants. To our knowledge, this was the first paper to explore the secondary metabolism in autotetraploid C. roseus induced by colchicine.

  10. Biochemical studies of mouse brain tubulin: colchicine binding (DEAE-cellulose filter) assay and subunits ( α and β) biosynthesis and degradation (in newborn brain)

    Energy Technology Data Exchange (ETDEWEB)

    Tse, Cek-Fyne [Univ. of Rochester, NY (United States)

    1978-01-01

    A DEAE-cellulose filter assay, measuring (3H)colchicine bound to colchicine binding protein (CBP) absorbed on filter discs, has been modified to include lM sucrose in the incubation medium for complexing colchicine to CBP in samples before applying the samples to filter discs (single point assay). Due to the much greater stability of colchicine binding capacity in the presence of lM sucrose, multiple time-point assays and least squares linear regression analysis were not necessary for accurate determination of CBP in hybrid mouse brain at different stages of development. The highest concentrations of CBP were observed in the 160,000g supernatant and pellet of newborn brain homogenate. Further studies of the modified filter assay documented that the assay has an overall counting efficiency of 27.3%, that DEAE-cellulose filters bind and retain all tubulin in the assay samples, and that one molecule of colchicine binds approximately one molecule of tubulin dimer. Therefore, millimoles of colchicine bound per milligram total protein can be used to calculate tubulin content. With this technique tubulin content of brain supernatant was found to be 11.9% for newborn, and 7.15% for 11 month old mice. Quantitative densitometry was also used to measure mouse brain supernatant actin content for these two stages. In vivo synthesis and degradation rates of tubulin ..cap alpha.. and ..beta.. subunits of two day mouse brain 100,000g supernatant were studied after intracerebral injection of (3H)leucine. Quantitative changes of the ratio of tritium specific activities of tubulin ..cap alpha.. and ..beta.. subunits with time were determined. The pattern of change was biphasic. During the first phase the ratio decreased; during the second phase the ratio increased continuously. An interpretation consistent with all the data in this study is that the ..cap alpha.. subunit is synthesized at a more rapid rate than the ..beta.. subunit. (ERB)

  11. Cerebroprotective activity of U-50488H: Relationship to interactions with excitatory amino acids and calcium

    Energy Technology Data Exchange (ETDEWEB)

    Camacho Ochoa, M.

    1987-01-01

    The mechanism underlying the anticonvulsant and cerebroprotective activity of U-50488H was evaluated using {sup 45}Ca{sup ++} uptake in rat Ficoll purified synaptosomes, ({sup 3}H)-2-deoxyglucose uptake in selected mouse brain regions, ({sup 3}H)kainic acid binding to mouse forebrain synaptic membranes and incidence of KA-induced lesions in the CA3 region of the mouse hippocampus. U-50488H causes reduction in K{sup +}-evoked {sup 45}Ca{sup ++} uptake. These effects are comparable to those of the calcium channel blockers verapamil and nifedipine and seem to be related to calcium dependent mechanisms. Changes in saturability, specificity and dissociation constant values of kainic acid receptor binding were demonstrated in the presence of U-50488H at concentrations similar to those used in {sup 45}Ca{sup ++} uptake studies and in the presence of calcium and chloride ions.

  12. The expanded clinical profile and the efficacy of colchicine therapy in Egyptian children suffering from familial Mediterranean fever: a descriptive study.

    Science.gov (United States)

    Talaat, Hala Salah El-Din; Mohamed, Mohamed Farouk; El Rifai, Nihal Mohamed; Gomaa, Mohamed Ali

    2012-12-04

    Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by self-limiting recurrent attacks of fever and serosal inflammation, leading to abdominal, thoracic or articular pain. To detect variable clinical presentations and genotypic distribution of different groups of FMF patients and the efficacy of colchicine therapy in treatment of these groups of FMF after one year. A cross-sectional study was conducted on 70 patients already diagnosed with FMF and following-up at the Rheumatology Clinic, Children's Hospital - Cairo University. Diagnosis of FMF was determined according to Tel Hashomer criteria for FMF. All patients were subjected to a questionnaire including detailed history with emphasis on clinical manifestations and colchicine dose to control attacks. Mutational analysis was performed for all study subjects covering 12 mutations in the MEFV gene: E148Q, P369S, F479L, M680I (G/C), M680I (G/A), I692del, M694V, M694I, K695R, V726A, A744S and R761H. Response to colchicine treatment was evaluated as complete, incomplete and unresponsive. Out of the 70 patients- 40 males and 30 females- fever was the most common presenting feature, followed by abdominal pain, and arthritis; documented in 95.7%, 94.3%, and 77.1% of cases respectively. Mutational analysis detected gene mutation on both alleles in 20 patients (homozygotes), on only 1 allele in 40 patients (heterozygotes), and on none of the alleles (uncharacterized cases). Mild to moderate disease severity score (according to Tel Hashomer key to severity score) was detected in a significant proportion of heterozygotes and the uncharacterized group than the homozygotes. All patients received colchicine therapy; 22.9% of them showed complete response, 74.3% showed incomplete response and 2.9% showed no response to therapy. The colchicine dose needed to control attacks was significantly lower in heterozygotes than the homozygotes(P=0.04). Also patients' response to colchicine therapy was

  13. Discovery of novel 2-aryl-4-benzoyl-imidazoles targeting the colchicines binding site in tubulin as potential anticancer agents

    Science.gov (United States)

    Chen, Jianjun; Wang, Zhao; Li, Chien-Ming; Lu, Yan; Vaddady, Pavan K.; Meibohm, Bernd; Dalton, James T.; Miller, Duane D.; Li, Wei

    2010-01-01

    A series of 2-aryl-4-benzoyl-imidazoles (ABI) was synthesized as a result of structural modifications based on the previous set of 2-aryl-imidazole-4-carboxylic amide (AICA) derivatives and 4-substituted methoxylbenzoyl-aryl-thiazoles (SMART). The average IC50 of the most active compound (5da) was 15.7 nM. ABI analogs have substantially improved aqueous solubility (48.9 μg/mL for 5ga vs. 0.909 μg/mL for SMART-1, 0.137 μg/mL for paclitaxel, and 1.04 μg/mL for Combretastatin A4). Mechanism of action studies indicate that the anticancer activity of ABI analogs is through inhibition of tubulin polymerization by interacting with the colchicine binding site. Unlike paclitaxel and colchicine, the ABI compounds were equally potent against multidrug resistant cancer cells and the sensitive parental melanoma cancer cells. In vivo results indicated that 5cb was more effective than DTIC in inhibiting melanoma xenograph tumor growth. Our results suggest that the novel ABI compounds may be developed to effectively treat drug-resistant tumors. PMID:20919720

  14. The glutamate receptor GluR5 agonist (S)-2-amino-3-(3-hydroxy-7,8-dihydro-6H-cyclohepta[d]isoxazol-4-yl)propionic acid and the 8-methyl analogue

    DEFF Research Database (Denmark)

    Clausen, Rasmus Prætorius; Naur, Peter; Kristensen, Anders Skov;

    2009-01-01

    GluRs). Functional characterization of 5 at cloned iGluRs using a calcium imaging assay and voltage-clamp recordings show a different activation of GluR5 compared to (S)-glutamic acid (Glu), kainic acid (KA, 1), and (S)-2-amino-3-(3-hydroxy-5-tert-butyl-4-isoxazolyl)propionic acid ((S)-ATPA, 3) as previously...

  15. The efficacy and safety of treatments for acute gout: results from a series of systematic literature reviews including Cochrane reviews on intraarticular glucocorticoids, colchicine, nonsteroidal antiinflammatory drugs, and interleukin-1 inhibitors.

    Science.gov (United States)

    Wechalekar, Mihir D; Vinik, Ophir; Moi, John H Y; Sivera, Francisca; van Echteld, Irene A A M; van Durme, Caroline; Falzon, Louise; Bombardier, Claire; Carmona, Loreto; Aletaha, Daniel; Landewé, Robert B; van der Heijde, Désirée M F M; Buchbinder, Rachelle

    2014-09-01

    To determine the efficacy and safety of glucocorticoids (GC), colchicine, nonsteroidal antiinflammatory drugs (NSAID), interleukin-1 (IL-1) inhibitors, and paracetamol to treat acute gout. We searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials to September 2011. Randomized controlled trials (RCT) or quasi-RCT in adults with acute gout that compared GC, colchicine, NSAID, IL-1 inhibitors, and paracetamol to no treatment, placebo, another intervention, or combination therapy were included. Two authors independently extracted data and assessed risk of bias. Primary endpoints were pain and adverse events. Data were pooled where appropriate. Twenty-six trials evaluating GC (N = 5), NSAID (N = 21), colchicine (N = 2), and canakinumab (N = 1) were included. No RCT assessed paracetamol or intraarticular (IA) GC. No RCT compared systemic GC with placebo. Moderate quality evidence (3 trials) concluded that systemic GC were as effective as NSAID but safer. Low quality evidence (1 trial) showed that both high- and low-dose colchicine were more effective than placebo, and low-dose colchicine was no different to placebo with respect to safety but safer than high-dose colchicine. Low quality evidence (1 trial) showed no difference between NSAID and placebo with regard to pain or inflammation. No NSAID was superior to another. Moderate quality evidence (1 trial) found that 150 mg canakinumab was more effective than a single dose of intramuscular GC (40 mg triamcinolone) and equally safe. GC, NSAID, low-dose colchicine, and canakinumab all effectively treat acute gout. There was insufficient evidence to rank them. Systemic GC appeared safer than NSAID and lower-dose colchicine was safer than higher-dose colchicine.

  16. Successful treatment with anti-tumor necrosis factor (anti-TNF)-alpha of proteinuria in a patient with familial mediterranean fever (FMF) resistant to colchicine: anti-TNF drugs and FMF.

    Science.gov (United States)

    Erten, S; Erten, S F; Altunoglu, A

    2012-04-01

    Familial mediterranean fever (FMF) is an autoinflammatory disease characterized by recurrent attacks of fever, peritonitis, pleuritis, and genetically by autosomal recessive inheritance. The major renal involvement in FMF is the occurrence of amyloidosis that can be prevented by a daily regimen of colchicine. About 5-10% of cases with familial mediterranean fever may be resistant to colchicine. In literature, there is a controversy about the treatment of FMF patients resistant to colchicine. We describe a case with FMF, proteinuria, and bilateral sacroiliitis, which responded to anti-TNF (tumor necrosis factor)-alpha therapy with infliximab and etanercept.

  17. Colchicine modulates oxidative stress in serum and neutrophil of patients with Behçet disease through regulation of Ca²⁺ release and antioxidant system.

    Science.gov (United States)

    Korkmaz, Selma; Erturan, Ijlal; Nazıroğlu, Mustafa; Uğuz, Abdulhadi Cihangir; Ciğ, Bilal; Övey, Ishak Suat

    2011-12-01

    Behçet disease (BD) is a chronic, inflammatory, and multisystemic condition with an uncertain pathogenesis. One of the major immunologic findings in BD pathogenesis is increase in activity of neutrophil. An increase in the cytosolic free Ca²⁺[Ca²⁺](i) concentration that induces Ca²⁺ signaling is an important step that participates in the neutrophil activation and reactive oxygen species production that leads to tissue damage in body cells. We aimed to investigate the effects of colchicine on oxidative stress and Ca²⁺ release in serum and neutrophil of BD patients with active and inactive periods. Twelve Behçet patients (6 active and 6 inactive) and 6 control subject were included in the study. Disease activity was considered by clinical findings. Serum and neutrophil samples were obtained from the patients and control subjects. Neutrophils from patients with active BD were divided into three subgroups and were incubated with colchicine, verapamil + diltiazem, and colchicine + verapamil + diltiazem, respectively. Erythrocyte sedimentation rate, leucocytes counts, serum C-reactive protein, neutrophil, and serum lipid peroxidation and intracellular Ca²⁺ release levels were higher in active and inactive groups than in the control group, although their levels were lower in active group than in inactive group. However, neutrophil Ca²⁺ release levels were decreased in colchicine, verapamil + diltiazem, and colchicine + verapamil + diltiazem groups group compared to active group. Serum glutathione, vitamin A, vitamin E, and β-carotene concentrations were lower in active and inactive groups than in the control group, although serum vitamin E and β-carotene concentrations were higher in the inactive group than in the active group. Neutrophil and serum glutathione peroxidase activity within the three groups did not change. In conclusion, we observed the importance of Ca²⁺ influx into the neutrophils and oxidative stress in the pathogenesis and

  18. 抗癌药秋水仙碱及其类似物构效关系研究进展%RECENT PROGRESS IN STRUCTURE-ACTIVITY RELATIONSHIP STUDIES ON THE ANTICANCER DRUG COLCHICINE AND ITS ANALOGUES

    Institute of Scientific and Technical Information of China (English)

    潘显道; 方唯硕

    2002-01-01

    @@ Colchicine (1) (Figure 1), the major alkaloid isolated from Colchicum autumnale in 1820, is a potent drug that interferes with microtubules both in vitro and in vivo, thereby causing cells to accumulate in apparent mitotic arrest during the cell cycle. Colchicine has been used in the treatment of acute gout, familial Mediterranean fever, scleroderma, amyloidosis, Behcet's disease and liver disorder, particularly cirrhosis[1]. Although colchicine is a potent antimitotic agent, its medicinal uses are limited due to its high toxicity. Virtually all its therapeutic and toxic effects were believed to be the consequence of its interaction with tubulin. Hence, colchicine has become an attractive molecule that the medicinal chemists were in pursuit of. It is a less toxic and more selective analogue which bind to tubulin.

  19. Exploring the Origin of Differential Binding Affinities of Human Tubulin Isotypes αβII, αβIII and αβIV for DAMA-Colchicine Using Homology Modelling, Molecular Docking and Molecular Dynamics Simulations.

    Science.gov (United States)

    Kumbhar, Bajarang Vasant; Borogaon, Anubhaw; Panda, Dulal; Kunwar, Ambarish

    2016-01-01

    Tubulin isotypes are found to play an important role in regulating microtubule dynamics. The isotype composition is also thought to contribute in the development of drug resistance as tubulin isotypes show differential binding affinities for various anti-cancer agents. Tubulin isotypes αβII, αβIII and αβIV show differential binding affinity for colchicine. However, the origin of differential binding affinity is not well understood at the molecular level. Here, we investigate the origin of differential binding affinity of a colchicine analogue N-deacetyl-N-(2-mercaptoacetyl)-colchicine (DAMA-colchicine) for human αβII, αβIII and αβIV isotypes, employing sequence analysis, homology modeling, molecular docking, molecular dynamics simulation and MM-GBSA binding free energy calculations. The sequence analysis study shows that the residue compositions are different in the colchicine binding pocket of αβII and αβIII, whereas no such difference is present in αβIV tubulin isotypes. Further, the molecular docking and molecular dynamics simulations results show that residue differences present at the colchicine binding pocket weaken the bonding interactions and the correct binding of DAMA-colchicine at the interface of αβII and αβIII tubulin isotypes. Post molecular dynamics simulation analysis suggests that these residue variations affect the structure and dynamics of αβII and αβIII tubulin isotypes, which in turn affect the binding of DAMA-colchicine. Further, the binding free-energy calculation shows that αβIV tubulin isotype has the highest binding free-energy and αβIII has the lowest binding free-energy for DAMA-colchicine. The order of binding free-energy for DAMA-colchicine is αβIV ≃ αβII > αβIII. Thus, our computational approaches provide an insight into the effect of residue variations on differential binding of αβII, αβIII and αβIV tubulin isotypes with DAMA-colchicine and may help to design new analogues with higher

  20. Exploring the Origin of Differential Binding Affinities of Human Tubulin Isotypes αβII, αβIII and αβIV for DAMA-Colchicine Using Homology Modelling, Molecular Docking and Molecular Dynamics Simulations.

    Directory of Open Access Journals (Sweden)

    Bajarang Vasant Kumbhar

    Full Text Available Tubulin isotypes are found to play an important role in regulating microtubule dynamics. The isotype composition is also thought to contribute in the development of drug resistance as tubulin isotypes show differential binding affinities for various anti-cancer agents. Tubulin isotypes αβII, αβIII and αβIV show differential binding affinity for colchicine. However, the origin of differential binding affinity is not well understood at the molecular level. Here, we investigate the origin of differential binding affinity of a colchicine analogue N-deacetyl-N-(2-mercaptoacetyl-colchicine (DAMA-colchicine for human αβII, αβIII and αβIV isotypes, employing sequence analysis, homology modeling, molecular docking, molecular dynamics simulation and MM-GBSA binding free energy calculations. The sequence analysis study shows that the residue compositions are different in the colchicine binding pocket of αβII and αβIII, whereas no such difference is present in αβIV tubulin isotypes. Further, the molecular docking and molecular dynamics simulations results show that residue differences present at the colchicine binding pocket weaken the bonding interactions and the correct binding of DAMA-colchicine at the interface of αβII and αβIII tubulin isotypes. Post molecular dynamics simulation analysis suggests that these residue variations affect the structure and dynamics of αβII and αβIII tubulin isotypes, which in turn affect the binding of DAMA-colchicine. Further, the binding free-energy calculation shows that αβIV tubulin isotype has the highest binding free-energy and αβIII has the lowest binding free-energy for DAMA-colchicine. The order of binding free-energy for DAMA-colchicine is αβIV ≃ αβII >> αβIII. Thus, our computational approaches provide an insight into the effect of residue variations on differential binding of αβII, αβIII and αβIV tubulin isotypes with DAMA-colchicine and may help to design new

  1. The expanded clinical profile and the efficacy of colchicine therapy in Egyptian children suffering from familial mediterranean fever: a descriptive study

    Directory of Open Access Journals (Sweden)

    Talaat Hala Salah El-Din

    2012-12-01

    Full Text Available Abstract Background Familial Mediterranean fever (FMF is an autosomal recessive disease characterized by self-limiting recurrent attacks of fever and serosal inflammation, leading to abdominal, thoracic or articular pain. Objective To detect variable clinical presentations and genotypic distribution of different groups of FMF patients and the efficacy of colchicine therapy in treatment of these groups of FMF after one year. Methods A cross-sectional study was conducted on 70 patients already diagnosed with FMF and following-up at the Rheumatology Clinic, Children's Hospital - Cairo University. Diagnosis of FMF was determined according to Tel Hashomer criteria for FMF. All patients were subjected to a questionnaire including detailed history with emphasis on clinical manifestations and colchicine dose to control attacks. Mutational analysis was performed for all study subjects covering 12 mutations in the MEFV gene: E148Q, P369S, F479L, M680I (G/C, M680I (G/A, I692del, M694V, M694I, K695R, V726A, A744S and R761H. Response to colchicine treatment was evaluated as complete, incomplete and unresponsive. Results Out of the 70 patients- 40 males and 30 females- fever was the most common presenting feature, followed by abdominal pain, and arthritis; documented in 95.7%, 94.3%, and 77.1% of cases respectively. Mutational analysis detected gene mutation on both alleles in 20 patients (homozygotes, on only 1 allele in 40 patients (heterozygotes, and on none of the alleles (uncharacterized cases. Mild to moderate disease severity score (according to Tel Hashomer key to severity score was detected in a significant proportion of heterozygotes and the uncharacterized group than the homozygotes. All patients received colchicine therapy; 22.9% of them showed complete response, 74.3% showed incomplete response and 2.9% showed no response to therapy. The colchicine dose needed to control attacks was significantly lower in heterozygotes than the homozygotes(P=0

  2. The expanded clinical profile and the efficacy of colchicine therapy in Egyptian children suffering from familial mediterranean fever: a descriptive study

    Science.gov (United States)

    2012-01-01

    Background Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by self-limiting recurrent attacks of fever and serosal inflammation, leading to abdominal, thoracic or articular pain. Objective To detect variable clinical presentations and genotypic distribution of different groups of FMF patients and the efficacy of colchicine therapy in treatment of these groups of FMF after one year. Methods A cross-sectional study was conducted on 70 patients already diagnosed with FMF and following-up at the Rheumatology Clinic, Children's Hospital - Cairo University. Diagnosis of FMF was determined according to Tel Hashomer criteria for FMF. All patients were subjected to a questionnaire including detailed history with emphasis on clinical manifestations and colchicine dose to control attacks. Mutational analysis was performed for all study subjects covering 12 mutations in the MEFV gene: E148Q, P369S, F479L, M680I (G/C), M680I (G/A), I692del, M694V, M694I, K695R, V726A, A744S and R761H. Response to colchicine treatment was evaluated as complete, incomplete and unresponsive. Results Out of the 70 patients- 40 males and 30 females- fever was the most common presenting feature, followed by abdominal pain, and arthritis; documented in 95.7%, 94.3%, and 77.1% of cases respectively. Mutational analysis detected gene mutation on both alleles in 20 patients (homozygotes), on only 1 allele in 40 patients (heterozygotes), and on none of the alleles (uncharacterized cases). Mild to moderate disease severity score (according to Tel Hashomer key to severity score) was detected in a significant proportion of heterozygotes and the uncharacterized group than the homozygotes. All patients received colchicine therapy; 22.9% of them showed complete response, 74.3% showed incomplete response and 2.9% showed no response to therapy. The colchicine dose needed to control attacks was significantly lower in heterozygotes than the homozygotes(P=0.04). Also patients

  3. On Tetraploid Induction of Vaccinium L.by Colchicine%秋水仙素诱导越橘四倍体研究

    Institute of Scientific and Technical Information of China (English)

    石佳; 郑文娟; 任广炼; 李政; 李凌

    2012-01-01

    In order to breed Vaccinium L. resource, which is agreeable to the climate of southwest China, and to provide basic research data for polyploid breeding, colchicine is used in the experiment to induce "3 # " australe Vaccinium L. tetraploid with the immersion method and the method of adding colchicine into medium. The result illustrates that: the immersion method is superior to that of adding colchicine into medium, and most of the mutagenesis plants are chimeras. The best mutagenesis condition is to soak shoot tip for 24h with 0. 1% of colchicine. The survival rate is 70% , the variation rate 13. 33%, and the rate of tetraploid plants 6.67%. Significant changes have been found between tetraploid and diploid by detecting morphological and physiological indicators in stems, leaves, stomatal, guard cells, the number of chromosomes and chlorophyll contents.%用秋水仙素浸渍法及培养基添加法对南高丛越橘组培苗“3#”进行了四倍体诱导,结果表明:浸渍法诱变效果优于培养基添加法,获得的变异株系多为嵌合体,0.1%的秋水仙素茎尖浸泡24h为最佳诱变组合,存活率为70%,变异率为13.33%,四倍体植株率为6.67%.通过对茎、叶、气孔、保卫细胞、染色体数目以及叶绿素含量等形态生理指标的检测,证明四倍体较二倍体发生了显著变化.

  4. A nootropic effect of Moringa oleifera on Ach and ChAT activity in colchicine induced experimental rat model of Alzheimer’s disease: Possible involvement of antioxidants

    Directory of Open Access Journals (Sweden)

    Chandan Roy

    2014-04-01

    Full Text Available Context: The fruit and leaf of Moringa oleifera (MO is an important ingredient of ‘Kusmanda lehyam’ (Ayurvedic medicine, which is widely used, in nervous disorders. Objective: To determine the cognition facilitating effect of MO leaf extract in colchicine induced experimental rat model of AD and to investigate the role of central cholinergic system in the nootropic effect of MO leaf extract with the possible involvement of antioxidant enzymes. Materials and methods: The behavior study, Acetylcholine concentration, cholineacetyl transferase activity, antioxidant level such as, superoxide dismutase (SOD, catalase (CAT, reduced glutathione (GSH and lipid peroxidation (LPO level were studied in different parts of the brain such as frontal cortex (FC and hippocampus (HPC in colchicine induced experimental Alzheimer rat model before and after treatment with MO. Results: MO (250 mg/kg p.o. induced statistically significant reversal of colchicine induced cognitive deficits. MO (250 mg/kg p.o. markedly induced frontal, cortical and hippocampal concentrations of Ach and ChAt activity, the effects being statistically significant on days 7, 14 and 21 respectively. Moreover, MO significantly increased SOD, CAT, GSH activities and significantly decreased LPO level on day 7, 14 and 21 respectively. Discussion and conclusion: The aqueous pulp extract of MO (250 mg/kg body weight containing vit- A, C, E results significant protection in the level of antioxidant status in frontal cortex and hippocampus after a certain period of co administration on colchicine induced oxidative stress without causing any general and metabolic toxicity and possibly thereby induced frontal cortical and hippocampal concentration of Ach and ChAT activity.

  5. Comparison of the efficacy of once- and twice-daily colchicine dosage in pediatric patients with familial Mediterranean fever--a randomized controlled noninferiority trial.

    Science.gov (United States)

    Polat, Adem; Acikel, Cengizhan; Sozeri, Betul; Dursun, Ismail; Kasapcopur, Ozgur; Gulez, Nesrin; Simsek, Dogan; Saldir, Mehmet; Dokurel, Ipek; Poyrazoglu, Hakan; Bakkaloglu, Sevcan; Delibas, Ali; Ekinci, Zelal; Ayaz, Nuray A; Kandur, Yasar; Peru, Harun; Kurt, Yasemin G; Polat, Safiye R; Unsal, Erbil; Makay, Balahan; Gok, Faysal; Ozen, Seza; Demirkaya, Erkan

    2016-04-07

    In this study, we examined the efficacy and safety of a once-daily dosage schema of colchicine compared with a twice-daily dosage schema in pediatric patients with familial Mediterranean fever (FMF). In this 24-week, multicenter, randomized controlled noninferiority trial, pediatric patients newly diagnosed with FMF carrying a homozygous or compound heterozygous mutation and not receiving any treatment were included. Patients were randomly assigned using a block randomization method to receive treatment with a once- or twice-daily dosage. Clinical and laboratory characteristics and medication side effects were recorded and compared between groups. The study was carried out in compliance with Good Clinical Practice and the Consolidated Standards for Reporting of Trials (CONSORT) statement. A total of 92 patients were selected, and 79 patients completed the study. There were 42 patients in the once-daily dosage group and 37 in the twice-daily dosage group. The results indicated that the once-daily dosage was not inferior to the twice-daily dosage regarding decrease in attack frequency and duration as well as improvement in clinical findings and Mor severity scores. Alterations in laboratory findings indicating inflammation, such as erythrocyte sedimentation rate, C-reactive protein, and serum amyloid A, were similar in both groups. The rates of drug side effects were similar between the once- and twice-daily dosage groups, implying comparable safety of colchicine, with the exception of diarrhea, which was slightly higher in the once-daily dosage group. Using colchicine with either a once- or twice-daily dosage provides similar clinical and laboratory improvements. Considering both efficacy and safety, colchicine can be prescribed with a once-daily dosage. ClinicalTrials.gov identifier NCT02602028 . Registered 5 November 2015.

  6. Oxalone and lactone moieties of podophyllotoxin exhibit properties of both the B and C rings of colchicine in its binding with tubulin.

    Science.gov (United States)

    Gupta, Suvroma; Das, Lalita; Datta, Ajit B; Poddar, Asim; Janik, Mark E; Bhattacharyya, Bhabatarak

    2006-05-23

    Thermodynamics of podophyllotoxin binding to tubulin and its multiple points of attachment with tubulin has been studied in detail using isothermal titration calorimetry. The calorimetric enthalpy of the association of podophyllotoxin with tubulin is negative and occurs with a negative heat capacity change (DeltaC(p) = -2.47 kJ mol(-)(1) K(-)(1)). The binding is unique with a simultaneous participation of both hydrophobic and hydrogen-bonding forces with unfavorable negative entropic contribution at higher temperature, favored with an enthalpy-entropy compensation. Interestingly, the binding of 2-methoxy-5-(2',3',4'-trimethoxyphenyl)tropone (AC, a colchicine analogue without the B ring) with tubulin is enthalpy-favored. However, the podophyllotoxin-tubulin association depending upon the temperature of the reaction has a favorable entropic and enthalpic component, which resembles both B- and C-ring properties of colchicine. On the basis of the crystal structure of the podophyllotoxin-tubulin complex, distance calculations have indicated a possible interaction between threonine 179 of alpha-tubulin and the hydroxy group on the D ring of podophyllotoxin. To confirm the involvement of the oxalone moiety as well as the lactone ring of podophyllotoxin in tubulin binding, analogues of podophyllotoxin are synthesized with methoxy substitution at the 4' position of ring D along with its isomer and another analogue epimerized at ring E. From these results, involvement of oxalone as well as the lactone ring of the drug in a specific orientation inclusive of ring A is indicated for podophyllotoxin-tubulin binding. Therefore, podophyllotoxin, like colchicine, behaves as a bifunctional ligand having properties of both the B and C rings of colchicine by making more than one point of attachment with the protein tubulin.

  7. Changes in the micro- and nanostructure of siliceous valves in the diatom Synedra acus under the effect of colchicine treatment at different stages of the cell cycle.

    Science.gov (United States)

    Kharitonenko, Ksenia V; Bedoshvili, Yekaterina D; Likhoshway, Yelena V

    2015-04-01

    The important role of the cytoskeleton in the morphogenesis of siliceous frustule components, which are synthesized within the diatom cells, has been revealed due to experiments with microtubule inhibitors. It has been shown that colchicine entering the diatom cell inhibits polymerization of tubulin, the main protein of microtubules, thereby disrupting the normal processes of biogenic silica deposition and daughter valve morphogenesis. In this study, experiments with a synchronized culture of the pennate diatom Synedra acus have been performed to determine the timing and duration of the formation of various valve components and analyze the effect of colchicine at a subtoxic concentration on the structure of daughter valves at different stages of their morphogenesis. Electron microscopic analysis has revealed several types of micro- and nanoscale anomalies in daughter valve morphology, with their frequency varying depending on the time of colchicine treatment. Laser scanning microscopy of preparations vitally stained with Tubulin Tracker Green has shown that polymerized tubulin at early stages of valve morphogenesis is localized along the periphery of the developing valve. This is evidence for an important role of microtubules in the horizontal growth of the valve at the stage when its general structural pattern is established, including its shape and arrangement of basic micro- and nanostructures. Treatment with a microtubule inhibitor at a certain stage of valve morphogenesis makes it possible to obtain new forms with a specific structure of siliceous components that hold promise for use in nanotechnologies.

  8. Exploring the size adaptability of the B ring binding zone of the colchicine site of tubulin with para-nitrogen substituted isocombretastatins.

    Science.gov (United States)

    Jiménez, Carmen; Ellahioui, Younes; Álvarez, Raquel; Aramburu, Laura; Riesco, Alejandra; González, Myriam; Vicente, Alba; Dahdouh, Abdelaziz; Ibn Mansour, Ahmed; Jiménez, Carlos; Martín, Diego; Sarmiento, Rogelio G; Medarde, Manuel; Caballero, Esther; Peláez, Rafael

    2015-07-15

    We have synthesized and assayed dimethylaminophenyl, pyrrolidin-1-ylphenyl and carbazole containing phenstatins and isocombretastatins as analogues of the highly potent indoleisocombretastatins with extended or reduced ring sizes. This is an attempt to explore beyond the structural constraints of the X-ray crystal structures the zone of the colchicine site where the tropolone ring of colchicine binds to tubulin (zone 1). The isocombretastatins display up to 30 fold increased water solubility when compared with combretastatin A-4, potent inhibition of tubulin polymerization, and nanomolar cytotoxicities against several human cancer cell lines irrespective of the size of the B ring. On the other hand, substitutions ortho to the nitrogen cause an important reduction in potency. We have also shown that representative compounds inhibit autophagy. These results show that zone 1 can adapt to systems of different size as far as they stay in a common plane, but does not tolerate substituents protruding above or below it. These results can help in the understanding of the binding modes of structures with similar systems and in the design of new colchicine site ligands.

  9. Body fluid and tissue analysis using filter paper sampling support prior to LC-MS/MS: application to fatal overdose with colchicine.

    Science.gov (United States)

    Lauer, Estelle; Widmer, Christèle; Versace, François; Staub, Christian; Mangin, Patrice; Sabatasso, Sara; Augsburger, Marc; Déglon, Julien

    2013-01-01

    Because of the various matrices available for forensic investigations, the development of versatile analytical approaches allowing the simultaneous determination of drugs is challenging. The aim of this work was to assess a liquid chromatography-tandem mass spectrometry (LC-MS/MS) platform allowing the rapid quantification of colchicine in body fluids and tissues collected in the context of a fatal overdose. For this purpose, filter paper was used as a sampling support and was associated with an automated 96-well plate extraction performed by the LC autosampler itself. The developed method features a 7-min total run time including automated filter paper extraction (2 min) and chromatographic separation (5 min). The sample preparation was reduced to a minimum regardless of the matrix analyzed. This platform was fully validated for dried blood spots (DBS) in the toxic concentration range of colchicine. The DBS calibration curve was applied successfully to quantification in all other matrices (body fluids and tissues) except for bile, where an excessive matrix effect was found. The distribution of colchicine for a fatal overdose case was reported as follows: peripheral blood, 29 ng/ml; urine, 94 ng/ml; vitreous humour and cerebrospinal fluid, paper is usually employed for DBS, we report here the extension of this alternative sampling support to the analysis of other body fluids and tissues. The developed platform represents a rapid and versatile approach for drug determination in multiple forensic media.

  10. The Effect of Alpha-Lipoic Acid on Learning and Memory Deficit in a Rat Model of Temporal Lobe Epilepsy

    Directory of Open Access Journals (Sweden)

    Narges Karimi

    2012-07-01

    Full Text Available Introduction : Epilepsy is a chronic neurological disorder in which patients experience spontaneous recurrent seizures and deficiency in learning and memory. Although the most commonly recommended therapy is drug treatment, some patients do not achieve adequate control of their seizures on existing drugs. New medications with novel mechanisms of action are needed to help those patients whose seizures are resistant to currently-available drugs. While alpha-lipoic acid as a antioxidant has some neuroprotective properties, but this action has not been investigated in models of epilepsy. Therefore, the protective effect of pretreatment with alpha-lipoic acid was evaluated in experimental model of temporal lobe epilepsy in male rats. Methods: In the present study, Wistar male rats were injected intrahippocampally with 0.9% saline(Sham-operated group, kainic acid(4 μg alone, or α-lipoic acid (25mg and 50mg/kg in association with kainic acid(4μg. We performed behavior monitoring(spontaneous seizure, learning and memory by Y-maze and passive avoidance test, intracranial electroencepholography (iEEG recording, histological analysis, to evaluate the anti- epilepsy effect of α-lipoic acid in kainate-induced epileptic rats.   Results: Behavior data showed that the kainate rats exhibit spontaneous seizures, lower spontaneous alternation score inY-maze tasks (p<0.01, impaired retention and recall capability in the passive avoidance test (p<0.05. Administration of alpha-lipoic acid, in both doses, significantly decrease the number of spontaneous seizures, improved alternation score in Y-maze task (p<0.005 and impaired retention and recall capability in the passive avoidance test (p<0.01 in kainite rats. Moreover, lipoic acid could improve the lipid peroxidation and nitrite level and superoxid dismutase activity.Conclusion: This study indicates that lipoic acid pretreatment attenuates kainic acid-induced impairment of short-term spatial memory in rats

  11. Micronucleated Erythrocytes in Peripheral Blood from Neonate Rats Exposed by Breastfeeding to Cyclophosphamide, Colchicine, or Cytosine-Arabinoside

    Directory of Open Access Journals (Sweden)

    Belinda C. Gómez-Meda

    2016-01-01

    Full Text Available Genotoxic exposure to chemical substances is common, and nursing mothers could transmit harmful substances or their metabolites to their offspring through breast milk. We explored the possibility of determining genotoxic effects in the erythrocytes of breastfeeding rat pups whose mothers received a genotoxic compound while nursing. Ten groups of female rats and five pups per dam were studied. The control group received sterile water, and the experimental groups received one of three different doses of cyclophosphamide, colchicine, or cytosine-arabinoside. Blood smears were prepared from samples taken from each dam and pup every 24 h for six days. There were increased numbers of micronucleated erythrocytes (MNEs and micronucleated polychromatic erythrocytes (MNPCEs in the samples from pups in the experimental groups (P<0.02 and increased MNPCE frequencies in the samples from the dams (P<0.05. These results demonstrate the vertical transmission of the genotoxic effect of the compounds tested. In conclusion, assessing MNEs in breastfeeding neonate rats to assess DNA damage may be a useful approach for identifying genotoxic compounds and/or cytotoxic effects. This strategy could help in screening for therapeutic approaches that are genotoxic during the lactation stage and these assessments might also be helpful for developing preventive strategies to counteract harmful effects.

  12. Micronucleated Erythrocytes in Peripheral Blood from Neonate Rats Exposed by Breastfeeding to Cyclophosphamide, Colchicine, or Cytosine-Arabinoside

    Science.gov (United States)

    Bañales-Martínez, Luis R.; Lemus-Varela, María de Lourdes; Trujillo, Xóchitl; Sánchez-Parada, María G.; Armendáriz-Borunda, Juan; Zúñiga-González, Guillermo M.

    2016-01-01

    Genotoxic exposure to chemical substances is common, and nursing mothers could transmit harmful substances or their metabolites to their offspring through breast milk. We explored the possibility of determining genotoxic effects in the erythrocytes of breastfeeding rat pups whose mothers received a genotoxic compound while nursing. Ten groups of female rats and five pups per dam were studied. The control group received sterile water, and the experimental groups received one of three different doses of cyclophosphamide, colchicine, or cytosine-arabinoside. Blood smears were prepared from samples taken from each dam and pup every 24 h for six days. There were increased numbers of micronucleated erythrocytes (MNEs) and micronucleated polychromatic erythrocytes (MNPCEs) in the samples from pups in the experimental groups (P < 0.02) and increased MNPCE frequencies in the samples from the dams (P < 0.05). These results demonstrate the vertical transmission of the genotoxic effect of the compounds tested. In conclusion, assessing MNEs in breastfeeding neonate rats to assess DNA damage may be a useful approach for identifying genotoxic compounds and/or cytotoxic effects. This strategy could help in screening for therapeutic approaches that are genotoxic during the lactation stage and these assessments might also be helpful for developing preventive strategies to counteract harmful effects. PMID:28018917

  13. Effect of Cytochalasin B, Lantrunculin B, Colchicine, Cycloheximid, Dimethyl Sulfoxide and Ion Channel Inhibitors on Biospeckle Activity in Apple Tissue.

    Science.gov (United States)

    Kurenda, Andrzej; Pieczywek, Piotr M; Adamiak, Anna; Zdunek, Artur

    2013-01-01

    The biospeckle phenomenon is used for non-destructive monitoring the quality of fresh fruits and vegetables, but in the case of plant tissues there is a lack of experimentally confirmed information about the biological origin of the biospeckle activity (BA). As a main sources of BA, processes associated with the movement inside the cell, such as cytoplasmic streaming, organelle movement and intra- and extracellular transport mechanisms, are considered. The aim of this study is to investigate the effect of metabolism inhibitors, connected with intracellular movement such as cytochalasin B, lantrunculin B, colchicine, cycloheximid, dimethyl sulfoxide (DMSO) and mixture of ion channel inhibitors, injected into apples, on BA. Two methods of BA analysis based on cross-correlation coefficient and Laser Speckle Contrast Analysis (LASCA) were used. DMSO, lantrunculin B and mixture of ion channel inhibitors have a significant effect on BA, and approximately 74 % of BA of apple tissue is potentially caused by biological processes. Results indicate that the functioning of actin microfilaments and ion channels significantly affect BA.

  14. Real-world treatment patterns of gout patients treated with colchicine or other common treatments for gout in acute care settings: a retrospective chart review study.

    Science.gov (United States)

    Shiozawa, Aki; Cloutier, Martin; Heroux, Julie; Guerin, Annie; Wu, Eric Q; Jackson, Robert

    2015-08-01

    To describe real-world treatment patterns of patients receiving colchicine or other treatments during a gout-related emergency room or acute care facility (ER/ACF) visit. An online physician-administered questionnaire was used to collect chart data on 500 patients with a gout-related ER/ACF visit after 16 October 2009; 250 patients receiving colchicine (Colchicine Cohort) and 250 receiving NSAIDs, systemic corticosteroids, narcotics, allopurinol, febuxostat, pegloticase, probenecid, or sulfinpyrazone (Other Cohort). Patient characteristics and treatment received/prescribed during the ER/ACF visit (Period 1 [P1]), at discharge (P2), and at the first follow-up visit (P3) are reported. A total of 45 rheumatologists and 63 primary care physicians participated in the study. Patient mean age was 51 years and 74.8% were male. The most common treatments in the Other Cohort were NSAIDs (59.6%), systemic corticosteroids (45.2%), and narcotics (33.6%). The 500 patients contributed 307 distinct treatment patterns from P1 to P3. Of the 20.6% patients not prescribed a treatment in P2, 60.2% were restarted on a treatment in P3. Of the 78.6% treated patients in P2, 27.0% had a treatment adjustment (dose increase, treatment add-on, or initiation of a different gout-related treatment - not with a urate lowering therapy only) in P3; for 72.6% of these patients, physicians justified the treatment adjustment by inadequacy of the treatment for maintenance therapy, insufficient dosage, or inadequate response. In the Colchicine Cohort, 60.8% of patients were prescribed colchicine consistently from P1 to P3, while 26.8% and 17.7% of patients in the Other Cohort were prescribed consistently NSAIDs and systemic corticosteroids from P1 to P3, respectively. Specific nature of the acute gout-related symptoms or potential attack/flare during the ER/ACF visit was not recorded. Real-world clinical practice reveals a substantial number of distinct treatment patterns and frequent treatment

  15. Domoic acid excretion in dungeness crabs, razor clams and mussels.

    Science.gov (United States)

    Schultz, Irvin R; Skillman, Ann; Woodruff, Dana

    2008-07-01

    Domoic acid (DA) is a neurotoxic amino acid produced by several marine algal species of the Pseudo-nitzschia (PN) genus. We studied the elimination of DA from hemolymph after intravascular (IV) injection in razor clams (Siliqua patula), mussels (Mytilus edulis) and Dungeness crabs (Cancer magister). Crabs were also injected with two other organic acids, dichloroacetic acid (DCAA) and kainic acid (KA). For IV dosing, hemolymph was repetitively sampled and DA concentrations measured by HPLC-UV. Toxicokinetic analysis of DA in crabs suggested most of the injected dose remained within hemolymph compartment with little extravascular distribution. This observation is in sharp contrast to results obtained from clams and mussels which exhibited similarly large apparent volumes of distribution despite large differences in overall clearance. These findings suggest fundamentally different storage and elimination processes are occurring for DA between bivalves and crabs.

  16. Dual Role of Vitamin C on the Neuroinflammation Mediated Neurodegeneration and Memory Impairments in Colchicine Induced Rat Model of Alzheimer Disease.

    Science.gov (United States)

    Sil, Susmita; Ghosh, Tusharkanti; Gupta, Pritha; Ghosh, Rupsa; Kabir, Syed N; Roy, Avishek

    2016-12-01

    The neurodegeneration in colchicine induced AD rats (cAD) is mediated by cox-2 linked neuroinflammation. The importance of ROS in the inflammatory process in cAD has not been identified, which may be deciphered by blocking oxidative stress in this model by a well-known anti-oxidant vitamin C. Therefore, the present study was designed to investigate the role of vitamin C on colchicine induced oxidative stress linked neuroinflammation mediated neurodegeneration and memory impairments along with peripheral immune responses in cAD. The impairments of working and reference memory were associated with neuroinflammation and neurodegeneration in the hippocampus of cAD. Administration of vitamin C (200 and 400 mg/kg BW) in cAD resulted in recovery of memory impairments, with prevention of neurodegeneration and neuroinflammation in the hippocampus. The neuroinflammation in the hippocampus also influenced the peripheral immune responses and inflammation in the serum of cAD and all of these parameters were also recovered at 200 and 400 mg dose of vitamin C. However, cAD treated with 600 mg dose did not recover but resulted in increase of memory impairments, neurodegeneration and neuroinflammation in hippocampus along with alteration of peripheral immune responses in comparison to cAD of the present study. Therefore, the present study showed that ROS played an important role in the colchicine induced neuroinflammation linked neurodegeneration and memory impairments along with alteration of peripheral immune responses. It also appears from the results that vitamin C at lower doses showed anti-oxidant effect and at higher dose resulted in pro-oxidant effects in cAD.

  17. The CYP4502D6 *4 and *6 alleles are the molecular genetic markers for drug response: implications in colchicine non-responder FMF patients.

    Science.gov (United States)

    Yalcıntepe, Sinem; Ozdemır, Ozturk; Sılan, Coskun; Ozen, Filiz; Uludag, Ahmet; Candan, Ferhan; Sılan, Fatma

    2016-06-01

    The cytochrome P450 2D6 (CYP2D6) is a cytochrome P450 enzyme involved in the oxidative biotransformation of the xenobiotics, carcinogens and various clinically important drugs. Patients are evaluated in three sub-groups of extensive (EM), intermediate (IM) and poor metabolizer (PM) phenotypes due to their drug-metabolising ability for the target CYP2D6 gene. Colchicine non-responsive FMF patients were prospectively genotyped for the major CYP2D6 alleles in the current study. Major CYP2D6 alleles of *1, *3, *4, *5, and *6 were genotyped for 30 responsive and 60 non-responsive FMF patients by multiplex PCR-based reverse-hybridization StripAssay and real-time PCR methods. DNA banks isolated from blood-EDTA were retrospectively used in the current patients and results were compared statistically. Increased CYP2D6 *4 and *6 allele frequencies were highly detected in the colchicine non-responsive FMF patients when compared to the responsive group. Results showed the frequencies of major CYP2D6 *1(wild), *3(2637A > delA), *4(G1934A), *5(total gene deletion) and *6(1707T del) alleles in 0.550, 0.042, 0.158, 0.025 and 0.225 for non-responder and 0.880 and 0.120 (CYP2D6*1 and *4) for the responder groups, respectively. Despite small sample size, this study suggests that there is an association between CYP2D6*4 and CYP2D6*6 alleles and drug intoxicants in colchicine non-responder FMF patients.

  18. Effects of anti-tumor necrosis factor agents for familial mediterranean fever patients with chronic arthritis and/or sacroiliitis who were resistant to colchicine treatment.

    Science.gov (United States)

    Bilgen, Sule Apras; Kilic, Levent; Akdogan, Ali; Kiraz, Sedat; Kalyoncu, Umut; Karadag, Omer; Ertenli, Ihsan; Dogan, Ismail; Calguneri, Meral

    2011-10-01

    Effectiveness of anti-tumor necrosis factor (anti-TNF) agents in colchicine-resistant familial Mediterranean fever (FMF) patients has attracted attention in recent years. We analyzed the effect of anti-TNF agents on clinical findings of colchicine-resistant FMF patients with chronic arthritis and/or sacroiliitis. Data from 10 FMF patients (5 male and 5 female patients: mean age, 30.1 [SD, 8.5] years) with chronic arthritis and/or sacroiliitis who were on anti-TNF agents are reviewed. Frequency of FMF attacks before and after treatment with anti-TNF agents was recorded from hospital files. The effects of the anti-TNF treatment were determined by using the number of tender and/or swollen joints, serum acute phase reactant levels, and Bath Ankylosing Spondylitis Disease Activity Index scores. Change in urine protein loss was also evaluated in patients with amyloidosis. In 6 patients, FMF attacks had been considered to be unresponsive to colchicine, and 4 patients were partial responders before treatment with anti-TNF agents. Mean attack frequency of the patients in the 3 months' period before anti-TNF agent treatment was 3.8 (SD, 3.1). After anti-TNF treatment, in 3 patients, FMF attack frequency decreased, and in the remaining 7 patients, no attack occurred. Serum acute phase reactant levels were decreased significantly at 3 and 6 months after anti-TNF treatment (P treatment Bath Ankylosing Spondylitis Disease Activity Index scores were also decreased significantly (6.2 [SD], 1.7 vs. 2.1 [SD], 1.7; P = 0.012). In all 3 patients with amyloidosis, urine protein loss decreased without any increase in serum creatinine levels. Anti-TNF treatment can have beneficial effects for controlling FMF attacks in FMF patients with chronic arthritis and/or sacroiliitis.

  19. Mediterranean fever (MEFV) Variant P369S/R408Q in a Patient with Entero-Behçet's Disease who Successfully Responded to Treatment with Colchicine

    OpenAIRE

    Fujikawa, Keita; Migita, Kiyoshi; Nagasato, Akio; Tsukada, Toshiaki; Kawakami, Atsushi; Eguchi, Katsumi

    2014-01-01

    A 57-year-old Japanese woman who had been diagnosed as having entero-Behçet's disease nine years earlier was admitted with a persistent high-grade fever. An Mediterranean fever (MEFV) gene analysis revealed the compound heterozygous P369S-R408Q variant. She was treated with colchicine, and her symptoms immediately improved. Prednisolone (PSL) was added to treat the punched-out ulcers in the terminal ileum, leading to remission. There has been no relapse since the PSL was discontinued. In Behç...

  20. N-methyl-D-aspartic acid receptor agonists

    DEFF Research Database (Denmark)

    Madsen, U; Frydenvang, Karla Andrea; Ebert, B

    1996-01-01

    (R,S)-2-Amino-2-(3-hydroxy-5-methyl-4-isoxazolyl)acetic acid [(R,S)-AMAA, 4] is a potent and selective agonist at the N-methyl-D-aspartic acid (NMDA) subtype of excitatory amino acid receptors. Using the Ugi "four-component condensation" method, the two diastereomers (2R)- and (2S)-2-[3-(benzyloxy......) showed peak affinity for [3H]AMPA receptor sites (IC50 = 72 +/- 13 microM) and was shown to be a more potent inhibitor of [3H]CPP binding (IC50 = 3.7 +/- 1.5 microM) than (S)-AMAA (9) (IC50 = 61 +/- 6.4 microM). Neither enantiomer of AMAA affected [3H]kainic acid receptor binding significantly...

  1. Low brain ascorbic acid increases susceptibility to seizures in mouse models of decreased brain ascorbic acid transport and Alzheimer's disease.

    Science.gov (United States)

    Warner, Timothy A; Kang, Jing-Qiong; Kennard, John A; Harrison, Fiona E

    2015-02-01

    Seizures are a known co-occurring symptom of Alzheimer's disease, and they can accelerate cognitive and neuropathological dysfunction. Sub-optimal vitamin C (ascorbic acid) deficiency, that is low levels that do not lead the sufferer to present with clinical signs of scurvy (e.g. lethargy, hemorrhage, hyperkeratosis), are easily obtainable with insufficient dietary intake, and may contribute to the oxidative stress environment of both Alzheimer's disease and epilepsy. The purpose of this study was to test whether mice that have diminished brain ascorbic acid in addition to carrying human Alzheimer's disease mutations in the amyloid precursor protein (APP) and presenilin 1 (PSEN1) genes, had altered electrical activity in the brain (electroencephalography; EEG), and were more susceptible to pharmacologically induced seizures. Brain ascorbic acid was decreased in APP/PSEN1 mice by crossing them with sodium vitamin C transporter 2 (SVCT2) heterozygous knockout mice. These mice have an approximately 30% decrease in brain ascorbic acid due to lower levels of SVCT2 that supplies the brain with ASC. SVCT2+/-APP/PSEN1 mice had decreased ascorbic acid and increased oxidative stress in brain, increased mortality, faster seizure onset latency following treatment with kainic acid (10 mg/kg i.p.), and more ictal events following pentylenetetrazol (50 mg/kg i.p.) treatment. Furthermore, we report the entirely novel phenomenon that ascorbic acid deficiency alone increased the severity of kainic acid- and pentylenetetrazol-induced seizures. These data suggest that avoiding ascorbic acid deficiency may be particularly important in populations at increased risk for epilepsy and seizures, such as Alzheimer's disease.

  2. MT119, a new planar-structured compound, targets the colchicine site of tubulin arresting mitosis and inhibiting tumor cell proliferation.

    Science.gov (United States)

    Zhang, Zhixiang; Meng, Tao; Yang, Na; Wang, Wei; Xiong, Bing; Chen, Yi; Ma, Lanping; Shen, Jingkang; Miao, Ze-Hong; Ding, Jian

    2011-07-01

    Microtubule-targeted drugs are now indispensable for the therapy of various cancer types worldwide. In this article, we report MT119 [6-[2-(4-methoxyphenyl) -ethyl]-9-[(pyridine-3-ylmethyl)amino]pyrido[2',1':2,3]imida-zo[4,5-c]isoquinolin-5(6H)-one] as a new microtubule-targeted agent. MT119 inhibited tubulin polymerization significantly both in tumor cells and in cell-free systems, which was followed by the disruption of mitotic spindle assembly. Surface plasmon resonance-based analyses showed that MT119 bound to purified tubulin directly, with the K(D) value of 10.6 μM. The binding of MT119 in turn caused tubulin conformational changes as evidenced by the quenched tryptophan fluorescence, the reduction of the bis-ANS reactivity and the decreased DTNB-sulfhydryl reaction rate. Competitive binding assays further revealed that MT119 bound to tubulin at its colchicine site. Consequently, by inhibiting tubulin polymerization, MT119 arrested different tumor cells at mitotic phase, which contributed to its potent antitumor activity in vitro. MT119 was also similarly cytotoxic to vincristine-, adriamycin- or mitoxantrone-resistant cancer cells and to their corresponding parental cells. Together, these data indicate that MT119 represents a new class of colchicine-site-targeted inhibitors against tubulin polymerization, which might be a promising starting point for future cancer therapeutics. Copyright © 2010 UICC.

  3. Effect of ketogenic diet on hippocampus mossy fiber sprouting and GluR5 expression in kainic acid induced rat model

    Institute of Scientific and Technical Information of China (English)

    XU Xiang-ping; SUN Ruo-peng; JIN Rui-feng

    2006-01-01

    @@ Ketogenic diet (KD) is a high fat, low protein, low carbohydrate diet. Its antiepileptic effect is certain but the underlying mechanism is unknown.1Mossy fiber sprouting in the inner molecular layer of the dentate gyrus causes the synaptic reorganization in the hippocampus, which is an important cause of temporal lobe epilepsy in animals and humans.1,2 It is also essential to the genesis and development of epilepsy. As the predominant excitatory neurotransmitter in the central nervous system, glutamate plays a role in synaptic reorganization and development of epilepsy. In recent years, the role of glutamate receptor 5 (GluR5) in the genesis of seizures has attracted more and more attention of researchers and this receptor has become a candidate target of new antiepileptic drugs.3,4 In this study, we investigated the possible antiepileptic mechanism of KD in terms of synaptic reorganization and GluR5 expression, attempting to provide a theoretical basis for the development of new antiepileptic drugs.

  4. Expression of sodium channel α subunits 1.1, 1.2 and 1.6 in rat hippocampus after kainic acid-induced epilepsy

    NARCIS (Netherlands)

    Qiao, X.; Werkman, T.R.; Gorter, J.A.; Wadman, W.J.; van Vliet, E.A.

    2013-01-01

    Voltage-gated Na(+) channels control neuronal excitability and are the primary target for the majority of anti-epileptic drugs. This study investigates the (sub)cellular expression patterns of three important brain-associated Na(+) channel α subunits: NaV1.1, NaV1.2 and NaV1.6 during epileptogenesis

  5. Discovery of a New Class of Ionotropic Glutamate Receptor Antagonists by the Rational Design of (2S,3R)-3-(3-Carboxyphenyl)-pyrrolidine-2-carboxylic Acid

    DEFF Research Database (Denmark)

    Larsen, Ann Møller; Venskutonyte, Raminta; Valadés, Elena Antón;

    2011-01-01

    -5. In this article, we present the discovery of (2S,3R)-3-(3-carboxyphenyl)-pyrrolidine-2-carboxylic acid (1) based on a rational design process. Target compound 1 was synthesized by a stereoselective strategy in 10 steps from commercially available starting materials. Binding affinities of 1 at native ionotropic......The kainic acid (KA) receptors belong to the class of glutamate (Glu) receptors in the brain and constitute a promising target for the treatment of neurological and/ or psychiatric diseases such as schizophrenia, major depression, and epilepsy. Five KA subtypes have been identified and named GluK1...

  6. Absence of neurotoxic effects in leopard sharks, Triakis semifasciata, following domoic acid exposure.

    Science.gov (United States)

    Schaffer, P; Reeves, C; Casper, D R; Davis, C R

    2006-06-01

    Domoic acid (DA), a potent neurotoxin produced by select species of algae and diatoms, kills neurons bearing kainic acid-type glutamate receptors. Studies have shown that DA bioaccumulates in invertebrates and fish that consume the diatoms. In every vertebrate species tested or observed in the wild, dietary or systemic DA causes neuronal damage or clinical signs of neurotoxicity. Sharks, like marine birds and mammals, are exposed to DA through their diet; however, no research has demonstrated the effect of DA on shark behavior or physiology. In this study, juvenile leopard sharks (Triakis semifasciata) were given DA by intracoelomic injection at doses of 0, 1, 3, 9, and 27 mg/kg and observed for 7 days. The sharks failed to demonstrate behavioral or histological changes in response to the toxin. We identified putative brain glutamate receptors by probing western blots with an antibody specific for kainic acid-type glutamate receptors and demonstrated receptor localization in the cerebellum with immunohistochemistry. Blood levels of DA in three sharks dosed at 9 mg/kg fell rapidly within 1.5h of injection. We show that leopard sharks possess the molecular target for DA but are resistant to doses of DA known to be toxic to other vertebrates.

  7. The Investigation of the Interaction between Human Serum Transferring with Colchicine in the Presence of Pb+2 Ions: Synchronous Fluorescence Measurements

    Directory of Open Access Journals (Sweden)

    Goldouzian Z. Goldouzian F., Momen-Heravi M. and Chamani J.

    2012-01-01

    Full Text Available The interaction between Holo-Transferin (HTF and Colchicine (COL was investigated in the present of Pb+2 ions under physiological conditions by using synchronous fluorescence spectra. The synchronous fluorescence spectra show a slight change of tryptophan residue micro-environment. Synchronous fluorescence spectra show that the structure of the tyrosine residue environment was altered by interaction of the COL and Pb+2 ions with HTF. The fluorescence intensity of HTF decreased regularly beside a small blue shift with increasing concentrations of COL and Pb+2 ions. The intrinsic fluorescence of HTF was quenched in the presence of drug and ion. Interaction of drugs with HTF and HTF-Pb+2 can elucidate the properties of drug-protein and ion- protein complex, as it may provide useful information about the structural feature that determines the therapeutic effectiveness of ion and drugs. Therefore, it has become a significant research field in life science, chemistry, biotechnology and clinical medicine.

  8. Impairment of blood brain barrier is related with the neuroinflammation induced peripheral immune status in intracerebroventricular colchicine injected rats: An experimental study with mannitol.

    Science.gov (United States)

    Sil, Susmita; Ghosh, Arijit; Ghosh, Tusharkanti

    2016-09-01

    The neurodegeneration in AD patients may be associated with changes of peripheral immune responses. Some peripheral immune responses are altered due to neuroinflammation in colchicine induced AD (cAD) rats. The leaky blood brain barrier (BBB) in cAD-rats may be involved in inducing peripheral inflammation, though there is no report in this regard. Therefore, the present study was designed to investigate the role of BBB in cADrats by altering the BBB in a time dependent manner with injection (i.v.) of mannitol (BBB opener). The inflammatory markers in the brain and serum along with the peripheral immune responses were measured after 30 and 60min of mannitol injection in cAD rats. The results showed higher inflammatory markers in the hippocampus and serum along with alterations in peripheral immune parameters in cAD rats. Although the hippocampal inflammatory markers did not further change after mannitol injection in cAD rats, the serum inflammatory markers and peripheral immune responses were altered and these changes were greater after 60min than that of 30min of mannitol injection. The present study shows that the peripheral immune responses in cAD rats after 30 and 60min of mannitol injection are related to magnitude of impairment of BBB in these conditions. It can be concluded from this study that impairment of BBB in cAD rats is related to the changes of peripheral immune responses observed in that condition.

  9. Analysis of Dermal Papilla Cell Interactome Using STRING Database to Profile the ex Vivo Hair Growth Inhibition Effect of a Vinca Alkaloid Drug, Colchicine

    Directory of Open Access Journals (Sweden)

    Ching-Wu Hsia

    2015-02-01

    Full Text Available Dermal papillae (DPs control the formation of hair shafts. In clinical settings, colchicine (CLC induces patients’ hair shedding. Compared to the control, the ex vivo hair fiber elongation of organ cultured vibrissa hair follicles (HFs declined significantly after seven days of CLC treatment. The cultured DP cells (DPCs were used as the experimental model to study the influence of CLC on the protein dynamics of DPs. CLC could alter the morphology and down-regulate the expression of alkaline phosphatase (ALP, the marker of DPC activity, and induce IκBα phosphorylation of DPCs. The proteomic results showed that CLC modulated the expression patterns (fold > 2 of 24 identified proteins, seven down-regulated and 17 up-regulated. Most of these proteins were presumably associated with protein turnover, metabolism, structure and signal transduction. Protein-protein interactions (PPI among these proteins, established by Search Tool for the Retrieval of Interacting Genes/Proteins (STRING database, revealed that they participate in protein metabolic process, translation, and energy production. Furthermore, ubiquitin C (UbC was predicted to be the controlling hub, suggesting the involvement of ubiquitin-proteasome system in modulating the pathogenic effect of CLC on DPC.

  10. Developing novel C-4 analogues of pyrrole-based antitubulin agents: weak but critical hydrogen bonding in the colchicine site.

    Science.gov (United States)

    Da, Chenxiao; Telang, Nakul; Hall, Kayleigh; Kluball, Emily; Barelli, Peter; Finzel, Kara; Jia, Xin; Gupton, John T; Mooberry, Susan L; Kellogg, Glen E

    2013-01-01

    The synthesis, biological evaluation and molecular modeling of a series of pyrrole compounds related to 3,5-dibromo-4-(3,4-dimethoxyphenyl)-1H-pyrrole-2-carboxylic acid that evaluates and optimizes C-4 substituents are reported. The key factor for microtubule depolymerization activity appears to be the presence of an appropriately positioned acceptor for Cys241β in the otherwise hydrophobic subpocket A.

  11. Resolution, configurational assignment, and enantiopharmacology at glutamate receptors of 2-amino-3-(3-carboxy-5-methyl-4-isoxazolyl)propionic acid (ACPA) and demethyl-ACPA

    DEFF Research Database (Denmark)

    Johansen, T N; Stensbøl, T B; Nielsen, B;

    2001-01-01

    We have previously described (RS)-2-amino-3-(3-carboxy-5-methyl-4-isoxazolyl)propionic acid (ACPA) as a potent agonist at the (RS)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) receptor subtype of (S)-glutamic acid (Glu) receptors. We now report the chromatographic resolution...... of ACPA and (RS)-2-amino-3-(3-carboxy-4-isoxazolyl)propionic acid (demethyl-ACPA) using a Sumichiral OA-5000 column. The configuration of the enantiomers of both compounds have been assigned based on X-ray crystallographic analyses, supported by circular dichroism spectra and elution orders on chiral HPLC...... columns. Furthermore, the enantiopharmacology of ACPA and demethyl-ACPA was investigated using radioligand binding and cortical wedge electrophysiological assay systems and cloned metabotropic Glu receptors. (S)-ACPA showed high affinity in AMPA binding (IC(50) = 0.025 microM), low affinity in kainic acid...

  12. Plantas autotetraplóides de citros sob tratamento in vitro com colchicina Citrus autotetraploid plants obtained by in vitro treatment with colchicine

    Directory of Open Access Journals (Sweden)

    Rodrigo Rocha Latado

    2007-10-01

    Full Text Available O objetivo deste trabalho foi obter plantas autotetraplóides de tangerina 'Ponkan', laranja 'Pêra-de-abril' e tangor 'Murcott', que serão usadas em cruzamentos com cultivares diplóides, visando à obtenção de indivíduos triplóides sem sementes. Utilizou-se o método de cultivo in vitro de segmentos de epicótilo em meio com colchicina (0,025, 0,05 e 0,1%, por diversos períodos (1, 2, 3, 7 e 14 dias, com subseqüente regeneração de brotações em meio sem a presença do alcalóide. As brotações foram microenxertadas in vitro e aclimatizadas em estufas. A determinação do nível de ploidia das plantas foi realizada por citometria de fluxo. A colchicina demonstrou ser tóxica aos explantes das três variedades, ocasionando redução significativa no número médio de brotações adventícias e aumento na porcentagem de explantes não-responsivos, em comparação com o controle. Entre as quatro plantas de laranja e uma de tangor obtidas, duas plantas de laranja e a de tangor, demonstraram ser autotetraplóides, apresentando folhas com maior espessura, arredondadas e coloração verde intensa. O método utilizado na duplicação cromossômica, com uso de colchicina, é eficiente em produzir plantas autotetraplóides de citros.The objective of this work was to obtain autotetraploid plants of 'Murcott' tangor, 'Ponkan' mandarin and 'Pêra-de-abril' sweet orange to be used in crosses with diploid cultivars, aiming to produce triploid seedless hybrids. The methodology used was the in vitro culture of epicotyl segments in media containing different concentrations of colchicine (0.025, 0.05 and 0.1%, for several periods of time (1, 2, 3, 7 and 14 days, followed by the regeneration of adventitious shoots in culture media without the alkaloid. All shoots obtained were micro-grafted, acclimatized and transferred to a greenhouse. The evaluation of the ploidy level of the plants was performed by flow citometry technique. Colchicine was toxic to

  13. Poliploidização em berinjela (Solanum melongena L.: I - Tratamento de sementes pela colquicina Polyplodization in Solanum melongena L.: I. seed treatments with colchicine

    Directory of Open Access Journals (Sweden)

    Dixier M. Medina

    1972-01-01

    Full Text Available Com o objetivo de conseguir plantas poliplóides de berinjela, foram realizados em 1970 alguns tratamentos com colquicina em sementes do cultivar Santa Genebra. Três séries de tratamentos foram efetuadas, era-pregando-se soluções de diferentes concentrações, variando a duração do tratamento e também seu momento de aplicação, isto é, antes, durante e até a germinação. O número de cromossomos nas raízes e o número de estornas do material tratado, quando comparados com o original diplóide, indicam que a completa poliploidização não foi conseguida. O máximo que se constatou até o estádio de desenvolvimento em que foram levadas as observações, foram plantas quiméricas, tanto na parte aérea como nas raízes, provenientes dos tratamentos de sementes em germinação e dos tratamentos mais fortes (0,4% e 0,6% aplicados antes da germinação das sementes.Polyploidization in egg-plant has been tried through colchicine treatments in seeds of the cultivar Santa Genebra from Instituto Agronômico. Several trials were made varying the strenght of the solution, the duration of the treatment and the time of its application, that is, before, during, and after seed germination. Chromosome numbers determined in roots as well as the number of stomata of treated material compared to those of original diploid one, indicate that complete polyploidization was not achieved. Instead, chimeric plants either in aerial part or in the roots were detected, that resulted from treatment of seeds in germination and from those stronger treatments (0.4 and 0.6% applied before germination.

  14. High-performance liquid chromatography coupled to ion spray mass spectrometry for the determination of colchicine at ppb levels in human biofluids.

    Science.gov (United States)

    Tracqui, A; Kintz, P; Ludes, B; Rougé, C; Douibi, H; Mangin, P

    1996-01-26

    An original method based upon high-performance liquid chromatography coupled to ion spray mass spectrometry (HPLC-ISP-MS) has been developed for the identification and quantification of colchicine (COL) in human blood, plasma or urine. After single-step liquid-liquid extraction by dichloromethane at pH 8.0 using tofisopam (TOF) as an internal standard, solutes are separated on a 5-microns C18 Microbore (Alltech) column (250 x 1.0 mm, I.D.), using acetonitrile-2 mM NH4COOH, pH 3 buffer (75: 25, v/v) as the mobile phase (flow-rate 50 microliters/min). Detection is done by a Perkin-Elmer Sciex API-100 mass analyzer equipped with a ISP interface (nebulizing and curtain gas: N2, quality U; main settings: ISP, +4.0 kV; OR, +50 V; Q0, -10 V; Q1, -13 V; electron multiplier, +2.2 kV); MS data are collected as either total ion current (TIC, m/z 100-500 or 380-405), or selected ion monitoring (SIM) at m/z 400 and 383 for COL and TOF, respectively. COL mass spectrum shows a prominent molecular ion [M + H]+ at m/z 400. Increasing OR potential fails to provide a significant fragmentation. Retention times are 2.70 and 4.53 min for COL and TOF, respectively. The quantification method shows a good linearity (r = 0.998) over a concentration range from 5 to 200 ng/ml. The lower limit of detection in SIM mode is 0.6 ng/ml COL, making the method convenient for both clinical and forensic purposes.

  15. Protective effect of parvalbumin on excitotoxic motor neuron death

    DEFF Research Database (Denmark)

    Van den Bosch, L.; Schwaller, B.; Vleminckx, V.

    2002-01-01

    Amyotrophic lateral sclerosis, ALS, AMPA receptor, calcium-binding proteins, calcium buffering, excitotoxity, kainic acid, motor neuron, parvalbumin......Amyotrophic lateral sclerosis, ALS, AMPA receptor, calcium-binding proteins, calcium buffering, excitotoxity, kainic acid, motor neuron, parvalbumin...

  16. Survival and development in vitro of Cattleya (Orchidaceae submitted to treatments with different treatments of colchicinesSobrevivência e desenvolvimento in vitro de Cattleya (Orchidaceae submetida a tratamentos com colchicina

    Directory of Open Access Journals (Sweden)

    Lúcia Sadayo Assari Takahashi

    2010-02-01

    Full Text Available Polyploidy produces desirable characteristicsin orchids that are represented by increase of the floral pieces, succulency degree, intensification of color, durability and larger resistance of flowers. The colchicine as polyploidy inductor agent in in vitro culture of plants has limitations, because when in high concentrations or very long treatments, it becomes poisonous for the vegetal tissues. The objective of this research work was to evaluate the influence of concentrations and times of exposition to the colchicine, on the survival and on the in vitro development of Cattleya tigrina. Protocorms were treated with colchicine in the concentrations of 0.5 and 1g.L-1 during 24, 48 and 72 hours. There were evaluated the tax of survival of the protocorms (%, percentage of plantlings with multiple buds and plant height after three and seven months. The increase of the concentration and of the time of exposition to colchicine caused a larger plant mortality and an increase of plantlings with reduced height. Nas orquidáceas, a poliploidia produz características desejáveis, que se traduzem em aumento das peças florais, grau de suculência, intensificação do colorido, durabilidade e maior resistência das flores. A colchicina como agente indutor de poliploidia em cultura de plantas in vitro tem suas limitações, pois em elevadas concentrações ou tratamentos muito prolongados, torna-se tóxica. O objetivo do trabalho foi avaliar a influência da concentração e do tempo de exposição à colchicina, na sobrevivência e no desenvolvimento in vitro de Cattleya tigrina. Protocormos foram tratados com colchicina em concentrações de 0,5 e 1g.L-1 durante 24, 48 e 72 horas. Foram avaliados taxa de sobrevivência dos protocormos (%, porcentagem de plântulas com múltiplas brotações e altura após três e sete meses. Com o aumento da concentração e do tempo de exposição à colchicina houve maior mortalidade e aumento do número de pl

  17. Excitotoxic death induced by released glutamate in depolarized primary cultures of mouse cerebellar granule cells is dependent on GABAA receptors and niflumic acid-sensitive chloride channels.

    Science.gov (United States)

    Babot, Zoila; Cristòfol, Rosa; Suñol, Cristina

    2005-01-01

    Excitotoxic neuronal death has been linked to neurological and neurodegenerative diseases. Several studies have sought to clarify the involvement of Cl(-) channels in neuronal excitotoxicity using either N-methyl-D-aspartic acid (NMDA) or alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainic acid agonists. In this work we induced excitotoxic death in primary cultures of cerebellar granule cells by means of endogenously released glutamate. Excitotoxicity was provoked by exposure to high extracellular K(+) concentrations ([K(+)](o)) for 5 min. Under these conditions, a Ca(2+)-dependent release of glutamate was evoked. When extracellular glutamate concentration rose to between 2 and 4 microM, cell viability was significantly reduced by 30-40%. The NMDA receptor antagonists (MK-801 and D-2-amino-5-phosphonopentanoic acid) prevented cell death. Exposure to high [K(+)](o) produced a (36)Cl(-) influx which was significantly reduced by picrotoxinin. In addition, the GABA(A) receptor antagonists (bicuculline, picrotoxinin and SR 95531) protected cells from high [K(+)](o)-triggered excitotoxicity and reduced extracellular glutamate concentration. The Cl(-) channel blockers niflumic acid and 5-nitro-2-(3-phenylpropylamino)benzoic acid also exerted a neuroprotective effect and reduced extracellular glutamate concentration, even though they did not reduce high [K(+)](o)-induced (36)Cl(-) influx. Primary cultures of cerebellar granule cells also contain a population of GABAergic neurons that released GABA in response to high [K(+)](o). Chronic treatment of primary cultures with kainic acid abolished GABA release and rendered granule cells insensitive to high [K(+)](o) exposure, even though NMDA receptors were functional. Altogether, these results demonstrate that, under conditions of membrane depolarization, low micromolar concentrations of extracellular glutamate might induce an excitotoxic process through both NMDA and GABA(A) receptors and niflumic acid-sensitive Cl

  18. MDMA decreases glutamic acid decarboxylase (GAD) 67-immunoreactive neurons in the hippocampus and increases seizure susceptibility: Role for glutamate.

    Science.gov (United States)

    Huff, Courtney L; Morano, Rachel L; Herman, James P; Yamamoto, Bryan K; Gudelsky, Gary A

    2016-12-01

    3,4-Methylenedioxy-methamphetamine (MDMA) is a unique psychostimulant that continues to be a popular drug of abuse. It has been well documented that MDMA reduces markers of 5-HT axon terminals in rodents, as well as humans. A loss of parvalbumin-immunoreactive (IR) interneurons in the hippocampus following MDMA treatment has only been documented recently. In the present study, we tested the hypothesis that MDMA reduces glutamic acid decarboxylase (GAD) 67-IR, another biochemical marker of GABA neurons, in the hippocampus and that this reduction in GAD67-IR neurons and an accompanying increase in seizure susceptibility involve glutamate receptor activation. Repeated exposure to MDMA (3×10mg/kg, ip) resulted in a reduction of 37-58% of GAD67-IR cells in the dentate gyrus (DG), CA1, and CA3 regions, as well as an increased susceptibility to kainic acid-induced seizures, both of which persisted for at least 30days following MDMA treatment. Administration of the NMDA antagonist MK-801 or the glutamate transporter type 1 (GLT-1) inducer ceftriaxone prevented both the MDMA-induced loss of GAD67-IR neurons and the increased vulnerability to kainic acid-induced seizures. The MDMA-induced increase in the extracellular concentration of glutamate in the hippocampus was significantly diminished in rats treated with ceftriaxone, thereby implicating a glutamatergic mechanism in the neuroprotective effects of ceftriaxone. In summary, the present findings support a role for increased extracellular glutamate and NMDA receptor activation in the MDMA-induced loss of hippocampal GAD67-IR neurons and the subsequent increased susceptibility to evoked seizures.

  19. 秋水仙素对辣椒生长的影响及多倍体诱导效应研究%Studies on the Influence of Colchicine on Growth and Multiploid Induction of Bush Redpepper Capsicum annuum L.

    Institute of Scientific and Technical Information of China (English)

    谢晓玲; 邓自发

    2009-01-01

    In this paper, the polyploidy-induction effects of colchicine on pepper Capsicum annuum L. With different concentration (0. 01%, 0. 03%, 0. 05%) and treated time (2 d, 4 d, 6 d) were studied. The results showed that the chromosome number of variant plants varied with cells which had 4 n = 48 chromosomes and some was 2 n = 24 chromosomes. Contrasted to normal diploid plants (ck), the induced plants exhibited the morphologic characteristics with thicker and larger leaves, larger stomata and stronger stems with longer length per stem stalk. Relevant indexes all showed significant or extreme significant differences, and the difference increased with intensity of treatment. Induced plants showed chimera through ploidy determinion (2 n to plant chimeras 2 n = 24 or 48). With the same treating time, the polyploidy-induction effects of colchicine on pepper Capsicum annuuml was different in different concentration, but in the same concentration, the number of leaves and stomata of induced plant had no obvious difference with different treating time(p >0.05), but others had extreme difference(p < 0.01). There had some interaction between colchicine concertration and treating time. In all treatments, only stomato area had no obvious difference, the others indexes were different significantly or extreme significantly each other. Based on the integrative analysis, it was concluded that the best combination of colchicine solution concentration and processing time was the best combination of 0.05% induced 6d, and the induction rate could reach 26.1 %.%以秋水仙素为诱变剂,比较了不同浓度和不同处理时长组合下辣椒(Capsicum annuum L.)的生长差异和多倍体诱导效应.结果表明:和对照植株相比,所有处理变异植株在形态上表现为叶片宽大,叶色较深,茎变粗且节间距长,气孔增大;相关指标都表现出显著或极显著的差异,而且随着处理强度的增加差异更为明显.秋水仙素诱导产生的变异植

  20. Colchicine in the treatment of the inflammatory phase of Graves' ophthalmopathy: a prospective and randomized trial with prednisone Colchicina no tratamento da fase inflamatória da oftalmopatia de Graves: um estudo prospectivo e randomizado com prednisona

    Directory of Open Access Journals (Sweden)

    Francisco José da Cunha Stamato

    2006-12-01

    Full Text Available PURPOSE: To investigate if colchicine is valuable in the treatment of Graves' ophthalmopathy (GO, we compared its effect with prednisone in 22 patients during the inflammatory phase of GO. METHODS: All patients, similar in age, sex and smoking habits, were euthyroid for at least 3 months and randomly divided into two groups, one treated with colchicine (1.5 mg/day and the other treated with prednisone (0.75 mg/kg/day. They were monitored with ophthalmologic assessment (clinical activity score-CAS and magnetic resonance imaging, using a signal intensity ratio (SIR of the recti muscles in comparison to the cerebral substantia alba. RESULTS: Amelioration of CAS was seen in 68% of the orbits in both groups. SIR also had a significant reduction after treatment: the initial median of 1.14 in G1 and 1.27 in G2, evolved, after treatment, to 1.07 in G1 and 0.69 in G2. The variation between both groups after treatment was not significant (p=0.22. None of the patients treated with colchicine had side effects; on the other hand, side effects in G2 were weight gain, edema, gastric complaints, hirsutism, weakness, depression, and alterations in blood pressure. CONCLUSION: Colchicine had a beneficial effect on the inflammatory phase of GO without the side effects of prednisone.OBJETIVO: Investigar se a colchicina é eficaz no tratamento da oftalmopatia de Graves, nós comparamos o seu efeito com a prednisona em 22 pacientes tratados na fase inflamatória da doença. MÉTODOS: Todos os pacientes, similares quanto à idade, sexo e hábitos de tabagismo, estavam em eutiroidismo por pelo menos três meses e foram randomizados em dois grupos. O grupo 1 (G1 recebeu colchicina (1,5 mg/dia e o grupo 2 (G2 foi tratado com prednisona (0,75 mg/kg/dia. Os pacientes foram acompanhados com avaliação oftalmológica (escore de atividade clínica - CAS e de imagem por meio da ressonância magnética, usando a relação da intensidade de sinal (SIR dos músculos reto em

  1. N-Phenyl-N'-(2-chloroethyl)ureas (CEUs) as potential antineoplastic agents. Part 3: role of carbonyl groups in the covalent binding to the colchicine-binding site.

    Science.gov (United States)

    Moreau, Emmanuel; Fortin, Sébastien; Lacroix, Jacques; Patenaude, Alexandre; Rousseau, Jean L C; C-Gaudreault, René

    2008-02-01

    In the course of the development of N-phenyl-N'-(2-chloroethyl)ureas (CEUs) as potential antineoplastic agents, we investigated the effect of carbonylated substituting chains of the aromatic ring of CEU on their covalent binding to the colchicine-binding site (C-BS). In this study, we found that CEU, 5e, 5f, 8e, and 8f substituted by either a methyl ester or a methyl ketyl group at the omega-position exhibited a significant antiproliferative activity on HT-29, M21, and MCF-7 tumor cells. SDS-PAGE assays and cell cycle analysis confirmed that 5e, 5f, 8e, and 8f covalently bind to the C-BS and arrest the cell division in G(2)/M phase. Surprisingly, the presence of omega-carboxyl, omega-ethyl esters or omega-amides decreased significantly both the antiproliferative activity and the specificity toward beta-tubulin.

  2. The familial Mediterranean fever (FMF) 50 score: does it work in a controlled clinical trial? Re-analysis of the trial of rilonacept for patients with colchicine-resistant or intolerant FMF.

    Science.gov (United States)

    Hashkes, Philip J; Huang, Bin

    2015-03-01

    The familial Mediterranean fever 50 score (FMF50) score was recently devised to define response to treatment and as an outcome measure for clinical trials of FMF. To examine the performance of the FMF50 score in a previously published trial of rilonacept for patients whose FMF was resistant or intolerant to colchicine. We re-analyzed the data from our controlled trial of rilonacept vs. placebo in 14 patients with colchicine-resistant or intolerant FMF using the FMF50 score as the primary outcome. The FMF50 score required improvement by ≥ 50 in five of six criteria (attack frequency, attack duration, global patient assessment, global physician assessment, frequency of attacks with arthritis, and levels of acute-phase reactants) without worsening of the sixth criterion. In the original trial rilonacept was considered effective according to the primary outcome measure (differences in the attack frequency) with eight analyzable patients considered responders and four as non-responders. According to the FMF50 score, only two participants would have been considered respondersto rilonacept, and one to placebo. Only two participants had ≥ 50% differences between rilonacept and placebo in five criteria. The major explanation for non-response to treatment was that with rilonacept the duration of attack decreased by ≥ 50% in only 2 participants and 5 participants had no attacks of arthritis either during screening (before randomization) or during treatment with rilonacept. The proposed FMF50 score did not differentiate well between responders and non-responders compared to the a priori defined primary outcome measure in this successful controlled study.

  3. Rational design and enantioselective synthesis of (1R,4S,5R,6S)-3-azabicyclo[3.3.0]octane-4,6-dicarboxylic acid - a novel inhibitor at human glutamate transporter subtypes 1, 2, and 3

    DEFF Research Database (Denmark)

    Bunch, Lennart; Nielsen, Birgitte; Jensen, Anders A.;

    2006-01-01

    The natural product kainic acid is used as template for the rational design of a novel conformationally restricted (S)-glutamic acid (Glu) analogue, (1R,4S,5R,6S)-3-azabicyclo[3.3.0]octane-4,6-dicarboxylic acid (1a). The target structure 1a was synthesized from commercially available (S......)-pyroglutaminol, in an enantioselective fashion, in 14 steps. Pharmacological characterization of 1a at human glutamate transporter subtypes 1, 2, and 3 yielded K(i) values of 127, 52, and 46 microM, respectively. Furthermore, binding studies at native ionotropic Glu (iGlu) receptors revealed low affinity for alpha-amino-3-hydroxy-5...

  4. 秋水仙素诱导抗枯1号香蕉多倍体试验%In vitro polyploid induction of banana Kangku 1 using colchicine

    Institute of Scientific and Technical Information of China (English)

    谭平; 唐晓华; 劳世辉; 魏岳荣; 洪林

    2012-01-01

    This study aimed to obtain polyploidy banana by chemical introduction in order to provide new banana breeding germplasm resources. [Method]In this research, the embryogenic cell suspension (ECS) of banana Kangku 1 was treated with colchicine at different concentrations and induction times. The corresponding results were recorded and analyzed. [ Result ]The results showed that some types of chromosome natural variation occurred at the ECS subculture stage. During this occurrence, the variation proportion reached up to 11.76%. On the other hand, the chromosome variation of treated regenerated seedlings was at a higher rate of 76.92% ~100.00% while accompanying with a small amount of chimera regeneration plants. Considering the numbers of regenerated seedlings and the variation proportion, the best effect could be obtained after treating the ECS with 0.1% colchicine for 12 hours. Three hexaploid banana plants and large number of aneuploid variation plants were successfully identified from the regenerated seedlings. [ Conclusion ]The natural variation of banana was produced during the subculture of Kangku 1 ECS, and the efficiency of polyploidy induction increased. The best treatment amongst all the ones tested was treating the ECS with 0.1% colchicine concentration for 12 hours.%[目的]通过多倍体诱导途径为香蕉育种提供新型种质资源.[方法]以抗枯1号香蕉胚性细胞悬浮系(ECS)为材料,利用秋水仙素进行多倍体诱导,探讨在秋水仙素不同浓度、不同处理时间条件下多倍体的获得情况.[结果]在未采用秋水仙素处理的条件下,抗枯1号香蕉ECS在继代培养过程中存在一定比例的染色体数目自然变异,变异率为11.76%;而秋水仙素处理后再生苗的染色体数目变异率介于76.92%~100.00%,且有少量的嵌合体再生植株;不同浓度秋水仙素及处理时间获得的再生苗数及其变异率不同,其中以0.1%秋水仙素处理12h的效果较好,共获得3

  5. Establishment and evaluation of epileptic model kindled by kainic acid microinjected into nucleus amygdalae in rats%海人酸杏仁核点燃大鼠癫痫模型的建立和评价

    Institute of Scientific and Technical Information of China (English)

    梁建民; 李秀杰; 崔新明; 蔡正旭; 张淑琴; 纪莉; 崔璐

    2005-01-01

    目的:建立和评价海人酸杏仁核微量注射点燃癫痫动物模型.方法:选用雄性Wistar大鼠,以杏仁核外侧基底核为给药靶点,在立体定位仪下,微量注射海人酸1μg后进行大鼠的行为学和电生理学观察,并分别于第6、12、72 h和7、14、21 d对大鼠脑组织进行病理学观察.结果:海人酸微量注射后实验大鼠出现典型的癫痫发作过程,顶叶皮层脑电图依次出现多种形式的痫性放电,HE染色显示海马和颞叶皮层神经细胞的相应病理变化,点燃成功率为90%.结论:采用杏仁核海人酸微量注射方法成功建立了Wistar大鼠点燃癫痫模型,该模型适用于颞叶癫痫的相关研究.

  6. High expression of snail in mouse cerebral cortex following kainic acid-induced status epilepticus%Snail在海人酸诱导癫痫持续状态小鼠皮层中高表达

    Institute of Scientific and Technical Information of China (English)

    王静; 王法祥; 杨云鹏; 吴海琴

    2016-01-01

    目的 观察snail因子在海人酸(KA)诱导癫痫持续状态(SE)小鼠皮层中的表达和分布,探讨snail在癫痫持续发作状态中的作用.方法 成年雄性C57/BL6小鼠64只,随机分成对照组和SE组,每组32只.对照组采用腹腔注射生理盐水,SE组采用KA腹腔注射诱发小鼠癫痫急性发作,并且各组分别在发作终止后的3、8、24、72 h进行取材.反转录PCR检测snail的mRNA表达水平,Western blot法检测snail的蛋白表达水平,免疫组织化学检测snail的形态分布,免疫荧光技术检测snail的定位.结果 与对照组相比,SE组snail mRNA和蛋白的表达水平明显上升,24 h达到高峰;免疫组织化学技术显示,在对照组,snail表达呈弱阳性.在SE组,snail在不同皮层神经元以及胶质状细胞都有广泛分布;免疫荧光技术进一步证明snail在神经元和星形胶质细胞均有表达.结论 Snail在KA诱导SE小鼠皮层神经元和星形胶质细胞内都有强表达,提示snail可能与癫痫的发作有一定的联系.

  7. 愈痫灵对红藻氨酸致痫大鼠行为的影响%The Influence of YuXianLing(YXL)on the Behavior of Experimental Epilepsia Rats Induced by Kainic Acid(KA)

    Institute of Scientific and Technical Information of China (English)

    钟艳; 王净净; 李振光; 何群; 顾星; 段祖珍

    2001-01-01

    为观察愈痫灵颗粒剂对致痫大鼠行为的影响,探讨该方的抗癫痫作用.采用红藻氨酸造模,随机将40只SD大鼠分为模型组、中药汤剂组、中药颗粒剂组、西药组,按Schultz-Krohn标准观察行为表现.结果显示愈痫灵汤剂组、颗粒剂组可延长癫痫发作潜伏时间(P<0.05),减少湿狗样抖动次数(P<0.05).提示愈痫灵颗粒剂有显著的抗痫作用.

  8. Chlorogenic acid protection of neuronal nitric oxide synthase-positive neurons in the hippocampus of mice with impaired learning and memory

    Institute of Scientific and Technical Information of China (English)

    Qiuyun Tu; Xiangqi Tang; Zhiping Hu

    2008-01-01

    BACKGROUND: Clinical practice and modern pharmacology have confirmed that ehlorogenic acid can ameliorate learning and memory impairments. OBJECTIVE: To observe the effects of chlorogenic acid on neuronal nitric oxide synthase (nNOS)-positive neurons in the mouse hippocampus, and to investigate the mechanisms underlying the beneficial effects of chlorogenic acid on learning and memory. DESIGN, TIME AND SETTING: The present randomized, controlled, neural cell morphological observation was performed at the Institute of Neurobiology, Central South University between January and May 2005.MATERIALS: Forty-eight female, healthy, adult, Kunming mice were included in this study. Learning and memory impairment was induced with an injection of 0.5 μL kainic acid (0.4 mg/mL) into the hippocampus.METHODS: The mice were randomized into three groups (n = 16): model, control, and chlorogenic acid-treated. At 2 days following learning and memory impairment induction, intragastric administration of physiological saline or chlorogenic acid was performed in the model and chlorogenic acid-treated groups, respectively. The control mice were administered 0.5 μ L physiological saline into the hippocampus, and 2 days later, they received an intragastric administration of physiological saline. Each mouse received two intragastric administrations (1 mL solution once) per day, for a total of 35 days. MAIN OUTCOME MEASURES: Detection of changes in hippocampal and cerebral cortical nNOS neurons by immunohistochemistry; determination of spatial learning and memory utilizing the Y-maze device.RESULTS: At day 7 and 35 after intervention, there was no significant difference in the number of nNOS-positive neurons in the cerebral cortex between the model, chlorogenic acid, and control groups (P > 0.05). Compared with the control group, the number of nNOS-positive neurons in the hippocampal CA1-4 region was significantly less in the model group (P 0.05). At day 7 following intervention, the number

  9. Spectroscopic and nano-molecular modeling investigation on the binary and ternary bindings of colchicine and lomefloxacin to Human serum albumin with the viewpoint of multi-drug therapy

    Energy Technology Data Exchange (ETDEWEB)

    Chamani, J., E-mail: Chamani@ibb.ut.ac.i [Department of Biology, Faculty of Sciences, Islamic Azad University-Mashhad Branch, Mashhad (Iran, Islamic Republic of); Asoodeh, A. [Department of Chemistry, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad (Iran, Islamic Republic of); Homayoni-Tabrizi, M. [Department of Biology, Faculty of Sciences, Islamic Azad University-Mashhad Branch, Mashhad (Iran, Islamic Republic of); Amiri Tehranizadeh, Z.; Baratian, A.; Saberi, M.R. [Medical Chemistry Department, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad (Iran, Islamic Republic of); Gharanfoli, M. [Department of Development Biology, Culture and Science University, Tehran (Iran, Islamic Republic of)

    2010-12-15

    Combination of several drugs is often necessary especially during long-term therapy. The competitive binding drugs can cause a decrease in the amount of drug bound to protein and increase the biological active fraction of the drug. The aim of this study is to analyze the interactions of Lomefloxacin (LMF) and Colchicine (COL) with human serum albumin (HSA) and to evaluate the mechanism of simultaneous binding of LMF and COL to protein. Fluorescence analysis was used to estimate the effect of drugs on the protein fluorescence and to define the binding and quenching properties of drugs-HSA complexes. The binding sites for LMF and COL were identified in tertiary structure of HSA with the use of spectrofluorescence analysis. The analysis of fluorescence quenching of HSA in the binary and ternary systems show that LMF does not affect the complex formed between COL and HSA. On the contrary, COL decreases the interaction between LMF and HSA. The results of synchronous fluorescence, resonance light scattering and circular dichroism spectra of binary and ternary systems show that binding of LMF and COL to HSA can induce micro-environmental and conformational changes in HSA. The simultaneous presence of LMF and COL in binding to HSA should be taken into account in the multi-drug therapy, and necessity of using a monitoring therapy owning to the possible increase of the uncontrolled toxic effects. Molecular modeling of the possible binding sites of LMF and COL in binary and ternary systems to HSA confirms the spectroscopic results.

  10. Etoposide; colchicine; mitomycin C and cyclophosphamide tested in the in vitro mammalian cell micronucleus test (MNvit) in Chinese hamster lung (CHL) cells at Covance laboratories; Harrogate UK in support of OECD draft Test Guideline 487.

    Science.gov (United States)

    Fowler, Paul; Whitwell, James; Jeffrey, Laura; Young, Jamie; Smith, Katie; Kirkland, David

    2010-10-29

    The following genotoxic chemicals were tested in the in vitro micronucleus assay, at Covance Laboratories, Harrogate, UK in the Chinese hamster lung cell line CHL. Etoposide (a topoisomerase inhibitor), colchicine (an aneugen), mitomycin C (a DNA cross linking agent) and cyclophosphamide (an alkylating agent requiring metabolic activation) were treated with and without cytokinesis block (by addition of cytochalasin B). This work formed part of a collaborative evaluation of the toxicity measures recommended in the draft OECD Test Guideline 487 for the in vitro micronucleus test. The toxicity measures used, detecting both cytostasis and cell death, were relative population doubling, relative increase in cell counts and relative cell counts for treatments in the absence of cytokinesis block, and replication index or cytokinesis blocked proliferation index in the presence of cytokinesis block. All of the chemicals tested gave significant increases in the percentage of micronucleated cells with and without cytokinesis block at concentrations giving approximately 60% toxicity (cytostasis and cell death) or less by all of the toxicity measures used. The outcomes from this series of tests support the use of relative increase in cell counts and relative population doubling, as well as relative cell counts, as appropriate measures of cytotoxicity for the non-cytokinesis blocked in vitro micronucleus assay.

  11. Mitomycin C, 5-fluoruracil, colchicine and etoposide tested in the in vitro mammalian cell micronucleus test (MNvit) in the human lymphoblastoid cell line TK6 at Novartis in support of OECD draft Test Guideline 487.

    Science.gov (United States)

    Elhajouji, Azeddine

    2010-10-29

    The following reference genotoxic agents were tested in the in vitro micronucleus test, at Novartis, Basel, Switzerland. Mitomycin C, 5-fluoruracil, colchicine and etoposide were tested in the human lymphoblastoid cell line TK6, with and without cytokinesis block (in the presence of cytochalasin B). This was done in support of the toxicity measures recommended in the draft OECD Test Guideline on In Vitro Mammalian Cell Micronucleus Test (MNvit) and was part of an international collaborative work. As toxicity measures, detecting cytostasis and cell death, relative cell counts (RCC), relative increase in cell counts (RICC), and relative population doubling (RPD) were used for treatments in the absence of cytokinesis block, and replication index (RI) or cytokinesis-blocked proliferation in the presence of cytokinesis block. All four reference agents were positive in the assay with and without cytokinesis block at concentrations giving approximately 50% toxicity or less as assessed by all of the toxicity measures used. Accordingly, the results of this work support the use of relative population doubling and relative increase in cell counts, as well as relative cell counts, as appropriate measures of toxicity for the non-cytokinesis-blocked in vitro micronucleus assay.

  12. Immunofluorescently labeling glutamic acid decarboxylase 65 coupled with confocal imaging for identifying GABAergic somata in the rat dentate gyrus-A comparison with labeling glutamic acid decarboxylase 67.

    Science.gov (United States)

    Wang, Xiaochen; Gao, Fei; Zhu, Jianchun; Guo, Enpu; Song, Xueying; Wang, Shuanglian; Zhan, Ren-Zhi

    2014-11-01

    As γ-aminobutyric acid (GABA) is synthesized by two isoforms of glutamic acid decarboxylase (GAD), namely, GAD65 and GAD67, immunohistochemically targeting either isoform of GAD is theoretically useful for identifying GABAergic cell bodies. In practice, targeting GAD67 remains to be a popular choice. However, identifying GABAergic cell bodies with GAD67 immunoreactivity in the hippocampal dentate gyrus, especially in the hilus, is not without pitfalls. In the present study, we compared the characteristics of GAD65 immunoreactivity to GAD67 immunoreactivity in the rat dentate gyrus and examined perikaryal expression of GAD65 in four neurochemically prevalent subgroups of interneurons in the hilus. Experiments were done in normal adult Sprague-Dawley rats and GAD67-GFP knock-in mice. Horizontal hippocampal slices cut from the ventral portion of hippocampi were immunofluorescently stained and scanned using a confocal microscope. Immunoreactivity for both GAD67 and GAD65 was visible throughout the dentate gyrus. Perikaryal GAD67 immunoreactivity was denser but variable in terms of distribution pattern and intensity among cells whereas perikaryal GAD65 immunoreactivity displayed similar distribution pattern and staining intensity. Among different layers of the dentate gyrus, GAD67 immunoreactivity was densest in the hilus despite GAD65 immunoreactivity being more intense in the granule cell layer. Co-localization experiments showed that GAD65, but not GAD67, was expressed in all hilar calretinin (CR)-, neuronal nitric oxide synthase (nNOS)-, parvalbumin (PV)- or somatostatin (SOM)-positive somata. Labeling CR, nNOS, PV, and SOM in sections obtained from GAD67-GFP knock-in mice revealed that a large portion of SOM-positive cells had weak GFP expression. In addition, double labeling of GAD65/GABA and GAD67/GABA showed that nearly all of GABA-immunoreactive cells had perikaryal GAD65 expression whereas more than one-tenth of GABA-immunoreactive cells lacked perikaryal GAD

  13. Effect of excitatory amino acids on serum TSH and thyroid hormone levels in freely moving rats.

    Science.gov (United States)

    Alfonso, M; Durán, R; Arufe, M C

    2000-01-01

    The actions of glutamate (L-Glu), and glutamate receptor agonists on serum thyroid hormones (T4 and T3) and TSH levels have been studied in conscious and freely moving adult male rats. The excitatory amino acids (EAA), L-Glu, N-methyl-D-aspartate (NMDA), kainic acid (KA) and domoic acid (Dom) were administered intraperitoneally. Blood samples were collected through a cannula implanted in the rats jugular 0--60 min after injection. Thyroid hormone concentrations were measured by enzyme immunoassay, and thyrotrophin (TSH) concentrations were determined by radioimmunoassay. The results showed that L-Glu (20 and 25 mg/kg) and NMDA (25 mg/kg) increased serum thyroxine (T4), triiodothyronine (T3) and TSH concentrations. Serum thyroid hormone levels increased 30 min after treatment, while serum TSH levels increased 5 min after i.p. administration, in both cases serum levels remained elevated during one hour. Injection of the non-NMDA glutamatergic agonists KA (30 mg/kg) and Dom (1 mg/kg) produced an increase in serum thyroid hormones and TSH levels. These results suggest the importance of EAAs in the regulation of hormone secretion from the pituitary-thyroid axis, as well as the importance of the NMDA and non-NMDA receptors in this stimulatory effect.

  14. Novel class of amino acid antagonists at non-N-methyl-D-aspartic acid excitatory amino acid receptors. Synthesis, in vitro and in vivo pharmacology, and neuroprotection

    Energy Technology Data Exchange (ETDEWEB)

    Krogsgaard-Larsen, P.; Ferkany, J.W.; Nielsen, E.O.; Madsen, U.; Ebert, B.; Johansen, J.S.; Diemer, N.H.; Bruhn, T.; Beattie, D.T.; Curtis, D.R. (Royal Danish School of Pharmacy, Copenhagen (Denmark))

    1991-01-01

    The isoxazole amino acid 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl) propionic acid (AMPA) (1), which is a highly selective agonist at the AMPA subtype of excitatory amino acid (EAA) receptors, has been used as a lead for the development of two novel EAA receptor antagonists. One of the compounds, 2-amino-3-(3-(carboxymethoxy)-5-methylisoxazol-4-yl)propionic acid (AMOA, 7), was synthesized via O-alkylation by ethyl chloroacetate of the amino acid protected AMPA derivative 4. The other compound, 2-amino-3-(2-(3-hydroxy-5-methylisoxazol-4-yl)-methyl-5-methyl-3-+ ++oxoisoxazolin -4-yl)propionic acid (AMNH, 14) was synthesized with use of 4-(chloromethyl)-3-methoxy-5-methylisoxazole (8) as the starting material. The intermediate 4-(chloromethyl)-2-(3-methoxy-5-methylisoxazol-4-yl)methyl-5-me thylisoxazolin- 3-one (11) was converted into the acetamidomalonate (12), which was stepwise deprotected to give 14. Compounds 7 and 14 were stable in aqueous solution at pH values close to physiological pH. Neither 7 nor 14 showed detectable affinities for the receptor, ion channel, or modulatory sites of the N-methyl-D-aspartic acid (NMDA) receptor complex. Quantitative receptor autoradiographic and conventional binding techniques were used to study the affinities of 7 and 14 for non-NMDA receptor sites. Both compounds were inhibitors of the binding of (3H)AMPA (IC50 = 90 and 29 microM, respectively). Compounds 14 and 7 were both very weak inhibitors of the high-affinity binding of radioactive kainic acid ((3H)KAIN). Compound 14, but not 7, was, however, shown to be an inhibitor of low-affinity (3H)KAIN binding as determined in the presence of 100 mM calcium chloride. In the rat cortical slice preparation, 7 was shown to antagonize excitation induced by 1 with some selectivity, whereas 14 proved to be a rather selective antagonist of KAIN-induced excitation.

  15. A severe autosomal-dominant periodic inflammatory disorder with renal AA amyloidosis and colchicine resistance associated to the MEFV H478Y variant in a Spanish kindred: an unusual familial Mediterranean fever phenotype or another MEFV-associated periodic inflammatory disorder?

    Science.gov (United States)

    Aldea, Anna; Campistol, Josep M; Arostegui, Juan I; Rius, Josefa; Maso, Montserrat; Vives, Jordi; Yagüe, Jordi

    2004-01-01

    Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurring short attacks of fever and serositis. Secondary AA amyloidosis is the worst complication of the disease and often determines the prognosis. The MEFV gene, on chromosome 16p13.3, is responsible for the disease and around 30 mutations have been reported to date. Colchicine is the standard FMF treatment today, and prevents both attacks and amyloid deposition in 95% of patients. Here we describe a three-generation Spanish kindred with five family members affected by a severe periodic inflammatory disorder associated with renal AA amyloidosis and colchicine unresponsiveness. Clinical diagnosis of definite FMF disease was made based on the Tel-Hashomer criteria set. Genetic analyses revealed that all subjects were heterozygous for the new H478Y MEFV variant, segregating with the disease. In addition, mutations in the TNFRSF1A and CIAS1/PYPAF1/NALP3 genes, related to the dominantly inherited autoinflammatory periodic syndromes, were ruled out. However, the dominant inheritance of the disease, the long fever episodes with a predominant joint involvement, and the resistance to colchicine in these patients raise the question of whether the periodic syndrome seen in this kindred is a true FMF disease with unusual manifestations or rather another MEFV-associated periodic syndrome. We conclude that the new H478Y MEFV mutation is the dominant pathological variant causing the inflammatory periodic syndrome in this kindred and that full-length analyses of the MEFV gene are needed to obtain an adequate diagnosis of patients with clinical suspicion of a hereditary periodic fever syndrome, especially those from non-ancestral populations.

  16. Cytotoxicity, antiviral and antimicrobial activities of alkaloids, flavonoids, and phenolic acids.

    Science.gov (United States)

    Ozçelik, Berrin; Kartal, Murat; Orhan, Ilkay

    2011-04-01

    Some natural products consisting of the alkaloids yohimbine and vincamine (indole-type), scopolamine and atropine (tropane-type), colchicine (tropolone-type), allantoin (imidazolidine-type), trigonelline (pyridine-type) as well as octopamine, synephrine, and capsaicin (exocyclic amine-type); the flavonoid derivatives quercetin, apigenin, genistein, naringin, silymarin, and silibinin; and the phenolic acids namely gallic acid, caffeic acid, chlorogenic acid, and quinic acid, were tested for their in vitro antiviral, antibacterial, and antifungal activities and cytotoxicity. Antiviral activity of the compounds was tested against DNA virus herpes simplex type 1 and RNA virus parainfluenza (type-3). Cytotoxicity of the compounds was determined using Madin-Darby bovine kidney and Vero cell lines, and their cytopathogenic effects were expressed as maximum non-toxic concentration. Antibacterial activity was assayed against following bacteria and their isolated strains: Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Klebsiella pneumoniae, Acinetobacter baumannii, Staphylococcus aureus, Enterococcus faecalis, and Bacillus subtilis, although they were screened by microdilution method against two fungi: Candida albicans and Candida parapsilosis. Atropine and gallic acid showed potent antiviral effect at the therapeutic range of 0.8-0.05 µg ml(-1), whilst all of the compounds exerted robust antibacterial effect. Antiviral and antimicrobial effects of the compounds tested herein may constitute a preliminary step for further relevant studies to identify the mechanism of action.

  17. Acidic deposition ("acid rain")

    Science.gov (United States)

    Schreiber, R. Kent; LaRoe, Edward T.; Farris, Gaye S.; Puckett, Catherine E.; Doran, Peter D.; Mac, Michael J.

    1995-01-01

    Acidic deposition, or "acid rain," describes any form of precipitation, including rain, snow, and fog, with a pH of 5.5 or below (Note: pH values below 7 are acidic; vinegar has a pH of 3). It often results when the acidity of normal precipitation is increased by sulfates and nitrates that are emitted into the atmosphere from burning fossil fuels. This form of airborne contamination is considered harmful, both directly and indirectly, to a host of plant and animal species.Although acid rain can fall virtually anywhere, ecological damages in environmentally sensitive areas downwind of industrial and urban emissions are a major concern. This includes areas that have a reduced capacity to neutralize acid inputs because of low alkalinity soils and areas that contain species with a low tolerance to acid conditions. To determine the distribution of acidic deposition and evaluate its biological effects, research and monitoring are being conducted by the federal government with support from states, universities, and private industry.            The national extent of the acid rain problem has been estimated by sampling water from 3,000 lakes and 500 streams (Irving 1991), representing more than 28,000 lakes and 56,000 stream reaches with a total of 200,000 km (125,000 mi). Some particularly sensitive areas, such as the Adirondack Mountain region, have been more intensively sampled and the biota examined in detail for effects from acidity.         To identify trends in aquatic ecosystems, present and historical survey data on water chemistry and associated biota are compared. In lakes, the chemical and biological history and pH trends may be inferred or reconstructed in some cases by examining assemblages of fossil diatoms and aquatic invertebrates in the sediment layers. In terrestrial ecosystems, vegetation damage is surveyed and effects of acidic deposition to plants and animals are determined from laboratory and field exposure experiments. Natural

  18. Aquisição de uma tarefa temporal (DRL por ratos submetidos a lesão seletiva do giro denteado The acquisition of a temporal task (DRL by dentate gyrus-selective colchicine lesioned rats

    Directory of Open Access Journals (Sweden)

    José Lino Oliveira Bueno

    2006-01-01

    Full Text Available A lesão seletiva do giro denteado (DG reduz a eficiência do desempenho de ratos treinados pré-operatoriamente em um esquema de reforçamento diferencial de baixas taxas (DRL; embora os animais lesados sejam capazes de suprimir a resposta de pressão na barra por determinado intervalo de tempo após a resposta anterior, eles subestimam esse intervalo, resultando em um desempenho menos eficiente. Como os animais tinham recebido treinamento pré-operatório, não ficou claro se a lesão interfere na aquisição da discriminação temporal. Este estudo avaliou o efeito da lesão do DG na aquisição de uma tarefa de DRL-20 s. Ratos foram submetidos à neurocirurgia e então ao treino na tarefa de DRL-20 s. Os resultados mostraram que embora os animais lesados se beneficiem do treinamento na tarefa, sua aquisição não é tão eficiente quanto a exibida pelos animais controle. Os resultados sugerem ainda que a lesão do giro denteado interfere na acuidade da discriminação temporal.Previous studies have shown that dentate gyrus damage render rats less efficient than sham-operated controls in the performance of a differential reinforcement of low rates of responding (DRL-20 s task acquired prior to the lesion; even though the lesioned rats were able to postpone their responses after a previous bar press, they seem to underestimate time relative to sham-operated controls, which interferes with their performance. This study investigated the effects of multiplesite, intradentate, colchicine injections on the acquisition and performance of a DRL-20 s task in rats not exposed to preoperatory training, i.e., trained after the lesion. Results showed that the lesioned rats improved along repetitive training in the DRL-20 s task; however, relative to the sham-operated controls, their acquisition rate was slower and the level of proficiency achieved was poorer, indicating that damage to the dentate gyrus interferes with temporal discrimination.

  19. 秋水仙碱对高脂血症新西兰兔血浆C RP和一氧化氮水平的影响%Effects of Colchicine therapy on plasma level of CRP and nitric oxide in New Zealand rabbits with hy-perlipidemia

    Institute of Scientific and Technical Information of China (English)

    朱潮潘; 丘若峰; 胡兵; 蔡安平; 邝健; 麦炜颐

    2013-01-01

    Objective To investigate the effects of Colchicine therapy on plasma level of CRP and (nitric oxide) NO in New Zealand rabbits with hyperlipidemia. Methods Hyperlipidemia model was induced by institution of high cholesterol diet in New Zealand rabbits,and colchicines (0.01 mg/kg body weight)was administered for 2 weeks when hyperlipidemia model was established. Plasma level of lipid profile,CRP and NO were evaluated in blank group,hyperlipidemia control group and hyperlipidemia intervention group. Re-sults With 8 weeks high cholesterol diet treatment,plasma level of lipid profile was significantly higher when compared to blank group;and the plasma level of CRP was also higher while NO was lower in hyperlipidemia groups. There was no significant difference of lipid profile in hyperlipidemia control group and hyperlipidemia intervention group after 2 weeks colchicine therapy,however the plasma level of CRP was significant lower while NO was significant higher in the hyperlipidemia intervention group when compared to the hyperlipidemia control group. Conclusion Endothelial functions was improved by colchicine therapy in hyperlipidemia rab-bit,which may be ascribed to the down-regulation of CRP,and this may be one of the potential mechanisms colchicine reduce cardiovascular events in patients with coronary artery diseases.%目的:探讨秋水仙碱对高脂血症新西兰兔血浆CRP和一氧化氮水平的影响。方法通过给予高脂饮食构建新西兰兔高脂血症模型,模型构建成功后干预组给予0.01 mg/kg秋水仙碱治疗,共2周。评估空白组、高脂血症对照组和高脂血症干预组3组新西兰兔血脂、CRP及一氧化氮水平。结果经8周高脂饮食饲养后,与空白组相比,高脂血症组新西兰兔血脂指标水平均明显升高,差异有统计学意义(均P<0.05);与空白组相比,血浆CRP水平在高脂血症组也明显升高,而一氧化氮水平则明显降低(P<0.05)。高脂血

  20. Treatment of primary biliary cholangitis ursodeoxycholic acid non-responders: A systematic review.

    Science.gov (United States)

    Suraweera, Duminda; Rahal, Harman; Jimenez, Melissa; Viramontes, Matthew; Choi, Gina; Saab, Sammy

    2017-05-18

    Primary biliary cholangitis (PBC), formerly known as primary biliary cirrhosis, is a chronic cholestatic liver disease characterized by an immune mediated destruction of intrahepatic bile ducts. Ursodeoxycholic acid (UDCA) has been the primary medication for the treatment of PBC, resulting in improved liver tests, resolution of symptoms and increased transplant free survival. However, not all patients respond to UDCA. The aim of this systematic review is to provide an evidence based assessment of the medications that have been studied in patients who are refractory to UDCA. We performed a systematic literature search on MEDLINE and the Cochrane Database of Systematic Reviews of the published literature. A total of 23 articles fulfilling our inclusion criteria were found. Several studies have shown an improvement in liver biochemistries with the use of obeticholic acid in conjunction with UDCA. Fibrates, including fenofibrate and bezafibrate, have evidence supporting benefit in this population but need more robust studies to confirm these observational results. Neither obeticholic acid nor fibrates have shown to increase transplant free survival. While there may be some benefit with methotrexate, colchicine, budesonide, mycophenolate mofetil and azathioprine, these findings were not consistent and the benefits were marginal. Further investigation is needed. In patients with PBC refractory to UDCA, obeticholic acid or a fibrate is a reasonable choice as an adjunctive treatment to UDCA. Further investigation with randomized controlled trials is needed to provide high quality evidence to formulate standardized therapies in this difficult to treat population. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Analysis of Efficacy and Safety of a Small Dose of Colchicine Combined With Meloxicam Capsules for the Treatment of Acute Gouty Arthritis%小剂量秋水仙碱联合美洛昔康胶囊治疗痛风性关节炎急性发作期的疗效与安全性分析

    Institute of Scientific and Technical Information of China (English)

    张利; 戴小良; 郑聪; 宋利梅; 高旭; 刘柳; 卢杰

    2016-01-01

    Objective A small dose of colchicine combined with Meloxicam Capsules to explore the effcacy and safety of the treatment of acute attack of gouty arthritis.Methods 80 cases of gout arthritis patients treated in our hospital from March 2015 to March 2016 were selected as the research object and divided into control group and experimental group according to the principle of random. Control group were treated with colchicines, experimental group, on the basis of the control group, was given small dose of colchicine combined with meloxicam capsules, evaluation of efficacy and safety after 2 weeks of treatment, the clinical effcacy of the two groups were compared and the adverse conditions were compared.Results The total effective rate of the control group (62.50%) was lower than that of experimental group (95%), the incidence of adverse reactions (25.00%) was higher than that of the experimental group (5.00%), and the difference was statistically signiifcant (P < 0.05). Conclusion A small dose of colchicine combined with meloxicam capsules in the treatment of acute exacerbation of the effects of gouty arthritis.%目的:探究小剂量秋水仙碱联合美洛昔康胶囊治疗痛风性关节炎急性发作期的疗效与安全性。方法选取我院2015年3月~2016年3月收治的符合标准的80例痛风性关节炎患者为研究对象,并按随机原则将其分为对照组与实验组,对照组采用秋水仙碱治疗,实验组在对照组的基础上予以小剂量秋水仙碱联合美洛昔康胶囊。治疗2周后,评价疗效及安全性,比较两组患者的临床疗效及产生的不良症状情况。结果对照组的总有效率为62.50%,低于实验组(95.00%),不良反应发生率(25.00%)高于实验组(5.00%),且比较结果,差异具有统计学意义(P<0.05)。结论小剂量秋水仙碱联合美洛昔康胶囊治疗痛风性关节炎急性发作期的疗效显著。

  2. Effects of concentration and treatment time of colchicine on growth and development of axillary buds of Jasminum sambac%秋水仙素浓度和处理时间对茉莉腋芽生长发育的影响

    Institute of Scientific and Technical Information of China (English)

    邓衍明; 孙晓波; 贾新平; 梁丽建; 苏家乐

    2016-01-01

    处理指数与细胞异常率呈极显著负相关。研究结果表明:秋水仙素浓度和处理时间对茉莉腋芽的生长发育有一定影响;综合考虑各生物学效应指标,茉莉腋芽适宜的诱导条件为用500 mg·L-1秋水仙素溶液处理3~5 mm腋芽24 h。此外,建议将处理指数作为秋水仙素对茉莉腋芽细胞减数分裂影响效应的评价指标之一。%In order to understand the effect of colchicine treatment on growth and development of axillary buds of Jasminum sambac (Linn.) Aiton, taking axillary buds with length of 0 (un-germinated), 3-5 and 8-10 mm as experimental materials, growth status of axillary buds and growth and development status of sprouting branches and leaves were analyzed after treated by 500 , 1 000 , and 2 000 mg · L-1 colchicine solution for 24 and 48 h, respectively. Meanwhile, meiotic behavior of pollen mother cells of different treatment groups was observed. On this basis, analysis on correlation among different biological effect indexes of axillary buds and sprouting branches of J. sambac after treated by colchicine was carried out. The results show that after treated by colchicine, growth rate and treatment index of axillary buds,length of sprouting branches, length of the longest internode, length of the largest leaf, width of the largest leaf, floral bud number, floral budding rate, length of the largest floral bud, width of the largest floral bud and flowering rate of different treatment groups are generally significantly ( P<0 . 05 ) lower than those of the control group ( un-germinated axillary buds treated by water for 48 h) , while inhibition rate and mortality of axillary buds are significantly higher than those of the control group. Overall, with increasing of mass concentration of colchicine, growth rate and treatment index of axillary buds decrease, while inhibition rate and mortality increase, lengths of sprouting branches and the longest internode shorten, flowering rate

  3. Effects of glutathione depletion by 2-cyclohexen-1-one on excitatory amino acids-induced enhancement of activator protein-1 DNA binding in murine hippocampus.

    Science.gov (United States)

    Ogita, K; Kitayama, T; Okuda, H; Yoneda, Y

    2001-03-01

    We have investigated the role of glutathione in mechanisms associated with excitatory amino acid signaling to the nuclear transcription factor activator protein-1 (AP1) in the brain using mice depleted of endogenous glutathione by prior treatment with 2-cyclohexen-1-one (CHX). In the hippocampus of animals treated with CHX 2 h before, a significant increase was seen in enhancement of AP1 DNA binding when determined 2 h after the injection of kainic acid (KA) at low doses. The sensitization to KA was not seen in animals injected with CHX 24 h before, in coincidence with the recovery of glutathione contents to the normal levels. By contrast, CHX did not significantly affect the potentiation by NMDA of AP1 binding under any experimental conditions. Prior treatment with CHX resulted in facilitation of behavioral changes induced by KA without affecting those induced by NMDA. These results suggest that endogenous glutathione may be at least in part involved in molecular mechanisms underlying transcriptional control by KA, but not by NMDA, signals of cellular functions.

  4. Valproic Acid

    Science.gov (United States)

    ... acid is in a class of medications called anticonvulsants. It works by increasing the amount of a ... older (about 1 in 500 people) who took anticonvulsants such as valproic acid to treat various conditions ...

  5. Amino acids

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002222.htm Amino acids To use the sharing features on this page, please enable JavaScript. Amino acids are organic compounds that combine to form proteins . ...

  6. Obeticholic Acid

    Science.gov (United States)

    Obeticholic acid is used alone or in combination with ursodiol (Actigall, Urso) to treat primary biliary cholangitis (PBC; a ... were not treated successfully with ursodiol alone. Obeticholic acid is in a class of medications called farnesoid ...

  7. Ascorbic Acid

    Science.gov (United States)

    Ascorbic acid is used to prevent and treat scurvy, a disease caused by a lack of vitamin C in ... Ascorbic acid comes in extended-release (long-acting) capsules and tablets, lozenges, syrup, chewable tablets, and liquid drops to ...

  8. Mefenamic Acid

    Science.gov (United States)

    Mefenamic acid is used to relieve mild to moderate pain, including menstrual pain (pain that happens before or during a menstrual period). Mefenamic acid is in a class of medications called NSAIDs. ...

  9. Acid mucopolysaccharides

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003368.htm Acid mucopolysaccharides To use the sharing features on this page, please enable JavaScript. Acid mucopolysaccharides is a test that measures the amount ...

  10. Ethacrynic Acid

    Science.gov (United States)

    Ethacrynic acid, a 'water pill,' is used to treat swelling and fluid retention caused by various medical problems. It ... Ethacrynic acid comes as a tablet to take by mouth. It is usually taken once or twice a day ...

  11. Aminocaproic Acid

    Science.gov (United States)

    Aminocaproic acid is used to control bleeding that occurs when blood clots are broken down too quickly. This type ... the baby is ready to be born). Aminocaproic acid is also used to control bleeding in the ...

  12. Aspartic acid

    Science.gov (United States)

    ... body work. It plays a role in: Hormone production and release Normal nervous system function Plant sources of aspartic acid include: avocado, asparagus, and molasses. Animal sources of aspartic acid include: ...

  13. Clavulanic acid does not affect convulsions in acute seizure tests in mice.

    Science.gov (United States)

    Gasior, Maciej; Socała, Katarzyna; Nieoczym, Dorota; Wlaź, Piotr

    2012-01-01

    Clavulanic acid (CLAV) inhibits bacterial β-lactamases and is commonly used to aid antibiotic therapy. Prompted by the initial evidence suggestive of the potential anticonvulsant and neuroprotective properties of CLAV, the present study was undertaken to systematically evaluate its acute effects on seizure thresholds in seizure tests typically used in primary screening of potential antiepileptic drugs (AEDs). In the present study, 6-Hz seizure threshold, maximal electroshock seizure threshold (MEST) test, and intravenous pentylenetetrazole (i.v. PTZ) seizure tests were used to determine anticonvulsant effects of intraperitoneally (i.p.) administered CLAV in mice. Acute effects on motor coordination and muscle strength were assessed in the chimney and grip-strength tests, respectively. Doses of CLAV studied in the present study were either comparable or extended the doses reported in the literature to be effective against kainic acid-induced convulsions in mice or behaviorally active in rodents and monkeys. CLAV had no effect on seizure thresholds in the 6-Hz (64 ng/kg to 1 mg/kg) and MEST (64 ng/kg to 5 mg/kg) seizure tests. Similarly, CLAV had no effect on seizure thresholds for i.v. PTZ-induced myoclonic twitch, clonic convulsions, and tonic convulsions (64 ng/kg to 5 mg/kg). Finally, CLAV (64 ng/kg to 5 mg/kg) had no effect on the motor performance and muscle strength in the chimney and grip-strength tests, respectively. In summary, CLAV failed to affect seizure thresholds in three seizure tests in mice. Although the results of the present study do not support further development of CLAV as an AED, its beneficial effects in chronic epilepsy models warrant further evaluation owing to its, for example, potential neuroprotective properties.

  14. Fatty acids - trans fatty acids

    Science.gov (United States)

    The data supporting a negative effect of dietary trans fatty acids on cardiovascular disease risk is consistent. The primary dietary sources of trans fatty acids include partially hydrogenated fat and rudiment fat. The adverse effect of trans fatty acids on plasma lipoprotein profiles is consisten...

  15. Análise citológica e cariométrica da ação da colchina sôbre a espermatogênese dos hemípteros Cytologic and caryometric analysis of the action of colchicine on the spermatogenesis in hemiptera

    Directory of Open Access Journals (Sweden)

    G. Schreiber

    1951-03-01

    Full Text Available The action of colchicine upon the spermatogenesis of Triatoma infestans, (Hemipt. Heteroptera, has been studied and the different categories of giant spermatids that appear during the treatment have been compared with the nuclear volumes of the whole series of normal spermatogenetic stages. The following facts have been ascertained: 1 4 hours after the treatment the gonial mitotic metaphases, and the 1st. and 2nd. metaphases of meiosis are stopped. The prophasic stages of meiosis and diakynesis appear to be normal. After 9 days of treatment, all the tetrads are broken in the meiotic metaphases and the cells appear with 44 and 22 chromosomes respectively, scattered in the cytoplasm. 2 At 9 days, practically all spermatogenetic stages have disappeared except for a few cysts of spermatogonia, and practically the whole testicle is full of cysts of spermatozoa and spermatid, with some large zones of necrosis with pycnotic nuclei. The spermatids appear to be of different sizes and the statistical analysis of the nuclear volumes gives a polymodal hystogram with 4 modes, whose volumes are in the ratio of 1:2:4:8. Ripe spermatozoa seem to have a certain volume variability, that has not been possible to analyse quantitatively. All these facts confirm what DOOLEY found in the colchicinized Orthoptera testicle. 3 The caryometric analysis conducted statistically on the normal stages of the spermatogenesis (resting spermatogonia, gonial prophases, leptotene, "confused stage", diakynesis, and spermatid revealed the following facts: a Considering the volume of the resting, spermatogonia as 1, their mitotic prophases have a volume of 2. Some rare prophases appear to have a volume of 4 and probably belong to tetraployd spermatogonia normally present in the testicle of Hemiptera. b The first spermatocyte at the beginning of the auxocitary growth (leptotene has a volume of 2, which is equal to that of them gonial prophase. It grows further during the "confused

  16. Folic Acid

    Science.gov (United States)

    ... damage. 10 Do I need folic acid after menopause? Yes. Women who have gone through menopause still need 400 micrograms of folic acid every ... United States: 2003–2006 . American Journal of Clinical Nutrition; 91(1): 231–237. Hamner, H.C., Cogswell, ...

  17. Folic acid

    Science.gov (United States)

    ... taking a specific nutritional supplement, containing vitamin B3 (nicotinamide), a compound isolated from grains (azelaic acid), zinc, ... lung cancer in most people. A type of skin cancer called melanoma. Limited research suggests that taking ...

  18. Folic Acid

    Science.gov (United States)

    ... B-complex vitamin needed by the body to manufacture red blood cells. A deficiency of this vitamin ... prepared from dried yeast, fruit, and fresh leafy green vegetables to increase the folic acid in your ...

  19. Ibotenic acid and thioibotenic acid

    DEFF Research Database (Denmark)

    Hermit, Mette B; Greenwood, Jeremy R; Nielsen, Birgitte

    2004-01-01

    with the conformations preferred by the ligands upon docking to mGlu1 and models of the other mGlu subtypes, we propose that unlike other subtypes, group III mGlu receptor binding sites require a ligand conformation at an energy level which is prohibitively expensive for ibotenic acid, but not for thioibotenic acid....... These studies demonstrate how subtle differences in chemical structures can result in profound differences in pharmacological activity....

  20. Acid Rain

    Science.gov (United States)

    Bricker, Owen P.; Rice, Karen C.; Dietrich, W.E.; Sposito, Garrison

    1997-01-01

    Acid deposition, or acid rain as it is more commonly referred to, has become a widely publicized environmental issue in the U.S. over the past decade. The term usually conjures up images of fish kills, dying forests, "dead" lakes, and damage to monuments and other historic artifacts. The primary cause of acid deposition is emission of S02 and NOx to the atmosphere during the combustion of fossil fuels. Oxidation of these compounds in the atmosphere forms strong acids - H2SO4 and HNO3 - which are returned to the Earth in rain, snow, fog, cloud water, and as dry deposition.Although acid deposition has only recently been recognized as an environmental problem in the U.S., it is not a new phenomenon (Cogbill & Likens 1974). As early as the middle of the 17th century in England, the deleterious effects of industrial emissions on plants, animals, and humans, and the atmospheric transport of pollutants between England and France had become issues of concern (Evelyn 1661, Graunt 1662). It is interesting that well over three hundred years ago in England, recommendations were made to move industry outside of towns and build higher chimneys to spread the pollution into "distant parts." Increasing the height of smokestacks has helped alleviate local problems, but has exacerbated others. In the U.S. the height of the tallest smokestack has more than doubled, and the average height of smokestacks has tripled since the 1950s (Patrick et al 1981). This trend occurred in most industrialized nations during the 20th century and has had the effect of transforming acid rain from a local urban problem into a problem of global scale.

  1. Perfluorooctanoic acid

    NARCIS (Netherlands)

    de Voogt, P.; Wexler, P.

    2014-01-01

    Perfluorooctanoic acid (PFOA, 335-67-1) is used in fluoropolymer production and firefighting foams and persists in the environment. Human exposure to PFOA is mostly through the diet. PFOA primarily affects the liver and can cause developmental and reproductive toxic effects in test animals.

  2. Electroenciphalogram changes of hippocampus and parietal cortex in epileptic rats kindled by kainic acid microinjection into nucleus amygdalae%海人酸杏仁核点燃癫痫大鼠海马和顶叶皮层脑电图改变

    Institute of Scientific and Technical Information of China (English)

    梁建民; 李秀杰; 时颖; 张淑琴; 纪莉; 崔璐

    2006-01-01

    目的:记录和比较海人酸(KA)杏仁核点燃癫痫大鼠海马和顶叶皮层脑电图.方法:选用雄性Wistar大鼠,以右侧杏仁核外侧基底核为给药靶点,在立体定位仪下,微量注射KA建立点燃癫痫模型,在对大鼠行为学观察的同时,连续记录大鼠点燃后6 h左侧海马和顶叶皮层脑电图.结果:大鼠点燃后脑电图依次出现多种形式的癫痫放电,以多发性棘波为主.海马和顶叶癫痫放电潜伏期,每小时放电持续时间、6 h总放电时间和波幅差异均无显著性.结论:KA杏仁核点燃大鼠脑电图改变符合颞叶癫痫特征,大鼠点燃急性早期癫痫放电在皮层间传播迅速,点燃灶对侧海马和顶叶皮层脑电图具有高度一致性,监测顶叶皮层脑电图可能更适用于对该模型的电生理学观察.

  3. Effect of ketogenic diet on hippocampus synaptic reorganization and GluR5 expression in kainic acid induced rat model of epilepsy%生酮饮食对海藻酸致癎大鼠海马突触重建和GluR5 表达的影响

    Institute of Scientific and Technical Information of China (English)

    徐向平; 孙若鹏; 金瑞峰

    2006-01-01

    目的探讨生酮饮食对海藻酸致癎大鼠海马突触重建和GluR5 表达的影响机制.方法以海藻酸(KA)致癎的幼鼠为研究对象,采用Timm′s 染色和尼氏染色,观察经不同饮食处理的动物海马结构和癫癎行为的变化;并用Western Blot和RT-PCR法检测海马GluR5及其mRNA的表达.结果生酮饮食组动物自发性反复惊厥的次数(140±103)次,明显少于正常饮食组(736±375)次.KA致癎大鼠海马齿状回内分子层异常Timm′s染色颗粒的平均A值均显著高于非致癎组,但生酮饮食组和正常饮食组间则无明显差异;各组动物CA3区锥体细胞层及始层的Timm′s 染色颗粒以及海马门区和CA1 、CA3区神经元的平均A值未见明显差异.KA致NFDA1后生酮饮食组大鼠海马GluR5的表达[(18938±4003)/mg总蛋白]明显高于正常饮食组[(12879±4651)/mg总蛋白],但两组间GluR5 mRNA比较,差异无统计学意义.结论苔藓纤维发芽可能是KA致癎动物癫癎产生的原因,酮食疗法对KA致癎大鼠确有抗癫癎作用,其抗癫癎机制可能与增加幼年大鼠CA1区中间神经元GluR5的表达,使海马内抑制性突触传递增强,进而阻止癫癎活动扩散有关.

  4. Hydroxycarboxylic acids and salts

    Energy Technology Data Exchange (ETDEWEB)

    Kiely, Donald E; Hash, Kirk R; Kramer-Presta, Kylie; Smith, Tyler N

    2015-02-24

    Compositions which inhibit corrosion and alter the physical properties of concrete (admixtures) are prepared from salt mixtures of hydroxycarboxylic acids, carboxylic acids, and nitric acid. The salt mixtures are prepared by neutralizing acid product mixtures from the oxidation of polyols using nitric acid and oxygen as the oxidizing agents. Nitric acid is removed from the hydroxycarboxylic acids by evaporation and diffusion dialysis.

  5. Hydrofluoric acid poisoning

    Science.gov (United States)

    Fluorhydric acid ... stomach, or intestine have holes (perforations) from the acid. ... Hydrofluoric acid is especially dangerous. The most common accidents involving hydrofluoric acid cause severe burns on the skin ...

  6. Long-lasting c-fos and NGF mRNA expressions and loss of perikaryal parvalbumin immunoreactivity in the development of epileptogenesis after ethacrynic acid-induced seizure.

    Science.gov (United States)

    Suzukawa, J; Omori, K; Okugawa, G; Fujiseki, Y; Heizmann, C W; Inagaki, C

    1999-07-10

    A single cerebroventricular injection of ethacrynic acid (EA), a Cl(-)-ATPase inhibitor, induces generalized tonic-clonic convulsions in mice. To clarify whether such convulsive stimulus triggers a long-lasting rearrangement of the neural circuitry culminating in seizure susceptibility, we examined molecular, cellular and behavioral changes following the EA-induced seizure. The expression of immediate early gene c-fos mRNA as an index for cellular activation increased biphasically, with an early transient increase at 60 min and a late prolonged increase on the 10th to 14th day post-EA administration, most remarkably in the hippocampus and pyriform cortex. On the 14th day post-EA seizure, subconvulsive dose of kainic acid (5-17.5 mg/kg) caused severe (stage 5) seizure in 77% of the mice, with 70% mortality. In addition, the expression of nerve growth factor (NGF) also showed biphasic increases with close spatiotemporal correlation with c-fos expression. Moreover, the number of cell somata and the density of axon fibers of parvalbumin (PARV)-positive cells, a subpopulation of GABAergic interneurons, decreased in area dentata, CA1 and CA3 on the 7th and 14th day post-EA seizure. In area dentata and CA1, the density of glutamic acid decarboxylase (GAD)-positive cells also decreased on the 14th day. Thus, the transient EA-induced seizures appear to develop seizure susceptibility by causing damage of a subpopulation of inhibitory interneurons along with increases in the expression of c-fos and NGF in limbic structures.

  7. Dehydroabietic acid

    Directory of Open Access Journals (Sweden)

    Xiao-Ping Rao

    2009-10-01

    Full Text Available The title compound [systematic name: (1R,4aS,10aR-7-isopropyl-1,4a-dimethyl-1,2,3,4,4a,9,10,10a-octahydrophenanthrene-1-carboxylic acid], C20H28O2, has been isolated from disproportionated rosin which is obtained by isomerizing gum rosin with a Pd-C catalyst.. Two crystallographically independent molecules exist in the asymmetric unit. In each molecule, there are three six-membered rings, which adopt planar, half-chair and chair conformations. The two cyclohexane rings form a trans ring junction with the two methyl groups in axial positions. The crystal structure is stabilized by intermolecular O—H...O hydrogen bonds.

  8. Amino acids in the sedimentary humic and fulvic acids

    Digital Repository Service at National Institute of Oceanography (India)

    Sardessai, S.

    to the coastal sedimentary humic acids implying higher association of amino acids with the carbonaceous and fine grained sedimentary humic acids. Both the humic and fulvic acids are composed of neutral, acidic, basic, aromatic and sulphur containing amino acids....

  9. [Teichoic acids from lactic acid bacteria].

    Science.gov (United States)

    Livins'ka, O P; Harmasheva, I L; Kovalenko, N K

    2012-01-01

    The current view of the structural diversity of teichoic acids and their involvement in the biological activity of lactobacilli has been reviewed. The mechanisms of effects of probiotic lactic acid bacteria, in particular adhesive and immunostimulating functions have been described. The prospects of the use of structure data of teichoic acid in the assessment of intraspecific diversity of lactic acid bacteria have been also reflected.

  10. Plasma amino acids

    Science.gov (United States)

    Amino acids blood test ... types of methods used to determine the individual amino acid levels in the blood. ... test is done to measure the level of amino acids in the blood. An increased level of a ...

  11. Uric acid test (image)

    Science.gov (United States)

    Uric acid urine test is performed to check for the amount of uric acid in urine. Urine is collected over a 24 ... testing. The most common reason for measuring uric acid levels is in the diagnosis or treatment of ...

  12. POLYELEOSTEARIC ACID VESICLES

    Institute of Scientific and Technical Information of China (English)

    LI Zichen; XIE Ximng; FAN Qinghua; FANG Yifei

    1992-01-01

    α-Eleostearic acid and β-eleostearic acid formed vesicles in aqueous medium when an ethanol solutionofeleostearic acid was injected rapidly into a vigorously vortexed aqueous phase. Formation of the vesicles was demonstrated by electron microscopic observation and bromothymol blue encapsulation experiments. Polymerizations of the eleostearic acids in the formed vesicles carried out by UV irradiation produced poly-α-eleostearic acid and poly-β-eleostearic acid vesicles.

  13. Acid distribution in phosphoric acid fuel cells

    Energy Technology Data Exchange (ETDEWEB)

    Okae, I.; Seya, A.; Umemoto, M. [Fuji Electric Co., Ltd., Chiba (Japan)

    1996-12-31

    Electrolyte acid distribution among each component of a cell is determined by capillary force when the cell is not in operation, but the distribution under the current load conditions had not been clear so far. Since the loss of electrolyte acid during operation is inevitable, it is necessary to store enough amount of acid in every cell. But it must be under the level of which the acid disturbs the diffusion of reactive gases. Accordingly to know the actual acid distribution during operation in a cell is very important. In this report, we carried out experiments to clarify the distribution using small single cells.

  14. Kainate-enhanced release of D-(3H)aspartate from cerebral cortex and striatum: reversal by baclofen and pentobarbital

    Energy Technology Data Exchange (ETDEWEB)

    Potashner, S.J.; Gerard, D.

    1983-06-01

    A study was made of the actions of the excitant neurotoxin, kainic acid, on the uptake and the release of D-(2,3-3H)aspartate (D-ASP) in slices of guinea pig cerebral neocortex and striatum. The slices took up D-ASP, reaching concentrations of the amino acid in the tissue which were 14-23 times that in the medium. Subsequently, electrical stimulation of the slices evoked a Ca2+-dependent release of a portion of the D-ASP. Kainic acid (10(-5)-10(-3) M) produced a dose-dependent inhibition of D-ASP uptake. The electrically evoked release of D-ASP was increased 1.6-2.0 fold by 10(-5) and 10(-4)M kainic acid. The kainate-enlarged release was Ca2+-dependent. Dihydrokainic acid, an analogue of kainic acid with little excitatory or toxic action, did not increase D-ASP release but depressed D-ASP uptake. Attempts were made to block the action of kainic acid with baclofen and pentobarbital, compounds which depress the electrically evoked release of L-glutamate (L-GLU) and L-aspartate (L-ASP). Baclofen (4 X 10(-6)M), an antispastic drug, and pentobarbital (10(-4)M), an anesthetic agent, each inhibited the electrically evoked release of D-ASP and prevented the enhancement of the release above control levels usually produced by 10(-4)M kainic acid. It is proposed that 10(-5) and 10(-4)M kainic acid may enhance the synaptic release of L-GLU and L-ASP from neurons which use these amino acids as transmitters. This action is prevented by baclofen and pentobarbital. In view of the possibility that cell death in Huntington's disease could involve excessive depolarization of striatal and other cells by glutamate, baclofen might be effective in delaying the loss of neurons associated with this condition.

  15. MEFV mutations affecting pyrin amino acid 577 cause autosomal dominant autoinflammatory disease

    NARCIS (Netherlands)

    Stoffels, Monique; Szperl, Agata; Simon, Anna; Netea, Mihai G.; Plantinga, Theo S.; van Deuren, Marcel; Kamphuis, Sylvia; Lachmann, Helen J.; Cuppen, Edwin; Kloosterman, Wigard P.; Frenkel, Joost; van Diemen, Cleo C.; Wijmenga, Cisca; van Gijn, Marielle; van der Meer, Jos W. M.

    2014-01-01

    Objectives Autoinflammatory disorders are disorders of the innate immune system. Standard genetic testing provided no correct diagnosis in a female patient from a non-consanguineous family of British descent with a colchicine-responsive autosomal dominant periodic fever syndrome. We aimed to unravel

  16. MEFV mutations affecting pyrin amino acid 577 cause autosomal dominant autoinflammatory disease

    NARCIS (Netherlands)

    Stoffels, M.; Szperl, A.; Simon, A.; Netea, M.G.; Plantinga, T.S.; Deuren, M. van; Kamphuis, S.; Lachmann, H.J.; Cuppen, E.; Kloosterman, W.P.; Frenkel, J.; Diemen, C.C. van; Wijmenga, C.; Gijn, M. van; Meer, J.W.M. van der

    2014-01-01

    OBJECTIVES: Autoinflammatory disorders are disorders of the innate immune system. Standard genetic testing provided no correct diagnosis in a female patient from a non-consanguineous family of British descent with a colchicine-responsive autosomal dominant periodic fever syndrome. We aimed to

  17. MEFV mutations affecting pyrin amino acid 577 cause autosomal dominant autoinflammatory disease

    NARCIS (Netherlands)

    Stoffels, Monique; Szperl, Agata; Simon, Anna; Netea, Mihai G.; Plantinga, Theo S.; van Deuren, Marcel; Kamphuis, Sylvia; Lachmann, Helen J.; Cuppen, Edwin; Kloosterman, Wigard P.; Frenkel, Joost; van Diemen, Cleo C.; Wijmenga, Cisca; van Gijn, Marielle; van der Meer, Jos W. M.

    Objectives Autoinflammatory disorders are disorders of the innate immune system. Standard genetic testing provided no correct diagnosis in a female patient from a non-consanguineous family of British descent with a colchicine-responsive autosomal dominant periodic fever syndrome. We aimed to unravel

  18. MEFV mutations affecting pyrin amino acid 577 cause autosomal dominant autoinflammatory disease

    NARCIS (Netherlands)

    Stoffels, Monique; Szperl, Agata; Simon, Anna; Netea, Mihai G; Plantinga, Theo S; van Deuren, Marcel; Kamphuis, Sylvia; Lachmann, Helen J; Cuppen, Edwin; Kloosterman, Wigard P; Frenkel, Joost; van Diemen, Cleo C; Wijmenga, Cisca; van Gijn, Marielle; van der Meer, Jos W M

    OBJECTIVES: Autoinflammatory disorders are disorders of the innate immune system. Standard genetic testing provided no correct diagnosis in a female patient from a non-consanguineous family of British descent with a colchicine-responsive autosomal dominant periodic fever syndrome. We aimed to

  19. Gas-phase Acidities of Aspartic Acid, Glutamic Acid, and their Amino Acid Amides.

    Energy Technology Data Exchange (ETDEWEB)

    Li, Zhong; Matus, Myrna H; Velazquez, Hector A; Dixon, David A; Cassady, Carolyn J

    2007-02-14

    Gas-phase acidities (GA or ΔGacid) for the two most acidic common amino acids, aspartic acid and glutamic acid, have been determined for the first time. Because of the amide linkage’s importance in peptides and as an aid in studying side chain versus main chain deprotonation, aspartic acid amide and glutamic acid amide were also studied. Experimental GA values were measured by proton transfer reactions in an electrospray ionization/Fourier transform ion cyclotron resonance mass spectrometer. Calculated GAs were obtained by density functional and molecular orbital theory approaches. The best agreement with experiment was found at the G3MP2 level; the MP2/CBS and B3LYP/aug-cc-pVDZ results are 3–4 kcal/mol more acidic than the G3MP2 results. Experiment shows that aspartic acid is more acidic than glutamic acid by ca. 3 kcal/mol whereas the G3MP2 results show a smaller acidity difference of 0.2 kcal/mol. Similarly, aspartic acid amide is experimentally observed to be ca. 2 kcal/mol more acidic than glutamic acid amide whereas the G3MP2 results show a correspondingly smaller energy difference of 0.7 kcal/mol. The computational results clearly show that the anions are all ring-like structures with strong hydrogen bonds between the OH or NH2 groups and the CO2- group from which the proton is removed. The two amino acids are main-chain deprotonated. In addition, use of the COSMO model for the prediction of the free energy differences in aqueous solution gave values in excellent agreement with the most recent experimental values for pKa. Glutamic acid is predicted to be more acidic than aspartic acid in aqueous solution due to differential solvation effects.

  20. Gas-phase acidities of aspartic acid, glutamic acid, and their amino acid amides

    Science.gov (United States)

    Li, Zhong; Matus, Myrna H.; Velazquez, Hector Adam; Dixon, David A.; Cassady, Carolyn J.

    2007-09-01

    Gas-phase acidities (GA or [Delta]Gacid) for the two most acidic common amino acids, aspartic acid and glutamic acid, have been determined for the first time. Because of the amide linkage's importance in peptides and as an aid in studying side chain versus main chain deprotonation, aspartic acid amide and glutamic acid amide were also studied. Experimental GA values were measured by proton transfer reactions in an electrospray ionization/Fourier transform ion cyclotron resonance mass spectrometer. Calculated GAs were obtained by density functional and molecular orbital theory approaches. The best agreement with experiment was found at the G3MP2 level; the MP2/CBS and B3LYP/aug-cc-pVDZ results are 3-4 kcal/mol more acidic than the G3MP2 results. Experiment shows that aspartic acid is more acidic than glutamic acid by ca. 3 kcal/mol whereas the G3MP2 results show a smaller acidity difference of 0.2 kcal/mol. Similarly, aspartic acid amide is experimentally observed to be ca. 2 kcal/mol more acidic than glutamic acid amide whereas the G3MP2 results show a correspondingly smaller energy difference of 0.7 kcal/mol. The computational results clearly show that the anions are all ring-like structures with strong hydrogen bonds between the OH or NH2 groups and the CO2- group from which the proton is removed. The two amino acids are main-chain deprotonated. In addition, use of the COSMO model for the prediction of the free energy differences in aqueous solution gave values in excellent agreement with the most recent experimental values for pKa. Glutamic acid is predicted to be more acidic than aspartic acid in aqueous solution due to differential solvation effects.

  1. Toxicity of adipic acid.

    Science.gov (United States)

    Kennedy, Gerald L

    2002-05-01

    Adipic acid has very low acute toxicity in rats with an LD50 > 5000 mg/kg. Adipic acid produced mild to no skin irritation on intact guinea pig skin as a 50% concentration in propylene glycol; it was not a skin sensitizer. Adipic acid caused mild conjunctival irritation in washed rabbit eyes; in unwashed rabbit eyes, there was mild conjunctival irritation, minimal iritis, but no corneal effects. Adipic acid dust may irritate the mucous membranes of the lungs and nose. In a 2-year feeding study, rats fed adipic acid at concentrations up to 5% in the diet exhibited only weight loss. Adipic acid is not genetically active in a wide variety of assay systems. Adipic acid caused no developmental toxicity in mice, rats, rabbits, or hamsters when administered orally. Adipic acid is partially metabolized in humans; the balance is eliminated unchanged in the urine. Adipic acid is slightly to moderately toxic to fish, daphnia, and algae in acute tests.

  2. Acid Thunder: Acid Rain and Ancient Mesoamerica

    Science.gov (United States)

    Kahl, Jonathan D. W.; Berg, Craig A.

    2006-01-01

    Much of Mesoamerica's rich cultural heritage is slowly eroding because of acid rain. Just as water dissolves an Alka-Seltzer tablet, acid rain erodes the limestone surfaces of Mexican archaeological sites at a rate of about one-half millimeter per century (Bravo et al. 2003). A half-millimeter may not seem like much, but at this pace, a few…

  3. Acid Thunder: Acid Rain and Ancient Mesoamerica

    Science.gov (United States)

    Kahl, Jonathan D. W.; Berg, Craig A.

    2006-01-01

    Much of Mesoamerica's rich cultural heritage is slowly eroding because of acid rain. Just as water dissolves an Alka-Seltzer tablet, acid rain erodes the limestone surfaces of Mexican archaeological sites at a rate of about one-half millimeter per century (Bravo et al. 2003). A half-millimeter may not seem like much, but at this pace, a few…

  4. Omega-3 Fatty Acids

    Science.gov (United States)

    Omega-3 fatty acids are used together with lifestyle changes (diet, weight-loss, exercise) to reduce the ... the blood in people with very high triglycerides. Omega-3 fatty acids are in a class of ...

  5. Omega-6 Fatty Acids

    Science.gov (United States)

    Omega-6 fatty acids are types of fats. Some types are found in vegetable oils, including corn, evening primrose seed, safflower, and soybean oils. Other types of omega-6 fatty acids are found in black currant ...

  6. Lactic acid test

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003507.htm Lactic acid test To use the sharing features on this page, please enable JavaScript. Lactic acid is mainly produced in muscle cells and red ...

  7. Catalytic Synthesis Lactobionic Acid

    Directory of Open Access Journals (Sweden)

    V.G. Borodina

    2014-07-01

    Full Text Available Gold nanoparticles are obtained, characterized and deposited on the carrier. Conducted catalytic synthesis of lactobionic acid from lactose. Received lactobionic acid identify on the IR spectrum.

  8. Amino Acid Metabolism Disorders

    Science.gov (United States)

    ... this process. One group of these disorders is amino acid metabolism disorders. They include phenylketonuria (PKU) and maple syrup urine disease. Amino acids are "building blocks" that join together to form ...

  9. Facts about Folic Acid

    Science.gov (United States)

    ... Partners About Us Information For… Media Policy Makers Facts About Folic Acid Language: English (US) Español ( ... a woman needs 400 micrograms (mcg) every day. Facts About Folic Acid Download and print this fact ...

  10. Azelaic Acid Topical

    Science.gov (United States)

    Azelaic acid gel and foam is used to clear the bumps, lesions, and swelling caused by rosacea (a skin ... redness, flushing, and pimples on the face). Azelaic acid cream is used to treat the pimples and ...

  11. Folic Acid Quiz

    Science.gov (United States)

    ... About Us Information For… Media Policy Makers Folic Acid Quiz Language: English (US) Español (Spanish) Recommend ... button beside the question. Good Luck! 1. Folic acid is: A a B vitamin B a form ...

  12. Immunoglobulin and fatty acids

    DEFF Research Database (Denmark)

    2009-01-01

    The present invention relates to a composition comprising 0.1-10 w/w % immunoglobulin (Ig), 4-14 w/w % saturated fatty acids, 4-14 w/w % mono-unsaturated fatty acids and 0-5 w/w % poly-unsaturated fatty acids, wherein the weight percentages are based on the content of dry matter in the composition...

  13. The Acid Rain Reader.

    Science.gov (United States)

    Stubbs, Harriett S.; And Others

    A topic which is often not sufficiently dealt with in elementary school textbooks is acid rain. This student text is designed to supplement classroom materials on the topic. Discussed are: (1) "Rain"; (2) "Water Cycle"; (3) "Fossil Fuels"; (4) "Air Pollution"; (5) "Superstacks"; (6) "Acid/Neutral/Bases"; (7) "pH Scale"; (8) "Acid Rain"; (9)…

  14. Stomach acid test

    Science.gov (United States)

    Gastric acid secretion test ... of the cells in the stomach to release acid. The stomach contents are then removed and analyzed. ... 3.5). These numbers are converted to actual acid production in units of milliequivalents per hour (mEq/ ...

  15. Acid Lipase Disease

    Science.gov (United States)

    ... Page You are here Home » Disorders » All Disorders Acid Lipase Disease Information Page Acid Lipase Disease Information Page What research is being ... research to understand lipid storage diseases such as acid lipase deficiency. Additional research studies hope to identify ...

  16. Acid Rain Study Guide.

    Science.gov (United States)

    Hunger, Carolyn; And Others

    Acid rain is a complex, worldwide environmental problem. This study guide is intended to aid teachers of grades 4-12 to help their students understand what acid rain is, why it is a problem, and what possible solutions exist. The document contains specific sections on: (1) the various terms used in conjunction with acid rain (such as acid…

  17. The Acid Rain Reader.

    Science.gov (United States)

    Stubbs, Harriett S.; And Others

    A topic which is often not sufficiently dealt with in elementary school textbooks is acid rain. This student text is designed to supplement classroom materials on the topic. Discussed are: (1) "Rain"; (2) "Water Cycle"; (3) "Fossil Fuels"; (4) "Air Pollution"; (5) "Superstacks"; (6) "Acid/Neutral/Bases"; (7) "pH Scale"; (8) "Acid Rain"; (9)…

  18. Demospongic Acids Revisited

    Directory of Open Access Journals (Sweden)

    Gilles Barnathan

    2010-10-01

    Full Text Available The well-known fatty acids with a D5,9 unsaturation system were designated for a long period as demospongic acids, taking into account that they originally occurred in marine Demospongia sponges. However, such acids have also been observed in various marine sources with a large range of chain-lengths (C16–C32 and from some terrestrial plants with short acyl chains (C18–C19. Finally, the D5,9 fatty acids appear to be a particular type of non-methylene-interrupted fatty acids (NMA FAs. This article reviews the occurrence of these particular fatty acids in marine and terrestrial organisms and shows the biosynthetic connections between D5,9 fatty acids and other NMI FAs.

  19. Acidic Ionic Liquids.

    Science.gov (United States)

    Amarasekara, Ananda S

    2016-05-25

    Ionic liquid with acidic properties is an important branch in the wide ionic liquid field and the aim of this article is to cover all aspects of these acidic ionic liquids, especially focusing on the developments in the last four years. The structural diversity and synthesis of acidic ionic liquids are discussed in the introduction sections of this review. In addition, an unambiguous classification system for various types of acidic ionic liquids is presented in the introduction. The physical properties including acidity, thermo-physical properties, ionic conductivity, spectroscopy, and computational studies on acidic ionic liquids are covered in the next sections. The final section provides a comprehensive review on applications of acidic ionic liquids in a wide array of fields including catalysis, CO2 fixation, ionogel, electrolyte, fuel-cell, membrane, biomass processing, biodiesel synthesis, desulfurization of gasoline/diesel, metal processing, and metal electrodeposition.

  20. [Biosynthesis of adipic acid].

    Science.gov (United States)

    Han, Li; Chen, Wujiu; Yuan, Fei; Zhang, Yuanyuan; Wang, Qinhong; Ma, Yanhe

    2013-10-01

    Adipic acid is a six-carbon dicarboxylic acid, mainly for the production of polymers such as nylon, chemical fiber and engineering plastics. Its annual demand is close to 3 million tons worldwide. Currently, the industrial production of adipic acid is based on the oxidation of aromatics from non-renewable petroleum resources by chemo-catalytic processes. It is heavily polluted and unsustainable, and the possible alternative method for adipic acid production should be developed. In the past years, with the development of synthetic biology and metabolic engineering, green and clean biotechnological methods for adipic acid production attracted more attention. In this study, the research advances of adipic acid and its precursor production are reviewed, followed by addressing the perspective of the possible new pathways for adipic acid production.

  1. Boric acid and boronic acids inhibition of pigeonpea urease.

    Science.gov (United States)

    Reddy, K Ravi Charan; Kayastha, Arvind M

    2006-08-01

    Urease from the seeds of pigeonpea was competitively inhibited by boric acid, butylboronic acid, phenylboronic acid, and 4-bromophenylboronic acid; 4-bromophenylboronic acid being the strongest inhibitor, followed by boric acid > butylboronic acid > phenylboronic acid, respectively. Urease inhibition by boric acid is maximal at acidic pH (5.0) and minimal at alkaline pH (10.0), i.e., the trigonal planar B(OH)3 form is a more effective inhibitor than the tetrahedral B(OH)4 -anionic form. Similarly, the anionic form of phenylboronic acid was least inhibiting in nature.

  2. Acid-Base Homeostasis.

    Science.gov (United States)

    Hamm, L Lee; Nakhoul, Nazih; Hering-Smith, Kathleen S

    2015-12-07

    Acid-base homeostasis and pH regulation are critical for both normal physiology and cell metabolism and function. The importance of this regulation is evidenced by a variety of physiologic derangements that occur when plasma pH is either high or low. The kidneys have the predominant role in regulating the systemic bicarbonate concentration and hence, the metabolic component of acid-base balance. This function of the kidneys has two components: reabsorption of virtually all of the filtered HCO3(-) and production of new bicarbonate to replace that consumed by normal or pathologic acids. This production or generation of new HCO3(-) is done by net acid excretion. Under normal conditions, approximately one-third to one-half of net acid excretion by the kidneys is in the form of titratable acid. The other one-half to two-thirds is the excretion of ammonium. The capacity to excrete ammonium under conditions of acid loads is quantitatively much greater than the capacity to increase titratable acid. Multiple, often redundant pathways and processes exist to regulate these renal functions. Derangements in acid-base homeostasis, however, are common in clinical medicine and can often be related to the systems involved in acid-base transport in the kidneys.

  3. Glycolic Acid 15% Plus Salicylic Acid 2%

    Science.gov (United States)

    Sánchez-Blanco, Elena

    2011-01-01

    Background: Facial flat warts are a contagious viral disease that can cause disturbing cosmetic problems. Topical glycolic acid has been reported to be effective in dermatological treatment depending on the exfoliant capacity, but has not often been reported to be effective in the treatment of facial flat warts. Objective: The aim of this paper was to evaluate the efficacy and safety of glycolic acid 15% topical gel plus salicylic acid 2% in the treatment of recalcitrant facial flat warts. Methods: A total of 20 consecutive patients 7 to 16 years of age with recalcitrant facial flat warts were enrolled in this study. Patients having warts by the eye and lip regions were excluded from the study. A fine layer of face gel was applied to the treatment area once daily. Most of the participants had tried different treatments with no success. Assessments for the response and the occurrence of side effects were performed every two weeks at Weeks 2, 4, 6, and 8. Results: All the patients were clinically cured within eight weeks. Seven patients cleared in four weeks, and 13 patients cleared in eight weeks. No noticeable adverse events were related to the skin. Conclusion: Topical gel of glycolic acid 15% plus salicylic acid 2% is safe and effective when applied to facial flat warts once daily until clearance and may be considered as first-line treatment. PMID:21938272

  4. Nitrogen Lewis Acids.

    Science.gov (United States)

    Pogoreltsev, Alla; Tulchinsky, Yuri; Fridman, Natalia; Gandelman, Mark

    2017-03-22

    Being a major conception of chemistry, Lewis acids have found countless applications throughout chemical enterprise. Although many chemical elements can serve as the central atom of Lewis acids, nitrogen is usually associated with Lewis bases. Here, we report on the first example of robust and modifiable Lewis acids centered on the nitrogen atom, which provide stable and well-characterized adducts with various Lewis bases. On the basis of the reactivity of nitrogen Lewis acids, we prepared, for the first time, cyclic triazanes, a class of cyclic organic compounds sequentially bearing three all-saturated nitrogen atoms (N-N-N motif). Reactivity abilities of these N-Lewis acids were explained by theoretical calculations. Properties and future applications of nitrogen Lewis acids are intriguing.

  5. Citric Acid Alternative to Nitric Acid Passivation

    Science.gov (United States)

    Lewis, Pattie L. (Compiler)

    2013-01-01

    The Ground Systems Development and Operations GSDO) Program at NASA John F. Kennedy Space Center (KSC) has the primary objective of modernizing and transforming the launch and range complex at KSC to benefit current and future NASA programs along with other emerging users. Described as the launch support and infrastructure modernization program in the NASA Authorization Act of 2010, the GSDO Program will develop and implement shared infrastructure and process improvements to provide more flexible, affordable, and responsive capabilities to a multi-user community. In support of the GSDO Program, the purpose of this project is to demonstratevalidate citric acid as a passivation agent for stainless steel. Successful completion of this project will result in citric acid being qualified for use as an environmentally preferable alternative to nitric acid for passivation of stainless steel alloys in NASA and DoD applications.

  6. USGS Tracks Acid Rain

    Science.gov (United States)

    Gordon, John D.; Nilles, Mark A.; Schroder, LeRoy J.

    1995-01-01

    The U.S. Geological Survey (USGS) has been actively studying acid rain for the past 15 years. When scientists learned that acid rain could harm fish, fear of damage to our natural environment from acid rain concerned the American public. Research by USGS scientists and other groups began to show that the processes resulting in acid rain are very complex. Scientists were puzzled by the fact that in some cases it was difficult to demonstrate that the pollution from automobiles and factories was causing streams or lakes to become more acidic. Further experiments showed how the natural ability of many soils to neutralize acids would reduce the effects of acid rain in some locations--at least as long as the neutralizing ability lasted (Young, 1991). The USGS has played a key role in establishing and maintaining the only nationwide network of acid rain monitoring stations. This program is called the National Atmospheric Deposition Program/National Trends Network (NADP/NTN). Each week, at approximately 220 NADP/NTN sites across the country, rain and snow samples are collected for analysis. NADP/NTN site in Montana. The USGS supports about 72 of these sites. The information gained from monitoring the chemistry of our nation's rain and snow is important for testing the results of pollution control laws on acid rain.

  7. Parenteral Nutrition: Amino Acids

    Science.gov (United States)

    Hoffer, Leonard John

    2017-01-01

    There is growing interest in nutrition therapies that deliver a generous amount of protein, but not a toxic amount of energy, to protein-catabolic critically ill patients. Parenteral amino acids can achieve this goal. This article summarizes the biochemical and nutritional principles that guide parenteral amino acid therapy, explains how parenteral amino acid solutions are formulated, and compares the advantages and disadvantages of different parenteral amino acid products with enterally-delivered whole protein products in the context of protein-catabolic critical illness. PMID:28287411

  8. Parenteral Nutrition: Amino Acids.

    Science.gov (United States)

    Hoffer, Leonard John

    2017-03-10

    There is growing interest in nutrition therapies that deliver a generous amount of protein, but not a toxic amount of energy, to protein-catabolic critically ill patients. Parenteral amino acids can achieve this goal. This article summarizes the biochemical and nutritional principles that guide parenteral amino acid therapy, explains how parenteral amino acid solutions are formulated, and compares the advantages and disadvantages of different parenteral amino acid products with enterally-delivered whole protein products in the context of protein-catabolic critical illness.

  9. Diterpenoid acids from Grindelia nana.

    Science.gov (United States)

    Mahmoud, A A; Ahmed, A A; Tanaka, T; Iinuma, M

    2000-03-01

    Two new norditerpenoid acids of the labdane-type (norgrindelic acids), 4,5-dehydro-6-oxo-18-norgrindelic acid (1) and 4beta-hydroxy-6-oxo-19-norgrindelic acid (2), as well as a new grindelic acid derivative, 18-hydroxy-6-oxogrindelic acid (3), were isolated from the aerial parts of Grindelia nana. In addition, the known compounds, 6-oxogrindelic acid, grindelic acid, methyl grindeloate, 7alpha,8alpha-epoxygrindelic acid, and 4alpha-carboxygrindelic acid were also isolated. The structures of the new compounds were characterized on the basis of spectroscopic analysis.

  10. Application of Rhodium-Catalyzed Cyclohydrocarbonylation to the Syntheses of Enantiopure Homokainoids.

    Science.gov (United States)

    Chiou, Wen-Hua; Schoenfelder, Angèle; Mann, André; Ojima, Iwao

    2008-01-01

    Kainic acid, rigidified (S)-glutamic acid, is a well-known kainite receptor agonist for the excitatory transmission in the central nerve system. Our interest in highly selective kainite ligands, prompted us to design a series of new kainic homologues, "homokainoids", i.e., conformationally rigidified (S)-glutamic acids. For the syntheses of enantiopure novel homokainoids (pipecolinoglutamic acids), we successfully applied cyclohydrocarbonylation (CHC) reaction that has been developed in these laboratories. Efficient total syntheses of enantiopure novel homokainoids from (R)-serine feature the highly diastereoselective conjugate addition and the regioselective CHC process in the key steps.

  11. Nucleic Acid Immunity.

    Science.gov (United States)

    Hartmann, G

    2017-01-01

    Organisms throughout biology need to maintain the integrity of their genome. From bacteria to vertebrates, life has established sophisticated mechanisms to detect and eliminate foreign genetic material or to restrict its function and replication. Tremendous progress has been made in the understanding of these mechanisms which keep foreign or unwanted nucleic acids from viruses or phages in check. Mechanisms reach from restriction-modification systems and CRISPR/Cas in bacteria and archaea to RNA interference and immune sensing of nucleic acids, altogether integral parts of a system which is now appreciated as nucleic acid immunity. With inherited receptors and acquired sequence information, nucleic acid immunity comprises innate and adaptive components. Effector functions include diverse nuclease systems, intrinsic activities to directly restrict the function of foreign nucleic acids (e.g., PKR, ADAR1, IFIT1), and extrinsic pathways to alert the immune system and to elicit cytotoxic immune responses. These effects act in concert to restrict viral replication and to eliminate virus-infected cells. The principles of nucleic acid immunity are highly relevant for human disease. Besides its essential contribution to antiviral defense and restriction of endogenous retroelements, dysregulation of nucleic acid immunity can also lead to erroneous detection and response to self nucleic acids then causing sterile inflammation and autoimmunity. Even mechanisms of nucleic acid immunity which are not established in vertebrates are relevant for human disease when they are present in pathogens such as bacteria, parasites, or helminths or in pathogen-transmitting organisms such as insects. This review aims to provide an overview of the diverse mechanisms of nucleic acid immunity which mostly have been looked at separately in the past and to integrate them under the framework nucleic acid immunity as a basic principle of life, the understanding of which has great potential to

  12. Peptide Nucleic Acids (PNA)

    DEFF Research Database (Denmark)

    2002-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  13. Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    1998-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  14. Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    2003-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  15. Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    2004-01-01

    A novel class of compounds known as peptide nucleic acids, bind complementary DNA and RNA strands, and generally do so more strongly than the corresponding DNA or RNA strands while exhibiting increased sequence specificity and solubility. The peptide nucleic acids comprise ligands selected from...

  16. Carbolic acid poisoning

    Science.gov (United States)

    ... you to. If the person swallowed the carbolic acid, give them water or milk right away, if a provider tells ... well someone does depends on how much carbolic acid they swallowed and how quickly they receive treatment. The faster medical help is given, the better ...

  17. Uric acid - blood

    Science.gov (United States)

    ... High levels of uric acid can sometimes cause gout or kidney disease. You may have this test if you have had or are about to have certain types of chemotherapy. Rapid weight loss, which may occur with such treatments, can increase the amount of uric acid in ...

  18. Neurotoxicity of Folic Acid

    NARCIS (Netherlands)

    Amsterdam van JGC; Jansen EHJM; A Opperhuizen; TOX

    2004-01-01

    The present review summarises the neurotoxicological effects of folic acid. Some studies in animals have shown that folic acid is neurotoxic and epileptogenic when applied directly to the brain. One poorly controlled and not further reproduced study from 1970 reported neurotoxic symptoms like

  19. Amino Acid Crossword Puzzle

    Science.gov (United States)

    Sims, Paul A.

    2011-01-01

    Learning the 20 standard amino acids is an essential component of an introductory course in biochemistry. Later in the course, the students study metabolism and learn about various catabolic and anabolic pathways involving amino acids. Learning new material or concepts often is easier if one can connect the new material to what one already knows;…

  20. Fats and fatty acids

    Science.gov (United States)

    The absolute fat requirement of the human species is the amount of essential fatty acids needed to maintain optimal fatty acid composition of all tissues and normal eicosanoid synthesis. At most, this requirement is no more than about 5% of an adequate energy intake. However, fat accounts for appro...

  1. Peptide Nucleic Acid Synthons

    DEFF Research Database (Denmark)

    2004-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  2. Chlorogenic acid and caffeic acid are absorbed in humans

    OpenAIRE

    2001-01-01

    Chlorogenic acid, an ester of caffeic acid and quinic acid, is a major phenolic compound in coffee; daily intake in coffee drinkers is 0.5-1 g. Chlorogenic acid and caffeic acid are antioxidants in vitro and might therefore contribute to the prevention of cardiovascular disease. However, data on the absorption of chlorogenic acid and caffeic acid in humans are lacking. We determined the absorption of chlorogenic acid and caffeic acid in a cross-over study with 4 female and 3 male healthy ileo...

  3. Chlorogenic acid and caffeic acid are absorbed in humans

    NARCIS (Netherlands)

    Olthof, M.R.; Hollman, P.C.H.; Katan, M.B.

    2001-01-01

    Chlorogenic acid, an ester of caffeic acid and quinic acid, is a major phenolic compound in coffee; daily intake in coffee drinkers is 0.5-1 g. Chlorogenic acid and caffeic acid are antioxidants in vitro and might therefore contribute to the prevention of cardiovascular disease. However, data on the

  4. Chlorogenic acid and caffeic acid are absorbed in humans

    NARCIS (Netherlands)

    Olthof, M.R.; Hollman, P.C.H.; Katan, M.B.

    2001-01-01

    Chlorogenic acid, an ester of caffeic acid and quinic acid, is a major phenolic compound in coffee; daily intake in coffee drinkers is 0.5-1 g. Chlorogenic acid and caffeic acid are antioxidants in vitro and might therefore contribute to the prevention of cardiovascular disease. However, data on the

  5. Halogenated fatty acids

    DEFF Research Database (Denmark)

    Mu, Huiling; Wesén, Clas; Sundin, Peter

    1997-01-01

    Chlorinated fatty acids have been found to be major contributors to organohalogen compounds in fish, bivalves, jellyfish, and lobster, and they have been indicated to contribute considerably to organohalogens in marine mammals. Brominated fatty acids have been found in marine sponges. Also......, chlorinated lipids have been found in meat exposed to hypochlorite disinfected water, and in chlorine-treated flour and in products made from such flour. Following exposure to chlorine bleached pulp mill effluents, aquatic organisms may have elevated concentrations of chlorinated fatty acids in their lipids....... However, a natural production of halogenated fatty acids is also possible. In this paper we summarize the present knowledge of the occurrence of halogenated fatty acids in lipids and suggested ways of their formation. In Part II (Trends Anal. Chem. 16 (1997) 274) we deal with methods...

  6. Phenolic acids enzymatic lipophilization.

    Science.gov (United States)

    Figueroa-Espinoza, Maria-Cruz; Villeneuve, Pierre

    2005-04-20

    Lipophilization is the esterification of a lipophilic moiety (fatty acid or fatty alcohol) on different substrates (phenolic acid, sugar, protein, ...), resulting in new molecules with modified hydrophilic/lipophilic balance. This reaction can be obtained chemically or enzymatically using different enzymes. Phenolic acids possess interesting biological properties (antioxidant, chelator, free radical scavenger, UV filter, antimicrobial, ...), but because of their relatively low solubility in aprotic media, their application in oil-based products is limited. Therefore, the esterification of their carboxylic acid function with a fatty alcohol enhances their hydrophobicity and results in a multifunctional amphiphilic molecule. Enzymatic lipophilization of phenolic acids is nowadays studied for potential industrial applications. Different systems have been proposed to perform the reaction yield [free or immobilized enzymes (lipase, feruloyl esterase, tannase, etc.), free or added organic solvent, addition of surfactant, microemulsion system, etc.]. Some of the functional properties of these esters have been demonstrated. This review presents a panorama of the advances in this field.

  7. 2-Methylaspartic acid monohydrate

    Directory of Open Access Journals (Sweden)

    Ray J. Butcher

    2013-12-01

    Full Text Available The title compound, C5H9NO4·H2O, is an isomer of the α-amino acid glutamic acid that crystallizes from water in its zwitterionic form as a monohydrate. It is not one of the 20 proteinogenic α-amino acids that are used in living systems and differs from the natural amino acids in that it has an α-methyl group rather than an α-H atom. In the crystal, an O—H...O hydrogen bond is present between the acid and water molecules while extensive N—H...O and O—H...O hydrogen bonds link the components into a three-dimensional array.

  8. Composition of amino acids, fatty acids and dietary fibre monomers ...

    African Journals Online (AJOL)

    Composition of amino acids, fatty acids and dietary fibre monomers in kernels of ... Nuts are rich in protein and essential amino acids, and have a high energy value ... of protein, especially when combined with foods with high lysine content.

  9. Amino acids analysis during lactic acid fermentation by single strain ...

    African Journals Online (AJOL)

    SAM

    2014-07-09

    Jul 9, 2014 ... of the three LAB strains to utilize amino acids for growth and lactic acid production were employed to ... Lactic acid bacteria (LAB), which are used for the ..... and characterization of potential probiotic lactobacilli from pig feces.

  10. Influence of BOL on hyaluronic acid, laminin and hyperplasia in hepatofibrotic rats

    Institute of Scientific and Technical Information of China (English)

    Li Yao; Zhen-Min Yao; Tao Yu

    2001-01-01

    AIM: To study the anti-hepatofibrosis mechanism of Bie Jie Jian oral liquid (BOL). METHODS: The model was induced by subcutaneous injection of CCl4. BOL was administered and the change of serum hyaluronic acid (HA) and laminin (LN) was observed and the degeneration of liver cells and the degree of fibre hyperplasia analyzed. Changes of ultra micro-structure in liver cells were observed in some samples. RESULTS: HA was reduced in both the groups with Iow and high dosage of BOL, which showed a remarkable difference as compared with that of the model group ( Iow dosage group: 376.15 μg/L ± 35.48 μg/L vs 806.07 μg/L ± 98.49 μg/L, P < 0.05; high dosage group: 340.14 μg/L ± 30.18 μg/L vs 806.07μg/L± 98.49 μg/L, P<0.05). The LN content of Iow and high dosage group of BOL was lower than that of model group (Iow dosage group: 71.99 μg/L± 8.15 μg/L vs 133.94μg/L± 14.45 μg/L, P< 0.01; high dosage group: 71.68 ig/L± 11.62 μg/L vs 133.94 μg/L ± 14.45 μg/L, P<0.01) and colchicine group (Iow dosage group: 71.99 μg/L ± 8.15 μg/Lvs 118.28 μg/L ± 16.13 μg/L, P< 0.05; high dosage group:71.68 μg/L ± 11.62 μg/L vs 118.28 μg/L ± 16.13 μg/L,P<0.05). Examined by Ridit, BOL could reduce the degeneration and necrosis of liver cells (X2 = 11.99P<0.05), the degree of fibre hyperplasia (X2 = 13.24P<0.05) and the pathological change of ultra micro-structure as well. CONCLUSION: The BOL has certain therapeutic effect on the experiment hepatofibrosis. Its mechanisms might include:protecting the function of liver cells, inhibiting excessive synthesis and secretion of extraceiluar matrix from hepatic stellate cells, relieving the cepillarization of hepatic sinueoid, improving liver micro-circulation, and regulating immune function.

  11. Trans Fatty Acids

    Science.gov (United States)

    Doyle, Ellin

    1997-09-01

    Fats and their various fatty acid components seem to be a perennial concern of nutritionists and persons concerned with healthful diets. Advice on the consumption of saturated, polyunsaturated, monounsaturated, and total fat bombards us from magazines and newspapers. One of the newer players in this field is the group of trans fatty acids found predominantly in partially hydrogenated fats such as margarines and cooking fats. The controversy concerning dietary trans fatty acids was recently addressed in an American Heart Association (AHA) science advisory (1) and in a position paper from the American Society of Clinical Nutrition/American Institute of Nutrition (ASCN/AIN) (2). Both reports emphasize that the best preventive strategy for reducing risk for cardiovascular disease and some types of cancer is a reduction in total and saturated fats in the diet, but a reduction in the intake of trans fatty acids was also recommended. Although the actual health effects of trans fatty acids remain uncertain, experimental evidence indicates that consumption of trans fatty acids adversely affects serum lipid levels. Since elevated levels of serum cholesterol and triacylglycerols are associated with increased risk of cardiovascular disease, it follows that intake of trans fatty acids should be minimized.

  12. Gluconic acid production.

    Science.gov (United States)

    Anastassiadis, Savas; Morgunov, Igor G

    2007-01-01

    Gluconic acid, the oxidation product of glucose, is a mild neither caustic nor corrosive, non toxic and readily biodegradable organic acid of great interest for many applications. As a multifunctional carbonic acid belonging to the bulk chemicals and due to its physiological and chemical characteristics, gluconic acid itself, its salts (e.g. alkali metal salts, in especially sodium gluconate) and the gluconolactone form have found extensively versatile uses in the chemical, pharmaceutical, food, construction and other industries. Present review article presents the comprehensive information of patent bibliography for the production of gluconic acid and compares the advantages and disadvantages of known processes. Numerous manufacturing processes are described in the international bibliography and patent literature of the last 100 years for the production of gluconic acid from glucose, including chemical and electrochemical catalysis, enzymatic biocatalysis by free or immobilized enzymes in specialized enzyme bioreactors as well as discontinuous and continuous fermentation processes using free growing or immobilized cells of various microorganisms, including bacteria, yeast-like fungi and fungi. Alternatively, new superior fermentation processes have been developed and extensively described for the continuous and discontinuous production of gluconic acid by isolated strains of yeast-like mold Aureobasidium pullulans, offering numerous advantages over the traditional discontinuous fungi processes.

  13. Sulfuric Acid on Europa

    Science.gov (United States)

    1999-01-01

    Frozen sulfuric acid on Jupiter's moon Europa is depicted in this image produced from data gathered by NASA's Galileo spacecraft. The brightest areas, where the yellow is most intense, represent regions of high frozen sulfuric acid concentration. Sulfuric acid is found in battery acid and in Earth's acid rain. This image is based on data gathered by Galileo's near infrared mapping spectrometer.Europa's leading hemisphere is toward the bottom right, and there are enhanced concentrations of sulfuric acid in the trailing side of Europa (the upper left side of the image). This is the face of Europa that is struck by sulfur ions coming from Jupiter's innermost moon, Io. The long, narrow features that crisscross Europa also show sulfuric acid that may be from sulfurous material extruded in cracks. Galileo, launched in 1989, has been orbiting Jupiter and its moons since December 1995. JPL manages the Galileo mission for NASA's Office of Space Science, Washington DC. JPL is a division of the California Institute of Technology, Pasadena, CA.

  14. Fusidic acid in dermatology

    DEFF Research Database (Denmark)

    Schöfer, Helmut; Simonsen, Lene

    1995-01-01

    efficacy and tolerability. Similarly, plain fusidic acid cream or ointment used two or three times daily in SSTIs such as impetigo are clinically and bacteriologically effective, with minimal adverse events. Combination formulations of fusidic acid with 1% hydrocortisone or 0.1% betamethasone achieve...... excellent results in infected eczema by addressing both inflammation and infection. A new lipid-rich combination formulation provides an extra moisturizing effect. Development of resistance to fusidic acid has remained generally low or short-lived and can be minimized by restricting therapy to no more than...

  15. Acid rain: An overview

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Summary of the effects of acid rain and related processes, sources, issues, corrective actions, research, current law, potential solutions, political solutions,...

  16. Fatty Acid Oxidation Disorders

    Science.gov (United States)

    ... acid oxidation disorders are tested for in newborn screening? The March of Dimes recommends that all babies ... in behavior Diarrhea, nausea (feeling sick to your stomach) and throwing up Drowsiness Fever Fussiness Little appetite ...

  17. Synthesis of aminoaldonic acids

    DEFF Research Database (Denmark)

    Jørgensen, Christel Thea

    With the aim of synthesising aminoaldonic acids, two 2-acetamido-2-deoxyaldonolactones with D-galacto (6) and D-arabino (11) configuration were prepared from acetylated sugar formazans in analogy with a known procedure. Empolying the same procedure to acetylated sugar phenylhydrazones gave mixtures....... The aziridino amides 43 and 51 were reductively cleaved with hydrazine to give 3-amino-2,3-dideoxyhexonhydrazides 83 and 85, which were easily converted into the corresponding lactone 84 and acid 86. The aziridine ring of 43 and 51 was also opened with acetic acid to give the 3-amino-3-deoxyhexonic acids 79...... and 82, respectively. The aminolactone 84 was converted into the corresponding amino sugar 89.With the aim of synthesising substrates for the Pictet-Spengler reaction three 4-aldehydo acetamidodideoxytetronolactones 92, 97 and 103 were prepared by periodate cleavage of the corresponding hexonolactones...

  18. [Hydrofluoric acid burns].

    Science.gov (United States)

    Holla, Robin; Gorter, Ramon R; Tenhagen, Mark; Vloemans, A F P M Jos; Breederveld, Roelf S

    2016-01-01

    Hydrofluoric acid is increasingly used as a rust remover and detergent. Dermal contact with hydrofluoric acid results in a chemical burn characterized by severe pain and deep tissue necrosis. It may cause electrolyte imbalances with lethal consequences. It is important to identify high-risk patients. 'High risk' is defined as a total affected body area > 3% or exposure to hydrofluoric acid in a concentration > 50%. We present the cases of three male patients (26, 31, and 39 years old) with hydrofluoric acid burns of varying severity and describe the subsequent treatments. The application of calcium gluconate 2.5% gel to the skin is the cornerstone of the treatment, reducing pain as well as improving wound healing. Nails should be thoroughly inspected and possibly removed if the nail is involved, to ensure proper healing. In high-risk patients, plasma calcium levels should be evaluated and cardiac monitoring is indicated.

  19. Azetidinic amino acids

    DEFF Research Database (Denmark)

    Bräuner-Osborne, Hans; Bunch, Lennart; Chopin, Nathalie

    2005-01-01

    A set of ten azetidinic amino acids, that can be envisioned as C-4 alkyl substituted analogues of trans-2-carboxyazetidine-3-acetic acid (t-CAA) and/or conformationally constrained analogues of (R)- or (S)-glutamic acid (Glu) have been synthesized in a diastereo- and enantiomerically pure form from...... of two diastereoisomers that were easily separated and converted in two steps into azetidinic amino acids. Azetidines 35-44 were characterized in binding studies on native ionotropic Glu receptors and in functional assays at cloned metabotropic receptors mGluR1, 2 and 4, representing group I, II and III...... beta-amino alcohols through a straightforward five step sequence. The key step of this synthesis is an original anionic 4-exo-tet ring closure that forms the azetidine ring upon an intramolecular Michael addition. This reaction was proven to be reversible and to lead to a thermodynamic distribution...

  20. Amino acid racemisation dating

    Energy Technology Data Exchange (ETDEWEB)

    Murray-Wallace, C.V. [University of Wollongong, Wollongong, NSW (Australia). School of Geosciences

    1999-11-01

    The potential of the time-dependent amino acid racemisation reaction as a method of age assessment was first reported by Hare and Abelson (1968). They noted that in specimens of the bivalve mollusc Mercenaria sp., greater concentrations of amino acids in the D-configuration with increasing fossil age. Hare and Abelson (1968) also reported negligible racemisation in a modern specimen of Mecanaria sp. On this basis they suggested that the extent of amino acid racemisation (epimerisation in the case of isoleucine) may be used to assess the age of materials within and beyond the range of radiocarbon dating. For the past thirty years amino acid racemisation has been extensively applied in Quaternary research as a method of relative and numeric dating, and a particularly large literature has emerged on the subject 12 refs.

  1. Folic acid - test

    Science.gov (United States)

    ... folic acid before and during pregnancy helps prevent neural tube defects, such as spina bifida. Women who are ... take more if they have a history of neural tube defects in earlier pregnancies. Ask your provider how ...

  2. Amino Acids and Chirality

    Science.gov (United States)

    Cook, Jamie E.

    2012-01-01

    Amino acids are among the most heavily studied organic compound class in carbonaceous chondrites. The abundance, distributions, enantiomeric compositions, and stable isotopic ratios of amino acids have been determined in carbonaceous chondrites fi'om a range of classes and petrographic types, with interesting correlations observed between these properties and the class and typc of the chondritcs. In particular, isomeric distributions appear to correlate with parent bodies (chondrite class). In addition, certain chiral amino acids are found in enantiomeric excess in some chondrites. The delivery of these enantiomeric excesses to the early Earth may have contributed to the origin of the homochirality that is central to life on Earth today. This talk will explore the amino acids in carbonaceous chondritcs and their relevance to the origin of life.

  3. Ethylenediaminetetraacetic acid in endodontics

    OpenAIRE

    Mohammadi, Zahed; Shalavi, Sousan; Jafarzadeh, Hamid

    2013-01-01

    Ethylenediaminetetraacetic acid (EDTA) is a chelating agent can bind to metals via four carboxylate and two amine groups. It is a polyamino carboxylic acid and a colorless, water-soluble solid, which is widely used to dissolve lime scale. It is produced as several salts, notably disodium EDTA and calcium disodium EDTA. EDTA reacts with the calcium ions in dentine and forms soluble calcium chelates. A review of the literature and a discussion of the different indications and considerations for...

  4. Bile acid sequestrants

    DEFF Research Database (Denmark)

    Hansen, Morten; Sonne, David P; Knop, Filip K

    2014-01-01

    Bile acids are synthesized in the liver from cholesterol and have traditionally been recognized for their role in absorption of lipids and in cholesterol homeostasis. In recent years, however, bile acids have emerged as metabolic signaling molecules that are involved in the regulation of lipid an......-lowering effect in patients with type 2 diabetes remain unclear. This article offers a review of the mechanisms behind the glucose-lowering effect of BASs, and the efficacy of BASs in the treatment of type 2 diabetes....... of the enterohepatic circulation. This increases bile acid synthesis and consequently reduces serum low-density lipoprotein cholesterol. Also, BASs improve glycemic control in patients with type 2 diabetes. Despite a growing understanding of the impact of BASs on glucose metabolism, the mechanisms behind their glucose...... and glucose metabolism, and possibly energy homeostasis, through activation of the bile acid receptors farnesoid X receptor (FXR) and TGR5. Bile acid sequestrants (BASs) constitute a class of drugs that bind bile acids in the intestine to form a nonabsorbable complex resulting in interruption...

  5. Fatty Acid Biosynthesis IX

    DEFF Research Database (Denmark)

    Carey, E. M.; Hansen, Heinz Johs. Max; Dils, R.

    1972-01-01

    # 1. I. [I-14C]Acetate was covalently bound to rabbit mammary gland fatty acid synthetase by enzymic transacylation from [I-14C]acetyl-CoA. Per mole of enzyme 2 moles of acetate were bound to thiol groups and up to I mole of acetate was bound to non-thiol groups. # 2. 2. The acetyl-fatty acid...... synthetase complex was isolated free from acetyl-CoA. It was rapidly hydrolysed at 30°C, but hydrolysis was greatly diminished at o°C and triacetic lactone synthesis occurred. In the presence of malonyl-CoA and NADPH, all the acetate bound to fatty acid synthetase was incorporated into long-chain fatty acids....... Hydrolysis of bound acetate and incorporation of bound acetate into fatty acids were inhibited to the same extent by guanidine hydrochloride. # 3. 3. Acetate was also covalently bound to fatty acid synthetase by chemical acetylation with [I-14C]acetic anhydride in the absence of CoASH. A total of 60 moles...

  6. Neutron Nucleic Acid Crystallography.

    Science.gov (United States)

    Chatake, Toshiyuki

    2016-01-01

    The hydration shells surrounding nucleic acids and hydrogen-bonding networks involving water molecules and nucleic acids are essential interactions for the structural stability and function of nucleic acids. Water molecules in the hydration shells influence various conformations of DNA and RNA by specific hydrogen-bonding networks, which often contribute to the chemical reactivity and molecular recognition of nucleic acids. However, X-ray crystallography could not provide a complete description of structural information with respect to hydrogen bonds. Indeed, X-ray crystallography is a powerful tool for determining the locations of water molecules, i.e., the location of the oxygen atom of H2O; however, it is very difficult to determine the orientation of the water molecules, i.e., the orientation of the two hydrogen atoms of H2O, because X-ray scattering from the hydrogen atom is very small.Neutron crystallography is a specialized tool for determining the positions of hydrogen atoms. Neutrons are not diffracted by electrons, but are diffracted by atomic nuclei; accordingly, neutron scattering lengths of hydrogen and its isotopes are comparable to those of non-hydrogen atoms. Therefore, neutron crystallography can determine both of the locations and orientations of water molecules. This chapter describes the current status of neutron nucleic acid crystallographic research as well as the basic principles of neutron diffraction experiments performed on nucleic acid crystals: materials, crystallization, diffraction experiments, and structure determination.

  7. Performance Comparison of New Combinations of Acids with Mud Acid in Sandstone Acidizing

    Directory of Open Access Journals (Sweden)

    Mian Umer Shafiq

    2014-01-01

    Full Text Available The aim of this research is to find the best suitable acid to acidize undamaged low permeable sandstone formation Stimulation of sandstone formations is a challenging task, which involves several chemicals and physical interactions of the acid with the formation. Mud acid has been successfully used to stimulate sandstone reservoirs for a number of years. Matrix acidizing may also be used to increase formation permeability in undamaged wells. The change may be up to 50 to 100% with the mud acid. For any acidizing process, the selection of acid (Formulation and Concentration and the design (Pre-flush, Main Acid, After-flush is very important. Different researchers are using different combinations of acids with different concentrations to get the best results for acidization. Mainly the common practice is combination of Hydrochloric Acid- Hydrofluoric with Concentration (3% HF-12% HCl. This study presents the results of a laboratory investigation of Orthophosphoric acid instead of hydrochloric acid in one combination and the second combination is Fluoboric and formic acid and the third one is formic and hydrofluoric acid. The results are compared with the mud acid and the results analyzed are porosity, permeability, strength, color change and FESEM Analysis. All of these new combinations shows that these have the potential to be used as acidizing acids on sandstone formations.

  8. Acidification and Acid Rain

    Science.gov (United States)

    Norton, S. A.; Veselã½, J.

    2003-12-01

    Air pollution by acids has been known as a problem for centuries (Ducros, 1845; Smith, 1872; Camuffo, 1992; Brimblecombe, 1992). Only in the mid-1900s did it become clear that it was a problem for more than just industrially developed areas, and that precipitation quality can affect aquatic resources ( Gorham, 1955). The last three decades of the twentieth century saw tremendous progress in the documentation of the chemistry of the atmosphere, precipitation, and the systems impacted by acid atmospheric deposition. Chronic acidification of ecosystems results in chemical changes to soil and to surface waters and groundwater as a result of reduction of base cation supply or an increase in acid (H+) supply, or both. The most fundamental changes during chronic acidification are an increase in exchangeable H+ or Al3+ (aluminum) in soils, an increase in H+ activity (˜concentration) in water in contact with soil, and a decrease in alkalinity in waters draining watersheds. Water draining from the soil is acidified and has a lower pH (=-log [H+]). As systems acidify, their biotic community changes.Acidic surface waters occur in many parts of the world as a consequence of natural processes and also due to atmospheric deposition of strong acid (e.g., Canada, Jeffries et al. (1986); the United Kingdom, Evans and Monteith (2001); Sweden, Swedish Environmental Protection Board (1986); Finland, Forsius et al. (1990); Norway, Henriksen et al. (1988a); and the United States (USA), Brakke et al. (1988)). Concern over acidification in the temperate regions of the northern hemisphere has been driven by the potential for accelerating natural acidification by pollution of the atmosphere with acidic or acidifying compounds. Atmospheric pollution ( Figure 1) has resulted in an increased flux of acid to and through ecosystems. Depending on the ability of an ecosystem to neutralize the increased flux of acidity, acidification may increase only imperceptibly or be accelerated at a rate that

  9. Inhibitory effect of ethanol, acetic acid, propionic acid and butyric acid on fermentative hydrogen production

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Bo; Wan, Wei; Wang, Jianlong [Laboratory of Environmental Technology, INET, Tsinghua University, Beijing 100084 (China)

    2008-12-15

    The inhibitory effect of added ethanol, acetic acid, propionic acid and butyric acid on fermentative hydrogen production by mixed cultures was investigated in batch tests using glucose as substrate. The experimental results showed that, at 35 C and initial pH 7.0, during the fermentative hydrogen production, the substrate degradation efficiency, hydrogen production potential, hydrogen yield and hydrogen production rate all trended to decrease with increasing added ethanol, acetic acid, propionic acid and butyric acid concentration from 0 to 300 mmol/L. The inhibitory effect of added ethanol on fermentative hydrogen production was smaller than those of added acetic acid, propionic acid and butyric acid. The modified Han-Levenspiel model could describe the inhibitory effects of added ethanol, acetic acid, propionic acid and butyric acid on fermentative hydrogen production rate in this study successfully. The modified Logistic model could describe the progress of cumulative hydrogen production. (author)

  10. Biochemical and functional interactions of a selective kappa opioid agonist with calcium

    Energy Technology Data Exchange (ETDEWEB)

    VonVoigtlander, P.F.; Ochoa, M.C.; Lewis, R.A.

    1987-01-01

    The discovery of the selective kappa opioid receptor agonist, U-50488H, has provided a tool for the study of the mechanisms and function of the kappa receptor-effector. We have investigated the interactions of this compound with calcium in several biochemical and functional studies to assess the involvement of calcium mechanisms in the kappa receptor-linked effector. In rat brain synaptosomes, U-50488H attenuated the uptake of /sup 45/Ca++ induced by K+ (40 mM) depolarization. This effect was concentration-related (U-50488H 10(-5) to 10(-7) M), was apparent in short (8-second) but not longer (1-minute) term incubations, and did not occur in the presence of a non-polarizing concentration (5.6 mM) of K+. Naloxone (10(-7) M) did not block this effect of U-50488H (10(-6) M), and higher concentrations (10(-5) M) alone blocked calcium uptake. We have found that the binding of the depolarizing amino acid analog, kainic acid, is enhanced by CaCl2. U-50488H (10(-4) to 10(-6) M) blocks this enhancement of /sup 3/H-kainic acid binding in vitro and also blocks the in vivo effects of kainic acid. In mice, intravenous injection of kainic acid causes scratching, convulsions, and death, depending on the dose administered. U-50488H blocks all of these effects (ED50 = 4.5 mg/kg for antagonism of convulsions induced by 27.5 mg/kg kainic acid). The convulsions induced by intracerebroventricularly administered kainic acid are also blocked by U-50488H as are those induced by similarly administered Bay K 8644, a calcium channel activator. All of these anticonvulsant effects of U-50488H were antagonized by naltrexone. Together these data indicate that the kappa agonist U-50488H has functionally relevant interactions with depolarization-related Ca++ mechanisms in the central nervous system.

  11. Synthesis and anticonvulsant activity of novel bicyclic acidic amino acids

    DEFF Research Database (Denmark)

    Conti, Paola; De Amici, Marco; Joppolo Di Ventimiglia, Samuele

    2003-01-01

    Bicyclic acidic amino acids (+/-)-6 and (+/-)-7, which are conformationally constrained homologues of glutamic acid, were prepared via a strategy based on a 1,3-dipolar cycloaddition. The new amino acids were tested toward ionotropic and metabotropic glutamate receptor subtypes; both of them...

  12. EFFECT OF ACIDITY ON ACID-SENSITIVE UV CURING SYSTEM

    Institute of Scientific and Technical Information of China (English)

    Qi-dao Chen; Bing Wu; Xiao-yin Hong

    1999-01-01

    By using diphenyliodonium salts with different counterions as photo acid generators (PAGs), the effect of acidity on ring-opening polymerization of epoxy monomers and polycondensation of polyol with hexamethoxymethyl melamine (HMMM) was studied. The result shows that the rate of ring-opening polymerization is evidently dependent on the acidity of the acid and strong photo-generated acid is required.However, there is a leveling effect in the polycondensation system; if the photo-generated acid is stronger than protonated HMMM, the acidity does not obviously affect the polycondensation rate.

  13. Determination of Sialic Acids by Acidic Ninhydrin Reaction

    Directory of Open Access Journals (Sweden)

    Yao,Kenzabroh

    1987-12-01

    Full Text Available A new acidic ninhydrin method for determining free sialic acids is described. The method is based on the reaction of sialic acids with Gaitonde's acid ninhydrin reagent 2 which yields a stable color with an absorption maximum at 470 nm. The standard curve is linear in the range of 5 to 500 nmol of N-acetylneuraminic acid per 0.9 ml of reaction mixture. The reaction was specific only for sialic acids among the various sugars and sugar derivatives examined. Some interference of this method by cysteine, cystine and tryptophan was noted, although their absorption maxima differed from that of sialic acids. The interference by these amino acids was eliminated with the use of a small column of cation-exchange resin. The acidic ninhydrin method provides a simple and rapid method for the determination of free sialic acids in biological materials.

  14. Domoic Acid Epileptic Disease

    Directory of Open Access Journals (Sweden)

    John S. Ramsdell

    2014-03-01

    Full Text Available Domoic acid epileptic disease is characterized by spontaneous recurrent seizures weeks to months after domoic acid exposure. The potential for this disease was first recognized in a human case study of temporal lobe epilepsy after the 1987 amnesic shellfish-poisoning event in Quebec, and was characterized as a chronic epileptic syndrome in California sea lions through investigation of a series of domoic acid poisoning cases between 1998 and 2006. The sea lion study provided a breadth of insight into clinical presentations, unusual behaviors, brain pathology, and epidemiology. A rat model that replicates key observations of the chronic epileptic syndrome in sea lions has been applied to identify the progression of the epileptic disease state, its relationship to behavioral manifestations, and to define the neural systems involved in these behavioral disorders. Here, we present the concept of domoic acid epileptic disease as a delayed manifestation of domoic acid poisoning and review the state of knowledge for this disease state in affected humans and sea lions. We discuss causative mechanisms and neural underpinnings of disease maturation revealed by the rat model to present the concept for olfactory origin of an epileptic disease; triggered in dendodendritic synapases of the olfactory bulb and maturing in the olfactory cortex. We conclude with updated information on populations at risk, medical diagnosis, treatment, and prognosis.

  15. Hydrogen production by fermentation using acetic acid and lactic acid.

    Science.gov (United States)

    Matsumoto, Mitsufumi; Nishimura, Yasuhiko

    2007-03-01

    Microbial hydrogen production from sho-chu post-distillation slurry solution (slurry solution) containing large amounts of organic acids was investigated. The highest hydrogen producer, Clostridium diolis JPCC H-3, was isolated from natural environment and produced hydrogen at 6.03+/-0.15 ml from 5 ml slurry solution in 30 h. Interestingly, the concentration of acetic acid and lactic acid in the slurry solution decreased during hydrogen production. The substrates for hydrogen production by C. diolis JPCC H-3, in particular organic acids, were investigated in an artificial medium. No hydrogen was produced from acetic acid, propionic acid, succinic acid, or citric acid on their own. Hydrogen and butyric acid were produced from a mixture of acetic acid and lactic acid, showing that C. diolis. JPCC H-3 could produce hydrogen from acetic acid and lactic acid. Furthermore, calculation of the Gibbs free energy strongly suggests that this reaction would proceed. In this paper, we describe for the first time microbial hydrogen production from acetic acid and lactic acid by fermentation.

  16. Halogenated fatty acids

    DEFF Research Database (Denmark)

    Mu, Huiling; Sundin, Peter; Wesén, Clas

    1997-01-01

    Halogenated fatty acids are the major contributors to organohalogen compounds in lipids of marine mammals, fish, and bivalves. For the initial characterization of these recently noticed compounds, a determination of the halogen concentration has usually been combined with some lipid isolation...... and separation method. This review covers separation by solid phase chromatography, gel permeation chromatography, and liquid-liquid extraction, followed by halogen determination. All studies performed according to this outline have indicated that the major organohalogen compounds are chlorinated fatty acids...... bound in different lipids. For the detection and identification of individual, halogenated fatty acid methyl esters (FAMEs) liberated from the lipids, gas chromatography (GC) has been employed together with detection methods such as electron capture detection, electrolytic conductivity detection (ELCD...

  17. Calorimetry of Nucleic Acids.

    Science.gov (United States)

    Rozners, Eriks; Pilch, Daniel S; Egli, Martin

    2015-12-01

    This unit describes the application of calorimetry to characterize the thermodynamics of nucleic acids, specifically, the two major calorimetric methodologies that are currently employed: differential scanning (DSC) and isothermal titration calorimetry (ITC). DSC is used to study thermally induced order-disorder transitions in nucleic acids. A DSC instrument measures, as a function of temperature (T), the excess heat capacity (C(p)(ex)) of a nucleic acid solution relative to the same amount of buffer solution. From a single curve of C(p)(ex) versus T, one can derive the following information: the transition enthalpy (ΔH), entropy (ΔS), free energy (ΔG), and heat capacity (ΔCp); the state of the transition (two-state versus multistate); and the average size of the molecule that melts as a single thermodynamic entity (e.g., the duplex). ITC is used to study the hybridization of nucleic acid molecules at constant temperature. In an ITC experiment, small aliquots of a titrant nucleic acid solution (strand 1) are added to an analyte nucleic acid solution (strand 2), and the released heat is monitored. ITC yields the stoichiometry of the association reaction (n), the enthalpy of association (ΔH), the equilibrium association constant (K), and thus the free energy of association (ΔG). Once ΔH and ΔG are known, ΔS can also be derived. Repetition of the ITC experiment at a number of different temperatures yields the ΔCp for the association reaction from the temperature dependence of ΔH.

  18. Whither acid rain?

    Science.gov (United States)

    Brimblecombe, P

    2001-04-04

    Acid rain, the environmental cause célèbre of the 1980s seems to have vanished from popular conscience. By contrast, scientific research, despite funding difficulties, has continued to produce hundreds of research papers each year. Studies of acid rain taught much about precipitation chemistry, the behaviour of snow packs, long-range transport of pollutants and new issues in the biology of fish and forested ecosystems. There is now evidence of a shift away from research in precipitation and sulfur chemistry, but an impressive theoretical base remains as a legacy.

  19. Ethylenediaminetetraacetic acid in endodontics.

    Science.gov (United States)

    Mohammadi, Zahed; Shalavi, Sousan; Jafarzadeh, Hamid

    2013-09-01

    Ethylenediaminetetraacetic acid (EDTA) is a chelating agent can bind to metals via four carboxylate and two amine groups. It is a polyamino carboxylic acid and a colorless, water-soluble solid, which is widely used to dissolve lime scale. It is produced as several salts, notably disodium EDTA and calcium disodium EDTA. EDTA reacts with the calcium ions in dentine and forms soluble calcium chelates. A review of the literature and a discussion of the different indications and considerations for its usage are presented.

  20. Locked nucleic acid

    DEFF Research Database (Denmark)

    Jepsen, Jan Stenvang; Sørensen, Mads D; Wengel, Jesper

    2004-01-01

    Locked nucleic acid (LNA) is a class of nucleic acid analogs possessing very high affinity and excellent specificity toward complementary DNA and RNA, and LNA oligonucleotides have been applied as antisense molecules both in vitro and in vivo. In this review, we briefly describe the basic...... physiochemical properties of LNA and some of the difficulties that may be encountered when applying LNA technology. The central part of the review focuses on the use of LNA molecules in regulation of gene expression, including delivery to cells, stability, unspecific effects, toxicity, pharmacokinetics...

  1. Whither Acid Rain?

    Directory of Open Access Journals (Sweden)

    Peter Brimblecombe

    2000-01-01

    Full Text Available Acid rain, the environmental cause célèbre of the 1980s seems to have vanished from popular conscience. By contrast, scientific research, despite funding difficulties, has continued to produce hundreds of research papers each year. Studies of acid rain taught much about precipitation chemistry, the behaviour of snow packs, long-range transport of pollutants and new issues in the biology of fish and forested ecosystems. There is now evidence of a shift away from research in precipitation and sulfur chemistry, but an impressive theoretical base remains as a legacy.

  2. Fatty acids of Thiobacillus thiooxidans.

    Science.gov (United States)

    Levin, R A

    1971-12-01

    Fatty acid spectra were made on Thiobacillus thiooxidans cultures both in the presence and absence of organic compounds. Small additions of glucose or acetate had no significant effect either on growth or fatty acid content. The addition of biotin had no stimulatory effect but did result in slight quantitative changes in the fatty acid spectrum. The predominant fatty acid was a C(19) cyclopropane acid.

  3. The Acid-Base Titration of a Very Weak Acid: Boric Acid

    Science.gov (United States)

    Celeste, M.; Azevedo, C.; Cavaleiro, Ana M. V.

    2012-01-01

    A laboratory experiment based on the titration of boric acid with strong base in the presence of d-mannitol is described. Boric acid is a very weak acid and direct titration with NaOH is not possible. An auxiliary reagent that contributes to the release of protons in a known stoichiometry facilitates the acid-base titration. Students obtain the…

  4. The Acid-Base Titration of a Very Weak Acid: Boric Acid

    Science.gov (United States)

    Celeste, M.; Azevedo, C.; Cavaleiro, Ana M. V.

    2012-01-01

    A laboratory experiment based on the titration of boric acid with strong base in the presence of d-mannitol is described. Boric acid is a very weak acid and direct titration with NaOH is not possible. An auxiliary reagent that contributes to the release of protons in a known stoichiometry facilitates the acid-base titration. Students obtain the…

  5. Catalytic acetoxylation of lactic acid to 2-acetoxypropionic acid, en route to acrylic acid

    NARCIS (Netherlands)

    Beerthuis, R.; Granollers, M.; Brown, D.R.; Salavagione, H.J.; Rothenberg, G.; Shiju, N.R.

    2015-01-01

    We present an alternative synthetic route to acrylic acid, starting from the platform chemical lactic acid and using heterogeneous catalysis. To improve selectivity, we designed an indirect dehydration reaction that proceeds via acetoxylation of lactic acid to 2-acetoxypropionic acid. This

  6. Lactic acid bacterial cell factories for gamma-aminobutyric acid.

    Science.gov (United States)

    Li, Haixing; Cao, Yusheng

    2010-11-01

    Gamma-aminobutyric acid is a non-protein amino acid that is widely present in organisms. Several important physiological functions of gamma-aminobutyric acid have been characterized, such as neurotransmission, induction of hypotension, diuretic effects, and tranquilizer effects. Many microorganisms can produce gamma-aminobutyric acid including bacteria, fungi and yeasts. Among them, gamma-aminobutyric acid-producing lactic acid bacteria have been a focus of research in recent years, because lactic acid bacteria possess special physiological activities and are generally regarded as safe. They have been extensively used in food industry. The production of lactic acid bacterial gamma-aminobutyric acid is safe and eco-friendly, and this provides the possibility of production of new naturally fermented health-oriented products enriched in gamma-aminobutyric acid. The gamma-aminobutyric acid-producing species of lactic acid bacteria and their isolation sources, the methods for screening of the strains and increasing their production, the enzymatic properties of glutamate decarboxylases and the relative fundamental research are reviewed in this article. And the potential applications of gamma-aminobutyric acid-producing lactic acid bacteria were also referred to.

  7. Aminolevulinic Acid Topical

    Science.gov (United States)

    ... on or under the skin that result from exposure to sunlight and can develop into skin cancer) of the ... acid will make your skin very sensitive to sunlight (likely to get sunburn). Avoid exposure of treated skin to direct sunlight or bright ...

  8. Multifunctional Cinnamic Acid Derivatives

    Directory of Open Access Journals (Sweden)

    Aikaterini Peperidou

    2017-07-01

    Full Text Available Our research to discover potential new multitarget agents led to the synthesis of 10 novel derivatives of cinnamic acids and propranolol, atenolol, 1-adamantanol, naphth-1-ol, and (benzylamino ethan-1-ol. The synthesized molecules were evaluated as trypsin, lipoxygenase and lipid peroxidation inhibitors and for their cytotoxicity. Compound 2b derived from phenoxyphenyl cinnamic acid and propranolol showed the highest lipoxygenase (LOX inhibition (IC50 = 6 μΜ and antiproteolytic activity (IC50 = 0.425 μΜ. The conjugate 1a of simple cinnamic acid with propranolol showed the higher antiproteolytic activity (IC50 = 0.315 μΜ and good LOX inhibitory activity (IC50 = 66 μΜ. Compounds 3a and 3b, derived from methoxylated caffeic acid present a promising combination of in vitro inhibitory and antioxidative activities. The S isomer of 2b also presented an interesting multitarget biological profile in vitro. Molecular docking studies point to the fact that the theoretical results for LOX-inhibitor binding are identical to those from preliminary in vitro study.

  9. Lactic acid and lactates

    NARCIS (Netherlands)

    Schreurs, V.V.A.M.

    2010-01-01

    This review aims to integrate the present state of knowledge on lactate metabolism in human and mammalian physiology as far as it could be subject to nutritional interventions. An integrated view on the nutritional, metabolic and physiological aspects of lactic acid and lactates might open a perspec

  10. Accidents with sulfuric acid

    Directory of Open Access Journals (Sweden)

    Rajković Miloš B.

    2006-01-01

    Full Text Available Sulfuric acid is an important industrial and strategic raw material, the production of which is developing on all continents, in many factories in the world and with an annual production of over 160 million tons. On the other hand, the production, transport and usage are very dangerous and demand measures of precaution because the consequences could be catastrophic, and not only at the local level where the accident would happen. Accidents that have been publicly recorded during the last eighteen years (from 1988 till the beginning of 2006 are analyzed in this paper. It is very alarming data that, according to all the recorded accidents, over 1.6 million tons of sulfuric acid were exuded. Although water transport is the safest (only 16.38% of the total amount of accidents in that way 98.88% of the total amount of sulfuric acid was exuded into the environment. Human factor was the common factor in all the accidents, whether there was enough control of the production process, of reservoirs or transportation tanks or the transport was done by inadequate (old tanks, or the accidents arose from human factor (inadequate speed, lock of caution etc. The fact is that huge energy, sacrifice and courage were involved in the recovery from accidents where rescue teams and fire brigades showed great courage to prevent real environmental catastrophes and very often they lost their lives during the events. So, the phrase that sulfuric acid is a real "environmental bomb" has become clearer.

  11. Uric acid and evolution

    National Research Council Canada - National Science Library

    Álvarez-Lario, Bonifacio; Macarrón-Vicente, Jesús

    2010-01-01

    Uric acid (UA) is the end product of purine metabolism in humans due to the loss of uricase activity by various mutations of its gene during the Miocene epoch, which led to humans having higher UA levels than other mammals. Furthermore, 90...

  12. Acid Rain Investigations.

    Science.gov (United States)

    Hugo, John C.

    1992-01-01

    Presents an activity in which students investigate the formation of solid ammonium chloride aerosol particles to help students better understand the concept of acid rain. Provides activity objectives, procedures, sample data, clean-up instructions, and questions and answers to help interpret the data. (MDH)

  13. The Acid Rain Game.

    Science.gov (United States)

    Rakow, Steven J.; Glenn, Allen

    1982-01-01

    Provides rationale for and description of an acid rain game (designed for two players), a problem-solving model for elementary students. Although complete instructions are provided, including a copy of the game board, the game is also available for Apple II microcomputers. Information for the computer program is available from the author.…

  14. Acid Rain Classroom Projects.

    Science.gov (United States)

    Demchik, Michael J.

    2000-01-01

    Describes a curriculum plan in which students learn about acid rain through instructional media, research and class presentations, lab activities, simulations, design, and design implementation. Describes the simulation activity in detail and includes materials, procedures, instructions, examples, results, and discussion sections. (SAH)

  15. Hyaluronic Acid Assays

    DEFF Research Database (Denmark)

    Itenov, Theis S; Kirkby, Nikolai S; Bestle, Morten H

    2015-01-01

    BACKGROUD: Hyaluronic acid (HA) is proposed as a marker of functional liver capacity. The aim of the present study was to compare a new turbidimetric assay for measuring HA with the current standard method. METHODS: HA was measured by a particle-enhanced turbidimetric immunoassay (PETIA) and enzyme...

  16. Koetjapic acid chloroform hemisolvate

    Directory of Open Access Journals (Sweden)

    Z. D. Nassar

    2010-06-01

    Full Text Available The asymmetric unit of the title compound, C30H46O4·0.5CHCl3, consists of one koetjapic acid [systematic name: (3R,4aR,4bS,7S,8S,10bS,12aS-7-(2-carboxyethyl-3,4b,7,10b,12a-pentamethyl-8-(prop-1-en-2-yl-1,2,3,4,4a,4b,5,6,7,8,9,10,10b,11,12,12a-hexadecahydrochrysene-3-carboxylic acid] molecule and one half-molecule of chloroform solvent, which is disordered about a twofold rotation axis. The symmetry-independent component is further disordered over two sites, with occupancies of 0.30 and 0.20. The koetjapic acid contains a fused four-ring system, A/B/C/D. The A/B, B/C and C/D junctions adopt E/trans/cis configurations, respectively. The conformation of ring A is intermediate between envelope and half-chair and ring B adopts an envelope conformation whereas rings C and D adopt chair conformations. A weak intramolecular C—H...O hydrogen bond is observed. The koetjapic acid molecules are linked into dimers by two pairs of intermolecular O—H...O hydrogen bonds. The dimers are stacked along the c axis.

  17. Phenylpyruvic acid in urine

    NARCIS (Netherlands)

    Meulemans, O.; Vergeer, E.G.

    1960-01-01

    The method of The, Fleury And Vink for the determination of phenylpyruvic acid (PPA) in urine is modified by measuring the extinction after the green colour with ferric chloride has faded, and subtracting this extinction from that found initially. More accurate values are obtained and low PPA values

  18. Acid Rain Classroom Projects.

    Science.gov (United States)

    Demchik, Michael J.

    2000-01-01

    Describes a curriculum plan in which students learn about acid rain through instructional media, research and class presentations, lab activities, simulations, design, and design implementation. Describes the simulation activity in detail and includes materials, procedures, instructions, examples, results, and discussion sections. (SAH)

  19. The Acid Rain Game.

    Science.gov (United States)

    Rakow, Steven J.; Glenn, Allen

    1982-01-01

    Provides rationale for and description of an acid rain game (designed for two players), a problem-solving model for elementary students. Although complete instructions are provided, including a copy of the game board, the game is also available for Apple II microcomputers. Information for the computer program is available from the author.…

  20. Acid Rain Investigations.

    Science.gov (United States)

    Hugo, John C.

    1992-01-01

    Presents an activity in which students investigate the formation of solid ammonium chloride aerosol particles to help students better understand the concept of acid rain. Provides activity objectives, procedures, sample data, clean-up instructions, and questions and answers to help interpret the data. (MDH)

  1. Effect of domoic acid on brain amino acid levels.

    Science.gov (United States)

    Durán, R; Arufe, M C; Arias, B; Alfonso, M

    1995-03-01

    The administration of Domoic Acid (Dom) in a 0.2 mg/kg i.p. dose induces changes in the levels of amino acids of neurochemical interest (Asp, Glu, Gly, Tau, Ala, GABA) in different rat brain regions (hypothalamus, hippocampus, amygdala, striatum, cortex and midbrain). The most affected amino acid is the GABA, the main inhibitory amino acid neurotransmitter, whereas glutamate, the main excitatory amino acid, is not affected. The rat brain regions that seem to be the main target of the Dom action belong to the limbic system (hippocampus, amygdala). The possible implication of the amino acids in the actions of Dom is also discussed.

  2. A Direct, Biomass-Based Synthesis of Benzoic Acid: Formic Acid-Mediated Deoxygenation of the Glucose-Derived Materials Quinic Acid and Shikimic Acid

    Energy Technology Data Exchange (ETDEWEB)

    Arceo, Elena; Ellman, Jonathan; Bergman, Robert

    2010-05-03

    An alternative biomass-based route to benzoic acid from the renewable starting materials quinic acid and shikimic acid is described. Benzoic acid is obtained selectively using a highly efficient, one-step formic acid-mediated deoxygenation method.

  3. Potentiometric determination of peroxodisulfuric acid during electrolysis sulfuric acid

    Directory of Open Access Journals (Sweden)

    Fedor Malchik

    2013-09-01

    Full Text Available Was proposed two potentiometric methods for determining peroxodisulfuric acid during electrolysis of sulfuric acid (potentiometric titration method and direct potentiometry, based on its interaction with a known excess of a solution Fe2+.

  4. Progress in engineering acid stress resistance of lactic acid bacteria.

    Science.gov (United States)

    Wu, Chongde; Huang, Jun; Zhou, Rongqing

    2014-02-01

    Lactic acid bacteria (LAB) are widely used for the production of a variety of fermented foods, and are considered as probiotic due to their health-promoting effect. However, LAB encounter various environmental stresses both in industrial fermentation and application, among which acid stress is one of the most important survival challenges. Improving the acid stress resistance may contribute to the application and function of probiotic action to the host. Recently, the advent of genomics, functional genomics and high-throughput technologies have allowed for the understanding of acid tolerance mechanisms at a systems level, and many method to improve acid tolerance have been developed. This review describes the current progress in engineering acid stress resistance of LAB. Special emphasis is placed on engineering cellular microenvironment (engineering amino acid metabolism, introduction of exogenous biosynthetic capacity, and overproduction of stress response proteins) and maintaining cell membrane functionality. Moreover, strategies to improve acid tolerance and the related physiological mechanisms are also discussed.

  5. Effect of phenolic acids on glucose and organic acid metabolism by lactic acid bacteria from wine.

    Science.gov (United States)

    Campos, Francisco M; Figueiredo, Ana R; Hogg, Tim A; Couto, José A

    2009-06-01

    The influence of phenolic (p-coumaric, caffeic, ferulic, gallic and protocatechuic) acids on glucose and organic acid metabolism by two strains of wine lactic acid bacteria (Oenococcus oeni VF and Lactobacillus hilgardii 5) was investigated. Cultures were grown in modified MRS medium supplemented with different phenolic acids. Cellular growth was monitored and metabolite concentrations were determined by HPLC-RI. Despite the strong inhibitory effect of most tested phenolic acids on the growth of O. oeni VF, the malolactic activity of this strain was not considerably affected by these compounds. While less affected in its growth, the capacity of L. hilgardii 5 to degrade malic acid was clearly diminished. Except for gallic acid, the addition of phenolic acids delayed the metabolism of glucose and citric acid in both strains tested. It was also found that the presence of hydroxycinnamic acids (p-coumaric, caffeic and ferulic) increased the yield of lactic and acetic acid production from glucose by O. oeni VF and not by L. hilgardii 5. The results show that important oenological characteristics of wine lactic acid bacteria, such as the malolactic activity and the production of volatile organic acids, may be differently affected by the presence of phenolic acids, depending on the bacterial species or strain.

  6. [Determination of scopolin, chlorogenic acid, scopoletin, isochlorogenic acid A, isochlorogenic acid B and isochlorogenic acid C in plants of Erycibe].

    Science.gov (United States)

    Xu, Xiao-kun; Chen, Zhi-yong; Liao, Li-ping; Zhang, Zi-jia; Wang, Zheng-tao

    2015-03-01

    An accurate and reliable analytical method for-simultaneous determination of six active components (scopolin, chlorogenic acid, scopoletin, isochlorogenic acid A, isochlorogenic acid B and isochlorogenic acid C) in plants of Erycibe was developed. Scopolin, chlorogenic acid, scopoletin, isochlorogenic acid A, isochlorogenic acid B and isochlorogenic acid C in the samples were well separated in analytical HPLC by gradual elution with methanol-0.1% formic acid solution. The chromatographic condictions: Agilent Poroshell 120 EC-C18 column, flowing rate being 1 mL x min(-1), detecting wavelength at 345 nm. Good linearities of scopolin, chlorogenic acid, scopoletin, isochlorogenic acid A, isochlorogenic acid B and isochlorogenic acid C were in the range of 0.026 8-2.68, 0.027 0-2.70, 0.008 1-0.81, 0.018 8-1.88, 0.017 6-1.76, 0.019 6-1.96 μg, respectively (r > 0.999 6). The average recoveries of the six components were 98.1%, 98.7%, 100.8%, 100.4%, 99.7%, 101.1%; the relative standard deviations were 2.67%, 2.86%, 2.62%, 1.98%, 2.76%, 2.19%. The method is simple, feasible and reproducible and can be used for the quality control of plants of Erycibe.

  7. Usnic acid controls the acidity tolerance of lichens.

    Science.gov (United States)

    Hauck, Markus; Jürgens, Sascha-René

    2008-11-01

    The hypotheses were tested that, firstly, lichens producing the dibenzofuran usnic acid colonize substrates characterized by specific pH ranges, secondly, this preferred pH is in a range where soluble usnic acid and its corresponding anion occur in similar concentrations, and thirdly, usnic acid makes lichens vulnerable to acidity. Lichens with usnic acid prefer an ambient pH range between 3.5 and 5.5 with an optimum between 4.0 and 4.5. This optimum is close to the pK(a1) value of usnic acid of 4.4. Below this optimum pH, dissolved SO(2) reduces the chlorophyll fluorescence yield more in lichens with than without their natural content of usnic acid. This suggests that usnic acid influences the acidity tolerance of lichens. The putative mechanism of the limited acidity tolerance of usnic acid-containing lichens is the acidification of the cytosol by molecules of protonated usnic acid shuttling protons through the plasma membrane at an apoplastic pH

  8. Circulating folic acid in plasma: relation to folic acid fortification

    Science.gov (United States)

    The implementation of folic acid fortification in the United States has resulted in unprecedented amounts of this synthetic form of folate in the American diet. Folic acid in circulation may be a useful measure of physiologic exposure to synthetic folic acid, and there is a potential for elevated co...

  9. Acetic acid extraction from aqueous solutions using fatty acids

    NARCIS (Netherlands)

    IJmker, H.M.; Gramblicka, M.; Kersten, Sascha R.A.; van der Ham, Aloysius G.J.; Schuur, Boelo

    2014-01-01

    A major challenge for production of acetic acid via bio-based routes is cost-effective concentration and purification of the acetic acid from the aqueous solutions, for which liquid–liquid extraction is a possible method. A main challenge in extraction of acetic acid from dilute aqueous solutions is

  10. Acetic acid extraction from aqueous solutions using fatty acids

    NARCIS (Netherlands)

    IJmker, H.M.; Gramblicka, M.; Kersten, S.R.A.; Ham, van der A.G.J.; Schuur, B.

    2014-01-01

    A major challenge for production of acetic acid via bio-based routes is cost-effective concentration and purification of the acetic acid from the aqueous solutions, for which liquid–liquid extraction is a possible method. A main challenge in extraction of acetic acid from dilute aqueous solutions is

  11. N-(3-Chlorophenylmaleamic acid

    Directory of Open Access Journals (Sweden)

    B. Thimme Gowda

    2010-07-01

    Full Text Available In the title compound, C10H8ClNO3, the molecular conformation is stabilized by two intramolecular hydrogen bonds. The first is a short O—H...O hydrogen bond within the maleamic acid unit and the second is a C—H...O hydrogen bond which connects the amide group with the phenyl ring. The maleamic acid unit is essentially planar, with an r.m.s. deviation of 0.044 Å, and makes a dihedral angle of 15.2 (1° with the phenyl ring. In the crystal, intermolecular N—H...O hydrogen bonds link the molecules into C(7 chains running [010].

  12. Acid hydrolysis of cellulose

    Energy Technology Data Exchange (ETDEWEB)

    Salazar, H.

    1980-12-01

    One of the alternatives to increase world production of etha nol is by the hydrolysis of cellulose content of agricultural residues. Studies have been made on the types of hydrolysis: enzimatic and acid. Data obtained from the sulphuric acid hydrolysis of cellulose showed that this process proceed in two steps, with a yield of approximately 95% glucose. Because of increases in cost of alternatives resources, the high demand of the product and the more economic production of ethanol from cellulose materials, it is certain that this technology will be implemented in the future. At the same time further studies on the disposal and reuse of the by-products of this production must be undertaken.

  13. Autohydrolysis of phytic acid.

    Science.gov (United States)

    Hull, S R; Gray, J S; Montgomery, R

    1999-09-10

    The autohydrolysis of phytic acid at 120 degrees C resulted in the formation of most of the phosphate esters of myo-inositol in varying amounts depending upon the reaction time. Eighteen of the 39 chromatographically distinct myo-inositol mono-, bis-, tris-, tetrakis-, pentakis-, and hexakisphosphates have been characterized using two different HPLC systems. These myo-inositol phosphates were partially purified by preparative anion-exchange chromatography under acidic and alkaline elution conditions. The combination of these two methods provides a two-tiered chromatographic approach to the rapid and sensitive identification of inositol phosphates in complex mixtures. Identification of the products was confirmed by 1D and 2D (1)H NMR analysis. The analytical procedure was applied to the autohydrolysis of the mixture of inositol phosphates from corn steep water.

  14. N-(3-Methylphenylsuccinamic acid

    Directory of Open Access Journals (Sweden)

    B. Thimme Gowda

    2010-02-01

    Full Text Available In the crystal structure of the title compound, C11H13NO3, the conformations of the N—H and C=O bonds in the amide segment are anti to each other, and that of the amide H atom is anti to the meta-methyl group in the benzene ring. Furthermore, the conformations of the amide oxygen and the carbonyl O atom of the acid segment are also anti to the adjacent –CH2 groups. The C=O and O—H bonds of the acid group are syn to each other. In the crystal, the molecules are packed into infinite chains through intermolecular N—H...O and O—H...O hydrogen bonds.

  15. Accidents with sulfuric acid

    OpenAIRE

    Rajković Miloš B.

    2006-01-01

    Sulfuric acid is an important industrial and strategic raw material, the production of which is developing on all continents, in many factories in the world and with an annual production of over 160 million tons. On the other hand, the production, transport and usage are very dangerous and demand measures of precaution because the consequences could be catastrophic, and not only at the local level where the accident would happen. Accidents that have been publicly recorded during the last eigh...

  16. Phenolic acids bioavailability

    OpenAIRE

    2011-01-01

    The daily intake of phenolic compounds does not necessarily reflect the dose at which they reach the physiological targets in the organisms. The biological activity of phenolic compounds metabolites found in blood, organs and target tissues, as a result of digestive and hepatic activity, may differ from those of the native forms of the substances. This review discusses the absorption and metabolism of phenolic acids, a class of phenolic compounds abundant in food, and the methodologies used f...

  17. Retention performance of a learned delayed-alternation task after chemical lesions of the cats mediodorsal nucleus.

    Science.gov (United States)

    Markowitsch, H J

    1982-03-01

    The mediodorsal nucleus of the thalamus was lesioned in cats, which had learned a spatial delayed-alternation task. Lesions were carried out with kainic acid or ibotenic acid. From altogether 29 cats, 9 cats with bilateral and 6 cats with unilateral lesions of the mediodorsal nucleus together with a control group of 4 cats, were included in the final data analysis. Lesions in the operated cats destroyed variable portions of the mediodorsal nucleus. Consistently, however, neither the midline nuclei, situated next to the damaged mediodorsal nucleus, nor fiber tracts traversing or by-passing the mediodorsal nucleus, were damaged. Furthermore, remote lesion effects were not detected either in the diazepam-pretreated cats with kainic acid-induced lesions or in the ibotenic acid-lesioned animals. Cats injected with ibotenic acid at a concentration 8-fold higher than the kainic acid solution, showed smaller thalamic lesions than kainic acid-injected cats. A direct correlation was found between the extent of neuronal damage within the mediodorsal nucleus and the degree of the behavioral impairment. Cats with complete or almost complete bilateral lesions of the mediodorsal nucleus manifested severe deficits in retention of the delayed-alternation task, while cats with small, bilateral lesions of the mediodorsal nucleus or with unilateral lesions were impaired less severely or even not at all.

  18. Omega-3 fatty acids (image)

    Science.gov (United States)

    Omega-3 fatty acids are a form of polyunsaturated fat that the body derives from food. Omega-3s (and omega-6s) are known as essential fatty acids (EFAs) because they are important for good health. ...

  19. Folic Acid Questions and Answers

    Science.gov (United States)

    ... What effect does taking folic acid have on arsenic poisoning? In many countries in the world, arsenic in ... What effect does taking folic acid have on arsenic poisoning? In many countries in the world, arsenic in ...

  20. Bile acids for viral hepatitis

    DEFF Research Database (Denmark)

    Chen, Weikeng; Liu, J; Gluud, C

    2007-01-01

    Trials have assessed bile acids for patients with viral hepatitis, but no consensus has been reached regarding their usefulness.......Trials have assessed bile acids for patients with viral hepatitis, but no consensus has been reached regarding their usefulness....