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Sample records for kainic acid ka-induced

  1. 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...

  2. 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.

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

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    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.

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

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    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.

  5. 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...

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

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    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

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

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    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.

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

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    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.

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

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    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.

  10. 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.

  11. 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.

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

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    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

  13. 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...

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

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    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.

  15. 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.

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

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    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.

  17. 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.

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

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    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.

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

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    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.

  20. 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.

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

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    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.

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

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    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.

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

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    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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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.

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

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    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.

  11. 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.

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

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    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.

  13. 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.

  14. 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.

  15. 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....

  16. 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.

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

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    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.

  18. 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...

  19. 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.

  20. 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.

  1. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  3. 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...

  4. 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

  5. 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.

  6. 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)

  7. 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.

  8. 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.

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

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    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

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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...

  8. 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.

  9. 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

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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...

  17. 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.

  18. 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.

  19. 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.

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. 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

  3. 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.

  4. 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.

  5. [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.

  6. 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

  7. 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.

  8. 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

  9. 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

  10. 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。

  11. 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.

  12. 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.

  13. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  15. 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.

  16. 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

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  19. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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

    Institute of Scientific and Technical Information of China (English)

    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

  9. 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

    Institute of Scientific and Technical Information of China (English)

    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

  10. 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

    Energy Technology Data Exchange (ETDEWEB)

    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

  11. 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

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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...

  18. Lead Can Inhibit NMDA-, K+-, QA/KA-Induced Increases in Intracellular Free Ca2+ in Cultured Rat Hippocampal Neurons

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective To examine the effects of Pb2+ on N-methyl-D-aspartate (NMDA)-, K+- and quisqualate(QA)/kainite(KA)-induced increases in intracellular free calcium concentration ([Ca2+]i) in cultured fetal rat hippocampal neurons in order to explain the cognitive and learning deficits produced by this heavy metal. Methods Laser scanning confocal microscopy was used. Results The results clearly demonstrated that adding Pb2+ before or after NMDA/glycine stimulation selectively inhibited the stimulated increases in [Ca2+]i in a concentration-dependent manner. In contrast, Pb2+ treatment did not markedly affect increases in [Ca2+]i induced by an admixture of QA and KA. The minimal inhibitory effect of Pb2+ occurred at 1 μ mol/L, and more than seventy percent abolition of the NMDA-stimulated increase in [Ca2+]iwas observed at 100 μmol/L Pb2+. Evaluation of pb2+-induced increase in [Ca2+]i response to elevating extracellular concentrations of NMDA, glycine or calcium revealed that Pb2+ was a noncompetitive antagonist of both NMDA and glycine, and a competitive antagonist of Ca2+ at NMDA receptor channels. In addition, Pb2+ inhibited depolarization-evoked increases in [Ca2+]i mediated by K+ stimulation (30 μmol/L), indicating that Pb2+ also depressed the voltage-dependent calcium channels. Also, the results showed that Pb2+ appeared to be able to elevate the resting levels of [Ca2+]i in cultured neurons, implying a reason for pb2+-enhanced spontaneous release of several neurotransmitters reported in several previous studies. Conclusion Lead can inhibit NMDA-, K+-, QA/KA-inducod increases in intracellular [Ca2+]i in cultured hippocampal neurons.

  19. Expression of GABAA Receptor γ2 Subunit in Hippocampus of Rats with KA-induced Temporal Lobe Epilepsy%GABAA 受体γ2亚单位在海人酸颞叶癫痫大鼠海马内的表达

    Institute of Scientific and Technical Information of China (English)

    戚月凤; 汤继宏; 李岩; 顾琴

    2015-01-01

    目的:探讨癫痫发作后 GABAA 受体γ2亚单位在海马各区的动态表达以及氯硝西泮干预对其表达的影响。方法:健康成年雄性 SD 大鼠40只,随机分为对照组5只,致痫组15只,干预组15只,干预对照组5只。大鼠海马 CA3区注射海人酸建立颞叶癫痫模型,干预组大鼠在致痫前予以氯硝西泮灌胃。于致痫后6 h、12 h和1 d 采用免疫组化法检测各组大鼠海马 CA1及 CA3区 γ-氨基丁酸 A 受体γ2亚单位(GABAARγ2)的动态表达水平。结果:致痫组在海人酸给药后6 h、12 h 及1 d,海马 CA3区 GABAARγ2蛋白表达均显著低于对照组(P<0.01);CA1区 GABAARγ2蛋白表达也下降,注射后1 d 显著低于对照组(P<0.01)。干预组在海人酸注射后1 d CA1和 CA3区 GABAARγ2蛋白表达低于对照组(P<0.05);海人酸注射后6 h、12 h 及1 d,CA3区 GABAARγ2蛋白表达均高于同时间点致痫组(P<0.05),CA1区于海人酸注射后1 d ,GABAARγ2蛋白表达显著高于同时间点致痫组(P<0.01)。结论:海人酸诱导的颞叶癫痫模型中,海马 GABAARγ2蛋白表达减少,氯硝西泮可缓解颞叶癫痫导致的 GABAARγ2蛋白表达减少。%Objective: To study the expression of GABAA receptor γ2 subunit (GABAARγ2) protein in hippocam-pus of rats with KA-induced temporal lobe epilepsy. To investigate the effect of clonazepam (CZP) administration on expression of GABAARγ2. Methods: Forty male SD rats were randomly divided into control group (n=5), epilepsy group (n=15), intervention group (n=15), and intervention control group (n=5). Temporal lobe epilepsy model was established by injecting kainic acid into CA3 region of the hippocampus in rats in both the epilepsy and intervention groups. Rats in the intervention group were treated with CZP. The expression of GABAARγ2 protein was investigated by immunohistochemistry at 6 h, 12 h and 1 d after operation respectively. Results: The

  20. 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...

  1. 依达拉奉对海人酸诱导癫痫大鼠海马神经元损伤的保护作用%Protective effect of edaravone against neuron injury in KA-induced seizure of rats

    Institute of Scientific and Technical Information of China (English)

    魏学文; 张晓伟; 常卫东

    2011-01-01

    目的:研究依达拉奉对海人酸诱导大鼠癫痫引起神经元损伤的保护作用及其分子机制.方法:SD大鼠随机分为癫痫对照组(saline组)、癫痫组(KA组)和药物对照组(KA+ saline组)及依达拉奉组(KA+ Ed组).采用脑室注射海人酸制作大鼠癫痫模型.取海马组织应用Western-blot法检测cleaved caspase-3、FasL和Fas的表达,以免疫共沉淀法检测FasL与Fas的结合;焦油紫染色来观察海马CA1区CA3/DG区锥体细胞形态并计数成活的细胞.结果:癫痫组和药物对照组FasL的表达及其与Fas的结合以及cleaved caspase-3的表达较癫痫对照组显著增加(P<0.05),而依达拉奉组较药物对照组显著降低(P<0.05),Fas的蛋白表达各组间差异未见显著性(P>0.05);依达拉奉明显改善海人酸诱导损伤的神经细胞形态,减少CA1区CA3区神经元的缺失(P<0.05).结论:依达拉奉可以通过抑制KA诱导FasL的表达及其与Fas的结合,抑制Fas/FasL通路,进而抑制easpase-3的活化对神经细胞发挥保护作用.%OBJECTIVE To investigate the neuroprotection of edaravone against neuronal death induced by kainic acid and to elucidate the molecular mechanisms. METHODS Adult male Sprague-Daley rats weighing 200-300 g were allotted into 4 groups as follows: control group (saline) .seizure group (KA) ,drug control group (KA+ saline) ,and edaravone group (Eld + KA). Seizures were induced by intracerebroventricular injection of KA dissolved in sterile saline. Edaravone was intraperitone-ally administrated to the rats 40 min before KA injection. Subsequently a series of methods including immunoprecipitation.im-munoblotting,histologic analysis were used to analyze the interaction,expression of relevant proteins as well as the survival of the CA1/CA3 pyramidal neurons. RESULTS Neuroprotective effect of edaravone was observed on neuronal injury induced by KA to hippocampal CA1 and CA3 pyramidal neurons. Edaravone could inhibit the expression of Fas

  2. 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...

  3. 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

  4. Status epilepticus results in reversible neuronal injury in infant rat hippocampus: novel use of a marker

    OpenAIRE

    Chang, Daniel; Tallie Z. Baram

    1994-01-01

    Despite ready induction of severe limbic status epilepticus by systemic kainic acid (KA) in infant rats, excitotoxic neuronal injury has not been observed. The mechanisms of this resistance of the immature hippocampus to excitotoxicity are unknown. Acid fuchsin stain has been used as a marker of irreversibly injured neurons in the adult brain. We speculated that the dye might map reversibly injured neurons in the infant. Subsequent to KA-induced status epilepticus in 11-day-old rats, acid fuc...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  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. Effects of eugenol on granule cell dispersion in a mouse model of temporal lobe epilepsy.

    Science.gov (United States)

    Jeong, Kyoung Hoon; Lee, Dong-Seok; Kim, Sang Ryong

    2015-09-01

    Granule cell dispersion (GCD), a structural abnormality, is characteristic of temporal lobe epilepsy (TLE). Eugenol (EUG) is an essential component of medicinal herbs and is suggested to exert anticonvulsant activity. However, it is unclear whether EUG ameliorates the abnormal morphological changes in granule cells induced by epileptic insults. In the present study, we examined whether intraperitoneal injection of EUG attenuated increased seizure activity and GCD following intrahippocampal injection of kainic acid (KA). Our results showed that EUG significantly increased the seizure threshold, resulting in delayed seizure onset, and reduced GCD in KA-induced epilepsy. Moreover, EUG treatment significantly attenuated KA-induced activation of mammalian target of rapamycin complex 1 (mTORC1), which is involved in GCD development, in the dentate gyrus (DG). These results suggest that EUG may have beneficial effects in the treatment of epilepsy through its ability to inhibit GCD via suppression of KA-induced mTORC1 activation in the hippocampal DG in vivo.

  11. 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...

  12. 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.

  13. 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...

  14. 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.

  15. 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...

  16. 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.

  17. 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...

  18. 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...

  19. Anticonvulsant and neuroprotective effects of oligosaccharides from Lingzhi or Reishi medicinal mushroom, Ganoderma lucidum (Higher Basidiomycetes).

    Science.gov (United States)

    Tello, Isaac; Campos-Pena, Victoria; Montiel, Elizur; Rodriguez, Veronica; Aguirre-Moreno, Alma; Leon-Rivera, Ismael; Del Rio-Portilla, Federico; Herrera-Ruiz, Maribel; Villeda-Hernandez, Juana

    2013-01-01

    An oligosaccharide fraction isolated from the mycelium of the Lingzhi or Reishi medicinal mushroom Ganoderma lucidum (GLOS) was separated by size-exclusion chromatography. The chemical structure of GLOS consists of a disaccharide repeating unit [-4-β-1-Galf(1-6)-O-(β-Glcp)-1-]n (n=3,4). In addition, this study was undertaken to determine the possible anticonvulsant and neuroprotective effects of GLOS (10-80 mg/kg) on kainic acid (KA)-induced seizures. The behavioral alterations and histopathology of hippocampal neurons were studied. Our results show that GLOS inhibited convulsions in rats from KA-induced seizures, reduced the degeneration pattern in the CA3 region of rats, decreased astrocytic reactivity, and reduced the expression of IL-1β and TNF-α induced by KA. These results indicate a potential anticonvulsant and neuroprotective effects of GLOS.

  20. 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

  1. 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.

  2. 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...

  3. 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.

  4. 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.

  5. 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

  6. 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...

  7. 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.

  8. Effects of AT1 receptor antagonism on kainate-induced seizures and concomitant changes in hippocampal extracellular noradrenaline, serotonin, and dopamine levels in Wistar-Kyoto and spontaneously hypertensive rats.

    Science.gov (United States)

    Tchekalarova, Jana; Loyens, Ellen; Smolders, Ilse

    2015-05-01

    In the management of epilepsy, AT1 receptor antagonists have been suggested as an additional treatment strategy. A hyperactive brain angiotensin (Ang) II system and upregulated AT1 receptors are implicated in the cerebrovascular alterations in a genetic form of hypertension. Uncontrolled hypertension could also, in turn, be a risk factor for a seizure threshold decrease and development of epileptogenesis. The present study aimed to assess the effects of the selective AT1 receptor antagonist ZD7155 on kainic acid (KA)-induced status epilepticus (SE) development and accompanying changes in the hippocampal extracellular (EC) neurotransmitter levels of noradrenaline (NAD), serotonin (5-HT), and dopamine (DA) in spontaneously hypertensive rats (SHRs) and their parent strain Wistar-Kyoto (WKY) rats, since monoamines are well-known neurotransmitters involved in mechanisms of both epilepsy and hypertension. Status epilepticus was evoked in freely moving rats by a repetitive intraperitoneal (i.p.) administration of KA in subconvulsant doses. In the treatment group, ZD7155 (5mg/kg i.p.) was coadministered with the first KA injection. Spontaneously hypertensive rats exhibited higher susceptibility to SE than WKY rats, but the AT1 receptor antagonist did not alter the development of SE in SHRs or in WKY rats. In vivo microdialysis demonstrated significant KA-induced increases of the hippocampal NAD and DA levels in SHRs and of NAD, 5-HT, and DA in WKY rats. Although SHRs developed more severe seizures while receiving a lower dose of KA compared to WKY rats, AT1 receptor antagonism completely prevented all KA-induced increases of hippocampal monoamine levels in both rat strains without affecting seizure development per se. These results suggest a lack of direct relationship between KA-induced seizure susceptibility and adaptive changes of hippocampal NAD, 5-HT, and DA levels in the effects of ZD7155 in WKY rats and SHRs.

  9. Ginseng Rb fraction protects glia, neurons and cognitive function in a rat model of neurodegeneration.

    Directory of Open Access Journals (Sweden)

    Kangning Xu

    Full Text Available The loss and injury of neurons play an important role in the onset of various neurodegenerative diseases, while both microgliosis and astrocyte loss or dysfunction are significant causes of neuronal degeneration. Previous studies have suggested that an extract enriched panaxadiol saponins from ginseng has more neuroprotective potential than the total saponins of ginseng. The present study investigated whether a fraction of highly purified panaxadiol saponins (termed as Rb fraction was protective for both glia and neurons, especially GABAergic interneurons, against kainic acid (KA-induced excitotoxicity in rats. Rats received Rb fraction at 30 mg/kg (i.p., 40 mg/kg (i.p. or saline followed 40 min later by an intracerebroventricular injection of KA. Acute hippocampal injury was determined at 48 h after KA, and impairment of hippocampus-dependent learning and memory as well as delayed neuronal injury was determined 16 to 21 days later. KA injection produced significant acute hippocampal injuries, including GAD67-positive GABAergic interneuron loss in CA1, paralbumin (PV-positive GABAergic interneuron loss, pyramidal neuron degeneration and astrocyte damage accompanied with reactive microglia in both CA1 and CA3 regions of the hippocampus. There was also a delayed loss of GAD67-positive interneurons in CA1, CA3, hilus and dentate gyrus. Microgliosis also became more severe 21 days later. Accordingly, KA injection resulted in hippocampus-dependent spatial memory impairment. Interestingly, the pretreatment with Rb fraction at 30 or 40 mg/kg significantly protected the pyramidal neurons and GABAergic interneurons against KA-induced acute excitotoxicity and delayed injury. Rb fraction also prevented memory impairments and protected astrocytes from KA-induced acute excitotoxicity. Additionally, microglial activation, especially the delayed microgliosis, was inhibited by Rb fraction. Overall, this study demonstrated that Rb fraction protected both

  10. Ginseng Rb fraction protects glia, neurons and cognitive function in a rat model of neurodegeneration.

    Science.gov (United States)

    Xu, Kangning; Zhang, Yufen; Wang, Yan; Ling, Peng; Xie, Xin; Jiang, Chenyao; Zhang, Zhizhen; Lian, Xiao-Yuan

    2014-01-01

    The loss and injury of neurons play an important role in the onset of various neurodegenerative diseases, while both microgliosis and astrocyte loss or dysfunction are significant causes of neuronal degeneration. Previous studies have suggested that an extract enriched panaxadiol saponins from ginseng has more neuroprotective potential than the total saponins of ginseng. The present study investigated whether a fraction of highly purified panaxadiol saponins (termed as Rb fraction) was protective for both glia and neurons, especially GABAergic interneurons, against kainic acid (KA)-induced excitotoxicity in rats. Rats received Rb fraction at 30 mg/kg (i.p.), 40 mg/kg (i.p. or saline followed 40 min later by an intracerebroventricular injection of KA. Acute hippocampal injury was determined at 48 h after KA, and impairment of hippocampus-dependent learning and memory as well as delayed neuronal injury was determined 16 to 21 days later. KA injection produced significant acute hippocampal injuries, including GAD67-positive GABAergic interneuron loss in CA1, paralbumin (PV)-positive GABAergic interneuron loss, pyramidal neuron degeneration and astrocyte damage accompanied with reactive microglia in both CA1 and CA3 regions of the hippocampus. There was also a delayed loss of GAD67-positive interneurons in CA1, CA3, hilus and dentate gyrus. Microgliosis also became more severe 21 days later. Accordingly, KA injection resulted in hippocampus-dependent spatial memory impairment. Interestingly, the pretreatment with Rb fraction at 30 or 40 mg/kg significantly protected the pyramidal neurons and GABAergic interneurons against KA-induced acute excitotoxicity and delayed injury. Rb fraction also prevented memory impairments and protected astrocytes from KA-induced acute excitotoxicity. Additionally, microglial activation, especially the delayed microgliosis, was inhibited by Rb fraction. Overall, this study demonstrated that Rb fraction protected both astrocytes and neurons

  11. Timing of ketogenic diet initiation in an experimental epilepsy model.

    Science.gov (United States)

    Su, S W; Cilio, M R; Sogawa, Y; Silveira, D C; Holmes, G L; Stafstrom, C E; Silveira, D

    2000-12-29

    Following kainic acid (KA)-induced status epilepticus (SE), the ketogenic diet (KD) retards the development of epileptogenesis, with fewer spontaneous recurrent seizures (SRS) and less mossy fiber sprouting than rats on a normal diet. In this study, we investigated whether there is a critical period for initiation of the KD, in terms of the diet's effectiveness in reducing SRS. In addition, we investigated whether early treatment with the KD prevents the deficits in spatial learning and memory that ordinarily follow KA-induced SE. Young rats (P30) underwent KA-induced SE, followed by assignment to one of three treatment groups: control diet ('KA'), KD begun 2 days after SE ('KD2'), and KD begun fourteen days after SE ('KD14'). For 12 weeks following SE, rats were monitored by closed circuit video recording (12 h/wk) to detect SRS. KD2 rats had significantly fewer SRS than rats in the control or KD14 groups. On water maze testing to assess spatial learning and memory, KD2 rats had significantly poorer acquisition of place learning than control (KA alone) or KD14 rats. KD2 rats also failed to gain weight well. There was no difference between groups on routine histologic examination of the hippocampus. In summary, P30 rats placed on the KD 2 days after SE were relatively protected from recurrent seizures, but showed behavioral and physical impairment. Rats placed on the KD 14 days after KA-induced SE did not differ from controls with regard to spontaneous seizure rate.

  12. 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...

  13. 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...

  14. Nitric Oxide Regulates Neurogenesis in the Hippocampus following Seizures

    Directory of Open Access Journals (Sweden)

    Bruno P. Carreira

    2015-01-01

    Full Text Available Hippocampal neurogenesis is changed by brain injury. When neuroinflammation accompanies injury, activation of resident microglial cells promotes the release of inflammatory cytokines and reactive oxygen/nitrogen species like nitric oxide (NO. In these conditions, NO promotes proliferation of neural stem cells (NSC in the hippocampus. However, little is known about the role of NO in the survival and differentiation of newborn cells in the injured dentate gyrus. Here we investigated the role of NO following seizures in the regulation of proliferation, migration, differentiation, and survival of NSC in the hippocampus using the kainic acid (KA induced seizure mouse model. We show that NO increased the proliferation of NSC and the number of neuroblasts following seizures but was detrimental to the survival of newborn neurons. NO was also required for the maintenance of long-term neuroinflammation. Taken together, our data show that NO positively contributes to the initial stages of neurogenesis following seizures but compromises survival of newborn neurons.

  15. 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

  16. The SHH/Gli pathway is reactivated in reactive glia and drives proliferation in response to neurodegeneration-induced lesions.

    Science.gov (United States)

    Pitter, Kenneth L; Tamagno, Ilaria; Feng, Xi; Ghosal, Kaushik; Amankulor, Nduka; Holland, Eric C; Hambardzumyan, Dolores

    2014-10-01

    In response to neurodegeneration, the adult mammalian brain activates a cellular cascade that results in reactive astrogliosis and microgliosis. The mechanism through which astrocytes become reactive and the physiological consequences of their activation in response to neurodegeneration is complex. While the activation and proliferation of astrocytes has been shown to occur during massive neuronal cell death, the functional relationship between these two events has not been clearly elucidated. Here we show that in response to kainic acid- (KA) induced neurodegeneration, the mitogen sonic hedgehog (SHH) is upregulated in reactive astrocytes. SHH activity peaks at 7 days and is accompanied by increased Gli activity and elevated proliferation in several cell types. To determine the functional role of SHH-Gli signaling following KA lesions, we used a pharmacological approach to show that SHH secreted by astrocytes drives the activation and proliferation of astrocytes and microglia. The consequences of SHH-Gli signaling in KA-induced lesions appear to be independent of the severity of neurodegeneration.

  17. 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.

  18. 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...

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. Retigabine, a Kv7.2/Kv7.3-Channel Opener, Attenuates Drug-Induced Seizures in Knock-In Mice Harboring Kcnq2 Mutations.

    Science.gov (United States)

    Ihara, Yukiko; Tomonoh, Yuko; Deshimaru, Masanobu; Zhang, Bo; Uchida, Taku; Ishii, Atsushi; Hirose, Shinichi

    2016-01-01

    The hetero-tetrameric voltage-gated potassium channel Kv7.2/Kv7.3, which is encoded by KCNQ2 and KCNQ3, plays an important role in limiting network excitability in the neonatal brain. Kv7.2/Kv7.3 dysfunction resulting from KCNQ2 mutations predominantly causes self-limited or benign epilepsy in neonates, but also causes early onset epileptic encephalopathy. Retigabine (RTG), a Kv7.2/ Kv7.3-channel opener, seems to be a rational antiepileptic drug for epilepsies caused by KCNQ2 mutations. We therefore evaluated the effects of RTG on seizures in two strains of knock-in mice harboring different Kcnq2 mutations, in comparison to the effects of phenobarbital (PB), which is the first-line antiepileptic drug for seizures in neonates. The subjects were heterozygous knock-in mice (Kcnq2Y284C/+ and Kcnq2A306T/+) bearing the Y284C or A306T Kcnq2 mutation, respectively, and their wild-type (WT) littermates, at 63-100 days of age. Seizures induced by intraperitoneal injection of kainic acid (KA, 12mg/kg) were recorded using a video-electroencephalography (EEG) monitoring system. Effects of RTG on KA-induced seizures of both strains of knock-in mice were assessed using seizure scores from a modified Racine's scale and compared with those of PB. The number and total duration of spike bursts on EEG and behaviors monitored by video recording were also used to evaluate the effects of RTG and PB. Both Kcnq2Y284C/+ and Kcnq2A306T/+ mice showed significantly more KA-induced seizures than WT mice. RTG significantly attenuated KA-induced seizure activities in both Kcnq2Y284C/+ and Kcnq2A306T/+ mice, and more markedly than PB. This is the first reported evidence of RTG ameliorating KA-induced seizures in knock-in mice bearing mutations of Kcnq2, with more marked effects than those observed with PB. RTG or other Kv7.2-channel openers may be considered as first-line antiepileptic treatments for epilepsies resulting from KCNQ2 mutations.

  5. Retigabine, a Kv7.2/Kv7.3-Channel Opener, Attenuates Drug-Induced Seizures in Knock-In Mice Harboring Kcnq2 Mutations.

    Directory of Open Access Journals (Sweden)

    Yukiko Ihara

    Full Text Available The hetero-tetrameric voltage-gated potassium channel Kv7.2/Kv7.3, which is encoded by KCNQ2 and KCNQ3, plays an important role in limiting network excitability in the neonatal brain. Kv7.2/Kv7.3 dysfunction resulting from KCNQ2 mutations predominantly causes self-limited or benign epilepsy in neonates, but also causes early onset epileptic encephalopathy. Retigabine (RTG, a Kv7.2/ Kv7.3-channel opener, seems to be a rational antiepileptic drug for epilepsies caused by KCNQ2 mutations. We therefore evaluated the effects of RTG on seizures in two strains of knock-in mice harboring different Kcnq2 mutations, in comparison to the effects of phenobarbital (PB, which is the first-line antiepileptic drug for seizures in neonates. The subjects were heterozygous knock-in mice (Kcnq2Y284C/+ and Kcnq2A306T/+ bearing the Y284C or A306T Kcnq2 mutation, respectively, and their wild-type (WT littermates, at 63-100 days of age. Seizures induced by intraperitoneal injection of kainic acid (KA, 12mg/kg were recorded using a video-electroencephalography (EEG monitoring system. Effects of RTG on KA-induced seizures of both strains of knock-in mice were assessed using seizure scores from a modified Racine's scale and compared with those of PB. The number and total duration of spike bursts on EEG and behaviors monitored by video recording were also used to evaluate the effects of RTG and PB. Both Kcnq2Y284C/+ and Kcnq2A306T/+ mice showed significantly more KA-induced seizures than WT mice. RTG significantly attenuated KA-induced seizure activities in both Kcnq2Y284C/+ and Kcnq2A306T/+ mice, and more markedly than PB. This is the first reported evidence of RTG ameliorating KA-induced seizures in knock-in mice bearing mutations of Kcnq2, with more marked effects than those observed with PB. RTG or other Kv7.2-channel openers may be considered as first-line antiepileptic treatments for epilepsies resulting from KCNQ2 mutations.

  6. 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.

  7. 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

  8. The PARP inhibitor benzamide protects against kainate and NMDA but not AMPA lesioning of the mouse striatum in vivo.

    Science.gov (United States)

    Cosi, Cristina; Guerin, Karen; Marien, Marc; Koek, Wouter; Rollet, Karin

    2004-01-16

    Overactivation of poly(ADP-ribose) polymerase (PARP) in response to genotoxic insults can cause cell death by energy deprivation. We previously reported that neurotoxic amounts of kainic acid (KA) injected into the rat striatum produce time-dependent changes in striatal PARP activity in vivo. Here, we have investigated the time-course of KA-induced toxicity and the effects of the PARP inhibitor benzamide on KA, AMPA and NMDA neurotoxicities in vivo, by measuring changes in the volume of the lesion and in NAD+ and ATP levels induced by the intra-striatal injection of these excitotoxins in C57Bl/6N mice. The KA-induced lesion volume was dependent on the amount of toxin injected and the survival time. The lesion was well developed at 48 h and was almost undetectable after one week. KA produced an extensive astrogliosis at one week. Benzamide partially prevented both KA- and NMDA- but not AMPA-induced lesions when measured at 48 h after the treatment. The effects of benzamide appeared to be in part related to changes in energy metabolism, since KA produced decreases in striatal levels of NAD+ and ATP that were partially prevented by benzamide at 48 h and which returned to control levels at one week. NMDA did not affect NAD+ and induced little alteration in ATP levels. Benzamide had no effect on AMPA-induced decreases in either NAD+ or ATP levels at 48 h. These results (1) indicate that PARP overactivation and energy depletion could be responsible in part for the cellular demise during the development of the lesion induced by KA; (2) confirm that PARP is involved in NMDA but not AMPA toxicities; (3) suggest the existence of differences between KA and AMPA-mediated toxicities; and (4) provide further evidence supporting PARP as a novel target for new drug treatments against neurodegenerative disorders.

  9. Pharmacological preconditioning with GYKI 52466: a prophylactic approach to neuroprotection

    Directory of Open Access Journals (Sweden)

    Chelsea S Goulton

    2010-08-01

    Full Text Available Some toxins and drugs can trigger lasting neuroprotective mechanisms that enable neurons to resist a subsequent severe insult. This ‘pharmacological preconditioning’ has far-reaching implications for conditions in which blood flow to the brain is interrupted. We have previously shown that in vitro preconditioning with the AMPA receptor antagonist GYKI 52466 induces tolerance to kainic acid (KA toxicity in hippocampus. This effect persists well after washout of the drug and may be mediated via inverse agonism of G protein linked receptors. Given the amplifying nature of metabotropic modulation, we hypothesised that GYKI 52466 may be effective in reducing seizure severity at doses well below those normally associated with adverse side effects. Here we report that pharmacological preconditioning with low-dose GYKI imparts a significant protection against KA-induced seizures in vivo. GYKI (3 mg/kg, s.c., 90 to 180 min. prior to high-dose KA, markedly reduced seizure scores, virtually abolished all level 3 and level 4 seizures, and completely suppressed KA-induced hippocampal cFOS expression. In addition, preconditioned animals exhibited significant reductions in high frequency/high amplitude spiking and ECoG power in the delta, theta, alpha and beta bands during KA. Adverse behaviours often associated with higher doses of GYKI were not evident during preconditioning. The fact that GYKI is effective at doses well-below, and at pre-administration intervals well-beyond previous studies, suggests that a classical blockade of ionotropic AMPA receptors does not underlie anticonvulsant effects. Low-dose GYKI preconditioning may represent a novel, prophylactic strategy for neuroprotection in a field almost completely devoid of effective pharmaceuticals.

  10. Vulnerability of hippocampal GABA-ergic interneurons to kainate-induced excitotoxic injury during old age.

    Science.gov (United States)

    Shetty, Ashok K; Hattiangady, Bharathi; Rao, Muddanna S

    2009-08-01

    Hippocampal inhibitory interneurons expressing glutamate decarboxylase-67 (GAD-67) considerably decline in number during old age. Studies in young adult animals further suggest that hippocampal GAD-67+ interneuron population is highly vulnerable to excitotoxic injury. However, the relative susceptibility of residual GAD-67+ interneurons in the aged hippocampus to excitotoxic injury is unknown. To elucidate this, using both adult and aged F344 rats, we performed stereological counting of GAD-67+ interneurons in different layers of the dentate gyrus and CA1 & CA3 sub-fields, at 3 months post-excitotoxic hippocampal injury inflicted through an intracerebroventricular administration of kainic acid (KA). Substantial reductions of GAD-67+ interneurons were found in all hippocampal layers and sub-fields after KA-induced injury in adult animals. Contrastingly, there was no significant change in GAD-67+ interneuron population in any of the hippocampal layers and sub-fields following similar injury in aged animals. Furthermore, the stability of GAD-67+ interneurons in aged rats after KA was not attributable to milder injury, as the overall extent of KA-induced hippocampal principal neuron loss was comparable between adult and aged rats. Interestingly, because of the age-related disparity in vulnerability of interneurons to injury, the surviving GAD-67+ interneuron population in the injured aged hippocampus remained comparable to that observed in the injured adult hippocampus despite enduring significant reductions in interneuron number with aging. Thus, unlike in the adult hippocampus, an excitotoxic injury to the aged hippocampus does not result in significantly decreased numbers of GAD-67+ interneurons. Persistence of GAD-67+ interneuron population in the injured aged hippocampus likely reflects an age-related change in the response of GAD-67+ interneurons to excitotoxic hippocampal injury. These results have implications towards understanding mechanisms underlying the

  11. ent-kaur-16-en-19-oic acid, isolated from the roots of Aralia continentalis, induces activation of Nrf2

    Science.gov (United States)

    Lyu, Ji-Hyo; Lee, Guem-San; Kim, Kyun-Ha; Kim, Hyung-Woo; Cho, Su-In; Jeong, Seung-Il; Kim, Hong-Jun; Ju, Young-Seung; Kim, Ho-Kyoung; Sadikot, Ruxana T.; Christman, John W.; Oh, Sei-Ryang; Lee, Hyeong-Kyu; Ahn, Kyung-Seop; Joo, Myungsoo

    2013-01-01

    Aim of the study Excessive inflammation can lead to tissue damage and dysfunction of vital organs. Hence, regulating inflammatory response is a viable therapeutic approach. In Asian countries, various inflammatory diseases have often effectively been treated with herbal remedies including the root extract of Aralia continentalis Kitagawa (Araliaceae). Here, we investigated the effect of kaurenoic acid (ent-kaur-16-en-19-oic acid: KA), a diterpenoid that is extracted from Aralia continentalis Kitagawa root, on inflammation. Results Western blot and RT-PCR analyses show that KA induced the nuclear localization of Nrf2 as low as 1 nM in concentration and that KA treatment induced the expression of Nrf2 dependent genes such as GCLC and HO-1. On the other hand, KA did not affect the degradation of cytoplasmic IκB-α, the nuclear localization of RelA (p65), and NF-κB transcriptional activity in RAW 264.7 cells treated with endotoxin. Consistent with these data, KA treatment failed to suppress gene expression of representative pro-inflammatory mediators including COX-2, nitric oxide, IL-1β, TNF-α, and IL-12, indicating that KA did not have an important impact on NF-κB activation. Conclusion Together, these results show that KA was an effective activator of Nrf2, and suggest that the beneficial effects of A. continentalis Kitagawa root extract are, at least in part, mediated by activating Nrf2. PMID:21884778

  12. Intercellular Signaling Pathway among Endothelia, Astrocytes and Neurons in Excitatory Neuronal Damage

    Directory of Open Access Journals (Sweden)

    Kanato Yamagata

    2013-04-01

    Full Text Available Neurons interact closely with astrocytes via glutamate; this neuron-glia circuit may play a pivotal role in synaptic transmission. On the other hand, astrocytes contact vascular endothelial cells with their end-feet. It is becoming obvious that non-neuronal cells play a critical role in regulating the neuronal activity in the brain. We find that kainic acid (KA administration induces the expression of microsomal prostaglandin E synthase-1 (mPGES-1 in venous endothelial cells and the prostaglandin E2 (PGE2 receptor prostaglandin E receptor (EP-3 on astrocytes. Endothelial mPGES-1 exacerbates KA-induced neuronal damage in in vivo experiments. In in vitro experiments, mPGES-1 produces PGE2, which enhances astrocytic Ca2+ levels via the EP3 receptor and increases Ca2+-dependent glutamate release, thus aggravating neuronal injury. This novel endothelium-astrocyte-neuron signaling pathway may be crucial for driving neuronal damage after repetitive seizures and could be a new therapeutic target for epilepsy and other brain disorders.

  13. A subset of μ-opioid receptor-expressing cells in the rostral ventromedial medulla contribute to thermal hyperalgesia in experimental neuropathic pain.

    Science.gov (United States)

    Mase, Hiroshi; Sakai, Atsushi; Sakamoto, Atsuhiro; Suzuki, Hidenori

    2011-05-01

    The rostral ventromedial medulla (RVM) is a major region for the descending modulation of pain at the spinal cord level, and neurons in the RVM have been implicated in the inhibition and facilitation of spinal nociceptive transmission. Although recent studies have established that the RVM facilitation of nociceptive transmission in the spinal cord contributes to neuropathic pain, the underlying mechanisms remain largely unknown. In the present study, we investigated the effects of kainic acid (KA)-induced RVM damage on neuropathic pain behavior and the expression of molecules implicated in pain modulation. KA was injected into the RVM midline region after neuropathic pain was established by chronic constrictive injury of the left sciatic nerve. Thermal hyperalgesia, but not mechanical allodynia, was persistently suppressed in the ipsilateral paw by a single KA injection into the RVM for at least the next 7 days in a rat neuropathic pain model. KA injection alone did not affect the nocifensive responses to mechanical and thermal stimuli on the intact side. Immunohistochemical analysis revealed that KA injection into the RVM significantly reduced the number of immunoreactive neurons for μ-opioid receptors, but not tryptophan hydroxylase, in association with the analgesic effect. These results suggest that a subset of RVM neurons expressing μ-opioid receptors contribute to the maintenance of thermal hyperalgesia in neuropathic pain.

  14. Astrocytic Expression of CTMP Following an Excitotoxic Lesion in the Mouse Hippocampus

    Science.gov (United States)

    Shin, Nara; Yi, Min-Hee; Kim, Sena; Baek, Hyunjung; Triantafillu, Ursula L.

    2017-01-01

    Akt (also known as protein kinase B, PKB) has been seen to play a role in astrocyte activation of neuroprotection; however, the underlying mechanism on deregulation of Akt signaling in brain injuries is not fully understood. We investigated the role of carboxy-terminal modulator protein (CTMP), an endogenous Akt inhibitor, in brain injury following kainic acid (KA)-induced neurodegeneration of mouse hippocampus. In control mice, there was a weak signal for CTMP in the hippocampus, but CTMP was markedly increased in the astrocytes 3 days after KA treatment. To further investigate the effectiveness of Akt signaling, the phosphorylation of CTMP was examined. KA treatment induced an increased p-CTMP expression in the astrocytes of hippocampus at 1 day. LPS/IFN-γ-treatment on primary astrocytes promoted the p-CTMP was followed by phosphorylation of Akt and finally upregulation of CTMP and p-CREB. Time-dependent expression of p-CTMP, p-Akt, p-CREB, and CTMP indicate that LPS/IFN-γ-induced phosphorylation of CTMP can activate Akt/CREB signaling, whereas lately emerging enhancement of CTMP can inhibit it. These results suggest that elevation of CTMP in the astrocytes may suppress Akt activity and ultimately negatively affect the outcome of astrocyte activation (astroglisiois). Early time point enhancers of phosphorylation of CTMP and/or late time inhibitors specifically targeting CTMP may be beneficial in astrocyte activation for neuroprotection within treatment in neuroinflammatory conditions.

  15. Anticonvulsant action of Dingxianning Keliji%定痫宁颗粒剂抗癫痫作用的实验研究

    Institute of Scientific and Technical Information of China (English)

    周大兴; 金国梁; 方伟

    2001-01-01

    目的:研究定痫宁颗粒剂的抗癫痫作用。方法:采用海人酸(KA)所致癫痫、最大电休克发作(maximal electroshock seizure, MES)、戊四氮最小阈发作(metrazol minimal threshold seizure, MET)以及士的宁惊厥为指标,观察定痫宁的抗癫痫作用。结果:定痫宁能显著抑制海人酸所致大鼠癫痫发作,对抗大鼠、小鼠的最大电休克发作和小鼠的戊四氮最小阈发作、士的宁的惊厥反应。结论:定痫宁具有明显的抗癫痫作用。%Objective: To observe the anticonvulsant action of Dingxianning Keliji (DXNKLJ). Methonds: The anticonvulsant action of DXNKLJ was investigated in Maximal Electroshock seizure (MES), Kainic acid (Ka)-induced convusion, strychine-induced convulsion, and Metrazol threshold seizure (MET), respectively. Results: DXNKLJ (24、16、8g/kg) had an obvious effect against MES in both mice or rats and MET in mice, had an antagonism tokainic acid、strychinine-induced convuision also. Conclusion: DXNKLJ had an obvious anticonvulsant effect.

  16. Naringin attenuates granule cell dispersion in the dentate gyrus in a mouse model of temporal lobe epilepsy.

    Science.gov (United States)

    Jang, Hannah; Jeong, Kyoung Hoon; Kim, Sang Ryong

    2016-07-01

    Morphological abnormalities of the dentate gyrus (DG) are an important phenotype in the hippocampus of patients with temporal lobe epilepsy. We recently reported that naringin, a bioflavonoid in grapefruit and citrus fruits, exerts beneficial effects in the kainic acid (KA) mouse model of epilepsy. We found that naringin treatment reduced seizure activities and decreased autophagic stress and neuroinflammation in the hippocampus following in vivo lesion with KA. However, it remains unclear whether naringin may also attenuate seizure-induced morphological changes in the DG, collectively known as granule cell dispersion (GCD). To clarify whether naringin treatment reduces GCD, we evaluated the effects of intraperitoneal injection of naringin on GCD and activation of mammalian target of rapamycin complex 1 (mTORC1), an important regulator of GCD, following intrahippocampal injection of KA. Our results showed that naringin treatment significantly reduced KA-induced GCD and mTORC1 activation, which was confirmed by assessing the phosphorylated form of the mTORC1 substrate, 4E-BP1, in the hippocampus. These results suggest that naringin treatment may help prevent epilepsy-induced hippocampal injury by inhibiting mTORC1 activation and thereby reducing GCD in the hippocampus in vivo.

  17. Decisive role of apurinic/apyrimidinic endonuclease/Ref-1 in initiation of cell death.

    Science.gov (United States)

    Cho, Kyoung Joo; Kim, Hyun Jeong; Park, Soo Chul; Kim, Hyun Woo; Kim, Gyung Whan

    2010-11-01

    The apurinic/apyrimidinic endonuclease/redox effector factor-1 (APE/Ref-1) is involved in the base excision repair of apurinic/apyrimidinic sites induced by oxidative DNA damage. APE/Ref-1 was decreased by kainic acid (KA) injury in a time-dependent manner at the level of proteins, not transcripts. We investigated whether alteration of APE/Ref-1 amounts would influence hippocampal cell fate, survival or death, after KA injury. Overexpression of APE/Ref-1 using adenovirus and restoration of APE small peptides significantly reduced KA-induced hippocampal cell death. Both silencing of APE/Ref-1 by siRNA and inhibition of endonuclease by an antibody significantly increased caspase-3 activity and apoptotic cell death triggered from the early time after exposure to KA. These findings suggest that cell death is initiated by reducing APE/Ref-1 protein and inhibiting its repair function in spite of enough protein amounts. In conclusion, APE/Ref-1 may be a regulator of cell death initiation, and APE small peptides could provide molecular mechanism-based therapies for neuroprotection in progressive excitotoxic neuronal damage.

  18. c-fos modulates brain-derived neurotrophic factor mRNA expression in mouse hippocampal CA3 and dentate gyrus neurons.

    Science.gov (United States)

    Dong, Mei; Wu, Yongfei; Fan, Yunxia; Xu, Ming; Zhang, Jianhua

    2006-05-29

    Excess neuronal excitation by glutamate induces neuron cell death, which may contribute to the pathogenesis of acute brain injuries and neurodegenerative diseases. Our previous studies using a mouse with hippocampal c-fos gene deletion showed that c-fos regulates neuronal excitability and excitotoxicity. Moreover, a delayed induction of brain-derived neurotrophic factor (BDNF) protein expression in response to kainic acid (KA) treatment was found in c-fos mutant mice compared to wildtype controls, suggesting that c-fos is important in the temporal control of BDNF induction. To further investigate mechanisms of in vivo regulation of c-fos on BDNF expression, we studied the expression of BDNF mRNA and its colocalization with c-Fos protein in the hippocampal formation in the presence and absence of KA. By in situ hybridization, we observed that the c-fos mutant and wildtype mice exhibited similar basal expression of BDNF in the absence of KA. In contrast, the KA-induced BDNF mRNA levels were significantly different in wildtype and c-fos mutant mice in CA3 and dentate gyrus regions. Our findings indicate that c-fos regulates expression of BDNF in distinct neuron populations of the hippocampal formation in vivo.

  19. 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.

  20. 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 ...

  1. 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 . ...

  2. 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 ...

  3. 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 ...

  4. 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. ...

  5. 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 ...

  6. 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 ...

  7. 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 ...

  8. 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: ...

  9. 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.

  10. 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...

  11. 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, ...

  12. 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 ...

  13. 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 ...

  14. 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....

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. HMGB1 Contributes to the Expression of P-Glycoprotein in Mouse Epileptic Brain through Toll-Like Receptor 4 and Receptor for Advanced Glycation End Products.

    Directory of Open Access Journals (Sweden)

    Yan Chen

    Full Text Available The objective of the present study was to investigate the role of high-mobility group box-1 (HMGB1 in the seizure-induced P-glycoprotein (P-gp overexpression and the underlying mechanism. Kainic acid (KA-induced mouse seizure model was used for in vivo experiments. Male C57BL/6 mice were divided into four groups: normal saline control (NS group, KA-induced epileptic seizure (EP group, and EP group pretreated with HMGB1 (EP+HMGB1 group or BoxA (HMGB1 antagonist, EP+BoxA group. Compared to the NS group, increased levels of HMGB1 and P-gp in the brain were observed in the EP group. Injection of HMGB1 before the induction of KA further increased the expression of P-gp while pre-treatment with BoxA abolished this up-regulation. Next, the regulatory role of HMGB1 and its potential involved signal pathways were investigated in mouse microvascular endothelial bEnd.3 cells in vitro. Cells were treated with HMGB1, HMGB1 plus lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS [toll-like receptor 4 (TLR4 antagonist], HMGB1 plus FPS-ZM1 [receptor for advanced glycation end products (RAGE inhibitor], HMGB1 plus SN50 [nuclear factor-kappa B (NF-κB inhibitor], or vehicle. Treatment with HMGB1 increased the expression levels of P-gp, TLR4, RAGE and the activation of NF-κB in bEnd.3 cells. These effects were inhibited by the pre-treatment with either LPS-RS or FPS-ZM1, and were abolished by the pre-treatment of SN50 or a combination treatment of both LPS-RS and FPS-ZM1. Luciferase reporter assays showed that exogenous expression of NF-κB p65 increased the promoter activity of multidrug resistance 1a (P-gp-encoding gene in endothelial cells. These data indicate that HMGB1 contributes to the overexpression of P-gp in mouse epileptic brain tissues via activation of TLR4/RAGE receptors and the downstream transcription factor NF-κB in brain microvascular endothelial cells.

  1. Both prolactin (PRL) and a molecular mimic of phosphorylated PRL, S179D-PRL, protect the hippocampus of female rats against excitotoxicity.

    Science.gov (United States)

    Morales, T; Lorenson, M; Walker, A M; Ramos, E

    2014-01-31

    Prolactin (PRL) has many functions in the CNS, including neuroprotection. During lactation, the dorsal hippocampus is protected from excitotoxic kainic acid (KA)-induced cellular damage. We have previously reported that systemic pre-treatment with ovine PRL had similar protective effects in female rats. Here, we asked (1) whether intracerebral human PRL (hPRL) would have the same action, (2) because phosphorylated PRL is high in lactation, whether a mimic of phosphorylated hPRL, human prolactin in which the normally phosphorylated serine at position 179 is replaced with an aspartate (S179D-PRL), had similar activity, and (3) what signaling pathways mediated the protective effect. Female ovariectomized (OVX, 1 month) rats were implanted with micro-osmotic pumps connected to unilateral icv cannulae directed at the right lateral ventricle. The pumps delivered 0.10 ng/h of hPRL, S179D-PRL, a combination of hPRL+S179D-PRL, or saline vehicle for 7 days prior to a systemic dose of 7.5mg/kg of KA. Rats were sacrificed 48 h after KA injection. Immunostaining for neuronal nuclei (Neu-N) revealed a significant KA-induced decrease in cell number in the CA1, CA3, and CA4 hippocampal areas of rats (∼55% of control). Treatment with either hPRL or S179D-PRL or the combination prevented the damaging effect of KA in these hippocampal regions (∼95% of corresponding control), but was not completely effective at preventing early seizure-related behaviors such as staring and wet dog shakes. Analysis of signals generated by hPRL and S179D-PRL showed no activation of signal transducer and activation of transcription 5 (Stat5) or other signaling molecules in the hippocampus, but activation of extracellular-regulated kinase (ERK)1/2 in the amygdala. These results support a central protective effect of both PRL forms and suggest that PRL could be exerting its protective action by indirectly modulating input signals to the hippocampus and thus regulating excitability.

  2. Cyclooxygenase-2 expression in oligodendrocytes increases sensitivity to excitotoxic death

    Directory of Open Access Journals (Sweden)

    Rojas Monica A

    2010-04-01

    Full Text Available Abstract Background We previously found that cyclooxygenase 2 (COX-2 was expressed in dying oligodendrocytes at the onset of demyelination in the Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD model of multiple sclerosis (MS (Carlson et al. J.Neuroimmunology 2006, 149:40. This suggests that COX-2 may contribute to death of oligodendrocytes. Objective The goal of this study was to examine whether COX-2 contributes to excitotoxic death of oligodendrocytes and potentially contributes to demyelination. Methods The potential link between COX-2 and oligodendrocyte death was approached using histopathology of MS lesions to examine whether COX-2 was expressed in dying oligodendrocytes. COX-2 inhibitors were examined for their ability to limit demyelination in the TMEV-IDD model of MS and to limit excitotoxic death of oligodendrocytes in vitro. Genetic manipulation of COX-2 expression was used to determine whether COX-2 contributes to excitotoxic death of oligodendrocytes. A transgenic mouse line was generated that overexpressed COX-2 in oligodendrocytes. Oligodendrocyte cultures derived from these transgenic mice were used to examine whether increased expression of COX-2 enhanced the vulnerability of oligodendrocytes to excitotoxic death. Oligodendrocytes derived from COX-2 knockout mice were evaluated to determine if decreased COX-2 expression promotes a greater resistance to excitotoxic death. Results COX-2 was expressed in dying oligodendrocytes in MS lesions. COX-2 inhibitors limited demyelination in the TMEV-IDD model of MS and protected oligodendrocytes against excitotoxic death in vitro. COX-2 expression was increased in wild-type oligodendrocytes following treatment with Kainic acid (KA. Overexpression of COX-2 in oligodendrocytes increased the sensitivity of oligodendrocytes to KA-induced excitotoxic death eight-fold compared to wild-type. Conversely, oligodendrocytes prepared from COX-2 knockout mice showed a

  3. 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 ...

  4. 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.

  5. 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.

  6. An adeno-associated virus-based intracellular sensor of pathological nuclear factor-κB activation for disease-inducible gene transfer.

    Directory of Open Access Journals (Sweden)

    Abdelwahed Chtarto

    Full Text Available Stimulation of resident cells by NF-κB activating cytokines is a central element of inflammatory and degenerative disorders of the central nervous system (CNS. This disease-mediated NF-κB activation could be used to drive transgene expression selectively in affected cells, using adeno-associated virus (AAV-mediated gene transfer. We have constructed a series of AAV vectors expressing GFP under the control of different promoters including NF-κB -responsive elements. As an initial screen, the vectors were tested in vitro in HEK-293T cells treated with TNF-α. The best profile of GFP induction was obtained with a promoter containing two blocks of four NF-κB -responsive sequences from the human JCV neurotropic polyoma virus promoter, fused to a new tight minimal CMV promoter, optimally distant from each other. A therapeutical gene, glial cell line-derived neurotrophic factor (GDNF cDNA under the control of serotype 1-encapsidated NF-κB -responsive AAV vector (AAV-NF was protective in senescent cultures of mouse cortical neurons. AAV-NF was then evaluated in vivo in the kainic acid (KA-induced status epilepticus rat model for temporal lobe epilepsy, a major neurological disorder with a central pathophysiological role for NF-κB activation. We demonstrate that AAV-NF, injected in the hippocampus, responded to disease induction by mediating GFP expression, preferentially in CA1 and CA3 neurons and astrocytes, specifically in regions where inflammatory markers were also induced. Altogether, these data demonstrate the feasibility to use disease-activated transcription factor-responsive elements in order to drive transgene expression specifically in affected cells in inflammatory CNS disorders using AAV-mediated gene transfer.

  7. Differential susceptibility of interneurons expressing neuropeptide Y or parvalbumin in the aged hippocampus to acute seizure activity.

    Directory of Open Access Journals (Sweden)

    Ramkumar Kuruba

    Full Text Available Acute seizure (AS activity in old age has an increased predisposition for evolving into temporal lobe epilepsy (TLE. Furthermore, spontaneous seizures and cognitive dysfunction after AS activity are often intense in the aged population than in young adults. This could be due to an increased vulnerability of inhibitory interneurons in the aged hippocampus to AS activity. We investigated this issue by comparing the survival of hippocampal GABA-ergic interneurons that contain the neuropeptide Y (NPY or the calcium binding protein parvalbumin (PV between young adult (5-months old and aged (22-months old F344 rats at 12 days after three-hours of AS activity. Graded intraperitoneal injections of the kainic acid (KA induced AS activity and a diazepam injection at 3 hours after the onset terminated AS-activity. Measurement of interneuron numbers in different hippocampal subfields revealed that NPY+ interneurons were relatively resistant to AS activity in the aged hippocampus in comparison to the young adult hippocampus. Whereas, PV+ interneurons were highly susceptible to AS activity in both age groups. However, as aging alone substantially depleted these populations, the aged hippocampus after three-hours of AS activity exhibited 48% reductions in NPY+ interneurons and 70% reductions in PV+ interneurons, in comparison to the young hippocampus after similar AS activity. Thus, AS activity-induced TLE in old age is associated with far fewer hippocampal NPY+ and PV+ interneuron numbers than AS-induced TLE in the young adult age. This discrepancy likely underlies the severe spontaneous seizures and cognitive dysfunction observed in the aged people after AS activity.

  8. Differential susceptibility of interneurons expressing neuropeptide Y or parvalbumin in the aged hippocampus to acute seizure activity.

    Science.gov (United States)

    Kuruba, Ramkumar; Hattiangady, Bharathi; Parihar, Vipan K; Shuai, Bing; Shetty, Ashok K

    2011-01-01

    Acute seizure (AS) activity in old age has an increased predisposition for evolving into temporal lobe epilepsy (TLE). Furthermore, spontaneous seizures and cognitive dysfunction after AS activity are often intense in the aged population than in young adults. This could be due to an increased vulnerability of inhibitory interneurons in the aged hippocampus to AS activity. We investigated this issue by comparing the survival of hippocampal GABA-ergic interneurons that contain the neuropeptide Y (NPY) or the calcium binding protein parvalbumin (PV) between young adult (5-months old) and aged (22-months old) F344 rats at 12 days after three-hours of AS activity. Graded intraperitoneal injections of the kainic acid (KA) induced AS activity and a diazepam injection at 3 hours after the onset terminated AS-activity. Measurement of interneuron numbers in different hippocampal subfields revealed that NPY+ interneurons were relatively resistant to AS activity in the aged hippocampus in comparison to the young adult hippocampus. Whereas, PV+ interneurons were highly susceptible to AS activity in both age groups. However, as aging alone substantially depleted these populations, the aged hippocampus after three-hours of AS activity exhibited 48% reductions in NPY+ interneurons and 70% reductions in PV+ interneurons, in comparison to the young hippocampus after similar AS activity. Thus, AS activity-induced TLE in old age is associated with far fewer hippocampal NPY+ and PV+ interneuron numbers than AS-induced TLE in the young adult age. This discrepancy likely underlies the severe spontaneous seizures and cognitive dysfunction observed in the aged people after AS activity.

  9. Control of Granule Cell Dispersion by Natural Materials Such as Eugenol and Naringin: A Potential Therapeutic Strategy Against Temporal Lobe Epilepsy.

    Science.gov (United States)

    Kim, Sang Ryong

    2016-08-01

    The hippocampus is an important brain area where abnormal morphological characteristics are often observed in patients with temporal lobe epilepsy (TLE), typically showing the loss of the principal neurons in the CA1 and CA3 areas of the hippocampus. TLE is frequently associated with widening of the granule cell layer of the dentate gyrus (DG), termed granule cell dispersion (GCD), in the hippocampus, suggesting that the control of GCD with protection of hippocampal neurons may be useful for preventing and inhibiting epileptic seizures. We previously reported that eugenol (EUG), which is an essential component of medicinal herbs and has anticonvulsant activity, is beneficial for treating epilepsy through its ability to inhibit GCD via suppression of mammalian target of rapamycin complex 1 (mTORC1) activation in the hippocampal DG in a kainic acid (KA)-treated mouse model of epilepsy in vivo. In addition, we reported that naringin, a bioflavonoid in citrus fruits, could exert beneficial effects, such as antiautophagic stress and antineuroinflammation, in the KA mouse model of epilepsy, even though it was unclear whether naringin might also attenuate the seizure-induced morphological changes of GCD in the DG. Similar to the effects of EUG, we recently observed that naringin treatment significantly reduced KA-induced GCD and mTORC1 activation, which are both involved in epileptic seizures, in the hippocampus of mouse brain. Therefore, these observations suggest that the utilization of natural materials, which have beneficial properties such as inhibition of GCD formation and protection of hippocampal neurons, may be useful in developing a novel therapeutic agent against TLE.

  10. 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....

  11. [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.

  12. 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 ...

  13. 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 ...

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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…

  1. 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…

  2. 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 ...

  3. 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 ...

  4. 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 ...

  5. 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.

  6. 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 ...

  7. 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 ...

  8. 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 ...

  9. 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 ...

  10. 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...

  11. 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)…

  12. 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/ ...

  13. 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 ...

  14. 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…

  15. 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)…

  16. 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.

  17. 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.

  18. [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.

  19. 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.

  20. 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.

  1. Comparison of excitotoxic profiles of ATPA, AMPA, KA and NMDA in organotypic hippocampal slice cultures.

    Science.gov (United States)

    Kristensen, B W; Noraberg, J; Zimmer, J

    2001-10-26

    The excitotoxic profiles of (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propionic acid (ATPA), (RS)-2-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), kainic acid (KA) and N-methyl-D-aspartate (NMDA) were evaluated using cellular uptake of propidium iodide (PI) as a measure for induced, concentration-dependent neuronal damage in hippocampal slice cultures. ATPA is in low concentrations a new selective agonist of the glutamate receptor subunit GluR5 confined to KA receptors and also in high concentrations an AMPA receptor agonist. The following rank order of estimated EC(50) values was found after 2 days of exposure: AMPA (3.7 mM)>NMDA (11 mM)=KA (13 mM)>ATPA (33 mM). Exposed to 30 microM ATPA, 3 microM AMPA and 10 microM NMDA, CA1 was the most susceptible subfield followed by fascia dentata and CA3. Using 8 microM KA, CA3 was the most susceptible subfield, followed by fascia dentata and CA1. In 100 microM concentrations, all four agonists induced the same, maximal PI uptake in all hippocampal subfields, corresponding to total neuronal degeneration. Using glutamate receptor antagonists, like GYKI 52466, NBQX and MK-801, inhibition data revealed that AMPA excitotoxicity was mediated primarily via AMPA receptors. Similar results were found for a high concentration of ATPA (30 microM). In low GluR5 selective concentrations (0.3-3 microM), ATPA did not induce an increase in PI uptake or a reduction in glutamic acid decarboxylase (GAD) activity of hippocampal interneurons. For KA, the excitotoxicity appeared to be mediated via both KA and AMPA receptors. NMDA receptors were not involved in AMPA-, ATPA- and KA-induced excitotoxicity, nor did NMDA-induced excitotoxicity require activation of AMPA and KA receptors. We conclude that hippocampal slice cultures constitute a feasible test system for evaluation of excitotoxic effects and mechanisms of new (ATPA) and classic (AMPA, KA and NMDA) glutamate receptor agonists. Comparison of concentration

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. EXPRESSIONOF TRKB AND P75NTR IN HIPPOCAMPUS OF RAT MODEL OF TEMPORAL LOBE EPILEPSY AND THE EFFECT OF TOPIRAMATE%TrkB、P75NTR在颞叶癫痫大鼠海马中的表达及托吡酯干预的研究

    Institute of Scientific and Technical Information of China (English)

    余璐; 梁秀琳; 郑金瓯

    2012-01-01

    目的:研究托吡酯(TPM)干预红藻氨酸(KA)致大鼠颞叶癫痫(TLE)后海马组织学变化特征及脑源性神经营养因子(BDNF)受体TrkB、P75NTR蛋白在大鼠海马内的表达,探讨TrkB及P75NTR在TLE中的作用及TPM的抗痫机制.方法:KA诱导建立TLE模型,观察大鼠行为学改变;于1 d,1,2,3,4周时间点,用免疫组化法观察各组大鼠TrkB、P75NTR蛋白在海马内表达的改变,Nissl染色观察海马神经元丢失的变化.结果:(1)TPM干预后KA致痫大鼠发作减少.(2)KA致痫后海马神经元丢失以门区和CA1区为主,4周达高峰;TPM干预后海马神经元损伤明显减少.(3)致痫后,TrkB的表达于1 d至4周在齿状回门区、CA3区明显增高(P<0.01),持续4周,在CA1区仅1 d时增高(P<0.01);P75NTR的表达在PoDG、CA1区、CA3区明显增高(P<0.01),并在PoDG和CA3区持续至2周(P<0.05);TPM干预后TrkB、P75NTR于上述各区在时间和空间上的表达均明显减少.结论:致痫后,海马内TrkB和P75NTR的持续较长时间表达增高通过其受体起作用,可能有助于癫痫异常兴奋性网络的形成.TPM干预对海马神经元损伤有明显的保护作用,其机制可能为通过下调海马内TrkB和P75NTR的表达,减少海马神经元损伤从而对癫痫发展起潜在的神经保护作用.%To investigate the characteristics of the histological changes and the brain derived neu-rotrophic factor (BDNF) receptor TrkB and P75NTR expression in hippocampus of a temporal lobe epilepsy (TLE) rat model induced by kainic acid (KA) after topiramate (TPM) intervention; and explore the effect of TrkB and P75NTR in TLE and the antiepileptic mechanism of topiramate. Methods: Adult rats were made to be a model of TLE by KA inducing status epilepticus. Behavioral changes were observed. TrkB and P75NTR protein was studied by immunohistochemistry at time points of Id, lw, 2w, 3w and 4w. Hipp-ocampal neuron loss was detected by Nissl's staining. Results: (1) epileptic seizures were

  11. Mechanism of hypothalamic paraventricular nucleus in regulating asthmatic attack

    Institute of Scientific and Technical Information of China (English)

    Jia Liu; Rong Dong; Jian Xiao; Nina Liu

    2006-01-01

    BACKGROUD: It has been confirmed that c-fos expession increased markedly in hypothalamic paraventricular nucleus(PVN)during asthmatic attack in rats,and PVN has extensive physiological functions,involving in the regulation of respiratory system,etc.OBJECTIVE: To observe the alteration of electroencephalogram(EEG)and power spectra in PVN during the asthmatic attack,and the alteraiton of lung function and diaphragmatic muscle discharge after bilateral PVN lesion in asthmatic rats.DESIGN:A randomized control study.SETTING: Laboratory of Physiology and Pharmacology,School of Basic Medical Sciences,Southeast University.MATERIALS: Forty-eight male adult SD rats of 260-300g were used.The rats were randomly divided into 6 groups(n=8):control group,asthma group,electrolytic lesion of PVN group,KA-induced lesion of PVN group,sham electrolytic lesion of PVN group and sham kainic acid(KA)-induced lesion of PVN group.KA,chicken ovalbumin and aluminum hydroxide were purchased from American Sigma Company.Bordetella pertrssis vaccine (Institute of Biological Products of Shanghai);stereotaxic apparartus (Jianwan Ⅱ,China);Iesion-producing device (YC-2 programmable stimulato,Chengdu Iustrument Company);MD2000 signal processing system(Nanjing Medical School); data acquisition system (RM6240B,Chengdu Instrument Company).METHODS:The experiments were carried out in the Laboratory of Physiology and Pharmacology,School of Basic Medical Sciences,Southeast University from January to August in 2006.①Rats except for control group were sensitized with an intraperitoneal injection of 100 mg chicken ovalbumin and 100 mg aluminum hydroxide and Bordetella pertussis vaccine containing 5×109 heat-killed in 1 mL of sterile saline.From the fifteenth to seventeenth days rats received three times aerosolized ovalbumin challenge. In rats of the control group and asthma group three steel electrodes were placed into the left PVN(AP-1.8 mm,LR 0.4 mm,OH-7.9 mm).parietal cortex and subcutaneous tissue in

  12. 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

  13. 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....

  14. 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....

  15. 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....

  16. 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...

  17. 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 ...

  18. 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 ...

  19. 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

  20. 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;…

  1. 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...

  2. 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....

  3. 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...

  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. 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

  6. 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...

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  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....

  1. (boric acid) against Blattella germanica

    African Journals Online (AJOL)

    ufuoma

    2013-05-01

    May 1, 2013 ... study of the ovaries was done following the toxicity assays after having evaluated the toxicity of the boric acid ... Key words: German cockroach, boric acid, reproduction, ovary, biochemical. ... MATERIALS AND METHODS.

  2. Enzymic Synthesis of Caffeoylglucaric Acid from Chlorogenic Acid and Glucaric Acid by a Protein Preparation from Tomato Cotyledons 1

    Science.gov (United States)

    Strack, Dieter; Gross, Wiltrud; Wray, Victor; Grotjahn, Lutz

    1987-01-01

    The phenylpropane metabolism of tomato (Lycopersicon esculentum Mill) cotyledons was investigated. The HPLC analysis revealed two hydroxycinnamic-acid conjugates as major components, identified as chlorogenic acid (5-O-caffeoylquinic acid) and caffeoylglucaric acid (2-O- or 5-O-caffeoyl-glucaric acid). Quantitative analyses indicated a precursor-product relationship between the chlorogenic and caffeoylglucaric acids. Protein preparations from tomato cotyledons were found to catalyze the formation of caffeoylglucaric acid with chlorogenic acid as acyl donor and free glucaric acid as acceptor molecule. This enzyme activity, possibly to be classified as hydroxycinnamoylquinic acid:glucaric acid hydroxycinnamoyltransferase, acts together with hydroxycinnamoyl-CoA: quinic acid hydroxycinnamoyltransferase. PMID:16665274

  3. Biological properties of lipoic acid

    Directory of Open Access Journals (Sweden)

    Anna Bilska

    2002-06-01

    Full Text Available Lipoic acid is a prostetic group of H-protein of the glycine cleavage system and the dihydrolipoamide acyltransferases (E2 of the pyruvate, alpha-ketoglutarate and branched-chain alpha-keto acid dehydrogenase complexes. Lipoic acid and its reduced form, dihydrolipoic acid, reacts with oxygen reactive species. This paper reviews the beneficial effects in oxidative stress models or clinical conditions.

  4. Lewis Acid Catalyzed Benzylic Bromination

    OpenAIRE

    Shibatomi, Kazutaka; Zhang, Yanhua; Yamamoto, Hisashi

    2008-01-01

    Lewis acid catalyzed bromination on aromatic side chain was achieved efficiently by using 1,3-dibromo-5,5-dimethylhydantoin (DBDMH) as a bromination reagent under mild conditions. Zirconium(IV) chloride showed the highest catalytic activity for the benzylic bromination. It was revealed that the present Lewis acid catalysis proceeds via the radical generation pathway. In contrast to Lewis acid catalysis, Brønsted acid promoted aromatic ring bromination without any benzylic bromination. Monobro...

  5. LACTIC ACID BACTERIA: PROBIOTIC APPLICATIONS

    OpenAIRE

    NEENA GARG

    2015-01-01

    Lactic acid bacteria (LAB) is a heterotrophic Gram-positive bacteria which under goes lactic acid fermentations and leads to production of lactic acid as an end product. LAB includes Lactobacillus, Leuconostoc, Pediococcus, Lactococcus and Streptococcus which are grouped together in the family lactobacillaceae. LAB shows numerous antimicrobial activities due to production of antibacterial and antifungal compounds such as organic acids, bacteriocins, diacetyl, hydrogen peroxide and reutrin. LA...

  6. Acids and bases solvent effects on acid-base strenght

    CERN Document Server

    Cox, Brian G

    2013-01-01

    Acids and bases are ubiquitous in chemistry. Our understanding of them, however, is dominated by their behaviour in water. Transfer to non-aqueous solvents leads to profound changes in acid-base strengths and to the rates and equilibria of many processes: for example, synthetic reactions involving acids, bases and nucleophiles; isolation of pharmaceutical actives through salt formation; formation of zwitter- ions in amino acids; and chromatographic separation of substrates. This book seeks to enhance our understanding of acids and bases by reviewing and analysing their behaviour in non-aqueous solvents. The behaviour is related where possible to that in water, but correlations and contrasts between solvents are also presented.

  7. Fumaric acid production by fermentation

    NARCIS (Netherlands)

    Roa Engel, C.A.; Straathof, A.J.J.; Zijlmans, T.W.; Van Gulik, W.M.; Van der Wielen, L.A.M.

    2008-01-01

    Abstract The potential of fumaric acid as a raw material in the polymer industry and the increment of cost of petroleum-based fumaric acid raises interest in fermentation processes for production of this compound from renewable resources. Although the chemical process yields 112% w/w fumaric acid fr

  8. Pantothenic acid biosynthesis in zymomonas

    Energy Technology Data Exchange (ETDEWEB)

    Tao, Luan; Tomb, Jean-Francois; Viitanen, Paul V.

    2014-07-01

    Zymomonas is unable to synthesize pantothenic acid and requires this essential vitamin in growth medium. Zymomonas strains transformed with an operon for expression of 2-dehydropantoate reductase and aspartate 1-decarboxylase were able to grow in medium lacking pantothenic acid. These strains may be used for ethanol production without pantothenic acid supplementation in seed culture and fermentation media.

  9. Acid Rain Limits Global Warming

    Institute of Scientific and Technical Information of China (English)

    Will Knight; 张林玲

    2004-01-01

    @@ Acid rain restricts global warming by reducing methane① emissions from natural wetland areas, suggests a global climate study. Acid rain is the result of industrial pollution,which causes rainwater to carry small quantities of acidic compoumds② such as sulphuric and nitric acid③. Contaminated rainwater can upset rivers and lakes, killing fish and other organisms and also damage plants, trees and buildings.

  10. Microbial degradation of poly(amino acid)s.

    Science.gov (United States)

    Obst, Martin; Steinbüchel, Alexander

    2004-01-01

    Natural poly(amino acid)s are a group of poly(ionic) molecules (ionomers) with various biological functions and putative technical applications and play, therefore, an important role both in nature and in human life. Because of their biocompatibility and their synthesis from renewable resources, poly(amino acid)s may be employed for many different purposes covering a broad spectrum of medical, pharmaceutical, and personal care applications as well as the domains of agriculture and of environmental applications. Biodegradability is one important advantage of naturally occurring poly(amino acid)s over many synthetic polymers. The intention of this review is to give an overview about the enzyme systems catalyzing the initial steps in poly(amino acid) degradation. The focus is on the naturally occurring poly(amino acid)s cyanophycin, poly(epsilon-L-lysine) and poly(gamma-glutamic acid); but biodegradation of structurally related synthetic polyamides such as poly(aspartic acid) and nylons, which are known from various technical applications, is also included.

  11. Molecular Interaction of Pinic Acid with Sulfuric Acid

    DEFF Research Database (Denmark)

    Elm, Jonas; Kurten, Theo; Bilde, Merete

    2014-01-01

    We investigate the molecular interactions between the semivolatile α-pinene oxidation product pinic acid and sulfuric acid using computational methods. The stepwise Gibbs free energies of formation have been calculated utilizing the M06-2X functional, and the stability of the clusters is evaluated...... from the corresponding ΔG values. The first two additions of sulfuric acid to pinic acid are found to be favorable with ΔG values of -9.06 and -10.41 kcal/mol. Addition of a third sulfuric acid molecule is less favorable and leads to a structural rearrangement forming a bridged sulfuric acid-pinic acid...... cluster. The involvement of more than one pinic acid molecule in a single cluster is observed to lead to the formation of favorable (pinic acid)2(H2SO4) and (pinic acid)2(H2SO4)2 clusters. The identified most favorable growth paths starting from a single pinic acid molecule lead to closed structures...

  12. Heterogeneous uptake of amines by citric acid and humic acid.

    Science.gov (United States)

    Liu, Yongchun; Ma, Qingxin; He, Hong

    2012-10-16

    Heterogeneous uptake of methylamine (MA), dimethylamine (DMA), and trimethylamine (TMA) onto citric acid and humic acid was investigated using a Knudsen cell reactor coupled to a quadrupole mass spectrometer at 298 K. Acid-base reactions between amines and carboxylic acids were confirmed. The observed uptake coefficients of MA, DMA, and TMA on citric acid at 298 K were measured to be 7.31 ± 1.13 × 10(-3), 6.65 ± 0.49 × 10(-3), and 5.82 ± 0.68 × 10(-3), respectively, and showed independence of sample mass. The observed uptake coefficients of MA, DMA, and TMA on humic acid at 298 K increased linearly with sample mass, and the true uptake coefficients of MA, DMA, and TMA were measured to be 1.26 ± 0.07 × 10(-5), 7.33 ± 0.40 × 10(-6), and 4.75 ± 0.15 × 10(-6), respectively. Citric acid, having stronger acidity, showed a higher reactivity than humic acid for a given amine; while the steric effect of amines was found to govern the reactivity between amines and citric acid or humic acid.

  13. Microbial transformations of isocupressic acid.

    Science.gov (United States)

    Lin, S J; Rosazza, J P

    1998-07-01

    Microbial transformations of the labdane-diterpene isocupressic acid (1) with different microorganisms yielded several oxygenated metabolites that were isolated and characterized by MS and NMR spectroscopic analyses. Nocardia aurantia (ATCC 12674) catalyzed the cleavage of the 13,14-double bond to yield a new nor-labdane metabolite, 2. Cunninghamella elegans (-) (NRRL 1393) gave 7beta-hydroxyisocupressic acid (3) and labda-7,13(E)-diene-6beta,15, 17-triol-19-oic acid (4), and Mucor mucedo (ATCC 20094) gave 2alpha-hydroxyisocupressic acid (5) and labda-8(17),14-diene-2alpha, 13-diol-19-oic acid (6).

  14. Amino Acid Catabolism in Plants.

    Science.gov (United States)

    Hildebrandt, Tatjana M; Nunes Nesi, Adriano; Araújo, Wagner L; Braun, Hans-Peter

    2015-11-02

    Amino acids have various prominent functions in plants. Besides their usage during protein biosynthesis, they also represent building blocks for several other biosynthesis pathways and play pivotal roles during signaling processes as well as in plant stress response. In general, pool sizes of the 20 amino acids differ strongly and change dynamically depending on the developmental and physiological state of the plant cell. Besides amino acid biosynthesis, which has already been investigated in great detail, the catabolism of amino acids is of central importance for adjusting their pool sizes but so far has drawn much less attention. The degradation of amino acids can also contribute substantially to the energy state of plant cells under certain physiological conditions, e.g. carbon starvation. In this review, we discuss the biological role of amino acid catabolism and summarize current knowledge on amino acid degradation pathways and their regulation in the context of plant cell physiology.

  15. Acidic aerosol in urban air

    Energy Technology Data Exchange (ETDEWEB)

    Fukuda, M.; Yamaoka, S.; Miyazaki, T.; Oka, M.

    1982-01-01

    The distribution and chemical composition of acidic aerosol in Osaka City were investigated. Samples were collected at five sites in the city from June to September, 1979. Acidic aerosol was determined by the acid-base titration method, sulfate ion by barium chloride turbidimetry, nitrate ion by the xylenol method, and chloride ion by the mercury thiocyanate method. The concentration of acidic aerosol at five sites ranged from 7.7 micrograms per cubic meter to 10.0 micrograms per cubic meter, but mean concentrations in the residential area were slightly higher than those in the industrial area. When acidic aerosol concentrations were compared with concentrations of sulfate, nitrate, and chloride ions, a significant correlation was found between acidic aerosol and sulfate ion. The sum of the ion equivalents of the three types showed good correlation with the acidic aerosol equivalent during the whole period.

  16. Nucleic Acid Vaccines

    Institute of Scientific and Technical Information of China (English)

    LU Shan

    2004-01-01

    @@ Anew method of immunization was discovered in the early 1990s. Several research groups independently demonstrated that direct inoculation of DNA plasmids coding for a specific protein antigen could elicit immune responses against that antigen[1-4].Since in theory the mRNA molecules also have the potential to be translated into the protein antigen, this vaccination approach was officially named by WHO as the nucleic acid vaccination even though the term DNA vaccine has been used more commonly in the literature. This novel approach is considered the fourth generation of vaccines after live attenuated vaccines, killed or inactivated vaccines and recombinant protein based subunit vaccines.

  17. Mycophenolic Acid in Silage

    Science.gov (United States)

    Schneweis, Isabell; Meyer, Karsten; Hörmansdorfer, Stefan; Bauer, Johann

    2000-01-01

    We examined 233 silage samples and found that molds were present in 206 samples with counts between 1 × 103 and 8.9 × 107 (mean, 4.7 × 106) CFU/g. Mycophenolic acid, a metabolite of Penicillium roqueforti, was detected by liquid chromatography-mass spectrometry in 74 (32%) of these samples at levels ranging from 20 to 35,000 (mean, 1,400) μg/kg. This compound has well-known immunosuppressive properties, so feeding with contaminated silage may promote the development of infectious diseases in livestock. PMID:10919834

  18. New Acid Combination for a Successful Sandstone Acidizing

    Science.gov (United States)

    Shafiq, M. U.; Mahmud, H. K. B.; Rezaee, R.

    2017-05-01

    With the development of new enhanced oil recovery techniques, sandstone acidizing has been introduced and played a pivotal role in the petroleum industry. Different acid combinations have been applied, which react with the formation, dissolve the soluble particles; thus increase the production of hydrocarbons. To solve the problems which occurred using current preflush sandstone acidizing technology (hydrochloric acid); a new acid combination has been developed. Core flooding experiments on sandstone core samples with dimensions 1.5 in. × 3 in. were conducted at a flow rate of 2 cm3/min. A series of hydrochloric-acetic acid mixtures with different ratios were tested under 150°F temperature. The core flooding experiments performed are aimed to dissolve carbonate, sodium, potassium and calcium particles from the core samples. These experiments are followed by few important tests which include, porosity-permeability, pH value, Inductively Coupled Plasma (ICP) analysis and Nuclear Magnetic Resonance (NMR measurements). All the results are compared with the results of conventional hydrochloric acid technology. NMR and porosity analysis concluded that the new acid combination is more effective in creating fresh pore spaces and thus increasing the reservoir permeability. It can be seen from the pore distribution before and after the acidizing. Prior applying acid; the large size of pores appears most frequently in the pore distribution while with the applied acid, it was found that the small pore size is most the predominant of the pore distribution. These results are validated using ICP analysis which shows the effective removal of calcium and other positive ions from the core sample. This study concludes that the combination of acetic-hydrochloric acid can be a potential candidate for the preflush stage of sandstone acidizing at high temperature reservoirs.

  19. Bicyclic glutamic acid derivatives.

    Science.gov (United States)

    Meyer, Udo; Bisel, Philippe; Weckert, Edgar; Frahm, August Wilhelm

    2006-05-15

    For the second-generation asymmetric synthesis of the trans-tris(homoglutamic) acids via Strecker reaction of chiral ketimines, the cyanide addition as the key stereodifferentiating step produces mixtures of diastereomeric alpha-amino nitrile esters the composition of which is independent of the reaction temperature and the type of the solvent, respectively. The subsequent hydrolysis is exclusively achieved with concentrated H(2)SO(4) yielding diastereomeric mixtures of three secondary alpha-amino alpha-carbamoyl-gamma-esters and two diastereomeric cis-fused angular alpha-carbamoyl gamma-lactams as bicyclic glutamic acid derivatives, gained from in situ stereomer differentiating cyclisation of the secondary cis-alpha-amino alpha-carbamoyl-gamma-esters. Separation was achieved by CC. The pure secondary trans-alpha-amino alpha-carbamoyl-gamma-esters cyclise on heating and treatment with concentrated H(2)SO(4), respectively, to diastereomeric cis-fused angular secondary alpha-amino imides. Their hydrogenolysis led to the enantiomeric cis-fused angular primary alpha-amino imides. The configuration of all compounds was completely established by NMR methods, CD-spectra, and by X-ray analyses of the (alphaR,1R,5R)-1-carbamoyl-2-(1-phenylethyl)-2-azabicyclo[3.3.0]octan-3-one and of the trans-alphaS,1S,2R-2-ethoxycarbonylmethyl-1-(1-phenylethylamino)cyclopentanecarboxamide.

  20. Cryoprotection from lipoteichoic acid

    Science.gov (United States)

    Rice, Charles V.; Middaugh, Amy; Wickham, Jason R.; Friedline, Anthony; Thomas, Kieth J.; Johnson, Karen; Zachariah, Malcolm; Garimella, Ravindranth

    2012-10-01

    Numerous chemical additives lower the freezing point of water, but life at sub-zero temperatures is sustained by a limited number of biological cryoprotectants. Antifreeze proteins in fish, plants, and insects provide protection to a few degrees below freezing. Microbes have been found to survive at even lower temperatures, and with a few exceptions, antifreeze proteins are missing. Survival has been attributed to external factors, such as the high salt concentration of brine veins and adhesion to particulates or ice crystal defects. We have discovered an endogenous cryoprotectant in the cell wall of bacteria, lipoteichoic acid biopolymers. Adding 1% LTA to bacteria cultures immediately prior to freezing provides 50% survival rate, similar to the results obtained with 1% glycerol. In the absence of an additive, bacterial survival is negligible as measured with the resazurin cell viability assay. The mode of action for LTA cryoprotection is unknown. With a molecular weight of 3-5 kDa, it is unlikely to enter the cell cytoplasm. Our observations suggest that teichoic acids could provide a shell of liquid water around biofilms and planktonic bacteria, removing the need for brine veins to prevent bacterial freezing.

  1. Acid Ceramidase in Melanoma

    DEFF Research Database (Denmark)

    Realini, Natalia; Palese, Francesca; Pizzirani, Daniela

    2016-01-01

    Acid ceramidase (AC) is a lysosomal cysteine amidase that controls sphingolipid signaling by lowering the levels of ceramides and concomitantly increasing those of sphingosine and its bioactive metabolite, sphingosine 1-phosphate. In the present study, we evaluated the role of AC-regulated sphing......Acid ceramidase (AC) is a lysosomal cysteine amidase that controls sphingolipid signaling by lowering the levels of ceramides and concomitantly increasing those of sphingosine and its bioactive metabolite, sphingosine 1-phosphate. In the present study, we evaluated the role of AC......-regulated sphingolipid signaling in melanoma. We found that AC expression is markedly elevated in normal human melanocytes and proliferative melanoma cell lines, compared with other skin cells (keratinocytes and fibroblasts) and non-melanoma cancer cells. High AC expression was also observed in biopsies from human...... generate lower amounts of ceramides than normal melanocytes do. This down-regulation in ceramide production appears to result from suppression of the de novo biosynthesis pathway. To test whether AC might contribute to melanoma cell proliferation, we blocked AC activity using a new potent (IC50 = 12 n...

  2. Kinetics of wet oxidation of formic acid and acetic acid

    Energy Technology Data Exchange (ETDEWEB)

    Shende, R.V.; Mahajani, V.V. [Univ. of Mumbai (India). Dept. of Chemical Technology

    1997-11-01

    Oxidation of lower molecular weight carboxylic acids such as formic, acetic, glyoxalic, and oxalic acids is often the rate-controlling step during wet oxidation (WO) of an aqueous waste stream exhibiting very high chemical oxygen demand (COD). The kinetics of WO of formic acid was studied in the absence and presence of a cupric sulfate as catalyst in the temperature range 150--240 C and oxygen partial pressure range 0.345--1.380 MPa. Wet oxidation of acetic acid was carried out in the presence of cupric sulfate in the temperature range 215--235 C. Homogeneous copper sulfate was found to be a very good catalyst for oxidation of formic acid and acetic acid.

  3. Solid acid catalysis from fundamentals to applications

    CERN Document Server

    Hattori, Hideshi

    2014-01-01

    IntroductionTypes of solid acid catalystsAdvantages of solid acid catalysts Historical overviews of solid acid catalystsFuture outlookSolid Acids CatalysisDefinition of acid and base -Brnsted acid and Lewis acid-Acid sites on surfacesAcid strengthRole of acid sites in catalysisBifunctional catalysisPore size effect on catalysis -shape selectivity-Characterization of Solid Acid Catalysts Indicator methodTemperature programmed desorption (TPD) of ammoniaCalorimetry of adsorption of basic moleculesInfrare

  4. Japodic Acid, A Novel Aliphatic Acid from Jatropha podagrica Hook

    OpenAIRE

    Aiyelaagbe, Olapeju O.; Gloer, James B.

    2008-01-01

    A new aliphatic acid named japodic acid (1) with a gem-dimethyl cyclopropane ring has been isolated from the roots of Jatropha podagrica. Its structure was established by 1D and 2D NMR and mass spectrometric data. Two other known compounds, erythrinasinate (2) and fraxidin (3) were also isolated from this plant for the first time. Japodic acid showed mild insect growth inhibition activity against Helicoverpa zea (37% growth reduction at 100 ppm). Fraxidin and erythrinasinate exhibited antibac...

  5. Electrolytic nature of aqueous sulfuric acid. 2. Acidity.

    Science.gov (United States)

    Fraenkel, Dan

    2012-09-27

    In part 1 of this study, I reported that the Debye-Hückel limiting law and the smaller-ion shell (SiS) model of strong electrolyte solutions fit nicely with the experimental mean ionic activity coefficient (γ(±)) of aqueous sulfuric acid as a function of concentration and of temperature when the acid is assumed to be a strong 1-3 electrolyte. Here, I report that the SiS-derived activity coefficient of H(+), γ(H(+)), of the 1-3 acid is comparable to that of aqueous HCl. This agrees with titration curves showing, as well-known, that sulfuric acid in water is parallel in strength to aqueous HCl. The calculated pH is in good accord with the Hammett acidity function, H(0), of aqueous sulfuric acid at low concentration, and differences between the two functions at high concentration are discussed and explained. This pH-H(0) relation is consistent with the literature showing that the H(0) of sulfuric acid (in the 1-9 M range) is similar to those of HCl and the other strong mineral monoprotic acids. The titration of aqueous sulfuric acid with NaOH does not agree with the known second dissociation constant of 0.010 23; rather, the constant is found to be ~0.32 and the acid behaves upon neutralization as a strong diprotic acid practically dissociating in one step. A plausible reaction pathway is offered to explain how the acid may transform, upon base neutralization, from a dissociated H(4)SO(5) (as 3H(+) and HSO(5)(3-)) to a dissociated H(2)SO(4) even though the equilibrium constant of the reaction H(+) + HSO(5)(3-) ↔ SO(4)(2-) + H(2)O, at 25 °C, is 10(-37) (part 1).

  6. Bile acid interactions with cholangiocytes

    Institute of Scientific and Technical Information of China (English)

    Xuefeng Xia; Heather Francis; Shannon Glaser; Gianfranco Alpini; Gene LeSage

    2006-01-01

    Cholangiocytes are exposed to high concentrations of bile acids at their apical membrane. A selective transporter for bile acids, the Apical Sodium Bile Acid Cotransporter (ASBT) (also referred to as Ibat; gene name Slc10a2)is localized on the cholangiocyte apical membrane. On the basolateral membrane, four transport systems have been identified (t-ASBT, multidrug resistance (MDR)3,an unidentified anion exchanger system and organic solute transporter (Ost) heteromeric transporter, OstαOstβ. Together, these transporters unidirectionally move bile acids from ductal bile to the circulation. Bile acids absorbed by cholangiocytes recycle via the peribiliaryplexus back to hepatocytes for re-secretion into bile.This recycling of bile acids between hepatocytes and cholangiocytes is referred to as the cholehepatic shunt pathway. Recent studies suggest that the cholehepatic shunt pathway may contribute in overall hepatobiliary transport of bile acids and to the adaptation to chronic cholestasis due to extrahepatic obstruction. ASBT is acutely regulated by an adenosine 3', 5'-monophosphate (cAMP)-dependent translocation to the apical membrane and by phosphorylation-dependent ubiquitination and proteasome degradation. ASBT is chronically regulated by changes in gene expression in response to biliary bile acid concentration and inflammatory cytokines.Another potential function of cholangiocyte ASBT is to allow cholangiocytes to sample biliary bile acids in order to activate intracellular signaling pathways. Bile acids trigger changes in intracellular calcium, protein kinase C (PKC), phosphoinositide 3-kinase (PI3K), mitogenactivated protein (MAP) kinase and extracellular signalregulated protein kinase (ERK) intracellular signals.Bile acids significantly alter cholangiocyte secretion,proliferation and survival. Different bile acids have differential effects on cholangiocyte intracellular signals,and in some instances trigger opposing effects on cholangiocyte secretion

  7. Citric acid production patent review.

    Science.gov (United States)

    Anastassiadis, Savas; Morgunov, Igor G; Kamzolova, Svetlana V; Finogenova, Tatiana V

    2008-01-01

    Current Review article summarizes the developments in citric acid production technologies in East and West last 100 years. Citric acid is commercially produced by large scale fermentation mostly using selected fungal or yeast strains in aerobe bioreactors and still remains one of the runners in industrial production of biotechnological bulk metabolites obtained by microbial fermentation since about 100 years, reflecting the historical development of modern biotechnology and fermentation process technology in East and West. Citric acid fermentation was first found as a fungal product in cultures of Penicillium glaucum on sugar medium by Wehmer in 1893. Citric acid is an important multifunctional organic acid with a broad range of versatile uses in household and industrial applications that has been produced industrially since the beginning of 20(th) century. There is a great worldwide demand for citric acid consumption due to its low toxicity, mainly being used as acidulant in pharmaceutical and food industries. Global citric acid production has reached 1.4 million tones, increasing annually at 3.5-4.0% in demand and consumption. Citric acid production by fungal submerged fermentation is still dominating, however new perspectives like solid-state processes or continuous yeast processes can be attractive for producers to stand in today's strong competition in industry. Further perspectives aiming in the improvement of citric acid production are the improvement of citric acid producing strains by classical and modern mutagenesis and selection as well as downstream processes. Many inexpensive by-products and residues of the agro-industry (e.g. molasses, glycerin etc.) can be economically utilized as substrates in the production of citric acid, especially in solid-state fermentation, enormously reducing production costs and minimizing environmental problems. Alternatively, continuous processes utilizing yeasts which reach 200-250 g/l citric acid can stand in today

  8. Role of Ribonucleic Acid Synthesis in Replication of Deoxyribonucleic Acid

    Science.gov (United States)

    Pato, Martin L.

    1975-01-01

    An experiment previously interpreted to show a ribonucleic acid requirement for propagation of deoxyribonucleic replication is reexamined and the earlier interpretation is shown to be incorrect. PMID:1090599

  9. Rotational study of the bimolecule acetic acid-fluoroacetic acid

    Science.gov (United States)

    Feng, Gang; Gou, Qian; Evangelisti, Luca; Caminati, Walther

    2017-01-01

    The rotational spectrum of the acetic acid-fluoroacetic acid bimolecule was measured by using a pulsed jet Fourier transform microwave spectrometer. One conformer, in which fluoroacetic acid is in trans form, has been observed. The rotational transitions are split into two component lines, due to the internal rotation of the methyl group of acetic acid. From these splittings, the corresponding V3 barrier has been determined. The dissociation energy of this complex has been estimated to 66 kJ/mol. An increase of the distance between the two monomers upon the OH → OD substitution (Ubbelohde effect) has been observed.

  10. Evaluation of ascorbic acid in protecting labile folic acid derivatives.

    OpenAIRE

    1983-01-01

    The use of ascorbic acid as a reducing agent to protect labile, reduced derivatives of folic acid has been evaluated by high-performance liquid chromatographic separations and Lactobacillus casei microbiological assay of eluate fractions. Upon heating for 10 min at 100 degrees C, solutions of tetrahydropteroylglutamic acid (H4PteGlu) in 2% sodium ascorbate gave rise to 5,10-methylene-H4PteGlu and 5-methyl-H4PteGlu. H2PteGlu acid gave rise to 5-methyl-H4PteGlu and PteGlu. 10-Formyl-H4PteGlu ga...

  11. Determination of acetylsalicylic acid and salicylic acid in foods, using HPLC with fluorescence detection.

    OpenAIRE

    Venema, D.P.; Hollman, P.C.H.; Janssen, P.L.T.M.K.; Katan, M B

    1996-01-01

    We developed a specific and sensitive HPLC method with fluorescence detection for the determination of free acetylsalicylic acid, free salicylic acid, and free salicylic acid plus salicylic acid after alkaline hydrolysis (free-plus-bound) in foods. Acetylsalicylic acid was detected after postcolumn hydrolysis to salicylic acid. With the method for free acetylsalicylic acid and salicylic acid, recovery was 95-98␏or acetylsalicylic acid added to foods and 92-102␏or salicylic acid. Recovery of a...

  12. Esterification by the Plasma Acidic Water: Novel Application of Plasma Acid

    Science.gov (United States)

    Gu, Ling

    2014-03-01

    This work explores the possibility of plasma acid as acid catalyst in organic reactions. Plasma acidic water was prepared by dielectric barrier discharge and used to catalyze esterification of n-heptanioc acid with ethanol. It is found that the plasma acidic water has a stable and better performance than sulfuric acid, meaning that it is an excellent acid catalyst. The plasma acidic water would be a promising alternative for classic mineral acid as a more environment friendly acid.

  13. 49 CFR 173.158 - Nitric acid.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Nitric acid. 173.158 Section 173.158... Nitric acid. (a) Nitric acid exceeding 40 percent concentration may not be packaged with any other material. (b) Nitric acid in any concentration which does not contain sulfuric acid or hydrochloric acid as...

  14. Molecular Simulation of Naphthenic Acid Removal on Acidic Catalyst Ⅱ. Experimental results of catalytic decarboxylation over acidic catalysts

    Institute of Scientific and Technical Information of China (English)

    Fu Xiaoqin; Tian Songbai; Hou Shuandi; Longjun; Wang Xieqing

    2008-01-01

    The energy barriers of thermal decarboxylation reactions of petroleum acids and catalytic decarboxylation reactions of Br(o)nsted acid and Lewis acid were analyzed using molecular simulation technology.Compared with thermal decarboxylation reactions of petroleum acids, the decarboxylation reactions by acid catalysts were easier to occur. The decarboxylaton effect by Lewis acid was better than Br(o)nsted acid. The mechanisms of catalytic decarboxylation over acid catalyst were also verified by experiments on a fixed bed and a fluidized bed, the experimental results showed that the rate of acid removal could reach up to 97% over the acidic catalyst at a temperature above 400℃.

  15. Nanoclusters of Cyanuric Acid

    Indian Academy of Sciences (India)

    M ELANGO; V SUBRAMANIAN; N SATHYAMURTHY

    2017-07-01

    In this article, the self-assembly of cyanuric acid (CA) molecules into nano-structures is examined. Equilibrium geometry of CA is planar and it belongs to the D3h point group. It is shown that CA clusters form three dimensional bowls and balls. Cyclic pentamer (5-bowl) is the basic motif responsible for these non-planar geometries. It is also shown that the cyclic hexamer based clusters can be non-planar if they contain a 5-bowl. A unified criterion for the formation of bowls and balls from basic molecular building blocks emerges from this study. The role of symmetry in supramolecular self-assembly is also clearly evident from the present study.

  16. Acid mine drainage

    Science.gov (United States)

    Bigham, Jerry M.; Cravotta, Charles A.

    2016-01-01

    Acid mine drainage (AMD) consists of metal-laden solutions produced by the oxidative dissolution of iron sulfide minerals exposed to air, moisture, and acidophilic microbes during the mining of coal and metal deposits. The pH of AMD is usually in the range of 2–6, but mine-impacted waters at circumneutral pH (5–8) are also common. Mine drainage usually contains elevated concentrations of sulfate, iron, aluminum, and other potentially toxic metals leached from rock that hydrolyze and coprecipitate to form rust-colored encrustations or sediments. When AMD is discharged into surface waters or groundwaters, degradation of water quality, injury to aquatic life, and corrosion or encrustation of engineered structures can occur for substantial distances. Prevention and remediation strategies should consider the biogeochemical complexity of the system, the longevity of AMD pollution, the predictive power of geochemical modeling, and the full range of available field technologies for problem mitigation.

  17. Enzymatic tRNA acylation by acid and alpha-hydroxy acid analogues of amino acids.

    Science.gov (United States)

    Owczarek, Alina; Safro, Mark; Wolfson, Alexey D

    2008-01-08

    Incorporation of unnatural amino acids with unique chemical functionalities has proven to be a valuable tool for expansion of the functional repertoire and properties of proteins as well as for structure-function analysis. Incorporation of alpha-hydroxy acids (primary amino group is substituted with hydroxyl) leads to the synthesis of proteins with peptide bonds being substituted by ester bonds. Practical application of this modification is limited by the necessity to prepare corresponding acylated tRNA by chemical synthesis. We investigated the possibility of enzymatic incorporation of alpha-hydroxy acid and acid analogues (lacking amino group) of amino acids into tRNA using aminoacyl-tRNA synthetases (aaRSs). We studied direct acylation of tRNAs by alpha-hydroxy acid and acid analogues of amino acids and corresponding chemically synthesized analogues of aminoacyl-adenylates. Using adenylate analogues we were able to enzymatically acylate tRNA with amino acid analogues which were otherwise completely inactive in direct aminoacylation reaction, thus bypassing the natural mechanisms ensuring the selectivity of tRNA aminoacylation. Our results are the first demonstration that the use of synthetic aminoacyl-adenylates as substrates in tRNA aminoacylation reaction may provide a way for incorporation of unnatural amino acids into tRNA, and consequently into proteins.

  18. Ghrelin and gastric acid secretion.

    Science.gov (United States)

    Yakabi, Koji; Kawashima, Junichi; Kato, Shingo

    2008-11-07

    Ghrelin, a novel growth hormone-releasing peptide, was originally isolated from rat and human stomach. Ghrelin has been known to increase the secretion of growth hormone (GH), food intake, and body weight gain when administered peripherally or centrally. Ghrelin is also known to stimulate the gastric motility and the secretion of gastric acid. In the previous studies, the action of ghrelin on acid secretion was shown to be as strong as that of histamine and gastrin in in-vivo experiment. In the studies, the mechanism for the action of ghrelin was also investigated. It was shown that vagotomy completely inhibited the action of ghrelin on the secretion of gastric acid suggesting that vagal nerve is involved in the mechanism for the action of ghrelin on acid secretion. As famotidine did not inhibit ghrelin-induced acid secretion in the study by Masuda et al, they concluded that histamine was not involved in the action of ghrelin on acid secretion. However, we have shown that famotidine completely inhibited ghrelin-induced acid secretion and histidine decarboxylase (HDC) mRNA was increased in gastric mucosa by ghrelin injection which is inhibited by vagotomy Our results indicate that histamine is involved in the action of ghrelin on acid secretion. Furthermore synergistic action of gastrin and ghrelin on gastric acid secretion was shown. Although gastrin has important roles in postprandial secretion of gastric acid, ghrelin may be related to acid secretion during fasting period or at night. However, further studies are needed to elucidate the physiological role of ghrelin in acid secretion.

  19. Racemization of Meteoritic Amino Acids

    Science.gov (United States)

    Cohen, Barbara A.; Chyba, Christopher F.

    2000-05-01

    Meteorites may have contributed amino acids to the prebiotic Earth, affecting the global ratio of right-handed to left-handed (D/L) molecules. We calculate D/L ratios for seven biological, α-hydrogen, protein amino acids over a variety of plausible parent body thermal histories, based on meteorite evidence and asteroid modeling. We show that amino acids in meteorites do not necessarily undergo complete racemization by the time they are recovered on Earth. If the mechanism of amino acid formation imposes some enantiomeric preference on the amino acids, a chiral signature can be retained through the entire history of the meteorite. Original enantiomeric excesses in meteorites such as Murchison, which have undergone apparently short and cool alteration scenarios, should have persisted to the present time. Of the seven amino acids for which relevant data are available, we expect glutamic acid, isoleucine, and valine, respectively, to be the most likely to retain an initial enantiomeric excess, and phenylalanine, aspartic acid, and alanine the least. Were the D/L ratio initially identical in each amino acid, final D/L ratios could be used to constrain the initial ratio and the thermal history experienced by the whole suite.

  20. Antibiofilm Properties of Acetic Acid

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Alhede, Morten; Jensen, Peter Østrup;

    2014-01-01

    of the infected implant, tissue, or organ and thereby the biofilm. Acetic acid is known for its antimicrobial effect on bacteria in general, but has never been thoroughly tested for its efficacy against bacterial biofilms. In this article, we describe complete eradication of both Gram-positive and Gram......-negative biofilms using acetic acid both as a liquid and as a dry salt. In addition, we present our clinical experience of acetic acid treatment of chronic wounds. In conclusion, we here present the first comprehensive in vitro and in vivo testing of acetic acid against bacterial biofilms....

  1. Preparation and characterization Al3+-bentonite Turen Malang for esterification fatty acid (palmitic acid, oleic acid and linoleic acid)

    Science.gov (United States)

    Abdulloh, Abdulloh; Aminah, Nanik Siti; Triyono, Mudasir, Trisunaryanti, Wega

    2016-03-01

    Catalyst preparation and characterization of Al3+-bentonite for esterification of palmitic acid, oleic acid and linoleic acid has been done. Al3+-bentonite catalyst was prepared from natural bentonite of Turen Malang through cation exchange reaction using AlCl3 solution. The catalysts obtained were characterized by XRD, XRF, pyridine-FTIR and surface area analyser using the BET method. Catalyst activity test of Al3+-bentonite for esterification reaction was done at 65°C using molar ratio of metanol-fatty acid of 30:1 and 0.25 g of Al3+-bentonite catalyst for the period of ½, 1, 2, 3, 4 and 5 hours. Based on the characterization results, the Al3+-bentonite Turen Malang catalyst has a d-spacing of 15.63 Ǻ, acid sites of Brönsted and Lewis respectively of 230.79 µmol/g and 99.39 µmol/g, surface area of 507.3 m2/g and the average of radius pore of 20.09 Å. GC-MS analysis results of the oil phase after esterification reaction showed the formation of biodiesel (FAME: Fatty acid methyl ester), namely methyl palmitate, methyl oleate and methyl linoleate. The number of conversions resulted in esterification reaction using Al3+-bentonite Turen Malang catalyst was 74.61%, 37.75%, and 20, 93% for the esterification of palmitic acid, oleic acid and linoleic acid respectively.

  2. [Hydrofluoric acid poisoning: case report].

    Science.gov (United States)

    Cortina, Tatiana Judith; Ferrero, Hilario Andrés

    2013-01-01

    Hydrofluoric acid is a highly dangerous substance with industrial and domestically appliances. Clinical manifestations of poisoning depend on exposure mechanism, acid concentration and exposed tissue penetrability. Gastrointestinal tract symptoms do not correlate with injury severity. Patients with history of hydrofluoric acid ingestion should undergo an endoscopy of the upper gastrointestinal tract. Intoxication requires immediate intervention because systemic toxicity can take place. We present a 5 year old girl who accidentally swallowed 5 ml of 20% hydrofluoric acid. We performed gastrointestinal tract endoscopy post ingestion, which revealed erythematous esophagus and stomach with erosive lesions. Two months later, same study was performed and revealed esophagus and stomach normal mucous membrane.

  3. ACETIC ACID AND A BUFFER

    DEFF Research Database (Denmark)

    2009-01-01

    The present invention relates to a composition comprising : a) 0.01-20% wt/wt acetic acid and b) a physiologically tolerable buffer capable of maintaining acetic acid at a pH in the range of 2-7; and use of such a composition as an antimicrobial agent.......The present invention relates to a composition comprising : a) 0.01-20% wt/wt acetic acid and b) a physiologically tolerable buffer capable of maintaining acetic acid at a pH in the range of 2-7; and use of such a composition as an antimicrobial agent....

  4. Retinoic acid and iron metabolism

    DEFF Research Database (Denmark)

    Chakraborty, Surajit; Bhattacharyya, Rajasri; Sayal, Kirtimaan

    2014-01-01

    tuberculosis controlling molecules in the days to come. Iron has proven to be essential for pathogenesis of tuberculosis and retinoic acid is known to influence the iron metabolism pathway. Retenoic acid is also known to exhibit antitubercular effect in in vivo system. Therefore there is every possibility...... that retinoic acid by affecting the iron metabolism pathway exhibits its antimycobacterial effect. These aspects are reviewed in the present manuscript for understanding the antimycobacterial role of retinoic acid in the context of iron metabolism and other immunological aspects....

  5. ACETIC ACID AND A BUFFER

    DEFF Research Database (Denmark)

    2009-01-01

    The present invention relates to a composition comprising : a) 0.01-20% wt/wt acetic acid and b) a physiologically tolerable buffer capable of maintaining acetic acid at a pH in the range of 2-7; and use of such a composition as an antimicrobial agent.......The present invention relates to a composition comprising : a) 0.01-20% wt/wt acetic acid and b) a physiologically tolerable buffer capable of maintaining acetic acid at a pH in the range of 2-7; and use of such a composition as an antimicrobial agent....

  6. Biotechnological production of citric acid

    National Research Council Canada - National Science Library

    Max, Belén; Salgado, José Manuel; Rodríguez, Noelia; Cortés, Sandra; Converti, Attilio; Domínguez, José Manuel

    2010-01-01

    This work provides a review about the biotechnological production of citric acid starting from the physicochemical properties and industrial applications, mainly in the food and pharmaceutical sectors...

  7. Fatty Acid Desaturases, Polyunsaturated Fatty Acid Regulation, and Biotechnological Advances.

    Science.gov (United States)

    Lee, Je Min; Lee, Hyungjae; Kang, SeokBeom; Park, Woo Jung

    2016-01-04

    Polyunsaturated fatty acids (PUFAs) are considered to be critical nutrients to regulate human health and development, and numerous fatty acid desaturases play key roles in synthesizing PUFAs. Given the lack of delta-12 and -15 desaturases and the low levels of conversion to PUFAs, humans must consume some omega-3 and omega-6 fatty acids in their diet. Many studies on fatty acid desaturases as well as PUFAs have shown that fatty acid desaturase genes are closely related to different human physiological conditions. Since the first front-end desaturases from cyanobacteria were cloned, numerous desaturase genes have been identified and animals and plants have been genetically engineered to produce PUFAs such as eicosapentaenoic acid and docosahexaenoic acid. Recently, a biotechnological approach has been used to develop clinical treatments for human physiological conditions, including cancers and neurogenetic disorders. Thus, understanding the functions and regulation of PUFAs associated with human health and development by using biotechnology may facilitate the engineering of more advanced PUFA production and provide new insights into the complexity of fatty acid metabolism.

  8. Peptide Nucleic Acids Having Amino Acid Side Chains

    DEFF Research Database (Denmark)

    1998-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary DNA and RNA strands more strongly than the corresponding DNA or RNA strands, and exhibit increased sequence specificity and solubility. The peptide nucleic acids comprise ligands selected from a group consisting...

  9. Fatty Acid Desaturases, Polyunsaturated Fatty Acid Regulation, and Biotechnological Advances

    Directory of Open Access Journals (Sweden)

    Je Min Lee

    2016-01-01

    Full Text Available Polyunsaturated fatty acids (PUFAs are considered to be critical nutrients to regulate human health and development, and numerous fatty acid desaturases play key roles in synthesizing PUFAs. Given the lack of delta-12 and -15 desaturases and the low levels of conversion to PUFAs, humans must consume some omega-3 and omega-6 fatty acids in their diet. Many studies on fatty acid desaturases as well as PUFAs have shown that fatty acid desaturase genes are closely related to different human physiological conditions. Since the first front-end desaturases from cyanobacteria were cloned, numerous desaturase genes have been identified and animals and plants have been genetically engineered to produce PUFAs such as eicosapentaenoic acid and docosahexaenoic acid. Recently, a biotechnological approach has been used to develop clinical treatments for human physiological conditions, including cancers and neurogenetic disorders. Thus, understanding the functions and regulation of PUFAs associated with human health and development by using biotechnology may facilitate the engineering of more advanced PUFA production and provide new insights into the complexity of fatty acid metabolism.

  10. Carbonic Acid Pretreatment of Biomass

    Energy Technology Data Exchange (ETDEWEB)

    G. Peter van Walsum; Kemantha Jayawardhana; Damon Yourchisin; Robert McWilliams; Vanessa Castleberry

    2003-05-31

    This project sought to address six objectives, outlined below. The objectives were met through the completion of ten tasks. 1) Solidify the theoretical understanding of the binary CO2/H2O system at reaction temperatures and pressures. The thermodynamics of pH prediction have been improved to include a more rigorous treatment of non-ideal gas phases. However it was found that experimental attempts to confirm theoretical pH predictions were still off by a factor of about 1.8 pH units. Arrhenius experiments were carried out and the activation energy for carbonic acid appears to be substantially similar to sulfuric acid. Titration experiments have not yet confirmed or quantified the buffering or acid suppression effects of carbonic acid on biomass. 2) Modify the carbonic acid pretreatment severity function to include the effect of endogenous acid formation and carbonate buffering, if necessary. It was found that the existing severity functions serve adequately to account for endogenous acid production and carbonate effects. 3) Quantify the production of soluble carbohydrates at different reaction conditions and severity. Results show that carbonic acid has little effect on increasing soluble carbohydrate concentrations for pretreated aspen wood, compared to pretreatment with water alone. This appears to be connected to the release of endogenous acids by the substrate. A less acidic substrate such as corn stover would derive benefit from the use of carbonic acid. 4) Quantify the production of microbial inhibitors at selected reaction conditions and severity. It was found that the release of inhibitors was correlated to reaction severity and that carbonic acid did not appear to increase or decrease inhibition compared to pretreatment with water alone. 5) Assess the reactivity to enzymatic hydrolysis of material pretreated at selected reaction conditions and severity. Enzymatic hydrolysis rates increased with severity, but no advantage was detected for the use of carbonic

  11. Carbonic Acid Retreatment of Biomass

    Energy Technology Data Exchange (ETDEWEB)

    Baylor university

    2003-06-01

    This project sought to address six objectives, outlined below. The objectives were met through the completion of ten tasks. (1) Solidify the theoretical understanding of the binary CO{sub 2}/H{sub 2}O system at reaction temperatures and pressures. The thermodynamics of pH prediction have been improved to include a more rigorous treatment of non-ideal gas phases. However it was found that experimental attempts to confirm theoretical pH predictions were still off by a factor of about 1.8 pH units. Arrhenius experiments were carried out and the activation energy for carbonic acid appears to be substantially similar to sulfuric acid. Titration experiments have not yet confirmed or quantified the buffering or acid suppression effects of carbonic acid on biomass. (2) Modify the carbonic acid pretreatment severity function to include the effect of endogenous acid formation and carbonate buffering, if necessary. It was found that the existing severity functions serve adequately to account for endogenous acid production and carbonate effects. (3) Quantify the production of soluble carbohydrates at different reaction conditions and severity. Results show that carbonic acid has little effect on increasing soluble carbohydrate concentrations for pretreated aspen wood, compared to pretreatment with water alone. This appears to be connected to the release of endogenous acids by the substrate. A less acidic substrate such as corn stover would derive benefit from the use of carbonic acid. (4) Quantify the production of microbial inhibitors at selected reaction conditions and severity. It was found that the release of inhibitors was correlated to reaction severity and that carbonic acid did not appear to increase or decrease inhibition compared to pretreatment with water alone. (5) Assess the reactivity to enzymatic hydrolysis of material pretreated at selected reaction conditions and severity. Enzymatic hydrolysis rates increased with severity, but no advantage was detected for

  12. Ghrelin and gastric acid secretion

    Institute of Scientific and Technical Information of China (English)

    Koji Yakabi; Junichi Kawashima; Shingo Kato

    2008-01-01

    Ghrelin, a novel growth hormone-releasing peptide, was originally isolated from rat and human stomach. Ghrelin has been known to increase the secretion of growth hormone (GH), food intake, and body weight gain when administered peripherally or centrally. Ghrelin is also known to stimulate the gastric motility and the secretion of gastric acid. In the previous studies, the action of ghrelin on acid secretion was shown to be as strong as that of histamine and gastrin in-vivo experiment. In the studies, the mechanism for the action of ghrelin was also investigated. It was shown that vagotomy completely inhibited the action of ghrelin on the secretion of gastric acid suggesting that vagal nerve is involved in the mechanism for the action of ghrelin on acid secretion. As famotidine did not inhibit ghrelin-in-duced acid secretion in the study by Masuda et al, they concluded that histamine was not involved in the action of ghrelin on acid secretion. However, we have shown that famotidine completely inhibited ghrelin-induced acid secretion and histidine decarboxylase (HDC) mRNA was increased in gastric mucosa by ghrelin injection which is inhibited by vagotomy Our results indicate that histamine is involved in the action of ghrelin on acid secretion. Furthermore synergistic action of gastrin and ghrelin on gastric add secretion was shown. Although gastrin has important roles in postprandial secretion of gastric acid, ghrelin may be related to acid secretion during fasting period or at night. However, further studies are needed to elucidate the physiological role of ghrelin in acid secretion.

  13. Amino acids in Arctic aerosols

    Directory of Open Access Journals (Sweden)

    E. Scalabrin

    2012-11-01

    Full Text Available Amino acids are significant components of atmospheric aerosols, affecting organic nitrogen input to marine ecosystems, atmospheric radiation balance, and the global water cycle. The wide range of amino acid reactivities suggest that amino acids may serve as markers of atmospheric transport and deposition of particles. Despite this potential, few measurements have been conducted in remote areas to assess amino acid concentrations and potential sources. Polar regions offer a unique opportunity to investigate atmospheric processes and to conduct source apportionment studies of such compounds. In order to better understand the importance of amino acid compounds in the global atmosphere, we determined free amino acids (FAAs in seventeen size-segregated aerosol samples collected in a polar station in the Svalbard Islands from 19 April until 14 September 2010. We used an HPLC coupled with a tandem mass spectrometer (ESI-MS/MS to analyze 20 amino acids and quantify compounds at fmol m−3 levels. Mean total FAA concentration was 1070 fmol m−3 where serine and glycine were the most abundant compounds in almost all samples and accounted for 45–60% of the total amino acid relative abundance. The other eighteen compounds had average concentrations between 0.3 and 98 fmol m−3. The higher amino acid concentrations were present in the ultrafine aerosol fraction (< 0.49 μm and accounted for the majority of the total amino acid content. Local marine sources dominate the boreal summer amino acid concentrations, with the exception of the regional input from Icelandic volcanic emissions.

  14. Amino acids in Arctic aerosols

    Directory of Open Access Journals (Sweden)

    E. Scalabrin

    2012-07-01

    Full Text Available Amino acids are significant components of atmospheric aerosols, affecting organic nitrogen input to marine ecosystems, atmospheric radiation balance, and the global water cycle. The wide range of amino acid reactivities suggest that amino acids may serve as markers of atmospheric transport and deposition of particles. Despite this potential, few measurements have been conducted in remote areas to assess amino acid concentrations and potential sources. Polar regions offer a unique opportunity to investigate atmospheric processes and to conduct source apportionment studies of such compounds. In order to better understand the importance of amino acid compounds in the global atmosphere, we determined free amino acids (FAAs in seventeen size-segregated aerosol samples collected in a polar station in the Svalbard Islands from 19 April until 14 September 2010. We used an HPLC coupled with a tandem mass spectrometer (ESI-MS/MS to analyze 20 amino acids to quantify compounds at fmol m−3 levels. Mean total FAA concentration was 1070 fmol m−3 where serine and glycine were the most abundant compounds in almost all samples and accounted for 45–60% of the total amino acid relative abundance. The other eighteen compounds had average concentrations between 0.3 and 98 fmol m−3. The higher amino acid concentrations were present in the ultrafine aerosol fraction (<0.49 μm and accounted for the majority of the total amino acid content. Local marine sources dominate the boreal summer amino acid concentrations, with the exception of the regional input from Icelandic volcanics.

  15. The acidic amino acids of tulip: isolation of γ-ethylideneglutamic acid

    Science.gov (United States)

    Fowden, L.

    1966-01-01

    1. γ-Ethylideneglutamic acid has been isolated from fruit capsules of tulip plants. 2. The assigned structure was indicated by examining the products formed after oxidation and catalytic hydrogenation and was confirmed by nuclear-magnetic-resonance spectroscopy and by synthesis of γ-ethylglutamic acid. 3. The ability of γ-ethylideneglutamic acid to participate in transamination and decarboxylation reactions was examined. PMID:5938664

  16. Infrared spectra of hydrogen-bonded salicylic acid and its derivatives : Salicylic acid and acetylsalicylic acid

    Science.gov (United States)

    Wójcik, Marek J.

    1981-11-01

    Infrared spectra of hydrogen-bonded salicylic acid, O-deutero-salicylic acid and acetylsalicylic acid crystals have been studied experimentally and theoretically. Interpretation of these spectra was based on the Witkowski-Maréchal model. Semi-quantitative agreement between experimental and theoretical spectra can be achieved with the simplest form of this model, with values of interaction parameters transferable for equivalent intermolecular hydrogen bonds.

  17. Alpha-MSH decreases core and brain temperature during global cerebral ischemia in rats

    DEFF Research Database (Denmark)

    Spulber, S.; Moldovan, Mihai; Oprica, M.

    2005-01-01

    A key pathological event during cerebral ischemia is the excitotoxic release of glutamate. We have shown previously that alpha-melanocyte-stimulating hormone (alpha-MSH) enhances the hypothermia induced by kainic acid. We have investigated the effects of systemic administration of alpha-MSH on four...

  18. Drug: D06792 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available e-lysine Digenea simplex Same as: E00161 Rhodomelaceae Digenea simplex algae Major component: Kainic acid [C...elmintic drugs D06792 Digenea Crude drugs [BR:br08305] Algae Red algae D06792 Digenea PubChem: 47208443 ...

  19. Expression and induction of secretory phospholipase A2 group IB in brain

    DEFF Research Database (Denmark)

    Kolko, Miriam; Christoffersen, Nanna R; Varoqui, Hélène

    2005-01-01

    as in neurons in primary culture. The distribution of sPLA2-IB seems to be mainly neuronal, with the highest abundance occurring in the cerebral cortex and hippocampus. We also find that genes encoding sPLA2-IB are induced by kainic acid and by electroshock-induced convulsions. Based on the present results we...

  20. Production of succinic Acid from citric Acid and related acids by lactobacillus strains.

    Science.gov (United States)

    Kaneuchi, C; Seki, M; Komagata, K

    1988-12-01

    A number of Lactobacillus strains produced succinic acid in de Man-Rogosa-Sharpe broth to various extents. Among 86 fresh isolates from fermented cane molasses in Thailand, 30 strains (35%) produced succinic acid; namely, 23 of 39 Lactobacillus reuteri strains, 6 of 18 L. cellobiosus strains, and 1 of 6 unidentified strains. All of 10 L. casei subsp. casei strains, 5 L. casei subsp. rhamnosus strains, 6 L. mali strains, and 2 L. buchneri strains did not produce succinic acid. Among 58 known strains including 48 type strains of different Lactobacillus species, the strains of L. acidophilus, L. crispatus, L. jensenii, and L. parvus produced succinic acid to the same extent as the most active fresh isolates, and those of L. alimentarius, L. collinoides, L. farciminis, L. fructivorans (1 of 2 strains tested), L. malefermentans, and L. reuteri were also positive, to lesser extents. Diammonium citrate in de Man-Rogosa-Sharpe broth was determined as a precursor of the succinic acid produced. Production rates were about 70% on a molar basis with two fresh strains tested. Succinic acid was also produced from fumaric and malic acids but not from dl-isocitric, alpha-ketoglutaric, and pyruvic acids. The present study is considered to provide the first evidence on the production of succinic acid, an important flavoring substance in dairy products and fermented beverages, from citrate by lactobacilli.

  1. Acid Rain: The Scientific Challenge.

    Science.gov (United States)

    Godfrey, Paul J.

    1991-01-01

    Documents the workings and findings of the Massachusetts Acid Rain Monitoring Project, which has pooled the volunteer efforts of more than 1,000 amateur and professional scientists since 1983. Reports on the origins of air pollution, the prediction of acid rain, and its effects on both water life and land resources. (JJK)

  2. Bile acids for viral hepatitis

    DEFF Research Database (Denmark)

    Chen, Weikeng; Liu, J; Gluud, C

    2003-01-01

    The viral hepatitides are common causes of liver diseases globally. Trials have assessed bile acids for patients with viral hepatitis, but no consensus was reached regarding their usefulness.......The viral hepatitides are common causes of liver diseases globally. Trials have assessed bile acids for patients with viral hepatitis, but no consensus was reached regarding their usefulness....

  3. Acid Rain: What's the Forecast?

    Science.gov (United States)

    Bybee, Rodger

    1984-01-01

    Discusses various types of acid rain, considered to be a century-old problem. Topics include: wet and dry deposition, effects on a variety of environments, ecosystems subject to detrimental effects, and possible solutions to the problem. A list of recommended resources on acid rain is provided. (BC)

  4. Bile acids for viral hepatitis

    DEFF Research Database (Denmark)

    Chen, Weikeng; Liu, J; Gluud, C

    2003-01-01

    The viral hepatitides are common causes of liver diseases globally. Trials have assessed bile acids for patients with viral hepatitis, but no consensus was reached regarding their usefulness.......The viral hepatitides are common causes of liver diseases globally. Trials have assessed bile acids for patients with viral hepatitis, but no consensus was reached regarding their usefulness....

  5. Protein and amino acid nutrition

    Science.gov (United States)

    Dairy cow protein and amino acid nutrition have a significant role in sustainable dairying. Protein, amino acids, and nitrogen are inextricably linked through effects in the rumen, metabolism of the cow, and environmental nutrient management. Feeding systems have been making progress toward emphasiz...

  6. Pantothenic acid (Vitamin B5)

    Science.gov (United States)

    ... vitamin B5 (pantothenic acid), vitamin B6 (pyridoxine), vitamin B12 (cyanocobalamin), and folic acid. However, some products do ... Pantothenas, Calcium D-Pantothenate, Calcium Pantothenate, Complexe de Vitamines B, D-Calcium Pantothenate, D-Panthenol, D-Panthénol, ...

  7. Phosphorus derivatives of salicylic acid

    Science.gov (United States)

    Chvertkina, L. V.; Khoklov, P. S.; Mironov, Vladimir F.

    1992-10-01

    The present state of work on the methods of synthesis, chemical properties, and practical applications of phosphorus-containing derivatives of salicylic acid has been reviewed. The characteristics of the chemical transformations of cyclic and acyclic phosphorus derivatives of salicylic acid related to the coordination state of the phosphorus atom have been examined. The bibliography includes 158 references.

  8. utilisation of synthetic amino acids

    African Journals Online (AJOL)

    student

    intake, bodyweight gain, egg weight or efficiency of lysine utilisation, but ... When modelling the amino acid requirements of broiler breeder ... Two hundred and forty Cobb broiler breeder hens aged 27 weeks were housed in individual cages. ..... feeds with synthetic amino acids is of importance not only on nutritional and.

  9. Acid Rain: What's the Forecast?

    Science.gov (United States)

    Bybee, Rodger

    1984-01-01

    Discusses various types of acid rain, considered to be a century-old problem. Topics include: wet and dry deposition, effects on a variety of environments, ecosystems subject to detrimental effects, and possible solutions to the problem. A list of recommended resources on acid rain is provided. (BC)

  10. Acid Rain: The Scientific Challenge.

    Science.gov (United States)

    Godfrey, Paul J.

    1991-01-01

    Documents the workings and findings of the Massachusetts Acid Rain Monitoring Project, which has pooled the volunteer efforts of more than 1,000 amateur and professional scientists since 1983. Reports on the origins of air pollution, the prediction of acid rain, and its effects on both water life and land resources. (JJK)

  11. Kinetics and Mechanism of Oxidation of Phenyl Acetic Acid and Dl-Mandelic Acid by Permanganate in Acid Medium

    Directory of Open Access Journals (Sweden)

    B.Syama Sundar

    2014-06-01

    Full Text Available Kinetics of oxidation of phenyl acetic acid and DL- Mandelic acid by potassium permanganate in aqueous acetic acid and perchloric acid mixture reveals that the kinetic orders are first order in oxidant, first order in H+ and zero order in substrate for phenyl acetic acid. DL-Mandelic acid exhibits first order in oxidant and zero order in substrate. The results are rationalised by a mechanism involving intermediate formation of mandelic acid in case of Phenyl acetic acid and ester formation with Mn (VII in case of DL-Mandelic acid. The following order of reactivity is observed: DL-Mandelic acid > Phenyl acetic acid. The high reactivity of DL-Mandelic acid over phenyl acetic acid may be due to different mechanisms operating with the two substrates and benzaldehyde is the final product in both the cases.

  12. N-(3-Nitrophenylmaleamic acid

    Directory of Open Access Journals (Sweden)

    B. Thimme Gowda

    2010-07-01

    Full Text Available In the title compound, C10H8N2O5, the molecule is slightly distorted from planarity. The molecular structure is stabilized by two intramolecular hydrogen bonds. The first is a short O—H...O hydrogen bond (H...O distance = 1.57 Å within the maleamic acid unit and the second is a C—H...O hydrogen bond (H...O distance = 2.24 Å which connects the amide group with the benzene ring. The nitro group is twisted by 6.2 (2° out of the plane of the benzene ring. The crystal structure manifests a variety of hydrogen bonding. The packing is dominated by a strong intermolecular N—H...O interaction which links the molecules into chains running along the b axis. The chains within a plane are further assembled by three additional types of intermolecular C—H...O hydrogen bonds to form a sheet parallel to the (overline{1}01 plane.

  13. Molten fatty acid based microemulsions.

    Science.gov (United States)

    Noirjean, Cecile; Testard, Fabienne; Dejugnat, Christophe; Jestin, Jacques; Carriere, David

    2016-06-21

    We show that ternary mixtures of water (polar phase), myristic acid (MA, apolar phase) and cetyltrimethylammonium bromide (CTAB, cationic surfactant) studied above the melting point of myristic acid allow the preparation of microemulsions without adding a salt or a co-surfactant. The combination of SANS, SAXS/WAXS, DSC, and phase diagram determination allows a complete characterization of the structures and interactions between components in the molten fatty acid based microemulsions. For the different structures characterized (microemulsion, lamellar or hexagonal phases), a similar thermal behaviour is observed for all ternary MA/CTAB/water monophasic samples and for binary MA/CTAB mixtures without water: crystalline myristic acid melts at 52 °C, and a thermal transition at 70 °C is assigned to the breaking of hydrogen bounds inside the mixed myristic acid/CTAB complex (being the surfactant film in the ternary system). Water determines the film curvature, hence the structures observed at high temperature, but does not influence the thermal behaviour of the ternary system. Myristic acid is partitioned in two "species" that behave independently: pure myristic acid and myristic acid associated with CTAB to form an equimolar complex that plays the role of the surfactant film. We therefore show that myristic acid plays the role of a solvent (oil) and a co-surfactant allowing the fine tuning of the structure of oil and water mixtures. This solvosurfactant behaviour of long chain fatty acid opens the way for new formulations with a complex structure without the addition of any extra compound.

  14. Pentadecanoic and Heptadecanoic Acids: Multifaceted Odd-Chain Fatty Acids.

    Science.gov (United States)

    Pfeuffer, Maria; Jaudszus, Anke

    2016-07-01

    The odd-chain fatty acids (OCFAs) pentadecanoic acid (15:0) and heptadecanoic acid (17:0), which account for only a small proportion of total saturated fatty acids in milk fat and ruminant meat, are accepted biomarkers of dairy fat intake. However, they can also be synthesized endogenously, for example, from gut-derived propionic acid (3:0). A number of studies have shown an inverse association between OCFA concentrations in human plasma phospholipids or RBCs and risk of type 2 diabetes and cardiovascular disease. We propose a possible involvement in metabolic regulation from the assumption that there is a link between 15:0 and 17:0 and the metabolism of other short-chain, medium-chain, and longer-chain OCFAs. The OCFAs 15:0 and 17:0 can be elongated to very-long-chain FAs (VLCFAs) such as tricosanoic acid (23:0) and pentacosanoic acid (25:0) in glycosphingolipids, particularly found in brain tissue, or can be derived from these VLCFAs. Their chains can be shortened, yielding propionyl-coenzyme A (CoA). Propionyl-CoA, by succinyl-CoA, can replenish the citric acid cycle (CAC) with anaplerotic intermediates and, thus, improve mitochondrial energy metabolism. Mitochondrial function is compromised in a number of disorders and may be impaired with increasing age. Optimizing anaplerotic intermediate availability for the CAC may help to cope with demands in times of increased metabolic stress and with aging. OCFAs may serve as substrates for synthesis of both odd-numbered VLCFAs and propionyl-CoA or store away excess propionic acid.

  15. Effect of Ferulic Acid on Learning-memory and Expression of GFAP in the Hippocampus Tissues of Alzheimer' s Disease-like Model Mice%阿魏酸对拟痴呆小鼠学习记忆和海马胶质 纤维酸性蛋白表达的影响

    Institute of Scientific and Technical Information of China (English)

    金蓓蓓; 陈勤; 陈庆林

    2011-01-01

    目的:探讨阿魏酸对阿尔茨海默病(AD)模型小鼠神经行为学和海马胶质纤维酸性蛋白(GFAP)表达的影响,分析阿魏酸对小鼠脑的保护作用.方法:海马CA1区注射微量红藻氨酸(KA)建立痴呆模型,然后对痴呆小鼠用不同剂量的阿魏酸(FA)灌胃治疗.Morris水迷宫实验观察小鼠行为学变化,免疫组织化学方法观察GFAP的表达.结果:与假手术组相比,模型组学习记忆能力明显降低(P<0.01)GFAP阳性细胞表达明显增多(P<0.01);与模型组相比,阿魏酸治疗组学习记忆能力均明显提高(P<O.01),GFAP阳性细胞表达均明显减少(P<0.01).结论:用不同剂量的阿魏酸治疗拟AD小鼠后,小鼠学习记忆能力得到明显改善,GFAP表达得到明显抑制,起到保护脑的作用.%Objective: To investigate the effects of ferulic acid on neurological behavior and the expression of glial fibril-lary acidic protein(GFAP) of hippocampus tissues in Alzheimer' s disease-like model mice, and to analyze the protective effects of ferulic acid on the brain. Methods: kainic acid ( KA) was injected into hippocampus CA1 region of mice and to establish Alzheimer' s disease-like model, then the drug group with different doses of ferulic acid gavage lasted a month. The learning and memory abilities of the mice were assessed through Morris water maze behavioral test, and GFAP were observed by immunohistochemistry respectively. Results: Compared with the normal group, the abilities of learning and memory of the mice in the model group significantly decreased (P < 0.01 ) and the expression of GFAP in the CA1 region were increased(P<0.01). Compared with the model group, the abilities of learning and memory of the mice in the ferulic acid group improved ( P < 0. 01 ) and the expressions of GFAP in the CA1 region decreased ( P < 0.01). Conclusion: The different doses of ferulic acid dealing with the Alzheimer disease-like model mice can improve the abilities of learning

  16. Fatty acid composition of selected prosthecate bacteria.

    Science.gov (United States)

    Carter, R N; Schmidt, J M

    1976-10-11

    The cellular fatty acid composition of 14 strains of Caulobacter speices and types, two species of Prosthecomicrobium, and two species of Asticcacaulis was determined by gas-liquid chromatography. In most of these bacteria, the major fatty acids were octadecenoic acid (C18:1), hexadecenoic acid (C16:1) and hexadecanoic acid (C16:0). Some cyclopropane and branched chain fatty acids were detected in addition to the straight chained acids. Hydroxytetradecanoic acid was an important component of P.enhydrum but significant amounts of hydroxy acids were not detected in other prosthecate bacteria examined.

  17. The Property and Application of Arachidonic Acid

    Institute of Scientific and Technical Information of China (English)

    王相勤; 姚建铭; 袁成凌; 王纪; 余增亮

    2002-01-01

    Arachidonic acid (AA) is one of the most important PUFAs (polyunsaturated fatty acids) in human body. A high-yield arachidonic acid-producing strain (mortierella alpina) was selected by ion implantation (the relative content of arachidonic acid is 70.2% among all fatty acids). This paper mainly introduced the structure, distribution, source, physiologic healthcare function and application of AA.

  18. Terahertz spectrum of gallic acid

    Science.gov (United States)

    Wu, Meng; Zhao, Guozhong; Wang, Haiyan; Liang, Chengshen

    2009-11-01

    Gallic acid is natural polyphenol compound found in many green plants. More and more experiments have demonstrated that the gallic acid has comprehensive applications. In the field of medicine, the gallic acid plays an important role in antianaphylaxis, antineoplastic, antimycotic, anti-inflammatory, antivirotic, antiasthmatic and inhibiting the degradation of insulin. It also has a lot of applications in chemical industry, food industry and light industry. So it is important to study the terahertz time-domain spectroscopy of gallic acid. Terahertz time-domain spectroscopy (THz-TDS) is a new coherent spectral technology based on the femtosecond laser. In this work, the spectral characteristics of gallic acid in the range of 0.4 THz to 2.6 THz have been measured by THz-TDS. We obtained its absorption and refraction spectra at room temperature. The vibration absorption spectrum of the single molecule between 0.4 THz and 2.6 THz is simulated based on the Density Functional Theory (DFT). It is found that the gallic acid has the spectral response to THz wave in this frequency range. The results show the abnormal dispersion at 1.51 THz and 2.05 THz. These results can be used in the qualitative analysis of gallic acid and the medicine and food inspection.

  19. Amino acids and immune function.

    Science.gov (United States)

    Li, Peng; Yin, Yu-Long; Li, Defa; Kim, Sung Woo; Wu, Guoyao

    2007-08-01

    A deficiency of dietary protein or amino acids has long been known to impair immune function and increase the susceptibility of animals and humans to infectious disease. However, only in the past 15 years have the underlying cellular and molecular mechanisms begun to unfold. Protein malnutrition reduces concentrations of most amino acids in plasma. Findings from recent studies indicate an important role for amino acids in immune responses by regulating: (1) the activation of T lymphocytes, B lymphocytes, natural killer cells and macrophages; (2) cellular redox state, gene expression and lymphocyte proliferation; and (3) the production of antibodies, cytokines and other cytotoxic substances. Increasing evidence shows that dietary supplementation of specific amino acids to animals and humans with malnutrition and infectious disease enhances the immune status, thereby reducing morbidity and mortality. Arginine, glutamine and cysteine precursors are the best prototypes. Because of a negative impact of imbalance and antagonism among amino acids on nutrient intake and utilisation, care should be exercised in developing effective strategies of enteral or parenteral provision for maximum health benefits. Such measures should be based on knowledge about the biochemistry and physiology of amino acids, their roles in immune responses, nutritional and pathological states of individuals and expected treatment outcomes. New knowledge about the metabolism of amino acids in leucocytes is critical for the development of effective means to prevent and treat immunodeficient diseases. These nutrients hold great promise in improving health and preventing infectious diseases in animals and humans.

  20. Phytic acid in green leaves.

    Science.gov (United States)

    Hadi Alkarawi, H; Zotz, G

    2014-07-01

    Phytic acid or phytate, the free-acid form of myo-inositolhexakiphosphate, is abundant in many seeds and fruits, where it represents the major storage form of phosphorus. Although also known from other plant tissues, available reports on the occurrence of phytic acid, e.g. in leaves, have never been compiled, nor have they been critically reviewed. We found 45 published studies with information on phytic acid content in leaves. Phytic acid was almost always detected when studies specifically tried to detect it, and accounted for up to 98% of total P. However, we argue that such extreme values, which rival findings from storage organs, are dubious and probably result from measurement errors. Excluding these high values from further quantitative analysis, foliar phytic acid-P averaged 2.3 mg·g(-1) , and represented, on average, 7.6% of total P. Remarkably, the ratio of phytic acid-P to total P did not increase with total P, we even detected a negative correlation of the two variables within one species, Manihot esculenta. This enigmatic finding warrants further attention.

  1. Determination of polyfluoroalkyl phosphoric acid diesters, perfluoroalkyl phosphonic acids, perfluoroalkyl phosphinic acids, perfluoroalkyl carboxylic acids, and perfluoroalkane sulfonic acids in lake trout from the Great Lakes region.

    Science.gov (United States)

    Guo, Rui; Reiner, Eric J; Bhavsar, Satyendra P; Helm, Paul A; Mabury, Scott A; Braekevelt, Eric; Tittlemier, Sheryl A

    2012-11-01

    A comprehensive method to extract perfluoroalkyl carboxylic acids, perfluoroalkane sulfonic acids, perfluoroalkyl phosphonic acids, perfluoroalkyl phosphinic acids, and polyfluoroalkyl phosphoric acid diesters simultaneously from fish samples has been developed. The recoveries of target compounds ranged from 78 % to 121 %. The new method was used to analyze lake trout (Salvelinus namaycush) from the Great Lakes region. The results showed that the total perfluoroalkane sulfonate concentrations ranged from 0.1 to 145 ng/g (wet weight) with perfluorooctane sulfonate (PFOS) as the dominant contaminant. Concentrations in fish between lakes were in the order of Lakes Ontario ≈ Erie > Huron > Superior ≈ Nipigon. The total perfluoroalkyl carboxylic acid concentrations ranged from 0.2 to 18.2 ng/g wet weight. The aggregate mean perfluorooctanoic acid (PFOA) concentration in fish across all lakes was 0.045 ± 0.023 ng/g. Mean concentrations of PFOA were not significantly different (p > 0.1) among the five lakes. Perfluoroalkyl phosphinic acids were detected in lake trout from Lake Ontario, Lake Erie, and Lake Huron with concentration ranging from non-detect (ND) to 0.032 ng/g. Polyfluoroalkyl phosphoric acid diesters were detected only in lake trout from Lake Huron, at levels similar to perfluorooctanoic acid.

  2. Pyroligneous acid-the smoky acidic liquid from plant biomass.

    Science.gov (United States)

    Mathew, Sindhu; Zakaria, Zainul Akmar

    2015-01-01

    Pyroligneous acid (PA) is a complex highly oxygenated aqueous liquid fraction obtained by the condensation of pyrolysis vapors, which result from the thermochemical breakdown or pyrolysis of plant biomass components such as cellulose, hemicellulose, and lignin. PA produced by the slow pyrolysis of plant biomass is a yellowish brown or dark brown liquid with acidic pH and usually comprises a complex mixture of guaiacols, catechols, syringols, phenols, vanillins, furans, pyrans, carboxaldehydes, hydroxyketones, sugars, alkyl aryl ethers, nitrogenated derivatives, alcohols, acetic acid, and other carboxylic acids. The phenolic components, namely guaiacol, alkyl guaiacols, syringol, and alkyl syringols, contribute to the smoky odor of PA. PA finds application in diverse areas, as antioxidant, antimicrobial, antiinflammatory, plant growth stimulator, coagulant for natural rubber, and termiticidal and pesticidal agent; is a source for valuable chemicals; and imparts a smoky flavor for food.

  3. ELECTRODIALYTIC PRODUCTION OF HYPOPHOSPHOROUS ACID

    Institute of Scientific and Technical Information of China (English)

    CHENG Jianzhong; ZHANG Yingzhe; ZHANG Baogui; ZHANG Zhengpu

    2001-01-01

    Disclosed is a method of preparing hypophosphorous acid comprising contacting an insoluble anode with an aqueous solution of hypophosphite anions and applying a direct current through the insoluble anode to a cathode in electrical contact with the aqueous solution to generate H+ ions in the aqueous solution thereby forming a hypophosphorous acid solution. The process is simple,low cost and high efficient, which can be tied into an existing process for producing sodium hypophosphite wherein the product of sodium hypophosphite process is used as a starting material in the hypophosphorous acid process.

  4. REACTIVE EXTRACTION OF TARTARIC ACID

    Directory of Open Access Journals (Sweden)

    Natalia Marchitan

    2009-12-01

    Full Text Available The present paper describes the results of reactive extraction of tartaric acid in model systems, which can be used for its separation from secondary wine products. As extractant have been used a normal/isododecyl mixed secondary amine Amberlite LA-2. The following parameters of the separation process have been varied: nature of diluent and modifier; modifier concentration; concentration, temperature and pH of the tartaric acid solution and the stirring time, and the work intervals have been established. It was concluded that in determinated conditions the extent of tartaric acid extraction attains value 85-95%.

  5. Amino Acids from a Comet

    Science.gov (United States)

    Cook, Jamie Elisla

    2009-01-01

    NASA's Stardust spacecraft returned samples from comet 81P/Wild 2 to Earth in January 2006. Examinations of the organic compounds in cometary samples can reveal information about the prebiotic organic inventory present on the early Earth and within the early Solar System, which may have contributed to the origin of life. Preliminary studies of Stardust material revealed the presence of a suite of organic compounds including several amines and amino acids, but the origin of these compounds (cometary- vs. terrestrial contamination) could not be identified. We have recently measured the carbon isotopic ratios of these amino acids to determine their origin, leading to the first detection of a coetary amino acid.

  6. Enhanced acid tolerance of Rhizopus oryzae during fumaric acid production.

    Science.gov (United States)

    Liu, Ying; Lv, Chunwei; Xu, Qing; Li, Shuang; Huang, He; Ouyang, Pingkai

    2015-02-01

    Ensuring a suitable pH in the culture broth is a major problem in microorganism-assisted industrial fermentation of organic acids. To address this issue, we investigated the physiological changes in Rhizopus oryzae at different extracellular pH levels and attempted to solve the issue of cell shortage under low pH conditions. We compared various parameters, such as membrane fatty acids' composition, intracellular pH, and adenosine triphosphate (ATP) concentration. It was found that the shortage of intracellular ATP might be the main reason for the low rate of fumaric acid production by R. oryzae under low pH conditions. When 1 g/l citrate was added to the culture medium at pH 3.0, the intracellular ATP concentration increased from 0.4 to 0.7 µmol/mg, and the fumaric acid titer was enhanced by 63% compared with the control (pH 3.0 without citrate addition). The final fumaric acid concentration at pH 3.0 reached 21.9 g/l after 96 h of fermentation. This strategy is simple and feasible for industrial fumaric acid production under low pH conditions.

  7. A reduced susceptibility to chemoconvulsant stimulation in adenylyl cyclase 8 knockout mice

    Science.gov (United States)

    Chen, Xia; Dong, Guoying; Zheng, Changhong; Wang, Hongbing; Yun, Wenwei; Zhou, Xianju

    2015-01-01

    Objective Adenylyl cyclases (ACs) catalyze the synthesis of cAMP from ATP, and cAMP signaling affects a large number of neuronal processes. Ca2+-stimualted adenylyl cyclase 8 (AC8) expressed in the CNS plays a role in synaptic plasticity, drug addiction and ethanol sensitivity, and chronic pain. This study was to aim at examining the contributions of AC8 to epileptogenesis. Methods In this study, we observed the seizure behavior induced by kainic acid (20mg/kg or 30mg/kg) or pilocarpine (350mg/kg) in AC8 KO and wild-type mice. Next we injected kainic acid or pilocarpine to induce status epilepticus (SE), and examined neuronal degeneration (by Fluoro-Jade B staining) and mossy fiber sprouting (by Timm staining) 24 hr and 2 weeks after SE termination in the hippocampus, respectively. Finally, 15min after intraperitoneal injection of kainic acid (30mg/kg), we examined phosphor-ERK1/2 in the hippocampus by western blot and immunochemistry staining. Results We first observed that AC8 KO mutants display reduced susceptibility (including seizure latency and episodes) to two chemoconvulsants, kainic acid and pilocarpine. Moreover, we found that degenerative neurons and mossy fiber sprouting induced by chemoconvulsants were significant decreased in the hippocampus. Further, western blot and immunochemistry analysis revealed that the MAPK signaling in the hippocampus was attenuated in kainic acid-injected AC8 KO mice. Conclusion AC8 is involved in epileptogenesis, and may serve as a potential target for the treatment of epilepsy. PMID:26656781

  8. Molar extinction coefficients of some fatty acids

    Science.gov (United States)

    Sandhu, G. K.; Singh, Kulwant; Lark, B. S.; Gerward, L.

    2002-10-01

    The attenuation of gamma rays in some fatty acids, viz. formic acid (CH 2O 2), acetic acid (C 2H 4O 2), propionic acid (C 3H 6O 2), butyric acid (C 4H 8O 2), n-hexanoic acid (C 6H 12O 2), n-caprylic acid (C 8H 16O 2), lauric acid (C 12H 24O 2), myristic acid (C 14H 28O 2), palmitic acid (C 16H 32O 2), oleic acid (C 18H 34O 2) and stearic acid (C 18H 36O 2), has been measured at the photon energies 81, 356, 511, 662, 1173 and 1332 keV. Experimental values for the molar extinction coefficient, the effective atomic number and the electron density have been derived and compared with theoretical calculations. There is good agreement between experiment and theory.

  9. Omega-3 Fatty Acids during Pregnancy

    Science.gov (United States)

    OMEGA-3 FATTY ACIDS DURING PREGNANCY S HARE W ITH W OMEN OMEGA-3 FATTY ACIDS DURING PREGNANCY During pregnancy, your ... the foods you eat and vitamins you take. Omega-3 fatty acids (omega-3s) are an important ...

  10. Folic Acid: MedlinePlus Health Topic

    Science.gov (United States)

    ... Article: Folic Acid Supplementation for the Prevention of Neural Tube Defects:... Article: Folic Acid Supplementation for the Prevention of Neural Tube Defects:... Article: Folic Acid Supplementation for Prevention of ...

  11. LACTIC ACID BACTERIA: PROBIOTIC APPLICATIONS

    Directory of Open Access Journals (Sweden)

    NEENA GARG

    2015-10-01

    Full Text Available Lactic acid bacteria (LAB is a heterotrophic Gram-positive bacteria which under goes lactic acid fermentations and leads to production of lactic acid as an end product. LAB includes Lactobacillus, Leuconostoc, Pediococcus, Lactococcus and Streptococcus which are grouped together in the family lactobacillaceae. LAB shows numerous antimicrobial activities due to production of antibacterial and antifungal compounds such as organic acids, bacteriocins, diacetyl, hydrogen peroxide and reutrin. LAB are used as starter culture, consortium members and bioprotective agents in food industry that improve food quality, safety and shelf life. A variety of probiotic LAB species are available including Lactobacillus acidophilus, L. bulgaricus, L. lactis, L. plantarum, L. rhamnosus, L. reuteri, L. fermentum, Bifidobacterium longum, B. breve, B. bifidum, B. esselnsis, B. lactis, B. infantis that are currently recommended for development of functional food products with health-promoting capacities.

  12. PHYSIOLOGY OF ACID BASE BALANCE

    Directory of Open Access Journals (Sweden)

    Awati

    2014-12-01

    Full Text Available Acid-base, electrolyte, and metabolic disturbances are common in the intensive care unit. Almost all critically ill patients often suffer from compound acid-base and electrolyte disorders. Successful evaluation and management of such patients requires recognition of common patterns (e.g., metabolic acidosis and the ability to dissect one disorder from another. The intensivists needs to identify and correct these condition with the easiest available tools as they are the associated with multiorgan failure. Understanding the elements of normal physiology in these areas is very important so as to diagnose the pathological condition and take adequate measures as early as possible. Arterial blood gas analysis is one such tool for early detection of acid base disorder. Physiology of acid base is complex and here is the attempt to simplify it in our day to day application for the benefit of critically ill patients.

  13. Bile acid sequestrants for cholesterol

    Science.gov (United States)

    ... ency/patientinstructions/000787.htm Bile acid sequestrants for cholesterol To use the sharing features on this page, ... are medicines that help lower your LDL (bad) cholesterol . Too much cholesterol in your blood can stick ...

  14. Compact oleic acid in HAMLET.

    Science.gov (United States)

    Fast, Jonas; Mossberg, Ann-Kristin; Nilsson, Hanna; Svanborg, Catharina; Akke, Mikael; Linse, Sara

    2005-11-07

    HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a complex between alpha-lactalbumin and oleic acid that induces apoptosis in tumor cells, but not in healthy cells. Heteronuclear nuclear magnetic resonance (NMR) spectroscopy was used to determine the structure of 13C-oleic acid in HAMLET, and to study the 15N-labeled protein. Nuclear Overhauser enhancement spectroscopy shows that the two ends of the fatty acid are in close proximity and close to the double bond, indicating that the oleic acid is bound to HAMLET in a compact conformation. The data further show that HAMLET is a partly unfolded/molten globule-like complex under physiological conditions.

  15. Low acid producing solid propellants

    Science.gov (United States)

    Bennett, Robert R.

    1995-01-01

    The potential environmental effects of the exhaust products of conventional rocket propellants have been assessed by various groups. Areas of concern have included stratospheric ozone, acid rain, toxicity, air quality and global warming. Some of the studies which have been performed on this subject have concluded that while the impacts of rocket use are extremely small, there are propellant development options which have the potential to reduce those impacts even further. This paper discusses the various solid propellant options which have been proposed as being more environmentally benign than current systems by reducing HCI emissions. These options include acid neutralized, acid scavenged, and nonchlorine propellants. An assessment of the acid reducing potential and the viability of each of these options is made, based on current information. Such an assessment is needed in order to judge whether the potential improvements justify the expenditures of developing the new propellant systems.

  16. Biotechnological production of citric acid

    Directory of Open Access Journals (Sweden)

    Belén Max

    2010-12-01

    Full Text Available This work provides a review about the biotechnological production of citric acid starting from the physicochemical properties and industrial applications, mainly in the food and pharmaceutical sectors. Several factors affecting citric acid fermentation are discussed, including carbon source, nitrogen and phosphate limitations, pH of culture medium, aeration, trace elements and morphology of the fungus. Special attention is paid to the fundamentals of biochemistry and accumulation of citric acid. Technologies employed at industrial scale such as surface or submerged cultures, mainly employing Aspergillus niger, and processes carried out with Yarrowia lipolytica, as well as the technology for recovering the product are also described. Finally, this review summarizes the use of orange peels and other by-products as feedstocks for the bioproduction of citric acid.

  17. Antibiofilm Properties of Acetic Acid

    Science.gov (United States)

    Bjarnsholt, Thomas; Alhede, Morten; Jensen, Peter Østrup; Nielsen, Anne K.; Johansen, Helle Krogh; Homøe, Preben; Høiby, Niels; Givskov, Michael; Kirketerp-Møller, Klaus

    2015-01-01

    Bacterial biofilms are known to be extremely tolerant toward antibiotics and other antimicrobial agents. These biofilms cause the persistence of chronic infections. Since antibiotics rarely resolve these infections, the only effective treatment of chronic infections is surgical removal of the infected implant, tissue, or organ and thereby the biofilm. Acetic acid is known for its antimicrobial effect on bacteria in general, but has never been thoroughly tested for its efficacy against bacterial biofilms. In this article, we describe complete eradication of both Gram-positive and Gram-negative biofilms using acetic acid both as a liquid and as a dry salt. In addition, we present our clinical experience of acetic acid treatment of chronic wounds. In conclusion, we here present the first comprehensive in vitro and in vivo testing of acetic acid against bacterial biofilms. PMID:26155378

  18. Nucleic Acid-Based Nanoconstructs

    Science.gov (United States)

    Focuses on the design, synthesis, characterization, and development of spherical nucleic acid constructs as effective nanotherapeutic, single-entity agents for the treatment of glioblastoma multiforme and prostate cancers.

  19. Anthranilic acid derivatives from Inula japonica

    Institute of Scientific and Technical Information of China (English)

    Jiang Jiang Qin; Hui Zi Jin; Jian Jun Fu; Xiao Jia Hu; Yan Zhu; Yun Heng Shen; Shi Kai Yan; Wei Dong Zhang

    2008-01-01

    Three new anthranilic acid derivatives, N-heneicosanoylanthranilic acid (1b), N-tricosanoylanthranilic acid (1d), N-tetra-cosanoylanthranilic acid (1e), and two known N-arachidylanthranilic acid (1a) and N-docosanoylanthranilic acid (1c) were isolatedfrom the aerial parts of Inula japonica Thunb. Their structures were established by spectroscopic and chemical methods.2008 Hui Zi Jin. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

  20. 21 CFR 184.1009 - Adipic acid.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Adipic acid. 184.1009 Section 184.1009 Food and... Substances Affirmed as GRAS § 184.1009 Adipic acid. (a) Adipic acid (C6H10O4, CAS Reg. No. 00124-04-9) is also known as 1,4-butanedicarboxylic acid or hexane-dioic acid. It is prepared by nitric acid oxidation...

  1. 21 CFR 172.862 - Oleic acid derived from tall oil fatty acids.

    Science.gov (United States)

    2010-04-01

    ... FOOD FOR HUMAN CONSUMPTION Multipurpose Additives § 172.862 Oleic acid derived from tall oil fatty acids. The food additive oleic acid derived from tall oil fatty acids may be safely used in food and as... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Oleic acid derived from tall oil fatty acids....

  2. Simultaneous analysis of small organic acids and humic acids using high performance size exclusion chromatography

    NARCIS (Netherlands)

    Qin, X.P.; Liu, F.; Wang, G.C.; Weng, L.P.

    2012-01-01

    An accurate and fast method for simultaneous determination of small organic acids and much larger humic acids was developed using high performance size exclusion chromatography. Two small organic acids, i.e. salicylic acid and 2,3-dihydroxybenzoic acid, and one purified humic acid material were used

  3. Cyanuric acid-epichlorohydrin prepolymers

    OpenAIRE

    Pedroso, L. M.; Simões, P; Portugal, A.

    2006-01-01

    In this study, we investigated the reaction of cyanuric acid and epichlorohydrin (ECH). SnCl4 was used as a catalyst. Several reaction conditions were tested, and the products were analyzed by means of Fourier transform infrared and 1H-NMR spectroscopy, hydroxyl group content, molar mass, elemental and thermal analysis, viscosity, and density. ECH reacted with the amine groups of the cyanuric acid ring to form lateral chains that contained chloroalkyl and hydroxyl end groups. Full substitutio...

  4. Nucleic Acid Aptamers Against Proteases

    DEFF Research Database (Denmark)

    Dupont, D M; Andersen, L M; Bøtkjær, Kenneth Alrø

    2011-01-01

    Proteases are potential or realized therapeutic targets in a wide variety of pathological conditions. Moreover, proteases are classical subjects for studies of enzymatic and regulatory mechanisms. We here review the literature on nucleic acid aptamers selected with proteases as targets. Designing...... strategies and of new principles for regulating the activity of the inhibitory action of aptamers of general interest to researchers working with nucleic acid aptamers...

  5. Alternative to Nitric Acid Passivation

    Science.gov (United States)

    Kessel, Kurt R.

    2016-01-01

    Corrosion is an extensive problem that affects the National Aeronautics and Space Administration (NASA) and European Space Agency (ESA). The deleterious effects of corrosion result in steep costs, asset downtime affecting mission readiness, and safety risks to personnel. It is vital to reduce corrosion costs and risks in a sustainable manner. The primary objective of this effort is to qualify citric acid as an environmentally-preferable alternative to nitric acid for passivation of stainless steel alloys.

  6. Biocatalytic reduction of carboxylic acids.

    Science.gov (United States)

    Napora-Wijata, Kamila; Strohmeier, Gernot A; Winkler, Margit

    2014-06-01

    An increasing demand for non-petroleum-based products is envisaged in the near future. Carboxylic acids such as citric acid, succinic acid, fatty acids, and many others are available in abundance from renewable resources and they could serve as economic precursors for bio-based products such as polymers, aldehyde building blocks, and alcohols. However, we are confronted with the problem that carboxylic acid reduction requires a high level of energy for activation due to the carboxylate's thermodynamic stability. Catalytic processes are scarce and often their chemoselectivity is insufficient. This review points at bio-alternatives: currently known enzyme classes and organisms that catalyze the reduction of carboxylic acids are summarized. Two totally distinct biocatalyst lines have evolved to catalyze the same reaction: aldehyde oxidoreductases from anaerobic bacteria and archea, and carboxylate reductases from aerobic sources such as bacteria, fungi, and plants. The majority of these enzymes remain to be identified and isolated from their natural background in order to evaluate their potential as industrial biocatalysts.

  7. [Women's knowledge of folic acid].

    Science.gov (United States)

    Salgues, Mathilde; Damase-Michel, Christine; Montastruc, Jean-Louis; Lacroix, Isabelle

    2017-06-01

    Many trials have shown that folic acid supplementation before and during pregnancy reduces the risk of neural tube defects in general population. We investigated the knowledge of folic acid in women of child-bearing age. Women of child-bearing age were interviewed by 20 pharmacists living in Haute-Garonne between January and February 2014. One hundred ninety-six women were included in the present study. Out of them, 36% of women never heard of folic acid and 82% were not aware of its benefits. Knowledge was higher in older women, women in a couple and women with higher educational level (Pfolic acid during pregnancy. Moreover, previous studies have shown that French women have low use of folic acid during peri-conceptional period. Information of general population will be required for a better prevention of folic acid-preventable NTDs. Copyright © 2016 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

  8. SATURATED PICRIC ACID PREVENTS AUTOPHAGIA

    Directory of Open Access Journals (Sweden)

    V Rahimi-Movaghar

    2008-08-01

    Full Text Available "nThe dysesthesia and paresthesia that occurs in laboratory rats after spinal cord injury (SCI results in autophagia. This self-destructive behavior interferes with functional assessments in designed studies and jeopardizes the health of the injured rat. In this study, we evaluated role of saturated picric acid in the prevention of autophagia and self-mutilation. All rats were anesthetized with an intraperitoneal injection of a mixture of ketamine (100 mg/kg and xylazine (10 mg/kg for the SCI procedures. In the first 39 rats, no solution applied to the hind limbs, but in the next 26 cases, we smeared the saturated picric acid on the tail, lower extremities, pelvic, and abdomen of the rats immediately after SCI. In the rats without picric acid, 23 rats died following autophagia, but in the 26 rats with picric acid, there was no autophagia (P < 0.001. Picric acid side effects in skin and gastrointestinal signs such as irritation, redness and diarrhea were not seen in any rat. Saturated picric acid is a topical solution that if used appropriately and carefully, might be safe and effectively prevents autophagia and self-mutilation. When the solution is applied to the lower abdomen and limbs, we presume that its bitterness effectively prevents the rat from licking and biting the limb.

  9. Evaluation of ascorbic acid in protecting labile folic acid derivatives.

    Science.gov (United States)

    Wilson, S D; Horne, D W

    1983-11-01

    The use of ascorbic acid as a reducing agent to protect labile, reduced derivatives of folic acid has been evaluated by high-performance liquid chromatographic separations and Lactobacillus casei microbiological assay of eluate fractions. Upon heating for 10 min at 100 degrees C, solutions of tetrahydropteroylglutamic acid (H4PteGlu) in 2% sodium ascorbate gave rise to 5,10-methylene-H4PteGlu and 5-methyl-H4PteGlu. H2PteGlu acid gave rise to 5-methyl-H4PteGlu and PteGlu. 10-Formyl-H4PteGlu gave rise to 5-formyl-H4PteGlu and 10-formyl-PteGlu. 5-Formyl-H4-PteGlu gave rise to a small amount of 10-formyl-PteGlu. 5-Methyl-H4PteGlu and PteGlu appeared stable to these conditions. These interconversions were not seen when solutions of these folate derivatives were kept at 0 degrees C in 1% ascorbate. These observations indicate that elevated temperatures are necessary for the interconversions of folates in ascorbate solutions. Assays of ascorbic acid solutions indicated the presence of formaldehyde (approximately equal to 6 mM). This was confirmed by the identification of 3,5-diacetyl-1,4-dihydrolutidine by UV, visible, and fluorescence spectroscopy and by thin-layer chromatography of chloroform extracts of the reaction mixture of ascorbic acid solutions, acetylacetone, and ammonium acetate. These results indicate that solutions of sodium ascorbate used at elevated temperatures are not suitable for extracting tissue for the subsequent assay of the individual folic acid derivatives.

  10. Performance of Different Acids on Sandstone Formations

    Directory of Open Access Journals (Sweden)

    M. A. Zaman

    2013-12-01

    Full Text Available Stimulation of sandstone formations is a challenging task, which involves several chemicals and physical interactions of the acid with the formation. Some of these reactions may result in formation damage. Mud acid has been successfully used to stimulate sandstone reservoirs for a number of years. It is a mixture of hydrofluoric (HF and hydrochloric (HCl acids designed to dissolve clays and siliceous fines accumulated in the near-wellbore region. 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 paper 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 calculated are porosity, permeability, and FESEM Analysis and Strength tests. All of these new combinations shows that these have the potential to be used as acidizing acids on sandstone formations.

  11. Vanadocene reactions with hydroxy acids. [Hydroxy acids: acetylsalicylic, gallic, lactic, salicyclic, orotic,. gamma. -hydroxybutyric acids

    Energy Technology Data Exchange (ETDEWEB)

    Latyaeva, V.N.; Lineva, A.N.; Zimina, S.V.; Ehllert, O.G.; Arsen' eva, T.I. (Gor' kovskij Meditsinskij Inst. (USSR))

    1984-03-01

    To prepare a series of vanadium cyclopentadienylcarboxylates soluble in water, the vanadocene reactions with lactic, ..gamma..-oxybutyric-, salicylic,- gallic-, orotic-, and acetylsalicylic acids have been studied. To determine the influence of cyclopentadienyl groups, bound with a vanadium atom, on the physiological activity of the complexes formed, vanadium halides are made to react with lactic acid. Only the vanadocene reaction with orotic acid was conducted in an aqueous medium, other interactions were realized in the diethyl ether, toluene, T, H, P medium. The interaction of vanadocene and vanadium halides with lactic-, salicylic-, acetylsalicylic- and gallic acids was found to lead to the formation of water-soluble vanadium complexes of Cp/sub 2/, VOCOR or CpV (OCOR)/sub 2/ type. The data on the produced compounds yield, their IR spectra, decomposition temperatures, solubility, effective magnetic moments are presented.

  12. An Efficient Procedure for Esterification of Aryloxyacetic Acid and Arylthioacetic Acid Catalyzed by Silica Sulfuric Acid

    Institute of Scientific and Technical Information of China (English)

    LI,Hong-Ya; LI,Ji-Tai; LI,Hui-Zhang

    2004-01-01

    @@ Aryloxyacetate and arylthioacetate are wildly used in herbicides, plant regulator and insecticides. Recently, Wille et al. have reported that methyl aryloxyacetate is an efficient agent to prevent and treat allergic contact dermatitis.[1] The most popular synthesis is by heating sodium phenoxide (mercaptide) with ethyl chloroacetate in DMF,[2] or by the esterification of acid with alcohol using concentrated H2SO4 as catalyst.[3] In this paper, synthesis of aryloxyacetate and aryl thioacetate from aryloxyacetic acid and arylthioacetic acid respectively in ether catalyzed by silica sulfuric acid in 83%~94% yields is described. The catalyst is reused for 3 times without significant loss of activity (Entry 4). Compared with common procedures, the present procedure possesses the advantages of the operational simplicity, short reaction time,less-corrosion, high yield and reusable catalyst.

  13. Fatty acid-amino acid conjugates diversification in lepidopteran caterpillars.

    Science.gov (United States)

    Yoshinaga, Naoko; Alborn, Hans T; Nakanishi, Tomoaki; Suckling, David M; Nishida, Ritsuo; Tumlinson, James H; Mori, Naoki

    2010-03-01

    Fatty acid amino acid conjugates (FACs) have been found in noctuid as well as sphingid caterpillar oral secretions; in particular, volicitin [N-(17-hydroxylinolenoyl)-L-glutamine] and its biochemical precursor, N-linolenoyl-L-glutamine, are known elicitors of induced volatile emissions in corn plants. These induced volatiles, in turn, attract natural enemies of the caterpillars. In a previous study, we showed that N-linolenoyl-L-glutamine in larval Spodoptera litura plays an important role in nitrogen assimilation which might be an explanation for caterpillars synthesizing FACs despite an increased risk of attracting natural enemies. However, the presence of FACs in lepidopteran species outside these families of agricultural interest is not well known. We conducted FAC screening of 29 lepidopteran species, and found them in 19 of these species. Thus, FACs are commonly synthesized through a broad range of lepidopteran caterpillars. Since all FAC-containing species had N-linolenoyl-L-glutamine and/or N-linoleoyl-L-glutamine in common, and the evolutionarily earliest species among them had only these two FACs, these glutamine conjugates might be the evolutionarily older FACs. Furthermore, some species had glutamic acid conjugates, and some had hydroxylated FACs. Comparing the diversity of FACs with lepidopteran phylogeny indicates that glutamic acid conjugates can be synthesized by relatively primitive species, while hydroxylation of fatty acids is limited mostly to larger and more developed macrolepidopteran species.

  14. Molecular screening of wine lactic acid bacteria degrading hydroxycinnamic acids.

    Science.gov (United States)

    de las Rivas, Blanca; Rodríguez, Héctor; Curiel, José Antonio; Landete, José María; Muñoz, Rosario

    2009-01-28

    The potential to produce volatile phenols from hydroxycinnamic acids was investigated for lactic acid bacteria (LAB) isolated from Spanish grape must and wine. A PCR assay was developed for the detection of LAB that potentially produce volatile phenols. Synthetic degenerate oligonucleotides for the specific detection of the pdc gene encoding a phenolic acid decarboxylase were designed. The pdc PCR assay amplifies a 321 bp DNA fragment from phenolic acid decarboxylase. The pdc PCR method was applied to 85 strains belonging to the 6 main wine LAB species. Lactobacillus plantarum, Lactobacillus brevis, and Pediococcus pentosaceus strains produce a positive response in the pdc PCR assay, whereas Oenococcus oeni, Lactobacillus hilgardii, and Leuconostoc mesenteroides strains did not produce the expected PCR product. The production of vinyl and ethyl derivatives from hydroxycinnamic acids in culture media was determined by high-performance liquid chromatography. A relationship was found between pdc PCR amplification and volatile phenol production, so that the LAB strains that gave a positive pdc PCR response produce volatile phenols, whereas strains that did not produce a PCR amplicon did not produce volatile phenols. The proposed method could be useful for a preliminary identification of LAB strains able to produce volatile phenols in wine.

  15. Gas-Phase Acidities of Phosphorylated Amino Acids.

    Science.gov (United States)

    Stover, Michele L; Plummer, Chelsea E; Miller, Sean R; Cassady, Carolyn J; Dixon, David A

    2015-11-19

    Gas-phase acidities and heats of formation have been predicted at the G3(MP2)/SCRF-COSMO level of theory for 10 phosphorylated amino acids and their corresponding amides, including phospho-serine (pSer), -threonine (pThr), and -tyrosine (pTyr), providing the first reliable set of these values. The gas-phase acidities (GAs) of the three named phosphorylated amino acids and their amides have been determined using proton transfer reactions in a Fourier transform ion cyclotron mass spectrometer. Excellent agreement was found between the experimental and predicted GAs. The phosphate group is the deprotonation site for pSer and pThr and deprotonation from the carboxylic acid generated the lowest energy anion for pTyr. The infrared spectra were calculated for six low energy anions of pSer, pThr, and pTyr. For deprotonated pSer and pThr, good agreement is found between the experimental IRMPD spectra and the calculated spectra for our lowest energy anion structure. For pTyr, the IR spectra for a higher energy phosphate deprotonated structure is in good agreement with experiment. Additional experiments tested electrospray ionization (ESI) conditions for pTyr and determined that variations in solvent, temperature, and voltage can result in a different experimental GA value, indicating that ESI conditions affect the conformation of the pTyr anion.

  16. [Regulating acid stress resistance of lactic acid bacteria--a review].

    Science.gov (United States)

    Wu, Chongde; Huang, Jun; Zhou, Rongqing

    2014-07-04

    As cell factories, lactic acid bacteria are widely used in food, agriculture, pharmaceutical and other industries. Acid stress is one the important survival challenges encountered by lactic acid bacteria both in fermentation process and in the gastrointestinal tract. Recently, the development of systems biology and metabolic engineering brings unprecedented opportunity for further elucidating the acid tolerance mechanisms and improving the acid stress resistance of lactic acid bacteria. This review addresses physiological mechanisms of lactic acid bacteria during acid stress. Moreover, strategies to improve the acid stress resistance of lactic acid were proposed.

  17. Extractive fermentation of acetic acid

    Energy Technology Data Exchange (ETDEWEB)

    Busche, R.M. [Bio En-Gene-Er Associates, Inc., Wilmington, DE (United States)

    1991-12-31

    In this technoeconomic evaluation of the manufacture of acetic acid by fermentation, the use of the bacterium: Acetobacter suboxydans from the old vinegar process was compared with expected performance of the newer Clostridium thermoaceticum bacterium. Both systems were projected to operate as immobilized cells in a continuous, fluidized bed bioreactor, using solvent extraction to recover the product. Acetobacter metabolizes ethanol aerobically to produce acid at 100 g/L in a low pH medium. This ensures that the product is in the form of a concentrated extractable free acid, rather than as an unextractable salt. Unfortunately, yields from glucose by way of the ethanol fermentation are poor, but near the biological limits of the organisms involved. Conversely, C. thermoaceticum is a thermophilic anaerobe that operates at high fermentation rates on glucose at neutral pH to produce acetate salts directly in substantially quantitative yields. However, it is severely inhibited by product, which restricts concentration to a dilute 20 g/L. An improved Acetobacter system operating with recycled cells at 50 g/L appears capable of producing acid at $0.38/lb, as compared with a $0.29/lb price for synthetic acid. However, this system has only a limited margin for process improvement. The present Clostridium system cannot compete, since the required selling price would be $0.42/lb. However, if the organism could be adapted to tolerate higher product concentrations at acid pH, selling price could be reduced to $0.22/lb, or about 80% of the price of synthetic acid.

  18. Anaerobic biotransformation of organoarsenical pesticides monomethylarsonic acid and dimethylarsinic acid

    Science.gov (United States)

    Sierra-Alvarez, R.; Yenal, U.; Feld, J.A.; Kopplin, M.; Gandolfi, A.J.; Garbarino, J.R.

    2006-01-01

    Monomethylarsonic acid (MMAV) and dimethylarsinic acid (DMAV) are extensively utilized as pesticides, introducing large quantities of arsenic into the environment. Once released into the environment, these organoarsenicals are subject to microbial reactions. Aerobic biodegradation of MMAV and DMAV has been evaluated, but little is known about their fate in anaerobic environments. The objective of this study was to evaluate the biotransformation of MMAV and DMAV in anaerobic sludge. Biologically mediated conversion occurred under methanogenic or sulfate-reducing conditions but not in the presence of nitrate. Monomethylarsonous acid (MMAIII) was consistently observed as an important metabolite of MMAV degradation, and it was recovered in molar yields ranging from 5 to 47%. The main biotransformation product identified from DMAV metabolism was MMAV, which was recovered in molar yields ranging from 8 to 65%. The metabolites indicate that reduction and demethylation are important steps in the anaerobic bioconversion of MMAV and DMAV, respectively. ?? 2006 American Chemical Society.

  19. Gallic Acid, Ellagic Acid and Pyrogallol Reaction with Metallic Iron

    Science.gov (United States)

    Jaén, J. A.; González, L.; Vargas, A.; Olave, G.

    2003-06-01

    The reaction between gallic acid, ellagic acid and pyrogallol with metallic iron was studied using infrared and Mössbauer spectroscopy. Most hydrolysable tannins with interesting anticorrosive or inhibition properties are structurally related to these compounds, thus they may be used as models for the study of hydrolysable tannins and related polyphenols. The interaction was followed up to 3 months. Results indicated two different behaviors. At polyphenol concentrations higher than 1% iron converts to sparingly soluble and amorphous ferric (and ferrous) polyphenolate complexes. At lower concentrations (0.1%), the hydrolysis reactions are dominant, resulting in the formation of oxyhydroxides, which can be further reduced to compounds like magnetite by the polyphenols.

  20. Kadcoccinic Acids A-J, Triterpene Acids from Kadsura coccinea.

    Science.gov (United States)

    Liang, Cheng-Qin; Shi, Yi-Ming; Wang, Wei-Guang; Hu, Zheng-Xi; Li, Yan; Zheng, Yong-Tang; Li, Xiao-Nian; Du, Xue; Pu, Jian-Xin; Xiao, Wei-Lie; Zhang, Hong-Bin; Sun, Han-Dong

    2015-08-28

    Eleven triterpene acids including 10 new compounds (kadcoccinic acids A-J, 1-10) were isolated from the stems of Kadsura coccinea. Except for 10, these compounds feature a rearranged lanostane skeleton with a 6/6/5/6 tetracyclic ring system, and compounds 1 and 2 are the first examples of 2,3-seco-6/6/5/6-fused tetracyclic triterpenoids. Their structures were established primarily by spectroscopic and spectrometric methods. Additionally, the absolute configuration of 3 was determined by single-crystal X-ray diffraction. Several of the compounds isolated were tested for their anti-HIV-1 and cytotoxic activities.

  1. Boronic acid-based autoligation of nucleic acids

    DEFF Research Database (Denmark)

    Barbeyron, R.; Vasseur, J.-J.; Smietana, M.;

    2013-01-01

    Abstract: The development of synthetic systems displaying dynamic and adaptive characteristics is a formidable challenge with wide applications from biotechnology to therapeutics. Recently, we described a dynamic and programmable nucleic acid-based system relying on the formation of reversible...... boronate internucleosidic linkages. The DNA- or RNA-templated system comprises a 5′-ended boronic acid probe connecting a 3′-ended ribonucleosidic oligonucleotide partner. To explore the dominant factors that control the reversible linkage, we synthesized a series of 3′-end modified ribonucleotidic strands...

  2. Isothermal Amplification of Nucleic Acids.

    Science.gov (United States)

    Zhao, Yongxi; Chen, Feng; Li, Qian; Wang, Lihua; Fan, Chunhai

    2015-11-25

    Isothermal amplification of nucleic acids is a simple process that rapidly and efficiently accumulates nucleic acid sequences at constant temperature. Since the early 1990s, various isothermal amplification techniques have been developed as alternatives to polymerase chain reaction (PCR). These isothermal amplification methods have been used for biosensing targets such as DNA, RNA, cells, proteins, small molecules, and ions. The applications of these techniques for in situ or intracellular bioimaging and sequencing have been amply demonstrated. Amplicons produced by isothermal amplification methods have also been utilized to construct versatile nucleic acid nanomaterials for promising applications in biomedicine, bioimaging, and biosensing. The integration of isothermal amplification into microsystems or portable devices improves nucleic acid-based on-site assays and confers high sensitivity. Single-cell and single-molecule analyses have also been implemented based on integrated microfluidic systems. In this review, we provide a comprehensive overview of the isothermal amplification of nucleic acids encompassing work published in the past two decades. First, different isothermal amplification techniques are classified into three types based on reaction kinetics. Then, we summarize the applications of isothermal amplification in bioanalysis, diagnostics, nanotechnology, materials science, and device integration. Finally, several challenges and perspectives in the field are discussed.

  3. Reclamation of acid coal refuse

    Energy Technology Data Exchange (ETDEWEB)

    Olsen, F.J.; Chong, S.K. (Southern Illinois Univ., Carbondale, IL (USA))

    1991-07-01

    Slurry (coal refuse), which contains pyritic materials, produces sulfuric acid when wetted and oxidized. The acidity, together with droughtiness and high surface temperatures, create a complex problem for revegetation. Four grasses, orchardgrass (Dactylis glomerata L.), redtop (Agrostis alba L.), reed canarygrass (Phalaris arundinacea L.) and tall fescue (Festuca arundinacea Shreb.), were planted on an acid slurry site at Captain Mine, Arch of Illinois Inc., Perry County, IL, USA, to evaluate the effects of soil amendments. Organic material from composted garbage (0, 112, 224 and 336 Mg/ha), limestone (0, 45, 90 and 135 Mg/ha) and a mixture of organic material and limestone (56/22.5, 112/45 and 168/67.5 Mg/ha) were incorporated into the slurry. All the grasses established succesfully and persisted best on treatments involving the addition of limestone. Tall fescue and reed canarygrass were the grasses best suited for the revegetation of the acid slurry impoundments. The grasses did not accumulate heavy metals to levels considered potentially toxic to livestock. The application of limestone with or without organic material appears to be a possible alternative method for revegetating acid slurry without the addition of a soil cover. 6 tabs., 12 refs.

  4. 21 CFR 582.5013 - Ascorbic acid.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ascorbic acid. 582.5013 Section 582.5013 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5013 Ascorbic acid. (a) Product. Ascorbic acid. 1 Amino acids listed in this subpart may...

  5. Microbial production of amino acids in Japan.

    Science.gov (United States)

    Kumagai, H

    2000-01-01

    The microbial biotechnology of amino acids production which was developed and industrialized in Japan have been summarized. The amino acids include L-glutamic acid, L-lysine, L-threonine, L-aspartic acid, L-alanine, L-cysteine, L-dihydroxyphenylalanine, D-p-hydroxyphenyl-glycine, and hydroxy-L-proline.

  6. 21 CFR 184.1097 - Tannic acid.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Tannic acid. 184.1097 Section 184.1097 Food and... Substances Affirmed as GRAS § 184.1097 Tannic acid. (a) Tannic acid (CAS Reg. No. 1401-55-4), or hydrolyzable gallotannin, is a complex polyphenolic organic structure that yields gallic acid and either glucose or quinic...

  7. Effect of propionic acid on citric acid fermentation in an integrated citric acid-methane fermentation process.

    Science.gov (United States)

    Xu, Jian; Bao, Jia-Wei; Su, Xian-Feng; Zhang, Hong-Jian; Zeng, Xin; Tang, Lei; Wang, Ke; Zhang, Jian-Hua; Chen, Xu-Sheng; Mao, Zhong-Gui

    2016-03-01

    In this study, an integrated citric acid-methane fermentation process was established to solve the problem of wastewater treatment in citric acid production. Citric acid wastewater was treated through anaerobic digestion and then the anaerobic digestion effluent (ADE) was further treated and recycled for the next batch citric acid fermentation. This process could eliminate wastewater discharge and reduce water resource consumption. Propionic acid was found in the ADE and its concentration continually increased in recycling. Effect of propionic acid on citric acid fermentation was investigated, and results indicated that influence of propionic acid on citric acid fermentation was contributed to the undissociated form. Citric acid fermentation was inhibited when the concentration of propionic acid was above 2, 4, and 6 mM in initial pH 4.0, 4.5 and, 5.0, respectively. However, low concentration of propionic acid could promote isomaltase activity which converted more isomaltose to available sugar, thereby increasing citric acid production. High concentration of propionic acid could influence the vitality of cell and prolong the lag phase, causing large amount of glucose still remaining in medium at the end of fermentation and decreasing citric acid production.

  8. Anions in Nucleic Acid Crystallography.

    Science.gov (United States)

    D'Ascenzo, Luigi; Auffinger, Pascal

    2016-01-01

    Nucleic acid crystallization buffers contain a large variety of chemicals fitting specific needs. Among them, anions are often solely considered for pH-regulating purposes and as cationic co-salts while their ability to directly bind to nucleic acid structures is rarely taken into account. Here we review current knowledge related to the use of anions in crystallization buffers along with data on their biological prevalence. Chloride ions are frequently identified in crystal structures but display low cytosolic concentrations. Hence, they are thought to be distant from nucleic acid structures in the cell. Sulfate ions are also frequently identified in crystal structures but their localization in the cell remains elusive. Nevertheless, the characterization of the binding properties of these ions is essential for better interpreting the solvent structure in crystals and consequently, avoiding mislabeling of electron densities. Furthermore, understanding the binding properties of these anions should help to get clues related to their potential effects in crowded cellular environments.

  9. Toxicologic Study of Monochloroacetic Acid

    Institute of Scientific and Technical Information of China (English)

    Lu Bo; Zhan Ping

    2006-01-01

    @@ Monochloroacetic Acid (MCA) is a chlorinated analog of acetic acids. MCA and its sodium salt (SMCA) are widely used as a chemical intermediate (primarily in the manufacture of chlorophenoxy herbicides,carboxymethylcelluose, glycine and indigoid dyes).Moreover, MCA has been found as a common by-product of the chlorination of drinking water. Chloroacetates are ubiquitous in the environment, and MCA is the most abundant among chloroacetates. A background level of 0.1 - 1μg/L is expected to occur in precipitation[1]. Total world wide annual production of MCA reported was about 400 000 tons[2]. Many studies have showed that MCA not only caused acute or chronic damage to the skin , liver, kidney, heart, brain and other organs, but also caused acute death systemically under high concentration[2,3]. So this article will discuss the toxic effect of Monochloroacetic Acid in Toxicology.

  10. Fauna of an acid stream

    Energy Technology Data Exchange (ETDEWEB)

    Jewell, M.E.

    1922-01-01

    The hydrogen-ion concentration of the water of the big muddy river was found to vary between pH 5.8 and pH 6.8 to 7.2, the higher acidity occurring during the winter. The bottom fauna was characterized by the abundance of clams and shrimp, and by the absence of branchiate snails and ephemerid nymphs. Fish fry and fingerlings were found in large numbers during the summer in weakly acid water, pH 6.8. Observations on our acid streams, continued over a considerable period of time, would tell us much concerning the adaptability of various species to different hydrogen-ion concentrations and are greatly needed in the interpretation of experimental data.

  11. Be an acid rain detective

    Energy Technology Data Exchange (ETDEWEB)

    Atwill, L.

    1982-07-01

    Acid rain is discussed in a question and answer format. The article is aimed at educating sport fishermen on the subject, and also to encourage them to write their congressmen, senators, and the President about the acid rain problem. The article also announces the availability of an acid rain test kit available through the magazine, ''Sports Afield.'' The kit consists of pH-test paper that turns different shades of pink and blue according to the pH of the water tested. The color of the test paper is then compared to a color chart furnished in the kit and an approximate pH can be determined.

  12. Political economy of acid rain

    Energy Technology Data Exchange (ETDEWEB)

    Regens, J.L.

    Over the past decade, acid rain has been transformed from a relatively unnoticed area of scientific inquiry into a major environmental issue of regional, national, and international concern. What is acid rain, why has it acquired such relatively sudden political prominence, and what are the prospects for the adoption of policies addressing this issue. These questions illustrate how the regional cleavages inherent in transboundary air pollution problems have fractured the political coalitions which supported earlier environmental legislation. Understanding the basis for that transformation, which requires information from the natural and physical sciences as well as insights into the economics and politics of the acid rain issue, is central to developing an appreciation of the constraints on policymaking for air-quality management in the United States. 35 references.

  13. Tumor Acidity as Evolutionary Spite

    Directory of Open Access Journals (Sweden)

    Mohammed E. A. Shayoub

    2011-01-01

    Full Text Available Most cancer cells shift their metabolic pathway from a metabolism reflecting the Pasteur-effect into one reflecting the Warburg-effect. This shift creates an acidic microenvironment around the tumor and becomes the driving force for a positive carcinogenesis feedback loop. As a consequence of tumor acidity, the tumor microenvironment encourages a selection of certain cell phenotypes that are able to survive in this caustic environment to the detriment of other cell types. This selection can be described by a process which can be modeled upon spite: the tumor cells reduce their own fitness by making an acidic environment, but this reduces the fitness of their competitors to an even greater extent. Moreover, the environment is an important dimension that further drives this spite process. Thus, diminishing the selective environment most probably interferes with the spite process. Such interference has been recently utilized in cancer treatment.

  14. Tumor Acidity as Evolutionary Spite

    Energy Technology Data Exchange (ETDEWEB)

    Alfarouk, Khalid O., E-mail: khalid.alfarouk@act.sd [Department of Biotechnology, Africa City of Technology, Khartoum (Sudan); Department of Pharmaceutics, Faculty of Pharmacy, University of Khartoum, Khartoum (Sudan); Muddathir, Abdel Khalig [Department of Pharmacognosy, Faculty of Pharmacy, University of Khartoum, Khartoum (Sudan); Shayoub, Mohammed E. A. [Department of Pharmaceutics, Faculty of Pharmacy, University of Khartoum, Khartoum (Sudan)

    2011-01-20

    Most cancer cells shift their metabolic pathway from a metabolism reflecting the Pasteur-effect into one reflecting the Warburg-effect. This shift creates an acidic microenvironment around the tumor and becomes the driving force for a positive carcinogenesis feedback loop. As a consequence of tumor acidity, the tumor microenvironment encourages a selection of certain cell phenotypes that are able to survive in this caustic environment to the detriment of other cell types. This selection can be described by a process which can be modeled upon spite: the tumor cells reduce their own fitness by making an acidic environment, but this reduces the fitness of their competitors to an even greater extent. Moreover, the environment is an important dimension that further drives this spite process. Thus, diminishing the selective environment most probably interferes with the spite process. Such interference has been recently utilized in cancer treatment.

  15. Solubilities of Isophthalic Acid in Acetic Acid + Water Solvent Mixtures

    Institute of Scientific and Technical Information of China (English)

    CHENG Youwei; HUO Lei; LI Xi

    2013-01-01

    The solubilities of isophthalic acid (1) in binary acetic acid (2) + water (3) solvent mixtures were determined in a pressurized vessel.The temperature range was from 373.2 to 473.2K and the range of the mole fraction of acetic acid in the solvent mixtures was from x2 =0 to 1.A new method to measure the solubility was developed,which solved the problem of sampling at high temperature.The experimental results indicated that within the temperature range studied,the solubilities of isophthalic acid in all mixtures showed an increasing trend with increasing temperature.The experimental solubilities were correlated by the Buchowski equation,and the calculate results showed good agreement with the experimental solubilities.Furthermore,the mixed solvent systems were found to exhibit a maximum solubility effect on the solubility,which may be attributed to the intermolecular association between the solute and the solvent mixture.The maximum solubility effect was well modeled by the modified Wilson equation.

  16. Ghrelin and gastric acid secretion

    OpenAIRE

    Yakabi, Koji; Kawashima, Junichi; Kato, Shingo

    2008-01-01

    Ghrelin, a novel growth hormone-releasing peptide, was originally isolated from rat and human stomach. Ghrelin has been known to increase the secretion of growth hormone (GH), food intake, and body weight gain when administered peripherally or centrally. Ghrelin is also known to stimulate the gastric motility and the secretion of gastric acid. In the previous studies, the action of ghrelin on acid secretion was shown to be as strong as that of histamine and gastrin in in-vivo experiment. In t...

  17. CACODYLIC ACID (DMAV): METABOLISM AND ...

    Science.gov (United States)

    The cacodylic acid (DMAV) issue paper discusses the metabolism and pharmacokinetics of the various arsenical chemicals; evaluates the appropriate dataset to quantify the potential cancer risk to the organic arsenical herbicides; provides an evaluation of the mode of carcinogenic action (MOA) for DMAV including a consideration of the key events for bladder tumor formation in rats, other potential modes of action; and also considers the human relevance of the proposed animal MOA. As part of tolerance reassessment under the Food Quality Protection Act for the August 3, 2006 deadline, the hazard of cacodylic acid is being reassessed.

  18. Spherical agglomeration of acetylsalicylic acid

    Directory of Open Access Journals (Sweden)

    Polowczyk Izabela

    2016-01-01

    Full Text Available In this paper spherical agglomeration of acetylsalicylic acid was described. In the first step, the system of good and poor solvents as well as bridging liquid was selected. As a result of a preliminary study, ethyl alcohol, water and carbon tetrachloride were used as the good solvent, poor one, and bridging liquid, respectively. Then, the amount of acetylsalicylic acid and the ratio of the solvents as well as the volume of the bridging liquid were examined. In the last step, the agglomeration conditions, such as mixing intensity and time, were investigated. The spherical agglomerates obtained under optimum conditions could be subjected to a tableting process afterwards.

  19. Salicylic acid-independent plant defence pathways

    OpenAIRE

    Pieterse, C.M.J.; Loon, L. C. Van

    1999-01-01

    Salicylic acid is an important signalling molecule involved in both locally and systemically induced disease resistance responses. Recent advances in our understanding of plant defence signalling have revealed that plants employ a network of signal transduction pathways, some of which are independent of salicylic acid. Evidence is emerging that jasmonic acid and ethylene play key roles in these salicylic acid-independent pathways. Cross-talk between the salicylic acid-dependent and the salicy...

  20. General consideration on sialic acid chemistry.

    Science.gov (United States)

    Cao, Hongzhi; Chen, Xi

    2012-01-01

    Sialic acids, also known as neuraminic acids, are a family of negatively charged α-keto acids with a nine-carbon backbone. These unique sugars have been found at the termini of many glycan chains of vertebrate cell surface, which play pivotal roles in mediating or modulating a variety of physiological and pathological processes. This brief review covers general approaches for synthesizing sialic acid containing structures. Recently developed synthetic methods along with structural diversities and biological functions of sialic acid are discussed.

  1. 21 CFR 186.1316 - Formic acid.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Formic acid. 186.1316 Section 186.1316 Food and... Substances Affirmed as GRAS § 186.1316 Formic acid. (a) Formic acid (CH2O2, CAS Reg. No. 64-18-6) is also referred to as methanoic acid or hydrogen carboxylic acid. It occurs naturally in some insects and is...

  2. Modulating the electronic structure of amino acids: interaction of model lewis acids with anthranilic acid

    Directory of Open Access Journals (Sweden)

    Tareq Irshaidat

    2014-01-01

    Full Text Available On the basis of theoretical B3LYP calculations, Yáñez and co-workers (J. Chem. Theory Comput. 2012, 8, 2293 illustrated that beryllium ions are capable of significantly modulating (changing the electronic structures of imidazole. In this computational organic chemistry study, the interaction of this β-amino acid and five model Lewis acids (BeF1+, Be2+, AlF2(1+, AlF2+, and Al3+ were investigated. Several aspects were addressed: natural bond orbitals, including second order perturbation analysis of intra-molecular charge delocalization and the natural population analysis atomic charges; molecular geometries; selected infrared stretching frequencies (C-N, C-O, and N-H, and selected ¹H-NMR chemical shifts. The data illustrate that this interaction can weaken the H-O bond and goes beyond strengthening the intra-molecular hydrogen bond (N...H-O to cause a spontaneous transfer of the proton to the nitrogen atom in five cases generating zwitterion structures. Many new features are observed. Most importantly, the zwitterion structures include a stabilizing hydrogen bond (N-H...O that varies in relative strength according to the Lewis acid. These findings explain the experimental observations of α-amino acids (for example: J. Am. Chem. Soc. 2001, 123, 3577 and are the first reported fundamental electronic structure characterization of β-amino acids in zwitterion form.

  3. Acid-functionalized polyolefin materials and their use in acid-promoted chemical reactions

    Energy Technology Data Exchange (ETDEWEB)

    Oyola, Yatsandra; Tian, Chengcheng; Bauer, John Christopher; Dai, Sheng

    2016-06-07

    An acid-functionalized polyolefin material that can be used as an acid catalyst in a wide range of acid-promoted chemical reactions, wherein the acid-functionalized polyolefin material includes a polyolefin backbone on which acid groups are appended. Also described is a method for the preparation of the acid catalyst in which a precursor polyolefin is subjected to ionizing radiation (e.g., electron beam irradiation) of sufficient power and the irradiated precursor polyolefin reacted with at least one vinyl monomer having an acid group thereon. Further described is a method for conducting an acid-promoted chemical reaction, wherein an acid-reactive organic precursor is contacted in liquid form with a solid heterogeneous acid catalyst comprising a polyolefin backbone of at least 1 micron in one dimension and having carboxylic acid groups and either sulfonic acid or phosphoric acid groups appended thereto.

  4. Amino Acid Analyses of Acid Hydrolysates in Desert Varnish

    Science.gov (United States)

    Perry, Randall S.; Staley, James T.; Dworkin, Jason P.; Engel, Mike

    2001-01-01

    There has long been a debate as to whether rock varnish deposits are microbially mediated or are deposited by inorganic processes. Varnished rocks are found throughout the world primarily in arid and semi-arid regions. The varnish coats are typically up to 200 microns thick and are composed of clays and alternating layers enriched in manganese and iron oxides. The individual layers range in thickness from 1 micron to greater than 10 microns and may continue laterally for more than a 100 microns. Overlapping botryoidal structures are visible in thin section and scanning electron micrographs. The coatings also include small amounts of organic mater and detrital grains. Amino-acid hydrolysates offer a means of assessing the organic composition of rock varnish collected from the Sonoran Desert, near Phoenix, AZ. Chromatographic analyses of hydrolysates from powdered samples of rock varnish suggest that the interior of rock varnish is relatively enriched in amino acids and specifically in d-alanine and glutamic acid. Peptidoglycan (murein) is the main structural component of gram-positive bacterial cell walls. The d-enantiomer of alanine and glutamic acid are specific to peptidoglycan and are consequently an indicator for the presence of bacteria. D-alanine is also found in teichoic acid which is only found in gram-positive bacteria. Several researchers have cultured bacteria from the surface of rock varnish and most have been gram-positive, suggesting that gram-positive bacteria are intimately associated with varnish coatings and may play a role in the formation of varnish coatings.

  5. Kinetics of wet air oxidation of glyoxalic acid and oxalic acid

    Energy Technology Data Exchange (ETDEWEB)

    Shende, R.V.; Mahajani, V.V. (Univ. of Bombay (India). Dept. of Chemical Technology)

    1994-12-01

    Oxidation of lower molecular weight monobasic and dibasic acids such as formic acid, acetic acid, glyoxalic acid, and oxalic acid is often the rate-controlling step during wet air oxidation (WAO) of an aqueous waste stream exhibiting very high chemical oxygen demand (COD). The kinetics of WAO of glyoxalic acid and oxalic acid was studied in absence and presence of a cupric sulfate catalyst in the temperature range of 120--245 C and oxygen partial pressure of 0.345--1.380 MPa. The wet oxidation of oxalic acid was found to require more severe conditions as compared to glyoxalic acid. The reaction mechanism and kinetic model have been discussed.

  6. Citric Acid Passivation of Stainless Steel

    Science.gov (United States)

    Yasensky, David; Reali, John; Larson, Chris; Carl, Chad

    2009-01-01

    Passivation is a process for cleaning and providing corrosion protection for stainless steel. Currently, on Kennedy Space Center (KSC), only parts passivated with nitric acid are acceptable for use. KSC disposes of approximately 125gal of concentrated nitric acid per year, and receives many parts from vendors who must also dispose of used nitric acid. Unfortunately, nitric acid presents health and environmental hazards. As a result, several recent industry studies have examined citric acid as an alternative. Implementing a citric acid-based passivation procedure would improve the health and environmental safety aspects of passivation process. However although there is a lack of published studies that conclusively prove citric acid is a technically sound passivation agent. In 2007, NASA's KSC Materials Advisory Working Group requested the evaluation of citric acid in place of nitric acid for passivation of parts at KSC. United Space Alliance Materials & Processes engineers have developed a three-phase test plan to evaluate citric acid as an alternative to nitric acid on three stainless steels commonly used at KSC: UNS S30400, S41000, and S17400. Phases 1 and 2 will produce an optimized citric acid treatment based on results from atmospheric exposure at NASA's Beach Corrosion Facility. Phase 3 will compare the optimized solution(s) with nitric acid treatments. If the results indicate that citric acid passivates as well or better than nitric acid, NASA intends to approve this method for parts used at the Kennedy Space Center.

  7. Acid Rain: What It Is -- How You Can Help!

    Science.gov (United States)

    National Wildlife Federation, Washington, DC.

    This publication discusses the nature and consequences of acid precipitation (commonly called acid rain). Topic areas include: (1) the chemical nature of acid rain; (2) sources of acid rain; (3) geographic areas where acid rain is a problem; (4) effects of acid rain on lakes; (5) effect of acid rain on vegetation; (6) possible effects of acid rain…

  8. Acid Rain: What It Is -- How You Can Help!

    Science.gov (United States)

    National Wildlife Federation, Washington, DC.

    This publication discusses the nature and consequences of acid precipitation (commonly called acid rain). Topic areas include: (1) the chemical nature of acid rain; (2) sources of acid rain; (3) geographic areas where acid rain is a problem; (4) effects of acid rain on lakes; (5) effect of acid rain on vegetation; (6) possible effects of acid rain…

  9. Analysis of proteins responsive to acetic acid in Acetobacter: molecular mechanisms conferring acetic acid resistance in acetic acid bacteria.

    Science.gov (United States)

    Nakano, Shigeru; Fukaya, Masahiro

    2008-06-30

    Acetic acid bacteria are used for industrial vinegar production because of their remarkable ability to oxidize ethanol and high resistance to acetic acid. Although several molecular machineries responsible for acetic acid resistance in acetic acid bacteria have been reported, the entire mechanism that confers acetic acid resistance has not been completely understood. One of the promising methods to elucidate the entire mechanism is global analysis of proteins responsive to acetic acid by two-dimensional gel electrophoresis. Recently, two proteins whose production was greatly enhanced by acetic acid in Acetobacter aceti were identified to be aconitase and a putative ABC-transporter, respectively; furthermore, overexpression or disruption of the genes encoding these proteins affected acetic acid resistance in A. aceti, indicating that these proteins are involved in acetic acid resistance. Overexpression of each gene increased acetic acid resistance in Acetobacter, which resulted in an improvement in the productivity of acetic acid fermentation. Taken together, the results of the proteomic analysis and those of previous studies indicate that acetic acid resistance in acetic acid bacteria is conferred by several mechanisms. These findings also provide a clue to breed a strain having high resistance to acetic acid for vinegar fermentation.

  10. 5-Caffeoylquinic acid and caffeic acid orally administered suppresses P-selectin expression on mouse platelets

    Science.gov (United States)

    Caffeic acid and 5-caffeoylquinic acid are a naturally occurring phenolic acid and its ester found in human diets. In this paper, potential effects of caffeic acid and 5-caffeoylquinic acid found in coffee and other plant sources on platelet activation were studied via investigating P-selectin expre...

  11. Fatty acid profile of Albizia lebbeck and Albizia saman seed oils: Presence of coronaric acid

    Science.gov (United States)

    In this work, the fatty acid profiles of the seed oils of Albizia lebbeck and Albizia saman (Samanea saman) are reported. The oils were analyzed by GC, GC-MS, and NMR. The most prominent fatty acid in both oils is linoleic acid (30-40%), followed by palmitic acid and oleic acid for A. lebbeck and ol...

  12. 21 CFR 172.350 - Fumaric acid and salts of fumaric acid.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Fumaric acid and salts of fumaric acid. 172.350... HUMAN CONSUMPTION Special Dietary and Nutritional Additives § 172.350 Fumaric acid and salts of fumaric acid. Fumaric acid and its calcium, ferrous, magnesium, potassium, and sodium salts may be safely used...

  13. Determination of acetylsalicylic acid and salicylic acid in foods, using HPLC with fluorescence detection.

    NARCIS (Netherlands)

    Venema, D.P.; Hollman, P.C.H.; Janssen, P.L.T.M.K.; Katan, M.B.

    1996-01-01

    We developed a specific and sensitive HPLC method with fluorescence detection for the determination of free acetylsalicylic acid, free salicylic acid, and free salicylic acid plus salicylic acid after alkaline hydrolysis (free-plus-bound) in foods. Acetylsalicylic acid was detected after postcolumn

  14. Determination of acetylsalicylic acid and salicylic acid in foods, using HPLC with fluorescence detection.

    NARCIS (Netherlands)

    Venema, D.P.; Hollman, P.C.H.; Janssen, P.L.T.M.K.; Katan, M.B.

    1996-01-01

    We developed a specific and sensitive HPLC method with fluorescence detection for the determination of free acetylsalicylic acid, free salicylic acid, and free salicylic acid plus salicylic acid after alkaline hydrolysis (free-plus-bound) in foods. Acetylsalicylic acid was detected after postcolumn

  15. Simultaneous liquid-chromatographic determination of urinary vanillylmandelic acid, homovanillic acid, and 5-hydroxyindoleacetic acid.

    Science.gov (United States)

    Gironi, A; Seghieri, G; Niccolai, M; Mammini, P

    1988-12-01

    We describe a liquid-chromatographic method for quantifying, simultaneously by a single procedure, vanillylmandelic acid (VMA), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) in urine. After solvent extraction of acidified urine, the analytes were chromatographed on a C8 column, with use of a mobile phase of phosphate buffer (20 mmol/L, pH 4.0) and methanol with a variable gradient elution, and detected fluorometrically. We report the analytical recovery, sensitivity, precision, working linear range, and potential for interference from similar molecules or drugs. The results of such tests demonstrate that the proposed method is sensitive and reproducible. It is, furthermore, easy to perform, and thus is suitable for use in the clinical laboratory.

  16. Acid mine drainage - the chemistry

    CSIR Research Space (South Africa)

    Garland, Rebecca M

    2011-01-01

    Full Text Available the hydronium ion. pH is calculated using the concentration of the hydronium ion. A high concentration of these ions will make a solution acidic. In this reaction pathway, the reactions are occurring in water and thus produce an aqueous solution that has a...

  17. Getting folic acid nutrition right

    Science.gov (United States)

    The two articles in this issue of the journal provide some definitive answers to questions relating to folic acid exposure and folate nutritional status of the US population in the post-fortification era, and, by implication, pose other questions. Most convincingly, these reports, which are based la...

  18. Adipic Acid: Vigorous Import Growth

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ Adipic acid is mainly used to manufacture nylon 6,6, plasticizers, grease, polyurethane etc. There are three major commercial production processes: cyclohexane process, cyclohexanol process, butadiene carbonylation process, and the air oxidation of cyclohexane process constitute 93% of the total.

  19. Boric Acid in Kjeldahl Analysis

    Science.gov (United States)

    Cruz, Gregorio

    2013-01-01

    The use of boric acid in the Kjeldahl determination of nitrogen is a variant of the original method widely applied in many laboratories all over the world. Its use is recommended by control organizations such as ISO, IDF, and EPA because it yields reliable and accurate results. However, the chemical principles the method is based on are not…

  20. Uric acid in multiple sclerosis

    NARCIS (Netherlands)

    Koch, M; De Keyser, J

    2006-01-01

    Peroxynitrite, a reactive oxidant formed by the reaction of nitric oxide with superoxide at sites of inflammation in multiple sclerosis (MS), is capable of damaging tissues and cells. Uric acid, a natural scavenger of peroxynitrite, reduces inflammatory demyelination in experimental allergic encepha