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Sample records for acids improve cholinergic

  1. Nerve growth factor protects cholinergic neurons against quinolinic acid-induced excitotoxicity in wistar rats

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    Vasiljević Ivana D.; Jovanović Marina D.; Čolić Miodrag J.; Mićić D.; Ninković Milica; Maličević Živorad

    2004-01-01

    The etiology of neuronal death in neurodegenerative diseases, including Huntington's disease (HD) is still unknown. There could be a complex interplay between altered energy metabolism, excitotoxicity and oxidative stress. Excitotoxic striatal lesions induced by quinolinic acid (QA), were used to test for the neuroprotective actions of nerve growth factor (NGF) on striatal cholinergic and GABAergic neurons. QA is an endogenous excitotoxin acting on N-methyl-D-aspartate (NMDA) rec...

  2. Chronic administration of sulbutiamine improves long term memory formation in mice: possible cholinergic mediation.

    Science.gov (United States)

    Micheau, J; Durkin, T P; Destrade, C; Rolland, Y; Jaffard, R

    1985-08-01

    Thiamine deficiency in both man and animals is known to produce memory dysfunction and cognitive disorders which have been related to an impairment of cholinergic activity. The present experiment was aimed at testing whether, inversely, chronic administration of large doses of sulbutiamine would have a facilitative effect on memory and would induce changes in central cholinergic activity. Accordingly mice received 300 mg/kg of sulbutiamine daily for 10 days. They were then submitted to an appetitive operant level press conditioning test. When compared to control subjects, sulbutiamine treated mice learned the task at the same rate in a single session but showed greatly improved performance when tested 24 hr after partial acquisition of the same task. Parallel neurochemical investigations showed that the treatment induced a slight (+ 10%) but significant increase in hippocampal sodium-dependent high affinity choline uptake. The present findings and previous results suggest that sulbutiamine improves memory formation and that this behavioral effect could be mediated by an increase in hippocampal cholinergic activity. PMID:4059305

  3. Altitude acclimatization improves submaximal cognitive performance in mice and involves an imbalance of the cholinergic system.

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    Guerra-Narbona, R; Delgado-García, J M; López-Ramos, J C

    2013-06-15

    The aim of this work was to reveal a hypothetical improvement of cognitive abilities in animals acclimatized to altitude and performing under ground level conditions, when looking at submaximal performance, once seen that it was not possible when looking at maximal scores. We modified contrasted cognitive tasks (object recognition, operant conditioning, eight-arm radial maze, and classical conditioning of the eyeblink reflex), increasing their complexity in an attempt to find performance differences in acclimatized animals vs. untrained controls. In addition, we studied, through immunohistochemical quantification, the expression of choline acetyltransferase and acetyl cholinesterase, enzymes involved in the synthesis and degradation of acetylcholine, in the septal area, piriform and visual cortexes, and the hippocampal CA1 area of animals submitted to acute hypobaric hypoxia, or acclimatized to this simulated altitude, to find a relationship between the cholinergic system and a cognitive improvement due to altitude acclimatization. Results showed subtle improvements of the cognitive capabilities of acclimatized animals in all of the tasks when performed under ground-level conditions (although not before 24 h), in the three tasks used to test explicit memory (object recognition, operant conditioning in the Skinner box, and eight-arm radial maze) and (from the first conditioning session) in the classical conditioning task used to evaluate implicit memory. An imbalance of choline acetyltransferase/acetyl cholinesterase expression was found in acclimatized animals, mainly 24 h after the acclimatization period. In conclusion, altitude acclimatization improves cognitive capabilities, in a process parallel to an imbalance of the cholinergic system. PMID:23599398

  4. Age-dependent improvement in passive avoidance learning of the young chick: cholinergic mediation?

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    Zolman, J F; Mattingly, B A

    1982-06-01

    Cholinergic mediation of the age-dependent improvement in response suppression of the young chick was studied by determining the performance of 4-day-old chicks, pretreated with scopolamine, during passive avoidance (PA) and extinction testing. In Experiment 1, chicks were trained briefly to key peck for heat reward (prepunishment training), and then tested for PA learning under immediate, 2-sec-delayed, or no shock condition. Half of the chicks in each wing-shock (5 mA, 5 sec) condition received saline injections before prepunishment training and .5 mg/kg scopolamine injections after prepunishment training. The rest of the chicks received .5 mg/kg scopolamine injections both before and after prepunishment training. For chicks in both scopolamine groups, delaying shock onset resulted in significantly less response suppression than immediate response-contingent shock. In Experiment 2, 4-day-old chicks injected with either saline or scopolamine were trained to key peck for heat reward and then tested for resistance to extinction under either response-contingent shock or nonshock conditions. Punishment decreased the number of extinction responses for both saline and scopolamine groups of chicks. Previous studies have shown that normal 1-day-old chicks do not show a significant delay of punishment effect during PA testing and that response-contingent punishment increases the number of their responses during extinction. Hence, the results of the present experiments indicate that the age-dependent improvement in response suppression of the young chick cannot be explained solely by a significant increase in central cholinergic functioning. PMID:7096681

  5. Mangifera indica Fruit Extract Improves Memory Impairment, Cholinergic Dysfunction, and Oxidative Stress Damage in Animal Model of Mild Cognitive Impairment

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    Jintanaporn Wattanathorn

    2014-01-01

    Full Text Available To date, the effective preventive paradigm against mild cognitive impairment (MCI is required. Therefore, we aimed to determine whether Mangifera indica fruit extract, a substance possessing antioxidant and cognitive enhancing effects, could improve memory impairment, cholinergic dysfunction, and oxidative stress damage in animal model of mild cognitive impairment. Male Wistar rats, weighing 180–200 g, were orally given the extract at doses of 12.5, 50, and 200 mg·kg−1 BW for 2 weeks before and 1 week after the bilateral injection of AF64A (icv. At the end of study, spatial memory, cholinergic neurons density, MDA level, and the activities of SOD, CAT, and GSH-Px enzymes in hippocampus were determined. The results showed that all doses of extract could improve memory together with the decreased MDA level and the increased SOD and GSH-Px enzymes activities. The increased cholinergic neurons density in CA1 and CA3 of hippocampus was also observed in rats treated with the extract at doses of 50 and 200 mg·kg−1 BW. Therefore, our results suggested that M. indica, the potential protective agent against MCI, increased cholinergic function and the decreased oxidative stress which in turn enhanced memory. However, further researches are essential to elucidate the possible active ingredients and detail mechanism.

  6. Alpha-asarone improves striatal cholinergic function and locomotor hyperactivity in Fmr1 knockout mice.

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    Qiu, Guozhen; Chen, Shengqiang; Guo, Jialing; Wu, Jie; Yi, Yong-Hong

    2016-10-01

    Hyperactivity is a symptom found in several neurological and psychiatric disorders, including Fragile X syndrome (FXS). The animal model of FXS, fragile X mental retardation gene (Fmr1) knockout (KO) mouse, exhibits robust locomotor hyperactivity. Alpha (α)-asarone, a major bioactive component isolated from Acorus gramineus, has been shown in previous studies to improve various disease conditions including central nervous system disorders. In this study, we show that treatment with α-asarone alleviates locomotor hyperactivity in Fmr1 KO mice. To elucidate the mechanism underlying this improvement, we evaluated the expressions of various cholinergic markers, as well as acetylcholinesterase (AChE) activity and acetylcholine (ACh) levels, in the striatum of Fmr1 KO mice. We also analyzed the AChE-inhibitory activity of α-asarone. Striatal samples from Fmr1 KO mice showed decreased m1 muscarinic acetylcholine receptor (m1 mAChR) expression, increased AChE activity, and reduced ACh levels. Treatment with α-asarone improved m1 mAChR expression and ACh levels, and attenuated the increased AChE activity. In addition, α-asarone dose-dependently inhibited AChE activity in vitro. These results indicate that direct inhibition of AChE activity and up-regulation of m1 mAChR expression in the striatum might contribute to the beneficial effects of α-asarone on locomotor hyperactivity in Fmr1 KO mice. These findings might improve understanding of the neurobiological mechanisms responsible for locomotor hyperactivity. PMID:27316341

  7. Catecholaminergic and cholinergic systems of mouse brain are modulated by LMN diet, rich in theobromine, polyphenols and polyunsaturated fatty acids.

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    Fernández-Fernández, Laura; Esteban, Gerard; Giralt, Mercedes; Valente, Tony; Bolea, Irene; Solé, Montse; Sun, Ping; Benítez, Susana; Morelló, José Ramón; Reguant, Jordi; Ramírez, Bartolomé; Hidalgo, Juan; Unzeta, Mercedes

    2015-04-01

    The possible modulatory effect of the functional LMN diet, rich in theobromine, polyphenols and polyunsaturated fatty acids, on the catecholaminergic and cholinergic neurotransmission, affecting cognition decline during aging has been studied. 129S1/SvlmJ mice were fed for 10, 20, 30 and 40 days with either LMN or control diets. The enzymes involved in catecholaminergic and cholinergic metabolism were determined by both immunohistological and western blot analyses. Noradrenalin, dopamine and other metabolites were quantified by HPLC analysis. Theobromine, present in cocoa, the main LMN diet component, was analysed in parallel using SH-SY5Y and PC12 cell lines. An enhanced modulatory effect on both cholinergic and catecholaminergic transmissions was observed on 20 day fed mice. Similar effect was observed with theobromine, besides its antioxidant capacity inducing SOD-1 and GPx expression. The enhancing effect of the LMN diet and theobromine on the levels of acetylcholine-related enzymes, dopamine and specially noradrenalin confirms the beneficial role of this diet on the "cognitive reserve" and hence a possible reducing effect on cognitive decline underlying aging and Alzheimer's disease. PMID:25756794

  8. Intrahippocampal Administration of Ibotenic Acid Induced Cholinergic Dysfunction via NR2A/NR2B Expression: Implications of Resveratrol against Alzheimer Disease Pathophysiology

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    Karthick, Chennakesavan; Periyasamy, Sabapathy; Jayachandran, Kesavan S.; Anusuyadevi, Muthuswamy

    2016-01-01

    Although several drugs revealed moderate amelioration of symptoms, none of them have sufficient potency to prevent or reverse the progression toward Alzheimer's disease (AD) pathology. Resveratrol (RSV), a polyphenolic compound has shown an outstanding therapeutic effect on a broad spectrum of diseases like age-associated neurodegeneration, inflammation etc. The present study was thus conducted to assess the therapeutic efficacy of RSV in ameliorating the deleterious effects of Ibotenic acid (IBO) in male Wistar rats. Stereotactic intrahippocampal administration of IBO (5 μg/μl) lesioned rats impairs cholinergic transmission, learning and memory performance that is rather related to AD and thus chosen as a suitable model to understand the drug efficacy in preventing AD pathophysiology. Since IBO is an agonist of glutamate, it is expected to exhibit an excitotoxic effect by altering glutamatergic receptors like NMDA receptor. The current study displayed significant alterations in the mRNA expression of NR2A and NR2B subunits of NMDA receptors, and further it is surprising to note that cholinergic receptors decreased in expression particularly α7-nAChR with increased m1AChR. RSV administration (20 mg/kg body weight, i.p.) significantly reduced these changes in IBO induced rats. Glutamatergic and cholinergic receptor alterations were associated with significant changes in the behavioral parameters of rats induced by IBO. While RSV improved spatial learning performance, attenuated immobility, and improvised open field activity in IBO induced rats. NR2B activation in the present study might mediate cell death through oxidative stress that form the basis of abnormal behavioral pattern in IBO induced rats. Interestingly, RSV that could efficiently encounter oxidative stress have significantly decreased stress markers viz., nitrite, PCO, and MDA levels by enhancing antioxidant status. Histopathological analysis displayed significant reduction in the hippocampal

  9. INTRAHIPPOCAMPAL ADMINISTRATION OF IBOTENIC ACID INDUCED CHOLINERGIC DYSFUNCTION via NR2A/NR2B EXPRESSION: IMPLICATIONS OF RESVERATROL AGAINST ALZHEIMER DISEASE PATHOPHYSIOLOGY

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    Chennakesavan eKarthick

    2016-04-01

    Full Text Available Although several drugs revealed moderate amelioration of symptoms, none of them have sufficient potency to prevent or reverse the progression towards Alzheimer’s disease (AD pathology. Resveratrol (RSV, a polyphenolic compound has shown an outstanding therapeutic effect on a broad spectrum of diseases like age-associated neurodegeneration, inflammation etc. The present study was thus conducted to assess the therapeutic efficacy of RSV in ameliorating the deleterious effects of Ibotenic acid (IBO in male Wistar rats. Stereotactic intrahippocampal administration of IBO (5µg/µl lesioned rats impairs cholinergic transmission, learning and memory performance that is rather related to AD and thus chosen as a suitable model to understand the drug efficacy in preventing AD pathophysiology. Since IBO is an agonist of glutamate, it is expected to exhibit an excitotoxic effect by altering glutamatergic receptors like NMDA receptor. The current study displayed significant alterations in the mRNA expression of NR2A and NR2B subunits of NMDA receptors, and further it is surprising to note that cholinergic receptors decreased in expression particularly α7-nAChR with increased m1AChR. RSV administration (20mg/kg body weight, i.p significantly reduced these changes in IBO induced rats. Glutamatergic and cholinergic receptor alterations were associated with significant changes in the behavioral parameters of rats induced by IBO. While RSV improved spatial learning performance, attenuated immobility and improvised open field activity in IBO induced rats. NR2B activation in the present study might mediate cell death through oxidative stress that form the basis of abnormal behavioral pattern in IBO induced rats. Interestingly, RSV that could efficiently encounter oxidative stress have significantly decreased stress markers viz., nitrite, PCO, and MDA levels by enhancing antioxidant status. Histopathological analysis displayed significant reduction in the

  10. Intrahippocampal Administration of Ibotenic Acid Induced Cholinergic Dysfunction via NR2A/NR2B Expression: Implications of Resveratrol against Alzheimer Disease Pathophysiology.

    Science.gov (United States)

    Karthick, Chennakesavan; Periyasamy, Sabapathy; Jayachandran, Kesavan S; Anusuyadevi, Muthuswamy

    2016-01-01

    Although several drugs revealed moderate amelioration of symptoms, none of them have sufficient potency to prevent or reverse the progression toward Alzheimer's disease (AD) pathology. Resveratrol (RSV), a polyphenolic compound has shown an outstanding therapeutic effect on a broad spectrum of diseases like age-associated neurodegeneration, inflammation etc. The present study was thus conducted to assess the therapeutic efficacy of RSV in ameliorating the deleterious effects of Ibotenic acid (IBO) in male Wistar rats. Stereotactic intrahippocampal administration of IBO (5 μg/μl) lesioned rats impairs cholinergic transmission, learning and memory performance that is rather related to AD and thus chosen as a suitable model to understand the drug efficacy in preventing AD pathophysiology. Since IBO is an agonist of glutamate, it is expected to exhibit an excitotoxic effect by altering glutamatergic receptors like NMDA receptor. The current study displayed significant alterations in the mRNA expression of NR2A and NR2B subunits of NMDA receptors, and further it is surprising to note that cholinergic receptors decreased in expression particularly α7-nAChR with increased m1AChR. RSV administration (20 mg/kg body weight, i.p.) significantly reduced these changes in IBO induced rats. Glutamatergic and cholinergic receptor alterations were associated with significant changes in the behavioral parameters of rats induced by IBO. While RSV improved spatial learning performance, attenuated immobility, and improvised open field activity in IBO induced rats. NR2B activation in the present study might mediate cell death through oxidative stress that form the basis of abnormal behavioral pattern in IBO induced rats. Interestingly, RSV that could efficiently encounter oxidative stress have significantly decreased stress markers viz., nitrite, PCO, and MDA levels by enhancing antioxidant status. Histopathological analysis displayed significant reduction in the hippocampal

  11. Nicotine increases impulsivity and decreases willingness to exert cognitive effort despite improving attention in "slacker" rats: insights into cholinergic regulation of cost/benefit decision making.

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    Jay G Hosking

    Full Text Available Successful decision making in our daily lives requires weighing an option's costs against its associated benefits. The neuromodulator acetylcholine underlies both the etiology and treatment of a number of illnesses in which decision making is perturbed, including Alzheimer's disease, attention-deficit/hyperactivity disorder, and schizophrenia. Nicotine acts on the cholinergic system and has been touted as a cognitive enhancer by both smokers and some researchers for its attention-boosting effects; however, it is unclear whether treatments that have a beneficial effect on attention would also have a beneficial effect on decision making. Here we utilize the rodent Cognitive Effort Task (rCET, wherein animals can choose to allocate greater visuospatial attention for a greater reward, to examine cholinergic contributions to both attentional performance and choice based on attentional demand. Following the establishment of baseline behavior, four drug challenges were administered: nicotine, mecamylamine, scopolamine, and oxotremorine (saline plus three doses for each. As per previous rCET studies, animals were divided by their baseline preferences, with "worker" rats choosing high-effort/high-reward options more than their "slacker" counterparts. Nicotine caused slackers to choose even fewer high-effort trials than at baseline, but had no effect on workers' choice. Despite slackers' decreased willingness to expend effort, nicotine improved their attentional performance on the task. Nicotine also increased measures of motor impulsivity in all animals. In contrast, scopolamine decreased animals' choice of high-effort trials, especially for workers, while oxotremorine decreased motor impulsivity for all animals. In sum, the cholinergic system appears to contribute to decision making, and in part these contributions can be understood as a function of individual differences. While nicotine has been considered as a cognitive enhancer, these data suggest

  12. Laser Acupuncture at HT7 Acupoint Improves Cognitive Deficit, Neuronal Loss, Oxidative Stress, and Functions of Cholinergic and Dopaminergic Systems in Animal Model of Parkinson’s Disease

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    Jintanaporn Wattanathorn

    2014-01-01

    Full Text Available To date, the therapeutic strategy against cognitive impairment in Parkinson’s disease (PD is still not in satisfaction level and requires novel effective intervention. Based the oxidative stress reduction and cognitive enhancement induced by laser acupuncture at HT7, the beneficial effect of laser acupuncture at HT7 against cognitive impairment in PD has been focused. In this study, we aimed to determine the effect of laser acupuncture at HT7 on memory impairment, oxidative stress status, and the functions of both cholinergic and dopaminergic systems in hippocampus of animal model of PD. Male Wistar rats, weighing 180–220 g, were induced unilateral lesion at right substantianigra by 6-OHDA and were treated with laser acupuncture continuously at a period of 14 days. The results showed that laser acupuncture at HT7 enhanced memory and neuron density in CA3 and dentate gyrus. The decreased AChE, MAO-B, and MDA together with increased GSH-Px in hippocampus of a 6-OHDA lesion rats were also observed. In conclusion, laser acupuncture at HT7 can improve neuron degeneration and memory impairment in animal model of PD partly via the decreased oxidative stress and the improved cholinergic and dopaminergic functions. More researches concerning effect of treatment duration are still required.

  13. Vitamin D₃ improves decline in cognitive function and cholinergic transmission in prefrontal cortex of streptozotocin-induced diabetic rats.

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    Alrefaie, Zienab; Alhayani, Abdulmone'em

    2015-01-01

    Complications of diabetes mellitus include cognitive impairments and functional changes in the brain. The present study aimed to investigate the possible beneficial effect of vitamin D3 on episodic memory and cholinergic transmission in the prefrontal cortex of streptozotocin-induced diabetic rats. Thirty male Wistar rats (150-200 g) were included into control, diabetic and diabetic supplemented with vitamin D3 groups. Diabetes was induced by single intraperitoneal injection of streptozotocin 45 mg/kg in citrate buffer. Vitamin D3 was administered orally in a dose of 500 IU/kg/day in corn oil for 10 weeks. Then rats were subjected to novel object recognition test to examine for episodic memory. Animals were sacrificed under diethyl ether anesthesia and prefrontal cortices were dissected to measure the activity of choline acetyl transferase (CAT) and acetyle choline esterase (ACE) enzymes to assess for cholinergic transmission. Diabetic rats spent significantly less time exploring the novel object compared to control animals. Vitamin D3 significantly attenuated the diabetes-induced impairment so that animals again spent significantly more time exploring the novel object. The CAT activity was significantly decreased in diabetic animals while the ACE activity was significantly increased compared to control non-diabetic animals. Diabetes-induced alterations in enzyme activity in the prefrontal cortex were mitigated by vitamin D3 supplementation. The present findings demonstrate the potential effect of vitamin D3 supplementation on cognitive function in diabetic animals. It is possible that this effect is mediated through enhancing the prefrontal cortex cholinergic transmission. PMID:25835318

  14. Cholinergic Mechanisms in Spinal Locomotion - Potential Target for Rehabilitation Approaches

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    L M Jordan

    2014-11-01

    Full Text Available Previous experiments implicate cholinergic brainstem and spinal systems in the control of locomotion. Our results demonstrate that the endogenous cholinergic propriospinal system, acting via M2 and M3 muscarinic receptors, is capable of consistently producing well-coordinated locomotor activity in the in vitro neonatal preparation, placing it in a position to contribute to normal locomotion and to provide a basis for recovery of locomotor capability in the absence of descending pathways. Tests of these suggestions, however, reveal that the spinal cholinergic system plays little if any role in the induction of locomotion, because MLR-evoked locomotion in decerebrate cats is not prevented by cholinergic antagonists. Furthermore, it is not required for the development of stepping movements after spinal cord injury, because cholinergic agonists do not facilitate the appearance of locomotion after spinal cord injury, unlike the dramatic locomotion-promoting effects of clonidine, a noradrenergic α-2 agonist. Furthermore, cholinergic antagonists actually improve locomotor activity after spinal cord injury, suggesting that plastic changes in the spinal cholinergic system interfere with locomotion rather than facilitating it. Changes that have been observed in the cholinergic innervation of motoneurons after spinal cord injury do not decrease motoneuron excitability, as expected. Instead, the development of a hyper-cholinergic state after spinal cord injury appears to enhance motoneuron output and suppress locomotion. A cholinergic suppression of afferent input from the limb after spinal cord injury is also evident from our data, and this may contribute to the ability of cholinergic antagonists to improve locomotion. Not only is a role for the spinal cholinergic system in supressing locomotion after SCI suggested by our results, but an obligatory contribution of a brainstem cholinergic relay to reticulospinal locomotor command systems is not confirmed

  15. The cholinergic antagonist gymnodimine improves Aβ and tau neuropathology in an in vitro model of Alzheimer disease.

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    Alonso, Eva; Vale, Carmen; Vieytes, Mercedes R; Laferla, Frank M; Giménez-Llort, Lydia; Botana, Luis M

    2011-01-01

    Gymnodimine (GYM) is a marine phycotoxin with a macrocyclic imine structure, isolated from extracts of the dinoflagellate Karenia selliformis known to act as a cholinergic antagonist with subtype selectivity. However, no data on the chronic effects of this compound has been reported so far. In this work, we evaluated the effect of long term exposure of cortical neurons to gymnodimine in the progress of Alzheimer disease (AD) pathology in vitro. Treatment of cortical neurons with 50 nM gymnodimine decreased the intracellular amyloid beta (Aβ) accumulation and the levels of the hyperphosphorylated isoforms of tau protein recognized by AT8 and AT100 antibodies. These results are suggested to be mediated by the increase in the inactive isoform of the glycogen synthase kinase-3 (phospho GSK-3 Ser9), the decrease in the levels of the active isoform of the ERK1/2 kinase and the increase in acetylcholine (Ach) synthesis elicited by long term exposure of cortical neurons to the toxin. Moreover, gymnodimine decreased glutamate-induced neurotoxicity in vitro. Altogether these results indicate that the marine phycotoxin gymnodimine may constitute a valuable tool for the development of drugs to treat neurodegenerative diseases. PMID:21691095

  16. Activation of Muscarinic Acetylcholine Receptor Subtype 4 is Essential for Cholinergic Stimulation of Gastric Acid Secretion - Relation To D Cell/Somatostatin -

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    Koji Takeuchi

    2016-08-01

    Full Text Available AbstractBackground/Aim: Muscarinic acetylcholine receptors exist in five subtypes (M1~M5, and they are widely expressed in various tissues to mediate diverse autonomic functions, including gastric secretion. In the present study, we demonstrated, using M1~M5 KO mice, the importance of M4 receptors in carbachol (CCh stimulation of acid secretion and investigated how the secretion is modulated by the activation of M4 receptors. Methods: C57BL/6J mice of wild-type (WT and M1-M5 KO were used. Under urethane anesthesia, acid secretion was measured in the stomach equipped with an acute fistula. CCh (30 µg/kg was given s.c. to stimulate acid secretion. Atropine or octreotide (a somatostatin analogue was given s.c. 20 min before the administration of CCh. CYN154806 (a somatostatin SST2 receptor antagonist was given i.p. 20 min before the administration of octreotide or CCh. Results: CCh caused an increase of acid secretion in WT mice, and the effect was totally inhibited by prior administration of atropine. The effect of CCh was similarly observed in the animals lacking M1, M2 or M5 receptors but significantly decreased in M3 or M4 KO mice. CYN154806, the SST2 receptor antagonist, dose-dependently and significantly reversed the decreased acid response to CCh in M4 but not M3 KO mice. Octreotide, the somatostatin analogue, inhibited the secretion of acid under CCh-stimulated conditions in WT mice. The immunohistochemical study showed the localization of M4 receptors on D cells in the stomach. Serum somatostatin levels in M4 KO mice were higher than WT mice under basal conditions, while those in WT mice were significantly decreased in response to CCh. Conclusions: These results suggest that under cholinergic stimulation the acid secretion is directly mediated by M3 receptors and indirectly modified by M4 receptors. It is assumed that the activation of M4 receptors inhibits the release of somatostatin from D cells and minimizes the acid inhibitory effect

  17. Cholinergic dysfunction in Parkinson's disease.

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    Müller, Martijn L T M; Bohnen, Nicolaas I

    2013-09-01

    There is increasing interest in the clinical effects of cholinergic basal forebrain and tegmental pedunculopontine complex (PPN) projection degeneration in Parkinson's disease (PD). Recent evidence supports an expanded role beyond cognitive impairment, including effects on olfaction, mood, REM sleep behavior disorder, and motor functions. Cholinergic denervation is variable in PD without dementia and may contribute to clinical symptom heterogeneity. Early in vivo imaging evidence that impaired cholinergic integrity of the PPN associates with frequent falling in PD is now confirmed by human post-mortem evidence. Brainstem cholinergic lesioning studies in primates confirm the role of the PPN in mobility impairment. Degeneration of basal forebrain cholinergic projections correlates with decreased walking speed. Cumulatively, these findings provide evidence for a new paradigm to explain dopamine-resistant features of mobility impairments in PD. Recognition of the increased clinical role of cholinergic system degeneration may motivate new research to expand indications for cholinergic therapy in PD. PMID:23943367

  18. Nematode cholinergic pharmacology

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    Segerberg, M.A.

    1989-01-01

    Nematode acetylcholine (ACh) receptors were characterized using both biochemical and electrophysiological techniques, including: (1) receptor binding studies in crude homogenates of the free-living nematode Caenorhabditis elegans and the parasitic nematode Ascaris lumbricoides with the high-affinity probe ({sup 3}H)N-methylscopolamine (({sup 3}H)NMS) which binds to muscarinic receptors in many vertebrate and invertebrate tissues (2) measurement of depolarization and contraction induced by a variety of cholinergic agents, including N-methylscopolamine (NMS), in an innervated dorsal muscle strip preparation of Ascaris; (3) examination of the antagonistic actions of d-tubocurarine (dTC) and NMS at dorsal neuromuscular junction; (4) measurement of input resistance changes in Ascaris commissural motorneurons induced by ACh, dTC, NMS, pilocarpine and other cholinergic drugs.

  19. Cholinergic imaging in dementia spectrum disorders.

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    Roy, Roman; Niccolini, Flavia; Pagano, Gennaro; Politis, Marios

    2016-07-01

    The multifaceted nature of the pathology of dementia spectrum disorders has complicated their management and the development of effective treatments. This is despite the fact that they are far from uncommon, with Alzheimer's disease (AD) alone affecting 35 million people worldwide. The cholinergic system has been found to be crucially involved in cognitive function, with cholinergic dysfunction playing a pivotal role in the pathophysiology of dementia. The use of molecular imaging such as SPECT and PET for tagging targets within the cholinergic system has shown promise for elucidating key aspects of underlying pathology in dementia spectrum disorders, including AD or parkinsonian dementias. SPECT and PET studies using selective radioligands for cholinergic markers, such as [(11)C]MP4A and [(11)C]PMP PET for acetylcholinesterase (AChE), [(123)I]5IA SPECT for the α4β2 nicotinic acetylcholine receptor and [(123)I]IBVM SPECT for the vesicular acetylcholine transporter, have been developed in an attempt to clarify those aspects of the diseases that remain unclear. This has led to a variety of findings, such as cortical AChE being significantly reduced in Parkinson's disease (PD), PD with dementia (PDD) and AD, as well as correlating with certain aspects of cognitive function such as attention and working memory. Thalamic AChE is significantly reduced in progressive supranuclear palsy (PSP) and multiple system atrophy, whilst it is not affected in PD. Some of these findings have brought about suggestions for the improvement of clinical practice, such as the use of a thalamic/cortical AChE ratio to differentiate between PD and PSP, two diseases that could overlap in terms of initial clinical presentation. Here, we review the findings from molecular imaging studies that have investigated the role of the cholinergic system in dementia spectrum disorders. PMID:26984612

  20. Cholinergic imaging in dementia spectrum disorders

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    Roy, Roman; Niccolini, Flavia; Pagano, Gennaro; Politis, Marios [Institute of Psychiatry, Psychology and Neuroscience, King' s College London, Neurodegeneration Imaging Group, Department of Basic and Clinical Neuroscience, London (United Kingdom)

    2016-07-15

    The multifaceted nature of the pathology of dementia spectrum disorders has complicated their management and the development of effective treatments. This is despite the fact that they are far from uncommon, with Alzheimer's disease (AD) alone affecting 35 million people worldwide. The cholinergic system has been found to be crucially involved in cognitive function, with cholinergic dysfunction playing a pivotal role in the pathophysiology of dementia. The use of molecular imaging such as SPECT and PET for tagging targets within the cholinergic system has shown promise for elucidating key aspects of underlying pathology in dementia spectrum disorders, including AD or parkinsonian dementias. SPECT and PET studies using selective radioligands for cholinergic markers, such as [{sup 11}C]MP4A and [{sup 11}C]PMP PET for acetylcholinesterase (AChE), [{sup 123}I]5IA SPECT for the α{sub 4}β{sub 2} nicotinic acetylcholine receptor and [{sup 123}I]IBVM SPECT for the vesicular acetylcholine transporter, have been developed in an attempt to clarify those aspects of the diseases that remain unclear. This has led to a variety of findings, such as cortical AChE being significantly reduced in Parkinson's disease (PD), PD with dementia (PDD) and AD, as well as correlating with certain aspects of cognitive function such as attention and working memory. Thalamic AChE is significantly reduced in progressive supranuclear palsy (PSP) and multiple system atrophy, whilst it is not affected in PD. Some of these findings have brought about suggestions for the improvement of clinical practice, such as the use of a thalamic/cortical AChE ratio to differentiate between PD and PSP, two diseases that could overlap in terms of initial clinical presentation. Here, we review the findings from molecular imaging studies that have investigated the role of the cholinergic system in dementia spectrum disorders. (orig.)

  1. [Cholinergic system of the heart].

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    Kučera, Matej; Hrabovská, Anna

    2015-12-01

    The cholinergic system of the heart can be either of neuronal or non-neuronal origin. The neuronal cholinergic system in the heart is represented by preganglionic parasympathetic pathways, intracardiac parasympathetic ganglia and postganglionic parasympathetic neurons projecting to the atria, SA node and AV node. The non-neuronal cholinergic system consists of cardiomyocytes that have complete equipment for synthesis and secretion of acetylcholine. Current knowledge suggests that the non-neuronal cholinergic system in the heart affects the regulation of the heart during sympathetic activation. The non-neuronal cholinergic system of the heart plays also a role in the energy metabolism of cardimyocites. Acetylcholine of both neuronal and non-neuronal origin acts in the heart through muscarinic and nicotinic receptors. The effect of acetylcholine in the heart is terminated by cholinesterases acetylcholinesterase and butyrylcholinesterase. Recently, papers suggest that the increased cholinergic tone in the heart by cholinesterase inhibitors has a positive effect on some cardiovascular disorders such as heart failure. For this reason, the cholinesterase inhibitors might be used in the treatment of certain cardiovascular disorders in the future.

  2. Comparative effects of ibotenic acid- and quisqualic acid-induced lesions of the substantia innominata on attentional function in the rat: further implications for the role of the cholinergic neurons of the nucleus basalis in cognitive processes.

    Science.gov (United States)

    Robbins, T W; Everitt, B J; Marston, H M; Wilkinson, J; Jones, G H; Page, K J

    1989-12-01

    Two experiments examined the effects of excitotoxic lesions of the substantia innominata on cholinergic activity in the neocortex and on performance in a paradigm measuring selective attention in the rat. In Expt. 1, ibotenate-induced lesions produced approximately 30% reductions in cortical choline acetyltransferase (ChAT) activity, and damage to wide regions of the substantia innominata and ventral pallidum. The rats were impaired in their ability to localize brief visual targets in a serial reaction time task, as measured by reduced choice accuracy. This impairment was particularly evident at short stimulus durations, but the lesioned rats did not exhibit evidence of primary visual sensory dysfunction and exhibited only minor deficits when the stimuli were presented unpredictably. The deficit was exacerbated when distracting white noise was interpolated into the task. The rats with lesions were also slower to respond correctly, probably resulting partly from the adoption of a speed/error trade-off strategy, and were slower to collect earned food pellets, although they made no more errors of omission than controls. In Expt. 2, quisqualate-induced lesions produced fewer signs of non-specific damage and 50% reductions in cortical ChAT activity. This lesion produced generally qualitatively similar, but weaker effects to those of ibotenate-induced lesions. It was notable that many of the deficits following either ibotenate- or quisqualate-induced lesions lasted for several months after surgery. The results are discussed in terms of the cholinergic hypothesis of cognitive dysfunction. It is argued that lesions of the substantia innominata, including the magnocellular cholinergic neurons of the nucleus basalis of Meynert, produce deficits in attentional processing, which may not result from damage specifically to cholinergic cells. However, the longevity of the effects makes these preparations suitable for further exploration of the restorative effects of cholinergic

  3. Improved Fatty Acid Profile Soybean MON 87705

    OpenAIRE

    Directorate, Issued by Health Canada's Food

    2014-01-01

    Health Canada has notified Monsanto Canada Inc. that it has no objection to the food use of Improved Fatty Acid Profile Soybean MON 87705. The Department conducted a comprehensive assessment of this variety according to its Guidelines for the Safety Assessment of Novel Foods. These Guidelines are based upon internationally accepted principles for establishing the safety of foods with novel traits. The following provides a summary of the notification from Monsanto Ca...

  4. Cholinergic Targets in Lung Cancer.

    Science.gov (United States)

    Spindel, Eliot R

    2016-01-01

    Lung cancers express an autocrine cholinergic loop in which secreted acetylcholine can stimulate tumor growth through both nicotinic and muscarinic receptors. Because activation of mAChR and nAChR stimulates growth; tumor growth can be stimulated by both locally synthesized acetylcholine as well as acetylcholine from distal sources and from nicotine in the high percentage of lung cancer patients who are smokers. The stimulation of lung cancer growth by cholinergic agonists offers many potential new targets for lung cancer therapy. Cholinergic signaling can be targeted at the level of choline transport; acetylcholine synthesis, secretion and degradation; and nicotinic and muscarinic receptors. In addition, the newly describe family of ly-6 allosteric modulators of nicotinic signaling such as lynx1 and lynx2 offers yet another new approach to novel lung cancer therapeutics. Each of these targets has their potential advantages and disadvantages for the development of new lung cancer therapies which are discussed in this review. PMID:26818857

  5. Cholinergic deficiency involved in vascular dementia:possible mechanism and strategy of treatment

    Institute of Scientific and Technical Information of China (English)

    Juan WANG; Hai-yan ZHANG; Xi-can TANG

    2009-01-01

    Vascular dementia (VaD) is a progressive neurodegenerative disease with a high prevalence.Several studies have recently reported that VaD patients present cholinergic deficits in the brain and cerebrospinal fluid (CSF) that may be closely related to the pathophysiology of cognitive impairment.Moreover,cholinergic therapies have shown promising effects on cognitive improvement in VaD patients.The precise mechanisms of these cholinergic agents are currently not fully understood;however,accumulating evidence indicates that these drugs may act through the cholinergic anti-inflammatory pathway,in which the efferent vagus nerve signals suppress pro-inflammatory cytokine release and inhibit inflammation,although regulation of oxidative stress and energy metabolism,alleviation of apoptosis may also be involved.In this paper,we provide a brief overview of the cholinergic treatment strategy for VaD and its relevant mechanisms of anti-inflammation.

  6. New Etiology of Cholinergic Urticaria.

    Science.gov (United States)

    Tokura, Yoshiki

    2016-01-01

    Cholinergic urticaria (CholU) is characterized by pinpoint-sized, highly pruritic wheals occurring upon sweating. Both direct and indirect theories in the interaction of acetylcholine (ACh) with mast cells have been put forward in the sweating-associated histamine release from mast cells. In the mechanism of indirect involvement of ACh, patients are hypersensitive to sweat antigen(s) and develop wheals in response to sweat substances leaking from the syringeal ducts to the dermis, possibly by obstruction of the ducts. Some patients with CholU exhibit a positive reaction to intradermal injection of their own diluted sweat, representing 'sweat allergy (hypersensitivity)'. Regarding the direct interaction theory between ACh and mast cells, we found that CholU with anhidrosis and hypohidrosis lacks cholinergic receptor M3 (CHRM3) expression in eccrine sweat gland epithelial cells. The expression of CHRM3 is completely absent in the anhidrotic areas and lowly expressed in the hypohidrotic areas. In the hypohidrotic area, where CholU occurs, it is hypothesized that ACh released from nerves cannot be completely trapped by cholinergic receptors of eccrine glands and overflows to the adjacent mast cells, leading to wheals. PMID:27584968

  7. Huperzine A protects sepsis associated encephalopathy by promoting the deficient cholinergic nervous function.

    Science.gov (United States)

    Zhu, Sen-Zhi; Huang, Wei-Ping; Huang, Lin-Qiang; Han, Yong-Li; Han, Qian-Peng; Zhu, Gao-Feng; Wen, Miao-Yun; Deng, Yi-Yu; Zeng, Hong-Ke

    2016-09-19

    Neuroinflammatory deregulation in the brain plays a crucial role in the pathogenesis of sepsis associated encephalopathy (SAE). Given the mounting evidence of anti-inflammatory and neuroprotective effects of the cholinergic nervous system, it is surprising that there is little information about its changes in the brain during sepsis. To elucidate the role of the cholinergic nervous system in SAE, hippocampal choline acetyltransferase, muscarinic acetylcholine receptor-1, acetylcholinesterase and acetylcholine were evaluated in LPS-induced sepsis rats. Expression of pro-inflammatory cytokines, neuronal apoptosis, and animal cognitive performance were also assessed. Furthermore, therapeutic effects of the acetylcholinesterase inhibitor Huperzine A (HupA) on the hippocampal cholinergic nervous function and neuroinflammation were evaluated. A deficiency of the cholinergic nervous function was revealed in SAE, accompanied with over-expressed pro-inflammatory cytokines, increase in neuronal apoptosis and brain cognitive impairment. HupA remarkably promoted the deficient cholinergic nervous function and attenuated the abnormal neuroinflammation in SAE, paralleled with the recovery of brain function. We suggest that the deficiency of the cholinergic nervous function and the abnormal neuroinflammation are synergistically implicated in the pathogenesis of SAE. Thus, HupA is a potential therapeutic candidate for SAE, as it improves the deficient cholinergic nervous function and exerts anti-inflammatory action.

  8. Cholinergic and perfusion brain networks in Parkinson disease dementia

    Science.gov (United States)

    McKeith, Ian G.; Burn, David J.; Wyper, David J.; O'Brien, John T.; Taylor, John-Paul

    2016-01-01

    Objective: To investigate muscarinic M1/M4 cholinergic networks in Parkinson disease dementia (PDD) and their association with changes in Mini-Mental State Examination (MMSE) after 12 weeks of treatment with donepezil. Methods: Forty-nine participants (25 PDD and 24 elderly controls) underwent 123I-QNB and 99mTc-exametazime SPECT scanning. We implemented voxel principal components (PC) analysis, producing a series of PC images of patterns of interrelated voxels across individuals. Linear regression analyses derived specific M1/M4 and perfusion spatial covariance patterns (SCPs). Results: We found an M1/M4 SCP of relative decreased binding in basal forebrain, temporal, striatum, insula, and anterior cingulate (F1,47 = 31.9, p < 0.001) in cholinesterase inhibitor–naive patients with PDD, implicating limbic-paralimbic and salience cholinergic networks. The corresponding regional cerebral blood flow SCP showed relative decreased uptake in temporoparietal and prefrontal areas (F1,47 = 177.5, p < 0.001) and nodes of the frontoparietal and default mode networks (DMN). The M1/M4 pattern that correlated with an improvement in MMSE (r = 0.58, p = 0.005) revealed relatively preserved/increased pre/medial/orbitofrontal, parietal, and posterior cingulate areas coinciding with the DMN and frontoparietal networks. Conclusion: Dysfunctional limbic-paralimbic and salience cholinergic networks were associated with PDD. Established cholinergic maintenance of the DMN and frontoparietal networks may be prerequisite for cognitive remediation following cholinergic treatment in this condition. PMID:27306636

  9. Transplantation of cholinergic neural stem cells in a mouse model of Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    WANG Qing-hua; XU Ru-xiang; Seigo Nagao

    2005-01-01

    @@ It is believed that the degeneration of cholinergic cells in the nucleus basalis of Meynert (NBM) and the loss of cortical cholinergic innervation cause dementia of Alzheimer's disease (AD).1 Currently available therapeutic interventions are mainly aimed at alleviating the cholinergic deficits. Unfortunately, these strategies do not prevent the disease, but instead offer limited symptomatic improvement.2 A recent study demonstrated that transplantation of in vitro expanded neural stem cells (NSCs) in an animal model of Parkinson's disease (PD) resulted in functional recovery of the animals to some extent,2 suggesting that such neural precursors might offer a useful future therapy for AD. In this study, we tried to find whether mouse embryonic stem (ES) cell derived cholinergic NSCs grafted in the prefrontal and parietal cortex have effects on the disruption of spatial memory following development of lesion in NBM.

  10. Improved Processes to Remove Naphthenic Acids

    Energy Technology Data Exchange (ETDEWEB)

    Aihua Zhang; Qisheng Ma; Kangshi Wang; Yongchun Tang; William A. Goddard

    2005-12-09

    In the past three years, we followed the work plan as we suggested in the proposal and made every efforts to fulfill the project objectives. Based on our large amount of creative and productive work, including both of experimental and theoretic aspects, we received important technical breakthrough on naphthenic acid removal process and obtained deep insight on catalytic decarboxylation chemistry. In detail, we established an integrated methodology to serve for all of the experimental and theoretical work. Our experimental investigation results in discovery of four type effective catalysts to the reaction of decarboxylation of model carboxylic acid compounds. The adsorption experiment revealed the effectiveness of several solid materials to naphthenic acid adsorption and acidity reduction of crude oil, which can be either natural minerals or synthesized materials. The test with crude oil also received promising results, which can be potentially developed into a practical process for oil industry. The theoretical work predicted several possible catalytic decarboxylation mechanisms that would govern the decarboxylation pathways depending on the type of catalysts being used. The calculation for reaction activation energy was in good agreement with our experimental measurements.

  11. Hormonal and cholinergic influences on pancreatic lysosomal and digestive enzymes in rats.

    Science.gov (United States)

    Evander, A; Ihse, I; Lundquist, I

    1983-01-01

    Hormonal and cholinergic influences on lysosomal and digestive enzyme activities in pancreatic tissue were studied in normal adult rats. Hormonal stimulation by the cholecystokinin analogue, caerulein, induced a marked enhancement of the activities of cathepsin D and N-acetyl-beta-D-glucosaminidase in pancreatic tissue, whereas the activities of amylase and lipase tended to decrease. Acid phosphatase activity was not affected. Further, caerulein was found to induce a significant increase of cathepsin D output in bile-pancreatic juice. This output largely parallelled that of amylase. Cholinergic stimulation by the muscarinic agonist carbachol, at a dose level giving the same output of amylase as caerulein, did not affect pancreatic activities of cathepsin D and N-acetyl-beta-D-glucosaminidase. Further, cholinergic stimulation induced an increase of amylase activity and a slight decrease of acid phosphatase activity in pancreatic tissue. Lipase activity was not affected. No apparent effect on cathepsin D output in bile-pancreatic juice was encountered after cholinergic stimulation. The activities of neither the digestive nor the lysosomal enzymes were influenced by the administration of secretin. The results suggest a possible lysosomal involvement in caerulein-induced secretion and/or inactivation of pancreatic digestive enzymes, whereas cholinergic stimulation seems to act through different mechanisms.

  12. A case of postganglionic cholinergic dysautonomia.

    OpenAIRE

    Takayama, H; Kazahaya, Y; Kashihara, N.; Kuroda, H.; Miyawaki, S; Ota, Z; Ogawa, N.

    1987-01-01

    A 24 year old female presented with signs and symptoms of postganglionic cholinergic autonomic dysfunction manifested by impaired lachrymation and salivation, mydriasis of the pupil, decreased gastrointestinal motility, atony of the bladder, and sweating and taste disturbance. Clinical and pharmacological studies confirmed that the abnormalities were restricted mainly to the postganglionic cholinergic autonomic systems. The titre of serum complement was low, antinuclear antibodies revealed a ...

  13. Postlesion estradiol treatment increases cortical cholinergic innervations via estrogen receptor-α dependent nonclassical estrogen signaling in vivo.

    Science.gov (United States)

    Koszegi, Zsombor; Szego, Éva M; Cheong, Rachel Y; Tolod-Kemp, Emeline; Ábrahám, István M

    2011-09-01

    17β-Estradiol (E2) treatment exerts rapid, nonclassical actions via intracellular signal transduction system in basal forebrain cholinergic (BFC) neurons in vivo. Here we examined the effect of E2 treatment on lesioned BFC neurons in ovariectomized mice and the role of E2-induced nonclassical action in this treatment. Mice given an N-methyl-d-aspartic acid (NMDA) injection into the substantia innominata-nucleus basalis magnocellularis complex (SI-NBM) exhibited cholinergic cell loss in the SI-NBM and ipsilateral cholinergic fiber loss in the cortex. A single injection of E2 after NMDA lesion did not have an effect on cholinergic cell loss in the SI-NBM, but it restored the ipsilateral cholinergic fiber density in the cortex in a time- and dose-dependent manner. The most effective cholinergic fiber restoration was observed with 33 ng/g E2 treatment at 1 h after NMDA lesion. The E2-induced cholinergic fiber restoration was absent in neuron-specific estrogen receptor-α knockout mice in vivo. Selective activation of nonclassical estrogen signaling in vivo by estren induced E2-like restorative actions. Selective blockade of the MAPK or protein kinase A pathway in vivo prevented E2's ability to restore cholinergic fiber loss. Finally, studies in intact female mice revealed an E2-induced restorative effect that was similar to that of E2-treated ovariectomized mice. These observations demonstrate that a single E2 treatment restores the BFC fiber loss in the cortex, regardless of endogenous E2 levels. They also reveal the critical role of nonclassical estrogen signaling via estrogen receptor-α and protein kinase A-MAPK pathways in E2-induced restorative action in the cholinergic system in vivo.

  14. GABAERGIC MODULATION OF STRIATAL CHOLINERGIC INTERNEURONS - AN IN-VIVO MICRODIALYSIS STUDY

    NARCIS (Netherlands)

    DEBOER, P; WESTERINK, BHC

    1994-01-01

    Striatal cholinergic interneurons have been shown to receive input from striatal gamma-aminobutyric acid (GABA)-containing cell elements. GABA is known to act on two different types of receptors, the GABA(A) and the GABA(B) receptor. Using in vivo microdialysis, we have studied the effect of intrast

  15. Neutralization of Tumor Acidity Improves Antitumor Responses to Immunotherapy.

    Science.gov (United States)

    Pilon-Thomas, Shari; Kodumudi, Krithika N; El-Kenawi, Asmaa E; Russell, Shonagh; Weber, Amy M; Luddy, Kimberly; Damaghi, Mehdi; Wojtkowiak, Jonathan W; Mulé, James J; Ibrahim-Hashim, Arig; Gillies, Robert J

    2016-03-15

    Cancer immunotherapies, such as immune checkpoint blockade or adoptive T-cell transfer, can lead to durable responses in the clinic, but response rates remain low due to undefined suppression mechanisms. Solid tumors are characterized by a highly acidic microenvironment that might blunt the effectiveness of antitumor immunity. In this study, we directly investigated the effects of tumor acidity on the efficacy of immunotherapy. An acidic pH environment blocked T-cell activation and limited glycolysis in vitro. IFNγ release blocked by acidic pH did not occur at the level of steady-state mRNA, implying that the effect of acidity was posttranslational. Acidification did not affect cytoplasmic pH, suggesting that signals transduced by external acidity were likely mediated by specific acid-sensing receptors, four of which are expressed by T cells. Notably, neutralizing tumor acidity with bicarbonate monotherapy impaired the growth of some cancer types in mice where it was associated with increased T-cell infiltration. Furthermore, combining bicarbonate therapy with anti-CTLA-4, anti-PD1, or adoptive T-cell transfer improved antitumor responses in multiple models, including cures in some subjects. Overall, our findings show how raising intratumoral pH through oral buffers therapy can improve responses to immunotherapy, with the potential for immediate clinical translation. PMID:26719539

  16. Central muscarinic cholinergic activation alters interaction between splenic dendritic cell and CD4+CD25- T cells in experimental colitis.

    Directory of Open Access Journals (Sweden)

    Peris Munyaka

    Full Text Available BACKGROUND: The cholinergic anti-inflammatory pathway (CAP is based on vagus nerve (VN activity that regulates macrophage and dendritic cell responses in the spleen through alpha-7 nicotinic acetylcholine receptor (a7nAChR signaling. Inflammatory bowel disease (IBD patients present dysautonomia with decreased vagus nerve activity, dendritic cell and T cell over-activation. The aim of this study was to investigate whether central activation of the CAP alters the function of dendritic cells (DCs and sequential CD4+/CD25-T cell activation in the context of experimental colitis. METHODS: The dinitrobenzene sulfonic acid model of experimental colitis in C57BL/6 mice was used. Central, intracerebroventricular infusion of the M1 muscarinic acetylcholine receptor agonist McN-A-343 was used to activate CAP and vagus nerve and/or splenic nerve transection were performed. In addition, the role of α7nAChR signaling and the NF-kB pathway was studied. Serum amyloid protein (SAP-A, colonic tissue cytokines, IL-12p70 and IL-23 in isolated splenic DCs, and cytokines levels in DC-CD4+CD25-T cell co-culture were determined. RESULTS: McN-A-343 treatment reduced colonic inflammation associated with decreased pro-inflammatory Th1/Th17 colonic and splenic cytokine secretion. Splenic DCs cytokine release was modulated through α7nAChR and the NF-kB signaling pathways. Cholinergic activation resulted in decreased CD4+CD25-T cell priming. The anti-inflammatory efficacy of central cholinergic activation was abolished in mice with vagotomy or splenic neurectomy. CONCLUSIONS: Suppression of splenic immune cell activation and altered interaction between DCs and T cells are important aspects of the beneficial effect of brain activation of the CAP in experimental colitis. These findings may lead to improved therapeutic strategies in the treatment of IBD.

  17. Improved Delivery of Caffeic Acid through Liposomal Encapsulation

    OpenAIRE

    Katuwavila, Nuwanthi P.; A. D. L. Chandani Perera; V. Karunaratne; Gehan A. J. Amaratunga; D. Nedra Karunaratne

    2016-01-01

    Photoageing resulting from long term exposure of the skin to UV light can be minimized by scavenging the reactive photochemical intermediates with antioxidants. For effective photoprotection, the antioxidant must overcome the barrier properties of the skin and reach the target site in significant amounts. The present study aims to improve the skin penetration of caffeic acid, a very effective free radical scavenger, by encapsulating in liposomes. Caffeic acid loaded liposomes prepared using t...

  18. Cholinergic regulation of the vasopressin neuroendocrine system

    Energy Technology Data Exchange (ETDEWEB)

    Michels, K.M.

    1987-01-01

    To clarify the physical and functional relationship between the cholinergic system, and the neurodocrine cells of the supraoptic nucleus, a combination of experiments on receptor binding, localization and function were carried out. The putative nicotinic receptor probe (/sup 125/I)alpha bungarotoxin ((/sup 125/I)alpha BTX) bound with high affinity and specificity to the vasopressin and oxytocin magnocellular neurons of the supraoptic nucleus, nucleus circularis, and paraventricular nucleus. Binding of (/sup 125/I)alpha BTX within the neural lobe was very low. In contrast, the muscarinic cholinergic receptor probe (/sup 3/H)quinuclidinylbenzilate ((/sup 3/H)QNB) did not bind to magnocellular vasopressin and oxytocin cell groups. The median eminence, which contains the neurosecretory axons, and the neural lobe of the pituitary contain low levels of (/sup 3/H)QNB binding. The physiological significance of these cholinergic receptors in regulation of vasopressin release was tested using an in vitro preparation of the supraoptic - neural lobe system.

  19. Rabbit Forebrain cholinergic system : Morphological characterization of nuclei and distribution of cholinergic terminals in the cerebral cortex and hippocampus

    NARCIS (Netherlands)

    Varga, C; Hartig, W; Grosche, J; Luiten, PGM; Seeger, J; Brauer, K; Harkany, T; Härtig, Wolfgang; Keijser, Jan N.

    2003-01-01

    Although the rabbit brain, in particular the basal forebrain cholinergic system, has become a common model for neuropathological changes associated with Alzheimer's disease, detailed neuroanatomical studies on the morphological organization of basal forebrain cholinergic nuclei and on their output p

  20. The cholinergic system, circadian rhythmicity, and time memory

    NARCIS (Netherlands)

    Hut, R. A.; Van der Zee, E. A.

    2011-01-01

    This review provides an overview of the interaction between the mammalian cholinergic system and circadian system, and its possible role in time memory. Several studies made clear that circadian (daily) fluctuations in acetylcholine (ACh) release, cholinergic enzyme activity and cholinergic receptor

  1. Quality Improvement of an Acid Treated Fuel Oil

    Directory of Open Access Journals (Sweden)

    Elizabeth Jumoke ETERIGHO

    2008-06-01

    Full Text Available The work on the quality improvement of fuel oil using acid treatment was carried out. The improvement of the fuel oil was done using sulphuric acid to remove contaminants. Sulphuric acid at different concentrations were mixed with the oil and kept at 45°C for four hours in the agitator vessel to allow reaction to take place. Acidic sludge was then drained off from the agitator and the oil was neutralized with sodium hydroxide. Centrifugation operation was used to extract the sulphonate dispersed in the oil. The treated and untreated oils were characterized for various properties and the results showed that the viscosity, total sulphur of fuel oil decreased from 6.0 to before 5.0 cst after acid treatment and 2.57 to 1.2225% w/w respectively while the flash point increased from 248 to 264°F. The water and sediment content increased from trace before to 0.6 after treatment. In addition, the calorific value increased from initial value of 44,368 to 44,805 and 44,715 kJ/kg at 50% and 75% conc. H2SO4 while decreasing with 85% and 90% conc. H2SO4. However, both carbon residue and ash content decreases with an increase in acid concentration.

  2. Fish oil supplementation improves docosahexaenoic acid status of malnourished infants

    NARCIS (Netherlands)

    Smit, EN; Oelen, EA; Seerat, E; Boersma, ER; Muskiet, FAJ

    2000-01-01

    Aim-To investigate whether the low docosahexaenoic acid (DHA) status of malnourished, mostly breast fed, Pakistani children can be improved by fish oil (FO) supplementation. Methods-Ten malnourished children (aged 8-30 months) received 500 mg FO daily for nine weeks. The supplement contained 62.8 mo

  3. Improvement in HPLC separation of acetic acid and levulinic acid in the profiling of biomass hydrolysate.

    Science.gov (United States)

    Xie, Rui; Tu, Maobing; Wu, Yonnie; Adhikari, Sushil

    2011-04-01

    5-Hydroxymethylfurfural (HMF) and furfural could be separated by the Aminex HPX-87H column chromatography, however, the separation and quantification of acetic acid and levulinic acid in biomass hydrolysate have been difficult with this method. In present study, the HPLC separation of acetic acid and levulinic acid on Aminex HPX-87H column has been investigated by varying column temperature, flow rate, and sulfuric acid content in the mobile phase. The column temperature was found critical in resolving acetic acid and levulinic acid. The resolution for two acids increased dramatically from 0.42 to 1.86 when the column temperature was lowered from 60 to 30 °C. So did the capacity factors for levulinic acid that was increased from 1.20 to 1.44 as the column temperature dropped. The optimum column temperature for the separation was found at 45 °C. Variation in flow rate and sulfuric acid concentration improved not as much as the column temperature did.

  4. Improvement in HPLC separation of acetic acid and levulinic acid in the profiling of biomass hydrolysate.

    Science.gov (United States)

    Xie, Rui; Tu, Maobing; Wu, Yonnie; Adhikari, Sushil

    2011-04-01

    5-Hydroxymethylfurfural (HMF) and furfural could be separated by the Aminex HPX-87H column chromatography, however, the separation and quantification of acetic acid and levulinic acid in biomass hydrolysate have been difficult with this method. In present study, the HPLC separation of acetic acid and levulinic acid on Aminex HPX-87H column has been investigated by varying column temperature, flow rate, and sulfuric acid content in the mobile phase. The column temperature was found critical in resolving acetic acid and levulinic acid. The resolution for two acids increased dramatically from 0.42 to 1.86 when the column temperature was lowered from 60 to 30 °C. So did the capacity factors for levulinic acid that was increased from 1.20 to 1.44 as the column temperature dropped. The optimum column temperature for the separation was found at 45 °C. Variation in flow rate and sulfuric acid concentration improved not as much as the column temperature did. PMID:21316945

  5. TIMING IS EVERYTHING, EVEN FOR CHOLINERGIC CONTROL

    OpenAIRE

    Berg, Darwin K.

    2011-01-01

    Synaptic plasticity is widely considered to be a cellular mechanism underlying learning and memory. In this issue of Neuron, Gu and Yakel show that the precise timing of a single cholinergic pulse of activity can determine whether plasticity will occur at a glutamatergic synapse and confer long-term potentiation versus depression.

  6. Acidic sandy soil improvement with biochar - A microcosm study.

    Science.gov (United States)

    Molnár, Mónika; Vaszita, Emese; Farkas, Éva; Ujaczki, Éva; Fekete-Kertész, Ildikó; Tolner, Mária; Klebercz, Orsolya; Kirchkeszner, Csaba; Gruiz, Katalin; Uzinger, Nikolett; Feigl, Viktória

    2016-09-01

    Biochar produced from a wide range of organic materials by pyrolysis has been reported as a means to improve soil physical properties, fertility and crop productivity. However, there is a lack of studies on the complex effects of biochar both on the degraded sandy soil physico-chemical properties and the soil biota as well as on toxicity, particularly in combined application with fertilizer and compost. A 7-week microcosm experiment was conducted to improve the quality of an acidic sandy soil combining variations in biochar types and amounts, compost and fertilizer application rates. The applied biochars were produced from different feedstocks such as grain husks, paper fibre sludge and wood screenings. The main purpose of the microcosm experiment was to assess the efficiency and applicability of different biochars as soil amendment prior to field trials and to choose the most efficient biochar to improve the fertility, biological activity and physical properties of acidic sandy soils. We complemented the methodology with ecotoxicity assessment to evaluate the possible risks to the soil as habitat for microbes, plants and animals. There was clear evidence of biochar-soil interactions positively affecting both the physico-chemical properties of the tested acidic sandy soil and the soil biota. Our results suggest that the grain husk and the paper fibre sludge biochars applied to the tested soil at 1% and 0.5 w/w% rate mixed with compost, respectively can supply a more liveable habitat for plants and soil living animals than the acidic sandy soil without treatment. PMID:26850860

  7. Cholinergic Circuit Control of Postnatal Neurogenesis

    Science.gov (United States)

    Asrican, Brent; Paez-Gonzalez, Patricia; Erb, Joshua; Kuo, Chay T.

    2016-01-01

    New neuron addition via continued neurogenesis in the postnatal/adult mammalian brain presents a distinct form of nervous system plasticity. During embryonic development, precise temporal and spatial patterns of neurogenesis are necessary to create the nervous system architecture. Similar between embryonic and postnatal stages, neurogenic proliferation is regulated by neural stem cell (NSC)-intrinsic mechanisms layered upon cues from their local microenvironmental niche. Following developmental assembly, it remains relatively unclear what may be the key driving forces that sustain continued production of neurons in the postnatal/adult brain. Recent experimental evidence suggests that patterned activity from specific neural circuits can also directly govern postnatal/adult neurogenesis. Here, we review experimental findings that revealed cholinergic modulation, and how patterns of neuronal activity and acetylcholine release may differentially or synergistically activate downstream signaling in NSCs. Higher-order excitatory and inhibitory inputs regulating cholinergic neuron firing, and their implications in neurogenesis control are also considered.

  8. Glucocorticoid programming of the mesopontine cholinergic system

    Directory of Open Access Journals (Sweden)

    Sónia eBorges

    2013-12-01

    Full Text Available Stress perception, response, adaptation and coping strategies are individually distinct, and the sequel of stress and/or glucocorticoids is also distinct between subjects. In the last years, it has become clear that early life stress is a powerful modulator of neuroendocrine stress-responsive circuits, programming intrinsic susceptibility to stress, and potentiating the appearance of stress-related disorders such as depression, anxiety and addiction. Herein we were interested in understanding how early life experiences reset the normal processing of negative stimuli, leading to emotional dysfunction. Animals prenatally exposed to glucocorticoids (iuGC present hyperanxiety, increased fear behaviour and hyper-reactivity to negative stimuli. In parallel, we found a remarkable increase in the number of aversive 22kHz ultrasonic vocalizations in response to an aversive cue. Considering the suggested role of the mesopontine tegmentum cholinergic pathway, arising from the laterodorsal tegmental nucleus (LDT and pedunculopontine tegmental nucleus (PPT, in the initiation of 22kHz vocalizations and hypothetically in the control of emotional arousal and tone, we decided to evaluate the condition of this circuit in iuGC animals. Notably, in a basal situation, iuGC animals present increased choline acetyltransferase (ChAT expression in the LDT and PPT, but not in other cholinergic nuclei, namely in the nucleus basalis of Meynert. In addition, and in accordance with the amplified response to an adverse stimulus of iuGC animals, we found marked changes in the cholinergic activation pattern of LDT and PPT regions. Altogether, our results suggest a specific cholinergic pathway programing by prenatal GC, and hint that this may be of relevance in setting individuals stress vulnerability threshold.

  9. Central cholinergic regulation of respiration: nicotinic receptors

    Institute of Scientific and Technical Information of China (English)

    Xuesi M SHAO; Jack L FELDMAN

    2009-01-01

    Nicotinic acetylcholine receptors (nAChRs) are expressed in brainstem and spinal cord regions involved in the control of breathing. These receptors mediate central cholinergic regulation of respiration and effects of the exogenous ligand nicotine on respiratory pattern. Activation of a4* nAChRs in the preBotzinger Complex (preBotC), an essential site for normal respiratory rhythm generation in mammals, modulates excitatory glutamatergic neurotransmission and depolarizes preBotC inspiratory neurons, leading to increases in respiratory frequency. nAChRs are also present in motor nuclei innervating respiratory muscles. Activation of post- and/or extra-synaptic a4* nAChRs on hypoglossal (XII) motoneurons depolarizes these neurons, potentiating tonic and respiratory-related rhythmic activity. As perinatal nicotine exposure may contribute to the pathogenesis of sudden infant death syndrome (SIDS), we discuss the effects of perinatal nicotine exposure on development of the cholinergic and other neurotransmitter systems involved in control of breathing. Advances in understanding of the mechanisms underlying central cholinergic/nicotinic modulation of respiration provide a pharmacological basis for exploiting nAChRs as therapeutic targets for neurological disorders related to neural control of breathing such as sleep apnea and SIDS.

  10. Lead/acid batteries in systems to improve power quality

    Science.gov (United States)

    Taylor, P.; Butler, P.; Nerbun, W.

    Increasing dependence on computer technology is driving needs for extremely high-quality power to prevent loss of information, material, and workers' time that represent billions of dollars annually. This cost has motivated commercial and Federal research and development of energy storage systems that detect and respond to power-quality failures in milliseconds. Electrochemical batteries are among the storage media under investigation for these systems. Battery energy storage systems that employ either flooded lead/acid or valve-regulated lead/acid battery technologies are becoming commercially available to capture a share of this emerging market. Cooperative research and development between the US Department of Energy and private industry have led to installations of lead/acid-based battery energy storage systems to improve power quality at utility and industrial sites and commercial development of fully integrated, modular battery energy storage system products for power quality. One such system by AC Battery Corporation, called the PQ2000, is installed at a test site at Pacific Gas and Electric Company (San Ramon, CA, USA) and at a customer site at Oglethorpe Power Corporation (Tucker, GA, USA). The PQ2000 employs off-the-shelf power electronics in an integrated methodology to control the factors that affect the performance and service life of production-model, low-maintenance, flooded lead/acid batteries. This system, and other members of this first generation of lead/acid-based energy storage systems, will need to compete vigorously for a share of an expanding, yet very aggressive, power quality market.

  11. Central Cholinergic Neurons Are Rapidly Recruited by Reinforcement Feedback.

    Science.gov (United States)

    Hangya, Balázs; Ranade, Sachin P; Lorenc, Maja; Kepecs, Adam

    2015-08-27

    Basal forebrain cholinergic neurons constitute a major neuromodulatory system implicated in normal cognition and neurodegenerative dementias. Cholinergic projections densely innervate neocortex, releasing acetylcholine to regulate arousal, attention, and learning. However, their precise behavioral function is poorly understood because identified cholinergic neurons have never been recorded during behavior. To determine which aspects of cognition their activity might support, we recorded cholinergic neurons using optogenetic identification in mice performing an auditory detection task requiring sustained attention. We found that a non-cholinergic basal forebrain population-but not cholinergic neurons-were correlated with trial-to-trial measures of attention. Surprisingly, cholinergic neurons responded to reward and punishment with unusual speed and precision (18 ± 3 ms). Cholinergic responses were scaled by the unexpectedness of reinforcement and were highly similar across neurons and two nuclei innervating distinct cortical areas. These results reveal that the cholinergic system broadcasts a rapid and precisely timed reinforcement signal, supporting fast cortical activation and plasticity. PMID:26317475

  12. Basal Forebrain Cholinergic Deficits Reduce Glucose Metabolism and Function of Cholinergic and GABAergic Systems in the Cingulate Cortex

    OpenAIRE

    Jeong, Da Un; Oh, Jin Hwan; Lee, Ji Eun; Lee, Jihyeon; Cho, Zang Hee; Chang, Jin Woo; Chang, Won Seok

    2015-01-01

    Purpose Reduced brain glucose metabolism and basal forebrain cholinergic neuron degeneration are common features of Alzheimer's disease and have been correlated with memory function. Although regions representing glucose hypometabolism in patients with Alzheimer's disease are targets of cholinergic basal forebrain neurons, the interaction between cholinergic denervation and glucose hypometabolism is still unclear. The aim of the present study was to evaluate glucose metabolism changes caused ...

  13. Slagment Cement Improve the Cement Resistance Toward Acids Attack During Acidizing Treatment

    Directory of Open Access Journals (Sweden)

    Nik Khairul Irfan Bin Nik Ab. Lah.

    2013-05-01

    Full Text Available Acidizing treatment in past experience shows several zonal isolation problems after the treatment. This study presents the effect of the acid treatment toward class G cement and slagment cement as the improvement method to improve the cement resistance toward the acid. Lab experiments were conducted by immerge the respective cement cubes into 12% HCl/3% HF solution for 40 min before several analysis were conducted. Based on the result, the mass loss and compressive strength loss of the cement cubes decrease as the curing temperature and pressure increase due to more evenly distributed cement chemical composition crystal in high curing condition as shown in Scanning Electron Microscopy (SEM analysis. From X-Ray Diffraction (XRD and X-Ray Fluorescence (XRF analysis, only the first layer of the cement cubes shows chemical component change due to the reaction between the acid. This study found that, replacing class G cement to slagment cement can reduce the mass loss and compressive strength loss up to 72% and 82%, respectively.

  14. Cholinergic pesticides cause mushroom body neuronal inactivation in honeybees

    OpenAIRE

    Palmer, Mary J; Moffat, Christopher; Saranzewa, Nastja; Harvey, Jenni; Wright, Geraldine A.; Connolly, Christopher N.

    2013-01-01

    Pesticides that target cholinergic neurotransmission are highly effective, but their use has been implicated in insect pollinator population decline. Honeybees are exposed to two widely used classes of cholinergic pesticide: neonicotinoids (nicotinic receptor agonists) and organophosphate miticides (acetylcholinesterase inhibitors). Although sublethal levels of neonicotinoids are known to disrupt honeybee learning and behaviour, the neurophysiological basis of these effects has not been shown...

  15. Anaerobic conditions improve germination of a gibberellic acid deficient rice

    Science.gov (United States)

    Frantz, Jonathan M.; Bugbee, Bruce

    2002-01-01

    Dwarf plants are useful in research because multiple plants can be grown in a small area. Rice (Oryza sativa L.) is especially important since its relatively simple genome has recently been sequenced. We are characterizing a gibberellic acid (GA) mutant of rice (japonica cv 'Shiokari,' line N-71) that is extremely dwarf (20 cm tall). Unfortunately, this GA mutation is associated with poor germination (70%) under aerobic conditions. Neither exogenous GA nor a dormancy-breaking heat treatment improved germination. However, 95% germination was achieved by germinating the seeds anaerobically, either in a pure N2 environment or submerged in unstirred tap water. The anaerobic conditions appear to break a mild post-harvest dormancy in this rice cultivar. Copyright 2002 Crop Science Society of America.

  16. Improved texture of polycrystalline hexaferrites using gluconic acid dispersant

    Science.gov (United States)

    Obi, O.; Burns, L.; Andalib, P.; Chang, H.; Chen, Y.; Harris, V. G.

    2014-05-01

    In this work, gluconic acid (GA), a low molecular weight, inexpensive and environmentally friendly solvent, was systematically investigated to determine its viability in enhancing the orientation of ferrite particles. Submicron-scale barium hexaferrite (BaM) powders were thoroughly dispersed via sonication for 30 min in various concentrations of GA (0, 2, 2.5, 5, 10, and 25 vol. %) in deionized water. An increase of ˜18% in squareness (SQ) and ˜69% in energy product ((BH)max) was observed with increase in GA concentration from 0 to 5 vol. %. However, further increase in GA concentration led to a decrease in SQ and (BH)max confirming that the effect of GA stems from an improved viscosity of the dispersant, which balances the freely rotating and stationary particles under dynamic compaction within a magnetic field.

  17. Colesevelam: a new and improved bile acid sequestrant?

    Science.gov (United States)

    Tziomalos, Konstantinos; Karagiannis, Asterios; Mikhailidis, Dimitri P; Athyros, Vasilios G

    2013-01-01

    Treatment with statins represents an essential component both of primary and secondary cardiovascular prevention strategies. However, a proportion of patients cannot reach low-density lipoprotein cholesterol (LDL-C) targets with the highest tolerable dose of a potent statin or is intolerant to statins. Several treatment options are available for these patients. Colesevelam is a relatively new bile acid sequestrant that decreases serum LDL-C levels. Moreover, colesevelam improves glycemic control and seems to be well-tolerated, at least in short-term studies. Therefore, colesevelam seems to be a useful tool for the management of high-risk patients who cannot achieve LDL-C targets with monotherapy with a potent statin.

  18. Cholinergic interneurons control local circuit activity and cocaine conditioning.

    Science.gov (United States)

    Witten, Ilana B; Lin, Shih-Chun; Brodsky, Matthew; Prakash, Rohit; Diester, Ilka; Anikeeva, Polina; Gradinaru, Viviana; Ramakrishnan, Charu; Deisseroth, Karl

    2010-12-17

    Cholinergic neurons are widespread, and pharmacological modulation of acetylcholine receptors affects numerous brain processes, but such modulation entails side effects due to limitations in specificity for receptor type and target cell. As a result, causal roles of cholinergic neurons in circuits have been unclear. We integrated optogenetics, freely moving mammalian behavior, in vivo electrophysiology, and slice physiology to probe the cholinergic interneurons of the nucleus accumbens by direct excitation or inhibition. Despite representing less than 1% of local neurons, these cholinergic cells have dominant control roles, exerting powerful modulation of circuit activity. Furthermore, these neurons could be activated by cocaine, and silencing this drug-induced activity during cocaine exposure (despite the fact that the manipulation of the cholinergic interneurons was not aversive by itself) blocked cocaine conditioning in freely moving mammals.

  19. Cholinergic Mechanisms in the Cerebral Cortex: Beyond Synaptic Transmission.

    Science.gov (United States)

    Ovsepian, Saak V; O'Leary, Valerie B; Zaborszky, Laszlo

    2016-06-01

    Functional overviews of cholinergic mechanisms in the cerebral cortex have traditionally focused on the release of acetylcholine with modulator and transmitter effects. Recently, however, data have emerged that extend the role of acetylcholine and cholinergic innervations to a range of housekeeping and metabolic functions. These include regulation of amyloid precursor protein (APP) processing with production of amyloid β (Aβ) and other APP fragments and control of the phosphorylation of microtubule-associated protein (MAP) tau. Evidence has been also presented for receptor-ligand like interactions of cholinergic receptors with soluble Aβ peptide and MAP tau, with modulator and signaling effects. Moreover, high-affinity binding of Aβ to the neurotrophin receptor p75 (p75NTR) enriched in basalo-cortical cholinergic projections has been implicated in clearance of Aβ and nucleation of amyloid plaques. Here, we critically evaluate these unorthodox cholinergic mechanisms and discuss their role in neuronal physiology and the biology of Alzheimer's disease. PMID:26002948

  20. The basal forebrain cholinergic system in aging and dementia : Rescuing cholinergic neurons from neurotoxic amyloid-beta 42 with memantine

    NARCIS (Netherlands)

    Nyakas, Csaba; Granic, Ivica; Halmy, Laszlo G.; Banerjee, Pradeep; Luiten, Paul G. M.

    2011-01-01

    The dysfunction and loss of basal forebrain cholinergic neurons and their cortical projections are among the earliest pathological events in the pathogenesis of Alzheimer's disease (AD). The evidence pointing to cholinergic impairments come from studies that report a decline in the activity of choli

  1. Cholinergic properties of neurons differentiated from an embryonal carcinoma cell-line (P19).

    Science.gov (United States)

    Parnas, D; Linial, M

    1995-11-01

    P19 is a mouse-derived embryonal carcinoma cell-line capable of differentiation toward ectodermal, mesodermal and endodermal lineages. Following treatment with retinoic acid these cells differentiate into neurons, astrocytes and fibroblast-like cells. We induced P19 differentiation under conditions which lead to a homogeneous neuronal culture (> 95% neurons). Under these conditions, most cells (approximately 85%) express high levels of the cholinergic markers acetyl cholinesterase and choline acetyltransferase while approximately 10% of cells express the GABAergic marker glutamic acid decarboxylase. While the proportion of the GABAergic neurons is constant at different culture conditions, the cholinergic phenotype is suppressed at high cell densities. The cholinergic nature of P19 neurons is also evident in their ability to form contacts with a muscle cell-line--C2. At day 10 of differentiation cells are capable of depolarization-dependent acetylcholine release. The release is Ca2+ dependent, and drops to baseline levels at 0.5 mM Ca2+. The cells also respond to sub-nM levels of alpha-latrotoxin by acetylcholine release. All major proteins implicated in synapse functionality are expressed prior to day 10 at both at RNA and protein levels. However, the expression pattern of each gene is unique. The genes include cytoskeletal proteins, synaptic vesicle proteins and terminal specific proteins. We suggest that this cell-line can serve as an in-vitro model system for the study of neuronal phenotype acquisition. Under our conditions, the P19 cells can also provide a system in which to study the differentiation of functional cholinergic neurons. PMID:8787867

  2. Improved physical stability of amorphous state through acid base interactions.

    Science.gov (United States)

    Telang, Chitra; Mujumdar, Siddharthya; Mathew, Michael

    2009-06-01

    To investigate role of specific interactions in aiding formation and stabilization of amorphous state in ternary and binary dispersions of a weakly acidic drug. Indomethacin (IMC), meglumine (MU), and polyvinyl pyrollidone (PVP) were the model drug, base, and polymer, respectively. Dispersions were prepared using solvent evaporation. Physical mixtures were cryogenically coground. XRPD, PLM, DSC, TGA, and FTIR were used for characterization. MU has a high crystallization tendency and is characterized by a low T(g) (17 degrees C). IMC crystallization was inhibited in ternary dispersion with MU compared to IMC/PVP alone. An amorphous state formed readily even in coground mixtures. Spectroscopic data are indicative of an IMC-MU amorphous salt and supports solid-state proton transfer. IMC-MU salt displays a low T(g) approximately 50 degrees C, but is more physically stable than IMC, which in molecular mixtures with MU, resisted crystallization even when present in stoichiometric excess of base. This is likely due to a disrupted local structure of amorphous IMC due to specific interactions. IMC showed improved physical stability on incorporating MU in polymer, in spite of low T(g) of the base indicating that chemical interactions play a dominant role in physical stabilization. Salt formation could be induced thermally and mechanically.

  3. GABAergic actions on cholinergic laterodorsal tegmental neurons

    DEFF Research Database (Denmark)

    Kohlmeier, K A; Kristiansen, Uffe

    2010-01-01

    Cholinergic neurons of the pontine laterodorsal tegmentum (LDT) play a critical role in regulation of behavioral state. Therefore, elucidation of mechanisms that control their activity is vital for understanding of how switching between wakefulness, sleep and anesthetic states is effectuated....... In vivo studies suggest that GABAergic mechanisms within the pons play a critical role in behavioral state switching. However, the postsynaptic, electrophysiological actions of GABA on LDT neurons, as well as the identity of GABA receptors present in the LDT mediating these actions is virtually unexplored...... neurons. Post-synaptic location of GABA(A) receptors was demonstrated by persistence of muscimol-induced inward currents in TTX and low Ca(2+) solutions. THIP, a selective GABA(A) receptor agonist with a preference for d-subunit containing GABA(A) receptors, induced inward currents, suggesting...

  4. Protective role of the cholinergic anti-inflammatory pathway in a mouse model of viral myocarditis.

    Directory of Open Access Journals (Sweden)

    Zheng Cheng

    Full Text Available Activation of the cholinergic anti-inflammatory pathway, which relies on the α7nAchR (alpha 7 nicotinic acetylcholine receptor, has been shown to decrease proinflammatory cytokines. This relieves inflammatory responses and improves the prognosis of patients with experimental sepsis, endotoxemia, ischemia/reperfusion injury, hemorrhagic shock, pancreatitis, arthritis and other inflammatory syndromes. However, whether the cholinergic anti-inflammatory pathway has an effect on acute viral myocarditis has not been investigated. Here, we studied the effects of the cholinergic anti-inflammatory pathway on acute viral myocarditis.In a coxsackievirus B3 murine myocarditis model (Balb/c, nicotine and methyllycaconitine were used to stimulate and block the cholinergic anti-inflammatory pathway, respectively. Relevant signal pathways were studied to compare their effects on myocarditis, survival rate, histopathological changes, ultrastructural changes, and cytokine levels. Nicotine treatments significantly improved survival rate, attenuated myocardial lesions, and downregulated the expression of TNF-α and IL-6. Methyllycaconitine decreased survival rate, aggravated myocardial lesions, and upregulated the expression of TNF-α and IL-6. In addition, levels of the signaling protein phosphorylated STAT3 were higher in the nicotine group and lower in the methyllycaconitine group compared with the untreated myocarditis group.These results show that nicotine protects mice from CVB3-induced viral myocarditis and that methyllycaconitine aggravates viral myocarditis in mice. Because nicotine is a α7nAchR agonist and methyllycaconitine is a α7nAchR antagonist, we conclude that α7nAchR activation increases the phosphorylation of STAT3, reduces the expression of TNF-α and IL-6, and, ultimately, alleviates viral myocarditis. We also conclude that blocking α7nAchR reduces the phosphorylation of STAT3, increases the expression of TNF-α and IL-6, aggravating viral

  5. Neurostimulation of the cholinergic anti-inflammatory pathway ameliorates disease in rat collagen-induced arthritis.

    Directory of Open Access Journals (Sweden)

    Yaakov A Levine

    Full Text Available INTRODUCTION: The inflammatory reflex is a physiological mechanism through which the nervous system maintains immunologic homeostasis by modulating innate and adaptive immunity. We postulated that the reflex might be harnessed therapeutically to reduce pathological levels of inflammation in rheumatoid arthritis by activating its prototypical efferent arm, termed the cholinergic anti-inflammatory pathway. To explore this, we determined whether electrical neurostimulation of the cholinergic anti-inflammatory pathway reduced disease severity in the collagen-induced arthritis model. METHODS: Rats implanted with vagus nerve cuff electrodes had collagen-induced arthritis induced and were followed for 15 days. Animals underwent active or sham electrical stimulation once daily from day 9 through the conclusion of the study. Joint swelling, histology, and levels of cytokines and bone metabolism mediators were assessed. RESULTS: Compared with sham treatment, active neurostimulation of the cholinergic anti-inflammatory pathway resulted in a 52% reduction in ankle diameter (p = 0.02, a 57% reduction in ankle diameter (area under curve; p = 0.02 and 46% reduction overall histological arthritis score (p = 0.01 with significant improvements in inflammation, pannus formation, cartilage destruction, and bone erosion (p = 0.02, accompanied by numerical reductions in systemic cytokine levels, not reaching statistical significance. Bone erosion improvement was associated with a decrease in serum levels of receptor activator of NF-κB ligand (RANKL from 132±13 to 6±2 pg/mL (mean±SEM, p = 0.01. CONCLUSIONS: The severity of collagen-induced arthritis is reduced by neurostimulation of the cholinergic anti-inflammatory pathway delivered using an implanted electrical vagus nerve stimulation cuff electrode, and supports the rationale for testing this approach in human inflammatory disorders.

  6. Lactic acid and methane: improved exploitation of biowaste potential.

    Science.gov (United States)

    Dreschke, G; Probst, M; Walter, A; Pümpel, T; Walde, J; Insam, H

    2015-01-01

    This feasibility study investigated a two-step biorefining approach to increase the value gained by recycling of organic municipal solid waste. Firstly, lactic acid was produced via batch fermentation at 37°C using the indigenous microbiome. Experiments revealed an optimal fermentation period of 24h resulting in high yields of lactic acid (up to 37gkg(-1)). The lactic acid proportion of total volatile fatty acid content reached up to 83%. Lactobacilli were selectively enriched to up to 75% of the bacterial community. Additionally conversion of organic matter to lactic acid was increased from 22% to 30% through counteracting end product inhibition by continuous lactic acid extraction. Secondly, fermentation residues were used as co-substrate in biomethane production yielding up to 618±41Nmlbiomethaneg(-1) volatile solids. Digestate, the only end product of this process can be used as organic fertilizer. PMID:25460983

  7. Omega-3 fatty acids improve psychomotor performance via mechanism not related to nitric acid production

    Directory of Open Access Journals (Sweden)

    Marwan S. M. Al-Nimer

    2012-01-01

    Full Text Available Omega-3 fatty acids (ω-3FAs are essential polyunsaturated fats that protect the brain from cognitive impairment. It increases the activity of endothelial nitric oxide synthetase (eNOS and thereby increases the nitric acid (NO production. This study aimed to explore the effect of ω-3FAs on psychomotor performance and to relate this effect to the reactive nitrogen species. This study was conducted in Department of Pharmacology, College of Medicine, Al-Mustansiriya University in Baghdad, Iraq. Twenty healthy subjects, allocated randomly from medical college students, were participated in the single blind clinical trial. Participants were divided into two groups, each of ten subjects to receive either placebo or (ω-3FAs (750 mg single oral dose daily for 5 days. They were asked to perform psychomotor performance before and after 5 days of treatment, and venous blood was obtained for determination of serum nitric oxide (NO and peroxynitrite (ONOO. ω-3FAs treated group was significantly different from placebo-treated group in reducing choice and motor reaction times as well as the critical flicker frequency threshold. The serum levels of NO and ONOO in ω-3FAs-treated group did not significantly differ from placebo-treated group. Short term supplementation of ω-3FAs improves the psychomotor performance in young healthy subjects via a mechanism not related to the production of nitric oxide production. Inflorescence is a panicle few flowered and fruit is a capsule. The data of the results obtained were presented and discussed.

  8. Suppression of glucocorticoid secretion enhances cholinergic transmission in rat hippocampus.

    Science.gov (United States)

    Mizoguchi, Kazushige; Shoji, Hirotaka; Ikeda, Ryuji; Tanaka, Yayoi; Maruyama, Wakako; Tabira, Takeshi

    2008-08-15

    We previously demonstrated that suppression of glucocorticoid secretion by adrenalectomy (ADX) impaired prefrontal cortex-sensitive working memory, but not reference memory. Since the cholinergic system in the hippocampus is also involved in these memories, we examined the effects of glucocorticoid suppression on cholinergic transmission in the rat hippocampus. A microdialysis study revealed that ADX did not affect the basal acetylcholine release, but enhanced the KCl-evoked response. This enhanced response was reversed by the corticosterone replacement treatment. The extracellular choline concentrations increased under both basal and KCl-stimulated conditions in the ADX rats, and these increases were also reversed by the corticosterone replacement. These results indicate that suppression of glucocorticoid secretion enhances cholinergic transmission in the hippocampus in response to stimuli. It is possible that this enhanced cholinergic transmission may not contribute to the ADX-induced working memory impairment, but it may be involved in maintenance of reference memory.

  9. Striatal cholinergic interneurons Drive GABA release from dopamine terminals.

    Science.gov (United States)

    Nelson, Alexandra B; Hammack, Nora; Yang, Cindy F; Shah, Nirao M; Seal, Rebecca P; Kreitzer, Anatol C

    2014-04-01

    Striatal cholinergic interneurons are implicated in motor control, associative plasticity, and reward-dependent learning. Synchronous activation of cholinergic interneurons triggers large inhibitory synaptic currents in dorsal striatal projection neurons, providing one potential substrate for control of striatal output, but the mechanism for these GABAergic currents is not fully understood. Using optogenetics and whole-cell recordings in brain slices, we find that a large component of these inhibitory responses derive from action-potential-independent disynaptic neurotransmission mediated by nicotinic receptors. Cholinergically driven IPSCs were not affected by ablation of striatal fast-spiking interneurons but were greatly reduced after acute treatment with vesicular monoamine transport inhibitors or selective destruction of dopamine terminals with 6-hydroxydopamine, indicating that GABA release originated from dopamine terminals. These results delineate a mechanism in which striatal cholinergic interneurons can co-opt dopamine terminals to drive GABA release and rapidly inhibit striatal output neurons.

  10. Periconceptional folic acid use : Still room to improve

    NARCIS (Netherlands)

    Zetstra-van der Woude, P.A.; de Walle, H.E.; de Jong-van den Berg, L.T.

    2012-01-01

    BACKGROUND: Folic acid use before and during pregnancy prevents neural tube defects. Since 1995, six surveys have been carried out among pregnant women to measure their knowledge and use of folic acid. The results of the most recent survey in 2009 will be discussed and compared with earlier surveys.

  11. Improved synthesis of isostearic acid using zeolite catalysts

    Science.gov (United States)

    Isostearic acids are unique and important biobased products with superior properties. Unfortunately, they are not widely utilized in industry because they are produced as byproducts from a process called clay-catalyzed oligomerization of tall oil fatty acids. Generally, this clay method results in...

  12. NO-flurbiprofen reduces amyloid-beta, is neuroprotective in cell culture, and enhances cognition in response to cholinergic blockade.

    Science.gov (United States)

    Abdul-Hay, Samer O; Luo, Jia; Ashghodom, Rezene T; Thatcher, Gregory R J

    2009-11-01

    The non-steroidal anti-inflammatory drug flurbiprofen is a selective amyloid lowering agent which has been studied clinically in Alzheimer's disease. HCT-1026 is an ester prodrug of flurbiprofen incorporating a nitrate carrier moiety that in vivo provides NO bioactivity and an improved safety profile. In vitro, HCT-1026 retained the cyclooxygenase inhibitory and non-steroidal anti-inflammatory drug activity of flurbiprofen, but at concentrations at which levels of amyloid-beta 1-42 amino acid were lowered by flurbiprofen, amyloid-beta 1-42 amino acid levels were elevated 200% by HCT-1026. Conversely, at lower concentrations, HCT-1026 behaved as a selective amyloid lowering agent with greater potency than flurbiprofen. The difference in concentration-responses between flurbiprofen and HCT-1026 in vitro suggests different cellular targets; and in no case did a combination of nitrate drug with flurbiprofen provide similar actions. In vivo, HCT-1026 was observed to reverse cognitive deficits induced by scopolamine in two behavioral assays; activity that was also shown by a classical nitrate drug, but not by flurbiprofen. The ability to restore aversive memory and spatial working and reference memory after cholinergic blockade has been demonstrated by other agents that stimulate NO/cGMP signaling. These observations add positively to the preclinical profile of HCT-1026 and NO chimeras in Alzheimer's disease.

  13. Culture density regulates both the cholinergic phenotype and the expression of the CNTF receptor in P19 neurons.

    Science.gov (United States)

    Parnas, D; Linial, M

    1997-04-01

    The P19 embryonal carcinoma cells differentiate into neurons, astrocytes, and fibroblast-like cells following induction with retinoic acid. The cells mature into functional neurons, as determined by their ability to release neurotransmitters in a Ca(2+)- and depolarization-dependent manner. P19 neurons in culture represent a mixed population in terms of their neurotransmitter phenotype. The cholinergic phenotype of these neurons is modulated by culture density. Cholinergic markers, such as the vesicular acetylcholine transporter, acetyl cholinesterase, and choline acetyltransferase, are expressed in about 85% of the cells in sparse cultures and are largely suppressed at high cell densities. In contrast, glutamate release is enhanced in dense P19 neuronal cultures. The factor mediating the density effect is concentrated exclusively on the cell membrane of P19 neurons and not on the nonneuronal cells, which also differentiate from P19 embryonal carcinoma cells. This membrane-associated component retains its functionality, even after membrane fixation. The downregulation of the cholinergic properties in dense cultures is paralleled by a downregulation of the alpha subunit of the ciliary neurotrophic factor (CNTF) receptor. Thus, it is suggested that the membrane-associated factor, which mediates the density effect, downregulates the cholinergic phenotype by inhibiting the responsiveness of these neurons to CNTF. We further suggest that the P19 cell line can serve as a model system for the study of neurotransmitter phenotype acquisition and plasticity throughout neuronal differentiation. PMID:9188041

  14. Cholinergic Mechanisms in Spinal Locomotion - Potential Target for Rehabilitation Approaches

    OpenAIRE

    Jordan, L M; Noga, B. R.; Cabaj, A. M.; J Provencher

    2014-01-01

    Previous experiments implicate cholinergic brainstem and spinal systems in the control of locomotion. Our results demonstrate that the endogenous cholinergic propriospinal system, acting via M2 and M3 muscarinic receptors, is capable of consistently producing well-coordinated locomotor activity in the in vitro neonatal preparation, placing it in a position to contribute to normal locomotion and to provide a basis for recovery of locomotor capability in the absence of descending pathways. Test...

  15. Astrocytes mediate in vivo cholinergic-induced synaptic plasticity.

    Directory of Open Access Journals (Sweden)

    Marta Navarrete

    2012-02-01

    Full Text Available Long-term potentiation (LTP of synaptic transmission represents the cellular basis of learning and memory. Astrocytes have been shown to regulate synaptic transmission and plasticity. However, their involvement in specific physiological processes that induce LTP in vivo remains unknown. Here we show that in vivo cholinergic activity evoked by sensory stimulation or electrical stimulation of the septal nucleus increases Ca²⁺ in hippocampal astrocytes and induces LTP of CA3-CA1 synapses, which requires cholinergic muscarinic (mAChR and metabotropic glutamate receptor (mGluR activation. Stimulation of cholinergic pathways in hippocampal slices evokes astrocyte Ca²⁺ elevations, postsynaptic depolarizations of CA1 pyramidal neurons, and LTP of transmitter release at single CA3-CA1 synapses. Like in vivo, these effects are mediated by mAChRs, and this cholinergic-induced LTP (c-LTP also involves mGluR activation. Astrocyte Ca²⁺ elevations and LTP are absent in IP₃R2 knock-out mice. Downregulating astrocyte Ca²⁺ signal by loading astrocytes with BAPTA or GDPβS also prevents LTP, which is restored by simultaneous astrocyte Ca²⁺ uncaging and postsynaptic depolarization. Therefore, cholinergic-induced LTP requires astrocyte Ca²⁺ elevations, which stimulate astrocyte glutamate release that activates mGluRs. The cholinergic-induced LTP results from the temporal coincidence of the postsynaptic activity and the astrocyte Ca²⁺ signal simultaneously evoked by cholinergic activity. Therefore, the astrocyte Ca²⁺ signal is necessary for cholinergic-induced synaptic plasticity, indicating that astrocytes are directly involved in brain storage information.

  16. Effects of pro-cholinergic treatment in patients suffering from spatial neglect

    Directory of Open Access Journals (Sweden)

    Nadia eLucas

    2013-09-01

    Full Text Available Spatial neglect is a neurological condition characterized by a breakdown of spatial cognition contralateral to hemispheric damage. Deficits in spatial attention towards the contralesional side are considered to be central to this syndrome. Brain lesions typically involve right fronto-parietal cortices mediating attentional functions and subcortical connections in underlying white matter. Convergent findings from neuroimaging and behavioral studies in both animals and humans suggest that the cholinergic system might also be critically implicated in selective attention by modulating cortical function via widespread projections from the basal forebrain. Here we asked whether deficits in spatial attention associated with neglect could partly result from a cholinergic deafferentation of cortical areas subserving attentional functions, and whether such disturbances could be alleviated by pro-cholinergic therapy. We examined the effect of a single-dose transdermal nicotine treatment on spatial neglect in 10 stroke patients in a double-blind placebo-controlled protocol, using a standardized battery of neglect tests. Nicotine induced systematic improvement on cancellation tasks and facilitated orienting to single visual targets, but had no significant effect on other tests. These results support a global effect of nicotine on attention and arousal, but no effect on other spatial mechanisms impaired in neglect.

  17. Effects of diazinon on the lymphocytic cholinergic system of Nile tilapia fish (Oreochromis niloticus).

    Science.gov (United States)

    Toledo-Ibarra, G A; Díaz-Resendiz, K J G; Pavón-Romero, L; Rojas-García, A E; Medina-Díaz, I M; Girón-Pérez, M I

    2016-08-01

    Fish rearing under intensive farming conditions can be easily disturbed by pesticides, substances that have immunotoxic properties and may predispose to infections. Organophosphorus pesticides (OPs) are widely used in agricultural activities; however, the mechanism of immunotoxicity of these substances is unclear. The aim of this study was to evaluate the effect of diazinon pesticides (OPs) on the cholinergic system of immune cells as a possible target of OP immunotoxicity. We evaluated ACh levels and cholinergic (nicotinic and muscarinic) receptor concentration. Additionally, AChE activity was evaluated in mononuclear cells of Nile tilapia (Oreochromis niloticus), a freshwater fish mostly cultivated in tropical regions around the world. The obtained results indicate that acute exposure to diazinon induces an increase in ACh concentration and a decrease in nAChR and mAChR concentrations and AChE activity in fish immune cells, This suggests that the non-neuronal lymphocytic cholinergic system may be the main target in the mechanism of OP immunotoxicity. This study contributes to the understanding of the mechanisms of immunotoxicity of pollutants and may help to take actions for animal health improvement. PMID:27260186

  18. Amyloid-β depresses excitatory cholinergic synaptic transmission in Drosophila

    Institute of Scientific and Technical Information of China (English)

    Liqun Fang; Jingjing Duan; Dongzhi Ran; Zihao Fan; Ying Yan; Naya Huang; Huaiyu Gu; Yulan Zhu

    2012-01-01

    Objective Decline,disruption,or alterations of nicotinic cholinergic mechanisms contribute to cognitive dysfunctions like Alzheimer's disease (AD).Although amyloid-β (Aβ) aggregation is a pathological hallmark of AD,the mechanisms by which Aβ peptides modulate cholinergic synaptic transmission and memory loss remain obscure.This study was aimed to investigate the potential synaptic modulation by Aβ of the cholinergic synapses between olfactory receptor neurons and projection neurons (PNs) in the olfactory lobe of the fruit fly.Methods Cholinergic spontaneous and miniature excitatory postsynaptic current (mEPSC) were recorded with whole-cell patch clamp from PNs in Drosophila AD models expressing Aβ40,Aβ42,or Aβ42Arc peptides in neural tissue.Results In fly pupae (2 days before eclosion),overexpression of Aβ42 or Aβ42Arc,but not Aβ40,led to a significant decrease of mEPSC frequency,while overexpression of Aβ40,Aβ42,or Aβ42Arc had no significant effect on mEPSC amplitude.In contrast,Pavlovian olfactory associative learning and lifespan assays showed that both short-term memory and lifespan were decreased in the Drosophila models expressing Aβ40,Aβ42,or Aβ42Arc.Conclusion Both electrophysiological and behavioral results showed an effect of Aβ peptide on cholinergic synaptic transmission and suggest a possible mechanism by which Aβ peptides cause cholinergic neuron degeneration and the consequent memory loss.

  19. Localization of the M2 muscarinic cholinergic receptor in dendrites, cholinergic terminals, and noncholinergic terminals in the rat basolateral amygdala: An ultrastructural analysis.

    Science.gov (United States)

    Muller, Jay F; Mascagni, Franco; Zaric, Violeta; Mott, David D; McDonald, Alexander J

    2016-08-15

    Activation of M2 muscarinic receptors (M2Rs) in the rat anterior basolateral nucleus (BLa) is critical for the consolidation of memories of emotionally arousing events. The present investigation used immunocytochemistry at the electron microscopic level to determine which structures in the BLa express M2Rs. In addition, dual localization of M2R and the vesicular acetylcholine transporter protein (VAChT), a marker for cholinergic axons, was performed to determine whether M2R is an autoreceptor in cholinergic axons innervating the BLa. M2R immunoreactivity (M2R-ir) was absent from the perikarya of pyramidal neurons, with the exception of the Golgi complex, but was dense in the proximal dendrites and axon initial segments emanating from these neurons. Most perikarya of nonpyramidal neurons were also M2R-negative. About 95% of dendritic shafts and 60% of dendritic spines were M2 immunoreactive (M2R(+) ). Some M2R(+) dendrites had spines, suggesting that they belonged to pyramidal cells, whereas others had morphological features typical of nonpyramidal neurons. M2R-ir was also seen in axon terminals, most of which formed asymmetrical synapses. The main targets of M2R(+) terminals forming asymmetrical (putative excitatory) synapses were dendritic spines, most of which were M2R(+) . The main targets of M2R(+) terminals forming symmetrical (putative inhibitory or neuromodulatory) synapses were unlabeled perikarya and M2R(+) dendritic shafts. M2R-ir was also seen in VAChT(+) cholinergic terminals, indicating a possible autoreceptor role. These findings suggest that M2R-mediated mechanisms in the BLa are very complex, involving postsynaptic effects in dendrites as well as regulating release of glutamate, γ-aminobutyric acid, and acetylcholine from presynaptic axon terminals. J. Comp. Neurol. 524:2400-2417, 2016. © 2016 Wiley Periodicals, Inc. PMID:26779591

  20. Monitoring cholinergic activity during attentional performance in mice heterozygous for the choline transporter: a model of cholinergic capacity limits.

    Science.gov (United States)

    Paolone, Giovanna; Mallory, Caitlin S; Koshy Cherian, Ajeesh; Miller, Thomas R; Blakely, Randy D; Sarter, Martin

    2013-12-01

    Reductions in the capacity of the human choline transporter (SLC5A7, CHT) have been hypothesized to diminish cortical cholinergic neurotransmission, leading to risk for cognitive and mood disorders. To determine the acetylcholine (ACh) release capacity of cortical cholinergic projections in a mouse model of cholinergic hypofunction, the CHT+/- mouse, we assessed extracellular ACh levels while mice performed an operant sustained attention task (SAT). We found that whereas SAT-performance-associated increases in extracellular ACh levels of CHT+/- mice were significantly attenuated relative to wildtype littermates, performance on the SAT was normal. Tetrodotoxin-induced blockade of neuronal excitability reduced both dialysate ACh levels and SAT performance similarly in both genotypes. Likewise, lesions of cholinergic neurons abolished SAT performance in both genotypes. However, cholinergic activation remained more vulnerable to the reverse-dialyzed muscarinic antagonist atropine in CHT+/- mice. Additionally, CHT+/- mice displayed greater SAT-disrupting effects of reverse dialysis of the nAChR antagonist mecamylamine. Receptor binding assays revealed a higher density of α4β2* nAChRs in the cortex of CHT+/- mice compared to controls. These findings reveal compensatory mechanisms that, in the context of moderate cognitive challenges, can overcome the performance deficits expected from the significantly reduced ACh capacity of CHT+/- cholinergic terminals. Further analyses of molecular and functional compensations in the CHT+/- model may provide insights into both risk and resiliency factors involved in cognitive and mood disorders.

  1. Striatal cholinergic interneuron regulation and circuit effects

    Directory of Open Access Journals (Sweden)

    Sean Austin Lim

    2014-10-01

    Full Text Available The striatum plays a central role in motor control and motor learning. Appropriate responses to environmental stimuli, including pursuit of reward or avoidance of aversive experience all require functional striatal circuits. These pathways integrate synaptic inputs from limbic and cortical regions including sensory, motor and motivational information to ultimately connect intention to action. Although many neurotransmitters participate in striatal circuitry, one critically important player is acetylcholine (ACh. Relative to other brain areas, the striatum contains exceptionally high levels of ACh, the enzymes that catalyze its synthesis and breakdown, as well as both nicotinic and muscarinic receptor types that mediate its postsynaptic effects. The principal source of striatal ACh is the cholinergic interneuron (ChI, which comprises only about 1-2% of all striatal cells yet sends dense arbors of projections throughout the striatum. This review summarizes recent advances in our understanding of the factors affecting the excitability of these neurons through acute effects and long term changes in their synaptic inputs. In addition, we discuss the physiological effects of ACh in the striatum, and how changes in ACh levels may contribute to disease states during striatal dysfunction.

  2. Intrinsic cholinergic neurons in the hippocampus: fact or artefact?

    Directory of Open Access Journals (Sweden)

    Jan Krzysztof Blusztajn

    2016-03-01

    Full Text Available It is generally agreed that hippocampal acetylcholine (ACh is synthesized and released exclusively from the terminals of the long-axon afferents whose cell bodies reside in the medial septum and diagonal band. The search for intrinsic cholinergic neurons in the hippocampus has a long history; however evidence for the existence of these neurons has been inconsistent, with most investigators failing to detect them using in situ hybridization or immunohistochemical staining of the cholinergic markers, choline acetyltransferase (CHAT or vesicular acetylcholine transporter (VACHT. Advances in the use of bacterial artificial chromosome (BAC transgenic mice expressing a reporter protein under the control of the genomic elements of the Chat gene (Chat-BAC mice have facilitated studies of cholinergic neurons. Such mice show robust and faithful expression of the reporter proteins in all known cholinergic cell populations. The availability of the Chat-BAC mice re-ignited interest in hippocampal cholinergic interneurons, because a small number of such reporter-expressing cells is frequently observed in the hippocampus of these mice. However, to date, attempts to confirm that these neurons co-express the endogenous cholinergic markers CHAT or VACHT, or release ACh, have been unsuccessful. Without such confirmatory evidence it is best to conclude that there are no cholinergic neurons in the hippocampus. Similar considerations apply to other BAC transgenic lines, whose utility as a discovery tool for cell populations heretofore not known to express the genes of interest encoded by the BACs, must be validated by methods that detect expression of the endogenous genes.

  3. An Improved Synthesis of Retinoic Acid from β-Ionone

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    A convenient and large-scale preparation of rctinoic acid 1 from β-ionone in five steps with 38% overall yield is described. The key steps are the epoxidization of 2 with a new methylated agent and the condensation 4 with tetraethyl methylenediphophonate in one-pot procedure to prepare 6.

  4. Orthogonal Fatty Acid Biosynthetic Pathway Improves Fatty Acid Ethyl Ester Production in Saccharomyces cerevisiae.

    Science.gov (United States)

    Eriksen, Dawn T; HamediRad, Mohammad; Yuan, Yongbo; Zhao, Huimin

    2015-07-17

    Fatty acid ethyl esters (FAEEs) are a form of biodiesel that can be microbially produced via a transesterification reaction of fatty acids with ethanol. The titer of microbially produced FAEEs can be greatly reduced by unbalanced metabolism and an insufficient supply of fatty acids, resulting in a commercially inviable process. Here, we report on a pathway engineering strategy in Saccharomyces cerevisiae for enhancing the titer of microbially produced FAEEs by providing the cells with an orthogonal route for fatty acid synthesis. The fatty acids generated from this heterologous pathway would supply the FAEE production, safeguarding endogenous fatty acids for cellular metabolism and growth. We investigated the heterologous expression of a Type-I fatty acid synthase (FAS) from Brevibacterium ammoniagenes coupled with WS/DGAT, the wax ester synthase/acyl-coenzyme that catalyzes the transesterification reaction with ethanol. Strains harboring the orthologous fatty acid synthesis yielded a 6.3-fold increase in FAEE titer compared to strains without the heterologous FAS. Variations in fatty acid chain length and degree of saturation can affect the quality of the biodiesel; therefore, we also investigated the diversity of the fatty acid production profile of FAS enzymes from other Actinomyces organisms. PMID:25594225

  5. Improved One-pot Synthesis of 4,6-Dihydroxyisophthalic Acid and 2,3-Dihydroxyterephthalic Acid

    Institute of Scientific and Technical Information of China (English)

    Guang Dong LEI; Li Xin LI; Zhi Yun LU; Ming Gui XIE

    2005-01-01

    An improved method for the large-scale preparation of 4,6-dihydroxyisophthalic acid and 2,3-dihydroxyterephthalic acid has been developed. Compared to the previous procedures,this new process requires much lower CO2 pressure of 0.3 Mpa and shorter reaction time, thus providing a convenient access for large-scale synthesis. The yield is high (93% and 65%,respectively), and the oxidation of phenol is nearly inhibited, neither decolorization nor further chromatographic purification is required.

  6. Ursodeoxycholic acid improves gastrointestinal motility defects in gallstone patients

    Institute of Scientific and Technical Information of China (English)

    A Colecchia; G Mazzella; L Sandri; F Azzaroli; M Magliuolo; P Simoni; ML Bacchi-Reggiani; E Roda; D Festi

    2006-01-01

    AIM: To simultaneously evaluate the presence of defects in gallbladder and gastric emptying, as well as in intestinal transit in gallstone patients (GS) and the effect of chronic ursodeoxycholic acid (UDCA) administration on these parameters and on serum bile acids and clinical outcome in GS and controls (CTR).METHODS: After a standard liquid test meal, gallbladder and gastric emptying (by ultrasound), oroileal transit time (OI∏) (by an immunoenzymatic technique)and serum bile acids (by HPLC) were evaluated before and after 3 mo of UDCA (12 mg/kg bw/d) or placebo administration in 10 symptomatic GS and 10 matched healthy CTR.RESULTS: OI∏ was longer in GS than in CTR (P <0.0001); UDCA significantly reduced OI∏ in GS (P <0.0001), but not in CTR. GS had longer gastric halfemptying time (t1/2) than CTR (P < 0.0044) at baseline;after UDCA, t1/2 significantly decreased (P < 0.006) in GS but not in CTR. Placebo administration had no effect on gastric emptying and intestinal transit in both GS and CTR.CONCLUSION: The gallstone patient has simultaneous multiple impairments of gallbladder and gastric emptying, as well as of intestinal transit. UDCA administration restores these defects in GS, without any effect in CTR. These results confirm the pathogenetic role of gastrointestinal motility in gallstone disease and suggest an additional mechanism of action for UDCA in reducing bile cholesterol supersaturation.

  7. Improved Detection of Domoic Acid Using Covalently Immobilised Antibody Fragments

    Directory of Open Access Journals (Sweden)

    J. Gerard Wall

    2013-03-01

    Full Text Available Antibody molecules, and antibody fragments in particular, have enormous potential in the development of biosensors for marine monitoring. Conventional immobilisation approaches used in immunoassays typically yield unstable and mostly incorrectly oriented antibodies, however, resulting in reduced detection sensitivities for already low concentration analytes. The 2H12 anti-domoic acid scFv antibody fragment was engineered with cysteine-containing linkers of two different lengths, distal to the antigen binding pocket, for covalent and correctly oriented immobilisation of the scFvs on functionalised solid supports. The Escherichia coli-produced, cysteine-engineered scFvs dimerised in solution and demonstrated similar efficiencies of covalent immobilisation on maleimide-activated plates and minimal non-covalent attachment. The covalently attached scFvs exhibited negligible leaching from the support under acidic conditions that removed almost 50% of the adsorbed wildtype fragment, and IC50s for domoic acid of 270 and 297 ng/mL compared with 1126 and 1482 ng/mL, respectively, for their non-covalently adsorbed counterparts. The expression and immobilisation approach will facilitate the development of stable, reusable biosensors with increased stability and detection sensitivity for marine neurotoxins.

  8. Cholinergic and adrenergic influence on the teleost heart in vivo.

    Science.gov (United States)

    Axelsson, M; Ehrenström, F; Nilsson, S

    1987-01-01

    The tonical cholinergic and adrenergic influence on the heart rate was investigated in vivo in seven species of marine teleosts (pollack, Pollachius pollachius; cuckoo wrasse, Labrus mixtus; ballan wrasse, Labrus berggylta; five-bearded rockling, Ciliata mustela; tadpole fish, Raniceps raninus; eel-pout, Zoarces viviparus and short-spined sea scorpion, Myoxocephalus scor pius) during rest and, in two of the species (P. pollachius and L. mixtus), also during moderate swimming exercise in a Blazka-type swim tunnel. Ventral aortic blood pressure and heart rate were recorded via a catheter implanted in an afferent branchial artery, and the influence of the cholinergic and adrenergic tonus on the heart rate was assessed by injection of atropine and sotalol respectively. During rest the adrenergic tonus was higher than the cholinergic tonus in all species except L. berggylta, where the reverse was true. In P. pollachius and L. mixtus, exercise appeared to produce a lowering of the cholinergic tonus on the heart and, possibly, a slight increase of the adrenergic tonus. The nature of the adrenergic tonus (humoral or neural) is not clear, but the low plasma concentrations of catecholamines both during rest and exercise could be interpreted in favour of a mainly neural adrenergic tonus on the teleost heart. These experiments are compatible with the view that both a cholinergic inhibitory tonus and an adrenergic excitatory tonus are general features in the control of the teleost heart in vivo, both at rest and during moderate swimming exercise.

  9. Effects of sustained proNGF blockade on attentional capacities in aged rats with compromised cholinergic system.

    Science.gov (United States)

    Yegla, B; Parikh, V

    2014-03-01

    Disruption in nerve growth factor (NGF) signaling via tropomyosin-related kinase A (trkA) receptors compromises the integrity of the basal forebrain (BF) cholinergic system, yielding cognitive, specifically attentional, impairments in Alzheimer's disease (AD). Although normal aging is considered a risk factor for AD, the mechanisms underlying the selective vulnerability of the aging cholinergic system to trkA disruption is not clear. The levels of proNGF, a proneurotrophin that possesses higher affinity for p75 receptors, increase in aging. The present study was designed to test the hypothesis that cholinergic and attentional dysfunction in aged rats with reduced BF trkA receptors occurs due to the overactivation of endogenous proNGF signaling. We employed a viral vector that produced trkA shRNA to suppress trkA receptors in the corticopetal cholinergic neurons of aged rats. BF trkA suppression impaired animals' performance on signal trials in both the sustained attention task (SAT) and the cognitively taxing distractor version of SAT (dSAT) and these deficits were normalized by chronic intracerebroventricular administration of proNGF antibody. Moreover, depolarization-evoked acetylcholine (ACh) release and the density of cortical cholinergic fibers were partially restored in these animals. However, SAT/dSAT scores reflecting overall performance did not improve following proNGF blockade in trkA knockdown rats due to impaired performance in non-signal trials. Sustained proNGF blockade alone did not alter baseline attentional performance but produced moderate impairments during challenging conditions. Collectively, our findings indicate that barring proNGF-p75 signaling may exert some beneficial effects on attentional capacities specifically when BF trkA signaling is abrogated. However, endogenous proNGF may also possess neurotrophic effects and blockade of this proneurotrophin may not completely ameliorate attentional impairments in AD and potentially hinder

  10. Satureja bachtiarica ameliorate beta-amyloid induced memory impairment, oxidative stress and cholinergic deficit in animal model of Alzheimer's disease.

    Science.gov (United States)

    Soodi, Maliheh; Saeidnia, Soodabeh; Sharifzadeh, Mohammad; Hajimehdipoor, Homa; Dashti, Abolfazl; Sepand, Mohammad Reza; Moradi, Shahla

    2016-04-01

    Extracellular deposition of Beta-amyloid peptide (Aβ) is the main finding in the pathophysiology of Alzheimer's disease (AD), which damages cholinergic neurons through oxidative stress and reduces the cholinergic neurotransmission. Satureja bachtiarica is a medicinal plant from the Lamiaceae family which was widely used in Iranian traditional medicine. The aim of the present study was to investigate possible protective effects of S. bachtiarica methanolic extract on Aβ induced spatial memory impairment in Morris Water Maze (MWM), oxidative stress and cholinergic neuron degeneration. Pre- aggregated Aβ was injected into the hippocampus of each rat bilaterally (10 μg/rat) and MWM task was performed 14 days later to evaluate learning and memory function. Methanolic extract of S.bachtiarica (10, 50 and 100 mg/Kg) was injected intraperitoneally for 19 consecutive days, after Aβ injection. After the probe test the brain tissue were collected and lipid peroxidation, Acetylcholinesterase (AChE) activity and Cholin Acetyl Transferees (ChAT) immunorectivity were measured in the hippocampus. Intrahipocampal injection of Aβ impaired learning and memory in MWM in training days and probe trail. Methanolic extract of S. bachtiarica (50 and 100 mg/Kg) could attenuate Aβ-induced memory deficit. ChAT immunostaining revealed that cholinergic neurons were loss in Aβ- injected group and S. bachtiarica (100 mg/Kg) could ameliorate Aβ- induced ChAT reduction in the hippocampus. Also S. bachtiarica could ameliorate Aβ-induced lipid peroxidation and AChE activity increase in the hippocampus. In conclusion our study represent that S.bachtiarica methanolic extract can improve Aβ-induced memory impairment and cholinergic loss then we recommended this extract as a candidate for further investigation in treatment of AD. PMID:26638718

  11. Morphine dependence and withdrawal induced changes in cholinergic signaling

    Science.gov (United States)

    Neugebauer, Nichole M.; Einstein, Emily B.; Lopez, Maria B.; McClure-Begley, Tristan D.; Mineur, Yann S.; Picciotto, Marina R.

    2013-01-01

    Cholinergic signaling is thought to be involved in morphine dependence and withdrawal, but the specific mechanisms involved remain unclear. The current study aimed to identify alterations in the cholinergic system that may contribute to the development of morphine dependence and withdrawal. Acetylcholinesterase (AChE) activity and [3H]-epibatidine binding were evaluated in order to determine if morphine dependence and withdrawal induces alterations in cholinergic signaling or expression of high affinity nicotinic acetylcholine receptors (nAChRs) in the midbrain (MB), medial habenula (MHb) and interpeduncular nucleus (IPN). The effect of cholinergic signaling through nAChRs on morphine-withdrawal induced jumping behavior was then determined. Lastly, the contribution of β4-containing nAChRs receptors in the MHb to morphine-withdrawal induced jumping behavior and neuronal activity as indicated by c-fos expression was assessed. Chronic morphine administration decreased AChE activity in MB and MHb, an effect that was no longer present following precipitated withdrawal. Morphine dependent mice showed increased nicotinic acetylcholine receptor (nAChR) levels in MB. Further, nicotine (0.4 mg/kg) and lobeline (3 mg/kg) decreased jumping behavior while mecamylamine (1 mg/kg) had no effect. Knock-down of β4 subunit-containing nAChRs in the MHb attenuated c-fos activation, but did not decrease morphine withdrawal-induced jumping. Thus, morphine withdrawal induces cholinergic signaling in the MHb, but this does not appear to be responsible for the effects of cholinergic drugs on somatic signs of opiate withdrawal, as measured by jumping behavior. PMID:23651795

  12. Ventral tegmental area GABA projections pause accumbal cholinergic interneurons to enhance associative learning.

    Science.gov (United States)

    Brown, Matthew T C; Tan, Kelly R; O'Connor, Eoin C; Nikonenko, Irina; Muller, Dominique; Lüscher, Christian

    2012-12-20

    The ventral tegmental area (VTA) and nucleus accumbens (NAc) are essential for learning about environmental stimuli associated with motivationally relevant outcomes. The task of signalling such events, both rewarding and aversive, from the VTA to the NAc has largely been ascribed to dopamine neurons. The VTA also contains GABA (γ-aminobutyric acid)-releasing neurons, which provide local inhibition and also project to the NAc. However, the cellular targets and functional importance of this long-range inhibitory projection have not been ascertained. Here we show that GABA-releasing neurons of the VTA that project to the NAc (VTA GABA projection neurons) inhibit accumbal cholinergic interneurons (CINs) to enhance stimulus-outcome learning. Combining optogenetics with structural imaging and electrophysiology, we found that VTA GABA projection neurons selectively target NAc CINs, forming multiple symmetrical synaptic contacts that generated inhibitory postsynaptic currents. This is remarkable considering that CINs represent a very small population of all accumbal neurons, and provide the primary source of cholinergic tone in the NAc. Brief activation of this projection was sufficient to halt the spontaneous activity of NAc CINs, resembling the pause recorded in animals learning stimulus-outcome associations. Indeed, we found that forcing CINs to pause in behaving mice enhanced discrimination of a motivationally important stimulus that had been associated with an aversive outcome. Our results demonstrate that VTA GABA projection neurons, through their selective targeting of accumbal CINs, provide a novel route through which the VTA communicates saliency to the NAc. VTA GABA projection neurons thus emerge as orchestrators of dopaminergic and cholinergic modulation in the NAc.

  13. High dose folic acid supplementation improves arterial endothelial function of coronary patients independent of homocysteine level

    Institute of Scientific and Technical Information of China (English)

    KS Woo; P Chook; M Qiao; AKY Chan; LLT Chan; WWM Chan; DS Celermajer

    2003-01-01

    @@ Background Hyperhomocysteinemia (prevalent in rural northern China)is an emerging risk factor for arterial endothelial dysfunction in CAD, which can be improved with folic acid supplementation. Such homocysteine-lowerying dosage of folio acid ( < 1 mg/d ) can reduce restenosis after PTCA, but not the cardiovascular events.Folic acid has additional vascular protection in antixidation, NO synthase protection, angiogenesis-promotion and cytokines reduction.

  14. Improved nucleic acids descriptors for siRNA efficacy prediction.

    OpenAIRE

    Sciabola, S.; Cao, Q; Orozco, M; Faustino, I; Stanton, R. V.

    2013-01-01

    Although considerable progress has been made recently in understanding how gene silencing is mediated by the RNAi pathway, the rational design of effective sequences is still a challenging task. In this article, we demonstrate that including three-dimensional descriptors improved the discrimination between active and inactive small interfering RNAs (siRNAs) in a statistical model. Five descriptor types were used: (i) nucleotide position along the siRNA sequence, (ii) nucleotide composition in...

  15. Cholinergic basis of memory improving effect of Ocimum tenuiflorum linn

    Directory of Open Access Journals (Sweden)

    Joshi H

    2006-01-01

    Full Text Available Dementia is one of the age-related mental problems and a characteristic symptom of Alzheimer′s disease. Nootropic agents are used in situations where there is organic disorder in learning abilities. The present work was undertaken to assess the potential of Ocimum tenuiflorum Linn. as a nootropic and anticholinesterase agent in mice. Ethanol extract of dried whole plant of O. tenuiflorum Linn. ameliorated the amnesic effect of scopolamine (0.4 mg/kg and aging-induced memory deficits in mice. Passive avoidance paradigm served as the exteroceptive behavioural model. O. tenuiflorum extract increased step-down latency and acetyl cholinesterase inhibition significantly. Hence, O. tenuiflorum can be employed in the treatment of cognitive disorders such as dementia and Alzheimer′s disease.

  16. Improvement in ionic conductivities of poly-(2-vinylpyridine) by treatment with crotonic acid and vinyl acetic acid

    Indian Academy of Sciences (India)

    Anna Gogoi; Neelotpal Sen Sarma

    2015-06-01

    The synthesis, characterization and improved ionic conductivities of the salts of poly-(2-vinylpyridine) with crotonic acid and vinyl acetic acid are reported here. In this study, the alternating current conductivity measurements were carried out within the temperature range of 30–90° C and the frequency range of 1 Hz–100 kHz in solid state. A two- to three-fold increase in conductivity was observed for vinyl acetic acid salt whereas one- to twofold increase was observed for crotonic acid salt. The ionic transport numbers of the salts were measured with the help of the Wagner polarization technique which reveals that the percentage of ionic character of the salts are significantly higher compared with the polymer. The percentage of water uptake by the polymer and its salts were also observed.

  17. Improvement of bone formation biomarkers after 1-year consumption with milk fortified with eicosapentaenoic acid, docosahexaenoic acid, oleic acid, and selected vitamins.

    Science.gov (United States)

    Martin-Bautista, Elena; Muñoz-Torres, Manuel; Fonolla, Juristo; Quesada, Miguel; Poyatos, Antonio; Lopez-Huertas, Eduardo

    2010-05-01

    The hypothesis of this study was that the replacement of regular milk with fortified milk in hyperlipidemic adults for 1 year would improve bone biomarkers. The fortified milk contained eicosapentaenoic acid and docosahexaenoic acid from fish oils, oleic acid, vitamins A, B(6), and E, as well as folic acid. We believe that the fortified milk will improve the blood fatty acid profile and vitamin status in subjects to benefit bone health biomarkers. From the 84 patients who accepted to participate, 11 of these were excluded for the presence of metabolic diseases and 1 was excluded for noncompliance with the protocol. Seventy-two hyperlipidemic patients (35-65 years) were randomly divided between 2 study groups. The supplement group (E; n = 39) consumed 0.5 L/d of fortified milk that contained fish oil, oleic acid, and vitamins. The control group (C; n = 33) consumed 0.5 L/d of semiskimmed milk containing the same amount of total fat. Blood samples were taken at T(0), T(3), T(6), and T(12) months to determine plasma fatty acids, vitamins B(6), E, and 25-hydroxyvitamin D and serum folate, calcium, soluble osteoprotegerin (OPG), soluble receptor activator of NF-kappaB ligand (RANKL), osteocalcin, parathormone, type I collagen carboxy-terminal telopeptide, and malondialdehyde. After 1 year, the E group showed a significant increase in plasma eicosapentaenoic acid (42%), docosahexaenoic acid (60%), vitamin B6 (38%), OPG (18%), RANKL (7%), OPG/RANKL (10%), red blood cell folate (21%), serum folate (53%), calcium (4%), vitamin D (11%), and osteocalcin (22%). Dietary supplementation with the fortified milk drink improved nutritional status and bone formation markers in adult hyperlipidemic patients. PMID:20579524

  18. 胆碱能神经干细胞在阿尔茨海默病小鼠的移植研究%Transplantation of cholinergic neural stem cells in a mouse model of Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    王清华; 徐如祥; 长尾省吾

    2008-01-01

    Objective To observe the therapeutic effect of cholinergic neural stem cell (NSC) transplantation in a mouse model of Alzheimer's disease (AD). Methods Ibotenic acid was injected into the nucleus basalis ofMeynert (NBM) of C57BL/6 mice to establish a mouse model of AD. Four weeks after the injection, mouse embryonic stem cell (ES)-derived cholinergic NSCs were transplanted into the frontal and the barrel field of the S1 cortex. Behavioral tests using eight-arm radial maze were conducted 8 weeks after the transplantation, and the survival and differentiation of the transplanted NSCs were evaluated with double staining of choline acetyltransferase (CHAT), serotonin, amyloid-a protein (Aa) and green fluorecent protein (GFP) 12 weeks after transplantation. Results The cholinergic NSCs transplanted into mouse cortices survived and produced a large number of adult ChAT-positive neurons and a small amount of serononin-positive neurons in and around the grafts. The expression of Aain the surrounding cortex was significantly reduced, and the working memory error significantly decreased in mice grafted with cholinergic NSCs. Conclusion Transplantation of cholinergic NSCs into the prefrontal and parietal cortices can partially reconstruct the cholinergic innervation and significantly improve recent memory disruption in mice with NBM damage.%目的 观察胆碱能神经干细胞移植对阿尔茨海默病(AD)小鼠的治疗效果.方法 C57BL/6小鼠基底巨细胞核注射Ibotenic酸制成AD模型.4周后于额叶和顶叶皮质移植小鼠胚胎干细胞源性胆碱能神经干细胞.存移植术后12周,应用HE染色和且日碱乙酰转移酶-绿色荧光蛋白免疫双标染色观察神经干细胞存活和分化情况,以8方向迷宫试验评价小鼠近事记忆的改善程度.结果 胆碱能神经十细胞移植至AD小鼠顶叶和额叶皮质后主要分化为成熟胆碱能神经元,并移行和整合至移植区周围皮质,该区皮质β-淀粉样蛋白表达

  19. Cholinergic modulation of event-related oscillations (ERO).

    Science.gov (United States)

    Sanchez-Alavez, Manuel; Robledo, Patricia; Wills, Derek N; Havstad, James; Ehlers, Cindy L

    2014-04-22

    The cholinergic system in the brain modulates patterns of activity involved in general arousal, attention processing, memory and consciousness. In the present study we determined the effects of selective cholinergic lesions of the medial septum area (MS) or nucleus basalis magnocellularis (NBM) on amplitude and phase characteristics of event related oscillations (EROs). A time-frequency based representation was used to determine ERO energy, phase synchronization across trials, recorded within a structure (phase lock index, PLI), and phase synchronization across trials, recorded between brain structures (phase difference lock index, PDLI), in the frontal cortex (Fctx), dorsal hippocampus (DHPC) and central amygdala (Amyg). Lesions in MS produced: (1) decreases in ERO energy in delta, theta, alpha, beta and gamma frequencies in Amyg, (2) reductions in gamma ERO energy and PLI in Fctx, (3) decreases in PDLI between the Fctx-Amyg in the theta, alpha, beta and gamma frequencies, and (4) decreases in PDLI between the DHPC-Amyg and Fctx-DHPC in the theta frequency bands. Lesions in NBM resulted in: (1) increased ERO energy in delta and theta frequency bands in Fctx, (2) reduced gamma ERO energy in Fctx and Amyg, (3) reductions in PLI in the theta, beta and gamma frequency ranges in Fctx, (4) reductions in gamma PLI in DHPC and (5) reduced beta PLI in Amyg. These studies suggest that the MS cholinergic system can alter phase synchronization between brain areas whereas the NBM cholinergic system modifies phase synchronization/phase resetting within a brain area. PMID:24594019

  20. Basal ganglia cholinergic and dopaminergic function in progressive supranuclear palsy.

    Science.gov (United States)

    Warren, Naomi M; Piggott, Margaret A; Greally, Elizabeth; Lake, Michelle; Lees, Andrew J; Burn, David J

    2007-08-15

    Progressive Supranuclear Palsy (PSP) is a progressive neurodegenerative disorder. In contrast to Parkinson's disease (PD) and dementia with Lewy bodies (DLB), replacement therapy with dopaminergic and cholinergic agents in PSP has been disappointing. The neurochemical basis for this is unclear. Our objective was to measure dopaminergic and cholinergic receptors in the basal ganglia of PSP and control brains. We measured, autoradiographically, dopaminergic (dopamine transporter, 125I PE2I and dopamine D2 receptors, 125I epidepride) and cholinergic (nicotinic alpha4beta2 receptors, 125I 5IA85380 and muscarinic M1 receptors, 3H pirenzepine) parameters in the striatum and pallidum of pathologically confirmed PSP cases (n=15) and controls (n=32). In PSP, there was a marked loss of dopamine transporter and nicotinic alpha4beta2 binding in the striatum and pallidum, consistent with loss of nigrostriatal neurones. Striatal D2 receptors were increased in the caudate and muscarinic M1 receptors were unchanged compared with controls. These results do not account for the poor response to dopaminergic and cholinergic replacement therapies in PSP, and suggest relative preservation of postsynaptic striatal projection neurones bearing D2/M1 receptors. PMID:17534953

  1. Application of peanut butter to improve fatty acid composition of biscuits.

    Science.gov (United States)

    Gajera, H P; Kapopara, M B; Patel, V H

    2010-06-01

    Biscuits prepared with different levels of hydrogenated fat (vanaspati) and peanut (Arachis hypogaea L.) butter (PB) (100:00, 75:25, 50;50, 25;75, 00:100) were evaluated for their fatty acid composition and textural property. Saturated fatty acids like myristic, palmitic, stearic acids were higher in control biscuits (100% vanaspati), which decreased with increasing proportion of PB in the experimental biscuits. Oleic acid and linoleic acid were lowest in control biscuits and it gradually increased upon incorporation of PB. The hardness of biscuits also increased with increasing proportion of PB. Overall sensory quality of experimental biscuits improved when 50% vanaspati replaced by PB in the standard biscuits recipe. Biscuits prepared with 50% supplementation of PB had better fatty acid composition with balanced oil quality and also had a greater acceptability by sensory evaluation panel.

  2. Seamustard (Undaria pinnatifida) Improves Growth, Immunity, Fatty Acid Profile and Reduces Cholesterol in Hanwoo Steers.

    Science.gov (United States)

    Hwang, J A; Islam, M M; Ahmed, S T; Mun, H S; Kim, G M; Kim, Y J; Yang, C J

    2014-08-01

    The study was designed to evaluate the effect of 2% seamustard (Undaria pinnatifida) by-product (SW) on growth performance, immunity, carcass characteristics, cholesterol content and fatty acid profile in Hanwoo steers. A total of 20 Hanwoo steers (ave. 22 months old; 619 kg body weight) were randomly assigned to control (basal diet) and 2% SW supplemented diet. Dietary SW supplementation significantly (pquality grade of meat and carcass yield grades evaluated at the end of the trial were found to be unaffected by SW supplementation. Dietary SW significantly reduced meat cholesterol concentration (p<0.05). Dietary SW supplementation significantly reduced the myristic acid (C14:0) and palmitoleic acid (C16:ln-7) concentration, while SW increased the concentration of stearic acid (C18:0) and linolenic acid (C18:3n-3) compared to control (p<0.05). Dietary SW supplementation had no effect on saturated fatty acids (SFA), unsaturated fatty acids, poly unsaturated fatty acid (PUFA) or mono unsaturated fatty acid content in muscles. A reduced ratio of PUFA/SFA and n-6/n-3 were found in SW supplemented group (p<0.05). In conclusion, 2% SW supplementation was found to improve growth, immunity and fatty acid profile with significantly reduced cholesterol of beef. PMID:25083105

  3. Transporter-targeted cholic acid-cytarabine conjugates for improved oral absorption.

    Science.gov (United States)

    Zhang, Dong; Li, Dongpo; Shang, Lei; He, Zhonggui; Sun, Jin

    2016-09-10

    Cytarabine has a poor oral absorption due to its rapid deamination and poor membrane permeability. Bile acid transporters are highly expressed both in enterocytes and hepatocytes and to increase the oral bioavailability and investigate the potential application of cytarabine for liver cancers, a transporter- recognizing prodrug strategy was applied to design and synthesize four conjugates of cytarabine with cholic acid (CA), chenodeoxycholic acid (CDCA), hyodeoxycholic acid (HDCA) and ursodeoxycholic acid (UDCA). The anticancer activities against HepG2 cells were evaluated by MTT assay and the role of bile acid transporters during cellular transport was investigated in a competitive inhibition experiment. The in vitro and in vivo metabolic stabilities of these conjugates were studied in rat plasma and liver homogenates. Finally, an oral bioavailability study was conducted in rats. All the cholic acid-cytarabine conjugates (40μM) showed potent antiproliferative activities (up to 70%) against HepG2 cells after incubation for 48h. The addition of bile acids could markedly reduce the antitumor activities of these conjugates. The N(4)-ursodeoxycholic acid conjugate of cytarabine (compound 5) exhibited optimal stability (t1/2=90min) in vitro and a 3.9-fold prolonged half-life of cytarabine in vivo. More importantly, compound 5 increased the oral bioavailability 2-fold compared with cytarabine. The results of the present study suggest that the prodrug strategy based on the bile acid transporters is suitable for improving the oral absorption and the clinical application of cytarabine. PMID:27377011

  4. Ursolic acid improves domoic acid-induced cognitive deficits in mice

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Dong-mei [School of Environment and Spatial Informatics, China University of Mining and Technology, Xuzhou 221008, Jiangsu Province (China); Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Xuzhou Normal University, Xuzhou 221116, Jiangsu Province (China); Lu, Jun, E-mail: lu-jun75@163.com [Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Xuzhou Normal University, Xuzhou 221116, Jiangsu Province (China); Zhang, Yan-qiu [School of Environment and Spatial Informatics, China University of Mining and Technology, Xuzhou 221008, Jiangsu Province (China); Zheng, Yuan-lin, E-mail: ylzheng@xznu.edu.cn [Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Xuzhou Normal University, Xuzhou 221116, Jiangsu Province (China); Hu, Bin [Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Xuzhou Normal University, Xuzhou 221116, Jiangsu Province (China); Cheng, Wei [School of Environment and Spatial Informatics, China University of Mining and Technology, Xuzhou 221008, Jiangsu Province (China); Zhang, Zi-feng; Li, Meng-qiu [Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Xuzhou Normal University, Xuzhou 221116, Jiangsu Province (China)

    2013-09-01

    Our previous findings suggest that mitochondrial dysfunction is the mechanism underlying cognitive deficits induced by domoic acid (DA). Ursolic acid (UA), a natural triterpenoid compound, possesses many important biological functions. Evidence shows that UA can activate PI3K/Akt signaling and suppress Forkhead box protein O1 (FoxO1) activity. FoxO1 is an important regulator of mitochondrial function. Here we investigate whether FoxO1 is involved in the oxidative stress-induced mitochondrial dysfunction in DA-treated mice and whether UA inhibits DA-induced mitochondrial dysfunction and cognitive deficits through regulating the PI3K/Akt and FoxO1 signaling pathways. Our results showed that FoxO1 knockdown reversed the mitochondrial abnormalities and cognitive deficits induced by DA in mice through decreasing HO-1 expression. Mechanistically, FoxO1 activation was associated with oxidative stress-induced JNK activation and decrease of Akt phosphorylation. Moreover, UA attenuated the mitochondrial dysfunction and cognitive deficits through promoting Akt phosphorylation and FoxO1 nuclear exclusion in the hippocampus of DA-treated mice. LY294002, an inhibitor of PI3K/Akt signaling, significantly decreased Akt phosphorylation in the hippocampus of DA/UA mice, which weakened UA actions. These results suggest that UA could be recommended as a possible candidate for the prevention and therapy of cognitive deficits in excitotoxic brain disorders. - Highlights: • Ursolic acid (UA) is a naturally triterpenoid compound. • UA attenuated the mitochondrial dysfunction and cognitive deficits. • Mechanistically, UA activates PI3K/Akt signaling and suppresses FoxO1 activity. • UA could be recommended as a possible candidate for anti-excitotoxic brain disorders.

  5. Improving the management of infertile acid soils in Southeast Asia: The approach of the IBSRAM Acid-Soils network

    International Nuclear Information System (INIS)

    The IBSRAM ASIALAND Management of Acid Soils network aims to improve the understanding of the broad range of biophysical and socio-economic production limitations on infertile acid soils of Southeast Asia, and to lead to development and implementation of sustainable land-management strategies for these important marginal areas. The main activities of the network are in Indonesia, Myanmar, Philippines, and Vietnam, with associated activity in Thailand, and minor involvement in Brunei, Cambodia, Laos, and Malaysia. The main experimental focus is through researcher-managed on-farm trials, to improve the management of phosphorus nutrition with inorganic and organic amendments. A generic design is used across the eight well characterised sites that form the core of the network. The results will be analysed across time and across sites. Improved methods for laboratory analyses, experimental management, socio-economic data collection, and data analysis and interpretation are critical components. Three important initiatives are associated with the core activities. These aim to establish a broader network on maintenance of quality laboratory analyses, to assess the potential for implementation of improved strategies through farmer-managed on-farm trials, and to improve our understanding of, and ways of estimating, nutrient budgets for diverse farming systems. (author)

  6. Evidence for the Gut Microbiota Short-Chain Fatty Acids as Key Pathophysiological Molecules Improving Diabetes

    OpenAIRE

    2014-01-01

    In type 2 diabetes, hyperglycemia, insulin resistance, increased inflammation, and oxidative stress were shown to be associated with the progressive deterioration of beta-cell function and mass. Short-chain fatty acids (SCFAs) are organic fatty acids produced in the distal gut by bacterial fermentation of macrofibrous material that might improve type 2 diabetes features. Their main beneficial activities were identified in the decrease of serum levels of glucose, insulin resistance as well as ...

  7. Conjugated linoleic acid and calcium co-supplementation improves bone health in ovariectomised mice

    OpenAIRE

    Park, Yooheon; Kim, Jonggun; Scrimgeour, Angus G.; Condlin, Michelle L.; Kim, Daeyoung; Park, Yeonhwa

    2013-01-01

    Osteoporosis is a significant health concern for the elderly; conjugated linoleic acid (CLA) has been shown to improve overall bone mass when calcium is included as a co-supplement. However, potential effects of CLA and calcium on bone mass during a period of bone loss have not been reported. The purpose of this study was to determine how dietary calcium modulates the effects of conjugated linoleic acid (CLA) in preventing bone loss, using an ovariectomised mouse model. CLA supplementation si...

  8. Improved soybean oil quality by targeted mutagenesis of the fatty acid desaturase 2 gene family.

    Science.gov (United States)

    Haun, William; Coffman, Andrew; Clasen, Benjamin M; Demorest, Zachary L; Lowy, Anita; Ray, Erin; Retterath, Adam; Stoddard, Thomas; Juillerat, Alexandre; Cedrone, Frederic; Mathis, Luc; Voytas, Daniel F; Zhang, Feng

    2014-09-01

    Soybean oil is high in polyunsaturated fats and is often partially hydrogenated to increase its shelf life and improve oxidative stability. The trans-fatty acids produced through hydrogenation pose a health threat. Soybean lines that are low in polyunsaturated fats were generated by introducing mutations in two fatty acid desaturase 2 genes (FAD2-1A and FAD2-1B), which in the seed convert the monounsaturated fat, oleic acid, to the polyunsaturated fat, linoleic acid. Transcription activator-like effector nucleases (TALENs) were engineered to recognize and cleave conserved DNA sequences in both genes. In four of 19 transgenic soybean lines expressing the TALENs, mutations in FAD2-1A and FAD2-1B were observed in DNA extracted from leaf tissue; three of the four lines transmitted heritable FAD2-1 mutations to the next generation. The fatty acid profile of the seed was dramatically changed in plants homozygous for mutations in both FAD2-1A and FAD2-1B: oleic acid increased from 20% to 80% and linoleic acid decreased from 50% to under 4%. Further, mutant plants were identified that lacked the TALEN transgene and only carried the targeted mutations. The ability to create a valuable trait in a single generation through targeted modification of a gene family demonstrates the power of TALENs for genome engineering and crop improvement.

  9. Antagonist of the amylin receptor blocks beta-amyloid toxicity in rat cholinergic basal forebrain neurons.

    Science.gov (United States)

    Jhamandas, Jack H; MacTavish, David

    2004-06-16

    Salvage of cholinergic neurons in the brain through a blockade of the neurotoxic effects of amyloidbeta protein (Abeta) is one of the major, but still elusive, therapeutic goals of current research in Alzheimer's disease (AD). To date, no receptor has been unequivocally identified for Abeta. Human amylin, which acts via a receptor composed of the calcitonin receptor-like receptor and a receptor-associated membrane protein, possesses amyloidogenic properties and has a profile of neurotoxicity that is strikingly similar to Abeta. In this study, using primary cultures of rat cholinergic basal forebrain neurons, we show that acetyl-[Asn30, Tyr32] sCT(8-37) (AC187), an amylin receptor antagonist, blocks Abeta-induced neurotoxicity. Treatment of cultures with AC187 before exposure to Abeta results in significantly improved neuronal survival as judged by MTT and live-dead cell assays. Quantitative measures of Abeta-evoked apoptotic cell death, using Hoechst and phosphotidylserine staining, confirm neuroprotective effects of AC187. We also demonstrate that AC187 attenuates the activation of initiator and effector caspases that mediate Abeta-induced apoptotic cell death. These data are the first to show that expression of Abeta toxicity may occur through the amylin receptor and suggest a novel therapeutic target for the treatment of AD. PMID:15201330

  10. Evidence for the Gut Microbiota Short-Chain Fatty Acids as Key Pathophysiological Molecules Improving Diabetes

    Directory of Open Access Journals (Sweden)

    Alessandra Puddu

    2014-01-01

    Full Text Available In type 2 diabetes, hyperglycemia, insulin resistance, increased inflammation, and oxidative stress were shown to be associated with the progressive deterioration of beta-cell function and mass. Short-chain fatty acids (SCFAs are organic fatty acids produced in the distal gut by bacterial fermentation of macrofibrous material that might improve type 2 diabetes features. Their main beneficial activities were identified in the decrease of serum levels of glucose, insulin resistance as well as inflammation, and increase in protective Glucagon-like peptide-1 (GLP-1 secretion. In this review, we updated evidence on the effects of SCFAs potentially improving metabolic control in type 2 diabetes.

  11. Improvement of tear trough by monophasic hyaluronic Acid and calcium hydroxylapatite.

    Science.gov (United States)

    Wollina, Uwe

    2014-10-01

    Tear trough deformities are a sign of facial aging. The anatomical base is well understood. In many patients, minimal invasive surgical procedures are useful to improve appearance. Here, the authors describe the use of monophasic hyaluronic acid dermal filler and calcium hydroxylapatite injection for correction. Forty female patients with a mean age of 50 years have been treated. On average, an improvement of one class of Hidman's severity score could be achieved by single treatment. Mean duration of the effect was 10.1 months for hyaluronic acid and 12.8 months for calcium hydroxylapatite. Adverse effects were mild and temporary. Patients satisfaction was high (95%). PMID:25371770

  12. ESC-Derived Basal Forebrain Cholinergic Neurons Ameliorate the Cognitive Symptoms Associated with Alzheimer’s Disease in Mouse Models

    Directory of Open Access Journals (Sweden)

    Wei Yue

    2015-11-01

    Full Text Available Degeneration of basal forebrain cholinergic neurons (BFCNs is associated with cognitive impairments of Alzheimer’s disease (AD, implying that BFCNs hold potentials in exploring stem cell-based replacement therapy for AD. However, studies on derivation of BFCNs from embryonic stem cells (ESCs are limited, and the application of ESC-derived BFCNs remains to be determined. Here, we report on differentiation approaches for directing both mouse and human ESCs into mature BFCNs. These ESC-derived BFCNs exhibit features similar to those of their in vivo counterparts and acquire appropriate functional properties. After transplantation into the basal forebrain of AD model mice, ESC-derived BFCN progenitors predominantly differentiate into mature cholinergic neurons that functionally integrate into the endogenous basal forebrain cholinergic projection system. The AD mice grafted with mouse or human BFCNs exhibit improvements in learning and memory performances. Our findings suggest a promising perspective of ESC-derived BFCNs in the development of stem cell-based therapies for treatment of AD.

  13. Coordination of glycerol utilization and clavulanic acid biosynthesis to improve clavulanic acid production in Streptomyces clavuligerus.

    Science.gov (United States)

    Guo, Dekun; Zhao, Youbao; Yang, Keqian

    2013-07-01

    The glycerol utilization (gyl) operon is involved in clavulanic acid (CA) production by Streptomyces clavuligerus, and possibly supplies the glyceraldehyde-3-phosphate (G3P) precursor for CA biosynthesis. The gyl operon is regulated by GylR and is induced by glycerol. To enhance CA production in S. clavuligerus, an extra copy of ccaR expressed from Pgyl (the gyl promoter) was integrated into the chromosome of S. clavuligerus NRRL 3585. This construct coordinated the transcription of CA biosynthetic pathway genes with expression of the gyl operon. In the transformants carrying the Pgyl-controlled regulatory gene ccaR, CA production was enhanced 3.19-fold in glycerol-enriched batch cultures, relative to the control strain carrying an extra copy of ccaR controlled by its own promoter (PccaR). Consistent with enhanced CA production, the transcription levels of ccaR, ceas2 and claR were significantly up-regulated in the transformants containing Pgyl-controlled ccaR.

  14. Membrane engineering via trans unsaturated fatty acids production improves Escherichia coli robustness and production of biorenewables.

    Science.gov (United States)

    Tan, Zaigao; Yoon, Jong Moon; Nielsen, David R; Shanks, Jacqueline V; Jarboe, Laura R

    2016-05-01

    Constructing microbial biocatalysts that produce biorenewables at economically viable yields and titers is often hampered by product toxicity. For production of short chain fatty acids, membrane damage is considered the primary mechanism of toxicity, particularly in regards to membrane integrity. Previous engineering efforts in Escherichia coli to increase membrane integrity, with the goal of increasing fatty acid tolerance and production, have had mixed results. Herein, a novel approach was used to reconstruct the E. coli membrane by enabling production of a novel membrane component. Specifically, trans unsaturated fatty acids (TUFA) were produced and incorporated into the membrane of E. coli MG1655 by expression of cis-trans isomerase (Cti) from Pseudomonas aeruginosa. While the engineered strain was found to have no increase in membrane integrity, a significant decrease in membrane fluidity was observed, meaning that membrane polarization and rigidity were increased by TUFA incorporation. As a result, tolerance to exogenously added octanoic acid and production of octanoic acid were both increased relative to the wild-type strain. This membrane engineering strategy to improve octanoic acid tolerance was found to require fine-tuning of TUFA abundance. Besides improving tolerance and production of carboxylic acids, TUFA production also enabled increased tolerance in E. coli to other bio-products, e.g. alcohols, organic acids, aromatic compounds, a variety of adverse industrial conditions, e.g. low pH, high temperature, and also elevated styrene production, another versatile bio-chemical product. TUFA permitted enhanced growth due to alleviation of bio-product toxicity, demonstrating the general effectiveness of this membrane engineering strategy towards improving strain robustness. PMID:26875445

  15. Cholinergic signals in mouse barrel cortex during active whisker sensing.

    Science.gov (United States)

    Eggermann, Emmanuel; Kremer, Yves; Crochet, Sylvain; Petersen, Carl C H

    2014-12-11

    Internal brain states affect sensory perception, cognition, and learning. Many neocortical areas exhibit changes in the pattern and synchrony of neuronal activity during quiet versus active behaviors. Active behaviors are typically associated with desynchronized cortical dynamics. Increased thalamic firing contributes importantly to desynchronize mouse barrel cortex during active whisker sensing. However, a whisking-related cortical state change persists after thalamic inactivation, which is mediated at least in part by acetylcholine, as we show here by using whole-cell recordings, local pharmacology, axonal calcium imaging, and optogenetic stimulation. During whisking, we find prominent cholinergic signals in the barrel cortex, which suppress spontaneous cortical activity. The desynchronized state of barrel cortex during whisking is therefore driven by at least two distinct signals with opposing functions: increased thalamic activity driving glutamatergic excitation of the cortex and increased cholinergic input suppressing spontaneous cortical activity.

  16. Cholinergic Signals in Mouse Barrel Cortex during Active Whisker Sensing

    Directory of Open Access Journals (Sweden)

    Emmanuel Eggermann

    2014-12-01

    Full Text Available Internal brain states affect sensory perception, cognition, and learning. Many neocortical areas exhibit changes in the pattern and synchrony of neuronal activity during quiet versus active behaviors. Active behaviors are typically associated with desynchronized cortical dynamics. Increased thalamic firing contributes importantly to desynchronize mouse barrel cortex during active whisker sensing. However, a whisking-related cortical state change persists after thalamic inactivation, which is mediated at least in part by acetylcholine, as we show here by using whole-cell recordings, local pharmacology, axonal calcium imaging, and optogenetic stimulation. During whisking, we find prominent cholinergic signals in the barrel cortex, which suppress spontaneous cortical activity. The desynchronized state of barrel cortex during whisking is therefore driven by at least two distinct signals with opposing functions: increased thalamic activity driving glutamatergic excitation of the cortex and increased cholinergic input suppressing spontaneous cortical activity.

  17. Cholinergic receptor binding in the frontal cortex of suicide victims

    International Nuclear Information System (INIS)

    Because there is a high incidence of individuals diagnosed as having an affective disorder who subsequently commit suicide, the author thought it would be of interest to determine QNB binding in the brains of a large sample of suicide victims, and to compare the findings with a well-matched control group. Brain samples were obtained at autopsy from 22 suicide victims and 22 controls. Frontal cortex samples were diseected, frozen, and stored until assayed. Samples of tissue homogenate were incubated in duplicate with 10 concentrations of tritium-QNB. Specific binding was determined with and without atropine. The results confirmed previous studies in which no changes were noted in suicide versus control brains. While the findings neither disprove nor support the cholinergic hypothesis of depression, they do suggest that the neurochemical basis for the in vivo observations of increased responsivity of depressed individuals to muscarinic cholinergic agents might not involve changes in receptors estimated by QNB binding

  18. Inhibition of airway surface fluid absorption by cholinergic stimulation

    OpenAIRE

    Nam Soo Joo; Krouse, Mauri E.; Jae Young Choi; Hyung-Ju Cho; Wine, Jeffrey J.

    2016-01-01

    In upper airways airway surface liquid (ASL) depth and clearance rates are both increased by fluid secretion. Secretion is opposed by fluid absorption, mainly via the epithelial sodium channel, ENaC. In static systems, increased fluid depth activates ENaC and decreased depth inhibits it, suggesting that secretion indirectly activates ENaC to reduce ASL depth. We propose an alternate mechanism in which cholinergic input, which causes copious airway gland secretion, also inhibits ENaC-mediated ...

  19. Improvement of Tear Trough by Monophasic Hyaluronic Acid and Calcium Hydroxylapatite

    OpenAIRE

    Wollina, Uwe

    2014-01-01

    Tear trough deformities are a sign of facial aging. The anatomical base is well understood. In many patients, minimal invasive surgical procedures are useful to improve appearance. Here, the authors describe the use of monophasic hyaluronic acid dermal filler and calcium hydroxylapatite injection for correction. Forty female patients with a mean age of 50 years have been treated. On average, an improvement of one class of Hidman’s severity score could be achieved by single treatment. Mean dur...

  20. Domoic Acid Improves the Competitive Ability of Pseudo-nitzschia delicatissima against the Diatom Skeletonema marinoi

    Directory of Open Access Journals (Sweden)

    Emily K. Prince

    2013-07-01

    Full Text Available Because domoic acid, a neurotoxic secondary metabolite produced by marine diatoms in the genus Pseudo-nitzschia, is hypothesized to be part of a high affinity iron uptake system, we investigated whether domoic acid could improve the competitive ability of Pseudo-nitzschia delicatissima, and whether the availability of iron changed the outcome of competition experiments. We found that domoic acid had a slight negative effect on growth of the diatom Skeletonema marinoi when it was grown in monocultures. However, when S. marinoi was cultured with P. delicatissima the presence of domoic acid resulted in a reduction of S. marinoi cells by up to 38% and an increase in P. delicatissima cell numbers by up to 17% under iron replete conditions. Similar effects were not observed in low iron treatments. Domoic acid was not taken up by P. delicatissima cells. Overall, our results indicate that domoic acid can improve the competitive ability of Pseudo-nitzschia spp. and that iron is likely to be involved. This study provides an unusual example of indirect inhibition of competitor growth mediated by a secondary metabolite.

  1. Segregated cholinergic transmission modulates dopamine neurons integrated in distinct functional circuits.

    Science.gov (United States)

    Dautan, Daniel; Souza, Albert S; Huerta-Ocampo, Icnelia; Valencia, Miguel; Assous, Maxime; Witten, Ilana B; Deisseroth, Karl; Tepper, James M; Bolam, J Paul; Gerdjikov, Todor V; Mena-Segovia, Juan

    2016-08-01

    Dopamine neurons in the ventral tegmental area (VTA) receive cholinergic innervation from brainstem structures that are associated with either movement or reward. Whereas cholinergic neurons of the pedunculopontine nucleus (PPN) carry an associative/motor signal, those of the laterodorsal tegmental nucleus (LDT) convey limbic information. We used optogenetics and in vivo juxtacellular recording and labeling to examine the influence of brainstem cholinergic innervation of distinct neuronal subpopulations in the VTA. We found that LDT cholinergic axons selectively enhanced the bursting activity of mesolimbic dopamine neurons that were excited by aversive stimulation. In contrast, PPN cholinergic axons activated and changed the discharge properties of VTA neurons that were integrated in distinct functional circuits and were inhibited by aversive stimulation. Although both structures conveyed a reinforcing signal, they had opposite roles in locomotion. Our results demonstrate that two modes of cholinergic transmission operate in the VTA and segregate the neurons involved in different reward circuits.

  2. Animal model of vascular dementia and its cholinergic mechanism

    Institute of Scientific and Technical Information of China (English)

    FAN Wen-hui; LI Lu-si; LIU Zhi-rong; ZHU Hong-yan; CHEN Kang-ning

    2001-01-01

    Objective: To establish a model of vascular dementia (VD) in aging rats and study primarily the cholinergic mechanism of hypomnesia. Methods: Chronic hypoperfusion of cerebral blood flow (CBF) in the forebrain was performed in aging rats with permanent bilateral common carotid arteries occlusion (PBCCAO). Then the rats were tested with a computerized shuttle-training case. The changes of cerebrovascular system were observed with digital subtraction angiography (DSA). The brain tissues were studied with immunohistochemical method with cholinergic acetyltransferase (ChAT) as a marker. Results: The cognitive function of rats was obviously reduced in 2 months after chronic cerebral hypoperfusion and became worse 2 months later, showing a more marked decrease of ChAT positive neurons and fibers in CA1 of the hippocampus as compared with the rats of the control, which had a significant positive correlation with memory ability. Conclusion: This rat model is successfully established to imitate human VD induced with chronic cerebral hypoperfusion. The mechanism of the hypomnesia of VD might be the impairment of cholinergic neurons in frontal cortex and hippocampus.

  3. PET study of cholinergic system in the brain

    International Nuclear Information System (INIS)

    Recently, we have developed a method to measure acetylcholinesterase (AChE) activity, a functional marker for cholinergic system, by positron emission tomography (PET) and carbon-11 labeled N-methyl-4-piperidyl acetate. Kinetic analysis of the radioactivity in the brain and the plasma yielded a rate constant ''k 3'' as an index of AChE activity. The ratios for the k 3 values for the cerebral cortex/thalamus/cerebellum/striatum found in healthy participants were 1/ 3/ 8/ 10, respectively, corresponding well with AChE activity ratios in the brain at necropsy (1/ 3/ 8/ 38), except for the striatum. In 23 healthy volunteers (age range: 24-89 years), there was no age-related decline of k 3 values in the cerebral cortex, suggesting AChE activity is preserved in aged cerebral cortex. In 11 patients with Alzheimer's disease, there was a significant reduction (-24%) of k 3 values in the cerebral cortex and hippocampus, suggesting a loss of ascending cholinergic system from the basal forebrain to the cerebral cortex and hippocampus. In 16 patients with Parkinson's disease, there was a significant reduction (-18%) of k 3 values in the cerebral cortex. In 10 patients with progressive supra nuclear palsy, there was a significant reduction (-38%) of k 3 values in the thalamus. This technique is useful for investigating central cholinergic system in neuro degenerative disorders with dementia. (author)

  4. PET study of cholinergic system in the brain

    Energy Technology Data Exchange (ETDEWEB)

    Shinotoh, Hitoshi [Chiba Univ. (Japan). School of Medicine

    1999-01-01

    Recently, we have developed a method to measure acetylcholinesterase (AChE) activity, a functional marker for cholinergic system, by positron emission tomography (PET) and carbon-11 labeled N-methyl-4-piperidyl acetate. Kinetic analysis of the radioactivity in the brain and the plasma yielded a rate constant ``k 3`` as an index of AChE activity. The ratios for the k 3 values for the cerebral cortex/thalamus/cerebellum/striatum found in healthy participants were 1/ 3/ 8/ 10, respectively, corresponding well with AChE activity ratios in the brain at necropsy (1/ 3/ 8/ 38), except for the striatum. In 23 healthy volunteers (age range: 24-89 years), there was no age-related decline of k 3 values in the cerebral cortex, suggesting AChE activity is preserved in aged cerebral cortex. In 11 patients with Alzheimer`s disease, there was a significant reduction (-24%) of k 3 values in the cerebral cortex and hippocampus, suggesting a loss of ascending cholinergic system from the basal forebrain to the cerebral cortex and hippocampus. In 16 patients with Parkinson`s disease, there was a significant reduction (-18%) of k 3 values in the cerebral cortex. In 10 patients with progressive supra nuclear palsy, there was a significant reduction (-38%) of k 3 values in the thalamus. This technique is useful for investigating central cholinergic system in neuro degenerative disorders with dementia. (author)

  5. Dysfunctional penile cholinergic nerves in diabetic impotent men

    Energy Technology Data Exchange (ETDEWEB)

    Blanco, R.; Saenz de Tejada, I.; Goldstein, I.; Krane, R.J.; Wotiz, H.H.; Cohen, R.A. (Boston Univ. School of Medicine, MA (USA))

    1990-08-01

    Impotence in the diabetic man may be secondary to a neuropathic condition of the autonomic penile nerves. The relationship between autonomic neuropathy and impotence in diabetes was studied in human corporeal tissue obtained during implantation of a penile prosthesis in 19 impotent diabetic and 15 nondiabetic patients. The functional status of penile cholinergic nerves was assessed by determining their ability to accumulate tritiated choline (34), and synthesize (34) and release (19) tritiated-acetylcholine after incubation of corporeal tissue with tritiated-choline (34). Tritiated-choline accumulation, and tritiated-acetylcholine synthesis and release were significantly reduced in the corporeal tissue from diabetic patients compared to that from nondiabetic patients (p less than 0.05). The impairment in acetylcholine synthesis worsened with the duration of diabetes (p less than 0.025). No differences in the parameters measured were found between insulin-dependent (11) and noninsulin-dependent (8) diabetic patients. The ability of the cholinergic nerves to synthesize acetylcholine could not be predicted clinically with sensory vibration perception threshold testing. It is concluded that there is a functional penile neuropathic condition of the cholinergic nerves in the corpus cavernosum of diabetic impotent patients that may be responsible for the erectile dysfunction.

  6. A cholinergic hypothesis of the unconscious in affective disorders.

    Directory of Open Access Journals (Sweden)

    Costa eVakalopoulos

    2013-11-01

    Full Text Available The interactions between distinct pharmacological systems are proposed as a key dynamic in the formation of unconscious memories underlying rumination and mood disorder, but also reflect the plastic capacity of neural networks that can aid recovery. An inverse and reciprocal relationship is postulated between cholinergic and monoaminergic receptor subtypes. M1-type muscarinic receptor transduction facilitates encoding of unconscious, prepotent behavioural repertoires at the core of affective disorders and ADHD. Behavioural adaptation to new contingencies is mediated by the classic prototype receptor: 5-HT1A (Gi/o and its modulation of m1-plasticity. Reversal of learning is dependent on increased phasic activation of midbrain monoaminergic nuclei and is a function of hippocampal theta. Acquired hippocampal dysfunction due to abnormal activation of the hypothalamic-pituitary-adrenal (HPA axis predicts deficits in hippocampal-dependent memory and executive function and further impairments to cognitive inhibition. Encoding of explicit memories is mediated by Gq/11 and Gs signalling of monoamines only. A role is proposed for the phasic activation of the basal forebrain cholinergic nucleus by cortical projections from the complex consisting of the insula and claustrum. Although controversial. recent studies suggest a common ontogenetic origin of the two structures and a functional coupling. Lesions of the region result in loss of motivational behaviour and familiarity based judgements. A major hypothesis of the paper is that these lost faculties result indirectly, from reduced cholinergic tone.

  7. Cholinergic mediation of small intestinal transit in the rat

    International Nuclear Information System (INIS)

    It has been reported that small intestinal transit (SIT) in the rat is not cholinergically mediated. The geometric mean of a marker may be a more powerful method for SIT studies. Therefore, it was their goal to evaluate the effect of muscarinic blockade in normal and prostaglandin E2 (PGE2)-enhanced SIT using this method. Male, food-fasted rats (190 to 240 g) were first dosed subcutaneously with atropine. 30 min after the atropine the rats received an oral dose of PGE2 at 5.0 mg/kg. 5 min after PGE2, a 51Cr-labeled marker was dosed intraduodenally, and a 25 min transit period followed. The results are: (1) 5.0 mg/kg of PGE2 significantly stimulates the geometric mean of the marker in agreement with previous findings and (2) atropine is inhibitory at doses as low as 0.20 mg/kg for basal SIT and 0.10 mg/kg for PGE2-stimulated SIT. This indicates (1) the rat has cholinergically mediated SIT, and (2) cholinergic activation may be important for PGE2 effects on SIT in the rat

  8. Applications for biotechnology: present and future improvements in lactic acid bacteria.

    Science.gov (United States)

    McKay, L L; Baldwin, K A

    1990-09-01

    The lactic acid bacteria are involved in the manufacture of fermented foods from raw agricultural materials such as milk, meat, vegetables, and cereals. These fermented foods are a significant part of the food processing industry and are often prepared using selected strains that have the ability to produce desired products or changes efficiently. The application of genetic engineering technology to improve existing strains or develop novel strains for these fermentations is an active research area world-wide. As knowledge about the genetics and physiology of lactic acid bacteria accumulates, it becomes possible to genetically construct strains with characteristics shaped for specific purposes. Examples of present and future applications of biotechnology to lactic acid bacteria to improve product quality are described. Studies of the basic biology of these bacteria are being actively conducted and must be continued, in order for the food fermentation industry to reap the benefits of biotechnology.

  9. Suspected Transfusion Related Acute Lung Injury Improving following Administration of Tranexamic Acid: A Case Report

    Directory of Open Access Journals (Sweden)

    Stan Ryniak

    2014-01-01

    Full Text Available A 16-year-old woman with craniofacial injury developed severe acute respiratory failure under the primary reconstructive surgical procedure requiring several units of blood and plasma. A transfusion related acute lung injury (TRALI was suspected and supportive treatment was initiated. Because of the severity of symptoms, acute extracorporeal membrane oxygenation (ECMO was planned. During preparation for ECMO, a single intravenous dose, 1 g of tranexamic acid, was administered and a remarkable improvement was observed shortly thereafter. The patient was placed on ECMO for 16 hours. The further course was uncomplicated and the patient was discharged from ICU on the 6th day after admission fully and she recovered. A clinical improvement was observed in a timely fashion following the administration of tranexamic acid. The handling of a suspected TRALI and potential benefit from administration of tranexamic acid are discussed in this case report.

  10. Acid etching and plasma sterilization fail to improve osseointegration of grit blasted titanium implants

    DEFF Research Database (Denmark)

    Mortensen, Mikkel Saksø; Jakobsen, Stig Storgaard; Saksø, Henrik;

    2012-01-01

    Interaction between implant surface and surrounding bone influences implant fixation. We attempted to improve the bone-implant interaction by 1) adding surface micro scale topography by acid etching, and 2) removing surface-adherent pro-inflammatory agents by plasma cleaning. Implant fixation...

  11. Optogenetic activation of cholinergic neurons in the PPT or LDT induces REM sleep

    OpenAIRE

    Van Dort, Christa J.; Zachs, Daniel P.; Kenny, Jonathan D.; Zheng, Shu; Goldblum, Rebecca R.; Gelwan, Noah A.; Ramos, Daniel M; Nolan, Michael A.; Wang, Karen; Weng, Feng-Ju; Lin, Yingxi; Wilson, Matthew A.; Emery N Brown

    2014-01-01

    Rapid eye movement (REM) sleep is a critical component of restful sleep, yet the mechanisms that control REM sleep are incompletely understood. Brainstem cholinergic neurons have been implicated in REM sleep regulation, but heterogeneous cell types in the area have made it difficult to determine the specific role of each population, leading to a debate about the importance of cholinergic neurons. Therefore, we selectively activated brainstem cholinergic neurons to determine their role in REM ...

  12. Aging-related deficits in orexin/hypocretin modulation of the septo-hippocampal cholinergic system

    OpenAIRE

    Stanley, Emily M.; Fadel, Jim

    2012-01-01

    The medial septum (MS) of the basal forebrain contains cholinergic neurons that project to the hippocampus, support cognitive function, and are implicated in age-related cognitive decline. Hypothalamic orexin/hypocretin neurons innervate and modulate basal forebrain cholinergic neurons and provide direct inputs to the hippocampus. However, the precise role of orexin in modulating hippocampal cholinergic transmission—and how these interactions are altered in aging—is unknown. Here, orexin A wa...

  13. Cholinergic signal activated renin angiotensin system associated with cardiovascular changes in the ovine fetus

    OpenAIRE

    Geng, Chunsong; Mao, Caiping; Wu, Lei; Cheng, Yu; Liu, Rulu; Chen, Bingxin; Chen, Ling; Zhang, Lubo; Xu, Zhice

    2010-01-01

    Aim: Cholinergic regulation is important in the control of cardiovascular and endocrine responses. The mechanisms behind cardiovascular responses induced by cholinergic activation are explored by studying hormonal systems, including renin-angiotensin and vasopressin (VP). Results: In chronically prepared fetal sheep, intravenous infusion of the cholinergic agonist carbachol increased fetal systolic, diastolic, and mean arterial pressure accompanied with bradycardia at near-term. Although int...

  14. Designed Amino Acid Feed in Improvement of Production and Quality Targets of a Therapeutic Monoclonal Antibody.

    Directory of Open Access Journals (Sweden)

    Fatemeh Torkashvand

    Full Text Available Cell culture feeds optimization is a critical step in process development of pharmaceutical recombinant protein production. Amino acids are the basic supplements of mammalian cell culture feeds with known effect on their growth promotion and productivity. In this study, we reported the implementation of the Plackett-Burman (PB multifactorial design to screen the effects of amino acids on the growth promotion and productivity of a Chinese hamster ovary DG-44 (CHO-DG44 cell line producing bevacizumab. After this screening, the amino acid combinations were optimized by the response surface methodology (RSM to determine the most effective concentration in feeds. Through this strategy, the final monoclonal antibody (mAb titre was enhanced by 70%, compared to the control group. For this particular cell line, aspartic acid, glutamic acid, arginine and glycine had the highest positive effects on the final mAb titre. Simultaneously, the impact of the designed amino acid feed on some critical quality attributes of bevacizumab was examined in the group with highest productivity. The product was analysed for N-glycan profiles, charge variant distribution, and low molecular weight forms. The results showed that the target product quality has been improved using this feeding strategy. It was shown how this strategy could significantly diminish the time and number of experiments in identifying the most effective amino acids and related concentrations in target product enhancement. This model could be successfully applied to other components of culture media and feeds.

  15. Heart failure causes cholinergic transdifferentiation of cardiac sympathetic nerves via gp130-signaling cytokines in rodents.

    Science.gov (United States)

    Kanazawa, Hideaki; Ieda, Masaki; Kimura, Kensuke; Arai, Takahide; Kawaguchi-Manabe, Haruko; Matsuhashi, Tomohiro; Endo, Jin; Sano, Motoaki; Kawakami, Takashi; Kimura, Tokuhiro; Monkawa, Toshiaki; Hayashi, Matsuhiko; Iwanami, Akio; Okano, Hideyuki; Okada, Yasunori; Ishibashi-Ueda, Hatsue; Ogawa, Satoshi; Fukuda, Keiichi

    2010-02-01

    Although several cytokines and neurotrophic factors induce sympathetic neurons to transdifferentiate into cholinergic neurons in vitro, the physiological and pathophysiological roles of this remain unknown. During congestive heart failure (CHF), sympathetic neural tone is upregulated, but there is a paradoxical reduction in norepinephrine synthesis and reuptake in the cardiac sympathetic nervous system (SNS). Here we examined whether cholinergic transdifferentiation can occur in the cardiac SNS in rodent models of CHF and investigated the underlying molecular mechanism(s) using genetically modified mice. We used Dahl salt-sensitive rats to model CHF and found that, upon CHF induction, the cardiac SNS clearly acquired cholinergic characteristics. Of the various cholinergic differentiation factors, leukemia inhibitory factor (LIF) and cardiotrophin-1 were strongly upregulated in the ventricles of rats with CHF. Further, LIF and cardiotrophin-1 secreted from cultured failing rat cardiomyocytes induced cholinergic transdifferentiation in cultured sympathetic neurons, and this process was reversed by siRNAs targeting Lif and cardiotrophin-1. Consistent with the data in rats, heart-specific overexpression of LIF in mice caused cholinergic transdifferentiation in the cardiac SNS. Further, SNS-specific targeting of the gene encoding the gp130 subunit of the receptor for LIF and cardiotrophin-1 in mice prevented CHF-induced cholinergic transdifferentiation. Cholinergic transdifferentiation was also observed in the cardiac SNS of autopsied patients with CHF. Thus, CHF causes target-dependent cholinergic transdifferentiation of the cardiac SNS via gp130-signaling cytokines secreted from the failing myocardium.

  16. Delirium Accompanied by Cholinergic Deficiency and Organ Failure in a 73-Year-Old Critically Ill Patient: Physostigmine as a Therapeutic Option

    Directory of Open Access Journals (Sweden)

    Benedikt Zujalovic

    2015-01-01

    Full Text Available Delirium is a common problem in ICU patients, resulting in prolonged ICU stay and increased mortality. A cholinergic deficiency in the central nervous system is supposed to be a relevant pathophysiologic process in delirium. Acetylcholine is a major transmitter of the parasympathetic nervous system influencing several organs (e.g., heart and kidneys and the inflammatory response too. This perception might explain that delirium is not an individual symptom, but rather a part of a symptom complex with various disorders of the whole organism. The cholinergic deficiency could not be quantified up to now. Using the possibility of bedside determination of the acetylcholinesterase activity (AChE activity, we assumed to objectify the cholinergic homeostasis within minutes. As reported here, the postoperative delirium was accompanied by a massive hemodynamic and renal deterioration of unclear genesis. We identified the altered AChE activity as a plausible pathophysiological mechanism. The pharmacological intervention with the indirect parasympathomimetic physostigmine led to a quick and lasting improvement of the patient’s cognitive, hemodynamic, and renal status. In summary, severe delirium is not always an attendant phenomenon of critical illness. It might be causal for multiple organ deterioration if it is based on cholinergic deficiency and has to be treated at his pathophysiological roots whenever possible.

  17. Strain improvement of Sporolactobacillus inulinus ATCC 15538 for acid tolerance and production of D-lactic acid by genome shuffling.

    Science.gov (United States)

    Zheng, Huijie; Gong, Jixian; Chen, Tao; Chen, Xun; Zhao, Xueming

    2010-02-01

    Improvement of acid tolerance and production of D-lactic acid by Sporolactobacillus inulinus ATCC 15538 was performed by using recursive protoplast fusion in a genome shuffling format. The starting population was generated by ultraviolet irradiation, diethyl sulfate mutagenesis, and pH-gradient filter and then, subjected for the recursive protoplast fusion. The concentration of lysozyme, time, and temperature for enzyme treatment were optimized by response surface methodology based on the central composite design. Based on contour plots and variance analysis, the model predicted a maximum Y (multiply protoplasts formation ratio by protoplasts regeneration ratio), 60.4%, and the corresponding above used values were 7.75 mg/ml lysozyme, 1.59 h, and 38 degrees C. A pH-5-resistant recombinant, F3-4, was obtained after three rounds of genome shuffling and its production of D-lactic acid reached 93.4 g/l in a 5 L bioreactor, which was increased by 39.8% and 119% in comparison with that of UV generated strain and the original strain S. inulinus ATCC 15538, respectively. The subculture experiments indicated that F3-4 was genetically stable. PMID:19777227

  18. Decreased Consumption of Branched-Chain Amino Acids Improves Metabolic Health

    Directory of Open Access Journals (Sweden)

    Luigi Fontana

    2016-07-01

    Full Text Available Protein-restricted (PR, high-carbohydrate diets improve metabolic health in rodents, yet the precise dietary components that are responsible for these effects have not been identified. Furthermore, the applicability of these studies to humans is unclear. Here, we demonstrate in a randomized controlled trial that a moderate PR diet also improves markers of metabolic health in humans. Intriguingly, we find that feeding mice a diet specifically reduced in branched-chain amino acids (BCAAs is sufficient to improve glucose tolerance and body composition equivalently to a PR diet via metabolically distinct pathways. Our results highlight a critical role for dietary quality at the level of amino acids in the maintenance of metabolic health and suggest that diets specifically reduced in BCAAs, or pharmacological interventions in this pathway, may offer a translatable way to achieve many of the metabolic benefits of a PR diet.

  19. Application of kaolin to improve citric acid production by a thermophilic Aspergillus niger.

    Science.gov (United States)

    Ali, Sikander

    2006-12-01

    Citric acid production by a thermophilic strain of the filamentous fungus Aspergillus niger IIB-6 in a medium containing blackstrap cane molasses was improved by the addition of kaolin to the fermentation medium. The fermentation was run in a 7.5-l stirred bioreactor (60% working volume). The optimal sugar concentration was found to be 150 g/l. Kaolin (1.0 ml) was added to the fermentation medium to enhance volumetric production. The best results in terms of product formation were observed when 15 parts per million (ppm) kaolin was added 24 h after inoculation. With added kaolin, citric acid production was enhanced 2.34-fold, compared to a control fermentation without added kaolin. The length of incubation to attain this product yield was shortened from 168 to 96 h. The comparison of kinetic parameters showed improved citrate synthase activity of the culture (Y (p/x)=7.046 g/g). When the culture grown at various kaolin concentrations was monitored for Q (p), Q (s), and q (p), there was significant improvement in these variables over the control. Specific production by the culture (q (p)=0.073 g/g cells/h) was improved several fold. The addition of kaolin substantially improved the enthalpy (DeltaH (D)=74.5 kJ/mol) and entropy of activation (DeltaS=-174 J/mol/K) for citric acid production, free energies for transition state formation, and substrate binding for sucrose hydrolysis. The performance of fuzzy logic control of the bioreactor was found to be very promising for an improvement ( approximately 4.2-fold) in the production of citric acid (96.88 g/l), which is of value in commercial applications. PMID:16871375

  20. Improved Acetic Acid Resistance in Saccharomyces cerevisiae by Overexpression of the WHI2 Gene Identified through Inverse Metabolic Engineering.

    Science.gov (United States)

    Chen, Yingying; Stabryla, Lisa; Wei, Na

    2016-01-29

    Development of acetic acid-resistant Saccharomyces cerevisiae is important for economically viable production of biofuels from lignocellulosic biomass, but the goal remains a critical challenge due to limited information on effective genetic perturbation targets for improving acetic acid resistance in the yeast. This study employed a genomic-library-based inverse metabolic engineering approach to successfully identify a novel gene target, WHI2 (encoding a cytoplasmatic globular scaffold protein), which elicited improved acetic acid resistance in S. cerevisiae. Overexpression of WHI2 significantly improved glucose and/or xylose fermentation under acetic acid stress in engineered yeast. The WHI2-overexpressing strain had 5-times-higher specific ethanol productivity than the control in glucose fermentation with acetic acid. Analysis of the expression of WHI2 gene products (including protein and transcript) determined that acetic acid induced endogenous expression of Whi2 in S. cerevisiae. Meanwhile, the whi2Δ mutant strain had substantially higher susceptibility to acetic acid than the wild type, suggesting the important role of Whi2 in the acetic acid response in S. cerevisiae. Additionally, overexpression of WHI2 and of a cognate phosphatase gene, PSR1, had a synergistic effect in improving acetic acid resistance, suggesting that Whi2 might function in combination with Psr1 to elicit the acetic acid resistance mechanism. These results improve our understanding of the yeast response to acetic acid stress and provide a new strategy to breed acetic acid-resistant yeast strains for renewable biofuel production.

  1. Emission control for precursors causing acid rain(V):Improvement of acid soil with the bio-briquette combustion ash

    Institute of Scientific and Technical Information of China (English)

    DONG Xu-hui; SAKAMOTO Kazuhiko; WANG Wei; GAO Shi-dong; ISOBE Yugo

    2004-01-01

    The bio-briquette technique which mixes coal, biomass and sulfur fixation agent and bio-briquettes under 3-5 t/cm2 line pressure has aroused people's attention in view of controlling the air pollution and the acid rain. In this paper, the physicochemical properties of bio-briquette and its ash were investigated. And the acid soil was improved by the bio-briquette combustion ash, which contained nutritive substances such as P, N, K and had the acid-neutralizing capacity(ANC). The pH, EC, effective nutrient elements(Ca, Mg, K, P and N), heavy metal elements(Al, Cu, Cd, Cr, Zn and Mn) and acid-neutralizing capacity change of ash-added soils within the range of 0%-10%, were also studied. Specially, when 5% bio-briquette combustion ash was added to the tested soil, the content of the effective elements such as Ca, Mg and K rose by 100 times, 7 times and twice, respectively. The total nitrogen also increased by about twice. The results showed the oxyanions such as that of Al, Cu, Cd, Cr, Zn and Mn were not potentially dangerous, because they were about the same as the averages of them in Chinese soil. It is shown that the ANC became stronger, though the ANC hardly increases in the ash-added soil. On the basis of the evaluation indices, it is concluded that the best mixture ratio is to add 2.5%-8% of the bio-briquette combustion ash to the tested soil.

  2. Improvement of Physiological Characteristic of Selenium-Enriched Candida utilis with Amino Acids Addition

    Directory of Open Access Journals (Sweden)

    Ge Xiaoguang

    2011-01-01

    Full Text Available The effects of amino acids addition on cell growth, glutathione biosynthesis, glutathione distribution, and the intracellular oxidation-reduction environment of Candida utilis SZU 07-01 during selenium enrichment were investigated in this study. Most amino acids under appropriate concentrations have positive effects on cell growth of the yeast strain, except for phenylalanine and proline, compared with the control without amino acid addition. The bioconversion of selenite to organic selenium induced the reduction of glutathione synthesis and intracellular distribution of glutathione. However, amino acids including cysteine, glutamine, glutamic acid, isoleucine, leucine, and tyrosine could effectively promote the selenium-enriched yeast to elevate glutathione production, especially increasing the intracellular glutathione content. Moreover, addition of these six different amino acids apparently decreased malondialdehyde concentration and recovered the normal intracellular redox environment of the selenium-enriched C. utilis SZU 07-01. The improvement of physiological characteristic of the selenium-enriched yeast by increasing intracellular glutathione content and lowering malondialdehyde content will undoubtedly help to widen application of selenium-enriched yeast as food or feed additives.

  3. Effects of superoxide generating systems on muscle tone, cholinergic and NANC responses in cat airway.

    Science.gov (United States)

    Bauer, V; Nakajima, T; Pucovsky, V; Onoue, H; Ito, Y

    2000-02-14

    To study the possible role of reactive oxygen species in airway hyperreactivity, we examined the effects of the superoxide anion radical (O(2)(-)) generating systems, pyrogallol and xanthine with xanthine oxidase, on muscle tone, excitatory and inhibitory neurotransmission in the cat airway. Smooth muscle contraction or non-adrenergic non-cholinergic (NANC) relaxation evoked by electrical field stimulation (EFS) were measured before or after O(2)(-) generating systems with or without diethydithiocarbamic acid (DEDTCA), an inhibitor of endogenous superoxide dismutase (SOD). Resting membrane potential or excitatory junction potential (EJP) were also measured in vitro. Both pyrogallol and xanthine/xanthine oxidase produced biphasic changes in basal and elevated (by 5-HT) muscle tone. After SOD pretreatment, both systems consistently produced a prolonged contraction, thereby indicating that O(2)(-) was converted to H(2)O(2) by the action of SOD and as a result the actions of O(2)(-) were lost but those of H(2)O(2) introduced. The O(2)(-) showed no significant effect on smooth muscle contraction or EJP evoked by EFS, however after DEDTCA pretreatment, it evoked initial enhancement followed by suppression of the contraction and EJP. DEDTCA pretreatment ameliorated the inhibitory action of pyrogallol and xanthine/xanthine oxidase on the NANC relaxation, probably because O(2)(-) could combine with endogenous NO to form peroxynitrite. These results indicate that the O(2)(-) generating systems have multiple actions, presumably due to the presence and simultaneous action of at least two different reactive oxygen species (O(2)(-) and H(2)O(2)). While H(2)O(2) seems to be responsible for elevation of muscle tone and augmentation of smooth muscle contraction by EFS, O(2)(-) inhibits muscle tone, cholinergic and NANC neurotransmission.

  4. VTA GABA neurons modulate specific learning behaviours through the control of dopamine and cholinergic systems

    Directory of Open Access Journals (Sweden)

    Meaghan C Creed

    2014-01-01

    Full Text Available The mesolimbic reward system is primarily comprised of the ventral tegmental area (VTA and the nucleus accumbens (NAc as well as their afferent and efferent connections. This circuitry is essential for learning about stimuli associated with motivationally-relevant outcomes. Moreover, addictive drugs affect and remodel this system, which may underlie their addictive properties. In addition to DA neurons, the VTA also contains approximately 30% ɣ-aminobutyric acid (GABA neurons. The task of signalling both rewarding and aversive events from the VTA to the NAc has mostly been ascribed to DA neurons and the role of GABA neurons has been largely neglected until recently. GABA neurons provide local inhibition of DA neurons and also long-range inhibition of projection regions, including the NAc. Here we review studies using a combination of in vivo and ex vivo electrophysiology, pharmacogenetic and optogenetic manipulations that have characterized the functional neuroanatomy of inhibitory circuits in the mesolimbic system, and describe how GABA neurons of the VTA regulate reward and aversion-related learning. We also discuss pharmacogenetic manipulation of this system with benzodiazepines (BDZs, a class of addictive drugs, which act directly on GABAA receptors located on GABA neurons of the VTA. The results gathered with each of these approaches suggest that VTA GABA neurons bi-directionally modulate activity of local DA neurons, underlying reward or aversion at the behavioural level. Conversely, long-range GABA projections from the VTA to the NAc selectively target cholinergic interneurons (CINs to pause their firing and temporarily reduce cholinergic tone in the NAc, which modulates associative learning. Further characterization of inhibitory circuit function within and beyond the VTA is needed in order to fully understand the function of the mesolimbic system under normal and pathological conditions.

  5. Clonidine, moxonidine, folic acid, and mecobalamin improve baroreflex function in stroke-prone, spontaneously hypertensive rats

    Institute of Scientific and Technical Information of China (English)

    Xiu-juan MA; Fu-ming SHEN; Ai-jun LIU; Ke-yong SHI; Ying-liang WU; Ding-feng SU

    2007-01-01

    Aim: To investigate the effect of clonidine, moxonidine, folic acid, and mecobalamin on arterial baroreflex (ABR) function in stroke-prone spontaneously hypertensive rats (SHR-SP) and the possible mechanisms involved.Methods: Eighty-one SHR-SP were divided into 7 groups. Four groups weredesignated for the intragastric (ig) administration of clonidine (1.0 and 10.0 μg/kg), moxonidine (0.1 and 1.0 mg/kg), folic acid (1.0 mg/kg), and mecobalamin(1.0 mg/kg). Three groups were for the intracerebroventricular (icv) injection of clonidine (4 μg/4 μL), moxonidine (5 μg/4 μL), and mecobalamin (20 μg/4 μL).Blood pressure (BP) was recorded in the conscious state for 30 min and baroreflex sensitivity (BRS) was determined respectively before and after drug administration. Results: Clonidine and moxonidine significantly decreased BP,prolonged the heart period (HP), and increased BRS when administered as either ig or icv injections. Both BP and HP were unchanged by ig folic acid or mecobalamin injection. However, BRS was significantly increased by both.Conclusion: Clonidine, moxonidine, folic acid, and mecobalamin improved impaired ABR function in SHR-SP. The central mechanism was involved in this effect of either clonidine or moxonidine. Mecobalamin improved ABR function through the peripheral mechanism.

  6. Acidic electrolyzed water efficiently improves the flavour of persimmon (Diospyros kaki L. cv. Mopan) wine.

    Science.gov (United States)

    Zhu, Wanqi; Zhu, Baoqing; Li, Yao; Zhang, Yanyan; Zhang, Bolin; Fan, Junfeng

    2016-04-15

    The ability of acidic (AcW) and alkaline electrolyzed waters (AlW) to improve the flavour of persimmon (Diospyros kaki L.) wine was evaluated. Wines made with AcW (WAcW) were significantly better than wines made with AlW or pure water (PW) in aroma, taste, and colour. Volatile analysis showed that WAcW has high alcohol and ester contents, including 2-phenylethanol, isopentanol, isobutanol, ethyl dodecanoate, phenethyl acetate, and butanedioic acid diethyl ester. The total amino acid content of persimmon slurry soaked with AcW reached 531.2 mg/l, which was much higher than those of the slurries soaked in AlW (381.3 mg/l) and PW (182.7 mg/l). The composition of major amino acids in the AcW-soaked slurry may contribute to the strong ester flavour of WAcW. This is the first report to suggest that electrolyzed functional water (EFW) can be used to improve wine flavour, leading to the possible use of EFW in food processing.

  7. Cholinergic Machinery as Relevant Target in Acute Lymphoblastic T Leukemia

    Science.gov (United States)

    Dobrovinskaya, Oxana; Valencia-Cruz, Georgina; Castro-Sánchez, Luis; Bonales-Alatorre, Edgar O.; Liñan-Rico, Liliana; Pottosin, Igor

    2016-01-01

    Various types of non-neuronal cells, including tumors, are able to produce acetylcholine (ACh), which acts as an autocrine/paracrine growth factor. T lymphocytes represent a key component of the non-neuronal cholinergic system. T cells-derived ACh is involved in a stimulation of their activation and proliferation, and acts as a regulator of immune response. The aim of the present work was to summarize the data about components of cholinergic machinery in T lymphocytes, with an emphasis on the comparison of healthy and leukemic T cells. Cell lines derived from acute lymphoblastic leukemias of T lineage (T-ALL) were found to produce a considerably higher amount of ACh than healthy T lymphocytes. Additionally, ACh produced by T-ALL is not efficiently hydrolyzed, because acetylcholinesterase (AChE) activity is drastically decreased in these cells. Up-regulation of muscarinic ACh receptors was also demonstrated at expression and functional level, whereas nicotinic ACh receptors seem to play a less important role and not form functional channels in cells derived from T-ALL. We hypothesized that ACh over-produced in T-ALL may act as an autocrine growth factor and play an important role in leukemic clonal expansion through shaping of intracellular Ca2+ signals. We suggest that cholinergic machinery may be attractive targets for new drugs against T-ALL. Specifically, testing of high affinity antagonists of muscarinic ACh receptors as well as antagomiRs, which interfere with miRNAs involved in the suppression of AChE expression, may be the first choice options. PMID:27630569

  8. Novel aspects of cholinergic regulation of colonic ion transport.

    Science.gov (United States)

    Bader, Sandra; Diener, Martin

    2015-06-01

    Nicotinic receptors are not only expressed by excitable tissues, but have been identified in various epithelia. One aim of this study was to investigate the expression of nicotinic receptors and their involvement in the regulation of ion transport across colonic epithelium. Ussing chamber experiments with putative nicotinic agonists and antagonists were performed at rat colon combined with reverse transcription polymerase chain reaction (RT-PCR) detection of nicotinic receptor subunits within the epithelium. Dimethylphenylpiperazinium (DMPP) and nicotine induced a tetrodotoxin-resistant anion secretion leading to an increase in short-circuit current (I sc) across colonic mucosa. The response was suppressed by the nicotinic receptor antagonist hexamethonium. RT-PCR experiments revealed the expression of α2, α4, α5, α6, α7, α10, and β4 nicotinic receptor subunits in colonic epithelium. Choline, the product of acetylcholine hydrolysis, is known for its affinity to several nicotinic receptor subtypes. As a strong acetylcholinesterase activity was found in colonic epithelium, the effect of choline on I sc was examined. Choline induced a concentration-dependent, tetrodotoxin-resistant chloride secretion which was, however, resistant against hexamethonium, but was inhibited by atropine. Experiments with inhibitors of muscarinic M1 and M3 receptors revealed that choline-evoked secretion was mainly due to a stimulation of epithelial M3 receptors. Although choline proved to be only a partial agonist, it concentration-dependently desensitized the response to acetylcholine, suggesting that it might act as a modulator of cholinergically induced anion secretion. Thus the cholinergic regulation of colonic ion transport - up to now solely explained by cholinergic submucosal neurons stimulating epithelial muscarinic receptors - is more complex than previously assumed. PMID:26236483

  9. Acid Etching and Plasma Sterilization Fail to Improve Osseointegration of Grit Blasted Titanium Implants

    OpenAIRE

    Saksø, Mikkel; Jakobsen, Stig S; Saksø, Henrik; Baas, Jørgen; Jakobsen, Thomas; Søballe, Kjeld

    2012-01-01

    Interaction between implant surface and surrounding bone influences implant fixation. We attempted to improve the bone-implant interaction by 1) adding surface micro scale topography by acid etching, and 2) removing surface-adherent pro-inflammatory agents by plasma cleaning. Implant fixation was evaluated by implant osseointegration and biomechanical fixation. The study consisted of two paired animal sub-studies where 10 skeletally mature Labrador dogs were used. Grit blasted titanium alloy ...

  10. Selection of folate-producing lactic acid bacteria for improving fermented goat milk

    OpenAIRE

    Sanna, Maria Giovanna; Mangia, Nicoletta Pasqualina; Giovanni GARAU; Murgia, Marco Ambrogio; Massa, Tomasina G.; Franco, Mario Andrea; Deiana, Pietrino

    2005-01-01

    Goat milk is a complete food but its low level of folic acid diminisches its nutritional efficacy. In this study, Streptococcus thermophilus, Lactobacillus delbrueckii subsp. bulgaricus, Lb. delbrueckii subsp. lactis and Lb. helveticus strains were selected for folate production in goat milk to improve its quality. A suitable HPLC method was developed to directly determine both total folate and its biologically active derivatives such as 5-methyl-tetrahydrofolate (5- CH3-H4-PteGlu), tetrah...

  11. Ellagic acid improves electrocardiogram waves and blood pressure against global cerebral ischemia rat experimental models

    OpenAIRE

    Nejad, Khojasteh Hoseiny; Dianat, Mahin; Sarkaki, Alireza; Naseri, Mohammad Kazem Gharib; Badavi, Mohammad; Farbood, Yaghoub

    2015-01-01

    Background: Global cerebral ischemia (GCIR) arises in patients that are shown a variety of clinical difficulty including cardiac arrest, asphyxia, and shock. In spite of advances in understanding of the brain, ischemia and protective effects to improve ischemic injury still remain unknown. The aim of our study was to investigate the effect of ellagic acid (EA) pretreatment in the rat models of global cerebral ischemia reperfusion. Methods: This experimental study was conducted in 2014 at the ...

  12. High-Temperature Synthesis of Ordered Mesoporous Aluminosilicates from ZSM-5 Nanoseeds with Improved Acidic Properties

    Directory of Open Access Journals (Sweden)

    Xuan Hoan Vu

    2014-08-01

    Full Text Available Ordered mesoporous SBA-15 analogs with different Si/Al ratios were successfully prepared in a two-step process from self-assembly of ZSM-5 nanoseeds at high temperature in mildly acidic media (473 K, pH 3.5. The obtained products were characterized as SAXS, XRD, N2 sorption, FTIR, TEM, NH3-TPD, AAS and ICP. The results show that the initial Si/Al molar ratio of ZSM-5 precursors strongly affects the final materials’ properties. A highly condensed, well-ordered mesoporous SBA-15 analog with improved hydrothermal stability and acidic properties can be prepared from low aluminum containing ZSM-5 precursors (Si/Al ≥ 20. Reducing the initial Si/Al molar ratio to 10, however, leads to the formation of a disordered mesoporous SBA-15 type material accompanied by degraded textural and acidic properties. The gas phase cracking of cumene, carried out as probe reaction to evaluate Brønsted acidity, reveals that an increased density of Brønsted acid sites has been achieved over the SBA-15 analogs compared to conventional Al-SBA-15 due to the preservation of zeolite building units in the mesopore walls of the SBA-15 analogs.

  13. Application of 10% Ascorbic Acid Improves Resin Shear Bond Stregth in Bleached Dentin

    Directory of Open Access Journals (Sweden)

    Kamizar Kamizar

    2014-10-01

    Full Text Available Normal 0 false false false IN X-NONE X-NONE MicrosoftInternetExplorer4 Restoration of the teeth immediately after bleaching with H2O2 35% is contraindicated due to the remnants of free radical that will stay inside dentin for 2-3 weeks which will compromise the adhesiveness of composite resin. Objective: The aim of this study was to evaluate the influence of 10% ascorbic acid on shear bond strength of composite placed on bleached dentin. Methods:Twenty seven samples were divided equally into three groups. Group 1: dentin was etched with 35% phosphoric acid; Group 2: dentin was bleached with 35% H2O2 followed by etching with 35% phosphoric acid; Group 3: dentin was bleached with 35% H2O2, followed by application of 10% ascorbic acid and etched with 35% phosphoric acid. All samples were then stored at 370C for 24 hours. The Universal Testing Machine was used to measure shear bond strength and the results were analyzed with Kruskal Wallis and Mann Whitney test. Results: After nine independent experiments, 10% ascorbic acid application on bleached dentin resulted in highest increased in bond stregth (56.04±11.06MPa compared to Group 2 (29.09±7.63MPa and Group 1 (25.55±2.22MPa and the difference was statistically significant (p<0.05. Conclusion: Application of 10% ascorbic acid to the bleached dentin improved the shear bond strength of resin composite.

  14. An improved method for separating quartz from rock using pyrophosphoric acid

    International Nuclear Information System (INIS)

    A method that employs hot dehydrated phosphoric acid (pyrophosphoric acid) to isolate quartz from rock for surface exposure dating with 10Be and 26Al has been improved so that up to 250 g of sample can be decomposed reasonably safely. Because pyrophosphoric acid is more selective in dissolving the silicate minerals than the commonly used mixture of dilute hydrofluoric and nitric acids, the yield of quartz is relatively high. However, serious hazards arise from using large volumes of hot concentrated phosphoric acid to decompose rock. When the acid is heated to evaporate water and initiate the reaction, the crushed rock settles to the bottom of the vessel causing the mixture to superheat and 'bump' severely. Then, as the reaction progresses, the mixture increases in viscosity and will form a solid gel if allowed to cool. Starting with a greater excess of phosphoric acid to reduce the viscosity is impractical for such large amounts of rock so, to avoid a solid gel at the end of the reaction, the mixture has to be diluted with cold water while it is still near 250 degrees C. This step is particularly dangerous as the water at first instantaneously turns to steam that can eject gel resulting in serious thermal burns even through thick gloves. We have mitigated these hazards by keeping the sample suspended using a mixer throughout the procedure. There is no superheating at the start and water can be added slowly at the end thus quenching the reaction and dispersing the particulate matter. Another hazard, boiling sodium hydroxide solution, has been minimised and may ultimately be eliminated. This report covers the prototype mixer, safety features of the new mixer under construction, and an interim procedure for decomposing rock and recovering pure quartz. (author)

  15. Cholinergic neurons in the dorsomedial hypothalamus regulate mouse brown adipose tissue metabolism

    Directory of Open Access Journals (Sweden)

    Jae Hoon Jeong

    2015-06-01

    Conclusion: DMH cholinergic neurons directly send efferent signals to sympathetic premotor neurons in the Rpa. Elevated cholinergic input to this area reduces BAT activity through activation of M2 mAChRs on serotonergic neurons. Therefore, the direct DMHACh–Rpa5-HT pathway may mediate physiological heat-defense responses to elevated environmental temperature.

  16. Ultrastructural localization of cholinergic muscarinic receptors in rat brain cortical capillaries

    NARCIS (Netherlands)

    Luiten, PGM; deJong, GI; VanderZee, EA; vanDijken, H; Dijken, H. van

    1996-01-01

    Cholinergic innervation of the cerebrovasculature is known to regulate vascular tone, perfusion rate and permeability of the microvascular wall. Notably the cholinergic innervation of cerebral capillaries is of interest since these capillaries form the blood-brain barrier. Although there is a genera

  17. Mechanisms mediating cholinergic antral circular smooth muscle contraction in rats

    Institute of Scientific and Technical Information of China (English)

    Helena F Wrzos; Tarun Tandon; Ann Ouyang

    2004-01-01

    AIM: To investigate the pathway (s) mediating rat antral circular smooth muscle contractile responses to the cholinomimetic agent, bethanechol and the subtypes of muscarinic receptors mediating the cholinergic contraction.METHODS: Circular smooth muscle strips from the antrum of Sprague-Dawley rats were mounted in muscle baths in Krebs buffer. Isometric tension was recorded. Cumulative concentration-response curves were obtained for (+)-cisdioxolane (cD), a nonspecific muscarinic agonist, at 10-8-10-4 mol/L, in the presence of tetrodotoxin (TTX, 10-7 mol/L).Results were normalized to cross sectional area. A repeat concentration-response curve was obtained after incubation of the muscle for 90 min with antagonists for M1 (pirenzepine),M2 (methoctramine) and M3 (darifenacin) muscarinic receptor subtypes. The sensitivity to PTX was tested by the ip injection of 100 mg/kg of PTX 5 d before the experiment. The antral circular smooth muscles were removed from PTX-treated and non-treated rats as strips and dispersed smooth muscle cells to identify whether PTX-linked pathway mediated the contractility to bethanechol.RESULTS: A dose-dependent contractile response observed with bethanechol, was not affected by TTX. The pretreatment of rats with pertussis toxin decreased the contraction induced by bethanechol. Lack of calcium as Well as the presence of the L-type calcium channel blocker, nifedipine, also inhibited the cholinergic contraction, with a reduction in response from 2.5±0.4 g/mm2 to 1.2±0.4 g/mm2 (P<0.05). The doseresponse curves were shifted to the right by muscarinic antagonists in the following order of affinity: darifenacin(M3)>methocramine (M2)>pirenzepine (M1).CONCLUSION: The muscarinic receptors-dependent contraction of rat antral circular smooth muscles was linked to the signal transduction pathway(s) involving pertussis-toxin sensitive GTP-binding proteins and to extracellular calcium via L-type voltage gated calcium channels. The presence of the

  18. Improving the environmental profile of wood panels via co-production of ethanol and acetic acid.

    Science.gov (United States)

    Earles, J Mason; Halog, Anthony; Shaler, Stephen

    2011-11-15

    The oriented strand board (OSB) biorefinery is an emerging technology that could improve the building, transportation, and chemical sectors' environmental profiles. By adding a hot water extraction stage to conventional OSB panel manufacturing, hemicellulose polysaccharides can be extracted from wood strands and converted to renewably sourced ethanol and acetic acid. Replacing fossil-based gasoline and acetic acid has the potential to reduce greenhouse gas (GHG) emissions, among other possible impacts. At the same time, hemicellulose extraction could improve the environmental profile of OSB panels by reducing the level of volatile organic compounds (VOCs) emitted during manufacturing. In this study, the life cycle significance of such GHG, VOC, and other emission reductions was investigated. A process model was developed based on a mix of laboratory and industrial-level mass and energy flow data. Using these data a life cycle assessment (LCA) model was built. Sensitive process parameters were identified and used to develop a target production scenario for the OSB biorefinery. The findings suggest that the OSB biorefinery's deployment could substantially improve human and ecosystem health via reduction of select VOCs compared to conventionally produced OSB, gasoline, and acetic acid. Technological advancements are needed, however, to achieve desirable GHG reductions. PMID:21967719

  19. Improvement of acetic acid tolerance of Saccharomyces cerevisiae using a zinc-finger-based artificial transcription factor and identification of novel genes involved in acetic acid tolerance.

    Science.gov (United States)

    Ma, Cui; Wei, Xiaowen; Sun, Cuihuan; Zhang, Fei; Xu, Jianren; Zhao, Xinqing; Bai, Fengwu

    2015-03-01

    Acetic acid is present in cellulosic hydrolysate as a potent inhibitor, and the superior acetic acid tolerance of Saccharomyces cerevisiae ensures good cell viability and efficient ethanol production when cellulosic raw materials are used as substrates. In this study, a mutant strain of S. cerevisiae ATCC4126 (Sc4126-M01) with improved acetic acid tolerance was obtained through screening strains transformed with an artificial zinc finger protein transcription factor (ZFP-TF) library. Further analysis indicated that improved acetic acid tolerance was associated with improved catalase (CAT) activity. The ZFP coding sequence associated with the improved phenotype was identified, and real-time RT-PCR analysis revealed that three of the possible genes involved in the enhanced acetic acid tolerance regulated by this ZFP-TF, namely YFL040W, QDR3, and IKS1, showed decreased transcription levels in Sc4126-M01 in the presence of acetic acid, compared to those in the control strain. Sc4126-M01 mutants having QDR3 and IKS1 deletion (ΔQDR3 and ΔIKS1) exhibited higher acetic acid tolerance than the wild-type strain under acetic acid treatment. Glucose consumption rate and ethanol productivity in the presence of 5 g/L acetic acid were improved in the ΔQDR3 mutant compared to the wild-type strain. Our studies demonstrated that the synthetic ZFP-TF library can be used to improve acetic acid tolerance of S. cerevisiae and that the employment of an artificial transcription factor can facilitate the exploration of novel functional genes involved in stress tolerance of S. cerevisiae. PMID:25698512

  20. Electroacupuncture-Induced Cholinergic Nerve Activation Enhances the Hypoglycemic Effect of Exogenous Insulin in a Rat Model of Streptozotocin-Induced Diabetes

    Directory of Open Access Journals (Sweden)

    Yu-Chen Lee

    2011-01-01

    Full Text Available The aim of this study is to explore the mechanisms by which electroacupuncture (EA enhances the hypoglycemic effect of exogenous insulin in a streptozotocin- (STZ- diabetic rats. Animals in the EA group were anesthetized and subjected to the insulin challenge test (ICT and EA for 60 minutes. In the control group, rats were subjected to the same treatment with the exception of EA stimulation. Blood samples were drawn to measure changes in plasma glucose, free fatty acids (FFA, and insulin levels. Western blot was used to assay proteins involved in insulin signaling. Furthermore, atropine, hemicholinium-3 (HC-3, and Eserine were used to explore the relationship between EA and cholinergic nerve activation during ICT. EA augmented the blood glucose-lowering effects of EA by activating the cholinergic nerves in STZ rats that had been exposed to exogenous insulin. This phenomenon may be related to enhancement of insulin signaling rather than to changes in FFA concentration.

  1. Linking Cholinergic Interneurons, Synaptic Plasticity, and Behavior during the Extinction of a Cocaine-Context Association.

    Science.gov (United States)

    Lee, Junuk; Finkelstein, Joel; Choi, Jung Yoon; Witten, Ilana B

    2016-06-01

    Despite the fact that cholinergic interneurons are a key cell type within the nucleus accumbens, a relationship between synaptic plasticity and the in vivo activity of cholinergic interneurons remains to be established. Here, we identify a three-way link between the activity of cholinergic interneurons, synaptic plasticity, and learning in mice undergoing the extinction of a cocaine-context association. We found that activity of cholinergic interneurons regulates extinction learning for a cocaine-context association and generates a sustained reduction in glutamatergic presynaptic strength onto medium spiny neurons. Interestingly, activation of cholinergic interneurons does not support reinforcement learning or plasticity by itself, suggesting that these neurons have a modulatory rather than a reinforcing function. PMID:27210555

  2. Reciprocal cholinergic and GABAergic modulation of the small ventrolateral pacemaker neurons of Drosophila's circadian clock neuron network.

    Science.gov (United States)

    Lelito, Katherine R; Shafer, Orie T

    2012-04-01

    The relatively simple clock neuron network of Drosophila is a valuable model system for the neuronal basis of circadian timekeeping. Unfortunately, many key neuronal classes of this network are inaccessible to electrophysiological analysis. We have therefore adopted the use of genetically encoded sensors to address the physiology of the fly's circadian clock network. Using genetically encoded Ca(2+) and cAMP sensors, we have investigated the physiological responses of two specific classes of clock neuron, the large and small ventrolateral neurons (l- and s-LN(v)s), to two neurotransmitters implicated in their modulation: acetylcholine (ACh) and γ-aminobutyric acid (GABA). Live imaging of l-LN(v) cAMP and Ca(2+) dynamics in response to cholinergic agonist and GABA application were well aligned with published electrophysiological data, indicating that our sensors were capable of faithfully reporting acute physiological responses to these transmitters within single adult clock neuron soma. We extended these live imaging methods to s-LN(v)s, critical neuronal pacemakers whose physiological properties in the adult brain are largely unknown. Our s-LN(v) experiments revealed the predicted excitatory responses to bath-applied cholinergic agonists and the predicted inhibitory effects of GABA and established that the antagonism of ACh and GABA extends to their effects on cAMP signaling. These data support recently published but physiologically untested models of s-LN(v) modulation and lead to the prediction that cholinergic and GABAergic inputs to s-LN(v)s will have opposing effects on the phase and/or period of the molecular clock within these critical pacemaker neurons.

  3. Collagen tissue treated with chitosan solutions in carbonic acid for improved biological prosthetic heart valves.

    Science.gov (United States)

    Gallyamov, Marat O; Chaschin, Ivan S; Khokhlova, Marina A; Grigorev, Timofey E; Bakuleva, Natalia P; Lyutova, Irina G; Kondratenko, Janna E; Badun, Gennadii A; Chernysheva, Maria G; Khokhlov, Alexei R

    2014-04-01

    Calcification of bovine pericardium dramatically shortens typical lifetimes of biological prosthetic heart valves and thus precludes their choice for younger patients. The aim of the present work is to demonstrate that the calcification is to be mitigated by means of treatment of bovine pericardium in solutions of chitosan in carbonic acid, i.e. water saturated with carbon dioxide at high pressure. This acidic aqueous fluid unusually combines antimicrobial properties with absolute biocompatibility as far as at normal pressure it decomposes spontaneously and completely into H2O and CO2. Yet, at high pressures it can protonate and dissolve chitosan materials with different degrees of acetylation (in the range of 16-33%, at least) without any further pretreatment. Even exposure of the bovine pericardium in pure carbonic acid solution without chitosan already favours certain reduction in calcification, somewhat improved mechanical properties, complete biocompatibility and evident antimicrobial activity of the treated collagen tissue. The reason may be due to high extraction ability of this peculiar compressed fluidic mixture. Moreover, exposure of the bovine pericardium in solutions of chitosan in carbonic acid introduces even better mechanical properties and highly pronounced antimicrobial activity of the modified collagen tissue against adherence and biofilm formation of relevant Gram-positive and Gram-negative strains. Yet, the most important achievement is the detected dramatic reduction in calcification for such modified collagen tissues in spite of the fact that the amount of the thus introduced chitosan is rather small (typically ca. 1wt.%), which has been reliably detected using original tritium labelling method. We believe that these improved properties are achieved due to particularly deep and uniform impregnation of the collagen matrix with chitosan from its pressurised solutions in carbonic acid. PMID:24582232

  4. The cholinergic anti-inflammatory pathway delays TLR-induced skin allograft rejection in mice: cholinergic pathway modulates alloreactivity.

    Directory of Open Access Journals (Sweden)

    Claude Sadis

    Full Text Available Activation of innate immunity through Toll-like receptors (TLR can abrogate transplantation tolerance by revealing hidden T cell alloreactivity. Separately, the cholinergic anti-inflammatory pathway has the capacity to dampen macrophage activation and cytokine release during endotoxemia and ischemia reperfusion injury. However, the relevance of the α7 nicotinic acetylcholine receptor (α7nAChR-dependent anti-inflammatory pathway in the process of allograft rejection or maintenance of tolerance remains unknown. The aim of our study is to investigate whether the cholinergic pathway could impact T cell alloreactivity and transplant outcome in mice. For this purpose, we performed minor-mismatched skin allografts using donor/recipient combinations genetically deficient for the α7nAChR. Minor-mismatched skin grafts were not rejected unless the mice were housed in an environment with endogenous pathogen exposure or the graft was treated with direct application of imiquimod (a TLR7 ligand. The α7nAChR-deficient recipient mice showed accelerated rejection compared to wild type recipient mice under these conditions of TLR activation. The accelerated rejection was associated with enhanced IL-17 and IFN-γ production by alloreactive T cells. An α7nAChR-deficiency in the donor tissue facilitated allograft rejection but not in recipient mice. In addition, adoptive T cell transfer experiments in skin-grafted lymphopenic animals revealed a direct regulatory role for the α7nAChR on T cells. Taken together, our data demonstrate that the cholinergic pathway regulates alloreactivity and transplantation tolerance at multiple levels. One implication suggested by our work is that, in an organ transplant setting, deliberate α7nAChR stimulation of brain dead donors might be a valuable approach for preventing donor tissue inflammation prior to transplant.

  5. Caffeic acid attenuates oxidative stress, learning and memory deficit in intra-cerebroventricular streptozotocin induced experimental dementia in rats.

    Science.gov (United States)

    Deshmukh, Rahul; Kaundal, Madhu; Bansal, Vikas; Samardeep

    2016-07-01

    Oxidative stress has been implicated in cognitive decline as seen during normal aging and in sporadic Alzheimer's disease (AD). Caffeic acid, a polyphenolic compound, has been reported to possess potent antioxidant and neuroprotective properties. The role of caffeic acid in experimental dementia is not fully understood. Thus the present study was designed to investigate the therapeutic potential of caffeic acid in streptozotocin (STZ)-induced experimental dementia of Alzheimer's type in rats. Streptozotocin (STZ) was administered intracerebroventrically (ICV) on day 1 and 3 (3mg/kg, ICV bilaterally) in Wistar rats. Caffeic acid was administered (10, 20 and 40mg/kg/day p.o.) 1h following STZ infusion upto 21st day. Morris water maze and object recognition task were used to assess learning and memory in rats. Terminally, acetylcholinesterase (AChE) activity and the levels of oxido-nitrosative stress markers were determined in cortical and hippocampal brain regions of rats. STZ produced significant (plearning and memory impairment, oxido-nitrosative stress and cholinergic deficit in rats. Whereas, caffeic acid treatment significantly (p<0.001) and dose dependently attenuated STZ induced behavioral and biochemical abnormalities in rats. The observed cognitive improvement following caffeic acid in STZ treated rats may be due to its antioxidant activity and restoration of cholinergic functions. Our results suggest the therapeutic potential of caffeic acid in cognitive disorders such as AD. PMID:27261577

  6. Low-level microwave irradiation and central cholinergic systems

    Energy Technology Data Exchange (ETDEWEB)

    Lai, H.; Carino, M.A.; Horita, A.; Guy, A.W. (Univ. of Washington School of Medicine, Seattle (USA))

    1989-05-01

    Our previous research showed that 45 min of exposure to low-level, pulsed microwaves (2450-MHz, 2-microseconds pulses, 500 pps, whole-body average specific absorption rate 0.6 W/kg) decreased sodium-dependent high-affinity choline uptake in the frontal cortex and hippocampus of the rat. The effects of microwaves on central cholinergic systems were further investigated in this study. Increases in choline uptake activity in the frontal cortex, hippocampus, and hypothalamus were observed after 20 min of acute microwave exposure, and tolerance to the effect of microwaves developed in the hypothalamus, but not in the frontal cortex and hippocampus, of rats subjected to ten daily 20-min exposure sessions. Furthermore, the effects of acute microwave irradiation on central choline uptake could be blocked by pretreating the animals before exposure with the narcotic antagonist naltrexone. In another series of experiments, rats were exposed to microwaves in ten daily sessions of either 20 or 45 min, and muscarinic cholinergic receptors in different regions of the brain were studied by 3H-QNB binding assay. Decreases in concentration of receptors occurred in the frontal cortex and hippocampus of rats subjected to ten 20-min microwave exposure sessions, whereas increase in receptor concentration occurred in the hippocampus of animals exposed to ten 45-min sessions. This study also investigated the effects of microwave exposure on learning in the radial-arm maze. Rats were trained in the maze to obtain food reinforcements immediately after 20 or 45 min of microwave exposure.

  7. Somatostatin modulates cholinergic neurotransmission in canine antral muscle

    International Nuclear Information System (INIS)

    Somatostatin has been shown to inhibit antral motility in vivo. To examine the effect of somatostatin on cholinergic neurotransmission in the canine antrum, we studied the mechanical response of and the release of [3H]acetylcholine from canine longitudinal antral muscle in response to substance P, gastrin 17, and electrical stimulation. In unstimulated tissues, somatostatin had a positive inotropic effect on spontaneous phasic contractions. In tissues stimulated with substance P and gastrin 17, but not with electrical stimulation, somatostatin inhibited the phasic inotropic response dose dependently. This inhibitory effect was abolished by indomethacin. Somatostatin stimulated the release of prostaglandin E2 radioimmunoreactivity, and prostaglandin E2 inhibited the release of [3H]acetylcholine induced by substance P and electrical stimulation. Somatostatin increased the release of [3H]acetylcholine from unstimulated tissues by a tetrodotoxin-sensitive mechanism but inhibited the release induced by substance P and electrical stimulation. These results suggest that somatostatin has a dual modulatory effect on cholinergic neutrotransmission in canine longitudinal antral muscle. This effect is excitatory in unstimulated tissues and inhibitory in stimulated tissues. The inhibitory effect is partially mediated by prostaglandins

  8. Collagen tissue treated with chitosan solutions in carbonic acid for improved biological prosthetic heart valves

    Energy Technology Data Exchange (ETDEWEB)

    Gallyamov, Marat O., E-mail: glm@spm.phys.msu.ru [Faculty of Physics, Lomonosov Moscow State University, Leninskie gory 1–2, Moscow 119991 (Russian Federation); Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilova 28, Moscow 119991 (Russian Federation); Chaschin, Ivan S. [Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilova 28, Moscow 119991 (Russian Federation); Khokhlova, Marina A. [Faculty of Physics, Lomonosov Moscow State University, Leninskie gory 1–2, Moscow 119991 (Russian Federation); Grigorev, Timofey E. [Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilova 28, Moscow 119991 (Russian Federation); Bakuleva, Natalia P.; Lyutova, Irina G.; Kondratenko, Janna E. [Bakulev Scientific Center for Cardiovascular Surgery of the Russian Academy of Medical Sciences, Roublyevskoe Sh. 135, Moscow 121552 (Russian Federation); Badun, Gennadii A.; Chernysheva, Maria G. [Radiochemistry Division, Faculty of Chemistry, Lomonosov Moscow State University, Leninskie gory 1–2, Moscow 119991 (Russian Federation); Khokhlov, Alexei R. [Faculty of Physics, Lomonosov Moscow State University, Leninskie gory 1–2, Moscow 119991 (Russian Federation); Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilova 28, Moscow 119991 (Russian Federation)

    2014-04-01

    Calcification of bovine pericardium dramatically shortens typical lifetimes of biological prosthetic heart valves and thus precludes their choice for younger patients. The aim of the present work is to demonstrate that the calcification is to be mitigated by means of treatment of bovine pericardium in solutions of chitosan in carbonic acid, i.e. water saturated with carbon dioxide at high pressure. This acidic aqueous fluid unusually combines antimicrobial properties with absolute biocompatibility as far as at normal pressure it decomposes spontaneously and completely into H{sub 2}O and CO{sub 2}. Yet, at high pressures it can protonate and dissolve chitosan materials with different degrees of acetylation (in the range of 16–33%, at least) without any further pretreatment. Even exposure of the bovine pericardium in pure carbonic acid solution without chitosan already favours certain reduction in calcification, somewhat improved mechanical properties, complete biocompatibility and evident antimicrobial activity of the treated collagen tissue. The reason may be due to high extraction ability of this peculiar compressed fluidic mixture. Moreover, exposure of the bovine pericardium in solutions of chitosan in carbonic acid introduces even better mechanical properties and highly pronounced antimicrobial activity of the modified collagen tissue against adherence and biofilm formation of relevant Gram-positive and Gram-negative strains. Yet, the most important achievement is the detected dramatic reduction in calcification for such modified collagen tissues in spite of the fact that the amount of the thus introduced chitosan is rather small (typically ca. 1 wt.%), which has been reliably detected using original tritium labelling method. We believe that these improved properties are achieved due to particularly deep and uniform impregnation of the collagen matrix with chitosan from its pressurised solutions in carbonic acid. - Highlights: • Treatment of GA

  9. Experimental study of retinoic acid on improving iodide uptake in MCF-7 breast cancer cells

    Institute of Scientific and Technical Information of China (English)

    FU Hong-Liang; WU Jing-Chuan; DU Xue-Liang; LI Jia-Ning; WU Zhen; ZOU Ren-Jian

    2005-01-01

    The study aims to investigate the effect of retinoic acid on the iodide uptake of MCF-7 cells and its mechanism. The iodide uptake and expression of hNIS(human sodium/iodide symporter)mRNA in the breast cancer MCF-7 cells were compared individually before and after the intervention of all-trans retinoic acid (ATRA) with the iodide uptake assay and RT-PCR. The following results are obtained: (1) when treated with all-trans retinoic acid in the concentration of 1.0 μmol/L, the capacity of iodide uptake of MCF-7 cells reached about 1.5 times of the basal state; (2) 12 h after the intervention of 1.0 μmol/L ATRA, the hNISmRNA expression of the MCF-7 cells reached maximum. The study shows that all-trans retinoic acid has the effect to improve the iodide uptake of the MCF-7 cells and this effect may result from its up-regulation of the hNISmRNA expression.

  10. Enhance nisin yield via improving acid-tolerant capability of Lactococcus lactis F44

    Science.gov (United States)

    Zhang, Jian; Caiyin, Qinggele; Feng, Wenjing; Zhao, Xiuli; Qiao, Bin; Zhao, Guangrong; Qiao, Jianjun

    2016-01-01

    Traditionally, nisin was produced industrially by using Lactococcus lactis in the neutral fermentation process. However, nisin showed higher activity in the acidic environment. How to balance the pH value for bacterial normal growth and nisin activity might be the key problem. In this study, 17 acid-tolerant genes and 6 lactic acid synthetic genes were introduced in L. lactis F44, respectively. Comparing to the 2810 IU/mL nisin yield of the original strain F44, the nisin titer of the engineered strains over-expressing hdeAB, ldh and murG, increased to 3850, 3979 and 4377 IU/mL, respectively. These engineered strains showed more stable intracellular pH value during the fermentation process. Improvement of lactate production could partly provide the extra energy for the expression of acid tolerance genes during growth. Co-overexpression of hdeAB, murG, and ldh(Z) in strain F44 resulted in the nisin titer of 4913 IU/mL. The engineered strain (ABGL) could grow on plates with pH 4.2, comparing to the surviving pH 4.6 of strain F44. The fed-batch fermentation showed nisin titer of the co-expression L. lactis strain could reach 5563 IU/mL with lower pH condition and longer cultivation time. This work provides a novel strategy of constructing robust strains for use in industry process. PMID:27306587

  11. Durability improvement assessment in different high strength bacterial structural concrete grades against different types of acids

    Indian Academy of Sciences (India)

    Ramin Andalib; M Zaimi Abd Majid; A Keyvanfar; Amirreza Talaiekhozan; Mohd Warid Hussin; A Shafaghat; Rosli Mohd Zin; Chew Tin Lee; Mohammad Ali Fulazzaky; Hasrul Haidar Ismail

    2014-12-01

    This paper provides an insight into a new biotechnological method based on calcite precipitation for achieving high strength bio-concrete durability. It is very clear that mineral precipitation has the potential to enhance construction material resistance towards degradation procedures. The appropriate microbial cell concentration (30 * 105 cells/ml) was introduced onto different structural concrete grades (40, 45 and 50 MPa) by mixing water. In order to study the durability of structural concrete against aggressive agents, specimens were immersed in different types of acids solution (5% H2SO4 and HCl) to compare their effects on 60th, 90th and 120th day. In general, sulphuric acid and hydrochloric acid are known to be the most aggressive natural threats from industrial waters which can penetrate concrete to transfer the soluble calcium salts away from the cement matrix. The experimental results demonstrated that bio-concrete has less weight and strength losses when compared to the ordinary Portland cement concrete without microorganism. It was also found that maximum compressive strength and weight loss occurred during H2SO4 acid immersion as compared to HCl immersion. The density and uniformity of bio-concrete were examined using ultrasonic pulse velocity (UPV) test. Microstructure chemical analysis was also quantified by energy dispersive spectrometer (EDS) to justify the durability improvement in bacterial concrete. It was observed that less sulphur and chloride were noticed in bacterial concrete against H2SO4 and HCl, respectively in comparison to the ordinary Portland cement concrete due to calcite deposition.

  12. Ionic liquid-assisted solublization for improved enzymatic esterification of phenolic acids

    DEFF Research Database (Denmark)

    Yang, Zhiyong; Guo, Zheng; Xu, Xuebing

    2012-01-01

    Phenolic acids are very difficult to dissolve in most of solvent, which lead to low yield and long reaction time for production of lipophilic phenolic derivatives according to previous studies.This work is focused on increasing production of lipophilic phenolic derivatives catalyzed by Novozym 435...... in a binary system, which is composed of ionic liquid tOMA•TFA (trioctylmethylammonium Trifluoroacetate) and octanol. Ionic liquid tOMA•TFA has great solubility towards most of phenolic acid. The strategy of increasing the solubility of phenolic in ionic liquid tOMA•TFA was proved to be an efficient way......C was slightly higher than at 60 oC and 80 oC. Removing water by molecular sieves and vacuum has significant improvement on the conversion. Even though the conversion was much higher when the concentration of DHCA was 0.4 M, the highest reaction rate was observed when the concertration of DHCA was 1.6 M, which...

  13. Linoleic acid derivative DCP-LA improves learning impairment in SAMP8.

    Science.gov (United States)

    Yaguchi, Takahiro; Nagata, Tetsu; Mukasa, Takeshi; Fujikawa, Hirokazu; Yamamoto, Hideyuki; Yamamoto, Satoshi; Iso, Hiroyuki; Tanaka, Akito; Nishizaki, Tomoyuki

    2006-01-23

    In the water-maze test, the linoleic acid derivative, 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA) (1 mg/kg, intraperitoneally), significantly shortened the prolonged latency for accelerated-senescence-prone mice 8 (SAMP8), reaching a level similar to the latency for accelerated-senescence-resistant mice 1 (SAMR1) as control. In the open-field test to assess motor activity, it was confirmed that the DCP-LA effect is not due to increased motor activity. In the passive avoidance test to assess fear memory, DCP-LA had no effect on the latency of acquisition and retention for SAMP8. The results of the present study, thus, suggest that DCP-LA could improve age-related learning impairment by enhancing cognitive functions.

  14. Effects of Ce3+ on improvement of spectral characteristics and function of chloroplasts damaged by linolenic acid in spinach

    Institute of Scientific and Technical Information of China (English)

    LIU Xiaoqing; ZE Yuguan; LIU Chao; ZHOU Min; LI Na; DUAN Yanmei; YIN Sitao; HONG Fashui

    2009-01-01

    Linolenic acid has great effects on the structure and function of chloroplast. We studied the effects of Ce3+ on the improvement of chloroplast spectral characteristics and oxygen evolution damaged by linolenic acid in spinach. Results showed that Ce3+ could decrease the light absorption increased by linolenic acid and promote the distribution of excitation energy to PS Ⅱ and alleviate the decrease of PS Ⅱ fluo-rescence yield caused by linolenic acid. The linolenic acid treatments in various concentrations reduced the oxygen-evolving rate of chloro-plasts, but the rate was accelerated since adding Ce3+.

  15. Effects of cholinergic and noradrenergic agents on locomotion in the mudpuppy (Necturus maculatus).

    Science.gov (United States)

    Fok, M; Stein, R B

    2002-08-01

    Some neurotransmitters act consistently on the central pattern generator (CPG) for locomotion in a wide range of vertebrates. In contrast, acetylcholine (ACh) and noradrenaline (NA) have various effects on locomotion in different preparations. The roles of ACh and NA have not been studied in amphibian walking, so we examined their effects in an isolated spinal cord preparation of the mudpuppy ( Necturus maculatus). This preparation contains a CPG that produces locomotor activity when N-methyl- D-aspartic acid (NMDA), an excitatory amino acid agonist, is added to the bath. The addition of carbachol, a long acting ACh agonist, to the bath disrupted the walking rhythm induced by NMDA, while not changing the level of activity in flexor and extensor motoneurons. Adding clonidine, an alpha(2)-noradrenergic agonist, had no effect on the NMDA-induced walking rhythm. Physostigmine, an ACh-esterase inhibitor, disrupted the walking rhythm, presumably by potentiating the effects of endogenously released ACh. Atropine, an ACh antagonist that binds to muscarinic ACh receptors, blocked the effects of carbachol, indicating that the action is mediated, at least in part, by muscarinic receptors. In the absence of carbachol, atropine had no effect. Locomotion was not induced by carbachol, atropine or clonidine in a resting spinal cord preparation. Cholinergic actions do not seem to be essential to the CPG for walking in the mudpuppy, but ACh may convert a rhythmic walking state to a more tonic state with occasional bursts of EMG activity for postural adjustments.

  16. Cholinergic Mesopontine Signals Govern Locomotion and Reward through Dissociable Midbrain Pathways.

    Science.gov (United States)

    Xiao, Cheng; Cho, Jounhong Ryan; Zhou, Chunyi; Treweek, Jennifer B; Chan, Ken; McKinney, Sheri L; Yang, Bin; Gradinaru, Viviana

    2016-04-20

    The mesopontine tegmentum, including the pedunculopontine and laterodorsal tegmental nuclei (PPN and LDT), provides major cholinergic inputs to midbrain and regulates locomotion and reward. To delineate the underlying projection-specific circuit mechanisms, we employed optogenetics to control mesopontine cholinergic neurons at somata and at divergent projections within distinct midbrain areas. Bidirectional manipulation of PPN cholinergic cell bodies exerted opposing effects on locomotor behavior and reinforcement learning. These motor and reward effects were separable via limiting photostimulation to PPN cholinergic terminals in the ventral substantia nigra pars compacta (vSNc) or to the ventral tegmental area (VTA), respectively. LDT cholinergic neurons also form connections with vSNc and VTA neurons; however, although photo-excitation of LDT cholinergic terminals in the VTA caused positive reinforcement, LDT-to-vSNc modulation did not alter locomotion or reward. Therefore, the selective targeting of projection-specific mesopontine cholinergic pathways may offer increased benefit in treating movement and addiction disorders.

  17. Puerarin partly counteracts the inflammatory response after cerebral ischemia/reperfusion via activating the cholinergic anti-inflammatory pathway

    Institute of Scientific and Technical Information of China (English)

    Xiaojie Liu; Zhigang Mei; Jingping Qian; Yongbao Zeng; Mingzhi Wang

    2013-01-01

    Puerarin, a major isoflavonoid derived from the Chinese medical herb radix puerariae (Gegen), has been reported to inhibit neuronal apoptosis and play an anti-inflammatory role in focal cerebral ischemia model rats. Recent findings regarding stroke pathophysiology have recognized that an-ti-inflammation is an important target for the treatment of ischemic stroke. The cholinergic an-ti-inflammatory pathway is a highly robust neural-immune mechanism for inflammation control. This study was to investigate whether activating the cholinergic anti-inflammatory pathway can be in-volved in the mechanism of inhibiting the inflammatory response during puerarin-induced cerebral ischemia/reperfusion in rats. Results showed that puerarin pretreatment (intravenous injection) re-duced the ischemic infarct volume, improved neurological deficit after cerebral ischemia/reperfusion and decreased the levels of interleukin-1β, interleukin-6 and tumor necrosis factor-αin brain tissue. Pretreatment with puerarin (intravenous injection) attenuated the inflammatory response in rats, which was accompanied by janus-activated kinase 2 (JAK2) and signal transducers and activators of transcription 3 (STAT3) activation and nuclear factor kappa B (NF-κB) inhibition. These observa-tions were inhibited by the alpha7 nicotinic acetylcholine receptor (α7nAchR) antagonistα-bungarotoxin (α-BGT). In addition, puerarin pretreatment increased the expression of α7nAchR mRNA in ischemic cerebral tissue. These data demonstrate that puerarin pretreatment strongly protects the brain against cerebral ischemia/reperfusion injury and inhibits the inflammatory re-sponse. Our results also indicated that the anti-inflammatory effect of puerarin may partly be me-diated through the activation of the cholinergic anti-inflammatory pathway.

  18. Improved zeolite regeneration processes for preparing saturated branched-chain fatty acids

    Science.gov (United States)

    Ferrierite zeolite solid is an excellent catalyst for the skeletal isomerization of unsaturated linear-chain fatty acids (i.e., oleic acid) to unsaturated branched-chain fatty acids (i.e., iso-oleic acid) follow by hydrogenation to give saturated branched-chain fatty acids (i.e., isostearic acid). ...

  19. Poly-Acrylic Acid Derivatives as Diesel Flow Improver for Paraffin-Based Daqing Diesel

    Institute of Scientific and Technical Information of China (English)

    Cuiyu Jiang; Ming Xu; Xiaoli Xi; Panlun Qi; Hongyan Shang

    2006-01-01

    Since the diesel products from paraffin-based Daqing crude oil showed low sensitivity to certain commercial diesel pour point depressant (PPDs) that resulted from the high content of paraffin, certain poly-acrylic acid derivatives (PADE) with-COOR,-COOH,-CONHR, and -COO-NH3+R groups by molecular design on the mechanics of diesel; PPDs were synthesized and evaluated as cold flow improver for Daqing 0# diesel in this paper. The pure PADE was superior to the commercial PPDs and displayed a substantial ability of wax crystals dispersion. There was a synergistic effect among the PADE and T1804 and secondary amine. The synergism clearly improved the low temperature performance of Daqing diesel products and could reduce the cold filter plugging point of 0# diesel by 6-7 ℃.

  20. Phosphoric acid pretreatment of Achyranthes aspera and Sida acuta weed biomass to improve enzymatic hydrolysis.

    Science.gov (United States)

    Siripong, Premjet; Duangporn, Premjet; Takata, Eri; Tsutsumi, Yuji

    2016-03-01

    Achyranthes aspera and Sida acuta, two types of weed biomass are abundant and waste in Thailand. We focus on them as novel feedstock for bio-ethanol production because they contain high-cellulose content (45.9% and 46.9%, respectively) and unutilized material. Phosphoric acid (70%, 75%, and 80%) was employed for the pretreatment to improve by enzymatic hydrolysis. The pretreatment process removed most of the xylan and a part of the lignin from the weeds, while most of the glucan remained. The cellulose conversion to glucose was greater for pretreated A. aspera (86.2 ± 0.3%) than that of the pretreated S. acuta (82.2 ± 1.1%). Thus, the removal of hemicellulose significantly affected the efficiency of the enzymatic hydrolysis. The scanning electron microscopy images showed the exposed fibrous cellulose on the cell wall surface, and this substantial change of the surface structure contributed to improving the enzyme accessibility.

  1. Improvement in Aqueous Solubility of Retinoic Acid Receptor (RAR) Agonists by Bending the Molecular Structure.

    Science.gov (United States)

    Hiramatsu, Michiaki; Ichikawa, Yuki; Tomoshige, Shusuke; Makishima, Makoto; Muranaka, Atsuya; Uchiyama, Masanobu; Yamaguchi, Takao; Hashimoto, Yuichi; Ishikawa, Minoru

    2016-08-01

    Aqueous solubility is a key requirement for many functional molecules, e. g., drug candidates. Decrease of the partition coefficient (log P) by chemical modification, i.e., introduction of hydrophilic group(s) into molecules, is a classical strategy for improving aqueous solubility. We have been investigating alternative strategies for improving the aqueous solubility of pharmaceutical compounds by disrupting intermolecular interactions. Here, we show that introducing a bend into the molecular structure of retinoic acid receptor (RAR) agonists by changing the substitution pattern from para to meta or ortho dramatically enhances aqueous solubility by up to 890-fold. We found that meta analogs exhibit similar hydrophobicity to the parent para compound, and have lower melting points, supporting the idea that the increase of aqueous solubility was due to decreased intermolecular interactions in the solid state as a result of the structural changes. PMID:27378357

  2. Biological Function of Acetic Acid-Improvement in Obesity and Glucose Tolerance by Acetic Acid in Type 2 Diabetic Rats.

    Science.gov (United States)

    Yamashita, Hiromi

    2016-07-29

    Fatty acids derived from adipose tissue are oxidized by β-oxidation to form ketone bodies as final products under the starving condition. Previously, we found that free acetic acid was formed concomitantly with the production of ketone bodies in isolated rat liver perfusion, and mitochondrial acetyl CoA hydrolase was appeared to be involved with the acetic acid production. It was revealed that acetic acid was formed as a final product of enhanced β-oxidation of fatty acids and utilized as a fuel in extrahepatic tissues under the starving condition. Under the fed condition, β-oxidation is suppressed and acetic acid production is decreased. When acetic acid was taken daily by obesity-linked type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats under the fed condition, it protected OLETF rats against obesity. Furthermore, acetic acid contributed to protect from the accumulation of lipid in the liver as well as abdominal fat in OLETF rats. Transcripts of lipogenic genes in the liver were decreased, while transcripts of myoglobin and Glut4 genes in abdominal muscles were increased in the acetic acid-administered OLETF rats. It is indicated that exogenously administered acetic acid would have effects on lipid metabolism in both the liver and the skeletal muscles, and have function that works against obesity and obesity-linked type 2 diabetes.

  3. The involvement of cholinergic neurons in the spreading of tau pathology

    Directory of Open Access Journals (Sweden)

    Diana eSimon

    2013-06-01

    Full Text Available Long time ago, it was described the selective loss of cholinergic neurons during the development of Alzheimer disease. Recently, it has been suggested that tau protein may play a role in that loss of cholinergic neurons through a mechanism involving the interaction of extracellular tau with M1/M3 muscarinic receptors present in the cholinergic neurons. This interaction between tau and muscarinic receptors may be a way, although not the only one, to explain the spreading of tau pathology occurring in Alzheimer disease.

  4. Cholinergic denervation of the hippocampal formation does not produce long-term changes in glucose metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Harrell, L.E.; Davis, J.N.

    1984-07-01

    Decreased glucose metabolism is found in Alzheimer's disease associated with a loss of cholinergic neurons. The relationship between the chronic cholinergic denervation produced by medial septal lesions and glucose metabolism was studied using 2-deoxy-D-(/sup 3/H)glucose in the rat hippocampal formation. Hippocampal glucose metabolism was increased 1 week after medial septal lesions. Three weeks after lesions, glucose metabolism was profoundly suppressed in all regions. By 3 months, intraregional hippocampal glucose metabolism had returned to control values. Our results demonstrate that chronic cholinergic denervation of the hippocampal formation does not result in permanent alterations of metabolic activity.

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

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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

  6. SULFATION OF PACHYMAN WITH CHLOROSULFONIC ACID USING THE IMPROVED WOLFROM METHOD

    Institute of Scientific and Technical Information of China (English)

    Qun Chen; Ai-yun Wang; Tian-tong Li; Cheng-fu Li; Qing-cai Jiao

    2006-01-01

    High purity polysaccharide of pachyman was isolated from the powder of Poria cocos sclerotium with an yield of 77.8%. The intrinsic viscosity of polysaccharide was found to be 78.95 mL/g in DMSO solution at 25℃. The isolated polysaccharide was reacted with chlorosulfonic acid to obtain pachyman sulfate using the improved Wolfrom method. The results of the orthogonality experiment on the sulfation reaction identified that the effectiveness of the reaction conditions on the degree of sulfation and the value of intrinsic viscosity is in the following order: molar ratio of chlorosulfonic acid to glucoside (3-5) > reaction temperature (60-80℃) > reaction time (1-2 h). The kinetic studies of the pachyman sulfationindicated that the hydrolysis is accompanied with the sulfation process. The decrease in intrinsic viscosity of the sulfated pachyman is proportional to the increase in the degree of sulfation under the mild reaction conditions of < 80℃,chlorosulfonic acid/glucoside mole ratio < 5, and reaction time < 2 h. Beyond the above reaction conditions, excessive loss of -OH group occurs during hydrolysis. The NMR results indicated a complete sulfation on C-6 and a partial sulfation on the C-2 and C-4 of glucoside.

  7. Improving phosphorus availability in an acid soil using organic amendments produced from agroindustrial wastes.

    Science.gov (United States)

    Ch'ng, Huck Ywih; Ahmed, Osumanu Haruna; Majid, Nik Muhamad Ab

    2014-01-01

    In acid soils, soluble inorganic phosphorus is fixed by aluminium and iron. To overcome this problem, acid soils are limed to fix aluminium and iron but this practice is not economical. The practice is also not environmentally friendly. This study was conducted to improve phosphorus availability using organic amendments (biochar and compost produced from chicken litter and pineapple leaves, resp.) to fix aluminium and iron instead of phosphorus. Amending soil with biochar or compost or a mixture of biochar and compost increased total phosphorus, available phosphorus, inorganic phosphorus fractions (soluble inorganic phosphorus, aluminium bound inorganic phosphorus, iron bound inorganic phosphorus, redundant soluble inorganic phosphorus, and calcium bound phosphorus), and organic phosphorus. This was possible because the organic amendments increased soil pH and reduced exchangeable acidity, exchangeable aluminium, and exchangeable iron. The findings suggest that the organic amendments altered soil chemical properties in a way that enhanced the availability of phosphorus in this study. The amendments effectively fixed aluminium and iron instead of phosphorus, thus rendering phosphorus available by keeping the inorganic phosphorus in a bioavailable labile phosphorus pool for a longer period compared with application of Triple Superphosphate without organic amendments. PMID:25032229

  8. Whiteness improvement of citric acid crosslinked cotton fabrics: H2O2 bleaching under alkaline condition.

    Science.gov (United States)

    Tang, Peixin; Ji, Bolin; Sun, Gang

    2016-08-20

    Polycarboxylic acids have been employed as formaldehyde-free crosslinking agents in anti-wrinkle treatment for cotton fabrics. Cotton fabrics treated by citric acid (CA) catalyzed with effective catalysts have shown satisfactory anti-wrinkle properties. Meanwhile, CA is a natural-based and environmental friendly compound. However, the yellowing of CA treated fabrics is a stumbling block for its practical application. Due to the fact that CA firstly forms aconitic acid (AA) before forming anhydrides, the cause of the yellowing, hydrogen peroxide (H2O2) bleaching was adopted to treat the CA treated fabrics in order to break the CC bond structure and reduce the yellow color but retaining the desired anti-wrinkle properties. Thermogravimetric analysis and Fourier transformed infrared spectroscopy were employed to investigate the reactions. The results revealed that the H2O2 bleaching can effectively improve the whiteness and also maintain a good anti-wrinkle performance of the CA treated fabrics under an appropriate bleaching temperature and time. PMID:27178918

  9. Microfluidic Preparation of Polymer-Nucleic Acid Nanocomplexes Improves Nonviral Gene Transfer

    Science.gov (United States)

    Grigsby, Christopher L.; Ho, Yi-Ping; Lin, Chao; Engbersen, Johan F. J.; Leong, Kam W.

    2013-11-01

    As the designs of polymer systems used to deliver nucleic acids continue to evolve, it is becoming increasingly apparent that the basic bulk manufacturing techniques of the past will be insufficient to produce polymer-nucleic acid nanocomplexes that possess the uniformity, stability, and potency required for their successful clinical translation and widespread commercialization. Traditional bulk-prepared products are often physicochemically heterogeneous and may vary significantly from one batch to the next. Here we show that preparation of bioreducible nanocomplexes with an emulsion-based droplet microfluidic system produces significantly improved nanoparticles that are up to fifty percent smaller, more uniform, and are less prone to aggregation. The intracellular integrity of nanocomplexes prepared with this microfluidic method is significantly prolonged, as detected using a high-throughput flow cytometric quantum dot Förster resonance energy transfer nanosensor system. These physical attributes conspire to consistently enhance the delivery of both plasmid DNA and messenger RNA payloads in stem cells, primary cells, and human cell lines. Innovation in processing is necessary to move the field toward the broader clinical implementation of safe and effective nonviral nucleic acid therapeutics, and preparation with droplet microfluidics represents a step forward in addressing the critical barrier of robust and reproducible nanocomplex production.

  10. Environmental Life Cycle Assessment of Diets with Improved Omega-3 Fatty Acid Profiles

    Science.gov (United States)

    Coelho, Carla R. V.; Pernollet, Franck; van der Werf, Hayo M. G.

    2016-01-01

    A high incidence of cardiovascular disease is observed worldwide, and dietary habits are one of the risk factors for these diseases. Omega-3 polyunsaturated fatty acids in the diet help to prevent cardiovascular disease. We used life cycle assessment to analyse the potential of two strategies to improve the nutritional and environmental characteristics of French diets: 1) modifying diets by changing the quantities and proportions of foods and 2) increasing the omega-3 contents in diets by replacing mainly animal foods with equivalent animal foods having higher omega-3 contents. We also investigated other possibilities for reducing environmental impacts. Our results showed that a diet compliant with nutritional recommendations for macronutrients had fewer environmental impacts than the current average French diet. Moving from an omnivorous to a vegetarian diet further reduced environmental impacts. Increasing the omega-3 contents in animal rations increased Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) in animal food products. Providing these enriched animal foods in human diets increased their EPA and DHA contents without affecting their environmental impacts. However, in diets that did not contain fish, EPA and DHA contents were well below the levels recommended by health authorities, despite the inclusion of animal products enriched in EPA and DHA. Reducing meat consumption and avoidable waste at home are two main avenues for reducing environmental impacts of diets. PMID:27504959

  11. Improving phosphorus availability in an acid soil using organic amendments produced from agroindustrial wastes.

    Science.gov (United States)

    Ch'ng, Huck Ywih; Ahmed, Osumanu Haruna; Majid, Nik Muhamad Ab

    2014-01-01

    In acid soils, soluble inorganic phosphorus is fixed by aluminium and iron. To overcome this problem, acid soils are limed to fix aluminium and iron but this practice is not economical. The practice is also not environmentally friendly. This study was conducted to improve phosphorus availability using organic amendments (biochar and compost produced from chicken litter and pineapple leaves, resp.) to fix aluminium and iron instead of phosphorus. Amending soil with biochar or compost or a mixture of biochar and compost increased total phosphorus, available phosphorus, inorganic phosphorus fractions (soluble inorganic phosphorus, aluminium bound inorganic phosphorus, iron bound inorganic phosphorus, redundant soluble inorganic phosphorus, and calcium bound phosphorus), and organic phosphorus. This was possible because the organic amendments increased soil pH and reduced exchangeable acidity, exchangeable aluminium, and exchangeable iron. The findings suggest that the organic amendments altered soil chemical properties in a way that enhanced the availability of phosphorus in this study. The amendments effectively fixed aluminium and iron instead of phosphorus, thus rendering phosphorus available by keeping the inorganic phosphorus in a bioavailable labile phosphorus pool for a longer period compared with application of Triple Superphosphate without organic amendments.

  12. Improving Phosphorus Availability in an Acid Soil Using Organic Amendments Produced from Agroindustrial Wastes

    Directory of Open Access Journals (Sweden)

    Huck Ywih Ch’ng

    2014-01-01

    Full Text Available In acid soils, soluble inorganic phosphorus is fixed by aluminium and iron. To overcome this problem, acid soils are limed to fix aluminium and iron but this practice is not economical. The practice is also not environmentally friendly. This study was conducted to improve phosphorus availability using organic amendments (biochar and compost produced from chicken litter and pineapple leaves, resp. to fix aluminium and iron instead of phosphorus. Amending soil with biochar or compost or a mixture of biochar and compost increased total phosphorus, available phosphorus, inorganic phosphorus fractions (soluble inorganic phosphorus, aluminium bound inorganic phosphorus, iron bound inorganic phosphorus, redundant soluble inorganic phosphorus, and calcium bound phosphorus, and organic phosphorus. This was possible because the organic amendments increased soil pH and reduced exchangeable acidity, exchangeable aluminium, and exchangeable iron. The findings suggest that the organic amendments altered soil chemical properties in a way that enhanced the availability of phosphorus in this study. The amendments effectively fixed aluminium and iron instead of phosphorus, thus rendering phosphorus available by keeping the inorganic phosphorus in a bioavailable labile phosphorus pool for a longer period compared with application of Triple Superphosphate without organic amendments.

  13. Environmental Life Cycle Assessment of Diets with Improved Omega-3 Fatty Acid Profiles.

    Science.gov (United States)

    Coelho, Carla R V; Pernollet, Franck; van der Werf, Hayo M G

    2016-01-01

    A high incidence of cardiovascular disease is observed worldwide, and dietary habits are one of the risk factors for these diseases. Omega-3 polyunsaturated fatty acids in the diet help to prevent cardiovascular disease. We used life cycle assessment to analyse the potential of two strategies to improve the nutritional and environmental characteristics of French diets: 1) modifying diets by changing the quantities and proportions of foods and 2) increasing the omega-3 contents in diets by replacing mainly animal foods with equivalent animal foods having higher omega-3 contents. We also investigated other possibilities for reducing environmental impacts. Our results showed that a diet compliant with nutritional recommendations for macronutrients had fewer environmental impacts than the current average French diet. Moving from an omnivorous to a vegetarian diet further reduced environmental impacts. Increasing the omega-3 contents in animal rations increased Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) in animal food products. Providing these enriched animal foods in human diets increased their EPA and DHA contents without affecting their environmental impacts. However, in diets that did not contain fish, EPA and DHA contents were well below the levels recommended by health authorities, despite the inclusion of animal products enriched in EPA and DHA. Reducing meat consumption and avoidable waste at home are two main avenues for reducing environmental impacts of diets. PMID:27504959

  14. In Vitro bile acid binding of kale, mustard greens, broccoli, cabbage and green bell pepper improves with microwave cooking

    Science.gov (United States)

    Bile acid binding potential of foods and food fractions has been related to lowering the risk of heart disease and that of cancer. Sautéing or steam cooking has been observed to significantly improve bile acid binding of green/leafy vegetables. It was hypothesized that microwave cooking could impr...

  15. Fed-batch Fermentation of Lactic Acid Bacteria to Improve Biomass Production: A Theoretical Approach

    Science.gov (United States)

    Beng Lee, Boon; Tham, Heng Jin; Chan, Eng Seng

    Recently, fed-batch fermentation has been introduced in an increasing number of fermentation processes. Previous researches showed that fed-batch fermentation can increase the biomass yield of many strains. Improvement of the biomass yield is interested because biomass from lactic acid bacteria (LAB) fermentation is widely used in food and pharmaceutical industry. The aim of this research is to study the ability and feasibility of fed-batch fermentation to improve biomass production of LAB. Appropriate model has been selected from literature. Monod equation described the substrate limitation of LAB and the product inhibition of LAB follows a non-competitive model. Furthermore, the lactic acid production follows Luedeking and Piret model. Then the models are applied to simulate the fermentation of batch and fed-batch cultures by using MATLAB. From the results of simulation, fed-batch fermentation showed that substrate limitation and substrate inhibition can be avoided. Besides that, the variable volume fed-batch fermentation also showed that product inhibition can be eliminated by diluting the product concentration with added fresh feed. However, it was found that fed-batch fermentation is not economically feasible because large amount of substrate is required to reduce the product inhibition effect. Therefore, fed-batch fermentation plays more importance role if the fermentation strain has high Ks value or low Kp value.

  16. Improved cadmium uptake and accumulation in the hyperaccumulator Sedum alfredii: the impact of citric acid and tartaric acid* #

    OpenAIRE

    Lu, Ling-li; Tian, Sheng-ke; Yang, Xiao-e; Peng, Hong-yun; Li, Ting-qiang

    2013-01-01

    The elucidation of a natural strategy for metal hyperaccumulation enables the rational design of technologies for the clean-up of metal-contaminated soils. Organic acid has been suggested to be involved in toxic metallic element tolerance, translocation, and accumulation in plants. The impact of exogenous organic acids on cadmium (Cd) uptake and translocation in the zinc (Zn)/Cd co-hyperaccumulator Sedum alfredii was investigated in the present study. By the addition of organic acids, short-t...

  17. Cholinergic urethral brush cells are widespread throughout placental mammals.

    Science.gov (United States)

    Deckmann, Klaus; Krasteva-Christ, Gabriela; Rafiq, Amir; Herden, Christine; Wichmann, Judy; Knauf, Sascha; Nassenstein, Christina; Grevelding, Christoph G; Dorresteijn, Adriaan; Chubanov, Vladimir; Gudermann, Thomas; Bschleipfer, Thomas; Kummer, Wolfgang

    2015-11-01

    We previously identified a population of cholinergic epithelial cells in murine, human and rat urethrae that exhibits a structural marker of brush cells (villin) and expresses components of the canonical taste transduction signaling cascade (α-gustducin, phospholipase Cβ2 (PLCβ2), transient receptor potential cation channel melanostatin 5 (TRPM5)). These cells serve as sentinels, monitoring the chemical composition of the luminal content for potentially hazardous compounds such as bacteria, and initiate protective reflexes counteracting further ingression. In order to elucidate cross-species conservation of the urethral chemosensory pathway we investigated the occurrence and molecular make-up of urethral brush cells in placental mammals. We screened 11 additional species, at least one in each of the five mammalian taxonomic units primates, carnivora, perissodactyla, artiodactyla and rodentia, for immunohistochemical labeling of the acetylcholine synthesizing enzyme, choline acetyltransferase (ChAT), villin, and taste cascade components (α-gustducin, PLCβ2, TRPM5). Corresponding to findings in previously investigated species, urethral epithelial cells with brush cell shape were immunolabeled in all 11 mammals. In 8 species, immunoreactivities against all marker proteins and ChAT were observed, and double-labeling immunofluorescence confirmed the cholinergic nature of villin-positive and chemosensory (TRPM5-positive) cells. In cat and horse, these cells were not labeled by the ChAT antiserum used in this study, and unspecific reactions of the secondary antiserum precluded conclusions about ChAT-expression in the bovine epithelium. These data indicate that urethral brush cells are widespread throughout the mammalian kingdom and evolved not later than about 64.5millionyears ago. PMID:26044348

  18. Cholinergic urethral brush cells are widespread throughout placental mammals.

    Science.gov (United States)

    Deckmann, Klaus; Krasteva-Christ, Gabriela; Rafiq, Amir; Herden, Christine; Wichmann, Judy; Knauf, Sascha; Nassenstein, Christina; Grevelding, Christoph G; Dorresteijn, Adriaan; Chubanov, Vladimir; Gudermann, Thomas; Bschleipfer, Thomas; Kummer, Wolfgang

    2015-11-01

    We previously identified a population of cholinergic epithelial cells in murine, human and rat urethrae that exhibits a structural marker of brush cells (villin) and expresses components of the canonical taste transduction signaling cascade (α-gustducin, phospholipase Cβ2 (PLCβ2), transient receptor potential cation channel melanostatin 5 (TRPM5)). These cells serve as sentinels, monitoring the chemical composition of the luminal content for potentially hazardous compounds such as bacteria, and initiate protective reflexes counteracting further ingression. In order to elucidate cross-species conservation of the urethral chemosensory pathway we investigated the occurrence and molecular make-up of urethral brush cells in placental mammals. We screened 11 additional species, at least one in each of the five mammalian taxonomic units primates, carnivora, perissodactyla, artiodactyla and rodentia, for immunohistochemical labeling of the acetylcholine synthesizing enzyme, choline acetyltransferase (ChAT), villin, and taste cascade components (α-gustducin, PLCβ2, TRPM5). Corresponding to findings in previously investigated species, urethral epithelial cells with brush cell shape were immunolabeled in all 11 mammals. In 8 species, immunoreactivities against all marker proteins and ChAT were observed, and double-labeling immunofluorescence confirmed the cholinergic nature of villin-positive and chemosensory (TRPM5-positive) cells. In cat and horse, these cells were not labeled by the ChAT antiserum used in this study, and unspecific reactions of the secondary antiserum precluded conclusions about ChAT-expression in the bovine epithelium. These data indicate that urethral brush cells are widespread throughout the mammalian kingdom and evolved not later than about 64.5millionyears ago.

  19. Impact of basal forebrain cholinergic inputs on basolateral amygdala neurons.

    Science.gov (United States)

    Unal, Cagri T; Pare, Denis; Zaborszky, Laszlo

    2015-01-14

    In addition to innervating the cerebral cortex, basal forebrain cholinergic (BFc) neurons send a dense projection to the basolateral nucleus of the amygdala (BLA). In this study, we investigated the effect of near physiological acetylcholine release on BLA neurons using optogenetic tools and in vitro patch-clamp recordings. Adult transgenic mice expressing cre-recombinase under the choline acetyltransferase promoter were used to selectively transduce BFc neurons with channelrhodopsin-2 and a reporter through the injection of an adeno-associated virus. Light-induced stimulation of BFc axons produced different effects depending on the BLA cell type. In late-firing interneurons, BFc inputs elicited fast nicotinic EPSPs. In contrast, no response could be detected in fast-spiking interneurons. In principal BLA neurons, two different effects were elicited depending on their activity level. When principal BLA neurons were quiescent or made to fire at low rates by depolarizing current injection, light-induced activation of BFc axons elicited muscarinic IPSPs. In contrast, with stronger depolarizing currents, eliciting firing above ∼ 6-8 Hz, these muscarinic IPSPs lost their efficacy because stimulation of BFc inputs prolonged current-evoked afterdepolarizations. All the effects observed in principal neurons were dependent on muscarinic receptors type 1, engaging different intracellular mechanisms in a state-dependent manner. Overall, our results suggest that acetylcholine enhances the signal-to-noise ratio in principal BLA neurons. Moreover, the cholinergic engagement of afterdepolarizations may contribute to the formation of stimulus associations during fear-conditioning tasks where the timing of conditioned and unconditioned stimuli is not optimal for the induction of synaptic plasticity.

  20. Epoxyeicosatrienoic acids pretreatment improves amyloid β-induced mitochondrial dysfunction in cultured rat hippocampal astrocytes.

    Science.gov (United States)

    Sarkar, Pallabi; Zaja, Ivan; Bienengraeber, Martin; Rarick, Kevin R; Terashvili, Maia; Canfield, Scott; Falck, John R; Harder, David R

    2014-02-15

    Amyloid-β (Aβ) has long been implicated as a causative protein in Alzheimer's disease. Cellular Aβ accumulation is toxic and causes mitochondrial dysfunction, which precedes clinical symptoms of Alzheimer's disease pathology. In the present study, we explored the possible use of epoxyeicosatrienoic acids (EETs), epoxide metabolites of arachidonic acid, as therapeutic target against Aβ-induced mitochondrial impairment using cultured neonatal hippocampal astrocytes. Inhibition of endogenous EET production by a selective epoxygenase inhibitor, MS-PPOH, caused a greater reduction in mitochondrial membrane potential in the presence of Aβ (1, 10 μM) exposure versus absence of Aβ. MS-PPOH preincubation also aggravated Aβ-induced mitochondrial fragmentation. Preincubation of the cells with either 14,15- or 11,12-EET prevented this mitochondrial depolarization and fragmentation. EET pretreatment also further improved the reduction observed in mitochondrial oxygen consumption in the presence of Aβ. Preincubation of the cells with EETs significantly improved cellular respiration under basal condition and in the presence of the protonophore, carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP). The uncoupling of ATP synthase from the electron transfer chain that occurred in Aβ-treated cells was also prevented by preincubation with EETs. Lastly, cellular reactive oxygen species production, a hallmark of Aβ toxicity, also showed significant reduction in the presence of EETs. We have previously shown that Aβ reduces EET synthesis in rat brain homogenates and cultured hippocampal astrocytes and neurons (Sarkar P, Narayanan J, Harder DR. Differential effect of amyloid beta on the cytochrome P450 epoxygenase activity in rat brain. Neuroscience 194: 241-249, 2011). We conclude that reduction of endogenous EETs may be one of the mechanisms through which Aβ inflicts toxicity and thus supplementing the cells with exogenous EETs improves mitochondrial dynamics and

  1. Inverse metabolic engineering based on transient acclimation of yeast improves acid-containing xylose fermentation and tolerance to formic and acetic acids.

    Science.gov (United States)

    Hasunuma, Tomohisa; Sakamoto, Takatoshi; Kondo, Akihiko

    2016-01-01

    Improving the production of ethanol from xylose is an important goal in metabolic engineering of Saccharomyces cerevisiae. Furthermore, S. cerevisiae must produce ethanol in the presence of weak acids (formate and acetate) generated during pre-treatment of lignocellulosic biomass. In this study, weak acid-containing xylose fermentation was significantly improved using cells that were acclimated to the weak acids during pre-cultivation. Transcriptome analyses showed that levels of transcripts for transcriptional/translational machinery-related genes (RTC3 and ANB1) were enhanced by formate and acetate acclimation. Recombinant yeast strains overexpressing RTC3 and ANB1 demonstrated improved ethanol production from xylose in the presence of the weak acids, along with improved tolerance to the acids. Novel metabolic engineering strategy based on the combination of short-term acclimation and system-wide analysis was developed, which can develop stress-tolerant strains in a short period of time, although conventional evolutionary engineering approach has required long periods of time to isolate inhibitor-adapted strains.

  2. Inverse metabolic engineering based on transient acclimation of yeast improves acid-containing xylose fermentation and tolerance to formic and acetic acids.

    Science.gov (United States)

    Hasunuma, Tomohisa; Sakamoto, Takatoshi; Kondo, Akihiko

    2016-01-01

    Improving the production of ethanol from xylose is an important goal in metabolic engineering of Saccharomyces cerevisiae. Furthermore, S. cerevisiae must produce ethanol in the presence of weak acids (formate and acetate) generated during pre-treatment of lignocellulosic biomass. In this study, weak acid-containing xylose fermentation was significantly improved using cells that were acclimated to the weak acids during pre-cultivation. Transcriptome analyses showed that levels of transcripts for transcriptional/translational machinery-related genes (RTC3 and ANB1) were enhanced by formate and acetate acclimation. Recombinant yeast strains overexpressing RTC3 and ANB1 demonstrated improved ethanol production from xylose in the presence of the weak acids, along with improved tolerance to the acids. Novel metabolic engineering strategy based on the combination of short-term acclimation and system-wide analysis was developed, which can develop stress-tolerant strains in a short period of time, although conventional evolutionary engineering approach has required long periods of time to isolate inhibitor-adapted strains. PMID:26521247

  3. Effects of cholinergic deafferentation of the rhinal cortex on visual recognition memory in monkeys

    Science.gov (United States)

    Turchi, Janita; Saunders, Richard C.; Mishkin, Mortimer

    2005-01-01

    Excitotoxic lesion studies have confirmed that the rhinal cortex is essential for visual recognition ability in monkeys. To evaluate the mnemonic role of cholinergic inputs to this cortical region, we compared the visual recognition performance of monkeys given rhinal cortex infusions of a selective cholinergic immunotoxin, ME20.4-SAP, with the performance of monkeys given control infusions into this same tissue. The immunotoxin, which leads to selective cholinergic deafferentation of the infused cortex, yielded recognition deficits of the same magnitude as those produced by excitotoxic lesions of this region, providing the most direct demonstration to date that cholinergic activation of the rhinal cortex is essential for storing the representations of new visual stimuli and thereby enabling their later recognition. PMID:15684066

  4. Choline metabolism as a basis for the selective vulnerability of cholinergic neurons

    Science.gov (United States)

    Wurtman, R. J.

    1992-01-01

    The unique propensity of cholinergic neurons to use choline for two purposes--ACh and membrane phosphatidylcholine synthesis--may contribute to their selective vulnerability in Alzheimer's disease and other cholinergic neurodegenerative disorders. When physiologically active, the neurons use free choline taken from the 'reservoir' in membrane phosphatidylcholine to synthesize ACh; this can lead to an actual decrease in the quantity of membrane per cell. Alzheimer's disease (but not Down's syndrome, or other neurodegenerative disorders) is associated with characteristic neurochemical lesions involving choline and ethanolamine: brain levels of these compounds are diminished, while those of glycerophosphocholine and glycerophosphoethanolamine (breakdown products of their respective membrane phosphatides) are increased, both in cholinergic and noncholinergic brain regions. Perhaps this metabolic disturbance and the tendency of cholinergic neurons to 'export' choline--in the form of ACh--underlie the selective vulnerability of the neurons. Resulting changes in membrane composition could abnormally expose intramembraneous proteins such as amyloid precursor protein to proteases.

  5. Outcome of Patients with Cholinergic Insecticide Poisoning Treated with Gastric Lavage: A Prospective Observational Cohort Study

    Directory of Open Access Journals (Sweden)

    Mekkattukunnel Andrews

    2014-12-01

    Conclusion: Number or timing of GL does not show any association with mortality while multiple GL had protective effect against development of late RF and IMS. Hence, GL might be beneficial in cholinergic insecticide poisoning.

  6. Optogenetic activation of cholinergic neurons in the PPT or LDT induces REM sleep.

    Science.gov (United States)

    Van Dort, Christa J; Zachs, Daniel P; Kenny, Jonathan D; Zheng, Shu; Goldblum, Rebecca R; Gelwan, Noah A; Ramos, Daniel M; Nolan, Michael A; Wang, Karen; Weng, Feng-Ju; Lin, Yingxi; Wilson, Matthew A; Brown, Emery N

    2015-01-13

    Rapid eye movement (REM) sleep is an important component of the natural sleep/wake cycle, yet the mechanisms that regulate REM sleep remain incompletely understood. Cholinergic neurons in the mesopontine tegmentum have been implicated in REM sleep regulation, but lesions of this area have had varying effects on REM sleep. Therefore, this study aimed to clarify the role of cholinergic neurons in the pedunculopontine tegmentum (PPT) and laterodorsal tegmentum (LDT) in REM sleep generation. Selective optogenetic activation of cholinergic neurons in the PPT or LDT during non-REM (NREM) sleep increased the number of REM sleep episodes and did not change REM sleep episode duration. Activation of cholinergic neurons in the PPT or LDT during NREM sleep was sufficient to induce REM sleep.

  7. A combined supplementation of vitamin B12 and omega-3 fatty acids across two generations improves cardiometabolic variables in rats.

    Science.gov (United States)

    Khaire, Amrita; Rathod, Richa; Randhir, Karuna; Kale, Anvita; Joshi, Sadhana

    2016-09-14

    Our earlier studies indicate that micronutrients (vitamin B12, folic acid) and omega-3 fatty acids especially docosahexaenoic acid (DHA) are interlinked in one carbon cycle. The present study examines the effects of a sustained vitamin B12 deficiency/supplementation in the presence of omega-3 fatty acids across two generations on the pregnancy outcome and cardiometabolic profile [blood pressure, plasma lipid profile (cholesterol and triglycerides), plasma/liver fatty acid profile and hepatic lipid metabolism] in the second generation adult Wistar rat offspring. Two generations of animals were fed the following diets: control; vitamin B12 deficient; vitamin B12 supplemented; vitamin B12 deficient diet supplemented with omega-3 fatty acids; vitamin B12 and omega-3 fatty acid supplemented diets. Male offspring were sacrificed at 3 months of age. Vitamin B12 deficiency lowered the weight gain (p pregnancy, increased systolic (p Vitamin B12 supplementation showed weight gain, blood pressure and the fatty acid profile similar to the control. However, it increased (p vitamin B12 deficient group lowered the weight gain although the levels of cardiometabolic variables were comparable to the control. Omega-3 fatty acid supplementation in the presence of vitamin B12 improved the pregnancy outcome and all cardio-metabolic variables. Our study highlights the adverse effects of sustained vitamin B12 deficiency across two generations on the pregnancy outcome, fatty acid profile and blood pressure while a combined supplementation of vitamin B12 and omega-3 fatty acids is beneficial. PMID:27528436

  8. Improving co-amorphous drug formulations by the addition of the highly water soluble amino acid proline

    DEFF Research Database (Denmark)

    Jensen, Katrine Birgitte Tarp; Löbmann, Korbinian; Rades, Thomas;

    2014-01-01

    by combining the model drug, naproxen (NAP), with an amino acid to physically stabilize the co-amorphous system (tryptophan, TRP, or arginine, ARG) and a second highly soluble amino acid (proline, PRO) for an additional improvement of the dissolution rate. Co-amorphous drug-amino acid blends were prepared......Co-amorphous drug amino acid mixtures were previously shown to be a promising approach to create physically stable amorphous systems with the improved dissolution properties of poorly water-soluble drugs. The aim of this work was to expand the co-amorphous drug amino acid mixture approach...... by ball milling and investigated for solid state characteristics, stability and the dissolution rate enhancement of NAP. All co-amorphous mixtures were stable at room temperature and 40 °C for a minimum of 84 days. PRO acted as a stabilizer for the co-amorphous system, including NAP–TRP, through enhancing...

  9. Omega-3 fatty acids plus rosuvastatin improves endothelial function in South Asians with dyslipidemia

    Directory of Open Access Journals (Sweden)

    Catalin Mindrescu

    2008-12-01

    Full Text Available Catalin Mindrescu1,2,3, Rakesh P Gupta1,3, Eileen V Hermance1, Mary C DeVoe1, Vikas R Soma1, John T Coppola1,2, Cezar S Staniloae1,21Comprehensive Cardiovascular Center, Saint Vincent’s Hospital Manhattan, New York, NY, USA; 2New York Medical College, Valhalla, NY, USA; 3Rakesh P Gupta and Catalin Mindrescu contributed equally to this article.Background: The present study was undertaken to investigate the effect of statins plus omega-3 polyunsaturated fatty acids (PUFAs on endothelial function and lipid profile in South Asians with dyslipidemia and endothelial dysfunction, a population at high risk for premature coronary artery disease.Methods: Thirty subjects were randomized to rosuvastatin 10 mg and omega-3-PUFAs 4 g or rosuvastatin 10 mg. After 4 weeks, omega-3-PUFAs were removed from the first group and added to subjects in the second group. All subjects underwent baseline, 4-, and 8-week assessment of endothelial function and lipid profile.Results: Compared to baseline, omega-3-PUFAs plus rosuvastatin improved endothelial-dependent vasodilation (EDV: −1.42% to 11.36%, p = 0.001, and endothelial-independent vasodilation (EIV: 3.4% to 17.37%, p = 0.002. These effects were lost when omega-3-PUFAs were removed (EDV: 11.36% to 0.59%, p = 0.003. In the second group, rosuvastatin alone failed to improve both EDV and EIV compared to baseline. However, adding omega-3-PUFAs to rosuvastatin, significantly improved EDV (−0.66% to 14.73%, p = 0.001 and EIV (11.02% to 24.5%, p = 0.001. Addition of omega-3-PUFAs further improved the lipid profile (triglycerides 139 to 91 mg/dl, p = 0.006, low-density lipoprotein cholesterol 116 to 88 mg/dl, p = 0.014.Conclusions: Combined therapy with omega-3-PUFAs and rosuvastatin improves endothelial function in South Asian subjects with dyslipidemia and endothelial dysfunction.Keywords: omega-3 fatty acids, endothelial function, South Asians, dyslipidemia, rosuvastatin

  10. Improved Proteomic Analysis Following Trichloroacetic Acid Extraction of Bacillus anthracis Spore Proteins

    Energy Technology Data Exchange (ETDEWEB)

    Kaiser, Brooke LD; Wunschel, David S.; Sydor, Michael A.; Warner, Marvin G.; Wahl, Karen L.; Hutchison, Janine R.

    2015-08-07

    Proteomic analysis of bacterial samples provides valuable information about cellular responses and functions under different environmental pressures. Proteomic analysis is dependent upon efficient extraction of proteins from bacterial samples without introducing bias toward extraction of particular protein classes. While no single method can recover 100% of the bacterial proteins, selected protocols can improve overall protein isolation, peptide recovery, or enrich for certain classes of proteins. The method presented here is technically simple and does not require specialized equipment such as a mechanical disrupter. Our data reveal that for particularly challenging samples, such as B. anthracis Sterne spores, trichloroacetic acid extraction improved the number of proteins identified within a sample compared to bead beating (714 vs 660, respectively). Further, TCA extraction enriched for 103 known spore specific proteins whereas bead beating resulted in 49 unique proteins. Analysis of C. botulinum samples grown to 5 days, composed of vegetative biomass and spores, showed a similar trend with improved protein yields and identification using our method compared to bead beating. Interestingly, easily lysed samples, such as B. anthracis vegetative cells, were equally as effectively processed via TCA and bead beating, but TCA extraction remains the easiest and most cost effective option. As with all assays, supplemental methods such as implementation of an alternative preparation method may provide additional insight to the protein biology of the bacteria being studied.

  11. Clavulanic acid production by Streptomyces clavuligerus: biogenesis, regulation and strain improvement.

    Science.gov (United States)

    Paradkar, Ashish

    2013-07-01

    Clavulanic acid (CA) is a potent β-lactamase inhibitor produced by Streptomyces clavuligerus and has been successfully used in combination with β-lactam antibiotics (for example, Augmentin) to treat infections caused by β-lactamase-producing pathogens. Since the discovery of CA in the late 1970s, significant information has accumulated on its biosynthesis, and regarding molecular mechanisms involved in the regulation of its production. Notably, the genes directing CA biosynthesis are clustered along with the genes responsible for the biosynthesis of the β-lactam antibiotic, cephamycin C, and co-regulated, which makes this organism unique in that the production of an antibiotic and production of a small molecule to protect the antibiotic from its enzymatic degradation are controlled by shared mechanisms. Traditionally, the industrial strain improvement programs have relied significantly on random mutagenesis and selection approach. However, the recent availability of the genome sequence of S. clavuligerus along with the capability to build metabolic models, and ability to engineer the organism by directed approaches, has created exciting opportunities to improve strain productivity more efficiently. This review will include focus mainly on the gene organization of the CA biosynthetic genes, regulatory mechanisms that affect its production, and will include perspectives on improving strain productivity.

  12. Improvement of Vegetative and Reproductive Growth of ‘Camarosa’ Strawberry: Role of Humic Acid, Zn, and B

    Directory of Open Access Journals (Sweden)

    Somaye Rafeii

    2015-03-01

    Full Text Available This experiment was conducted with the aim to improve vegetative and reproductive growth of strawberry (Fragaria × ananassa Duch. cv. ‘Camarosa’ using humic acid, zinc sulfate (ZnSO4, and boric acid. We evaluated applications of humic acid at 0, 20 and 40 mg·L-1, ZnSO4 at 0, 50 and 100 mg·L-1, and boric acid at 0, 50 and 100 mg·L-1 at 30 days after planting and blooming stage on growth of strawberry cv. ‘Camarosa’. Results indicated that humic acid, ZnSo4, and boric acid application improved reproductive and vegetative characteristics compared to control treatment. The results showed, that plants treated with humic acid, ZnSO4, and boric acid at higher their concentrations exhibited generally higher dry weight of roots and shoots, number of flowers and inflorescences, leaf area, length of roots and shoots, length of flowering period, yield, weight of primary and secondary fruits and number of their achenes. Total yield was significantly increased by all treatments compared to control treatment at both stages of application, especially at blooming stage. Moreover, conclusion showed that the mentioned materials could have impact on vegetative and reproductive growth of strawberry generally. In this study humic acid at 40 mg L-1 at blooming stage resulted in best effects on development of strawberry cv. ‘Camarosa’.

  13. Neuroinflammation not associated with cholinergic degeneration in aged-impaired brain

    OpenAIRE

    McQuail, Joseph A.; Riddle, David R.; Nicolle, Michelle M.

    2010-01-01

    Degeneration of the cholinergic neurons in the basal forebrain and elevation of inflammatory markers are well-established hallmarks of Alzheimer's disease; however, the interplay of these processes in normal aging is not extensively studied. Consequently, we conducted a neuroanatomical investigation to quantify cholinergic neurons and activated microglia in the medial septum/vertical diagonal band (MS/VDB) of young (6 months) and aged (28 months) Fisher 344 × Brown Norway F1 rats. Aged rats i...

  14. Coordinated regulation of cholinergic motor neuron traits through a conserved terminal selector gene

    OpenAIRE

    Kratsios, Paschalis; Stolfi, Alberto; Levine, Michael; Hobert, Oliver

    2011-01-01

    Cholinergic motor neurons are defined by the co-expression of a battery of genes which encode proteins that act sequentially to synthesize, package and degrade acetylcholine and reuptake its breakdown product, choline. How expression of these critical motor neuron identity determinants is controlled and coordinated is not understood. We show here that in the nematode Caenorhabditis elegans all members of the cholinergic gene battery, as well as many other markers of terminal motor neuron fate...

  15. Higher sensitivity to cadmium induced cell death of basal forebrain cholinergic neurons: A cholinesterase dependent mechanism

    International Nuclear Information System (INIS)

    Cadmium is an environmental pollutant, which is a cause of concern because it can be greatly concentrated in the organism causing severe damage to a variety of organs including the nervous system which is one of the most affected. Cadmium has been reported to produce learning and memory dysfunctions and Alzheimer like symptoms, though the mechanism is unknown. On the other hand, cholinergic system in central nervous system (CNS) is implicated on learning and memory regulation, and it has been reported that cadmium can affect cholinergic transmission and it can also induce selective toxicity on cholinergic system at peripheral level, producing cholinergic neurons loss, which may explain cadmium effects on learning and memory processes if produced on central level. The present study is aimed at researching the selective neurotoxicity induced by cadmium on cholinergic system in CNS. For this purpose we evaluated, in basal forebrain region, the cadmium toxic effects on neuronal viability and the cholinergic mechanisms related to it on NS56 cholinergic mourine septal cell line. This study proves that cadmium induces a more pronounced, but not selective, cell death on acetylcholinesterase (AChE) on cholinergic neurons. Moreover, MTT and LDH assays showed a dose dependent decrease of cell viability in NS56 cells. The ACh treatment of SN56 cells did not revert cell viability reduction induced by cadmium, but siRNA transfection against AChE partially reduced it. Our present results provide new understanding of the mechanisms contributing to the harmful effects of cadmium on the function and viability of neurons, and the possible relevance of cadmium in the pathogenesis of neurodegenerative diseases

  16. Cholinergic axon length reduced by 300 meters in the brain of an Alzheimer mouse model

    DEFF Research Database (Denmark)

    Nikolajsen, Gitte; Jensen, Morten Skovgaard; West, Mark J.

    2011-01-01

    Modern stereological techniques have been used to show that the total length of the cholinergic fibers in the cerebral cortex of the APPswe/PS1deltaE9 mouse is reduced by almost 300 meters at 18 months of age and has a nonlinear relationship to the amount of transgenetically-induced amyloidosis. ....... These data provide rigorous quantitative morphological evidence that Alzheimer's-like amyloidosis affects the axons of the cholinergic enervation of the cerebral cortex....

  17. Ultrastructural localization of cholinergic muscarinic receptors in rat brain cortical capillaries

    OpenAIRE

    Luiten, PGM; DEJONG, GI; VANDERZEE, EA; vanDijken, H; van Dijken, H.

    1996-01-01

    Cholinergic innervation of the cerebrovasculature is known to regulate vascular tone, perfusion rate and permeability of the microvascular wall. Notably the cholinergic innervation of cerebral capillaries is of interest since these capillaries form the blood-brain barrier. Although there is a general consensus as to the presence of nicotinic and muscarinic receptors in the domain of the capillary wall, their precise anatomical position is unknown. The subcellular localization of muscarinic re...

  18. EEG sleep and the cholinergic REM induction test in anorexic and bulimic patients

    OpenAIRE

    Lauer, C.; Zulley, Jürgen; Krieg, J. C.; Riemann, D.; Berger , M.

    1988-01-01

    The electroencephalographic (EEG) sleep of 20 anorexic patients, 10 bulimic patients, and 10 age-matched healthy controls was studied. In addition, six anorexic patients and six bulimic patients had a cholinergic rapid eye movement (REM) sleep induction test (RIT) performed with the cholinergic agent RS 86. The three samples showed no major differences in sleep patterns. The same held true when attention was focused on patients who additionally met DSM-III criteria for major depression. The R...

  19. Protein kinase C mediates cholinergically regulated protein phosphorylation in a Cl(-)-secreting epithelium.

    Science.gov (United States)

    Cohn, J A

    1990-02-01

    T84 cell monolayers were used to study the cholinergic regulation of protein phosphorylation in epithelial cells. When T84 cell monolayers are labeled with 32Pi and stimulated with carbachol, six proteins exhibit altered phosphorylation. The most prominent response is a fivefold increase in labeling of p83, an acidic protein of Mr 83,000. Increasing labeling of p83 parallels stimulated secretion with respect to the onset of agonist action, agonist potency, and antagonism by atropine. However, the p83 and secretory responses differ in that the p83 response is more sustained. When T84 cell fractions are incubated with [gamma-32P]ATP, Ca2(+)-phospholipid stimulates p83 labeling. Phosphorylation of p83 also occurs when a T84 cell extract is incubated with purified protein kinase C and when intact cells are exposed to phorbol myristate acetate. p83 does not become phosphorylated in cell fractions incubated with adenosine 3',5'-cyclic monophosphate (cAMP) or in monolayers stimulated with agonists acting via cAMP. Thus carbachol stimulates the phosphorylation of an endogenous substrate for protein kinase C in T84 cells. The duration of this phosphorylation response suggests that protein kinase C may mediate a sustained response to carbachol, possibly acting to limit the duration of stimulated secretion.

  20. Significant improvement in the pore properties of SBA-15 brought about by carboxylic acids and hydrothermal treatment

    Indian Academy of Sciences (India)

    Milan Kanti Naskar; M Eswaramoorthy

    2008-01-01

    A comparative study of the pore properties of SBA-15 samples prepared under nonhydrothermal and hydrothermal conditions, in the absence and presence of carboxylic acids such as succinic, tartaric and citric acids has been carried out. In the absence of carboxylic acid, flake-like and spheroid particles were generally obtained irrespective of the preparative procedures. On the other hand, stirring of the pre-mix induces a rod-like morphology in presence of carboxylic acids. The samples prepared under non-hydrothermal conditions exhibit a higher degree of silicate condensation compared to those synthesized under hydrothermal conditions. SBA-15 samples prepared under hydrothermal conditions show higher values of the d (100) spacing independent of the presence of carboxylic acids. Presence of carboxylic acids as well as hydrothermal treatment improves the pore properties of SBA-15.

  1. Basal forebrain neurons suppress amygdala kindling via cortical but not hippocampal cholinergic projections in rats.

    Science.gov (United States)

    Ferencz, I; Leanza, G; Nanobashvili, A; Kokaia, M; Lindvall, O

    2000-06-01

    Intraventricular administration of the immunotoxin 192 IgG-saporin in rats has been shown to cause a selective loss of cholinergic afferents to the hippocampus and cortical areas, and to facilitate seizure development in hippocampal kindling. Here we demonstrate that this lesion also accelerates seizure progression when kindling is induced by electrical stimulations in the amygdala. However, whereas intraventricular 192 IgG-saporin facilitated the development of the initial stages of hippocampal kindling, the same lesion promoted the late stages of amygdala kindling. To explore the role of various parts of the basal forebrain cholinergic system in amygdala kindling, selective lesions of the cholinergic projections to either hippocampus or cortex were produced by intraparenchymal injections of 192 IgG-saporin into medial septum/vertical limb of the diagonal band or nucleus basalis, respectively. Cholinergic denervation of the cortical regions caused acceleration of amygdala kindling closely resembling that observed after the more widespread lesion induced by intraventricular 192 IgG-saporin. In contrast, removal of the cholinergic input to the hippocampus had no effect on the development of amygdala kindling. These data indicate that basal forebrain cholinergic neurons suppress kindling elicited from amygdala, and that this dampening effect is mediated via cortical but not hippocampal projections.

  2. Cholinergic Depletion in Alzheimer’s Disease Shown by [18F]FEOBV Autoradiography

    Directory of Open Access Journals (Sweden)

    Maxime J. Parent

    2013-01-01

    Full Text Available Rationale. Alzheimer’s Disease (AD is a neurodegenerative condition characterized in part by deficits in cholinergic basalocortical and septohippocampal pathways. [18F]Fluoroethoxybenzovesamicol ([18F]FEOBV, a Positron Emission Tomography ligand for the vesicular acetylcholine transporter (VAChT, is a potential molecular agent to investigate brain diseases associated with presynaptic cholinergic losses. Purpose. To demonstrate this potential, we carried out an [18F]FEOBV autoradiography study to compare postmortem brain tissues from AD patients to those of age-matched controls. Methods. [18F]FEOBV autoradiography binding, defined as the ratio between regional grey and white matter, was estimated in the hippocampus (13 controls, 8 AD and prefrontal cortex (13 controls, 11 AD. Results. [18F]FEOBV binding was decreased by 33% in prefrontal cortex, 25% in CA3, and 20% in CA1. No changes were detected in the dentate gyrus of the hippocampus, possibly because of sprouting or upregulation toward the resilient glutamatergic neurons of the dentate gyrus. Conclusion. This is the first demonstration of [18F]FEOBV focal binding changes in cholinergic projections to the cortex and hippocampus in AD. Such cholinergic synaptic (and more specifically VAChT alterations, in line with the selective basalocortical and septohippocampal cholinergic losses documented in AD, indicate that [18F]FEOBV is indeed a promising ligand to explore cholinergic abnormalities in vivo.

  3. Evaluating the evidence surrounding pontine cholinergic involvement in REM sleep generation

    Directory of Open Access Journals (Sweden)

    Kevin P Grace

    2015-09-01

    Full Text Available Rapid eye movement (REM sleep - characterized by vivid dreaming, motor paralysis, and heightened neural activity - is one of the fundamental states of the mammalian central nervous system. Initial theories of rapid eye movement (REM sleep generation posited that induction of the state required activation of the ‘pontine REM sleep generator’ by cholinergic inputs. Here we review and evaluate the evidence surrounding cholinergic involvement in REM sleep generation. We submit that: (i the capacity of pontine cholinergic neurotransmission to generate REM sleep has been firmly established by gain-of-function experiments, (ii the function of endogenous cholinergic input to REM sleep generating sites cannot be determined by gain-of-function experiments; rather, loss-of-function studies are required, (iii loss-of-function studies show that endogenous cholinergic input to the PFT is not required for REM sleep generation, and (iv Cholinergic input to the pontine REM sleep generating sites serve an accessory role in REM sleep generation: reinforcing non-REM-to-REM sleep transitions making them quicker and less likely to fail.

  4. Impairment of reward-related learning by cholinergic cell ablation in the striatum.

    Science.gov (United States)

    Kitabatake, Yasuji; Hikida, Takatoshi; Watanabe, Dai; Pastan, Ira; Nakanishi, Shigetada

    2003-06-24

    The striatum in the basal ganglia-thalamocortical circuitry is a key neural substrate that is implicated in motor balance and procedural learning. The projection neurons in the striatum are dynamically modulated by nigrostriatal dopaminergic input and intrastriatal cholinergic input. The role of intrastriatal acetylcholine (ACh) in learning behaviors, however, remains to be fully clarified. In this investigation, we examine the involvement of intrastriatal ACh in different categories of learning by selectively ablating the striatal cholinergic neurons with use of immunotoxin-mediated cell targeting. We show that selective ablation of cholinergic neurons in the striatum impairs procedural learning in the tone-cued T-maze memory task. Spatial delayed alternation in the T-maze learning test is also impaired by cholinergic cell elimination. In contrast, the deficit in striatal ACh transmission has no effect on motor learning in the rota-rod test or spatial learning in the Morris water-maze test or on contextual- and tone-cued conditioning fear responses. We also report that cholinergic cell elimination adaptively up-regulates nicotinic ACh receptors not only within the striatum but also in the cerebral cortex and substantia nigra. The present investigation indicates that cholinergic modulation in the local striatal circuit plays a pivotal role in regulation of neural circuitry involving reward-related procedural learning and working memory. PMID:12802017

  5. Lesions of the basal forebrain cholinergic system in mice disrupt idiothetic navigation.

    Directory of Open Access Journals (Sweden)

    Adam S Hamlin

    Full Text Available Loss of integrity of the basal forebrain cholinergic neurons is a consistent feature of Alzheimer's disease, and measurement of basal forebrain degeneration by magnetic resonance imaging is emerging as a sensitive diagnostic marker for prodromal disease. It is also known that Alzheimer's disease patients perform poorly on both real space and computerized cued (allothetic or uncued (idiothetic recall navigation tasks. Although the hippocampus is required for allothetic navigation, lesions of this region only mildly affect idiothetic navigation. Here we tested the hypothesis that the cholinergic medial septo-hippocampal circuit is important for idiothetic navigation. Basal forebrain cholinergic neurons were selectively lesioned in mice using the toxin saporin conjugated to a basal forebrain cholinergic neuronal marker, the p75 neurotrophin receptor. Control animals were able to learn and remember spatial information when tested on a modified version of the passive place avoidance test where all extramaze cues were removed, and animals had to rely on idiothetic signals. However, the exploratory behaviour of mice with cholinergic basal forebrain lesions was highly disorganized during this test. By contrast, the lesioned animals performed no differently from controls in tasks involving contextual fear conditioning and spatial working memory (Y maze, and displayed no deficits in potentially confounding behaviours such as motor performance, anxiety, or disturbed sleep/wake cycles. These data suggest that the basal forebrain cholinergic system plays a specific role in idiothetic navigation, a modality that is impaired early in Alzheimer's disease.

  6. Evaluating the Evidence Surrounding Pontine Cholinergic Involvement in REM Sleep Generation.

    Science.gov (United States)

    Grace, Kevin P; Horner, Richard L

    2015-01-01

    Rapid eye movement (REM) sleep - characterized by vivid dreaming, motor paralysis, and heightened neural activity - is one of the fundamental states of the mammalian central nervous system. Initial theories of REM sleep generation posited that induction of the state required activation of the "pontine REM sleep generator" by cholinergic inputs. Here, we review and evaluate the evidence surrounding cholinergic involvement in REM sleep generation. We submit that: (i) the capacity of pontine cholinergic neurotransmission to generate REM sleep has been firmly established by gain-of-function experiments, (ii) the function of endogenous cholinergic input to REM sleep generating sites cannot be determined by gain-of-function experiments; rather, loss-of-function studies are required, (iii) loss-of-function studies show that endogenous cholinergic input to the PTF is not required for REM sleep generation, and (iv) cholinergic input to the pontine REM sleep generating sites serve an accessory role in REM sleep generation: reinforcing non-REM-to-REM sleep transitions making them quicker and less likely to fail.

  7. Improved lead recovery and sulphate removal from used lead acid battery through electrokinetic technique.

    Science.gov (United States)

    Soundarrajan, C; Sivasankar, A; Maruthamuthu, S; Veluchamy, A

    2012-05-30

    This paper presents improvement in lead (Pb) recovery and sulphate removal from used Pb acid battery (ULAB) through Electrokinetic technique, a process aimed to eliminate environmental pollution that arises due to emission of gases and metal particles from the existing high temperature pyrometallurgical process. Two different cell configurations, (1) one with Nafion membrane placed between anode and middle compartments and Agar membrane between cathode and middle compartments and (2) another with only Agar membrane placed between both sides of the middle compartments were designed for the Pb and sulphate separation from ULAB. This paper concludes that the cell with only Agar membranes performed better than the cell with Nafion and Agar membranes in combinations and also explains the mechanism underlying the chemical and electrochemical processes in the cell.

  8. Combined Sewer Overflow pretreatment with chemical coagulation and a particle settler for improved peracetic acid disinfection

    DEFF Research Database (Denmark)

    Chhetri, Ravi Kumar; Bonnerup, Arne; Andersen, Henrik Rasmus

    2016-01-01

    Full scale disinfection by peracetic acid (PAA) was achieved on Combined Sewer Overflow (CSO) water, which was pre-treated physically by a fast settling-filtration unit. Disinfection of untreated CSO water using PAA was compared to treatment using a particle separator (Hydro......Separator, followed by PAA treatment during a CSO event, the treatment was sufficient to maintain microbial quality in the recipient water.......Separator®) and additional coagulation with poly-aluminum-chloride. Disinfection for Enterococcus increased with the applied dose of PAA and additional improvement was achieved when it was preceded by chemical coagulation with 5 mg L−1 poly-aluminum-chloride. When Enterococcus was reduced by treatment in the Hydro...

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

    Science.gov (United States)

    Van Hirtum, A.; Berckmans, D.

    2003-09-01

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

  10. Improved production, characterization and flocculation properties of poly (-glutamic acid produced from Bacillus Subtilis

    Directory of Open Access Journals (Sweden)

    Bhunia B

    2012-04-01

    Full Text Available Bacillus subtilis 2063 produced extracellular biopolymer whichshowed excellent flocculation activity. The biopolymer wasconfirmed as poly (γ-glutamic acid (PGA by using productcharacterization. HPLC profile showed that molecular weight ofPGA was found to be 5.8×106 Da. Improved production,Characterization and flocculation properties of PGA produced byBacillus species were studied. PGA produced by B. subtilis wasdevoid of any polysaccharides. The flocculating activity wasmarkedly stimulated by the addition of cations. The pH of reaction mixture also influenced the flocculating activity. Glycerol and ammonium chloride were found to be most useful carbon and nitrogen sources. An overall 4.24-fold increase in protease production was achieved in the design medium composed with Glycerol and ammonium chloride as a carbon and nitrogen sources as compared with basal media. PGA production increased significantly with optimized medium (21.42 gl-1 when compared with basal medium (5.06 gl-1.

  11. Lecithin-Based Nano-emulsification Improves the Bioavailability of Conjugated Linoleic Acid.

    Science.gov (United States)

    Heo, Wan; Kim, Jun Ho; Pan, Jeong Hoon; Kim, Young Jun

    2016-02-17

    In this study, we investigated the effects of lecithin-based nano-emulsification on the heat stability and bioavailability of conjugated linoleic acid (CLA) in different free fatty acid (FFA) and triglyceride (TG) forms. CLA nano-emulsion in TG form exhibited a small droplet size (70-120 nm) compared to CLA nano-emulsion in FFA form (230-260 nm). Nano-emulsification protected CLA isomers in TG form, but not in free form, against thermal decomposition during the heat treatment. The in vitro bioavailability test using monolayers of Caco-2 human intestinal cells showed that nano-emulsification increased the cellular uptake of CLA in both FFA and TG forms. More importantly, a rat feeding study showed that CLA content in small intestinal tissues or plasma was higher when CLA was emulsified, indicating an enhanced oral bioavailability of CLA by nano-emulsification. These results provide important information for development of nano-emulsion-based delivery systems that improve thermal stability and bioavailability of CLA.

  12. Age-related changes in nicotine response of cholinergic and non-cholinergic laterodorsal tegmental neurons: implications for the heightened adolescent susceptibility to nicotine addiction

    DEFF Research Database (Denmark)

    Christensen, Mark Holm; Ishibashi, Masaru; Nielsen, Michael Linnemann;

    2014-01-01

    The younger an individual starts smoking, the greater the likelihood that addiction to nicotine will develop, suggesting that neurobiological responses vary across age to the addictive component of cigarettes. Cholinergic neurons of the laterodorsal tegmental nucleus (LDT) are importantly involved...... intracellular calcium transients and inward currents. Nicotine induced a greater number of excitatory synaptic currents in the youngest animals, whereas larger amplitude inhibitory synaptic events were induced in cells from the oldest animals (P15–P34). Nicotine increased neuronal firing of cholinergic cells...

  13. Triiodothyronine activates lactate oxidation without impairing fatty acid oxidation and improves weaning from extracorporeal membrane oxygenation

    Energy Technology Data Exchange (ETDEWEB)

    Kajimoto, Masaki; Ledee, Dolena R.; Xu, Chun; Kajimoto, Hidemi; Isern, Nancy G.; Portman, Michael A.

    2014-01-01

    Background: Extracorporeal membrane oxygenation (ECMO) provides a rescue for children with severe cardiac failure. We previously showed that triiodothyronine (T3) improves cardiac function by modulating pyruvate oxidation during weaning. This study was focused on fatty acid (FA) metabolism modulated by T3 for weaning from ECMO after cardiac injury. Methods: Nineteen immature piglets (9.1-15.3 kg) were separated into 3 groups with ECMO (6.5 hours) and wean: normal circulation (Group-C);transient coronary occlusion (10 minutes) followed by ECMO (Group-IR); and IR with T3 supplementation (Group-IR-T3). 13-Carbon labeled lactate, medium-chain and long-chain FAs were infused as oxidative substrates. Substrate fractional contribution to the citric acid cycle (FC) was analyzed by 13-Carbon nuclear magnetic resonance. Results: ECMO depressed circulating T3 levels to 40% baseline at 4 hours and were restored in Group-IR-T3. Group-IR decreased cardiac power, which was not fully restorable and 2 pigs were lost because of weaning failure. Group-IR also depressed FC-lactate, while the excellent contractile function and energy efficiency in Group-IR-T3 occurred along with a marked FC-lactate increase and [ATP]/[ADP] without either decreasing FC-FAs or elevating myocardial oxygen consumption over Group-C or -IR. Conclusions: T3 releases inhibition of lactate oxidation following ischemia-reperfusion injury without impairing FA oxidation. These findings indicate that T3 depression during ECMO is maladaptive, and that restoring levels improves metabolic flux and enhances contractile function during weaning.

  14. Exogenous application of abscisic acid may improve the growth and yield of sunflower hybrids under drought

    International Nuclear Information System (INIS)

    Sunflower genotypes perform differently under different water regimes. Drought stress at various growth stages drastically reduces the growth, development and yield of sunflower hybrids. However, exogenous application of abscisic acid helps in mitigating drought stress by improving growth, development and yield of sunflower. In the present study, three sunflower hybrids viz. DK-4040 (large stature), S-278 (medium stature) and SF-187 (short stature) were exposed to varied irrigation regimes and abscisic acid application schedule i.e. T1: four irrigations with schedule (25DAS, at bud, flower initiation and at achene formation) and with no ABA spray,T/sub 2/: three irrigations with schedule (25DAS, at flower initiation and at achene formation) and with no ABA spray, T/sub 3/: three irrigations with schedule (25DAS, at flower initiation and at achene formation) and with 8 mu MABA spray at bud initiation, T/sub 4/: three irrigations with schedule (25DAS, at bud initiation and at achene formation) and with no ABA spray, T/sub 5/: three irrigations with schedule (25DAS, at bud initiation and at achene formation) and with 8 mu M ABA spray at flower initiation. Experiment was laid out in Randomized Complete Design with factorial arrangement having three replications. ABA application at bud or at flower initiation under drought stress helped in mitigating the detrimental effects by improving growth and yield of sunflower hybrids. Enhancement in drought tolerance of sunflower genotypes was better when ABA was applied at bud initiation stage than that of at flower initiation stage under drought. Improvements in head diameter, achenes per head, 1000-achene weight, achene yield, oil yield, biological yield, harvest index, leaf area index and crop growth rate was recorded. Sunflower hybrid DK-4040 showed more improvement in drought tolerance byfoliar application of ABA under water deficit stress than that of the SF-187 and S-278. It is suggested that sunflower hybrid DK 4040

  15. Improved cadmium uptake and accumulation in the hyperaccumulator Sedum alfredii:the impact of citric acid and tartaric acid

    Institute of Scientific and Technical Information of China (English)

    Ling-li LU; Sheng-ke TIAN; Xiao-e YANG; Hong-yun PENG; Ting-qiang LI

    2013-01-01

    The elucidation of a natural strategy for metal hyperaccumulation enables the rational design of technologies for the clean-up of metal-contaminated soils.Organic acid has been suggested to be involved in toxic metallic element tolerance,translocation,and accumulation in plants.The impact of exogenous organic acids on cadmium(Cd)uptake and translocation in the zinc(Zn)/Cd co-hyperaccumulator Sedum alfredii was investigated in the present study.By the addition of organic acids,short-term(2 h)root uptake of 109Cd increased significantly,and higher 109Cd contents in roots and shoots were noted 24 h after uptake,when compared to controls.About 85% of the 109Cd taken up was distributed to the shoots in plants with citric acid(CA)treatments,as compared with 75% within controls.No such effect was observed for tartaric acid(TA).Reduced growth under Cd stress was significantly alleviated by low CA.Long-term application of the two organic acids both resulted in elevated Cd in plants,but the effects varied with exposure time and levels.The results imply that CA may be involved in the processes of Cd uptake,translocation and tolerance in S.alfredii,whereas the impact of TA is mainly on the root uptake of Cd.

  16. Improved cadmium uptake and accumulation in the hyperaccumulator Sedum alfredii: the impact of citric acid and tartaric acid.

    Science.gov (United States)

    Lu, Ling-li; Tian, Sheng-ke; Yang, Xiao-e; Peng, Hong-yun; Li, Ting-qiang

    2013-02-01

    The elucidation of a natural strategy for metal hyperaccumulation enables the rational design of technologies for the clean-up of metal-contaminated soils. Organic acid has been suggested to be involved in toxic metallic element tolerance, translocation, and accumulation in plants. The impact of exogenous organic acids on cadmium (Cd) uptake and translocation in the zinc (Zn)/Cd co-hyperaccumulator Sedum alfredii was investigated in the present study. By the addition of organic acids, short-term (2 h) root uptake of (109)Cd increased significantly, and higher (109)Cd contents in roots and shoots were noted 24 h after uptake, when compared to controls. About 85% of the (109)Cd taken up was distributed to the shoots in plants with citric acid (CA) treatments, as compared with 75% within controls. No such effect was observed for tartaric acid (TA). Reduced growth under Cd stress was significantly alleviated by low CA. Long-term application of the two organic acids both resulted in elevated Cd in plants, but the effects varied with exposure time and levels. The results imply that CA may be involved in the processes of Cd uptake, translocation and tolerance in S. alfredii, whereas the impact of TA is mainly on the root uptake of Cd. PMID:23365009

  17. Improved cadmium uptake and accumulation in the hyperaccumulator Sedum alfredii: the impact of citric acid and tartaric acid* #

    Science.gov (United States)

    Lu, Ling-li; Tian, Sheng-ke; Yang, Xiao-e; Peng, Hong-yun; Li, Ting-qiang

    2013-01-01

    The elucidation of a natural strategy for metal hyperaccumulation enables the rational design of technologies for the clean-up of metal-contaminated soils. Organic acid has been suggested to be involved in toxic metallic element tolerance, translocation, and accumulation in plants. The impact of exogenous organic acids on cadmium (Cd) uptake and translocation in the zinc (Zn)/Cd co-hyperaccumulator Sedum alfredii was investigated in the present study. By the addition of organic acids, short-term (2 h) root uptake of 109Cd increased significantly, and higher 109Cd contents in roots and shoots were noted 24 h after uptake, when compared to controls. About 85% of the 109Cd taken up was distributed to the shoots in plants with citric acid (CA) treatments, as compared with 75% within controls. No such effect was observed for tartaric acid (TA). Reduced growth under Cd stress was significantly alleviated by low CA. Long-term application of the two organic acids both resulted in elevated Cd in plants, but the effects varied with exposure time and levels. The results imply that CA may be involved in the processes of Cd uptake, translocation and tolerance in S. alfredii, whereas the impact of TA is mainly on the root uptake of Cd. PMID:23365009

  18. Designing improved poly lactic-co-glycolic acid microspheres for a malarial vaccine: incorporation of alginate and polyinosinic-polycytidilic acid.

    Science.gov (United States)

    Salvador, Aiala; Igartua, Manoli; Hernández, Rosa María; Pedraz, José Luis

    2014-01-01

    Vaccination using proteins and peptides is currently gaining importance. One of the major drawbacks of this approach is the lack of an efficient immune response when the antigens are administered without adjuvants. In this study, we have taken the advantage of a combined adjuvant system in order to improve the immunogenicity of the SPf66 malarial antigen. For that purpose, we have combined poly (lactic-co-glycolic) acid microspheres, alginate, and polyinosinic polycytidilic acid. Our results show that microspheres can enhance the IgG production obtained with Freund's complete adjuvant. We have attributed this improvement to the presence of polyinosinic polycytidilic acid, since formulations comprising this adjuvant overcame the immune response from the others. In addition, our microspheres produced both IgG1 and IgG2a, leading to mixed Th1/Th2 activation, optimal for malaria vaccination. In conclusion, we have designed a preliminary formulation with a high potential for the treatment of malaria.

  19. Determination of organic acids evolution during apple cider fermentation using an improved HPLC analysis method

    NARCIS (Netherlands)

    Zhang, H.; Zhou, F.; Ji, B.; Nout, M.J.R.; Fang, Q.; Zhang, Z.

    2008-01-01

    An efficient method for analyzing ten organic acids in food, namely citric, pyruvic, malic, lactic, succinic, formic, acetic, adipic, propionic and butyric acids, using HPLC was developed. Boric acid was added into the mobile phase to separate lactic and succinic acids, and a post-column buffer solu

  20. Slight Fermentation with Lactobacillus fermentium Improves the Taste (Sugar:Acid Ratio) of Citrus (Citrus reticulata cv. chachiensis) Juice.

    Science.gov (United States)

    Yu, Yuanshan; Xiao, Gengsheng; Xu, Yujuan; Wu, Jijun; Fu, Manqin; Wen, Jing

    2015-11-01

    The aim of this study was to evaluate the hypothesis that fermentation with Lactobacillus fermentium, which can metabolize citric acid, could be applied in improving the taste (sugar:acid ratio) of citrus juice. During fermentation, the strain of L. fermentium can preferentially utilize citric acid of citrus (Citrus reticulata cv. Chachiensis) juice to support the growth without the consumption of sugar. After 6 h of fermentation with L. fermentium at 30 °C, the sugar:acid ratio of citrus juice increased to 22:1 from 12:1, which resulted in that the hedonic scores of sweetness, acidity and overall acceptability of fermented-pasteurized citrus juice were higher than the unfermented-pasteurized citrus juice. Compared with unfermented-pasteurized citrus juice, the ORAC value and total amino acid showed a reduction, and no significant change (P > 0.05) in the L*, a*, b*, total soluble phenolics and ascorbic acid (Vc) content in the fermented-pasteurized citrus juice was observed as compared with unfermented-pasteurized citrus juice. Hence, slight fermentation with L. fermentium can be used for improving the taste (sugar:acid ratio) of citrus juice with the well retaining of quality. PMID:26447635

  1. Slight Fermentation with Lactobacillus fermentium Improves the Taste (Sugar:Acid Ratio) of Citrus (Citrus reticulata cv. chachiensis) Juice.

    Science.gov (United States)

    Yu, Yuanshan; Xiao, Gengsheng; Xu, Yujuan; Wu, Jijun; Fu, Manqin; Wen, Jing

    2015-11-01

    The aim of this study was to evaluate the hypothesis that fermentation with Lactobacillus fermentium, which can metabolize citric acid, could be applied in improving the taste (sugar:acid ratio) of citrus juice. During fermentation, the strain of L. fermentium can preferentially utilize citric acid of citrus (Citrus reticulata cv. Chachiensis) juice to support the growth without the consumption of sugar. After 6 h of fermentation with L. fermentium at 30 °C, the sugar:acid ratio of citrus juice increased to 22:1 from 12:1, which resulted in that the hedonic scores of sweetness, acidity and overall acceptability of fermented-pasteurized citrus juice were higher than the unfermented-pasteurized citrus juice. Compared with unfermented-pasteurized citrus juice, the ORAC value and total amino acid showed a reduction, and no significant change (P > 0.05) in the L*, a*, b*, total soluble phenolics and ascorbic acid (Vc) content in the fermented-pasteurized citrus juice was observed as compared with unfermented-pasteurized citrus juice. Hence, slight fermentation with L. fermentium can be used for improving the taste (sugar:acid ratio) of citrus juice with the well retaining of quality.

  2. Chilling Tolerance Improving of Watermelon Seedling by Salicylic Acid Seed and Foliar Application

    Directory of Open Access Journals (Sweden)

    Mohammad SAYYARI

    2013-02-01

    Full Text Available Chilling temperatures lead to numerous physiological disturbances in the cells of chilling-sensitive plants and result in chilling injury and death of tropical and subtropical plants such as watermelon. In this study, the possibility of cold stress tolerance enhancing of watermelon seedling (Citrullus lanatus by exogenous application of Salicylic acid (SA was investigated. SA was applied through seed soaking or foliar spray at 0, 0.5, 1 and 1.5 mM concentration. After SA treatment, the seedlings were subjected to chilling 5 h/day at 4°C for 5 days. Statistical analysis showed significant effects of the application methods and SA concentrations on plant growth parameters, photosynthetic pigments, electrolyte leakage, proline and chilling injury index. SA application improved growth parameters and increased chlorophyll content of watermelon seedling subjected to chilling stress and provided significant protection against chilling stress compared to non-SA-treated seedlings. Although two SA application methods improved chilling stress tolerance, seed soaking method provided better protection compared to foliar spray method. SA ameliorated the injury caused by chilling stress via inhibiting proline accumulation and leaf electrolyte leakage. The highest cold tolerance was obtained with 0.5 mM SA application. Results indicate that SA could be used effectively to protect watermelon seedling from damaging effects of chilling stress at the early stages of growth.

  3. Improved microscopical detection of acid-fast bacilli by the modified bleach method in lymphnode aspirates

    Directory of Open Access Journals (Sweden)

    Annam Vamseedhar

    2009-07-01

    Full Text Available Objectives: To improve the smear microscopy for detection of acid-fast bacilli (AFB in fine needle aspiration cytology (FNAC of lymph node using the bleach method and also to compare this with cytological diagnosis and the conventional Ziehl-Neelsen (ZN method. Study Design: In 99 consecutive patients with clinical suspicion of tuberculosis (TB presenting with lymphadenopathy, FNACs were performed. Smears from the aspirates were processed for routine cytology and the conventional ZN method. The remaining material in the needle hub and/or the syringe was used for the bleach method. The significance of the bleach method over the conventional ZN method and cytology was analyzed using the χ2 test. Results: Of 99 aspirates, 93 were studied and the remaining six were excluded from the study due to diagnosis of malignancy in 4.04% (4/6 and inadequate aspiration in 2.02% (2/6. Among the 93 aspirates, 33.33% (31/93 were positive for AFB on conventional ZN method, 41.94% (39/93 were indicative of TB on cytology and the smear positivity increased to 63.44% (59/93 on bleach method. Conclusion: The bleach method is simple, inexpensive and potent disinfectant, also limiting the risk of laboratory-acquired infections. The implementation of the bleach method clearly improves microscopic detection and can be a useful contribution to routine cytology.

  4. Improvement of Functional Properties of Wheat Gluten Using Acid Protease from Aspergillus usamii

    Science.gov (United States)

    Deng, Lingli; Wang, Zhaoxia; Yang, Sheng; Song, Junmei; Que, Fei; Zhang, Hui; Feng, Fengqin

    2016-01-01

    Hydrolysis parameters (temperature, E/S ratio, pH, and time) for acid protease (from Aspergillus usamii) hydrolysis of wheat gluten were optimized by response surface methodology (RSM) using emulsifying activity index (EAI) as the response factor. A temperature of 48.9°C, E/S ratio of 1.60%, pH 3.0, hydrolysis time of 2.5 h was found to be the optimum condition to obtain wheat gluten hydrolysate with higher EAI. The solubility of wheat gluten was greatly improved by hydrolysis and became independent of pH over the studied range. Enzymatic hydrolysis resulted in dramatically increase in EAI, water and oil holding capacity. Molecular weight distribution results showed that most of the peptides above 10 kDa have been hydrolyzed into smaller peptides. The results of FTIR spectra and disulfide bond (SS) and sulfhydryl (SH) content suggested that a more extensional conformation was formed after hydrolysis, which could account for the improved functional properties. PMID:27467884

  5. Improvement of Functional Properties of Wheat Gluten Using Acid Protease from Aspergillus usamii.

    Science.gov (United States)

    Deng, Lingli; Wang, Zhaoxia; Yang, Sheng; Song, Junmei; Que, Fei; Zhang, Hui; Feng, Fengqin

    2016-01-01

    Hydrolysis parameters (temperature, E/S ratio, pH, and time) for acid protease (from Aspergillus usamii) hydrolysis of wheat gluten were optimized by response surface methodology (RSM) using emulsifying activity index (EAI) as the response factor. A temperature of 48.9°C, E/S ratio of 1.60%, pH 3.0, hydrolysis time of 2.5 h was found to be the optimum condition to obtain wheat gluten hydrolysate with higher EAI. The solubility of wheat gluten was greatly improved by hydrolysis and became independent of pH over the studied range. Enzymatic hydrolysis resulted in dramatically increase in EAI, water and oil holding capacity. Molecular weight distribution results showed that most of the peptides above 10 kDa have been hydrolyzed into smaller peptides. The results of FTIR spectra and disulfide bond (SS) and sulfhydryl (SH) content suggested that a more extensional conformation was formed after hydrolysis, which could account for the improved functional properties. PMID:27467884

  6. Partition dataset according to amino acid type improves the prediction of deleterious non-synonymous SNPs

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Jing; Li, Yuan-Yuan [School of Biotechnology, East China University of Science and Technology, Shanghai 200237 (China); Shanghai Center for Bioinformation Technology, Shanghai 200235 (China); Li, Yi-Xue, E-mail: yxli@sibs.ac.cn [School of Biotechnology, East China University of Science and Technology, Shanghai 200237 (China); Shanghai Center for Bioinformation Technology, Shanghai 200235 (China); Ye, Zhi-Qiang, E-mail: yezq@pkusz.edu.cn [Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055 (China); Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China)

    2012-03-02

    Highlights: Black-Right-Pointing-Pointer Proper dataset partition can improve the prediction of deleterious nsSNPs. Black-Right-Pointing-Pointer Partition according to original residue type at nsSNP is a good criterion. Black-Right-Pointing-Pointer Similar strategy is supposed promising in other machine learning problems. -- Abstract: Many non-synonymous SNPs (nsSNPs) are associated with diseases, and numerous machine learning methods have been applied to train classifiers for sorting disease-associated nsSNPs from neutral ones. The continuously accumulated nsSNP data allows us to further explore better prediction approaches. In this work, we partitioned the training data into 20 subsets according to either original or substituted amino acid type at the nsSNP site. Using support vector machine (SVM), training classification models on each subset resulted in an overall accuracy of 76.3% or 74.9% depending on the two different partition criteria, while training on the whole dataset obtained an accuracy of only 72.6%. Moreover, the dataset was also randomly divided into 20 subsets, but the corresponding accuracy was only 73.2%. Our results demonstrated that partitioning the whole training dataset into subsets properly, i.e., according to the residue type at the nsSNP site, will improve the performance of the trained classifiers significantly, which should be valuable in developing better tools for predicting the disease-association of nsSNPs.

  7. Polylactic acid with improved heat deflection temperatures and self-healing properties for durable goods applications.

    Science.gov (United States)

    Wertz, J T; Mauldin, T C; Boday, D J

    2014-11-12

    A method to recover fracture toughness after failure and increase thermal properties of polylactic acid (PLA) for use within durable goods applications is presented. Microcapsules were incorporated into PLA to form a composite material in which the microcapsules served the dual purpose of (1) releasing self-healing additives to fracture regions and (2) serving as nucleating agents to improve the PLA composite's thermal tolerance. Self-healing was achieved though embedment of dicyclopentadiene-filled microcapsules and Grubbs' first generation ruthenium metathesis catalyst, the former being autonomically released into damage volumes and undergoing polymerization in the presence of the catalyst. This approach led to up to 84% recovery of the polymer composite's initial fracture toughness. Additionally, PLA's degree of crystallinity and heat deflection temperature were improved by ∼ 11% and ∼ 21 °C, respectively, relative to nonfilled virgin PLA, owing to microcapsule-induced nucleation. The self-healing system developed here overcomes many property limitations of PLA that can potentially lead to its incorporation into various durable goods.

  8. Pharmacological Mechanisms of Cortical Enhancement Induced by the Repetitive Pairing of Visual/Cholinergic Stimulation.

    Directory of Open Access Journals (Sweden)

    Jun-Il Kang

    Full Text Available Repetitive visual training paired with electrical activation of cholinergic projections to the primary visual cortex (V1 induces long-term enhancement of cortical processing in response to the visual training stimulus. To better determine the receptor subtypes mediating this effect the selective pharmacological blockade of V1 nicotinic (nAChR, M1 and M2 muscarinic (mAChR or GABAergic A (GABAAR receptors was performed during the training session and visual evoked potentials (VEPs were recorded before and after training. The training session consisted of the exposure of awake, adult rats to an orientation-specific 0.12 CPD grating paired with an electrical stimulation of the basal forebrain for a duration of 1 week for 10 minutes per day. Pharmacological agents were infused intracortically during this period. The post-training VEP amplitude was significantly increased compared to the pre-training values for the trained spatial frequency and to adjacent spatial frequencies up to 0.3 CPD, suggesting a long-term increase of V1 sensitivity. This increase was totally blocked by the nAChR antagonist as well as by an M2 mAChR subtype and GABAAR antagonist. Moreover, administration of the M2 mAChR antagonist also significantly decreased the amplitude of the control VEPs, suggesting a suppressive effect on cortical responsiveness. However, the M1 mAChR antagonist blocked the increase of the VEP amplitude only for the high spatial frequency (0.3 CPD, suggesting that M1 role was limited to the spread of the enhancement effect to a higher spatial frequency. More generally, all the drugs used did block the VEP increase at 0.3 CPD. Further, use of each of the aforementioned receptor antagonists blocked training-induced changes in gamma and beta band oscillations. These findings demonstrate that visual training coupled with cholinergic stimulation improved perceptual sensitivity by enhancing cortical responsiveness in V1. This enhancement is mainly mediated by n

  9. Effect of bilobalide B on cholinergic hippocampal neurons exposed to cholesterol and apoliprotein E4

    Institute of Scientific and Technical Information of China (English)

    Xijuan Jiang; Bin Lu; Yingchang Fan

    2008-01-01

    BACKGROUND: Extracts of ginkgo biloba leaves have been reported to improve nerve function and activity in Alzheimer's disease, which is associated with reduced secretion of cholinergic neurotransmitter in hippocampal neurons.OBJECTIVE: To validate the protective effect of bilobalide B against in vitro injury of cholinergic neurons of the hippocampus induced by combined cholesterol and apoE4DESIGN, TIME AND SETTING: This randomized, controlled animal experiment was performed in the Pathology Laboratory, Tianjin University of Traditional Chinese Medicine from July 2003 to July 2006.MATERIALS: Neonatal Wistar rats, 1-day-old, both male and female, and mean body mass of 5g were selected for this study. Cholesterol and apolipoprotein E4 (apoE4) were purchased from Sigma Company (USA), bilobalide B was purchased from Tianjin Zhongyi Pharmaceutical Factory, batch number 20050312.METHODS: Hippocampal neurons were divided into three groups; a normal control group (routinely added media), a model group (exposed to media containing 40mg/L cholesterol and 30mg/L apoE4 for 24 hours) and a bilobalide B group (exposed to media containing 160mg/L bilobalide B for 16 hours, and then with addition of 40mg/L cholesterol and 30mg/L apoE4 for an additional 24 hours).MAIN OUTCOME MEASURES: Levels of acetylcholine (ACh) and activity of acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) in hippocampal neurons were determined by microdosage hydroxylamine colorimetry, hydroxylamine colorimetry and radiological chemistry, respectively.RESULTS: The ACh level was significantly lower in the model group than that in the normal control group (P0.05). Activity of ChAT was significantly lower in the model group than in the normal control group (P<0.01), while the activity was significantly higher in the bilobalide B group than in the model group (P<0.05).CONCLUSION: Bilobalide B can enhance the ACh level of hippocampal neurons damaged by combined cholesterol and apoE4, by promoting

  10. Improving Co-Amorphous Drug Formulations by the Addition of the Highly Water Soluble Amino Acid, Proline

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    Katrine Tarp Jensen

    2014-07-01

    Full Text Available Co-amorphous drug amino acid mixtures were previously shown to be a promising approach to create physically stable amorphous systems with the improved dissolution properties of poorly water-soluble drugs. The aim of this work was to expand the co-amorphous drug amino acid mixture approach by combining the model drug, naproxen (NAP, with an amino acid to physically stabilize the co-amorphous system (tryptophan, TRP, or arginine, ARG and a second highly soluble amino acid (proline, PRO for an additional improvement of the dissolution rate. Co-amorphous drug-amino acid blends were prepared by ball milling and investigated for solid state characteristics, stability and the dissolution rate enhancement of NAP. All co-amorphous mixtures were stable at room temperature and 40 °C for a minimum of 84 days. PRO acted as a stabilizer for the co-amorphous system, including NAP–TRP, through enhancing the molecular interactions in the form of hydrogen bonds between all three components in the mixture. A salt formation between the acidic drug, NAP, and the basic amino acid, ARG, was found in co-amorphous NAP–ARG. In comparison to crystalline NAP, binary NAP–TRP and NAP–ARG, it could be shown that the highly soluble amino acid, PRO, improved the dissolution rate of NAP from the ternary co-amorphous systems in combination with either TRP or ARG. In conclusion, both the solubility of the amino acid and potential interactions between the molecules are critical parameters to consider in the development of co-amorphous formulations.

  11. Cholinergic modulation of cognitive processing: insights drawn from computational models

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    Ehren L Newman

    2012-06-01

    Full Text Available Acetylcholine plays an important role in cognitive function, as shown by pharmacological manipulations that impact working memory, attention, episodic memory and spatial memory function. Acetylcholine also shows striking modulatory influences on the cellular physiology of hippocampal and cortical neurons. Modeling of neural circuits provides a framework for understanding how the cognitive functions may arise from the influence of acetylcholine on neural and network dynamics. We review the influences of cholinergic manipulations on behavioral performance in working memory, attention, episodic memory and spatial memory tasks, the physiological effects of acetylcholine on neural and circuit dynamics, and the computational models that provide insight into the functional relationships between the physiology and behavior. Specifically, we discuss the important role of acetylcholine in governing mechanisms of active maintenance in working memory tasks and in regulating network dynamics important for effective processing of stimuli in attention and episodic memory tasks. We also propose that theta rhythm play a crucial role as an intermediary between the physiological influences of acetylcholine and behavior in episodic and spatial memory tasks. We conclude with a synthesis of the existing modeling work and highlight future directions that are likely to be rewarding given the existing state of the literature for both empiricists and modelers.

  12. Exposure to omega-3 fatty acids at early age accelerate bone growth and improve bone quality.

    Science.gov (United States)

    Koren, Netta; Simsa-Maziel, Stav; Shahar, Ron; Schwartz, Betty; Monsonego-Ornan, Efrat

    2014-06-01

    Omega-3 fatty acids (FAs) are essential nutritional components that must be obtained from foods. Increasing evidence validate that omega-3 FAs are beneficial for bone health, and several mechanisms have been suggested to mediate their effects on bone, including alterations in calcium absorption and urinary calcium loss, prostaglandin synthesis, lipid oxidation, osteoblast formation and inhibition of osteoclastogenesis. However, to date, there is scant information regarding the effect of omega-3 FAs on the developing skeleton during the rapid growth phase. In this study we aim to evaluate the effect of exposure to high levels of omega-3 FAs on bone development and quality during prenatal and early postnatal period. For this purpose, we used the fat-1 transgenic mice that have the ability to convert omega-6 to omega-3 fatty acids and the ATDC5 chondrogenic cell line as models. We show that exposure to high concentrations of omega-3 FAs at a young age accelerates bone growth through alterations of the growth plate, associated with increased chondrocyte proliferation and differentiation. We further propose that those effects are mediated by the receptors G-protein coupled receptor 120 (GPR120) and hepatic nuclear factor 4α, which are expressed by chondrocytes in culture. Additionally, using a combined study on the structural and mechanical bone parameters, we show that high omega-3 levels contribute to superior trabecular and cortical structure, as well as to stiffer bones and improved bone quality. Most interestingly, the fat-1 model allowed us to demonstrate the role of maternal high omega-3 concentration on bone growth during the gestation and postnatal period.

  13. Illuminating the role of cholinergic signaling in circuits of attention and emotionally salient behaviors

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    Antonio eLuchicchi

    2014-10-01

    Full Text Available Acetylcholine (ACh signaling underlies specific aspects of cognitive functions and behaviors, including attention, learning, memory and motivation. Alterations in ACh signaling are involved in the pathophysiology of multiple neuropsychiatric disorders. In the central nervous system, ACh transmission is mainly guaranteed by dense innervation of select cortical and subcortical regions from disperse groups of cholinergic neurons within the basal forebrain (e.g. diagonal band, medial septal, nucleus basalis and the pontine-mesencephalic nuclei, respectively. Despite the fundamental role of cholinergic signaling in the CNS and the long standing knowledge of the organization of cholinergic circuitry, remarkably little is known about precisely how ACh release modulates cortical and subcortical neural activity and the behaviors these circuits subserve. Growing interest in cholinergic signaling in the CNS focuses on the mechanism(s of action by which endogenously released ACh regulates cognitive functions, acting as a neuromodulator and /or as a direct transmitter via nicotinic and muscarinic receptors. The development of optogenetic techniques has provided a valuable toolbox with which we can address these questions, as it allows the selective manipulation of the excitability of cholinergic inputs to the diverse array of cholinergic target fields within cortical and subcortical domains. Here, we review recent papers that use the light-sensitive opsins in the cholinergic system to elucidate the role of ACh in circuits related to attention and emotionally salient behaviors. In particular, we highlight recent optogenetic studies which have tried to disentangle the precise role of ACh in the modulation of cortical-, hippocampal- and striatal-dependent functions.

  14. Neuroligin 2 is expressed in synapses established by cholinergic cells in the mouse brain.

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    Virág T Takács

    Full Text Available Neuroligin 2 is a postsynaptic protein that plays a critical role in the maturation and proper function of GABAergic synapses. Previous studies demonstrated that deletion of neuroligin 2 impaired GABAergic synaptic transmission, whereas its overexpression caused increased inhibition, which suggest that its presence strongly influences synaptic function. Interestingly, the overexpressing transgenic mouse line showed increased anxiety-like behavior and other behavioral phenotypes, not easily explained by an otherwise strengthened GABAergic transmission. This suggested that other, non-GABAergic synapses may also express neuroligin 2. Here, we tested the presence of neuroligin 2 at synapses established by cholinergic neurons in the mouse brain using serial electron microscopic sections double labeled for neuroligin 2 and choline acetyltransferase. We found that besides GABAergic synapses, neuroligin 2 is also present in the postsynaptic membrane of cholinergic synapses in all investigated brain areas (including dorsal hippocampus, somatosensory and medial prefrontal cortices, caudate putamen, basolateral amygdala, centrolateral thalamic nucleus, medial septum, vertical- and horizontal limbs of the diagonal band of Broca, substantia innominata and ventral pallidum. In the hippocampus, the density of neuroligin 2 labeling was similar in GABAergic and cholinergic synapses. Moreover, several cholinergic contact sites that were strongly labeled with neuroligin 2 did not resemble typical synapses, suggesting that cholinergic axons form more synaptic connections than it was recognized previously. We showed that cholinergic cells themselves also express neuroligin 2 in a subset of their input synapses. These data indicate that mutations in human neuroligin 2 gene and genetic manipulations of neuroligin 2 levels in rodents will potentially cause alterations in the cholinergic system as well, which may also have a profound effect on the functional properties

  15. Improving the antioxidant activity and enriching salvianolic acids by the fermentation of Salvia miltiorrhizae with Geomyces luteus.

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    Xing, Yun; Cai, Le; Yin, Tian-Peng; Chen, Yang; Yu, Jing; Wang, Ya-Rong; Ding, Zhong-Tao

    2016-05-01

    The antioxidant activities and total phenolic content of fermented Salvia miltiorrhiza with fungus Geomyces luteus were investigated. The results revealed that G. luteus fermentation could significantly improve the antioxidant activity and total phenolic content of S. miltiorrhiza. The main antioxidant constituents were characterized by spectroscopic analysis as salvianolic acids. High-performance liquid chromatography (HPLC) quantification also showed the enhanced content of salvianolic acid B after fermentation. The present study suggests that G. luteus fermentations are effective in the S. miltiorrhiza salvianolic acids' enrichment process. PMID:27143267

  16. Glycolic acid chemical peeling improves inflammatory acne eruptions through its inhibitory and bactericidal effects on Propionibacterium acnes.

    Science.gov (United States)

    Takenaka, Yuko; Hayashi, Nobukazu; Takeda, Mikiko; Ashikaga, Sayaka; Kawashima, Makoto

    2012-04-01

    Glycolic acid chemical peeling is effective for treating comedones, and some clinical data show that it also improves inflammatory eruptions. The purpose of this study was to identify the mechanism of glycolic acid chemical peeling to improve inflammatory acne. To assess growth inhibitory and bactericidal effects of glycolic acid on Propionibacterium acnes in vitro, we used an agar diffusion method and a time-kill method. To reveal bactericidal effects in vivo, we established an agar-attached method which correlated well with the ordinary swab-wash method, and we used the agar-attached method to compare the numbers of propionibacteria on the cheek treated with glycolic acid chemical peeling. Our results show that 30% glycolic acid (at pH 1.5, 3.5 and 5.5) formed growth inhibitory circles in the agar diffusion method, but the diameters of those circles were smaller than with 1% nadifloxacin lotion or 1% clindamycin gel. In the time-kill method, 30% glycolic acid (at pH 1.5 and 3.5) or 1% nadifloxacin lotion reduced the number of P. acnes to less than 100 CFU/mL within 5 min. In contrast, in 30% glycolic acid (at pH 5.5) or in 1% clindamycin gel, P. acnes survived for more than 4 h. Chemical peeling with 35% glycolic acid (at pH 1.2) decreased the number of propionibacteria on the cheeks of patients compared with untreated controls (P glycolic acid has moderate growth inhibitory and bactericidal effects on P. acnes, and that chemical peeling with glycolic acid works on inflammatory acne via those effects.

  17. POSSIBLE RELATIONSHIP OF FOLIC ACID SUPPLEMENTATION AND IMPROVED FLOW-MEDIATED DILATION IN PREMENOPAUSAL, EUMENORRHEIC ATHLETIC WOMEN

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    Anne Z. Hoch

    2009-03-01

    Full Text Available The purpose of this study was to determine if six weeks of folic acid supplementation would improve brachial artery endothelial-dependent flow-mediated dilation in eumenorrheic female runners with previously normal serum folate levels. This was a prospective, double-blinded, randomized pilot study with convenience sampling. Sixteen eumenorrheic subjects who were not taking birth control pills and who ran at least 20 miles/week were randomly assigned to 10 mg/day of folic acid supplementation or placebo for at least 6 weeks. Serum folate levels and brachial artery measurements were made during the early follicular phase of the menstrual cycle, in a sedentary state, following an 8 hour fast; a standard ultrasound technique was used. The brachial artery vasodilator response to reactive hyperemia was similar between the folic acid (6.6% ± 0.8%, mean ± SE and placebo groups (6.5% ± 0.7% at baseline. After six weeks, there was a significantly higher change in flow-mediated dilation for the folic acid group (3.5% ± 0.6% compared to the placebo group (0.1% ± 0.2% (p = 0.01. Serum folate levels also increased significantly in the folic acid group following six weeks of folic acid supplementation. This study demonstrates that brachial artery flow-mediated dilation improves significantly in eumenorrheic female runners with previously normal serum folate levels after 6 weeks of supplementation with folic acid

  18. Absence of Rtt109p, a fungal-specific histone acetyltransferase, results in improved acetic acid tolerance of Saccharomyces cerevisiae.

    Science.gov (United States)

    Cheng, Cheng; Zhao, Xinqing; Zhang, Mingming; Bai, Fengwu

    2016-03-01

    RTT109 is a histone acetyltransferase for the acetylation of histone H3. It is still not clear whether RTT109 plays a role in regulation of gene expression under environmental stresses. In this study, the involvement of RTT109 in acetic acid stress tolerance of Saccharomyces cerevisiae was investigated. It was revealed that the absence of RTT109 enhanced resistance to 5.5 g L(-1) acetic acid, which was indicated by improved growth of RTT109Δ mutant compared with that of the wild-type BY4741 strain. Meanwhile, the lag phase was shortened for 48 h and glucose consumption completed 36 h in advance for RTT109Δ mutant compared to the wild-type strain, with ethanol production rate increased from 0.39 to 0.60 g L(-1) h(-1). Significantly, elevated transcription levels of HSP12, CTT1 and GSH1, as well as increased activities of antioxidant enzymes were observed in RTT109Δ under acetic acid stress. Improved flocculation of RTT109Δ compared to that of the control strain BY4741 under the acetic acid stress was also observed. These results suggest that the absence of RTT109 not only activates transcription of stress responsive genes, but also improves resistance to oxidative stress, which ultimately contributes to improved acetic acid tolerance in S. cerevisiae.

  19. Maximized PUFA measurements improve insight in changes in fatty acid composition in response to temperature

    NARCIS (Netherlands)

    Dooremalen, van C.; Pel, R.; Ellers, J.

    2009-01-01

    A general mechanism underlying the response of ectotherms to environmental changes often involves changes in fatty acid composition. Theory predicts that a decrease in temperature causes an increase in unsaturation of fatty acids, with an important role for long-chain poly-unsaturated fatty acids (P

  20. Reduced by-product formation and modified oxygen availability improve itaconic acid production in Aspergillus niger.

    NARCIS (Netherlands)

    Li, A.; Pfelzer, N.; Zuijderwijk, R.; Brickwedde, A.; Zeijl, C. van; Punt, P.

    2013-01-01

    Aspergillus niger has an extraordinary potential to produce organic acids as proven by its application in industrial citric acid production. Previously, it was shown that expression of the cis-aconitate decarboxylase gene (cadA) from Aspergillus terreus converted A. niger into an itaconic acid produ

  1. Improvement of pea biomass and seed productivity by simultaneous increase of phloem and embryo loading with amino acids.

    Science.gov (United States)

    Zhang, Lizhi; Garneau, Matthew G; Majumdar, Rajtilak; Grant, Jan; Tegeder, Mechthild

    2015-01-01

    The development of sink organs such as fruits and seeds strongly depends on the amount of nitrogen that is moved within the phloem from photosynthetic-active source leaves to the reproductive sinks. In many plant species nitrogen is transported as amino acids. In pea (Pisum sativum L.), source to sink partitioning of amino acids requires at least two active transport events mediated by plasma membrane-localized proteins, and these are: (i) amino acid phloem loading; and (ii) import of amino acids into the seed cotyledons via epidermal transfer cells. As each of these transport steps might potentially be limiting to efficient nitrogen delivery to the pea embryo, we manipulated both simultaneously. Additional copies of the pea amino acid permease PsAAP1 were introduced into the pea genome and expression of the transporter was targeted to the sieve element-companion cell complexes of the leaf phloem and to the epidermis of the seed cotyledons. The transgenic pea plants showed increased phloem loading and embryo loading of amino acids resulting in improved long distance transport of nitrogen, sink development and seed protein accumulation. Analyses of root and leaf tissues further revealed that genetic manipulation positively affected root nitrogen uptake, as well as primary source and sink metabolism. Overall, the results suggest that amino acid phloem loading exerts regulatory control over pea biomass production and seed yield, and that import of amino acids into the cotyledons limits seed protein levels.

  2. Use of tannins to improve fatty acids profile of meat and milk quality in ruminants: A review

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    Rodrigo Morales

    2015-06-01

    Full Text Available This paper reviews how tannins, through their effects on rumen lipid metabolism, can affect the composition of ruminants' meat and milk fat. Tannins are a heterogeneous group of plant secondary compounds known for both beneficial and detrimental effects on animals' digestive physiology. Tannins supplementation of ruminants' diets alters both in vivo and in vitro unsaturated fatty acids biohydrogenation and hence the profile of fatty acids outflowing the rumen, which can influence milk and meat content of beneficial fatty acids such as linolenic acid (c9,c12,c15-18:3, vaccenic acid (ti 1-18:1 and rumenic acid (c9,t11-18:2, among others. Published information indicates that tannins could inhibit biohydrogenation though affecting ruminal microorganisms. Some studies found increments in linolenic, rumenic and/or vaccenic acids in meat and milk fat using different sources of tannins; however, the effects of tannins supplementation on milk and meat fatty acid profile are not consistent, and there are contradictory results published in the literature. Effects of tannin supplementation on fatty acids biohydrogenation are affected by the chemical type of tannins, the complexity of their interactions with dietary components, and the potential microbial adaptation to tannins. In addition, the duration of the tannins-feeding period may also affect milk and meat fatty acid profile. Characterizing the effects of each specific tannic compound on different biohydrogenation steps and on the microbial species conducting them, as well as the interaction between specific tannin compounds and other dietary components can help to take greater advantage of tannins potential to contribute to improve human health through promoting beneficial fatty acids in ruminants products.

  3. Improved Resin–Zirconia Bonding by Room Temperature Hydrofluoric Acid Etching

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    Mun-Hwan Lee

    2015-03-01

    Full Text Available This in vitro study was conducted to evaluate the shear bond strength of “non-self-adhesive” resin to dental zirconia etched with hydrofluoric acid (HF at room temperature and to compare it to that of air-abraded zirconia. Sintered zirconia plates were air-abraded (control or etched with 10%, 20%, or 30% HF for either 5 or 30 min. After cleaning, the surfaces were characterized using various analytical techniques. Three resin cylinders (Duo-Link were bonded to each treated plate. All bonded specimens were stored in water at 37 °C for 24 h, and then half of them were additionally thermocycled 5000 times prior to the shear bond-strength tests (n = 12. The formation of micro- and nano-porosities on the etched surfaces increased with increasing concentration and application time of the HF solution. The surface wettability of zirconia also increased with increasing surface roughness. Higher concentrations and longer application times of the HF solution produced higher bond-strength values. Infiltration of the resin into the micro- and nano-porosities was observed by scanning electron microscopy. This in vitro study suggests that HF slowly etches zirconia ceramic surfaces at room temperature, thereby improving the resin–zirconia bond strength by the formation of retentive sites.

  4. Biomimetic hydroxyapatite coating on pore walls improves osteointegration of poly(L-lactic acid) scaffolds.

    Science.gov (United States)

    Deplaine, H; Lebourg, M; Ripalda, P; Vidaurre, A; Sanz-Ramos, P; Mora, G; Prósper, F; Ochoa, I; Doblaré, M; Gómez Ribelles, J L; Izal-Azcárate, I; Gallego Ferrer, G

    2013-01-01

    Polymer-ceramic composites obtained as the result of a mineralization process hold great promise for the future of tissue engineering. Simulated body fluids (SBFs) are widely used for the mineralization of polymer scaffolds. In this work an exhaustive study with the aim of optimizing the mineralization process on a poly(L-lactic acid) (PLLA) macroporous scaffold has been performed. We observed that when an air plasma treatment is applied to the PLLA scaffold its hydroxyapatite nucleation ability is considerably improved. However, plasma treatment only allows apatite deposition on the surface of the scaffold but not in its interior. When a 5 wt % of synthetic hydroxyapatite (HAp) nanoparticles is mixed with PLLA a more abundant biomimetic hydroxyapatite layer grows inside the scaffold in SBF. The morphology, amount, and composition of the generated biomimetic hydroxyapatite layer on the pores' surface have been analyzed. Large mineralization times are harmful to pure PLLA as it rapidly degrades and its elastic compression modulus significantly decreases. Degradation is retarded in the composite scaffolds because of the faster and extensive biomimetic apatite deposition and the role of HAp to control the pH. Mineralized scaffolds, covered by an apatite layer in SBF, were implanted in osteochondral lesions performed in the medial femoral condyle of healthy sheep. We observed that the presence of biomimetic hydroxyapatite on the pore's surface of the composite scaffold produces a better integration in the subchondral bone, in comparison to bare PLLA scaffolds. PMID:23152082

  5. An improved HPLC-DAD method for clavulanic acid quantification in fermentation broths of Streptomyces clavuligerus.

    Science.gov (United States)

    Ramirez-Malule, Howard; Junne, Stefan; López, Carlos; Zapata, Julian; Sáez, Alex; Neubauer, Peter; Rios-Estepa, Rigoberto

    2016-02-20

    Clavulanic acid (CA) is an important secondary metabolite commercially produced by cultivation of Streptomyces clavuligerus (Sc). It is a potent inhibitor of bacterial β-lactamases. In this work, a specific and improved high performance liquid chromatography (HPLC) method, using a C-18 reversed phase column, diode array detector and gradient elution for CA quantification in fermentation broths of Sc, was developed and successfully validated. Samples were imidazole-derivatized for the purpose of creating a stable chromophore (clavulanate-imidazole). The calibration curve was linear over a typical range of CA concentration between 0.2 and 400mg/L. The detection and quantification limits were 0.01 and 0.02mg/L, respectively. The precision of the method was evaluated for CA spiked into production media and a recovery of 103.8%, on average, was obtained. The clavulanate-imidazole complex was not stable when the samples were not cooled during the analysis. The recovery rate was 39.3% on average. This assay was successfully tested for CA quantification in samples from Sc fermentation, using both, a chemically defined and a complex medium.

  6. Salvianolic Acids Attenuate Rat Hippocampal Injury after Acute CO Poisoning by Improving Blood Flow Properties

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    Li Guan

    2015-01-01

    Full Text Available Carbon monoxide (CO poisoning causes the major injury and death due to poisoning worldwide. The most severe damage via CO poisoning is brain injury and mortality. Delayed encephalopathy after acute CO poisoning (DEACMP occurs in forty percent of the survivors of acute CO exposure. But the pathological cause for DEACMP is not well understood. And the corresponding therapy is not well developed. In order to investigate the effects of salvianolic acid (SA on brain injury caused by CO exposure from the view point of hemorheology, we employed a rat model and studied the dynamic of blood changes in the hemorheological and coagulative properties over acute CO exposure. Compared with the groups of CO and 20% mannitol + CO treatments, the severe hippocampal injury caused by acute CO exposure was prevented by SA treatment. These protective effects were associated with the retaining level of hematocrit (Hct, plasma viscosity, fibrinogen, whole blood viscosities and malondialdehyde (MDA levels in red blood cells (RBCs. These results indicated that SA treatment could significantly improve the deformation of erythrocytes and prevent the damage caused by CO poisoning. Meanwhile, hemorheological indexes are good indicators for monitoring the pathological dynamic after acute CO poisoning.

  7. Acid etching does not improve CoCrMo implant osseointegration in a canine implant model.

    Science.gov (United States)

    Jakobsen, Stig S; Baas, Jorgen; Jakobsen, Thomas; Soballe, Kjeld

    2010-01-01

    Induction of bone ingrowth by topographical changes to implant surfaces is an attractive concept. Topographical modifications achieved by acid etching are potentially applicable to complex 3D surfaces. Using clinically relevant implant models, we explored the effect of wet etching porous bead-coated CoCrMo. The study was designed as two paired animal experiments with 10 dogs. Each dog received four implants; one in each medial femoral condyle (loaded 0.75-mm-gap model) and one in each proximal tibia (press-fit). The implants were observed for 6 weeks and were evaluated by biomechanical pushout tests and histomorphometry. We found that wet etching porous bead-coated CoCrMo implants failed to improve implant performance. Moreover, a tendency towards increased fibrous tissue formation, decreased new bone formation, and decreased mechanical fixation was observed. Surface topography on implants is able to stimulate bone-forming cells, but the clinical performance of an implant surface perhaps relies more on 3D geometrical structure and biocompatibility. Caution should be exercised regarding the results of wet etching of porous bead-coated CoCrMo and there is a need for more preclinical trials. PMID:20544657

  8. Improved focal liver lesion detection by increasing flip angle during gadoxetic acid-enhancement in MRI

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Se Jy [Dept. of Medical science Graduate school, Chonnam National University, Kwangju (Korea, Republic of); Kim, Young Keun [Dept. of Radiotechnology, Gwang-ju Health university, Gwangju (Korea, Republic of)

    2015-06-15

    To study the differences of focal liver lesion image detection at 3 minute, 10 minute and 15 minute time points on gadoxetic acid (GA)’s enhanced MR imaging with a flip angle (FA) of 30° compared with a 11°. The subjects were 69 patients evaluated with GA enhanced MR imaging with 3.0T MR scanner. The patients are total 35(23 men and 7 women at the mean age of 60.4 years), hepatocellular carcinoma(23) and metastsis(12) except for normal, cyst and hemangioma. After GA was injected, FA 11° and 30° images were obtained at 3 minute, 10 minute and 15 minute time points respectively. After quantitative and qualitative assessment of each image was done, statistical analysis was performed by using the independent sample T-test. From both quantitative and qualitative assessment of 3 minute and 10 minute MR images after the injection of GA, FA 30° images was found to be superior than FA 11°, but there were no statistical significance. However, at 15 minute time point, Statistically significant FA 30° image(p<0.05) was better than FA 11° therefore, the FA 30° improves the focal liver lesion detection. FA 30° of MR image can detect liver lesion more sensitively than the existing FA11° image after GA contrast enhancement at 15 minute time point.

  9. BMP9 protects septal neurons from axotomy-evoked loss of cholinergic phenotype.

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    Ignacio Lopez-Coviella

    Full Text Available BACKGROUND: Cholinergic projection from the septum to the hippocampus is crucial for normal cognitive function and degeneration of cells and nerve fibers within the septohippocampal pathway contributes to the pathophysiology of Alzheimer's disease. Bone morphogenetic protein (BMP 9 is a cholinergic differentiating factor during development both in vivo and in vitro. METHODOLOGY/PRINCIPAL FINDINGS: To determine whether BMP9 could protect the adult cholinergic septohippocampal pathway from axotomy-evoked loss of the cholinergic phenotype, we performed unilateral fimbria-fornix transection in mice and treated them with a continuous intracerebroventricular infusion of BMP9 for six days. The number of choline acetyltransferase (CHAT-positive cells was reduced by 50% in the medial septal nucleus ipsilateral to the lesion as compared to the intact, contralateral side, and BMP9 infusion prevented this loss in a dose-dependent manner. Moreover, BMP9 prevented most of the decline of hippocampal acetylcholine levels ipsilateral to the lesion, and markedly increased CHAT, choline transporter CHT, NGF receptors p75 (NGFR-p75 and TrkA (NTRK1, and NGF protein content in both the lesioned and unlesioned hippocampi. In addition, BMP9 infusion reduced bilaterally hippocampal levels of basic FGF (FGF2 protein. CONCLUSIONS/SIGNIFICANCE: These data indicate that BMP9 administration can prevent lesion-evoked impairment of the cholinergic septohippocampal neurons in adult mice and, by inducing NGF, establishes a trophic environment for these cells.

  10. Chronic Cerebral Ischaemia Forms New Cholinergic Mechanisms of Learning and Memory

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    E. I. Zakharova

    2010-01-01

    Full Text Available The purpose of this research was a comparative analysis of cholinergic synaptic organization following learning and memory in normal and chronic cerebral ischaemic rats in the Morris water maze model. Choline acetyltransferase and protein content were determined in subpopulations of presynapses of “light” and “heavy” synaptosomal fractions of the cortex and the hippocampus, and the cholinergic projective and intrinsic systems of the brain structures were taken into consideration. We found a strong involvement of cholinergic systems, both projective and intrinsic, in all forms of cognition. Each form of cognition had an individual cholinergic molecular profile and the cholinergic synaptic compositions in the ischaemic rat brains differed significantly from normal ones. Our data demonstrated that under ischaemic conditions, instead of damaged connections new key synaptic relationships, which were stable against pathological influences and able to restore damaged cognitive functions, arose. The plasticity of neurochemical links in the individual organization of certain types of cognition gave a new input into brain pathology and can be used in the future for alternative corrections of vascular and other degenerative dementias.

  11. [Advances in the research of effects of cholinergic anti-inflammatory pathway on vital organ function and its mechanism].

    Science.gov (United States)

    Li, X H; Yao, Y M

    2016-07-20

    Serious major burns, trauma and surgical stress can easily develop into sepsis, and further result in septic shock or even multiple organ dysfunction syndrome (MODS). The mechanism of MODS is complicated, including excessive inflammation, immune dysfunction, coagulation disorder, and ischemia-reperfusion injury. Recent studies have demonstrated that the nervous system could significantly and quickly suppress systemic inflammatory response via the vagus nerve, which might improve multiple organ damage following acute injury. This article is to brief our understanding concerning the structure characteristics of cholinergic anti-inflammatory pathway, and its effects on vital organ function and the regulatory mechanism, which might be of great significance to seek a novel way for interventional strategy of MODS. PMID:27464633

  12. Tolerance to acetic acid is improved by mutations of the TATA-binding protein gene.

    Science.gov (United States)

    An, Jieun; Kwon, Hyeji; Kim, Eunjung; Lee, Young Mi; Ko, Hyeok Jin; Park, Hongjae; Choi, In-Geol; Kim, Sooah; Kim, Kyoung Heon; Kim, Wankee; Choi, Wonja

    2015-03-01

    Screening a library of overexpressing mutant alleles of the TATA-binding gene SPT15 yielded two Saccharomyces cerevisiae strains (MRRC 3252 and 3253) with enhanced tolerance to acetic acid. They were also tolerant to propionic acid and hydrogen peroxide. Transcriptome profile analysis identified 58 upregulated genes and 106 downregulated genes in MRRC 3252. Stress- and protein synthesis-related transcription factors were predominantly enriched in the upregulated and downregulated genes respectively. Eight deletion mutants for some of the highly downregulated genes were acetic acid-tolerant. The level of intracellular reactive oxygen species was considerably lessened in MRRC 3252 and 3253 upon exposure to acetic acid. Metabolome profile analysis revealed that intracellular concentrations of 5 and 102 metabolites were increased and decreased, respectively, in MRRC 3252, featuring a large increase of urea and a significant decrease of amino acids. The dur1/2Δmutant, in which the urea degradation gene DUR1/2 is deleted, displayed enhanced tolerance to acetic acid. Enhanced tolerance to acetic acid was also observed on the medium containing a low concentration of amino acids. Taken together, this study identified two SPT15 alleles, nine gene deletions and low concentration of amino acids in the medium that confer enhanced tolerance to acetic acid.

  13. Chemical and physical characteristics of a soybean beverage with improved flavor by addition of ethylenediaminetetraacetic acid

    Directory of Open Access Journals (Sweden)

    Guzmán, Carlos A.

    2000-10-01

    Full Text Available A new method to obtain a soybean (SB with improved flavor characteristics was developed by adding ethylenediaminetetraacetic acid (EDTA. The SB was evaluated for pH, viscosity and density, as well as for protein, oil and ash contents, fatty acid composition and lipoxygenase activity. A water/bean ratio of 4.5:1 was selected because it provided the best protein (4.22 g 100 ml-1 and total solids (8.80 g 100 ml-1 contents. Sensory ratings for flavor and aroma intensities were also determined and compared with those of a commercial soymilk and a soybean beverage without EDTA. Samples from SB had the lowest ratings for green/beany and rancid flavors. The results indicated that the addition of EDTA may reduce off-flavors in soybean products.Se ha desarrollado un nuevo método para obtener un alimento líquido de soja (ALS con mejores cualidades organolépticas mediante adición de ácido etilendiaminotetraacético (EDTA. En el producto obtenido se evaluaron el pH, la viscosidad y la densidad, así como también los contenidos de proteínas, grasas y cenizas, la composición en ácidos grasos y la actividad de lipoxigenasa. Se seleccionó una relación agua/haba de soja equivalente a 4.5:1 puesto que la misma produjo los más altos contenidos de proteínas (4.22 g 100 ml-1 y sólidos totales (8.80 g 100 ml-1. Se realizó una evaluación sensorial, mediante pruebas de aceptabilidad, del aroma y sabor del ALS y se compararon con los de una «leche de soja» comercial y un alimento líquido de soja sin agregado de EDTA. Las muestras de ALS presentaron las evaluaciones más bajas para sabores rancio y «afrijolado». Los resultados obtenidos indicaron que la adición de EDTA puede reducir sabores desagradables en productos de soja.

  14. Wetlands serve as natural sources for improvement of stream ecosystem health in regions affected by acid deposition

    Science.gov (United States)

    Pound, Katrina L; Lawrence, Gregory B.; Passy, Sophia I.

    2013-01-01

    For over 40 years, acid deposition has been recognized as a serious international environmental problem, but efforts to restore acidified streams and biota have had limited success. The need to better understand the effects of different sources of acidity on streams has become more pressing with the recent increases in surface water organic acids, or 'brownification' associated with climate change and decreased inorganic acid deposition. Here, we carried out a large scale multi-seasonal investigation in the Adirondacks, one of the most acid-impacted regions in the United States, to assess how acid stream producers respond to local and watershed influences and whether these influences can be used in acidification remediation. We explored the pathways of wetland control on aluminum chemistry and diatom taxonomic and functional composition. We demonstrate that streams with larger watershed wetlands have higher organic content, lower concentrations of acidic anions, and lower ratios of inorganic to organic monomeric aluminum, all beneficial for diatom biodiversity and guilds producing high biomass. Although brownification has been viewed as a form of pollution, our results indicate that it may be a stimulating force for biofilm producers with potentially positive consequences for higher trophic levels. Our research also reveals that the mechanism of watershed control of local stream diatom biodiversity through wetland export of organic matter is universal in running waters, operating not only in hard streams, as previously reported, but also in acid streams. Our findings that the negative impacts of acid deposition on Adirondack stream chemistry and biota can be mitigated by wetlands have important implications for biodiversity conservation and stream ecosystem management. Future acidification research should focus on the potential for wetlands to improve stream ecosystem health in acid-impacted regions and their direct use in stream restoration, for example, through

  15. Improvement of l-lactic acid productivity from sweet sorghum juice by repeated batch fermentation coupled with membrane separation.

    Science.gov (United States)

    Wang, Yong; Meng, Hongyu; Cai, Di; Wang, Bin; Qin, Peiyong; Wang, Zheng; Tan, Tianwei

    2016-07-01

    In order to efficiently produce l-lactic acid from non-food feedstocks, sweet sorghum juice (SSJ), which is rich of fermentable sugars, was directly used for l-lactic acid fermentation by Lactobacillus rhamnosus LA-04-1. A membrane integrated repeated batch fermentation (MIRB) was developed for productivity improvement. High-cell-density fermentation was achieved with a final cell density (OD620) of 42.3, and the CCR effect was overcomed. When SSJ (6.77gL(-1) glucose, 4.51gL(-1) fructose and 50.46gL(-1) sucrose) was used as carbon source in MIRB process, l-lactic acid productivity was increased significantly from 1.45gL(-1)h(-1) (batch 1) to 17.55gL(-1)h(-1) (batch 6). This process introduces an effective way to produce l-lactic acid from SSJ. PMID:27023384

  16. Improvement of Biodegradable Biocide’s Activity of Peroxyacetic Acid Basis Using Surfactants: Characterization and Stability

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    Esther Asensio

    2015-01-01

    Full Text Available This paper deals with the study of the kinetics decomposition reaction of the peroxyacetic acid under influence of surfactant additives. The peroxyacetic acid shows a decomposition rate of 1.70 × 10−3 h−1 and its activation energy is 66 kJ mol−1. The influence of temperature on the reaction of spontaneous decomposition of peroxyacetic acid was studied at two seasonal periods. Peroxyacetic acid standard and four prototypes of biocide samples with known concentration of peroxyacetic acid and hydrogen peroxide were studied. Finally, a factorial analysis ANOVA was carried out to establish significant differences (p<0.003 between the four biocide samples over time with respect to peroxyacetic acid and hydrogen peroxide concentration. From the study carried out, it can be concluded that the biocide with surfactant substances in its composition offers the best stability and its difference versus the other biocides may guarantee a better behaviour.

  17. Folic acid and prevention of neural tube defects in 2000 improved awareness--low peri-conceptional uptake.

    Science.gov (United States)

    Oleary, M; Donnell, R M; Johnson, H

    2001-06-01

    Eight years have passed since recommendations were made by the Irish Department of Health on the importance of folic acid in the prevention of neural tube defects (NTD). There is currently no mandatory fortification of foodstuffs with folic acid in Ireland, with reliance placed on campaigns promoting increased dietary folate intake and supplements. We assessed knowledge and use of folic acid among 300 women attending ante-natal clinics in Dublin maternity hospitals in the year 2000 using an interviewer administered questionnaire. Qualitative information was obtained through means of a focus group. Ninety two percent of respondents had heard of folic acid and 67% knew it could prevent NTD. Thirty per cent were advised to take it peri-conceptionally but overall only 18% did so; 39% of women had planned their pregnancy. The focus group indicated that folic acid was not 'visible' enough and that fortification of food was more realistic. This study shows that improved folic acid awareness has not been accompanied by corresponding peri-conceptional uptake in 2000. Folic acid promotional campaigns should be continuous and targeted. Mandatory food fortification should be strongly considered.

  18. Removal of boron from aqueous solution using magnetic carbon nanotube improved with tartaric acid

    OpenAIRE

    Zohdi, Nima; Mahdavi, Fariba; Abdullah, Luqman Chuah; Choong, Thomas SY

    2014-01-01

    Boron removal capacity of multi-walled carbon nanotubes (MWCNTs) modified with tartaric acid was investigated in this study. Modification of MWCNTs with tartaric acid was confirmed by Boehm surface chemistry method and fourier transform infra-red (FT-IR) spectroscopy. Experiments were performed to determine the adsorption isotherm and adsorption thermodynamic parameters of boron adsorption on tartaric acid modified MWCNTs (TA-MWCNTs). The effect of variables including initial pH, dosage of ad...

  19. Improvement Effect of Rosmarinic Acid on Serum Testosterone Level after Exposing with Electromagnetic Fields

    OpenAIRE

    Arezoo Farsi; Arash Khaki; Fatemeh Fathiazad; Fatemeh Afshari; Laleh Hajhossini; Amir Afshin Kahki

    2013-01-01

    Objective: Rosmarinic acid has antioxidant, anti-inflammatory and antimicrobial activities and helps to prevent cell damage caused by free radicals and other sources.Material and methods: Male Wistar rats (n = 40) were allocated to four groups, a control group (n = 10) and three treatment groups (n = 30). The first treatment group received rosmarinic acid (5 mg/kg body weight) by gavage method, the second test group received rosmarinic acid (5mg/kg body weight) by gavage and electromagnetic f...

  20. INHIBITION OF BILE ACID ACCUMULATION DECREASED THE EXCESSIVE HEPATOCYTE APOPTOSIS AND IMPROVED THE LIVER SECRETION FUNCTIONS ON OBSTRUCTIVE JAUNDICE PATIENTS

    Directory of Open Access Journals (Sweden)

    Akmal Taher

    2011-06-01

    Full Text Available Excessive hepatocyte apoptosis induced by bile acid accumulation occurred in severe obstructive jaundice, and impair the liver secretion function. The objective of this study is to determine whether the inhibition of bile acid accumulation through bile duct decompression affect the excessive hepatocyte apoptosis and caused improvement the liver secretion functions on human model. In this study we use a before and after study on severe obstructive jaundice patients due to extra hepatic bile duct tumor was decompressed. Bile duct decompression was performed as a model of the role of inhibition of bile acid accumulation inhibition bile acid accumulation and excessive hepatocyte apoptosis. Bile acid and marker of liver secretion functions were serially measured. Liver biopsy pre and post decompression was performed for Hepatocyte apoptosis pathologic examination by TUNEL fluorescing, which measured by 2 people in double blinded system. Total bile acid, and liver secretion functions were measured by automated chemistry analyzer. The result of this study shows that twenty one severe obstructive jaundice patients were included. After decompression the hepatocyte apoptosis index decreased from an average of 53.1 (SD 105 to 11.7 (SD 13.6 (p < 0.05. Average of bile acid serum decreased from 96.4 (SD 53.8 to 19.9 (SD 39.5 until 13.0 (SD 12.6 μmol/L (p < 0.05 Total ilirubin decreased from 20.0 (SD 8.9 to 13.3 (SD 5.0 until 6.2 (SD 4.0 mg/dL (p < 0.05, while the phosphates alkaline (ALP and γ-glutamil transpeptidase (γ-GT activities also decreased ignificantly. In conclusion, bile acids accumulation and excessive hepatocyte poptosis through bile duct decompression improve the liver secretion functions by inhibition mechanism.

  1. Axotomy-induced neurotrophic withdrawal causes the loss of phenotypic differentiation and downregulation of NGF signalling, but not death of septal cholinergic neurons

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    Inestrosa Nibaldo C

    2010-01-01

    Full Text Available Abstract Background Septal cholinergic neurons account for most of the cholinergic innervations of the hippocampus, playing a key role in the regulation of hippocampal synaptic activity. Disruption of the septo-hippocampal pathway by an experimental transection of the fimbria-fornix drastically reduces the target-derived trophic support received by cholinergic septal neurons, mainly nerve growth factor (NGF from the hippocampus. Axotomy of cholinergic neurons induces a reduction in the number of neurons positive for cholinergic markers in the medial septum. In several studies, the reduction of cholinergic markers has been interpreted as analogous to the neurodegeneration of cholinergic cells, ruling out the possibility that neurons lose their cholinergic phenotype without dying. Understanding the mechanism of cholinergic neurodegeneration after axotomy is relevant, since this paradigm has been extensively explored as an animal model of the cholinergic impairment observed in neuropathologies such as Alzheimer's disease. The principal aim of this study was to evaluate, using modern quantitative confocal microscopy, neurodegenerative changes in septal cholinergic neurons after axotomy and to assess their response to delayed infusion of NGF in rats. Results We found that there is a slow reduction of cholinergic cells labeled by ChAT and p75 after axotomy. However, this phenomenon is not accompanied by neurodegenerative changes or by a decrease in total neuronal number in the medial septum. Although the remaining axotomized-neurons appear healthy, they are unable to respond to delayed NGF infusion. Conclusions Our results demonstrate that at 3 weeks, axotomized cholinergic neurons lose their cholinergic phenotype without dying and down-regulate their NGF-receptors, precluding the possibility of a response to NGF. Therefore, the physiological role of NGF in the adult septal cholinergic system is to support phenotypic differentiation and not survival

  2. Cerebral cortical astroglia from the trisomy 16 mouse, a model for Down syndrome, produce neuronal cholinergic deficits in cell culture

    OpenAIRE

    Nelson, P. G.; Fitzgerald, S.; Rapoport, S I; Neale, E A; Galdzicki, Z; Dunlap, V.; Bowers, L; v. Agoston, D.

    1997-01-01

    Trisomy 21 (Down syndrome) is associated with a high incidence of Alzheimer disease and with deficits in cholinergic function in humans. We used the trisomy 16 (Ts16) mouse model for Down syndrome to identify the cellular basis for the cholinergic dysfunction. Cholinergic neurons and cerebral cortical astroglia, obtained separately from Ts16 mouse fetuses and their euploid littermates, were cultured in various combinations. Choline acetyltransferase activity and cholinergic neuron number were...

  3. A short-chain α-neurotoxin from Naja naja atra produces potent cholinergic-dependent analgesia

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective To investigate the analgesia induced by cobrotoxin (CT) from venom of Naja naja atra, and the effects of atropine and naloxone on the antinociceptive activity of CT in rodent pain models. Methods CT was administered intraperitoneally (33.3, 50, 75 μg/kg), intra-cerebral venticularly (2.4 μg/kg) or microinjected into periaqueductal gray ( PAG, 1.2 μg/kg). The antinociceptive action was tested using the hot-plate test and the acetic acid writhing test in mice and rats. The involvement of cholinergic system and the opioid system in CT-induced analgesia was examined by pretreatment of animals with atropine (0.5 mg/kg, im or 10 mg/kg, ip) or naloxone (3 mg/kg, ip). The effect of CT on motor activity was tested using the Animex test. Results CT (33.3, 50 and 75 μg/kg, ip) exhibited a dosedependent analgesic action in mice as determined with hot-plate test and acetic acid writhing test. In the mouse acetic acid writhing test, the intra-cerebral ventricle administration of CT 2.4 μg/kg (1/23th of a systemic dose) produced marked analgesic effects. Microinjection of CT 1.2 μg/kg ( 1/46th of systemic dose) into the PAG also elicited a robust analgesic action in the hot-plate test in rats. Atropine at 0.5 mg/kg (im) or naloxone at 3 mg/kg (ip) failed to block the analgesic effects of CT, but atropine at 10 mg/kg (ip) did antagonize the analgesia mediated by CT in the mouse acetic acid writhing test. At the highest effective dose of antinociception (75 μg/kg), CT did not change the spontaneous mobility of mice. Conclusion These results suggest that CT from Naja naja atra venom has analgesic effects. Central nervous system may be involved in CT' analgesic effects and the PAG may be the primary central site where CT exerts its effects. The central cholinergic system but not opioid system appears to be involved in the antinociceptive action of CT.

  4. Checks and balances on cholinergic signaling in brain and body function.

    Science.gov (United States)

    Soreq, Hermona

    2015-07-01

    A century after the discovery of acetylcholine (ACh), we recognize both ACh receptors, transporters, and synthesizing and degrading enzymes and regulators of their expression as contributors to cognition, metabolism, and immunity. Recent discoveries indicate that pre- and post-transcriptional ACh signaling controllers coordinate the identity, functioning, dynamics, and brain-to-body communication of cholinergic cells. Checks and balances including epigenetic mechanisms, alternative splicing, and miRNAs may all expand or limit the diversity of these cholinergic components by consistently performing genome-related surveillance. This regulatory network enables homeostatic maintenance of brain-to-body ACh signaling as well as reactions to nicotine, Alzheimer's disease anticholinesterase therapeutics, and agricultural pesticides. Here I review recent reports on the functional implications of these controllers of cholinergic signaling in and out of the brain. PMID:26100140

  5. Cholinergic Neurons - Keeping Check on Amyloid beta in the Cerebral Cortex

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    Saak V. Ovsepian

    2013-12-01

    Full Text Available The physiological relevance of the uptake of ligands with no apparent trophic functions via the p75 neurotrophin receptor (p75NTR remains unclear. Herein, we propose a homeostatic role for this in clearance of amyloid β (Aβ in the brain. We hypothesize that uptake of Aβ in conjunction with p75NTR followed by its degradation in lysosomes endows cholinergic basalo-cortical projections enriched in this receptor a facility for maintaining physiological levels of Aβ in target areas. Thus, in addition to the diffuse modulator influence and channeling of extra-thalamic signals, cholinergic innervations could supply the cerebral cortex with an elaborate system for Aβ drainage. Interpreting the emerging relationship of new molecular data with established role of cholinergic modulator system in regulating cortical network dynamics should provide new insights into the brain physiology and mechanisms of neuro-degenerative diseases.

  6. Cholinergic neuromuscular junctions in Brachionus calyciflorus and Lecane quadridentata (Rotifera:Monogononta)

    Institute of Scientific and Technical Information of China (English)

    Ignacio Alejandro Prez-Legaspi; Alma Lilin Guerrero-Barrera; Ivn Jos Galvn-Mendoza; Jos Luis Quintanar; Roberto Rico-Martnez

    2014-01-01

    Objective:To identify the presence of joint muscular and cholinergic systems in two freshwater rotifer species, Brachionus calyciflorus and Lecane quadridentata. Methods: The muscle actin fibers were stained with phalloidin-linked fluorescent dye, and acetylcholine was detected with Amplex Red Acetylcholine/Acetylcholinesterase Assay Kit, and then confocal scanning laser microscopy was used. Results:The musculature of Brachionus calyciflorus showed a pattern similar to other species of the same genus, while that of Lecane quadridentata was different from other rotifer genera described previously. The cholinergic system was determined by co-localization of both muscles and acetylcholine labels in the whole rotifer, suggesting the presence of neuromuscular junctions. Conclusions: The distribution pattern of muscular and acetylcholine systems showed considerable differences between the two species that might be related to different adaptations to particular ecological niches. The confirmation of a cholinergic system in rotifers contributes to the development of potential neuro-pharmacological and toxicological studies using rotifers as model organism.

  7. Selective Activation of Cholinergic Interneurons Enhances Accumbal Phasic Dopamine Release: Setting the Tone for Reward Processing

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    Roger Cachope

    2012-07-01

    Full Text Available Dopamine plays a critical role in motor control, addiction, and reward-seeking behaviors, and its release dynamics have traditionally been linked to changes in midbrain dopamine neuron activity. Here, we report that selective endogenous cholinergic activation achieved via in vitro optogenetic stimulation of nucleus accumbens, a terminal field of dopaminergic neurons, elicits real-time dopamine release. This mechanism occurs via direct actions on dopamine terminals, does not require changes in neuron firing within the midbrain, and is dependent on glutamatergic receptor activity. More importantly, we demonstrate that in vivo selective activation of cholinergic interneurons is sufficient to elicit dopamine release in the nucleus accumbens. Therefore, the control of accumbal extracellular dopamine levels by endogenous cholinergic activity results from a complex convergence of neurotransmitter/neuromodulator systems that may ultimately synergize to drive motivated behavior.

  8. Libidibia ferrea Mature Seeds Promote Antinociceptive Effect by Peripheral and Central Pathway: Possible Involvement of Opioid and Cholinergic Receptors

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    Luis Armando Sawada

    2014-01-01

    Full Text Available Libidibia ferrea (LF is a medicinal plant that holds many pharmacological properties. We evaluated the antinociceptive effect in the LF aqueous seed extract and Lipidic Portion of Libidibia ferrea (LPLF, partially elucidating their mechanisms. Histochemical tests and Gas chromatography of the LPLF were performed to characterize its fatty acids. Acetic acid-induced abdominal constriction, formalin-induced pain, and hot-plate test in mice were employed in the study. In all experiments, aqueous extract or LPLF was administered systemically at the doses of 1, 5, and 10 mg/kg. LF aqueous seed extract and LPLF demonstrated a dose-dependent antinociceptive effect in all tests indicating both peripheral anti-inflammatory and central analgesia properties. Also, the use of atropine (5 mg/kg, naloxone (5 mg/kg in the abdominal writhing test was able to reverse the antinociceptive effect of the LPLF, indicating that at least one of LF lipids components is responsible for the dose related antinociceptive action in chemical and thermal models of nociception in mice. Together, the present results suggested that Libidibia ferrea induced antinociceptive activity is possibly related to its ability to inhibit opioid, cholinergic receptors, and cyclooxygenase-2 pathway, since its main component, linoleic acid, has been demonstrated to produce such effect in previous studies.

  9. Libidibia ferrea Mature Seeds Promote Antinociceptive Effect by Peripheral and Central Pathway: Possible Involvement of Opioid and Cholinergic Receptors

    Science.gov (United States)

    Sawada, Luis Armando; Monteiro, Vanessa Sâmia da Conçeição; Rabelo, Guilherme Rodrigues; Dias, Germana Bueno; Da Cunha, Maura; do Nascimento, José Luiz Martins; Bastos, Gilmara de Nazareth Tavares

    2014-01-01

    Libidibia ferrea (LF) is a medicinal plant that holds many pharmacological properties. We evaluated the antinociceptive effect in the LF aqueous seed extract and Lipidic Portion of Libidibia ferrea (LPLF), partially elucidating their mechanisms. Histochemical tests and Gas chromatography of the LPLF were performed to characterize its fatty acids. Acetic acid-induced abdominal constriction, formalin-induced pain, and hot-plate test in mice were employed in the study. In all experiments, aqueous extract or LPLF was administered systemically at the doses of 1, 5, and 10 mg/kg. LF aqueous seed extract and LPLF demonstrated a dose-dependent antinociceptive effect in all tests indicating both peripheral anti-inflammatory and central analgesia properties. Also, the use of atropine (5 mg/kg), naloxone (5 mg/kg) in the abdominal writhing test was able to reverse the antinociceptive effect of the LPLF, indicating that at least one of LF lipids components is responsible for the dose related antinociceptive action in chemical and thermal models of nociception in mice. Together, the present results suggested that Libidibia ferrea induced antinociceptive activity is possibly related to its ability to inhibit opioid, cholinergic receptors, and cyclooxygenase-2 pathway, since its main component, linoleic acid, has been demonstrated to produce such effect in previous studies. PMID:24860820

  10. Particle size tailoring of ursolic acid nanosuspensions for improved anticancer activity by controlled antisolvent precipitation.

    Science.gov (United States)

    Wang, Yancai; Song, Ju; Chow, Shing Fung; Chow, Albert H L; Zheng, Ying

    2015-10-15

    The present study was aimed at tailoring the particle size of ursolic acid (UA) nanosuspension for improved anticancer activity. UA nanosuspensions were prepared by antisolvent precipitation using a four-stream multi-inlet vortex mixer (MIVM) under defined conditions of varying solvent composition, drug feeding concentration or stream flow rate. The resulting products were characterized for particle size and polydispersity. Two of the UA nanosuspensions with mean particle sizes of 100 and 300 nm were further assessed for their in-vitro activity against MCF-7 breast cancer cells using fluorescence microscopy with 4',6-diamidino-2-phenylindole (DAPI) staining, as well as flow cytometry with propidium (PI) staining and with double staining by fluorescein isothiocyanate. It was revealed that the solvent composition, drug feeding concentration and stream flow rate were critical parameters for particle size control of the UA nanosuspensions generated with the MIVM. Specifically, decreasing the UA feeding concentration or increasing the stream flow rate or ethanol content resulted in a reduction of particle size. Excellent reproducibility for nanosuspension production was demonstrated for the 100 and 300 nm UA preparations with a deviation of not more than 5% in particle size from the mean value of three independent batches. Fluorescence microscopy and flow cytometry revealed that these two different sized UA nanosuspensions, particularly the 300 nm sample, exhibited a higher anti-proliferation activity against the MCF-7 cells and afforded a larger population of these cells in both early and late apoptotic phases. In conclusion, MIVM is a robust and pragmatic tool for tailoring the particle size of the UA nanosuspension. Particle size appears to be a critical determinant of the anticancer activity of the UA nanoparticles.

  11. Sexually dimorphic effects of the Lhx7 null mutation on forebrain cholinergic function.

    Science.gov (United States)

    Fragkouli, A; Stamatakis, A; Zographos, E; Pachnis, V; Stylianopoulou, F

    2006-01-01

    It has been reported recently that mice lacking both alleles of the LIM-homeobox gene Lhx7, display dramatically reduced number of forebrain cholinergic neurons. In the present study, we investigated whether the Lhx7 mutation affects male and female mice differently, given the fact that gender differences are consistently observed in forebrain cholinergic function. Our results show that in adult male as well as female Lhx7 homozygous mutants there is a dramatic loss of choline acetyltransferase immunoreactive forebrain neurons, both projection and interneurons. The reduction of forebrain choline acetyltransferase immunoreactive neurons in Lhx7 homozygous mutants is accompanied by a decrease of acetylcholinesterase histochemical staining in all forebrain cholinergic neuron target areas of both male and female homozygous mutants. Furthermore, there was an increase of M1-, but not M2-, muscarinic acetylcholine receptor binding site density in the somatosensory cortex and basal ganglia of only the female homozygous mutant mice. Such an increase can be regarded as a mechanism acting to compensate for the dramatically reduced cholinergic input, raising the possibility that the forebrain cholinergic system in female mice may be more plastic and responsive to situations of limited neurotransmitter availability. Finally, our study provides additional data for the sexual dimorphism of the forebrain cholinergic system, as female mice appear to have a lower density of M1-muscarinic acetylcholine receptors in the striatal areas of the basal ganglia and a higher density of M2-muscarinic acetylcholine receptors, in a number of cortical areas, as well as the striatal areas of the basal ganglia. PMID:16338089

  12. State dependency of the effects of microinjection of cholinergic drugs into the nucleus pontis oralis.

    Science.gov (United States)

    López-Rodríguez, F; Kohlmeier, K; Morales, F R; Chase, M H

    1994-06-27

    The microinjection of cholinergic drugs into the pontine reticular formation elicits active sleep-like states that are comprised of the principal physiological patterns of activity that characterize naturally-occurring active sleep, i.e., EEG desynchronization, PGO waves, rapid eye movements and atonia. We have reported that other behavioral states arise even when cholinergic drugs are injected into the exact same reticular location. The present study was conducted to explore the basis for the differences in the drug effect. A combination of acetylcholine and neostigmine was injected by microiontophoresis into the dorsal region of the nucleus pontis oralis in four chronic, unanesthetized cats. The states that were induced by cholinergic drug injection depended on the state of the animal at the time of the injection. When the animal was awake, cholinergic injections resulted in a waking-dissociated state, which was characterized by EEG desynchronization and muscle atonia in a cat that appeared to be awake and was able to track objects in its visual field. If the cat was in quiet sleep at the time of the injection, an active sleep-like state followed that was indistinguishable from naturally-occurring active sleep; on a few occasions following cholinergic injections during quiet sleep there was a quiet sleep-dissociated state, which was characterized by PGO waves and muscle atonia in the cat that by other indices appeared to be in quiet sleep. The results of this study indicate that the state of the animal at the time of drug injection is a critical variable that influences the responses which are induced by cholinergic stimulation of the pontine reticular formation. PMID:7953643

  13. Ventral tegmental area cholinergic mechanisms mediate behavioral responses in the forced swim test.

    Science.gov (United States)

    Addy, N A; Nunes, E J; Wickham, R J

    2015-07-15

    Recent studies revealed a causal link between ventral tegmental area (VTA) phasic dopamine (DA) activity and pro-depressive and antidepressant-like behavioral responses in rodent models of depression. Cholinergic activity in the VTA has been demonstrated to regulate phasic DA activity, but the role of VTA cholinergic mechanisms in depression-related behavior is unclear. The goal of this study was to determine whether pharmacological manipulation of VTA cholinergic activity altered behavioral responding in the forced swim test (FST) in rats. Here, male Sprague-Dawley rats received systemic or VTA-specific administration of the acetylcholinesterase inhibitor, physostigmine (systemic; 0.06 or 0.125mg/kg, intra-cranial; 1 or 2μg/side), the muscarinic acetylcholine receptor (AChR) antagonist scopolamine (2.4 or 24μg/side), or the nicotinic AChR antagonist mecamylamine (3 or 30μg/side), prior to the FST test session. In control experiments, locomotor activity was also examined following systemic and intra-cranial administration of cholinergic drugs. Physostigmine administration, either systemically or directly into the VTA, significantly increased immobility time in FST, whereas physostigmine infusion into a dorsal control site did not alter immobility time. In contrast, VTA infusion of either scopolamine or mecamylamine decreased immobility time, consistent with an antidepressant-like effect. Finally, the VTA physostigmine-induced increase in immobility was blocked by co-administration with scopolamine, but unaltered by co-administration with mecamylamine. These data show that enhancing VTA cholinergic tone and blocking VTA AChRs has opposing effects in FST. Together, the findings provide evidence for a role of VTA cholinergic mechanisms in behavioral responses in FST.

  14. Cholinergic Enhancement of Brain Activation in Mild Cognitive Impairment (MCI during Episodic Memory Encoding

    Directory of Open Access Journals (Sweden)

    Shannon L Risacher

    2013-09-01

    Full Text Available Objective: To determine the physiological impact of treatment with donepezil (Aricept on neural circuitry supporting episodic memory encoding in patients with amnestic mild cognitive impairment (MCI using functional MRI (fMRI. Methods: 18 patients with MCI and 20 age-matched healthy controls (HC were scanned twice while performing an event-related verbal episodic encoding task. MCI participants were scanned before treatment and after approximately 3 months on donepezil; HC were untreated but rescanned at the same interval. Voxel-level analyses assessed treatment effects in activation profile relative to retest changes in non-treated HC. Changes in task-related connectivity in medial temporal circuitry were also evaluated, as were associations between brain activation pattern, task-related functional connectivity, task performance, and clinical measures of cognition.Results: At baseline, the MCI group showed reduced activation during encoding relative to HC in the right medial temporal lobe (MTL; hippocampal/parahippocampal and additional regions, as well as attenuated task-related deactivation, relative to rest, in a medial parietal lobe cluster. After treatment, the MCI group showed normalized MTL activation and improved parietal deactivation. These changes were associated with cognitive performance. After treatment, the MCI group also demonstrated increased task-related functional connectivity from the right MTL cluster seed region to a network of other sites including the basal nucleus/caudate and bilateral frontal lobes. Increased functional connectivity was associated with improved task performance.Conclusions: Pharmacologic enhancement of cholinergic function in amnestic MCI is associated with changes in brain activation pattern and functional connectivity during episodic memory processing which are in turn related to increased cognitive performance. fMRI is a promising biomarker for assessing treatment related changes in brain function.

  15. Pathway for interferon-gamma to promote the differentiation of cholinergic neurons in rat embryonic basal forebrain/septal nuclei

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: The supernatant of interferon-gamma (IFN γ ) co-cultured with neonatal rat cortical glia can promote the cells in embryonic basal forebrain/septal nuclei to differentiate into cholinergic neurons, but the mechanism is still unclear.OBJECTIVE: To analyze the pathways for IFN γ to promote the differentiation of primarily cultured cholinergic neurons in rat embryonic basal forebrain/septal nuclei through culture in different conditioned medium.DESIGN: A controlled experiment taking cells as the observational target.SETTINGS: Department of Biochemistry and Molecular Biology, Youjiang Medical College for Nationalities; Department of Cell Biology, Beijing University Health Science Center.MATERIALS: Sixty-four pregnant Wistar rats for 16 days (250 - 350 g) and 84 Wistar rats (either male or female, 5 - 7 g) of 0 - 1 day after birth were provided by the experimental animal department of Beijing University Health Science Center. Rat IFN γ were provided by Gibco Company; Glial fibrillary acidic protein by Huamei Company.METHODS: The experiments were carried out in the Department of Cell Biology, Beijing University Health Science Center and Daheng Image Company of Chinese Academy of Science from July 1995 to December 2002. ① Interventions: The nerve cells in the basal forebrain/septal nuclei of the pregnant Wistar rats for 16 days were primarily cultured, and then divided into four groups: Blank control group (not any supernatant and medium was added); Control group (added by mixed glial cell or astrocyte conditioned medium); IFN γ group (added by mixed glial cell or astrocyte conditioned medium+IFN γ ). Antibody group (added by mixed glial cell or astrocyte conditioned medium+IFN γ +Ab-IFN γ ). Mixed glial cell or astrocyte conditioned medium was prepared using cerebral cortex of Wistar rats of 0 - 1 day after birth. ② Evaluation: The immunohistochemical method was used to perform the choline acetyltransferase (ChAT) staining of cholinergic neurons

  16. Long-chain n-3 fatty acids - New anabolic compounds improving protein metabolism

    Science.gov (United States)

    Previous animal studies demonstrated that chronic feeding of long-chain n-3 polyunsaturated fatty acids (LCn-3PUFA) that modifies muscle membrane fatty acid composition promotes protein anabolism by blunting the age-associated deterioration in insulin sensitivity. The current study assessed, as a pr...

  17. Liquid–liquid extraction combined with differential isotope dimethylaminophenacyl labeling for improved metabolomic profiling of organic acids

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Jun; Li, Liang, E-mail: Liang.Li@ualberta.ca

    2013-11-25

    Graphical abstract: -- Highlights: •An improved method for profiling the carboxylic acid sub-metabolome is reported. •Liquid–liquid extraction was used for separating the organic acids from the amines. •{sup 12}C/{sup 13}C-p-dimethylaminophenacyl (DmPA) labeling of the organic acids was carried out on the extract. •Detection interference by amines and labeling efficiency reduction by water were reduced. •About 2500 {sup 12}C/{sup 13}C-peak pairs or putative metabolites could be detected from 20 μL of human urine. -- Abstract: A large fraction of the known human metabolome belong to organic acids. However, comprehensive profiling of the organic acid sub-metabolome is a major analytical challenge. In this work, we report an improved method for detecting organic acid metabolites. This method is based on the use of liquid–liquid extraction (LLE) to selectively extract the organic acids, followed by using differential isotope p-dimethylaminophenacyl (DmPA) labeling of the acid metabolites. The {sup 12}C-/{sup 13}C-labeled samples are analyzed by liquid chromatography Fourier-transform ion cyclotron resonance mass spectrometry (LC–FTICR–MS). It is shown that this LLE DmPA labeling method offers superior performance over the method of direct DmPA labeling of biofluids such as human urine. LLE of organic acids reduces the interference of amine-containing metabolites that may also react with DmPA. It can also remove water in a biofluid that can reduce the labeling efficiency. Using human urine as an example, it is demonstrated that about 2500 peak pairs or putative metabolites could be detected in a 30-min gradient LC–MS run, which is about 3 times more than that detected in a sample prepared using direct DmPA labeling. About 95% of the 1000 or so matched metabolites to the Human Metabolome Database (HMDB) are organic acids. It is further shown that this method can be used to handle as small as 10 μL of urine. We believe that this method opens the

  18. Diffusion-weighted magnetic resonance imaging detection of basal forebrain cholinergic degeneration in a mouse model.

    Science.gov (United States)

    Kerbler, Georg M; Hamlin, Adam S; Pannek, Kerstin; Kurniawan, Nyoman D; Keller, Marianne D; Rose, Stephen E; Coulson, Elizabeth J

    2013-02-01

    Loss of basal forebrain cholinergic neurons is an early and key feature of Alzheimer's disease, and magnetic resonance imaging (MRI) volumetric measurement of the basal forebrain has recently gained attention as a potential diagnostic tool for this condition. The aim of this study was to determine whether loss of basal forebrain cholinergic neurons underpins changes which can be detected through diffusion MRI using diffusion tensor imaging (DTI) and probabilistic tractography in a mouse model. To cause selective basal forebrain cholinergic degeneration, the toxin saporin conjugated to a p75 neurotrophin receptor antibody (mu-p75-SAP) was used. This resulted in ~25% loss of the basal forebrain cholinergic neurons and significant loss of terminal cholinergic projections in the hippocampus, as determined by histology. To test whether lesion of cholinergic neurons caused basal forebrain, hippocampal, or whole brain atrophy, we performed manual segmentation analysis, which revealed no significant atrophy in lesioned animals compared to controls (Rb-IgG-SAP). However, analysis by DTI of the basal forebrain area revealed a significant increase in fractional anisotropy (FA; +7.7%), mean diffusivity (MD; +6.1%), axial diffusivity (AD; +8.5%) and radial diffusivity (RD; +4.0%) in lesioned mice compared to control animals. These parameters strongly inversely correlated with the number of choline acetyl transferase-positive neurons, with FA showing the greatest association (r(2)=0.72), followed by MD (r(2)=0.64), AD (r(2)=0.64) and RD (r(2)=0.61). Moreover, probabilistic tractography analysis of the septo-hippocampal tracts originating from the basal forebrain revealed an increase in streamline MD (+5.1%) and RD (+4.3%) in lesioned mice. This study illustrates that moderate loss of basal forebrain cholinergic neurons (representing only a minor proportion of all septo-hippocampal axons) can be detected by measuring either DTI parameters of the basal forebrain nuclei or

  19. Loss of bonded phase in reversed-phase liquid chromatography in acidic eluents and practical ways to improve column stability.

    Science.gov (United States)

    Ma, Lianjia; Carr, Peter W

    2007-06-15

    Silica-based, reversed-phase liquid chromatographic (RPLC) stationary phases are very widely used to separate basic compounds in acidic eluents due to their high efficiency, good mechanical strength, and the versatile selectivity offered by different functional groups and the chemistry on the silica surface. However, the stability in acid of most silica-based stationary phases is poor, especially at elevated temperatures, due to hydrolysis of the siloxane bonds, which hold silanes on the silica substrate. This hydrolysis is commonly believed to be solely the result of catalysis by protons. However, we show that various metal cations (principally Fe3+/Fe2+, Ni2+, and Cr3+) released from acid corrosion of the stainless steel inlet frit greatly accelerate the hydrolysis of the siloxane bond. Furthermore, these metal cations, and not the high acidity per se, are mainly responsible for column instability. We show that removing the stainless steel inlet frit, or use of a titanium frit, greatly reduces or totally eliminates corrosion of the inlet frit and radically improves retention stability. The effects of various acids and types of organic modifier were also studied. These observations suggest a number of practical approaches that can significantly extend the lifetime of any RPLC stationary phase in acidic media at elevated temperature. PMID:17506522

  20. Study on chemical and volume control system design improvement of pressurized water reactor to use the enriched boric acid

    International Nuclear Information System (INIS)

    This study analyzes and determines the technical and economic feasibility of conversion from natural boric acid to enriched boric acid based on YGN 1,2 for existing plants and UCN 5,6 for new plants. The use of enriched boric acid may result in lower plant radiation exposure, lower stress corrosion cracking of Alloy 600, and the improvement of the water chemistry operation for PWR plants, since it is viewed as possibly a safer way of proceeding with an increase in RCS pH with less LiOH. The conversion of enriched boric acid would not affect core design, safety analysis licensing, etc.. The economic analysis shows that for the higher B-10 concentration, the existing power plants are more economical than new plants. It is expected that information and technology gained from this study would be utilized for the optimized CVCS design of the future nuclear power plants. It is also expected that the utilization of the enriched boric acid would become favourable for extended fuel cycle and especially MOX (Mixed Oxide) nuclear fuel because high boric acid concentration should be maintained for the beginning of the fuel cycle. 19 tabs., 20 figs., 20 refs. (Author)

  1. Maximized PUFA measurements improve insight in changes in fatty acid composition in response to temperature.

    Science.gov (United States)

    van Dooremalen, Coby; Pel, Roel; Ellers, Jacintha

    2009-10-01

    A general mechanism underlying the response of ectotherms to environmental changes often involves changes in fatty acid composition. Theory predicts that a decrease in temperature causes an increase in unsaturation of fatty acids, with an important role for long-chain poly-unsaturated fatty acids (PUFAs). However, PUFAs are particularly unstable and susceptible to peroxidation, hence subtle differences in fatty acid composition can be challenging to detect. We determined the fatty acid composition in springtail (Collembola) in response to two temperatures (5 degrees C and 25 degrees C). First, we tested different sample preparation methods to maximize PUFAs. Treatments consisted of different solvents for primary lipid extraction, mixing with antioxidant, flushing with inert gas, and using different temperature exposures during saponification. Especially slow saponification at low temperature (90 min at 70 degrees C) in combination with replacement of headspace air with nitrogen during saponification and methylation maximized PUFAs for GC analysis. Applying these methods to measure thermal responses in fatty acid composition, the data showed that the (maximized) proportion of C(20) PUFAs increased at low acclimation temperature. However, C(18) PUFAs increased at high acclimation temperature, which is contrary to expectations. Our study illustrates that PUFA levels in lipids may often be underestimated and this may hamper a correct interpretation of differential responses of fatty acid composition. PMID:19557745

  2. Maximized PUFA measurements improve insight in changes in fatty acid composition in response to temperature.

    Science.gov (United States)

    van Dooremalen, Coby; Pel, Roel; Ellers, Jacintha

    2009-10-01

    A general mechanism underlying the response of ectotherms to environmental changes often involves changes in fatty acid composition. Theory predicts that a decrease in temperature causes an increase in unsaturation of fatty acids, with an important role for long-chain poly-unsaturated fatty acids (PUFAs). However, PUFAs are particularly unstable and susceptible to peroxidation, hence subtle differences in fatty acid composition can be challenging to detect. We determined the fatty acid composition in springtail (Collembola) in response to two temperatures (5 degrees C and 25 degrees C). First, we tested different sample preparation methods to maximize PUFAs. Treatments consisted of different solvents for primary lipid extraction, mixing with antioxidant, flushing with inert gas, and using different temperature exposures during saponification. Especially slow saponification at low temperature (90 min at 70 degrees C) in combination with replacement of headspace air with nitrogen during saponification and methylation maximized PUFAs for GC analysis. Applying these methods to measure thermal responses in fatty acid composition, the data showed that the (maximized) proportion of C(20) PUFAs increased at low acclimation temperature. However, C(18) PUFAs increased at high acclimation temperature, which is contrary to expectations. Our study illustrates that PUFA levels in lipids may often be underestimated and this may hamper a correct interpretation of differential responses of fatty acid composition.

  3. Improvement on stability of square planar rhodium (Ⅰ) complexes for carbonylation of methanol to acetic acid

    Institute of Scientific and Technical Information of China (English)

    蒋华; 潘平来; 袁国卿; 陈新滋

    1999-01-01

    A series of square planar cis-dicarbonyl polymer coordinated rhodium complexes with uncoordinated donors near the central rhodium atoms for carbonylation of methanol to acetic acid are reported. Data of IR, XPS and thermal analysis show that these complexes are very stable. The intramolecular substitution reaction is proposed for their high stability. These complexes show excellent catalytic activity, selectivity and less erosion to the equipment for the methanol carbonylation to acetic acid. The distillation process may be used instead of flash vaporization in the manufacture of acetic acid, which reduces the investment on the equipment.

  4. Improved In Vitro Antileukemic Activity of All-Trans Retinoic Acid Loaded in Cholesteryl Butyrate Solid Lipid Nanoparticles.

    Science.gov (United States)

    Silva, Elton Luiz; Lima, Flávia Alves; Carneiro, Guilherme; Ramos Jonas Periera; Gomes, Dawidson Assis; de Souza-Fagundes, Elaine Maria; Ferreira, Lucas Antônio Miranda

    2016-02-01

    All-trans retinoic acid, a hydrophobic drug, has become one of the most successful examples of differentiation agents used for treatment of acute promyelocytic leukemia. On the other hand, histone deacetylase inhibitors, such as cholesteryl butyrate, present differentiating activity and.can potentiate action of drugs such as all-trans retinoic acid. Solid lipid nanoparticles represent a promising alternative for administration of hydrophobic drugs such as ATRA. This study aimed to develop, characterize, and evaluate the cytotoxicity of all-trans retinoic acid-loaded solid lipid nanoparticles for leukemia treatment. The influence of in situ formation of an ion pairing between all-trans retinoic acid and lipophilic amines on the characteristics of the particles (size, zeta potential, encapsulation efficiency) was evaluated. Cholesteryl butyrate, a butyric acid donor, was used as a component of the lipid matrix. In vitro activity on cell viability and distribution of cell cycle phases were evaluated for HL-60, Jurkat, and THP-1 cell lines. The encapsulation efficiency of all-trans retinoic acid in cholesteryl butyrate-solid lipid nanoparticles was significantly increased by the presence of the amine. Inhibition of cell viability by all-trans retinoic acid-loaded solid lipid nanoparticles was more pronounced than the free drug. Analysis of the distribution of cell cycle phases also showed increased activity for all-trans retinoic acid-loaded cholesteryl butyrate-solid lipid nanoparticles, with a clear increase in subdiploid DNA content. The ion pair formation in SLN containing cholesteryl butyrate can be explored as a simple and inexpensive strategy to improve the efficacy and bioavail-ability of ATRA in the treatment of the cancer and metabolic diseases in which this retinoid plays an important role. PMID:27433579

  5. Development of an Acid-Resistant Salmonella Typhi Ty21a Attenuated Vector For Improved Oral Vaccine Delivery

    Science.gov (United States)

    Feuille, Catherine M.; Starke, Carly Elizabeth C.; Bhagwat, Arvind A.; Stibitz, Scott; Kopecko, Dennis J.

    2016-01-01

    The licensed oral, live-attenuated bacterial vaccine for typhoid fever, Salmonella enterica serovar Typhi strain Ty21a, has also been utilized as a vaccine delivery platform for expression of diverse foreign antigens that stimulate protection against shigellosis, anthrax, plague, or human papilloma virus. However, Ty21a is acid-labile and, for effective oral immunization, stomach acidity has to be either neutralized with buffer or by-passed with Ty21a in an enteric-coated capsule (ECC). Several studies have shown that efficacy is reduced when Ty21a is administered in an ECC versus as a buffered liquid formulation, the former limiting exposure to GI tract lymphoid tissues. However, the ECC was selected as a more practical delivery format for both packaging/shipping and vaccine administration ease. We have sought to increase Ty21a acid-resistance to allow for removal from the ECC and immune enhancement. To improve Ty21a acid-resistance, glutamate-dependent acid resistance genes (GAD; responsible for Shigella spp. survival at very low pH) were cloned on a multi-copy plasmid (pGad) under a controllable arabinose-inducible promoter. pGad enhanced acid survival of Ty21a by 5 logs after 3 hours at pH 2.5, when cells were pre-grown in arabinose and under conditions that promote an acid-tolerance response (ATR). For genetically 100% stable expression, we inserted the gad genes into the Ty21a chromosome, using a method that allowed for subsequent removal of a selectable antibiotic resistance marker. Further, both bacterial growth curves and survival assays in cultured human monocytes/macrophages suggest that neither the genetic methods employed nor the resulting acid-resistance conferred by expression of the Gad proteins in Ty21a had any effect on the existing attenuation of this vaccine strain. PMID:27673328

  6. Improving the Keeping Quality and Vase Life of Cut Alstroemeria Flowers by Pre and Post-harvest Salicylic Acid Treatments

    Directory of Open Access Journals (Sweden)

    Elnaz SOLEIMANY-FARD

    2013-08-01

    Full Text Available Keeping quality and length of vase life are important factors for evaluation of cut flowers quality, for both domestic and export markets. Studding the effect of pre- and post-harvest salicylic acid applications on keeping quality and vase life of cut alstroemeria flowers during vase period is the approach taken. Aqueous solutions of salicylic acid at 0.0 (with distilled water, 1, 2 and 3 mM were sprayed to run-off (approximately 500 mL per plant, about two weeks before flowers harvest. The cut flowers were harvested in the early morning and both of cut flowers treated (sprayed and untreated were kept in vase solutions containing salicylic acid at 0.0 (with distilled water, 1, 2 and 3 mM. Sucrose at 4% was added to all treatments as a base solution. The changes in relative fresh weight, water uptake, water loss, water balance, total chlorophyll content and vase life were estimated during vase period. The results showed that the relative fresh weight, water uptake, water balance, total chlorophyll content and vase life decreased significantly while the water loss increased significantly during experiment for all treatments. A significant difference between salicylic acid and control treatments in all measured parameters is observed. During vase period, the salicylic acid treatments maintained significantly a more favourable relative fresh weight, water uptake, water balance, total chlorophyll content and supressed significantly water loss, as compared to control treatment. Also, the results showed that the using salicylic acid increased significantly the vase life cut alstroemeria flowers, over control. The highest values of measured parameters were found when plants were treated by pre + post-harvest application of salicylic acid at 3 mM. The result revealed that the quality attributes and vase life of cut alstroemeria flowers were improved by the use of salicylic acid treatment.

  7. Improved Butanol-Methanol (BUME) Method by Replacing Acetic Acid for Lipid Extraction of Biological Samples.

    Science.gov (United States)

    Cruz, Mutya; Wang, Miao; Frisch-Daiello, Jessica; Han, Xianlin

    2016-07-01

    Extraction of lipids from biological samples is a critical step in lipidomics, especially for shotgun lipidomics where lipid extracts are directly infused into a mass spectrometer. The butanol-methanol (BUME) extraction method was originally developed to extract lipids from plasma samples with 1 % acetic acid. Considering some lipids are sensitive to acidic environments, we modified this protocol by replacing acetic acid with lithium chloride solution and extended the modified extraction to tissue samples. Although no significant reduction of plasmalogen levels in the acidic BUME extracts of rat heart samples was found, the modified method was established to extract various tissue samples, including rat liver, heart, and plasma. Essentially identical profiles of the majority of lipid classes were obtained from the extracts of the modified BUME and traditional Bligh-Dyer methods. However, it was found that neither the original, nor the modified BUME method was suitable for 4-hydroxyalkenal species measurement in biological samples. PMID:27245345

  8. Improving bioethanol production from olive pruning biomass by deacetylation step prior acid hydrolysis and fermentation processes.

    Science.gov (United States)

    Moya, Alberto J; Peinado, Silvia; Mateo, Soledad; Fonseca, Bruno G; Sánchez, Sebastián

    2016-11-01

    In order to produce bioethanol from olive tree pruning biomass, deacetylation was performed employing sodium hydroxide. Optimal conditions were determined using experimental design techniques. The highest acetic acid removal (3.8g/dm(3)), obtained by response surface methodology, was at optimum pretreatment conditions of temperature 60°C, 0.8% NaOH and residence time 60min. After oxalic acid hydrolysis of pretreated biomass, the hydrolysates were directly used for ethanol production without further detoxification process. Ethanol yields ranged from 0.19 to 0.45g/g, reaching the maximum yield value when pretreatment was carried out at 130°C with 100mM oxalic acid, involving a combined severity factor (CSF) of 1.05. The highest ethanol concentration obtained from pretreated biomass was 6.2g/dm(3) at 150°C, using 75mM of oxalic acid (CSF=1.53). PMID:27579798

  9. Endophytic Fungi from Frankincense Tree Improves Host Growth and Produces Extracellular Enzymes and Indole Acetic Acid.

    Directory of Open Access Journals (Sweden)

    Abdul Latif Khan

    Full Text Available Boswellia sacra, an economically important frankincense-producing tree found in the desert woodlands of Oman, is least known for its endophytic fungal diversity and the potential of these fungi to produce extracellular enzymes and auxins. We isolated various fungal endophytes belonging to Eurotiales (11.8%, Chaetomiaceae (17.6%, Incertae sadis (29.5%, Aureobasidiaceae (17.6%, Nectriaceae (5.9% and Sporomiaceae (17.6% from the phylloplane (leaf and caulosphere (stem of the tree. Endophytes were identified using genomic DNA extraction, PCR amplification and sequencing the internal transcribed spacer regions, whereas a detailed phylogenetic analysis of the same gene fragment was made with homologous sequences. The endophytic colonization rate was significantly higher in the leaf (5.33% than the stem (0.262%. The Shannon-Weiner diversity index was H' 0.8729, while Simpson index was higher in the leaf (0.583 than in the stem (0.416. Regarding the endophytic fungi's potential for extracellular enzyme production, fluorogenic 4-methylumbelliferone standards and substrates were used to determine the presence of cellulases, phosphatases and glucosidases in the pure culture. Among fungal strains, Penicillum citrinum BSL17 showed significantly higher amounts of glucosidases (62.15±1.8 μM-1min-1mL and cellulases (62.11±1.6 μM-1min-1mL, whereas Preussia sp. BSL10 showed significantly higher secretion of glucosidases (69.4±0.79 μM-1min-1mL and phosphatases (3.46±0.31μM-1min-1mL compared to other strains. Aureobasidium sp. BSS6 and Preussia sp. BSL10 showed significantly higher potential for indole acetic acid production (tryptophan-dependent and independent pathways. Preussia sp. BSL10 was applied to the host B. sacra tree saplings, which exhibited significant improvements in plant growth parameters and accumulation of photosynthetic pigments. The current study concluded that endophytic microbial resources producing extracellular enzymes and auxin

  10. Endophytic Fungi from Frankincense Tree Improves Host Growth and Produces Extracellular Enzymes and Indole Acetic Acid

    Science.gov (United States)

    Khan, Abdul Latif; Al-Harrasi, Ahmed; Al-Rawahi, Ahmed; Al-Farsi, Zainab; Al-Mamari, Aza; Waqas, Muhammad; Asaf, Sajjad; Elyassi, Ali; Mabood, Fazal; Shin, Jae-Ho; Lee, In-Jung

    2016-01-01

    Boswellia sacra, an economically important frankincense-producing tree found in the desert woodlands of Oman, is least known for its endophytic fungal diversity and the potential of these fungi to produce extracellular enzymes and auxins. We isolated various fungal endophytes belonging to Eurotiales (11.8%), Chaetomiaceae (17.6%), Incertae sadis (29.5%), Aureobasidiaceae (17.6%), Nectriaceae (5.9%) and Sporomiaceae (17.6%) from the phylloplane (leaf) and caulosphere (stem) of the tree. Endophytes were identified using genomic DNA extraction, PCR amplification and sequencing the internal transcribed spacer regions, whereas a detailed phylogenetic analysis of the same gene fragment was made with homologous sequences. The endophytic colonization rate was significantly higher in the leaf (5.33%) than the stem (0.262%). The Shannon-Weiner diversity index was H′ 0.8729, while Simpson index was higher in the leaf (0.583) than in the stem (0.416). Regarding the endophytic fungi’s potential for extracellular enzyme production, fluorogenic 4-methylumbelliferone standards and substrates were used to determine the presence of cellulases, phosphatases and glucosidases in the pure culture. Among fungal strains, Penicillum citrinum BSL17 showed significantly higher amounts of glucosidases (62.15±1.8 μM-1min-1mL) and cellulases (62.11±1.6 μM-1min-1mL), whereas Preussia sp. BSL10 showed significantly higher secretion of glucosidases (69.4±0.79 μM-1min-1mL) and phosphatases (3.46±0.31μM-1min-1mL) compared to other strains. Aureobasidium sp. BSS6 and Preussia sp. BSL10 showed significantly higher potential for indole acetic acid production (tryptophan-dependent and independent pathways). Preussia sp. BSL10 was applied to the host B. sacra tree saplings, which exhibited significant improvements in plant growth parameters and accumulation of photosynthetic pigments. The current study concluded that endophytic microbial resources producing extracellular enzymes and auxin

  11. Phosphatidylcholine liposomes as carriers to improve topical ascorbic acid treatment of skin disorders

    Directory of Open Access Journals (Sweden)

    Serrano G

    2015-12-01

    Full Text Available Gabriel Serrano,1,* Patricia Almudéver,2,* Juan-Manuel Serrano,1 Javier Milara,2–5 Ana Torrens,1 Inmaculada Expósito,1 Julio Cortijo2–51Sesderma Laboratorios, 2Department of Pharmacology, Faculty of Medicine, University of Valencia, 3Clinical Research Unit, University General Hospital Consortium, 4CIBERES, Health Institute Carlos III, 5Research Foundation of the University General Hospital of Valencia, Valencia, Spain*These authors contributed equally to this workAbstract: Liposomes have been intensively investigated as carriers for different applications in dermatology and cosmetics. Ascorbic acid has potent antioxidant and anti-inflammatory properties preventing photodamage of keratinocytes; however, due to its instability and low skin penetration, an appropriate carrier is mandatory to obtain desirable efficacy. The present work investigates the ability of a specific ascorbate phosphatidylcholine (PC liposome to overcome the barrier of the stratum corneum and deliver the active agent into the dermis to prevent photodamage. Abdominal skin from ten patients was used. Penetration of PC liposomes was tested ex vivo in whole skin, epidermis, and dermis by means of fluorescein and sodium ascorbate. Histology and Franz diffusion cells were used to monitor the percutaneous absorption. Ultraviolet (UV-high performance liquid chromatography was used to analyze diffusion of sodium ascorbate through the different skin layers, while spectrofluorimetry and fluorescent microscopy were used for fluorescein monitoring. UVA/UVB irradiation of whole skin was applied to analyze the antioxidant capacity by Trolox assay and anti-inflammatory effects by tumor necrosis factor alpha and interleukin 1 beta enzyme-linked immunoassay. PC liposomal formulation improved skin penetration of fluorescein and ascorbate. Fluorescein PC liposomes showed better diffusion through epidermis than dermis while ascorbate liposomes showed better diffusion through the dermis than

  12. Endophytic Fungi from Frankincense Tree Improves Host Growth and Produces Extracellular Enzymes and Indole Acetic Acid.

    Science.gov (United States)

    Khan, Abdul Latif; Al-Harrasi, Ahmed; Al-Rawahi, Ahmed; Al-Farsi, Zainab; Al-Mamari, Aza; Waqas, Muhammad; Asaf, Sajjad; Elyassi, Ali; Mabood, Fazal; Shin, Jae-Ho; Lee, In-Jung

    2016-01-01

    Boswellia sacra, an economically important frankincense-producing tree found in the desert woodlands of Oman, is least known for its endophytic fungal diversity and the potential of these fungi to produce extracellular enzymes and auxins. We isolated various fungal endophytes belonging to Eurotiales (11.8%), Chaetomiaceae (17.6%), Incertae sadis (29.5%), Aureobasidiaceae (17.6%), Nectriaceae (5.9%) and Sporomiaceae (17.6%) from the phylloplane (leaf) and caulosphere (stem) of the tree. Endophytes were identified using genomic DNA extraction, PCR amplification and sequencing the internal transcribed spacer regions, whereas a detailed phylogenetic analysis of the same gene fragment was made with homologous sequences. The endophytic colonization rate was significantly higher in the leaf (5.33%) than the stem (0.262%). The Shannon-Weiner diversity index was H' 0.8729, while Simpson index was higher in the leaf (0.583) than in the stem (0.416). Regarding the endophytic fungi's potential for extracellular enzyme production, fluorogenic 4-methylumbelliferone standards and substrates were used to determine the presence of cellulases, phosphatases and glucosidases in the pure culture. Among fungal strains, Penicillum citrinum BSL17 showed significantly higher amounts of glucosidases (62.15±1.8 μM-1min-1mL) and cellulases (62.11±1.6 μM-1min-1mL), whereas Preussia sp. BSL10 showed significantly higher secretion of glucosidases (69.4±0.79 μM-1min-1mL) and phosphatases (3.46±0.31μM-1min-1mL) compared to other strains. Aureobasidium sp. BSS6 and Preussia sp. BSL10 showed significantly higher potential for indole acetic acid production (tryptophan-dependent and independent pathways). Preussia sp. BSL10 was applied to the host B. sacra tree saplings, which exhibited significant improvements in plant growth parameters and accumulation of photosynthetic pigments. The current study concluded that endophytic microbial resources producing extracellular enzymes and auxin could

  13. Chlorogenic acid improves late diabetes through adiponectin receptor signaling pathways in db/db mice.

    Directory of Open Access Journals (Sweden)

    Shasha Jin

    Full Text Available The aim of this study was to examine the effects of chlorogenic acid (CGA on glucose and lipid metabolism in late diabetic db/db mice, as well as on adiponectin receptors and their signaling molecules, to provide evidence for CGA in the prevention of type 2 diabetes. We randomly divided 16 female db/db mice into db/db-CGA and db/db-control (CON groups equally; db/m mice were used as control mice. The mice in both the db/db-CGA and db/m-CGA groups were administered 80 mg/kg/d CGA by lavage for 12 weeks, whereas the mice in both CON groups were given equal volumes of phosphate-buffered saline (PBS by lavage. At the end of the intervention, we assessed body fat and the parameters of glucose and lipid metabolism in the plasma, liver and skeletal muscle tissues as well as the levels of aldose reductase (AR and transforming growth factor-β1 (TGF-β1 in the kidneys and measured adiponectin receptors and the protein expression of their signaling molecules in liver and muscle tissues. After 12 weeks of intervention, compared with the db/db-CON group, the percentage of body fat, fasting plasma glucose (FPG and glycosylated hemoglobin (HbA1c in the db/db-CGA group were all significantly decreased; TGF-β1 protein expression and AR activity in the kidney were both decreased; and the adiponectin level in visceral adipose was increased. The protein expression of adiponectin receptors (ADPNRs, the phosphorylation of AMP-activated protein kinase (AMPK in the liver and muscle, and the mRNA and protein levels of peroxisome proliferator-activated receptor alpha (PPAR-α in the liver were all significantly greater. CGA could lower the levels of fasting plasma glucose and HbA1c during late diabetes and improve kidney fibrosis to some extent through the modulation of adiponectin receptor signaling pathways in db/db mice.

  14. Lactic acid bacteria in the quality improvement and depreciation of wine.

    Science.gov (United States)

    Lonvaud-Funel, A

    1999-01-01

    The winemaking process includes two main steps: lactic acid bacteria are responsible for the malolactic fermentation which follows the alcoholic fermentation by yeasts. Both types of microorganisms are present on grapes and on cellar equipment. Yeasts are better adapted to growth in grape must than lactic acid bacteria, so the alcoholic fermentation starts quickly. In must, up to ten lactic acid bacteria species can be identified. They belong to the Lactobacillus, Pediococcus, Leuconostoc and Oenococcus genera. Throughout alcoholic fermentation, a natural selection occurs and finally the dominant species is O. oeni, due to interactions between yeasts and bacteria and between bacteria themselves. After bacterial growth, when the population is over 10(6) CFU/ml, malolactic transformation is the obvious change in wine composition. However, many other substrates can be metabolized. Some like remaining sugars and citric acid are always assimilated by lactic acid bacteria, thus providing them with energy and carbon. Other substrates such as some amino acids may be used following pathways restricted to strains carrying the adequate enzymes. Some strains can also produce exopolysaccharides. All these transformations greatly influence the sensory and hygienic quality of wine. Malic acid transformation is encouraged because it induces deacidification. Diacetyl produced from citric acid is also helpful to some extent. Sensory analyses show that many other reactions change the aromas and make malolactic fermentation beneficial, but they are as yet unknown. On the contrary, an excess of acetic acid, the synthesis of glucane, biogenic amines and precursors of ethylcarbamate are undesirable. Fortunately, lactic acid bacteria normally multiply in dry wines; moreover some of these activities are not widespread. Moreover, the most striking trait of wine lactic acid bacteria is their capacity to adapt to a hostile environment. The mechanisms for this are not yet completely elucidated

  15. Improvement of surface acidity and structural regularity of Zr-modified mesoporous MCM-41

    International Nuclear Information System (INIS)

    This work reports the synthesis and surface characterization of a Zr-modified mesoporous MCM-41 solid with an ordered hexagonal arrangement, prepared through a templated synthesis route, using cetyltrimethylammonium chloride as the template. The surface features, crystalline structure, textural properties and surface acidity of the materials were characterized by in situ Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), N2 physisorption isotherms, 29Si MAS-NMR and in situ FT-IR of pyridine adsorption. It is evident that the surfactant cations inserted into the network of the solids during the preparation could be removed by calcination of the sample above 500 deg. C. The resultant material showed a large surface area of 680.6 m2 g-1 with a uniform pore diameter distribution in a very narrow range centered at approximately 2.5 nm. Zirconium incorporation into the Si-MCM-41 framework, confirmed by 29Si MAS-NMR analysis, increased not only the wall thickness of the mesopores but also the long-range order of the periodically hexagonal structure. Both, Lewis and Broensted acid sites, were formed on the surface of the Zr-modified MCM-41 solid. Compared to Si-MCM-41 on which only very weak Lewis acid sites were formed, the densities of both Lewis and Broensted acid sites and the strength of the acidity on the Zr-modified sample were significantly increased, indicating that the incorporation of zirconium greatly enhances the acidity of the material

  16. Improving succinic acid production by Actinobacillus succinogenes from raw industrial carob pods.

    Science.gov (United States)

    Carvalho, Margarida; Roca, Christophe; Reis, Maria A M

    2016-10-01

    Carob pods are an inexpensive by-product of locust bean gum industry that can be used as renewable feedstock for bio-based succinic acid. Here, for the first time, unprocessed raw carob pods were used to extract a highly enriched sugar solution, afterwards used as substrate to produce succinic acid using Actinobacillus succinogenes. Batch fermentations containing 30g/L sugars resulted in a production rate of 1.67gSA/L.h and a yield of 0.39gSA/g sugars. Taking advantage of A. succinogenes' metabolism, uncoupling cell growth from succinic acid production, a fed-batch mode was implemented to increase succinic acid yield and reduce by-products formation. This strategy resulted in a succinic acid yield of 0.94gSA/g sugars, the highest yield reported in the literature for fed-batch and continuous experiments, while maintaining by-products at residual values. Results demonstrate that raw carob pods are a highly efficient feedstock for bio-based succinic acid production. PMID:27394995

  17. Improvement Effect of Rosmarinic Acid on Serum Testosterone Level after Exposing with Electromagnetic Fields

    Directory of Open Access Journals (Sweden)

    Arezoo Farsi

    2013-07-01

    Full Text Available Objective: Rosmarinic acid has antioxidant, anti-inflammatory and antimicrobial activities and helps to prevent cell damage caused by free radicals and other sources.Material and methods: Male Wistar rats (n = 40 were allocated to four groups, a control group (n = 10 and three treatment groups (n = 30. The first treatment group received rosmarinic acid (5 mg/kg body weight by gavage method, the second test group received rosmarinic acid (5mg/kg body weight by gavage and electromagnetic field (EMF exposure at 50 Hz for 42 consecutive days, whilst the third test group just received EMF exposure for 42 consecutive days respectively; however, control group received 5cc Normal saline (0.9% NaCl daily by gavage method.Results: In 42nd day of research, 5 cc blood was collected for testosterone level measurement from whole groups. The level of testosterone significantly increased in groups that received Rosmarinic acid (PConclusion: Since in our study administration of 5mg/kg Rosmarinic acid significantly have increasing effect on decreased testosterone that is caused by EMF, it seems that using Rosmarinic acid as food additive can be efficient for supporting people living in EMF environmental pollution.

  18. An improved direct colorimetric method for the quantitative analysis of urinary hippuric acid as an index of toluene exposure

    Directory of Open Access Journals (Sweden)

    Ogata,Masana

    1977-08-01

    Full Text Available An improved direct colorimetric method for determining the concentration of urinary hippuric acid as an index of toluene exposure was described. One tenth ml of urine was diluted with 0.4 ml 0.01 M phosphate buffer H 6.9 and mixed with 0.5 ml pyridine. The mixture was layered on 0.2 ml benzenesulfonyl chloride. The reaction was started by mixing for one min with a mechanical shaker. The colored solution was allowed to stand for 30 min, diluted with 5 ml ethanol, and absorbance measured at 410 nm within 30 min after the dilution. The coefficient of variation of this method was 6% and the recovery 103% when urine contains about 0.2-0.5 mg hippuric acid per ml of urine. The concentration was linear up to 2.0 mg per ml hippuric acid in a specimen.

  19. Dose-dependent improvement of myoclonic hyperkinesia due to Valproic acid in eight Huntington's Disease patients: a case series

    Directory of Open Access Journals (Sweden)

    Przuntek Horst

    2006-02-01

    Full Text Available Abstract Background Chorea in Huntington's Disease (HD is usually treated with antidopaminergic neuroleptics like haloperidol, olanzapine and tiaprid or dopamine depleting drugs like tetrabenazine. Some patients with hyperkinesia, however, react to treatment with antidopaminergic drugs by developing extrapyramidal side effects. In earlier studies valproic acid showed no beneficial effect on involuntary choreatic movements. Myoclonus is rare in HD and is often overseen or misdiagnosed as chorea. Methods In this report, we present eight patients whose main symptom is myoclonic hyperkinesia. All patients were treated with valproic acid and scored by using the Unified Huntington's Disease Rating Scale (UHDRS motor score before and after treatment. In addition to this, two patients agreed to be videotaped. Results In seven patients myoclonus and, therefore the UHDRS motor score improved in a dose dependent manner. In three of these patients antidopaminergic medication could be reduced. Conclusion In the rare subgroup of HD patients suffering from myoclonic hyperkinesia, valproic acid is a possible alternative treatment.

  20. PREFRONTAL CORTICAL PROJECTIONS TO THE CHOLINERGIC NEURONS IN THE BASAL FOREBRAIN

    NARCIS (Netherlands)

    GAYKEMA, RPA; VANWEEGHEL, R; HERSH, LB; LUITEN, PGM

    1991-01-01

    The prefrontal cortex (PFC) projections to the basal forebrain cholinergic cell groups in the medial septum (MS), vertical and horizontal limbs of the diagonal band of Broca (VDB and HDB), and the magnocellular basal nucleus (MBN) in the rat were investigated by anterograde transport of Phaseolus vu

  1. Cholinergic Septo-Hippocampal Innervation Is Required for Trace Eyeblink Classical Conditioning

    Science.gov (United States)

    Fontan-Lozano, Angela; Troncoso, Julieta; Munera, Alejandro; Carrion, Angel Manuel; Delgado-Garcia, Jose Maria

    2005-01-01

    We studied the effects of a selective lesion in rats, with 192-IgG-saporin, of the cholinergic neurons located in the medial septum/diagonal band (MSDB) complex on the acquisition of classical and instrumental conditioning paradigms. The MSDB lesion induced a marked deficit in the acquisition, but not in the retrieval, of eyeblink classical…

  2. Cholinergic Modulation during Acquisition of Olfactory Fear Conditioning Alters Learning and Stimulus Generalization in Mice

    Science.gov (United States)

    Pavesi, Eloisa; Gooch, Allison; Lee, Elizabeth; Fletcher, Max L.

    2013-01-01

    We investigated the role of cholinergic neurotransmission in olfactory fear learning. Mice receiving pairings of odor and foot shock displayed fear to the trained odor the following day. Pretraining injections of the nicotinic antagonist mecamylamine had no effect on subsequent freezing, while the muscarinic antagonist scopolamine significantly…

  3. Long-Term Effects of Maternal Deprivation on Cholinergic System in Rat Brain

    Directory of Open Access Journals (Sweden)

    Branka Marković

    2014-01-01

    Full Text Available Numerous clinical studies have demonstrated an association between early stressful life events and adult life psychiatric disorders including schizophrenia. In rodents, early life exposure to stressors such as maternal deprivation (MD produces numerous hormonal, neurochemical, and behavioral changes and is accepted as one of the animal models of schizophrenia. The stress induces acetylcholine (Ach release in the forebrain and the alterations in cholinergic neurotransmitter system are reported in schizophrenia. The aim of this study was to examine long-term effects of maternal separation on acetylcholinesterase (AChE activity in different brain structures and the density of cholinergic fibers in hippocampus and retrosplenial (RS cortex. Wistar rats were separated from their mothers on the postnatal day (P 9 for 24 h and sacrificed on P60. Control group of rats was bred under the same conditions, but without MD. Brain regions were collected for AChE activity measurements and morphometric analysis. Obtained results showed significant decrease of the AChE activity in cortex and increase in the hippocampus of MD rats. Density of cholinergic fibers was significantly increased in CA1 region of hippocampus and decreased in RS cortex. Our results indicate that MD causes long-term structure specific changes in the cholinergic system.

  4. Pitx3 deficiency in mice affects cholinergic modulation of GABAergic synapses in the nucleus accumbens

    NARCIS (Netherlands)

    de Rover, Mischa; Lodder, Johannes C.; Smidt, Marten P.; Brussaard, Arjen B.

    2006-01-01

    Pitx3 deficiency in mice affects cholinergic modulation of GABAergic synapses in the nucleus accumbens. J Neurophysiol 96: 2034-2041, 2006. First published July 12, 2006; doi:10.1152/jn.00333.2006. We investigated to what extent Pitx3 deficiency, causing hyperdopaminergic transmission in the nucleus

  5. Cognitive impairment as a central cholinergic deficit in patients with Myasthenia Gravis

    Directory of Open Access Journals (Sweden)

    Antonia Kaltsatou

    2015-06-01

    Conclusions: VCmax and ACmax are governed mainly by the action of the Parasympathetic Nervous System, through acetylcholine. The results of this study demonstrate that the CNS may be affected in MG and support the hypothesis that MG has central cholinergic effects manifested by cognitive dysfunction.

  6. Dysautonomia due to reduced cholinergic neurotransmission causes cardiac remodeling and heart failure.

    Science.gov (United States)

    Lara, Aline; Damasceno, Denis D; Pires, Rita; Gros, Robert; Gomes, Enéas R; Gavioli, Mariana; Lima, Ricardo F; Guimarães, Diogo; Lima, Patricia; Bueno, Carlos Roberto; Vasconcelos, Anilton; Roman-Campos, Danilo; Menezes, Cristiane A S; Sirvente, Raquel A; Salemi, Vera M; Mady, Charles; Caron, Marc G; Ferreira, Anderson J; Brum, Patricia C; Resende, Rodrigo R; Cruz, Jader S; Gomez, Marcus Vinicius; Prado, Vania F; de Almeida, Alvair P; Prado, Marco A M; Guatimosim, Silvia

    2010-04-01

    Overwhelming evidence supports the importance of the sympathetic nervous system in heart failure. In contrast, much less is known about the role of failing cholinergic neurotransmission in cardiac disease. By using a unique genetically modified mouse line with reduced expression of the vesicular acetylcholine transporter (VAChT) and consequently decreased release of acetylcholine, we investigated the consequences of altered cholinergic tone for cardiac function. M-mode echocardiography, hemodynamic experiments, analysis of isolated perfused hearts, and measurements of cardiomyocyte contraction indicated that VAChT mutant mice have decreased left ventricle function associated with altered calcium handling. Gene expression was analyzed by quantitative reverse transcriptase PCR and Western blotting, and the results indicated that VAChT mutant mice have profound cardiac remodeling and reactivation of the fetal gene program. This phenotype was attributable to reduced cholinergic tone, since administration of the cholinesterase inhibitor pyridostigmine for 2 weeks reversed the cardiac phenotype in mutant mice. Our findings provide direct evidence that decreased cholinergic neurotransmission and underlying autonomic imbalance cause plastic alterations that contribute to heart dysfunction.

  7. Cholinergic modulation of the cerebral metabolic response to citalopram in Alzheimer's disease

    OpenAIRE

    Smith, Gwenn S.; Kramer, Elisse; Ma, Yilong; Hermann, Carol R.; Dhawan, Vijay; Chaly, Thomas; Eidelberg, David

    2009-01-01

    Pre-clinical and human neuropharmacological evidence suggests a role of cholinergic modulation of monoamines as a pathophysiological and therapeutic mechanism in Alzheimer's disease. The present study measured the effects of treatment with the cholinesterase inhibitor and nicotinic receptor modulator, galantamine, on the cerebral metabolic response to the selective serotonin reuptake inhibitor, citalopram. Seven probable Alzheimer's disease patients and seven demographically comparable contro...

  8. Activation of vascular cholinergic and adrenergic receptors induced by gamma rays

    International Nuclear Information System (INIS)

    Activation of vascular cholinergic receptors and adrenoceptors plays an important role in vasomotoricity and peripheric vascular resistance. These factors are essential in maintaining a stable blood pressure. The aim of this study is to investigate the radiosensitivity differences between vascular cholinergic receptors and adrenoceptors, and consequently to determinate the effects of ionizing radiation (whole body irradiation) on contractile response regulation of vascular smooth muscle fibers VSMF isolated from rat portal vein. Our results show that Clonidine, (non-specific adrenergic agonist), and phenylephrine which is more specific α1-adrenoceptor agonist, increase the VSMF contractions. The maximum effect is obtained at 10-5 - 3.10-5 M. On irradiated rats (1-3-5 Gy), there is an important shift thus, the maximal response (Emax) can be obtained in lower concentrations of clonidine and phenylephrine. Irradiation deceases the contractile responses of VSMF mediated by cholinergic stimulation, in a dose dependant manner. With Emax 1 Gy>Emax 3 Gy>Emax 5 Gy. Irradiated muscular fibers became less sensitive to acetylcholine, thus 3.10-8 M. A. ch induced more than 50% of contraction force increase in normal conditions. This concentration induce generally a negligible effect after irradiation. The results reveal the existence of radiosensitivity differences between vascular cholinergic and adrenergic receptors. (author)

  9. Cholinergic involvement in vascular and glucoregulatory actions of insulin in rats.

    Science.gov (United States)

    Lévesque, Martin; Santuré, Marta; Pitre, Maryse; Nadeau, André; Bachelard, Hélène

    2006-02-01

    This study was designed to test the glucose metabolic and vasodilator actions of insulin in rats and its relation to cholinergic system-dependent mechanisms. The first group of rats had pulsed Doppler flow probes and intravascular catheters implanted to determine blood pressure, heart rate, and regional blood flows. Insulin sensitivity was assessed by the euglycemic-hyperinsulinemic clamp technique carried out in the absence or presence of atropine. The second group of rats was used to determine the cholinergic contribution to in vivo insulin-mediated glucose utilization in individual muscles. Glucose uptake was examined by using [(3)H]2-deoxy-D-glucose. Muscarinic cholinergic blockade was found to significantly (P = 0.002) reduce insulin sensitivity and to completely abrogate the renal (P = 0.008) and hindquarter (P = 0.02) vasodilator responses to euglycemic infusion of insulin. A significant reduction in insulin-stimulated in vivo glucose uptake was also noted in soleus (P = 0.006), quadriceps (P = 0.03), gastrocnemius (P = 0.02), and extensor digitorum longus (EDL) (P = 0.001) muscles, when insulin was infused at a rate of 4 mU . kg(-1) . min(-1), whereas at the rate of 16 mU . kg(-1) . min(-1), a significant reduction in glucose uptake was only observed in EDL (P = 0.03) and quadriceps (P = 0.01) muscles. Together, these results demonstrate a potential role for cholinergic involvement with physiological insulin actions in glucose clearance and blood flow regulation in rats.

  10. Degeneration of beta-amyloid-associated cholinergic structures in transgenic APP SW mice.

    Science.gov (United States)

    Lüth, Hans-Joachim; Apelt, Jenny; Ihunwo, Amadi O; Arendt, Thomas; Schliebs, Reinhard

    2003-07-01

    Cholinergic dysfunction is a consistent feature of Alzheimer's disease, and the interrelationship between beta-amyloid deposits, inflammation and early cholinergic cell loss is still not fully understood. To characterize the mechanisms by which beta-amyloid and pro-inflammatory cytokines may exert specific degenerating actions on cholinergic cells ultrastructural investigations by electron microscopy were performed in brain sections from transgenic Tg2576 mice that express the Swedish double mutation of the human amyloid precursor protein and progressively develop beta-amyloid plaques during aging. Both light and electron microscopical investigations of the cerebral cortex of 19-month-old transgenic mice revealed a number of pathological tissue responses in close proximity of beta-amyloid plaques, such as activated microglia, astroglial proliferation, increased number of fibrous astrocytes, brain edema, degeneration of nerve cells, dendrites and axon terminals. Ultrastructural detection of choline acetyl transferase (ChAT)-immunostaining in cerebral cortical sections of transgenic mice clearly demonstrated degeneration of ChAT-immunoreactive fibres in the environment of beta-amyloid plaques and activated glial cells suggesting a role of beta-amyloid and/or inflammation in specific degeneration of cholinergic synaptic structures. PMID:12788508

  11. Hippocampal cholinergic interneurons visualized with the choline acetyltransferase promoter: anatomical distribution, intrinsic membrane properties, neurochemical characteristics, and capacity for cholinergic modulation

    Directory of Open Access Journals (Sweden)

    Feng eYi

    2015-03-01

    Full Text Available Release of acetylcholine (ACh in the hippocampus (HC occurs during exploration, arousal, and learning. Although the medial septum-diagonal band of Broca (MS-DBB is the major extrinsic source of cholinergic input to the HC, cholinergic neurons intrinsic to the HC also exist but remain poorly understood. Here, ChAT-tauGFP and ChAT-CRE/Rosa26YFP (ChAT-Rosa mice were examined in HC. The HC of ChAT-tauGFP mice was densely innervated with GFP-positive axons, often accompanied by large GFP-positive structures, some of which were Neurotrace/DAPI-negative and likely represent large axon terminals. In the HC of ChAT-Rosa mice, ChAT-YFP cells were Neurotrace-positive and more abundant in CA3 and dentate gyrus than CA1 with partial overlapping with calretinin/VIP. Moreover, an anti-ChAT antibody consistently showed ChAT immunoreactivity in ChAT-YFP cells from MS-DBB but rarely from HC. Furthermore, ChAT-YFP cells from CA1 stratum radiatum/stratum lacunosum moleculare (SR/SLM exhibited a stuttering firing phenotype but a delayed firing phenotype in stratum pyramidale (SP of CA3. Input resistance and capacitance were also different between CA1 SR/LM and CA3 SP ChAT-YFP cells. Bath application of ACh increased firing frequency in all ChAT-YFP cells; however, cholinergic modulation was larger in CA1 SR/SLM than CA3 SP ChAT-YFP cells. Finally, CA3 SP ChAT-YFP cells exhibited a wider AP half-width and weaker cholinergic modulation than YFP-negative CA3 pyramidal cells. Consistent with CRE expression in a subpopulation of principal cells, optogenetic stimulation evoked glutamatergic postsynaptic currents in CA1 SR/SLM interneurons. In conclusion, the presence of fluorescently labeled hippocampal cells common to both ChAT-Rosa and ChAT-tauGFP mice are in good agreement with previous reports on the existence of cholinergic interneurons, but both transgenic mouse lines exhibited unexpected anatomical features that departed considerably from earlier observations.

  12. Simultaneous improvement in production of microalgal biodiesel and high-value alpha-linolenic acid by a single regulator acetylcholine

    OpenAIRE

    Parsaeimehr, Ali; Sun, Zhilan; Dou, Xiao; Chen, Yi-Feng

    2015-01-01

    Background Photoautotrophic microalgae are a promising avenue for sustained biodiesel production, but are compromised by low yields of biomass and lipids at present. We are developing a chemical approach to improve microalgal accumulation of feedstock lipids as well as high-value alpha-linolenic acid which in turn might provide a driving force for biodiesel production. Results We demonstrate the effectiveness of the small bioactive molecule “acetylcholine” on accumulation of biomass, total li...

  13. Long-term ω-3 fatty acid supplementation induces anti-stress effects and improves learning in rats

    OpenAIRE

    Pérez, Miguel Á; Terreros, Gonzalo; Dagnino-Subiabre, Alexies

    2013-01-01

    Chronic stress leads to secretion of the adrenal steroid hormone corticosterone, inducing hippocampal atrophy and dendritic hypertrophy in the rat amygdala. Both alterations have been correlated with memory impairment and increased anxiety. Supplementation with ω-3 fatty acids improves memory and learning in rats. The aim of this study was to evaluate the effects of ω-3 supplementation on learning and major biological and behavioral stress markers. Male Sprague–Dawley rats were randomly assig...

  14. Improving beef hamburger quality and fatty acid profiles through dietary manipulation and exploitation of fat depot heterogeneity

    OpenAIRE

    Mapiye, Cletos; Aalhus, Jennifer L; Vahmani, Payam; Rolland, David C.; McAllister, Timothy A.; Block, Hushton C; Uttaro, Bethany; Proctor, Spencer D.; Michael E.R. Dugan

    2014-01-01

    Background Hamburger is the most consumed beef product in North America, but lacks in nutritional appeal due to its high fat content and high proportion of saturated fatty acids (SFA). Objectives of the present study were to improve the FA profiles of hamburgers made with perirenal fat (PRF) and subcutaneous fat (SCF) when feeding steers different diets along with examining differences in sensory attributes and oxidative stability. Diets included a control diet containing 70:30 red clover sil...

  15. Hydrolysis of Pentosan for Furfural Preparing Using Sulfuric Acid Catalyst to Improve Diesel Engine Fuel Quality

    International Nuclear Information System (INIS)

    The investigation on furfural preparation from peanut shell using sulfuric acid catalyst has been done. Furfural is an organic solvent used in industry especially petroleum industry. The purpose of this investigation is to know the effects of sulfuric acid concentration and solvent feed ratio towards furfural resulted and the reaction kinetics. The experiment was performed in the batch reactor. The result of this investigation showed that the process optimum condition was reached at sulfuric acid concentration of 7% and the solvent feed ratio of 12.5. The result at the optimum condition above was 5.97% of furfural. The relation between percentage of furfural resulted (Y) and sulfuric acid concentration (X) is Y = 0.893 X1.7023 . e-0.2554X with average deviation of 5.880 %. The relation between percentage of furfural resulted (Y) and solvent feed ratio (X) is Y = -53.0411 + 9.4137 X - 0.3780 X2 with average deviation 5.154 %. The relation between reaction rate constant (Y) and sulfuric acid concentration (X) is Y = 3.1916 . 10-3 + 8.2432 . 10-3 X - 5.2324 . 10-4 X2 with average deviation 8.024 %. (author)

  16. Sourdough fermentation or addition of organic acids or corresponding salts to bread improves nutritional properties of starch in healthy humans.

    Science.gov (United States)

    Liljeberg, H G; Lönner, C H; Björck, I M

    1995-06-01

    Postprandial blood glucose and insulin responses to barley bread containing organic acids or corresponding salts were evaluated in healthy human subjects. The satiety score and the rate and extent of in vitro starch digestion were also studied. Lactic acid was generated by use of a homofermentative starter culture or added to the dough. In addition, products were baked with Ca-lactate, or with Na-propionate at two different concentrations. Consumption of the product baked with a high concentration of Na-propionate significantly lowered the postprandial blood glucose and insulin responses, and significantly prolonged the duration of satiety compared with all other breads. When subjects consumed the breads baked with sourdough, lactic acid and Na-propionate, their glucose and insulin responses were reduced compared with the wholemeal bread alone. The rate of in vitro amylolysis was reduced only by ingestion of the breads containing lactic acid, suggesting that the beneficial impact of Na-propionate on metabolic responses and satiety was related to effects other than a reduced rate of starch hydrolysis. All bread products had a similar concentration of in vitro resistant starch of 1.3-2.1 g/100 g (starch basis). It is concluded that sourdough baking and other fermentation processes may improve the nutritional features of starch. The results also demonstrate that certain salts of organic acids may have metabolic effects.

  17. Improved detection of coastal acid sulfate soil hotspots through biomonitoring of metal(loid) accumulation in water lilies (Nymphaea capensis).

    Science.gov (United States)

    Stroud, Jacqueline L; Collins, Richard N

    2014-07-15

    Anthropogenically disturbed coastal acid sulfate soils along the east coast of Australia, and worldwide, periodically result in the discharge of acid waters containing high concentrations of metals. Identifying priority sites (hotspots) within a catchment for acid sulfate soil remediation activities typically involves long-term monitoring of drainwater chemistry, including the capture of data on unpredictable rain-induced groundwater discharge events. To improve upon this monitoring approach, this study investigated using the water lily (Nymphaea capensis) as a biomonitor of drainage waters to identify hotspots in three acid sulfate soil impacted catchments (83 km(2)) in north-eastern New South Wales, Australia. In one catchment where the location of hotspots was known, water lily lamina concentrations of a suite of metal(loid)s were significantly (pcatchment-scale water lily sampling program undertaken in catchments with unidentified hotspots revealed within catchment variation of plant metal concentrations up to 70-fold. High resolution maps produced from these results, therefore, provided strong evidence for the location of potential hotspots which were confirmed with measurements of drainwater chemistry during rain-induced groundwater discharge events. Median catchment lily accumulation was ca. 160 mg Al kg(-1) and 1,300 mg Fe kg(-1), with hotspots containing up to 6- and 10-fold higher Al and Fe concentrations. These findings suggest that biomonitoring with N. capensis can be an important tool to rapidly identify priority sites for remediation in acid sulfate soil impacted landscapes. PMID:24805963

  18. The Cholinergic Signaling Responsible for the Expression of a Memory-Related Protein in Primary Rat Cortical Neurons.

    Science.gov (United States)

    Chen, Tsan-Ju; Chen, Shun-Sheng; Wang, Dean-Chuan; Hung, Hui-Shan

    2016-11-01

    Cholinergic dysfunction in the brain is closely related to cognitive impairment including memory loss. In addition to the degeneration of basal forebrain cholinergic neurons, deficits in the cholinergic receptor signaling may also play an important role. In the present study, to examine the cholinergic signaling pathways responsible for the induction of a memory-related postsynaptic protein, a cholinergic agonist carbachol was used to induce the expression of activity-regulated cytoskeleton associated protein (Arc) in primary rat cortical neurons. After pretreating neurons with various antagonists or inhibitors, the levels of carbachol-induced Arc protein expression were detected by Western blot analysis. The results show that carbachol induces Arc protein expression mainly through activating M1 acetylcholine receptors and the downstream phospholipase C pathway, which may lead to the activation of the MAPK/ERK signaling pathway. Importantly, carbachol-mediated M2 receptor activation exerts negative effects on Arc protein expression and thus counteracts the enhanced effects of M1 activation. Furthermore, it is suggested for the first time that M1-mediated enhancement of N-methyl-D-aspartate receptor (NMDAR) responses, leading to Ca(2+) entry through NMDARs, contributes to carbachol-induced Arc protein expression. These findings reveal a more complete cholinergic signaling that is responsible for carbachol-induced Arc protein expression, and thus provide more information for developing treatments that can modulate cholinergic signaling and consequently alleviate cognitive impairment. J. Cell. Physiol. 231: 2428-2438, 2016. © 2016 Wiley Periodicals, Inc. PMID:26895748

  19. Cerebrolysin modulates pronerve growth factor/nerve growth factor ratio and ameliorates the cholinergic deficit in a transgenic model of Alzheimer's disease.

    Science.gov (United States)

    Ubhi, Kiren; Rockenstein, Edward; Vazquez-Roque, Ruben; Mante, Michael; Inglis, Chandra; Patrick, Christina; Adame, Anthony; Fahnestock, Margaret; Doppler, Edith; Novak, Philip; Moessler, Herbert; Masliah, Eliezer

    2013-02-01

    Alzheimer's disease (AD) is characterized by degeneration of neocortex, limbic system, and basal forebrain, accompanied by accumulation of amyloid-β and tangle formation. Cerebrolysin (CBL), a peptide mixture with neurotrophic-like effects, is reported to improve cognition and activities of daily living in patients with AD. Likewise, CBL reduces synaptic and behavioral deficits in transgenic (tg) mice overexpressing the human amyloid precursor protein (hAPP). The neuroprotective effects of CBL may involve multiple mechanisms, including signaling regulation, control of APP metabolism, and expression of neurotrophic factors. We investigate the effects of CBL in the hAPP tg model of AD on levels of neurotrophic factors, including pro-nerve growth factor (NGF), NGF, brain-derived neurotrophic factor (BDNF), neurotropin (NT)-3, NT4, and ciliary neurotrophic factor (CNTF). Immunoblot analysis demonstrated that levels of pro-NGF were increased in saline-treated hAPP tg mice. In contrast, CBL-treated hAPP tg mice showed levels of pro-NGF comparable to control and increased levels of mature NGF. Consistently with these results, immunohistochemical analysis demonstrated increased NGF immunoreactivity in the hippocampus of CBL-treated hAPP tg mice. Protein levels of other neurotrophic factors, including BDNF, NT3, NT4, and CNTF, were unchanged. mRNA levels of NGF and other neurotrophins were also unchanged. Analysis of neurotrophin receptors showed preservation of the levels of TrKA and p75(NTR) immunoreactivity per cell in the nucleus basalis. Cholinergic cells in the nucleus basalis were reduced in the saline-treated hAPP tg mice, and treatment with CBL reduced these cholinergic deficits. These results suggest that the neurotrophic effects of CBL might involve modulation of the pro-NGF/NGF balance and a concomitant protection of cholinergic neurons. PMID:23152192

  20. Cerebrolysin modulates pronerve growth factor/nerve growth factor ratio and ameliorates the cholinergic deficit in a transgenic model of Alzheimer's disease.

    Science.gov (United States)

    Ubhi, Kiren; Rockenstein, Edward; Vazquez-Roque, Ruben; Mante, Michael; Inglis, Chandra; Patrick, Christina; Adame, Anthony; Fahnestock, Margaret; Doppler, Edith; Novak, Philip; Moessler, Herbert; Masliah, Eliezer

    2013-02-01

    Alzheimer's disease (AD) is characterized by degeneration of neocortex, limbic system, and basal forebrain, accompanied by accumulation of amyloid-β and tangle formation. Cerebrolysin (CBL), a peptide mixture with neurotrophic-like effects, is reported to improve cognition and activities of daily living in patients with AD. Likewise, CBL reduces synaptic and behavioral deficits in transgenic (tg) mice overexpressing the human amyloid precursor protein (hAPP). The neuroprotective effects of CBL may involve multiple mechanisms, including signaling regulation, control of APP metabolism, and expression of neurotrophic factors. We investigate the effects of CBL in the hAPP tg model of AD on levels of neurotrophic factors, including pro-nerve growth factor (NGF), NGF, brain-derived neurotrophic factor (BDNF), neurotropin (NT)-3, NT4, and ciliary neurotrophic factor (CNTF). Immunoblot analysis demonstrated that levels of pro-NGF were increased in saline-treated hAPP tg mice. In contrast, CBL-treated hAPP tg mice showed levels of pro-NGF comparable to control and increased levels of mature NGF. Consistently with these results, immunohistochemical analysis demonstrated increased NGF immunoreactivity in the hippocampus of CBL-treated hAPP tg mice. Protein levels of other neurotrophic factors, including BDNF, NT3, NT4, and CNTF, were unchanged. mRNA levels of NGF and other neurotrophins were also unchanged. Analysis of neurotrophin receptors showed preservation of the levels of TrKA and p75(NTR) immunoreactivity per cell in the nucleus basalis. Cholinergic cells in the nucleus basalis were reduced in the saline-treated hAPP tg mice, and treatment with CBL reduced these cholinergic deficits. These results suggest that the neurotrophic effects of CBL might involve modulation of the pro-NGF/NGF balance and a concomitant protection of cholinergic neurons.

  1. Involvement of nicotinic and muscarinic receptors in the endogenous cholinergic modulation of the balance between excitation and inhibition in the young rat visual cortex.

    Science.gov (United States)

    Lucas-Meunier, Estelle; Monier, Cyril; Amar, Muriel; Baux, Gérard; Frégnac, Yves; Fossier, Philippe

    2009-10-01

    This study aims to clarify how endogenous release of cortical acetylcholine (ACh) modulates the balance between excitation and inhibition evoked in visual cortex. We show that electrical stimulation in layer 1 produced a significant release of ACh measured intracortically by chemoluminescence and evoked a composite synaptic response recorded intracellularly in layer 5 pyramidal neurons of rat visual cortex. The pharmacological specificity of the ACh neuromodulation was determined from the continuous whole-cell voltage clamp measurement of stimulation-locked changes of the input conductance during the application of cholinergic agonists and antagonists. Blockade of glutamatergic and gamma-aminobutyric acid (GABAergic) receptors suppressed the evoked response, indicating that stimulation-induced release of ACh does not directly activate a cholinergic synaptic conductance in recorded neurons. Comparison of cytisine and mecamylamine effects on nicotinic receptors showed that excitation is enhanced by endogenous evoked release of ACh through the presynaptic activation of alpha(*)beta4 receptors located on glutamatergic fibers. DHbetaE, the selective alpha4beta2 nicotinic receptor antagonist, induced a depression of inhibition. Endogenous ACh could also enhance inhibition by acting directly on GABAergic interneurons, presynaptic to the recorded cell. We conclude that endogenous-released ACh amplifies the dominance of the inhibitory drive and thus decreases the excitability and sensory responsiveness of layer 5 pyramidal neurons. PMID:19176636

  2. Improved method to obtain pfaffic acid as a marker for quality control

    Energy Technology Data Exchange (ETDEWEB)

    Rodrigues, Marili Villa Nova; Vedovello, Amanda; Rodrigues, Rodney Alexandre Ferreira; Montanari Junior, Ilio; Rehder, Vera Lucia Garcia, E-mail: rodney@cpqba.unicamp.br [Centro Pluridisciplinar de Pesquisas Quimicas, Biologicas e Agricolas, Universidade Estadual de Campinas, SP (Brazil)

    2013-09-01

    Pfaffic acid, a marker of Hebanthe eriantha (Brazilian ginseng), was first isolated in 1983 but is not yet commercially available. This lack of availability compromises the quality control of this plant and its derivatives. This paper proposes a process for pfaffic acid isolation from roots of H. eriantha at a purity suitable for analytical purposes. The steps involved in this process included extraction, hydrolysis, fractionation and purification by preparative HPLC. This process led to isolation of pfaffic acid with a chromatographic purity of 98.5% in a 0.25% yield from dried roots of H. eriantha; this yield is more than forty times higher than that of the current method in the literature. (author)

  3. Improved method to obtain pfaffic acid as a marker for quality control

    Directory of Open Access Journals (Sweden)

    Marili Villa Nova Rodrigues

    2013-01-01

    Full Text Available Pfaffic acid, a marker of Hebanthe eriantha (Brazilian ginseng, was first isolated in 1983 but is not yet commercially available. This lack of availability compromises the quality control of this plant and its derivatives. This paper proposes a process for pfaffic acid isolation from roots of H. eriantha at a purity suitable for analytical purposes. The steps involved in this process included extraction, hydrolysis, fractionation and purification by preparative HPLC. This process led to isolation of pfaffic acid with a chromatographic purity of 98.5% in a 0.25% yield from dried roots of H. eriantha; this yield is more than forty times higher than that of the current method in the literature.

  4. Improvement in electrochemical capacitance of activated carbon from scrap tires by nitric acid treatment

    Science.gov (United States)

    Han, Yan; Zhao, Ping-Ping; Dong, Xiao-Ting; Zhang, Cui; Liu, Shuang-Xi

    2014-12-01

    Activated carbon (AC) obtained from the industrial pyrolytic tire char is treated by concentrated nitric acid (AC-HNO3) and then used as the electrode material for supercapacitors. Surface properties and electrochemical capacitances of AC and ACHNO3 are studied. It is found that the morphology and the porous texture for AC and AC-HNO3 have little difference, while the oxygen content increases and functional groups change after the acid treatment. Electrochemical results demonstrate that the AC-HNO3 electrode displays higher specific capacitance, better stability and cycling performance, and lower equivalent series resistance, indicating that AC obtained from the industrial pyrolytic tire char treated by concentrated nitric acid is applicable for supercapacitors.

  5. Improved sensitivity of an acid sphingomyelinase activity assay using a C6:0 sphingomyelin substrate

    OpenAIRE

    Wei-Lien Chuang; Joshua Pacheco; Samantha Cooper; Kingsbury, Jonathan S.; John Hinds; Pavlina Wolf; Petra Oliva; Joan Keutzer; Cox, Gerald F.; Kate Zhang

    2015-01-01

    Short-chain C6-sphingomyelin is an artificial substrate that was used in an acid sphingomyelinase activity assay for a pilot screening study of patients with Niemann–Pick disease types A and B. Using previously published multiplex and single assay conditions, normal acid sphingomyelinase activity levels (i.e. false negative results) were observed in two sisters with Niemann–Pick B who were compound heterozygotes for two missense mutations, p.C92W and p.P184L, in the SMPD1 gene. Increasing the...

  6. Endogenous cholinergic input to the pontine REM sleep generator is not required for REM sleep to occur.

    Science.gov (United States)

    Grace, Kevin P; Vanstone, Lindsay E; Horner, Richard L

    2014-10-22

    Initial theories of rapid eye movement (REM) sleep generation posited that induction of the state required activation of the pontine subceruleus (SubC) by cholinergic inputs. Although the capacity of cholinergic neurotransmission to contribute to REM sleep generation has been established, the role of cholinergic inputs in the generation of REM sleep is ultimately undetermined as the critical test of this hypothesis (local blockade of SubC acetylcholine receptors) has not been rigorously performed. We used bilateral microdialysis in freely behaving rats (n = 32), instrumented for electroencephalographic and electromyographic recording, to locally manipulate neurotransmission in the SubC with select drugs. As predicted, combined microperfusion of D-AP5 (glutamate receptor antagonist) and muscimol (GABAA receptor agonist) in the SubC virtually eliminated REM sleep. However, REM sleep was not reduced by scopolamine microperfusion in this same region, at a concentration capable of blocking the effects of cholinergic receptor stimulation. This result suggests that transmission of REM sleep drive to the SubC is acetylcholine-independent. Although SubC cholinergic inputs are not majorly involved in REM sleep generation, they may perform a minor function in the reinforcement of transitions into REM sleep, as evidenced by increases in non-REM-to-REM sleep transition duration and failure rate during cholinergic receptor blockade. Cholinergic receptor antagonism also attenuated the normal increase in hippocampal θ oscillations that characterize REM sleep. Using computational modeling, we show that our in vivo results are consistent with a mutually excitatory interaction between the SubC and cholinergic neurons where, importantly, cholinergic neuron activation is gated by SubC activity.

  7. Effects of 12-Week Bacopa monnieri Consumption on Attention, Cognitive Processing, Working Memory, and Functions of Both Cholinergic and Monoaminergic Systems in Healthy Elderly Volunteers

    Directory of Open Access Journals (Sweden)

    Tatimah Peth-Nui

    2012-01-01

    Full Text Available At present, the scientific evidence concerning the effect of Bacopa monnieri on brain activity together with working memory is less available. Therefore, we aimed to determine the effect of B. monnieri on attention, cognitive processing, working memory, and cholinergic and monoaminergic functions in healthy elderly. A randomized double-blind placebo-controlled design was utilized. Sixty healthy elderly subjects (mean age 62.62 years; SD 6.46, consisting of 23 males and 37 females, received either a standardized extract of B. monnieri (300 and 600 mg or placebo once daily for 12 weeks. The cholinergic and monoaminergic systems functions were determined using AChE and MAO activities. Working memory was assessed using percent accuracy and reaction time of various memory tests as indices, whereas attention and cognitive processing were assessed using latencies and amplitude of N100 and P300 components of event-related potential. All assessments were performed before treatment, every four weeks throughout study period, and at four weeks after the cessation of intervention. B. monnieri-treated group showed improved working memory together with a decrease in both N100 and P300 latencies. The suppression of plasma AChE activity was also observed. These results suggest that B. monnieri can improve attention, cognitive processing, and working memory partly via the suppression of AChE activity.

  8. Biotransformation and improved enzymatic extraction of chlorogenic acid from coffee pulp by filamentous fungi.

    Science.gov (United States)

    Torres-Mancera, María Teresa; Baqueiro-Peña, Itzamná; Figueroa-Montero, Arturo; Rodríguez-Serrano, Gabriela; González-Zamora, Eduardo; Favela-Torres, Ernesto; Saucedo-Castañeda, Gerardo

    2013-01-01

    The highest enzymatic extraction of covalent linked chlorogenic (36.1%) and caffeic (CA) (33%) acids from coffee pulp (CP) was achieved by solid-state fermentation with a mixture of three enzymatic extracts produced by Aspergillus tamarii, Rhizomucor pusillus, and Trametes sp. Enzyme extracts were produced in a practical inexpensive way. Synergistic effects on the extraction yield were observed when more than one enzyme extract was used. In addition, biotransformation of chlorogenic acid (ChA) by Aspergillus niger C23308 was studied. Equimolar transformation of ChA into CA and quinic acids (QA) was observed during the first 36 h in submerged culture. Subsequently, after 36 h, equimolar transformation of CA into protocatechuic acid was observed; this pathway is being reported for the first time for A. niger. QA was used as a carbon source by A. niger C23308. This study presents the potential of using CP to produce enzymes and compounds such as ChA with biological activities.

  9. Targeted modification of storage protein content resulting in improved amino acid composition of barley grain

    DEFF Research Database (Denmark)

    Sikdar, Md. Shafiqul Islam; Bowra, S; Schmidt, Daiana;

    2016-01-01

    C-hordein in barley and ω-gliadins in wheat are members of the prolamins protein families. Prolamins are the major component of cereal storage proteins and composed of non-essential amino acids (AA) such as proline and glutamine therefore have low nutritional value. Using double stranded RNAi sil...

  10. Biotransformation and improved enzymatic extraction of chlorogenic acid from coffee pulp by filamentous fungi.

    Science.gov (United States)

    Torres-Mancera, María Teresa; Baqueiro-Peña, Itzamná; Figueroa-Montero, Arturo; Rodríguez-Serrano, Gabriela; González-Zamora, Eduardo; Favela-Torres, Ernesto; Saucedo-Castañeda, Gerardo

    2013-01-01

    The highest enzymatic extraction of covalent linked chlorogenic (36.1%) and caffeic (CA) (33%) acids from coffee pulp (CP) was achieved by solid-state fermentation with a mixture of three enzymatic extracts produced by Aspergillus tamarii, Rhizomucor pusillus, and Trametes sp. Enzyme extracts were produced in a practical inexpensive way. Synergistic effects on the extraction yield were observed when more than one enzyme extract was used. In addition, biotransformation of chlorogenic acid (ChA) by Aspergillus niger C23308 was studied. Equimolar transformation of ChA into CA and quinic acids (QA) was observed during the first 36 h in submerged culture. Subsequently, after 36 h, equimolar transformation of CA into protocatechuic acid was observed; this pathway is being reported for the first time for A. niger. QA was used as a carbon source by A. niger C23308. This study presents the potential of using CP to produce enzymes and compounds such as ChA with biological activities. PMID:23341203

  11. Seamustard (Undaria pinnatifida) Improves Growth, Immunity, Fatty Acid Profile and Reduces Cholesterol in Hanwoo Steers

    OpenAIRE

    Hwang, J. A.; Islam, M. M.; Ahmed, S. T.; Mun, H. S.; G. M. Kim; Kim, Y. J.; Yang, C. J.

    2014-01-01

    The study was designed to evaluate the effect of 2% seamustard (Undaria pinnatifida) by-product (SW) on growth performance, immunity, carcass characteristics, cholesterol content and fatty acid profile in Hanwoo steers. A total of 20 Hanwoo steers (ave. 22 months old; 619 kg body weight) were randomly assigned to control (basal diet) and 2% SW supplemented diet. Dietary SW supplementation significantly (p

  12. Polyethersulfone improves isothermal nucleic acid amplification compared to current paper-based diagnostics.

    Science.gov (United States)

    Linnes, J C; Rodriguez, N M; Liu, L; Klapperich, C M

    2016-04-01

    Devices based on rapid, paper-based, isothermal nucleic acid amplification techniques have recently emerged with the potential to fill a growing need for highly sensitive point-of-care diagnostics throughout the world. As this field develops, such devices will require optimized materials that promote amplification and sample preparation. Herein, we systematically investigated isothermal nucleic acid amplification in materials currently used in rapid diagnostics (cellulose paper, glass fiber, and nitrocellulose) and two additional porous membranes with upstream sample preparation capabilities (polyethersulfone and polycarbonate). We compared amplification efficiency from four separate DNA and RNA targets (Bordetella pertussis, Chlamydia trachomatis, Neisseria gonorrhoeae, and Influenza A H1N1) within these materials using two different isothermal amplification schemes, helicase dependent amplification (tHDA) and loop-mediated isothermal amplification (LAMP), and traditional PCR. We found that the current paper-based diagnostic membranes inhibited nucleic acid amplification when compared to membrane-free controls; however, polyethersulfone allowed for efficient amplification in both LAMP and tHDA reactions. Further, observing the performance of traditional PCR amplification within these membranes was not predicative of their effects on in situ LAMP and tHDA. Polyethersulfone is a new material for paper-based nucleic acid amplification, yet provides an optimal support for rapid molecular diagnostics for point-of-care applications. PMID:26906904

  13. Desmodium genetic resources for improving flavonoid concentrations, oil, and fatty acid content

    Science.gov (United States)

    Seed from several Desmodium species adapted to the Griffin, GA environment have potential as nutraceutical supplements for livestock. Flavonoids, oil, and fatty acid profiles identified from 25 accessions representing 5 species (D. discolor, D. incanum, D. intortum, D. sandwicense, and D. tortuosum)...

  14. Systems biology and metabolic engineering of lactic acid bacteria for improved fermented foods

    NARCIS (Netherlands)

    Flahaut, N.A.L.; Vos, de W.M.

    2014-01-01

    Lactic acid bacteria have long been used in industrial dairy and other food fermentations that make use of their metabolic activities leading to products with specific organoleptic properties. Metabolic engineering is a rational approach to steer fermentations toward the production of desired compou

  15. Improvement of clavulanic acid production in Streptomyces clavuligerus by genetic manipulation of structural biosynthesis genes.

    Science.gov (United States)

    Jnawali, Hum Nath; Yoo, Jin Cheol; Sohng, Jae Kyung

    2011-06-01

    To enhance clavulanic acid production, four structural clavulanic acid biosynthesis genes, carboxyethylarginine synthase (ceas2), β-lactam synthetase (bls2), clavaminate synthase (cas2) and proclavaminate amidinohydrolase (pah2), were amplified from Streptomyces clavuligerus genomic DNA. They were cloned in the pSET152 integration and pIBR25 expression vectors containing the strong ermE* promoter to generate pHN18 and pHN19, respectively, and both plasmids were introduced into S. clavuligerus by protoplast transformation. Clavulanic acid production was increased by 8.7-fold (to ~310 mg/l) in integrative pHN18 transformants and by 5.1-fold in pHN19 transformants compared to controls. Transcriptional analyses showed that the expression levels of ceas2, bls2, cas2 and pah2 were markedly increased in both transformants as compared with wild-type. The elevation of the ceas2, bls2, cas2 and pah2 transcripts was consistent with the enhanced production of clavulanic acid.

  16. Improving farm management by modeling the contamination of farm tank milk with butyric acid bacteria

    NARCIS (Netherlands)

    Vissers, M.M.M.; Driehuis, F.; Giffel, te M.C.; Jong, de P.; Lankveld, J.M.G.

    2006-01-01

    Control of contamination of farm tank milk (FTM) with the spore-forming butyric acid bacteria (BAB) is important to prevent the late-blowing defect in semi-hard cheeses. The risk of late blowing can be decreased via control of the contamination level of FTM with BAB. A modeling approach was applied

  17. Lewis base additives improve the zeolite ferrierite-catalyzed synthesis of isostearic acid

    Science.gov (United States)

    Isostearic acid (IA) is of interest for industrial purposes especially in the area of biolubricants, such as cosmetics and slip additives for polyolefin and related copolymer films. This study was designed to develop a zeolitic catalysis process for IA production through isomerization of fatty aci...

  18. Amino Acid Prodrugs: An Approach to Improve the Absorption of HIV-1 Protease Inhibitor, Lopinavir

    Directory of Open Access Journals (Sweden)

    Mitesh Patel

    2014-04-01

    Full Text Available Poor systemic concentrations of lopinavir (LPV following oral administration occur due to high cellular efflux by P-glycoprotein (P-gp and multidrug resistance-associated proteins (MRPs and extensive metabolism by CYP3A4 enzymes. In this study, amino acid prodrugs of LPV were designed and investigated for their potential to circumvent efflux processes and first pass effects. Three amino acid prodrugs were synthesized by conjugating isoleucine, tryptophan and methionine to LPV. Prodrug formation was confirmed by the LCMS/MS and NMR technique. Interaction of LPV prodrugs with efflux proteins were carried out in P-gp (MDCK-MDR1 and MRP2 (MDCK-MRP2 transfected cells. Aqueous solubility studies demonstrated that prodrugs generate higher solubility relative to LPV. Prodrugs displayed higher stability under acidic conditions and degraded significantly with rise in pH. Uptake and transport data suggested that prodrugs carry significantly lower affinity towards P-gp and MRP2 relative to LPV. Moreover, prodrugs exhibited higher liver microsomal stability relative to LPV. Hence, amino acid prodrug modification might be a viable approach for enhancing LPV absorption across intestinal epithelial and brain endothelial cells which expresses high levels of P-gp and MRP2.

  19. Investigating the use of coupling agents to improve the interfacial properties between a resorbable phosphate glass and polylactic acid matrix.

    Science.gov (United States)

    Hasan, Muhammad Sami; Ahmed, Ifty; Parsons, Andrew J; Rudd, Chris D; Walker, Gavin S; Scotchford, Colin A

    2013-09-01

    Eight different chemicals were investigated as potential candidate coupling agents for phosphate glass fibre reinforced polylactic acid composites. Evidence of reaction of the coupling agents with phosphate glass and their effect on surface wettability and glass degradation were studied along with their principle role of improving the interface between glass reinforcement and polymer matrix. It was found that, with an optimal amount of coupling agent on the surface of the glass/polymer, interfacial shear strength improved by a factor of 5. Evidence of covalent bonding between agent and glass was found for three of the coupling agents investigated, namely: 3-aminopropyltriethoxysilane; etidronic acid and hexamethylene diisocyanate. These three coupling agents also improved the interfacial shear strength and increased the hydrophobicity of the glass surface. It is expected that this would provide an improvement in the macroscopic properties of full-scale composites fabricated from the same materials which may also help to retain these properties for the desired length of time by retarding the breakdown of the fibre/matrix interface within these composites.

  20. Cognitive disorder and changes in cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor following brain injury

    Institute of Scientific and Technical Information of China (English)

    Weiliang Zhao; Dezhi Kang; Yuanxiang Lin

    2008-01-01

    BACKGROUND: Learning and memory damage is one of the most permanent and the severest symptoms of traumatic brain injury; it can seriously influence the normal life and work of patients. Some research has demonstrated that cognitive disorder is closely related to nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor. OBJECTIVE: To summarize the cognitive disorder and changes in nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor following brain injury. RETRIEVAL STRATEGY: A computer-based online search was conducted in PUBMED for English language publications containing the key words "brain injured, cognitive handicap, acetylcholine, N-methyl-D aspartate receptors, neural cell adhesion molecule, brain-derived neurotrophic factor" from January 2000 to December 2007. There were 44 papers in total. Inclusion criteria: ① articles about changes in nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor following brain injury; ② articles in the same researching circle published in authoritative journals or recently published. Exclusion criteria: duplicated articles.LITERATURE EVALUATION: References were mainly derived from research on changes in these four factors following brain injury. The 20 included papers were clinical or basic experimental studies. DATA SYNTHESIS: After craniocerebral injury, changes in these four factors in brain were similar to those during recovery from cognitive disorder, to a certain degree. Some data have indicated that activation of nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor could greatly improve cognitive disorder following brain injury. However, there are still a lot of questions remaining; for example, how do these

  1. Improvement on the Nutritive Quality of Napier Grass Silage through Inoculation of Lactobacillus plantarum and Formic Acid

    Directory of Open Access Journals (Sweden)

    Saprilian Stya Hapsari

    2016-08-01

    Full Text Available The potential availability of forage feed is high, but in reality this potential has not been able to meet the requirement of feed both in sustainable quantity and quality. Silage made with the use of liquid fermentation additive (FA can be a solution for those problems. The use of  different levels of FA and addition of Lactobacillus plantarum bacteria as well as formic acid were expected to improve the nutritive quality of napier grass silage. The first experiment was designed to measure the fermentative quality of napier grass silage. The treatments used were the levels of FA, L. plantarum, and formic acid supplementations. The experiment used a completely randomized design with a 3x2x2 factorial arrangement with 3 replications. The first factor was the level of liquid FA (5%, 7.5%, and 10%, and the second factor was the inoculation of L. plantarum (without and with inoculation of the L. plantarum, and the third factor was the addition of formic acid (without and with the addition of 0.15% formic acid. The second experiment was aimed to evaluate chemical and microbiological characteristics, and in vitro digestibility of selected napier grass silage. The results showed that napier grass silage from all treatments showed good qualities. There were interactions between FA, L. plantarum, and formic acid on DM content (P<0.05 and ammonia production (P<0.01. The use of FA showed an interaction (P<0.01 with the addition of L. plantarum and formic acid in Fleigh point. Ammonia production in rumen (P<0.01, total VFA (P<0.05, and in vitro digestibility (P<0.01 were significantly affected by the treatments. The optimal level of liquid FA was 7.5%. Based on the nutritive quality of silage, L. plantarum addition was as effective as control treatment to improve nutritive quality of napier grass silage through the increased  of fermentation characteristics i.e., low pH, high DM product, high fermentation product (VFA, and digestible on rumen. Formic acid

  2. Improved sensitivity of an acid sphingomyelinase activity assay using a C6:0 sphingomyelin substrate.

    Science.gov (United States)

    Chuang, Wei-Lien; Pacheco, Joshua; Cooper, Samantha; Kingsbury, Jonathan S; Hinds, John; Wolf, Pavlina; Oliva, Petra; Keutzer, Joan; Cox, Gerald F; Zhang, Kate

    2015-06-01

    Short-chain C6-sphingomyelin is an artificial substrate that was used in an acid sphingomyelinase activity assay for a pilot screening study of patients with Niemann-Pick disease types A and B. Using previously published multiplex and single assay conditions, normal acid sphingomyelinase activity levels (i.e. false negative results) were observed in two sisters with Niemann-Pick B who were compound heterozygotes for two missense mutations, p.C92W and p.P184L, in the SMPD1 gene. Increasing the sodium taurocholate detergent concentration in the assay buffer lowered the activity levels of these two patients into the range observed with other patients with clear separation from normal controls. PMID:26937397

  3. Expression of PprI from Deinococcus radiodurans Improves Lactic Acid Production and Stress Tolerance in Lactococcus lactis.

    Directory of Open Access Journals (Sweden)

    Xiangrong Dong

    Full Text Available PprI is a general switch protein that regulates the expression of certain proteins involved in pathways of cellular resistance in the extremophilic bacterium Deinococcus radiodurans. In this study, we transformed pprI into Lactococcus lactis strain MG1363 using the lactococcal shuttle vector pMG36e and investigated its effects on the tolerance and lactic acid production of L. lactis while under stress. PprI was stably expressed in L. lactis as confirmed by western blot assays. L. lactis expressing PprI exhibited significantly improved resistance to oxidative stress and high osmotic pressure. This enhanced cellular tolerance to stressors might be due to the regulation of resistance-related genes (e.g., recA, recO, sodA, and nah by pprI. Moreover, transformed L. lactis demonstrated increased lactic acid production, attributed to enhanced lactate dehydrogenase activity. These results suggest that pprI can improve the tolerance of L. lactis to environmental stresses, and this transformed bacterial strain is a promising candidate for industrial applications of lactic acid production.

  4. Expression of PprI from Deinococcus radiodurans Improves Lactic Acid Production and Stress Tolerance in Lactococcus lactis.

    Science.gov (United States)

    Dong, Xiangrong; Tian, Bing; Dai, Shang; Li, Tao; Guo, Linna; Tan, Zhongfang; Jiao, Zhen; Jin, Qingsheng; Wang, Yanping; Hua, Yuejin

    2015-01-01

    PprI is a general switch protein that regulates the expression of certain proteins involved in pathways of cellular resistance in the extremophilic bacterium Deinococcus radiodurans. In this study, we transformed pprI into Lactococcus lactis strain MG1363 using the lactococcal shuttle vector pMG36e and investigated its effects on the tolerance and lactic acid production of L. lactis while under stress. PprI was stably expressed in L. lactis as confirmed by western blot assays. L. lactis expressing PprI exhibited significantly improved resistance to oxidative stress and high osmotic pressure. This enhanced cellular tolerance to stressors might be due to the regulation of resistance-related genes (e.g., recA, recO, sodA, and nah) by pprI. Moreover, transformed L. lactis demonstrated increased lactic acid production, attributed to enhanced lactate dehydrogenase activity. These results suggest that pprI can improve the tolerance of L. lactis to environmental stresses, and this transformed bacterial strain is a promising candidate for industrial applications of lactic acid production.

  5. Memory and Motor Coordination Improvement by Folic Acid Supplementation in Healthy Adult Male Rats

    OpenAIRE

    Shooshtari, Maryam Khombi; Moazedi, Ahmad Ali; Parham, Gholam Ali

    2012-01-01

    Objective(s) Previous studies have shown that vitamin B as well as folate supplementation has been implicated in cognitive and neurodegenerative disorders including Alzheimer’s and Parkinson's diseases. The aim of present study was to evaluate the effects of folic acid on passive avoidance task and motor coordination in healthy adult male rats. Materials and Methods Animals were randomly divided into five groups with 10 in each. 1) Sham treated (Veh); received same volume of normal saline as ...

  6. Improving the Malting Qualities of Rice Grain Using Gibberellic Acid (GA3)

    OpenAIRE

    Owusu-Mensah, E.; Oduro, I.; Dziedzoave, N. T.; Sarfo, K. J.

    2011-01-01

    Application of exogenous gibberellic acid stimulates high production of hydrolytic enzymes in malts. To investigate this effect on rice malt, different concentrations of the GA3 hormone were applied with the aim of establishing the optimum level that significantly affects rice malting qualities. Parameters evaluated included germination energy, shoot length, and enzymatic activity (diastatic and alpha amylase) of the rice malt. Shoot length, and enzyme activity were significantly affected by ...

  7. Ascorbic acid improves embryonic cardiomyoblast cell survival and promotes vascularization in potential myocardial grafts in vivo

    OpenAIRE

    Martinez, E. C.; Wang, J; Gan, S U; Singh, R.; Lee, C. N.; Kofidis, T

    2010-01-01

    Organ restoration via cell therapy and tissue transplantation is limited by impaired graft survival. We tested the hypothesis that ascorbic acid (AA) reduces cell death in myocardial grafts both in vitro and in vivo and introduced a new model of autologous graft vascularization for later transplantation. Luciferase (Fluc)- and green fluorescent protein (GFP)-expressing H9C2 cardiomyoblasts were seeded in gelatin scaffolds to form myocardial artificial grafts (MAGs). MAGs were supplemented wit...

  8. improving citric acid production from some carbohydrates by-products using irradiated aspergillus niger

    International Nuclear Information System (INIS)

    Twenty strains of A. niger were isolated from different sources, screened for their capacity to produce citric acid. All the isolated strains were able to produce citric acid in different quantities at different time intervals i.e. 4, 8 and 12 days on indicator medium. The best incubation period for production for all isolates was 12 days. The most potent strains for production were A1, A4 and A5, while A8, A16, A18 and A19 recorded weak production on that medium. Citric acid productivity were obtained by all strains when using different concentrations of four carbohydrate by-products (maize straw, potato peel wastes, sugar beet pulp and molasses) when each used alone without any additions after 12 days incubation and the production enhanced when the fermentation medium amended with the same concentrations of the mentioned substrates. Type and concentration of carbohydrate by-product affect the production of citric acid by A. niger strains under the study. Increasing substrate concentration led to increase in production, the best concentration for production was 25% for all carbohydrate by-products. As recorded with indicator medium, A1, A4 and A5 are also the most potent strains for production when growing on the four carbohydrate by-products supplemented to the basal medium, while A8, A6, A18 and A19 recorded the weak production with the carbohydrate by-products used.production of the parental isolates A1, A4 and A5 on indicator medium were: 0.96, 0.95 and 0.99 (mg/ml) respectively after 12 days incubation, while maximum production by the obtaining resulting isolates (Treated by UV irradiation) were: 1.78, 1.70 and 1.73 (mg/ml) from A4T2 (5 min.), A4T1 (10 min.) and A1T1 (5 min.), respectively.

  9. Polyunsaturated fatty acids improve exercise capacity in chronic obstructive pulmonary disease

    OpenAIRE

    Broekhuizen, R; Wouters, E.; Creutzberg, E; Weling-Scheepers, C; Schols, A

    2005-01-01

    Background: Muscle wasting and decreased muscle oxidative capacity commonly occur in patients with chronic obstructive pulmonary disease (COPD). Polyunsaturated fatty acids (PUFA) have been shown to mediate several inflammatory and metabolic pathways which may be involved in the pathogenesis of muscle impairment in COPD. The aim of this study was to investigate the effect of PUFA modulation on systemic inflammation, reversal of muscle wasting, and functional status in COPD.

  10. Resistance Training in Type 2 Diabetic Patients Improves Uric Acid Levels

    Directory of Open Access Journals (Sweden)

    R. Sousa Moisés S.S.

    2014-12-01

    Full Text Available Resistance training (RT can provide several benefits for individuals with Type 2 diabetes. The aim of this study was to investigate the effects of resistance training on the strength levels and uric acid (UA concentration in individuals with Type 2 diabetes. The study included 68 patients (57.7±9.0 years that participated in an organized program of RT for 12 weeks. The volunteers were divided into two groups: an experimental group (EG; n=34 that performed the resistance training program consisting of seven exercises executed in an alternating order based on segments; and a control group (CG; n=34 that maintained their normal daily life activities. Muscle strength and uric acid were measured both pre- and post-experiment. The results showed a significant increase in strength of the subjects in the EG for all exercises included in the study (p<0.001. Comparing the strength levels of the post-test, intergroup differences were found in supine sitting (p<0.001, leg extension (p<0.001, shoulder press (p<0.001, leg curl (p=0.001, seated row (p<0.001, leg press (p=0.001 and high pulley (p<0.001. The measured uric acid was significantly increased in both experimental and control groups (p<0.001 and p=0.001, respectively. The intergroup comparison showed a significant increase for the EG (p=0.024. We conclude that the training program was effective for strength gains despite an increase in uric acid in Type 2 diabetics.

  11. Eicosapentaenoic Acid Enriched Enteral Nutrition Improves Lean Body Mass in Esophageal, Head and Neck Cancer Patients

    OpenAIRE

    Shieh, Christine

    2015-01-01

    OBJECTIVE: Cachexia is a nutrient deficient condition affecting millions of cancer patients. Cancers of the upper gastrointestinal tract, head and neck are often the most severely affected. Currently, there is no established therapy for cachexia, although several potential anti-cachectic agents are being explored. A meta-analysis was conducted to review the effect of eicosapentaenoic acid (EPA) enriched enteral nutrition on lean body mass (LBM) in esophageal, head and neck cancer patients at ...

  12. Ursolic acid attenuates oxidative stress in nigrostriatal tissue and improves neurobehavioral activity in MPTP-induced Parkinsonian mouse model.

    Science.gov (United States)

    Rai, Sachchida Nand; Yadav, Satyndra Kumar; Singh, Divakar; Singh, Surya Pratap

    2016-01-01

    Parkinson's disease (PD) is characterized by a slow and progressive degeneration of dopaminergic neurons in substantia nigra pars compacta (SNpc) region of brain. Oxidative stress and inflammation plays important role in the neurodegeneration and development of PD. Ursolic Acid (UA: 3β-hydroxy-urs-12-en-28-oic acid) is a natural pentacyclic triterpenoid found in various medicinal plants. Its anti-inflammatory and antioxidant activity is a well-established fact. In this paper, the neuroprotective efficiency of UA in MPTP induced PD mouse model has been explored. For this purpose, we divided 30 mice into 5 different groups; first was control, second was MPTP-treated, third, fourth and fifth were different doses of UA viz., 5 mg/kg, 25 mg/kg, and 50 mg/kg body weight (wt) respectively, along with MPTP. After 21 days of treatment, different behavioral parameters and biochemical assays were conducted. Tyrosine hydroxylase (TH) immunostaining of SN dopaminergic neurons as well as HPLC quantification of dopamine and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA) were also performed. Our results proved that, UA improves behavioral deficits, restored altered dopamine level and protect dopaminergic neurons in the MPTP intoxicated mouse. Among three different doses, 25 mg/kg body wt was the most effective dose for the PD. This work reveals the potential of UA as a promising drug candidate for PD treatment. PMID:26686287

  13. Thyroid hormone reverses aging-induced myocardial fatty acid oxidation defects and improves the response to acutely increased afterload.

    Directory of Open Access Journals (Sweden)

    Dolena Ledee

    Full Text Available BACKGROUND: Subclinical hypothyroidism occurs during aging in humans and mice and may contribute to the development of heart failure. Aging also impairs myocardial fatty acid oxidation, causing increased reliance on flux through pyruvate dehydrogenase (PDH to maintain function. We hypothesize that the metabolic changes in aged hearts make them less tolerant to acutely increased work and that thyroid hormone supplementation reverses these defects. METHODS: Studies were performed on young (Young, 4-6 months and aged (Old, 22-24 months C57/BL6 mice at standard (50 mmHg and high afterload (80 mmHg. Another aged group received thyroid hormone for 3 weeks (Old-TH, high afterload only. Function was measured in isolated working hearts along with substrate fractional contributions (Fc to the citric acid cycle (CAC using perfusate with (13C labeled lactate, pyruvate, glucose and unlabeled palmitate and insulin. RESULTS: Old mice maintained cardiac function under standard workload conditions, despite a marked decrease in unlabeled (presumably palmitate Fc and relatively similar individual carbohydrate contributions. However, old mice exhibited reduced palmitate oxidation with diastolic dysfunction exemplified by lower -dP/dT. Thyroid hormone abrogated the functional and substrate flux abnormalities in aged mice. CONCLUSION: The aged heart shows diminished ability to increase cardiac work due to substrate limitations, primarily impaired fatty acid oxidation. The heart accommodates slightly by increasing efficiency through oxidation of carbohydrate substrates. Thyroid hormone supplementation in aged mice significantly improves cardiac function potentially through restoration of fatty acid oxidation.

  14. Anode modification with formic acid: A simple and effective method to improve the power generation of microbial fuel cells

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Weifeng; Cheng, Shaoan, E-mail: shaoancheng@zju.edu.cn; Guo, Jian

    2014-11-30

    Highlights: • Carbon cloth anode is modified with formic acid by a simple and reliable approach. • The modification significantly enhances the power output of microbial fuel cells. • The modified anode surface favors the bacterial attachment and growth on anode. • The electron transfer rate of anode is promoted. - Abstract: The physicochemical properties of anode material directly affect the anodic biofilm formation and electron transfer, thus are critical for the power generation of microbial fuel cells (MFCs). In this work, carbon cloth anode was modified with formic acid to enhance the power production of MFCs. Formic acid modification of anode increased the maximum power density of a single-chamber air-cathode MFC by 38.1% (from 611.5 ± 6 mW/m{sup 2} to 877.9 ± 5 mW/m{sup 2}). The modification generated a cleaner electrode surface and a reduced content of oxygen and nitrogen groups on the anode. The surface changes facilitated bacterial growth on the anode and resulted in an optimized microbial community. Thus, the electron transfer rate on the modified anodes was enhanced remarkably, contributing to a higher power output of MFCs. Anode modification with formic acid could be an effective and simple method for improving the power generation of MFCs. The modification method holds a huge potential for large scale applications and is valuable for the scale-up and commercialization of microbial fuel cells.

  15. The role of amino acids in improvement in salt tolerance of crop plants

    Directory of Open Access Journals (Sweden)

    Abd El-Samad H. M.

    2010-09-01

    Full Text Available The present work has been performed to study the growth and metabolic activities of maize and broad bean plants which are shown to have a degree of sensitivity to salinity and to determine the role of amino acids proline or phenylalanine in increasing the salt tolerance of theses plants. Dry mass, water content, leaf area and photosynthetic pigment of maize and broad bean plants decreased with increasing salinity. These changes were accompanied with a drop in the contents of soluble sugars, soluble proteins and amino acids. This was accompanied by a marked increase in the proline content. When maize and broad bean plants sprayed with proline or phenylalanine the opposite effect was occurred, saccharides as well as proteins progressively increased at all sanitization levels and proline concentration significantly declined. Salinity significantly increased the sodium content in both shoots and roots of maize and broad bean plants, while a decline in the accumulation of K+, Ca++, Mg++ and P was observed. Amino acids treatments markedlyaltered the selectivity of Na+, K+, Ca++ and P in both maize and broad bean plants. Spraying with any of either proline orphenylalanine restricted Na+ uptake and enhanced the uptake of K+, K+/Na+ ratio, Ca++ and P selectivity in maize and broad bean plants.

  16. Lactic acid bacteria activating innate immunity improve survival in bacterial infection model of silkworm.

    Science.gov (United States)

    Nishida, Satoshi; Ono, Yasuo; Sekimizu, Kazuhisa

    2016-02-01

    Lactic acid bacteria (LAB) have been thought to be helpful for human heath in the gut as probiotics. It recently was noted that activity of LAB stimulating immune systems is important. Innate immune systems are conserved in mammals and insects. Silkworm has innate immunity in response to microbes. Microbe-associated molecular pattern (ex. peptidoglycan and β-glucan) induces a muscle contraction of silkworm larva. In this study, we established an efficient method to isolate lactic acid bacteria derived from natural products. We selected a highly active LAB to activate the innate immunity in silkworm by using the silkworm muscle contraction assay, as well. The assay revealed that Lactococcus lactis 11/19-B1 was highly active on the stimulation of the innate immunity in silkworm. L. lactis 11/19-B1 solely fermented milk with casamino acid and glucose. This strain would be a starter strain to make yogurt. Compared to commercially available yogurt LAB, L. lactis 11/19-B1 has higher activity on silkworm contraction. Silkworm normally ingested an artificial diet mixed with L. lactis 11/19-B1 or a yogurt fermented with L. lactis 11/19-B1. Interestingly, silkworms that ingested the LAB showed tolerance against the pathogenicity of Pseudomonas aeruginosa. These data suggest that Lactococcus lactis 11/19-B1 would be expected to be useful for making yogurt and probiotics to activate innate immunity. PMID:26971556

  17. Improvement of bioavailability for iron from vegetarian meals by ascorbic acid

    International Nuclear Information System (INIS)

    There are two kinds of iron in the diet with respect to the mechanism of absorption, heme-iron which is present as haemoglobin or myoglobin in meat and blood products, and, non-heme iron which is the main source of dietary iron. The bioavailability of the non-heme food iron is much lower than heme-iron. Vegetarian diets contain only non-heme iron. Iron intake from vegetarian meals are generally satisfied with the requirements, however, the bioavailabilities for non-heme iron is determined not only by iron content byt also the balance between different dietary factors enhancing and inhibiting iron absorption. The main enhancing factor in vegetarian meals is ascorbic acid in fruits and vegetables, inhibitors are phytate in cereals and grains, and tannins in some spices and vegetables. It has been reported that iron deficiency is one of the common micronutrient problems associated with unplanned vegetarian diets. In the present study the absorption of non-heme iron was measured from 2 vegetarian meals containing considerable amounts of phytate and tannin. The extrinsic tay method (59Fe/ 55Fe) was used to labelled the non-heme iron. The mean percentage absorption of non-heme iron from both meals was slightly different due to differences in their dietary contents. Their initial percentages iron absorption were apparent low (3.5% and 4.1%), however, the absorption progressively increased with increase in the level of ascorbic acid, 2-3 times with 100 mg and 4-5 times with 200 mg of ascorbic acid. The average amount of iron absorbed per 2000 kcal increased from 0.37 mg to 0.86 mg and 1.45 mg with the addition of 100 mg and 200 mg ascorbic acid respectively (p < 0.001). Considering the limited caloric intakes and the iron content in the meals, the amount of iron absorbed from vegetarian meals without ascorbic acid was not able to meet certain requirements for children, adolescents and menstruating women. The minimal requirement for dietary iron needed to be absorbed is 0

  18. Improvement of Haramay Fiber by Pre-treatment of Retting Process withPhosphoric Acid

    International Nuclear Information System (INIS)

    Haramay as bast fiber contains of cellulose fiber as the main part, mixedwith hemi cellulose, pectin, and lignin as binding material for cellulosefiber to keep it together in the bundle form. For textile material, this bastfiber has to be freed from its binding material, called as retting process,before subjecting to scouring, dyeing and finishing process in textileindustry. In the retting process the dissolve of binding material can be doneeither by using enzyme in bio technology or extraction with strong alkalinecondition in common technology. Using sodium hydroxide for dissolving thebinding material can be carried out easily with good dissolving ability, butcan render the strength retention of the cellulose fiber. Pre-treatment ofthe bast fiber with phosphoric acid (H3PO4), is expected to hydrolyze someof the binding materials that can not be dissolved in alkaline condition,including natural pigment that colored the fiber with creamy white. In thisstudy, the pre-treatment process before retting with phosphoric acid wascarried out in various condition, such as concentration of phosphoric acid (5ml/l- 25 ml/l), time and temperature of pre-treatment (1-3 hours at 50 oC or12-24 hours at room temperature), followed by neutralization in dilutealkaline. The retting process was carried out by means of scouring in variousconcentration of sodium hydroxide (NaOH 38oBe, 10 ml/l-30 m/l), and then wascontinued with bleaching process in hydrogen peroxide solution. Aftercarrying out those experiment, the bast fiber that called haramay wassubjected to testing for weight reduction, strength retention and degree ofwhiteness. From the testing results it is concluded that pre-treatment withphosphoric acid can increase the weight reduction, strength retention ortenacity and degree of whiteness of haramay fiber compared to the oneswithout pre-treatment with phosphoric acid. The best result was obtained bypre-treatment with 5 ml/l H3PO4 at 50 oC for 2 hours, continued by rettingprocess

  19. A 9-wk docosahexaenoic acid-enriched supplementation improves endurance exercise capacity and skeletal muscle mitochondrial function in adult rats.

    Science.gov (United States)

    Le Guen, Marie; Chaté, Valérie; Hininger-Favier, Isabelle; Laillet, Brigitte; Morio, Béatrice; Pieroni, Gérard; Schlattner, Uwe; Pison, Christophe; Dubouchaud, Hervé

    2016-02-01

    Decline in skeletal muscle mass and function starts during adulthood. Among the causes, modifications of the mitochondrial function could be of major importance. Polyunsaturated fatty (ω-3) acids have been shown to play a role in intracellular functions. We hypothesize that docosahexaenoic acid (DHA) supplementation could improve muscle mitochondrial function that could contribute to limit the early consequences of aging on adult muscle. Twelve-month-old male Wistar rats were fed a low-polyunsaturated fat diet and were given DHA (DHA group) or placebo (control group) for 9 wk. Rats from the DHA group showed a higher endurance capacity (+56%, P supplementation could be of potential interest for the muscle function in adults and for fighting the decline in exercise tolerance with age that could imply energy-sensing pathway, as suggested by changes in phospho-AMPK/AMPK ratio. PMID:26646102

  20. Hypouricemic effect of allopurinol are improved by Pallidifloside D based on the uric acid metabolism enzymes PRPS, HGPRT and PRPPAT.

    Science.gov (United States)

    Li, Hong-Gang; Hou, Pi-Yong; Zhang, Xi; He, Yi; Zhang, Jun; Wang, Shu-Qing; Anderson, Samantha; Zhang, Yan-Wen; Wu, Xiao-Hui

    2016-09-01

    Allopurinol is a commonly used medication to treat hyperuricemia and its complications. Pallidifloside D, a saponin glycoside constituent from the total saponins of Smilax riparia, had been proved to enhanced hypouricemic effect of allopurinol based on uric acid metabolism enzyme XOD. In this study, we evaluated whether Pallidifloside D (5mg/kg) enhanced hypouricemic effect of allopurinol (5mg/kg) related to others uric acid metabolism enzymes such as PRPS, HGPRT and PRPPAT. We found that, compared with allopurinol alone, the combination of allopurinol and Pallidifloside D significantly up-regulated HGPRT mRNA expression and down-regulated the mRNA expression of PRPS and PRPPAT in PC12 cells (all P<0.01). These results strongly suggest that hypouricemic effect of allopurinol are improved by Pallidifloside D via numerous mechanisms and our data may have a potential value in clinical practice in the treatment of gout and other hyperuricemic conditions. PMID:27370097

  1. Rescue of NGF-deficient mice II: basal forebrain cholinergic projections require NGF for target innervation but not guidance.

    Science.gov (United States)

    Phillips, Heidi S; Nishimura, Merry; Armanini, Mark P; Chen, Karen; Albers, Kathryn M; Davis, Brian M

    2004-04-29

    Basal forebrain cholinergic (BFC) neurons are an important substrate of cognitive function and are hypothesized to require the presence of nerve growth factor (NGF) for survival and target innervation. NGF-deficient mice develop BFC neurons that extend projections into telencephalic targets, but the mice perish before innervation is fully established. Rescue of NGF-deficient mice by transgenic expression of NGF under the keratin promoter yields viable mice with disrupted CNS expression of NGF. In the current study, rescued NGF-deficient mice contain normal numbers of septal cholinergic neurons yet reveal severe compromise of cholinergic innervation of both cortex and hippocampus. Surprisingly, intracerebroventricular infusion of NGF into juvenile mice can induce an essentially normal pattern of cholinergic innervation of the hippocampus. These results indicate that NGF is required for induction of proper innervation by BFC neurons, but that the cellular pattern of expression of this factor is not critical for specifying the distribution of axon terminals. PMID:15093680

  2. Cholinergic neuronal lesions in the medial septum and vertical limb of the diagonal bands of Broca induce contextual fear memory generalization and impair acquisition of fear extinction.

    Science.gov (United States)

    Knox, Dayan; Keller, Samantha M

    2016-06-01

    Previous research has shown that the ventral medial prefrontal cortex (vmPFC) and hippocampus (Hipp) are critical for extinction memory. Basal forebrain (BF) cholinergic input to the vmPFC and Hipp is critical for neural function in these substrates, which suggests BF cholinergic neurons may be critical for extinction memory. In order to test this hypothesis, we applied cholinergic lesions to different regions of the BF and observed the effects these lesions had on extinction memory. Complete BF cholinergic lesions induced contextual fear memory generalization, and this generalized fear was resistant to extinction. Animals with complete BF cholinergic lesions could not acquire cued fear extinction. Restricted cholinergic lesions in the medial septum and vertical diagonal bands of Broca (MS/vDBB) mimicked the effects that BF cholinergic lesions had on contextual fear memory generalization and acquisition of fear extinction. Cholinergic lesions in the horizontal diagonal band of Broca and nucleus basalis (hDBB/NBM) induced a small deficit in extinction of generalized contextual fear memory with no accompanying deficits in cued fear extinction. The results of this study reveal that MS/vDBB cholinergic neurons are critical for inhibition and extinction of generalized contextual fear memory, and via this process, may be critical for acquisition of cued fear extinction. Further studies delineating neural circuits and mechanisms through which MS/vDBB cholinergic neurons facilitate these emotional memory processes are needed. © 2015 Wiley Periodicals, Inc.

  3. Rapid pyramiding of low phytic acid mutation and ferritin gene for improvement of mineral nutritional quality of rice

    International Nuclear Information System (INIS)

    Nutritional quality is an important component of the rice grain. Development of low phytic acid (lpa) crops, in which the PA phosphorus (Pi) content is significantly reduced in grains, has recently been considered as a potential way to increase bioavailability of Zn2+ and Fe3+ in the rice grain. Another potential approach to improve nutritional quality is to express ferritin gene from legume crops to increase iron content in rice grain. We have isolated a low phytic acid rice mutant (lpa- XS110-1) and obtained transgenic rice expressing the ferritin gene from pea. Two transgenic lines (Fer34 and Fer65) had iron content about five times that of the parent XS110 (Ye et al 2007). To pyramid the low phytic acid mutation and ferritin gene into one line, two crosses were made between Fer34 and lpa-XS110-1 and between Fer65/ lpa-XS110-1. The F1 anthers were subjected to anther culture to obtain stable homozygous plants. A total of 43 doubled haploid (DH) lines were obtained from the Fer34/ lpa-XS110-1 cross, and 86 DH lines from Fer65/ lpa-XS110-1. For individual trait, both low phytic acid and the Ferritin gene (indirectly assayed with Gus) were inherited as a single locus. In combination, four recombinant traits were obtained, i.e high inorganic pi (lpa)/Gus+, lpa/Gus-, low inorganic pi/Gus+, and low inorganic pi/Gus-, the ratio of each recombinant was in accordance with the ratio of 1: 1: 1; 1, , indicating that lpa and Fer gene were not linked, and segregated as a single locus. The results suggest doubled haploid production is a rapid approach to pyramid useful genes from different origin for rice improvement. This study was jointly supported by funds from IAEA (12229), the Science and Technology Department of Zhejiang Province. (author)

  4. THYROID HORMONE REVERSES AGING-INDUCED MYOCARDIAL FATTY ACID OXIDATION DEFECTS AND IMPROVES THE RESPONSE TO ACUTELY INCREASED AFTERLOAD

    Energy Technology Data Exchange (ETDEWEB)

    Ledee, Dolena; Portman, Michael A.; Kajimoto, Masaki; Isern, Nancy G.; Olson, Aaron

    2013-06-07

    Background: Subclinical hypothyroidism occurs during aging in humans and mice and may contribute to development of heart failure. Aging also impairs myocardial fatty acid oxidation, causing increased reliance on flux through pyruvate dehydrogenase (PDH) to maintain function. We hypothesize that the metabolic changes in aged hearts make them less tolerant to acutely increased work and that thyroid hormone reverses these defects. Methods: Studies were performed on young (Young, 4-6 months) and aged (Old, 22-24 months) C57/BL6 mice at standard (50 mmHg) and high afterload (80 mmHg). Another aged group received thyroid hormone for 3 weeks (Old-TH, high afterload only). Function was measured in isolated working hearts along with substrate fractional contributions (Fc) to the citric acid cycle (CAC) using perfusate with 13C labeled lactate, pyruvate, glucose and unlabeled palmitate and insulin. Results: Cardiac function was similar between Young and Old mice at standard afterload. Palmitate Fc was reduced but no individual carbohydrate contributions differed. CAC and individual substrate fluxes decreased in aged. At high afterload, -dP/dT was decreased in Old versus Young. Similar to low afterload, palmitate Fc was decreased in Old. Thyroid hormone reversed aging-induced changes in palmitate Fc and flux while significantly improving cardiac function. Conclusion: The aged heart shows diminished ability to increase cardiac work due to substrate limitations, primarily impaired fatty acid oxidation. The heart accommodates slightly by increasing efficiency through oxidation of carbohydrate substrates. Thyroid hormone supplementation in aged mice significantly improves cardiac function potentially through restoration of fatty acid oxidation.

  5. Response of acid mobilization of iron-containing mineral dust to improvement of air quality projected in the future

    Directory of Open Access Journals (Sweden)

    A. Ito

    2013-10-01

    Full Text Available Acidification of dust aerosols may increase aerosol iron (Fe solubility, which is linked to mineral properties. Combustion aerosols can also elevate aerosol iron solubility when aerosol loading is low. Here, we use an atmospheric chemical transport model to investigate the deposition of filterable iron and its response to changes in anthropogenic emissions of both combustion aerosols and precursor gases. By introducing three classes of iron-containing minerals into the detailed aerosol chemistry model, we provide a theoretical examination of the effects of different dissolution behaviors on the acid mobilization of iron. Comparisons of modeled Fe dissolution curves with the measured dissolution rates for African (Tibesti and Asian (Beijing dust samples show overall good agreement under acidic conditions. The improved treatment of Fe in mineral dust and its dissolution scheme results in reasonable predictive capability for iron solubility over the oceans in the Northern Hemisphere. Our model results suggest that the improvement of air quality projected in the future will lead to a decrease of the filterable iron deposition from iron-containing mineral dust to the northeastern Pacific due to less acidification in Asian dust, which is mainly associated with the reduction of nitrogen oxides (NOx emissions. These results could have important implications for iron fertilization of phytoplankton growth, and highlight the necessity of improving the process-based quantitative understanding of the response of the chemical modification in iron-containing minerals to environmental changes.

  6. Improving aqueous solubility and antitumor effects by nanosized gambogic acid-mPEG2000 micelles

    Directory of Open Access Journals (Sweden)

    Cai LL

    2013-12-01

    Full Text Available Lulu Cai,1,* Neng Qiu,2,* Mingli Xiang,3,* Rongsheng Tong,1 Junfeng Yan,1 Lin He,1 Jianyou Shi,1 Tao Chen,4 Jiaolin Wen,3 Wenwen Wang,3 Lijuan Chen31Department of Pharmacy, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, 2College of Materials and Chemistry and Chemical Engineering, Chengdu University of Technology, 3State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China; 4Faculty of Pharmacy, University of Montreal, Montreal, QC, Canada *These authors contributed equally to this paperAbstract: The clinical application of gambogic acid, a natural component with promising antitumor activity, is limited due to its extremely poor aqueous solubility, short half-life in blood, and severe systemic toxicity. To solve these problems, an amphiphilic polymer-drug conjugate was prepared by attachment of low molecular weight (ie, 2 kDa methoxy poly(ethylene glycol methyl ether (mPEG to gambogic acid (GA-mPEG2000 through an ester linkage and characterized by 1H nuclear magnetic resonance. The GA-mPEG2000 conjugates self-assembled to form nanosized micelles, with mean diameters of less than 50 nm, and a very narrow particle size distribution. The properties of the GA-mPEG2000 micelles, including morphology, stability, molecular modeling, and drug release profile, were evaluated. MTT (3-(4,5-dimethylthiazol-2-yl-2,5 diphenyl tetrazolium bromide tests demonstrated that the GA-mPEG2000 micelle formulation had obvious cytotoxicity to tumor cells and human umbilical vein endothelial cells. Further, GA-mPEG2000 micelles were effective in inhibiting tumor growth and prolonged survival in subcutaneous B16-F10 and C26 tumor models. Our findings suggest that GA-mPEG2000 micelles may have promising applications in tumor therapy.Keywords: gambogic acid, poly(ethylene glycol-drug conjugate, micelle, antitumor, toxicity

  7. Weigners fixative-an alternative to formalin fixation for histology with improved preservation of nucleic acids.

    Science.gov (United States)

    Klopfleisch, R; von Deetzen, M; Weiss, A Th; Weigner, J; Weigner, F; Plendl, J; Gruber, A D

    2013-01-01

    Formalin fixation and paraffin embedding (FFPE) is the standard method for tissue storage in histopathology. However, FFPE has disadvantages in terms of user health, environment, and nucleic acid integrity. Weigners fixative has been suggested as an alternative for embalming cadavers in human and veterinary anatomy. The present study tested the applicability of Weigners for histology and immunohistochemistry and the preservation of nucleic acids. To this end, a set of organs was fixed for 2 days and up to 6 months in Weigners (WFPE) or formalin. WFPE tissues from the skin, brain, lymphatic tissues, liver, and muscle had good morphologic preservation, comparable to formalin fixation. The quality of kidney and lung samples was inferior to FFPE material due to less accentuated nuclear staining and retention of proteinaceous interstitial fluids. Azan, Turnbull blue, toluidin, and immunohistochemical stainings for CD79a, cytokeratin, vimentin, and von Willebrand factor led to comparable results with both fixates. Of note, immunohistochemical detection of CD3 was possible after 6 months in WFPE but not in FFPE tissues. mRNA, miRNA, and DNA from WFPE tissues had superior quality and allowed for amplification of miRNA, 400-bp-long mRNA, and 1000-bp-long DNA fragments after 6 months of fixation in WFPE. In summary, Weigners fixative is a nonhazardous alternative to formalin, which provides a good morphologic preservation of most organs, a similar sensitivity for protein detection, and a superior preservation of nucleic acids. Weigners may therefore be a promising alternative to cryopreservation and may be embraced by people affected by formalin allergies.

  8. Improved thrombin binding aptamer by incorporation of a single unlocked nucleic acid monomer

    DEFF Research Database (Denmark)

    Pasternak, Anna; Hernandez, Frank J; Rasmussen, Lars Melholt;

    2011-01-01

    A 15-mer DNA aptamer (named TBA) adopts a G-quadruplex structure that strongly inhibits fibrin-clot formation by binding to thrombin. We have performed thermodynamic analysis, binding affinity and biological activity studies of TBA variants modified by unlocked nucleic acid (UNA) monomers. UNA...... that a UNA monomer is allowed in many positions of the aptamer without significantly changing the thrombin-binding properties. The biological effect of a selection of the modified aptamers was tested by a thrombin time assay and showed that most of the UNA-modified TBAs possess anticoagulant properties...

  9. Total salvianolic acid improves ischemia-reperfusion-induced microcirculatory disturbance in rat mesentery

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To investigate the effect of total salvianolic acid(TSA) on ischemia-reperfusion(I/R)-induced rat mesenteric microcirculatory dysfunctions.METHODS:Male Wistar rats were randomly distributed into 5 groups(n = 6 each):Sham group and I/R group(infused with saline),TSA group,TSA + I/R group and I/R + TSA group(infused with TSA,5 mg/kg per hour).Mesenteric I/R were conducted by a ligation of the mesenteric artery and vein(10 min) and subsequent release of the occlusion.TSA was continuously infused either sta...

  10. An improved procedure for the synthesis of DL-[2-[sup 13]C]-glutamic acid

    Energy Technology Data Exchange (ETDEWEB)

    Potrzebowski, M.J.; Stolowich, N.J.; Scott, A.I. (Texas A and M Univ., College Station, TX (United States). Dept. of Chemistry)

    1990-03-01

    A convenient two-step chemical synthesis of DL-[2-[sup 13]C]-glutamic acid from methyl acrylate and diethylacetamidomalonate is described. Synthesis of the Michael adduct (III) was effected in quantitative yield by employing strong amino bases as catalysts. The reactivities of three such catalysts, tetramethyl guanidine (TMG), 1,8-diazobicyclo [5,4,0]-undec-7-ene (1,5-5) (DBU) and 1,5-diazobicyclo [4,3,0] non-5-ene (DBN) were compared by [sup 13]C NMR and all are shown to catalyse the reaction quantitatively, however at markedly different rates. (Author).

  11. Improved Inhibition of Telomerase by Short Twisted Intercalating Nucleic Acids under Molecular Crowding Conditions

    DEFF Research Database (Denmark)

    Agarwal, Tani; Pradhan, Devranjan; Géci, Imrich;

    2012-01-01

    crowding conditions mimicking physiological milieu, stabilization of the telomeric G-quadruplex is often lost. We attempted to demonstrate the enhanced G-quadruplex stabilizing ability under molecular conditions by using twisted intercalating nucleic acids (TINA)-modified oligonucleotides. We have shown......-based telomerase repeat amplification assay (TRAP) assay as well as nondenaturing polyacrylamide gel electrophoresis-based TRAP, we demonstrate remarkable enhancement in their anti-telomerase activity even under molecular crowding conditions. This is the first time in which a G-quadruplex stabilizing agent has...... demonstrated enhanced activity even under molecular crowding conditions....

  12. Improving the Bioavailability of Seed Phosphorous in Low Phytic Acid Soybean Mutants

    OpenAIRE

    Ashok Badigannavar and J. G. Manjaya

    2012-01-01

    Phytic acid, the heat stable anti-nutritional factor forms 75% of the total Phosphorous (P) in soybean seeds. It acts as strong chelatingagent binding to metal ions reducing the bioavailability of Fe, Zn, Mg and Ca in human and non-ruminant livestock. In the presentstudy, 106 soybean germplasm lines were screened to estimate the seed phytate. It ranged from 0.16 to 4.741mg per g soy flour. Highyielding, low phytate cultivar were selected and subjected to 250 Gy gamma ray irradiation. In M3 ge...

  13. Tetrahydrofuran amino acid-containing gramicidin S analogues with improved biological profiles.

    Science.gov (United States)

    Pal, Sudip; Singh, Gajendra; Singh, Shyam; Tripathi, Jitendra Kumar; Ghosh, Jimut Kanti; Sinha, Sudhir; Ampapathi, Ravi Sankar; Chakraborty, Tushar Kanti

    2015-06-28

    Gramicidin S (GS) is a cyclic cationic antimicrobial peptide (CAP) with a wide spectrum of antibiotic activities whose usage has been limited to topical applications owing to its cytotoxic side effects. We have synthesized tetrahydrofuran amino acid (Taa)-containing GS analogues, and we have carried out conformational analysis and explored their structure activity relationships by evaluating their antitubercular, antibacterial and cytotoxic properties. Two of these analogues showed impressive as well as selective activity against Mycobacterium tuberculosis (MTB) without toxicity towards mammalian Vero cells or human RBCs, and are promising as potential leads. PMID:26008215

  14. Has Stewart approach improved our ability to diagnose acid-base disorders in critically ill patients?

    OpenAIRE

    Masevicius, Fabio D; Dubin, Arnaldo

    2015-01-01

    The Stewart approach-the application of basic physical-chemical principles of aqueous solutions to blood-is an appealing method for analyzing acid-base disorders. These principles mainly dictate that pH is determined by three independent variables, which change primarily and independently of one other. In blood plasma in vivo these variables are: (1) the PCO2; (2) the strong ion difference (SID)-the difference between the sums of all the strong (i.e., fully dissociated, chemically nonreacting...

  15. Improved Resin–Zirconia Bonding by Room Temperature Hydrofluoric Acid Etching

    OpenAIRE

    Mun-Hwan Lee; Jun Sik Son; Kyo-Han Kim; Tae-Yub Kwon

    2015-01-01

    This in vitro study was conducted to evaluate the shear bond strength of “non-self-adhesive” resin to dental zirconia etched with hydrofluoric acid (HF) at room temperature and to compare it to that of air-abraded zirconia. Sintered zirconia plates were air-abraded (control) or etched with 10%, 20%, or 30% HF for either 5 or 30 min. After cleaning, the surfaces were characterized using various analytical techniques. Three resin cylinders (Duo-Link) were bonded to each treated plate. All bond...

  16. Chlorogenic Acid Improves Late Diabetes through Adiponectin Receptor Signaling Pathways in db/db Mice

    OpenAIRE

    Shasha Jin; Cuiqing Chang; Lantao Zhang; Yang Liu; Xianren Huang; Zhimin Chen

    2015-01-01

    The aim of this study was to examine the effects of chlorogenic acid (CGA) on glucose and lipid metabolism in late diabetic db/db mice, as well as on adiponectin receptors and their signaling molecules, to provide evidence for CGA in the prevention of type 2 diabetes. We randomly divided 16 female db/db mice into db/db-CGA and db/db-control (CON) groups equally; db/m mice were used as control mice. The mice in both the db/db-CGA and db/m-CGA groups were administered 80 mg/kg/d CGA by lavage f...

  17. Improving amino-acid identification, fit and C(alpha) prediction using the Simplex method in automated model building.

    Science.gov (United States)

    Romo, Tod D; Sacchettini, James C; Ioerger, Thomas R

    2006-11-01

    Automated methods for protein model building in X-ray crystallography typically use a two-phased approach that involves first modeling the protein backbone followed by building in the side chains. The latter phase requires the identification of the amino-acid side-chain type as well as fitting of the side-chain model into the observed electron density. While mistakes in identification of individual side chains are common for a number of reasons, sequence alignment can sometimes be used to correct errors by mapping fragments into the true (expected) amino-acid sequence and exploiting contiguity constraints among neighbors. However, side chains cannot always be confidently aligned; this depends on having sufficient accuracy in the initial calls. The recognition of amino-acid side-chains based on the surrounding pattern of electron density, whether by features, density correlation or free atoms, can be sensitive to inaccuracies in the coordinates of the predicted backbone C(alpha) atoms to which they are anchored. By incorporating a Nelder-Mead Simplex search into the side-chain identification and model-building routines of TEXTAL, it is demonstrated that this form of residue-by-residue rigid-body real-space refinement (in which the C(alpha) itself is allowed to shift) can improve the initial accuracy of side-chain selection by over 25% on average (from 25% average identity to 32% on a test set of five representative proteins, without corrections by sequence alignment). This improvement in amino-acid selection accuracy in TEXTAL is often sufficient to bring the pairwise amino-acid identity of chains in the model out of the so-called ;twilight zone' for sequence-alignment methods. When coupled with sequence alignment, use of the Simplex search yielded improvements in side-chain accuracy on average by over 13 percentage points (from 64 to 77%) and up to 38 percentage points (from 40 to 78%) in one case compared with using sequence alignment alone. PMID:17057345

  18. Cholinergic-mediated IP3-receptor activation induces long-lasting synaptic enhancement in CA1 pyramidal neurons

    OpenAIRE

    Fernández de Sevilla, D.; Núñez Molina, Ángel; Borde, M.; Malinow, R.; Buño, Washinton

    2008-01-01

    Cholinergic-glutamatergic interactions influence forms of synaptic plasticity that are thought to mediate memory and learning. We tested in vitro the induction of long-lasting synaptic enhancement at Schaffer collaterals by acetylcholine (ACh) at the apical dendrite of CA1 pyramidal neurons and in vivo by stimulation of cholinergic afferents. In vitro ACh induced a Ca2+ wave and synaptic enhancement mediated by insertion of AMPA receptors in spines. Activation of muscarinic ACh receptors (mAC...

  19. Elimination of the vesicular acetylcholine transporter in the striatum reveals regulation of behaviour by cholinergic-glutamatergic co-transmission.

    OpenAIRE

    Monica S Guzman; Xavier De Jaeger; Sanda Raulic; Souza, Ivana A; Li, Alex X.; Susanne Schmid; Menon, Ravi S.; Gainetdinov, Raul R.; Caron, Marc G.; Robert Bartha; Prado, Vania F.; Prado, Marco A. M.

    2011-01-01

    Cholinergic neurons in the striatum are thought to play major regulatory functions in motor behaviour and reward. These neurons express two vesicular transporters that can load either acetylcholine or glutamate into synaptic vesicles. Consequently cholinergic neurons can release both neurotransmitters, making it difficult to discern their individual contributions for the regulation of striatal functions. Here we have dissected the specific roles of acetylcholine release for striatal-dependent...

  20. Amyloid-β peptides act as allosteric modulators of cholinergic signalling through formation of soluble BAβACs.

    Science.gov (United States)

    Kumar, Rajnish; Nordberg, Agneta; Darreh-Shori, Taher

    2016-01-01

    -β interacts readily in an apolipoprotein-facilitated manner with butyrylcholinesterase, forming highly stable and soluble complexes, BAβACs, which can be separated in their native states by sucrose density gradient technique. Enzymological analyses further evinced that amyloid-β concentration dependently increased the acetylcholine-hydrolyzing capacity of cholinesterases. In silico biomolecular analysis further deciphered the allosteric amino acid fingerprint of the amyloid-β-cholinesterase molecular interaction in formation of BAβACs. In the case of butyrylcholinesterase, the results indicated that amyloid-β interacts with a putative activation site at the mouth of its catalytic tunnel, most likely leading to increased acetylcholine influx into the catalytic site, and thereby increasing the intrinsic catalytic rate of butyrylcholinesterase. In conclusion, at least one of the native physiological functions of amyloid-β is allosteric modulation of the intrinsic catalytic efficiency of cholinesterases, and thereby regulation of synaptic and extrasynaptic cholinergic signalling. High apolipoprotein-E may pathologically alter the biodynamics of this amyloid-β function.

  1. Improvement Enzymatic Hydrolysis of Wheat Straw for Bioethanol Production by Combined Treatment of Radiation and Acid

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Sung Hyun; Lee, Seung Sik; Bai, Hyoung Woo; Chung, Byung Yeoup [Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of)

    2012-05-15

    The cost of ethanol production from starch and sucrose for use as a vehicle fuel is ultimately high. Consequently, it has been suggested that the large-scale use of ethanol as a fuel will require the utilization of cellulosic feedstock. Lignocellulosic biomass has the potential to serve as a low cost and renewable feedstock for bioconversion into fermentable sugars, which can be further utilized for biofuel production. It is estimated that there is over one billion tons of biomass available for conversion into biofuels on a renewable basis to displace a substantial portion of the fossil fuels currently consumed within the transportation sector. Among different pretreatment methods such as biological, physical, chemical, and physic-chemical pretreatments, chemical pretreatment using dilute acid as catalyst, which has been extensively evaluated for treating a variety of lignocellulosic feedstocks, is reported as one of the leading pretreatment technologies. Ionizing radiation can easily penetrate lignocellulosic structure and undoubtedly produce free radicals useful in modification of lignin structure as well as breakdown cellulose crystal regions. Phenoxy radicals appeared to be important radical intermediates that ultimately transformed into o-quinonoid structures in lignin. Therefore, ionizing radiation such as gamma ray and electron beam can be a great alternative. In this study, the effect of ionizing irradiation of wheat straw prior to dilute sulfuric acid treatment is investigated. The combined pretreatment for wheat straw was performed to evaluate the efficiency of enzymatic hydrolysis and compared with that of the effect of enzymatic hydrolysis by individual pretreatment

  2. Evaluation of improved γ-aminobutyric acid production in yogurt using Lactobacillus plantarum NDC75017.

    Science.gov (United States)

    Shan, Y; Man, C X; Han, X; Li, L; Guo, Y; Deng, Y; Li, T; Zhang, L W; Jiang, Y J

    2015-04-01

    Most γ-aminobutyric acid (GABA)-producing microorganisms are lactic acid bacteria (LAB), but the yield of GABA is limited in most of these GABA-producing strains. In this study, the production of GABA was carried out by using Lactobacillus plantarum NDC75017, a strain screened from traditional fermented dairy products in China. Concentrations of substrate (l-monosodium glutamate, L-MSG) and coenzyme (pyridoxal-5-phosphate, PLP) of glutamate decarboxylase (GAD) and culture temperature were investigated to evaluate their effects on GABA yield of Lb. plantarum NDC75017. The results indicated that GABA production was related to GAD activity and biomass of Lb. plantarum NDC75017. Response surface methodology was used to optimize conditions of GABA production. The optimal factors for GABA production were L-MSG at 80 mM, PLP at 18 μM, and a culture temperature of 36 °C. Under these conditions, production of GABA was maximized at 314.56 mg/100 g. Addition of Lb. plantarum NDC75017 to a commercial starter culture led to higher GABA production in fermented yogurt. Flavor and texture of the prepared yogurt and the control yogurt did not differ significantly. Thus, Lb. plantarum NDC75017 has good potential for manufacture of GABA-enriched fermented milk products.

  3. Ursodeoxycholic Acid Can Improve Liver Transaminase Quantities in Children with Anticonvulsant Drugs Hepatotoxicity: a Pilot Study.

    Directory of Open Access Journals (Sweden)

    Masoumeh Asgarshirazi

    2015-06-01

    Full Text Available The present study has been directed to investigate Ursodeoxycholic Acid (UDCA effect in children, to reduce the high Liver transaminases induced by Anticonvulsant drugs (drug induced hepatitis. This idea has been driven from Cytoprotective and antioxidant properties of UDCA to be used in drug induced inflammation in Liver. Twenty two epileptic patients aged between 4 mo - 3 yr whom were under anticonvulsant therapy with drugs such as valperoic acid, primidone, levetiracetam, Phenobarbital or any combination of them and had shown Liver transaminases rise , after rule out of Viral-Autoimmune, Metabolic and Anatomic causes, have been prescribed UDCA in dose of 10-15 mg/kg/day, at least for 6 months. Any patient who have shown confusing factors such as genetic disorders with liver involvement or spontaneous decline in enzymes or had not treatment compliance has been excluded from the study. Transaminases range changes as well as Probable side effects of the drug have been monitored. The results indicated that UDCA is effective and well tolerable in the children with drug induced hyper transaminasemia. No side effect has been seen and recorded in this study. Based on this study and its results, we recommend UDCA as a safe and effective choice in drug induced hepatotoxicities.

  4. Phenolic compounds in juice of “Isabel” grape treated with abscisic acid for color improvement

    Directory of Open Access Journals (Sweden)

    Yamamoto Lilian Yukari

    2015-01-01

    Full Text Available Isabel grape is the main cultivar used to produce juice in Brazil, which has rusticity and high productivity, but it is deficient in anthocyanins, a pigment responsible for the color. Thus, an alternative is the application of abscisic acid (S-ABA, which is responsible to promote the synthesis of anthocyanins. The aim of this work was to evaluate the phenolic compounds composition in “Isabel” grape juice treated with S-ABA, by HPLC-DAD–ESI-MS/MS technique. The results showed the increasing in total anthocyanin concentration in juices, with S-ABA treatments, as well as the proportion of B-ring tri-substituted anthocyanidins. Regarding total flavonols, differences were only significant in juices obtained in 2012 season. S-ABA treatments did not significantly affect the hydroxycinnamic acid derivatives, flavan-3-ols, resveratrol and antioxidant capacity of juices. Juice from “Isabel” grapes treated with S-ABA provides an enhancement of total anthocyanin concentration, mainly when grapes are treated before or at the onset of véraison.

  5. An improved extraction chromatographic resin for the separation of uranium from acidic nitrate media

    Energy Technology Data Exchange (ETDEWEB)

    Dietz, M.L.; Horwitz, E.P.; Sajdak, L.R.; Chiarizia, R. [Chemistry Division, Argonne National Laboratory, 60439 Argonne, IL (United States)

    2001-07-06

    The preparation and characterization of a new extraction chromatographic resin exhibiting extraordinarily strong retention of hexavalent uranyl ion over a wide range of nitric acid concentrations and very high selectivity for U(VI) over Fe(III) and numerous other cations is described. This new material (designated U/TEVA-2) comprises a novel liquid stationary phase consisting of an equimolar mixture of diamyl amylphosphonate (DA[AP]) and Cyanex 923{sup registered} (a commercially available trialkyl-phosphine oxide, TRPO) sorbed on silanized silica or Amberchrom CG-71. Cyanex 923 is shown to be preferable to a related TRPO, Cyanex 925{sup registered}, due to its lower viscosity and higher selectivity for U(VI) over Fe(III). The retention of uranyl nitrate by the U/TEVA-2 resin, as measured by the k' values (number of free column values to peak maximum) is >5000 from approximately 0.1 to 8 M HNO{sub 3}. The ability of the new resin to strongly and selectively retain U(VI) from such a wide range of acid concentrations, along with its favorable physical properties, make it a good candidate for application in the separation and preconcentration of U(VI) from complex environmental, biological, and nuclear waste samples for subsequent determination.

  6. An improved extraction chromatographic resin for the separation of uranium from acidic nitrate media.

    Science.gov (United States)

    Dietz, M L; Horwitz, E P; Sajdak, L R; Chiarizia, R

    2001-07-01

    The preparation and characterization of a new extraction chromatographic resin exhibiting extraordinarily strong retention of hexavalent uranyl ion over a wide range of nitric acid concentrations and very high selectivity for U(VI) over Fe(III) and numerous other cations is described. This new material (designated U/TEVA-2) comprises a novel liquid stationary phase consisting of an equimolar mixture of diamyl amylphosphonate (DA[AP]) and Cyanex 923((R)) (a commercially available trialkyl-phosphine oxide, TRPO) sorbed on silanized silica or Amberchrom CG-71. Cyanex 923 is shown to be preferable to a related TRPO, Cyanex 925((R)), due to its lower viscosity and higher selectivity for U(VI) over Fe(III). The retention of uranyl nitrate by the U/TEVA-2 resin, as measured by the k' values (number of free column values to peak maximum) is >5000 from approximately 0.1 to 8 M HNO(3). The ability of the new resin to strongly and selectively retain U(VI) from such a wide range of acid concentrations, along with its favorable physical properties, make it a good candidate for application in the separation and preconcentration of U(VI) from complex environmental, biological, and nuclear waste samples for subsequent determination.

  7. Biochar Application in Malaysian Sandy and Acid Sulfate Soils: Soil Amelioration Effects and Improved Crop Production over Two Cropping Seasons

    OpenAIRE

    Theeba Manickam; Gerard Cornelissen; Robert T. Bachmann; Illani Z. Ibrahim; Jan Mulder; Hale, Sarah E.

    2015-01-01

    The use of biochar as an agricultural soil improvement was tested in acid sulfate and sandy soils from Malaysia, cropped with rice and corn. Malaysia has an abundance of waste rice husks that could be used to produce biochar. Rice husk biochar was produced in a gasifier at a local mill in Kelantan as well as in the laboratory using a controlled, specially designed, top lift up draft system (Belonio unit). Rice husk biochar was applied once to both soils at two doses (2% and 5%), in a pot set ...

  8. Dietary Alpha Lipoic Acid Improves Body Composition, Meat Quality and Decreases Collagen Content in Muscle of Broiler Chickens

    OpenAIRE

    El-Senousey, H. K.; Fouad, A. M.; Yao, J. H.; Zhang, Z.G.; Shen, Q. W.

    2013-01-01

    A total of 192 broiler chicks were used to evaluate the influence of dietary α-lipoic acid (ALA) on growth performance, carcass characteristics and meat quality of broiler chickens with the purpose of developing a strategy to prevent the occurrence of pale, soft, and exudative (PSE) meat and to improve the meat quality of broilers. At 22 d of age, birds were allocated to 4 ALA treatments (0, 400, 800, and 1200 ppm). The results showed that dietary ALA significantly decreased average feed inta...

  9. A kinetic model for the frequency dependence of cholinergic modulation at hippocampal GABAergic synapses.

    Science.gov (United States)

    Stone, Emily; Haario, Heikki; Lawrence, J Josh

    2014-12-01

    In this paper we use a simple model of presynaptic neuromodulation of GABA signaling to decipher paired whole-cell recordings of frequency dependent cholinergic neuromodulation at CA1 parvalbumin-containing basket cell (PV BC)-pyramidal cell synapses. Variance-mean analysis is employed to normalize the data, which is then used to estimate parameters in the mathematical model. Various parameterizations and hidden parameter dependencies are investigated using Markov Chain Monte Carlo (MCMC) parameter estimation techniques. This analysis reveals that frequency dependence of cholinergic modulation requires both calcium-dependent recovery from depression and mAChR-induced inhibition of presynaptic calcium entry. A reduction in calcium entry into the presynaptic terminal in the kinetic model accounted for the frequency-dependent effects of mAChR activation.

  10. A kinetic model for the frequency dependence of cholinergic modulation at hippocampal GABAergic synapses.

    Science.gov (United States)

    Stone, Emily; Haario, Heikki; Lawrence, J Josh

    2014-12-01

    In this paper we use a simple model of presynaptic neuromodulation of GABA signaling to decipher paired whole-cell recordings of frequency dependent cholinergic neuromodulation at CA1 parvalbumin-containing basket cell (PV BC)-pyramidal cell synapses. Variance-mean analysis is employed to normalize the data, which is then used to estimate parameters in the mathematical model. Various parameterizations and hidden parameter dependencies are investigated using Markov Chain Monte Carlo (MCMC) parameter estimation techniques. This analysis reveals that frequency dependence of cholinergic modulation requires both calcium-dependent recovery from depression and mAChR-induced inhibition of presynaptic calcium entry. A reduction in calcium entry into the presynaptic terminal in the kinetic model accounted for the frequency-dependent effects of mAChR activation. PMID:25445738

  11. Spontaneous Synaptic Activation of Muscarinic Receptors by Striatal Cholinergic Neuron Firing.

    Science.gov (United States)

    Mamaligas, Aphroditi A; Ford, Christopher P

    2016-08-01

    Cholinergic interneurons (CHIs) play a major role in motor and learning functions of the striatum. As acetylcholine does not directly evoke postsynaptic events at most striatal synapses, it remains unclear how postsynaptic cholinergic receptors encode the firing patterns of CHIs in the striatum. To examine the dynamics of acetylcholine release, we used optogenetics and paired recordings from CHIs and medium spiny neurons (MSNs) virally overexpressing G-protein-activated inwardly rectifying potassium (GIRK) channels. Due to the efficient coupling between endogenous muscarinic receptors and GIRK channels, we found that firing of individual CHIs resulted in monosynaptic spontaneous inhibitory post-synaptic currents (IPSCs) in MSNs. Paired CHI-MSN recordings revealed that the high probability of acetylcholine release at these synapses allowed muscarinic receptors to faithfully encode physiological activity patterns from individual CHIs without failure. These results indicate that muscarinic receptors in striatal output neurons reliably decode CHI firing. PMID:27373830

  12. Augmentation of cholinergic-mediated amylase release by forskolin in mouse parotid gland

    International Nuclear Information System (INIS)

    Cholinergic-mediated amylase release in mouse parotid acini was augmented by forskolin; the potency but not the maximal response to carbachol was altered. Amylase released by carbachol plus forskolin was dependent on extracellular calcium and was mimicked by the calcium ionophore, A23187 plus forskolin. Forskolin was also shown to enhance carbachol-stimulated 45Ca2+ uptake into isolated acini. Hydroxylamine, nitroprusside, and 8-bromo-c-GMP each in combination with forskolin mimicked the effects of carbachol plus forskolin on amylase release. In the presence of carbachol (10-8M) forskolin did not augment c-AMP levels. However, in the presence of carbachol (5 x 10-7 M) or hydroxylamine (50 μM) forskolin did significantly augment c-AMP accumulation. These results suggest that calcium and c-GMP may mediate the augmentation of cholinergic-mediated amylase release by effects on c-AMP metabolism. 21 references, 1 figure, 3 tables

  13. Uranium chronic contamination effects on the cholinergic system: in vivo and in vitro approaches

    International Nuclear Information System (INIS)

    Uranium (U) is a heavy metal which occurs naturally in the environment. It is both a chemical and a radiological toxicant. The aim of this work was: (i) to assess the effects of U chronic exposure on the cholinergic system (biosynthesis and breakdown enzymes, receptors and on behaviour of adult, young or predisposed to neuro-degenerative illness (ApoE KO) rodents; (ii) to grasp the neurotoxic effects of U on human neuronal cells. In vivo, this work shows a structure- (cortex more sensitive than hippocampus), rodent model- (young more sensitive than adults), time- (sub-chronic exposure more harmful than chronic exposure), exposure level- and isotope-dependent effect of U. In vitro, the study underlined the neuro-cytotoxic U potential and the presence of uranium precipitates in cells. These results show the deleterious impact of U on neuronal cells, and demonstrate that U induces impairments on the cholinergic system and the behaviour of rodents. (author)

  14. Urotensin II modulates rapid eye movement sleep through activation of brainstem cholinergic neurons

    DEFF Research Database (Denmark)

    Huitron-Resendiz, Salvador; Kristensen, Morten Pilgaard; Sánchez-Alavez, Manuel;

    2005-01-01

    dorsal tegmental nuclei. This distribution suggests that the UII system is involved in functions regulated by acetylcholine, such as the sleep-wake cycle. Here, we tested the hypothesis that UII influences cholinergic PPT neuron activity and alters rapid eye movement (REM) sleep patterns in rats. Local...... administration of UII into the PPT nucleus increases REM sleep without inducing changes in the cortical blood flow. Intracerebroventricular injection of UII enhances both REM sleep and wakefulness and reduces slow-wave sleep 2. Intracerebroventricular, but not local, administration of UII increases cortical...... synaptic transmission because it persisted in the presence of TTX and antagonists of ionotropic glutamate, GABA, and glycine receptors. Collectively, these results suggest that UII plays a role in the regulation of REM sleep independently of its cerebrovascular actions by directly activating cholinergic...

  15. "Click" Chemistry-Tethered Hyaluronic Acid-Based Contact Lens Coatings Improve Lens Wettability and Lower Protein Adsorption.

    Science.gov (United States)

    Deng, Xudong; Korogiannaki, Myrto; Rastegari, Banafsheh; Zhang, Jianfeng; Chen, Mengsu; Fu, Qiang; Sheardown, Heather; Filipe, Carlos D M; Hoare, Todd

    2016-08-31

    Improving the wettability of and reducing the protein adsorption to contact lenses may be beneficial for improving wearer comfort. Herein, we describe a simple "click" chemistry approach to surface functionalize poly(2-hydroxyethyl methacrylate) (pHEMA)-based contact lenses with hyaluronic acid (HA), a carbohydrate naturally contributing to the wettability of the native tear film. A two-step preparation technique consisting of laccase/TEMPO-mediated oxidation followed by covalent grafting of hydrazide-functionalized HA via simple immersion resulted in a model lens surface that is significantly more wettable, more water retentive, and less protein binding than unmodified pHEMA while maintaining the favorable transparency, refractive, and mechanical properties of a native lens. The dipping/coating method we developed to covalently tether the HA wetting agent is simple, readily scalable, and a highly efficient route for contact lens modification. PMID:27509015

  16. Alpha-lipoic acid-mediated activation of muscarinic receptors improves hippocampus- and amygdala-dependent memory.

    Science.gov (United States)

    Mahboob, Aamra; Farhat, Syeda Mehpara; Iqbal, Ghazala; Babar, Mustafeez Mujtaba; Zaidi, Najam-us-Sahar Sadaf; Nabavi, Seyed Mohammad; Ahmed, Touqeer

    2016-04-01

    Aluminum (Al) is a neurotoxic agent which readily crosses the blood-brain-barrier (BBB) and accumulates in the brain leading to neurodegenerative disorders, characterised by cognitive impairment. Alpha-lipoic acid (ALA) is an antioxidant and has a potential to improve cognitive functions. This study aimed to evaluate the neuroprotective effect of ALA in AlCl3-induced neurotoxicity mouse model. Effect of ALA (25mg/kg/day) was evaluated in the AlCl3-induced neurotoxicity (AlCl3 150 mg/kg/day) mouse model on learning and memory using behaviour tests and on the expression of muscarinic receptor genes (using RT-PCR), in hippocampus and amygdala. Following ALA treatment, the expression of muscarinic receptor genes M1, M2 and choline acetyltransferase (ChaT) were significantly improved (penhanced fear memory (pmemory was remarkably restored (penhancement thus presenting it an enviable therapeutic candidate for the treatment of neurodegenerative disorders. PMID:26912408

  17. Using protein-fatty acid complexes to improve vitamin D stability

    DEFF Research Database (Denmark)

    Pedersen, Jannik Nedergaard; Frislev, Henriette Kristina Søster; Pedersen, Jan Skov;

    2016-01-01

    and evaluated their ability to protect vitD upon exposure to heating or intense UV light. Additionally, the stability of liprotides toward pH, Ca(2+), and BSA was determined. The best results were obtained with liprotides made from α-lactalbumin and oleate. These liprotides were able to completely solubilize...... to those made at 20°C. Nevertheless, the fatty acid binding protein BSA reduced the ability of both liprotides to protect vitD; the amount of vitD left after 20 d at 20°C fell from 79 ± 3% in the absence of BSA to 49 ± 4 and 23 ± 3% in the presence of BSA for liprotides made at 80 and 20°C, respectively...

  18. Graft polymerization of acrylic acid onto chitin nanofiber to improve dispersibility in basic water.

    Science.gov (United States)

    Ifuku, Shinsuke; Iwasaki, Masayoshi; Morimoto, Minoru; Saimoto, Hiroyuki

    2012-09-01

    Graft copolymerization of acrylic acid (AA) on chitin nanofibers was carried out with potassium persulfate as a free radical initiator in an aqueous medium. The molar ratio of grafted AA increased with the AA concentration. The grafted chitin nanofibers were characterized by FT-IR, FE-SEM, UV-vis, XRD, and TGA. After polymerization, the characteristic morphology of chitin nanofibers was maintained. Chitin nanofibers grafted with AA were efficiently dissociated and dispersed homogeneously in basic water because of the electrostatic repulsion effect between nanofibers. AA was grafted on the surface and amorphous part of chitin nanofibers, and the original crystalline structure of α-chitin was maintained. At 330 °C, the weight residue of the graft copolymer increased with the grafted AA content. PMID:24751085

  19. Compound amino acids added in media improved Solanum nigrum L. phytoremediating CD-PAHS contaminated soil.

    Science.gov (United States)

    Wei, Shuhe; Bai, Jiayi; Yang, Chuanjie; Zhang, Qianru; Knorrm, Klaus-Holger; Zhan, Jie; Gao, Qianhui

    2016-01-01

    Cd hyperaccumulator Solanum nigrum L. was a promising plant used to simultaneously remediate Cd-PAHs combined pollution soil through its extra accumulation capacity and rhizosphere degradation. This article compared the strengthening remediation role of cysteine (Cys), glycine (Gly) and glutamic acid (Glu) with EDTA and TW80. The results showed that the addition of 0.03 mmol L(-1) Cys, Gly, and Glu didn't significantly impact (p Cd concentration. Therefore, Cd capacity (µg pot(-1)) in shoots of S. nigrum was significantly increased (p Cd might lie in the addition of Cys, Gly, and Glu which reduced pH and increased extractable Cd concentration in rhizosphere and phytochelatines (PCs) concentration in leaves. As for the degradation of PAHs in rhizosphere, increased microorganism number might be play important role.

  20. Exogenous abscisic acid application during grain filling in winter wheat improves cold tolerance of offspring's seedlings

    DEFF Research Database (Denmark)

    Li, X.; Cai, J.; Liu, Fulai;

    2014-01-01

    Low temperature seriously depresses seed germination and seedling growth in winter wheat (Triticum aestivum L.). In this study, wheat plants were sprayed with abscisic acid (ABA) and fluridone (inhibitor of ABA biosynthesis) at 19 days after anthesis (DAA) and repeated at 26 DAA. The seeds of those...... plants were harvested, and seed germination and offspring's seedling growth under low temperature were evaluated. The results showed that exogenous ABA application decreased seed weight and slightly reduced seed set and seed number per spike. Under low temperature, seeds from ABA-treated plants showed...... reduced germination rate, germination index, growth of radicle and coleoptile, amylase activity and depressed starch degradation as compared with seeds from non-ABA-treated plants; however, activities of the antioxidant enzymes in both germinating seeds and seedling were enhanced from those exposed...

  1. Ellagic acid improved arrhythmias induced by CaCL2 in the rat stress model

    Directory of Open Access Journals (Sweden)

    Mahin Dianat

    2015-02-01

    Full Text Available Objective: In ventricular arrhythmias, due to their free radical scavenging action, antioxidant agents are usually used in the treatment of cardiovascular disease. Since stress is considered as risk factor for increased mortality by causing malignant arrhythmias, the study was designed to evaluate the cardioprotective effects of ellagic acid (EA on CaCl2-induced arrhythmias in rat stress model. Materials and Methods: Male Sprague-Dawley rats (200-250 g were divided into four groups: Group I: Control rats (2 ml of saline by gavage, Group II: Rats treated with EA (15 mg/kg, gavage, Group III: stress group, Group IV: received EA plus stress. Stress was applied in a restrainer box (6 hour/day, 21 days. After induction of anesthesia, lead II electrocardiogram was recorded for calculating heart rate and QRS complex. The arrhythmia was produced by injection of CaCl2 solution (140 mg/kg, iv and incidences of Ventricular fibrillation, Ventricular premature beats and Ventricular tachycardia were recorded. Results were analyzed by using one-way ANOVA and Fisher`s exact test. pResults: The results showed a positive inotropic effect and negative chronotropic effect for the EA group in comparison with the control group. Incidence rates (% of premature beats, ventricular fibrillation and ventricular tachycardia in stress group and all the arrhythmia parameters decreased in groups which received EA. Conclusions:  By decreasing the incidence rates of premature beats, fibrillation and ventricular tachycardia in groups which received EA, ellagic acid probably acted as an anti-arrhythmic agent which showed to have aprotective functionin heart.

  2. Presenilin-1 Mutation Impairs Cholinergic Modulation of Synaptic Plasticity and Suppresses NMDA Currents in Hippocampus slices

    OpenAIRE

    Wang, Yue; Greig, Nigel H.; Yu, Qian-Sheng; Mattson, Mark P.

    2008-01-01

    Presenilin-1 (PS1) mutations cause many cases of early-onset inherited Alzheimer's disease, in part, by increasing the production of neurotoxic forms of amyloid β-peptide (A β). However, Aβ -independent effects of mutant PS1 on neuronal Ca2+ homeostasis and sensitivity to excitatory neurotransmitters have been reported. Here we show that cholinergic modulation of hippocampal synaptic plasticity is impaired in PS1 mutant knockin (PS1KI) mice. Whereas activation of muscarinic receptors enhances...

  3. Acetylcholine as a neuromodulator: cholinergic signaling shapes nervous system function and behavior

    OpenAIRE

    Picciotto, Marina R.; Higley, Michael J.; Mineur, Yann S.

    2012-01-01

    Acetylcholine in the brain alters neuronal excitability, influences synaptic transmission, induces synaptic plasticity and coordinates the firing of groups of neurons. As a result, it changes the state of neuronal networks throughout the brain and modifies their response to internal and external inputs: the classical role of a neuromodulator. Here we identify actions of cholinergic signaling on cellular and synaptic properties of neurons in several brain areas and discuss the consequences of ...

  4. Attention, prediction and sequence learning : roles of the cholinergic basal forebrain and the retrosplenial cortex

    OpenAIRE

    Córdova, Christopher Andy

    2005-01-01

    Our ability to foresee and shape biologically important events relies on a combination of visuospatial attention, memory capacities, and an ability to learn new sequences of goal-directed action. A novel set of behavioral studies were conducted to investigate neurobiological processes that underlie selective attention and visuospatial sequence learning. The first experiment assessed a theorized computational role of basal forebrain cholinergic neurons in modulating attention by increasing sti...

  5. Novel Fast Adapting Interneurons Mediate Cholinergic-Induced Fast GABAA IPSCs In Striatal Spiny Neurons

    OpenAIRE

    Faust, Thomas W.; Assous, Maxime; Shah, Fulva; Tepper, James M.; Koós, Tibor

    2015-01-01

    Previous work suggests that neostriatal cholinergic interneurons control the activity of several classes of GABAergic interneurons through fast nicotinic receptor mediated synaptic inputs. Although indirect evidence has suggested the existence of several classes of interneurons controlled by this mechanism only one such cell type, the neuropeptide-Y expressing neurogliaform neuron, has been identified to date. Here we tested the hypothesis that in addition to the neurogliaform neurons that el...

  6. Acetylcholinesterase loosens the brain's cholinergic anti-inflammatory response and promotes epileptogenesis

    Directory of Open Access Journals (Sweden)

    Yehudit eGnatek

    2012-05-01

    Full Text Available Recent studies show a key role of brain inflammation in epilepsy. However, the mechanisms controlling brain immune response are only partly understood. In the periphery, acetylcholine (ACh release by the vagus nerve restrains inflammation by inhibiting the activation of leukocytes. Recent reports suggested a similar anti-inflammatory effect for ACh in the brain. Since brain cholinergic dysfunction are documented in epileptic animals, we explored changes in brain cholinergic gene expression and associated immune response during pilocarpine-induced epileptogenesis. Levels of acetylcholinesterase (AChE and inflammatory markers were measured using real-time RT-PCR, in-situ hybridization and immunostaining in wild type (WT and transgenic mice over-expressing the "synaptic" splice variant AChE-S (TgS. One month following pilocarpine, mice were video-monitored for spontaneous seizures. To test directly the effect of ACh on the brain's innate immune response, cytokines expression levels were measured in acute brain slices treated with cholinergic agents. We report a robust upregulation of AChE as early as 48 hrs following pilocarpine-induced status epilepticus (SE. AChE was expressed in hippocampal neurons, microglia and endothelial cells but rarely in astrocytes. TgS mice overexpressing AChE showed constitutive increased microglial activation, elevated levels of pro-inflammatory cytokines 48 hrs after SE and accelerated epileptogenesis compared to their WT counterparts. Finally we show a direct, muscarine-receptor dependant, nicotine-receptor independent anti-inflammatory effect of ACh in brain slices maintained ex vivo. Our work demonstrates for the first time, that ACh directly suppresses brain innate immune response and that AChE up-regulation after SE is associated with enhanced immune response, facilitating the epileptogenic process. Our results highlight the cholinergic system as a potential new target for the prevention of seizures and epilepsy.

  7. Sleep pattern and learning in knockdown mice with reduced cholinergic neurotransmission

    Directory of Open Access Journals (Sweden)

    C.M. Queiroz

    2013-01-01

    Full Text Available Impaired cholinergic neurotransmission can affect memory formation and influence sleep-wake cycles (SWC. In the present study, we describe the SWC in mice with a deficient vesicular acetylcholine transporter (VAChT system, previously characterized as presenting reduced acetylcholine release and cognitive and behavioral dysfunctions. Continuous, chronic ECoG and EMG recordings were used to evaluate the SWC pattern during light and dark phases in VAChT knockdown heterozygous (VAChT-KDHET, n=7 and wild-type (WT, n=7 mice. SWC were evaluated for sleep efficiency, total amount and mean duration of slow-wave, intermediate and paradoxical sleep, as well as the number of awakenings from sleep. After recording SWC, contextual fear-conditioning tests were used as an acetylcholine-dependent learning paradigm. The results showed that sleep efficiency in VAChT-KDHET animals was similar to that of WT mice, but that the SWC was more fragmented. Fragmentation was characterized by an increase in the number of awakenings, mainly during intermediate sleep. VAChT-KDHET animals performed poorly in the contextual fear-conditioning paradigm (mean freezing time: 34.4±3.1 and 44.5±3.3 s for WT and VAChT-KDHET animals, respectively, which was followed by a 45% reduction in the number of paradoxical sleep episodes after the training session. Taken together, the results show that reduced cholinergic transmission led to sleep fragmentation and learning impairment. We discuss the results on the basis of cholinergic plasticity and its relevance to sleep homeostasis. We suggest that VAChT-KDHET mice could be a useful model to test cholinergic drugs used to treat sleep dysfunction in neurodegenerative disorders.

  8. Neuro-immune interactions via the cholinergic anti-inflammatory pathway

    OpenAIRE

    Gallowitsch-Puerta, Margot; Pavlov, Valentin A.

    2007-01-01

    The overproduction of TNF and other cytokines can cause the pathophysiology of numerous diseases. Controlling cytokine synthesis and release is critical for preventing unrestrained inflammation and maintaining health. Recent studies identified an efferent vagus nerve-based mechanism termed “the cholinergic anti-inflammatory pathway” that controls cytokine production and inflammation. Here we review current advances related to the role of this pathway in neuro-immune interactions that prevent ...

  9. Impairment of reward-related learning by cholinergic cell ablation in the striatum

    OpenAIRE

    Kitabatake, Yasuji; Hikida, Takatoshi; Watanabe, Dai; Pastan, Ira; Nakanishi, Shigetada

    2003-01-01

    The striatum in the basal ganglia-thalamocortical circuitry is a key neural substrate that is implicated in motor balance and procedural learning. The projection neurons in the striatum are dynamically modulated by nigrostriatal dopaminergic input and intrastriatal cholinergic input. The role of intrastriatal acetylcholine (ACh) in learning behaviors, however, remains to be fully clarified. In this investigation, we examine the involvement of intrastriatal ACh in different categories of...

  10. Carbachol can be released at a cholinergic ganglionic synapse as a false transmitter.

    OpenAIRE

    Baux, G; Tauc, L

    1983-01-01

    Carbachol was injected into a presynaptic cholinergic neuron in the buccal ganglion of Aplysia and the quantal aspects of the Cl- -dependent postsynaptic response to a prolonged stimulation were analyzed by a statistical fluctuation method. The calculated amplitude of the miniature postsynaptic current was increased with respect to control. Statistical fluctuation analysis was also used to analyze the postsynaptic response obtained during ionophoretic application of acetylcholine and carbacho...

  11. Presynaptic transmitter content controls the number of quanta released at a neuro-neuronal cholinergic synapse.

    OpenAIRE

    Poulain, B; Baux, G; Tauc, L

    1986-01-01

    In the buccal ganglion of Aplysia the overloading of the cholinergic presynaptic neuron by exogenous acetylcholine (AcCho) led to an enhancement of the postsynaptic response. The deprivation of choline in the presynaptic neuron by extra- and/or intracellularly applied choline oxidase to prevent AcCho synthesis resulted in a decrease of the postsynaptic response. In both cases, the size of the calculated miniature postsynaptic current (i.e., the size of the quantum) remained unchanged. It was ...

  12. Cholinergic Dysfunction in Fragile X Syndrome and Potential Intervention: A Preliminary 1H MRS Study

    OpenAIRE

    Kesler, Shelli R.; Lightbody, Amy A.; Reiss, Allan L.

    2009-01-01

    Males with fragile X syndrome are at risk for significant cognitive and behavioral deficits, particularly those involving executive prefrontal systems. Disruption of the cholinergic system secondary to fragile X mental retardation protein deficiency may contribute to the cognitive-behavioral impairments associated with fragile X. We measured choline in the dorsolateral prefrontal cortex of 9 males with fragile X syndrome and 9 age-matched typically developing controls using 1H magnetic resona...

  13. Unraveling the mechanism of neuroprotection of curcumin in arsenic induced cholinergic dysfunctions in rats

    International Nuclear Information System (INIS)

    Earlier, we found that arsenic induced cholinergic deficits in rat brain could be protected by curcumin. In continuation to this, the present study is focused to unravel the molecular mechanisms associated with the protective efficacy of curcumin in arsenic induced cholinergic deficits. Exposure to arsenic (20 mg/kg body weight, p.o) for 28 days in rats resulted to decrease the expression of CHRM2 receptor gene associated with mitochondrial dysfunctions as evident by decrease in the mitochondrial membrane potential, activity of mitochondrial complexes and enhanced apoptosis both in the frontal cortex and hippocampus in comparison to controls. The ultrastructural images of arsenic exposed rats, assessed by transmission electron microscope, exhibited loss of myelin sheath and distorted cristae in the mitochondria both in the frontal cortex and hippocampus as compared to controls. Simultaneous treatment with arsenic (20 mg/kg body weight, p.o) and curcumin (100 mg/kg body weight, p.o) for 28 days in rats was found to protect arsenic induced changes in the mitochondrial membrane potential and activity of mitochondrial complexes both in frontal cortex and hippocampus. Alterations in the expression of pro- and anti-apoptotic proteins and ultrastructural damage in the frontal cortex and hippocampus following arsenic exposure were also protected in rats simultaneously treated with arsenic and curcumin. The data of the present study reveal that curcumin could protect arsenic induced cholinergic deficits by modulating the expression of pro- and anti-apoptotic proteins in the brain. More interestingly, arsenic induced functional and ultrastructural changes in the brain mitochondria were also protected by curcumin. - Highlights: • Neuroprotective mechanism of curcumin in arsenic induced cholinergic deficits studied • Curcumin protected arsenic induced enhanced expression of stress markers in rat brain • Arsenic compromised mitochondrial electron transport chain protected

  14. Unraveling the mechanism of neuroprotection of curcumin in arsenic induced cholinergic dysfunctions in rats

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, Pranay [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Yadav, Rajesh S. [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Department of Crimnology and Forensic Science, Harisingh Gour University, Sagar 470 003 (India); Chandravanshi, Lalit P.; Shukla, Rajendra K.; Dhuriya, Yogesh K.; Chauhan, Lalit K.S. [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Dwivedi, Hari N. [Babu Banarasi Das University, BBD City, Faizabad Road, Lucknow 227 015 (India); Pant, Aditiya B. [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Khanna, Vinay K., E-mail: vkkhanna1@gmail.com [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India)

    2014-09-15

    Earlier, we found that arsenic induced cholinergic deficits in rat brain could be protected by curcumin. In continuation to this, the present study is focused to unravel the molecular mechanisms associated with the protective efficacy of curcumin in arsenic induced cholinergic deficits. Exposure to arsenic (20 mg/kg body weight, p.o) for 28 days in rats resulted to decrease the expression of CHRM2 receptor gene associated with mitochondrial dysfunctions as evident by decrease in the mitochondrial membrane potential, activity of mitochondrial complexes and enhanced apoptosis both in the frontal cortex and hippocampus in comparison to controls. The ultrastructural images of arsenic exposed rats, assessed by transmission electron microscope, exhibited loss of myelin sheath and distorted cristae in the mitochondria both in the frontal cortex and hippocampus as compared to controls. Simultaneous treatment with arsenic (20 mg/kg body weight, p.o) and curcumin (100 mg/kg body weight, p.o) for 28 days in rats was found to protect arsenic induced changes in the mitochondrial membrane potential and activity of mitochondrial complexes both in frontal cortex and hippocampus. Alterations in the expression of pro- and anti-apoptotic proteins and ultrastructural damage in the frontal cortex and hippocampus following arsenic exposure were also protected in rats simultaneously treated with arsenic and curcumin. The data of the present study reveal that curcumin could protect arsenic induced cholinergic deficits by modulating the expression of pro- and anti-apoptotic proteins in the brain. More interestingly, arsenic induced functional and ultrastructural changes in the brain mitochondria were also protected by curcumin. - Highlights: • Neuroprotective mechanism of curcumin in arsenic induced cholinergic deficits studied • Curcumin protected arsenic induced enhanced expression of stress markers in rat brain • Arsenic compromised mitochondrial electron transport chain protected

  15. Cholinergic degeneration and memory loss delayed by vitamin E in a Down syndrome mouse model

    OpenAIRE

    Lockrow, Jason; Prakasam, Annamalai; Huang, Peng; Bimonte-Nelson, Heather; Sambamurti, Kumar; Granholm, Ann-Charlotte

    2008-01-01

    Down syndrome (DS) individuals develop several neuropathological hallmarks seen in Alzheimer's disease, including cognitive decline and the early loss of cholinergic markers in the basal forebrain. These deficits are replicated in the Ts65Dn mouse, which contains a partial trisomy of murine chromosome 16, the orthologous genetic segment to human chromosome 21. Oxidative stress levels are elevated early in DS, and may contribute to the neurodegeneration seen in these individuals. We evaluated ...

  16. Improvement of the fermentative activity of lactic acid bacteria starter culture by the addition of Mn²⁺.

    Science.gov (United States)

    Cheng, Xin; Dong, Ying; Su, Ping; Xiao, Xiang

    2014-11-01

    Production of lactic acid bacteria (LAB) starter with raw material has received much scientific investigation, but little information is available on the influences of some trace elements on the growth and fermentative activity of LAB. Based on this fact, this paper aimed to investigate the effects of Mn(2+) on the performance of Lactobacillus plantarum CX-15 starter with Jerusalem artichoke (JA) as the main medium substrate. The results showed that Mn(2+) addition had a significant beneficial affect on the fermentative activity of L. plantarum CX-15 starter. In contrast, the lack of Mn(2+) would cause the subsequent fermentation significantly slower, whether the cell density in starter culture was higher or lower. The possible mechanism of these phenomenons was further elucidated by the time course analysis of the specific activities of metabolism key enzymes during the culture processes of L. plantarum CX-15 starter. Compared to the fermentation processes without Mn(2+) addition, it was found that Mn(2+) addition would enhance the lactate dehydrogenase (LDH) activity but reduce the activities of pyruvate dehydrogenase (PDH) and ATPase activity. Therefore, it could be concluded that the improvement of L. plantarum starter fermentative activity was probably a consequence of Mn(2+) acting as "metabolic switch," which regulated the metabolic flux from pyruvic acid to lactic acid and other metabolism pathway. PMID:25146195

  17. Improvement of L(+)-Lactic Acid Production of Rhizopus Oryzae by Low-Energy Ions and Analysis of Its Mechanism

    Institute of Scientific and Technical Information of China (English)

    GE Chunmei; YANG Yingge; FAN Yonghong; LI Wen; PAN Renrui; ZHENG Zhiming; YU Zengliang

    2008-01-01

    The wild type strain Rhizopus oryzae PW352 was mutated by means of nitrogen ion implantation (15 keV, 7.8 × 104 ~ 2.08 × 105 ions/cm2) to find an industrial strain with a higher L(+)-lactic acid yield, and two mutants RE3303 and RF9052 were isolated. In order to discuss the mechanism primarily,Lactate Dehydrogenase of Rhizopus oryzae was studied. While the two mutants produced L(+)-lactic acid by 75% more than the wild strain did, their specific activity of Lactate Dehydrogenase was found to be higher than that in the wild strain. The optimum temperature of Lactate Dehydrogenase in Rhizopus oryzae RF9052 was higher. Compared to the wild strain, the Michaelis constant (Km) value of Lactate Dehydrogenase in the mutants was Changed. All these changes show that L(+)-lactic acid production has a correlation with the specific activity of Lactate Dehydrogenase. The low-energy ions, implanted into the strain, may improve the specific activity of Lactate Dehydrogenase by influencing its gene structure and protein structure.

  18. Metabolic Control in Mammalian Fed-Batch Cell Cultures for Reduced Lactic Acid Accumulation and Improved Process Robustness

    Directory of Open Access Journals (Sweden)

    Viktor Konakovsky

    2016-01-01

    Full Text Available Biomass and cell-specific metabolic rates usually change dynamically over time, making the “feed according to need” strategy difficult to realize in a commercial fed-batch process. We here demonstrate a novel feeding strategy which is designed to hold a particular metabolic state in a fed-batch process by adaptive feeding in real time. The feed rate is calculated with a transferable biomass model based on capacitance, which changes the nutrient flow stoichiometrically in real time. A limited glucose environment was used to confine the cell in a particular metabolic state. In order to cope with uncertainty, two strategies were tested to change the adaptive feed rate and prevent starvation while in limitation: (i inline pH and online glucose concentration measurement or (ii inline pH alone, which was shown to be sufficient for the problem statement. In this contribution, we achieved metabolic control within a defined target range. The direct benefit was two-fold: the lactic acid profile was improved and pH could be kept stable. Multivariate Data Analysis (MVDA has shown that pH influenced lactic acid production or consumption in historical data sets. We demonstrate that a low pH (around 6.8 is not required for our strategy, as glucose availability is already limiting the flux. On the contrary, we boosted glycolytic flux in glucose limitation by setting the pH to 7.4. This new approach led to a yield of lactic acid/glucose (Y L/G around zero for the whole process time and high titers in our labs. We hypothesize that a higher carbon flux, resulting from a higher pH, may lead to more cells which produce more product. The relevance of this work aims at feeding mammalian cell cultures safely in limitation with a desired metabolic flux range. This resulted in extremely stable, low glucose levels, very robust pH profiles without acid/base interventions and a metabolic state in which lactic acid was consumed instead of being produced from day 1. With

  19. Novel information on the non-neuronal cholinergic system in orthopedics provides new possible treatment strategies for inflammatory and degenerative diseases

    Directory of Open Access Journals (Sweden)

    Sture Forsgren

    2009-07-01

    Full Text Available Anti-cholinergic agents are used in the treatment of several pathological conditions. Therapy regimens aimed at up-regulating cholinergic functions, such as treatment with acetylcholinesterase inhibitors, are also currently prescribed. It is now known that not only is there a neuronal cholinergic system but also a non-neuronal cholinergic system in various parts of the body. Therefore, interference with the effects of acetylcholine (ACh brought about by the local production and release of ACh should also be considered. Locally produced ACh may have proliferative, angiogenic, wound-healing, and immunomodulatory functions. Interestingly, cholinergic stimulation may lead to anti-inflammatory effects. Within this review, new findings for the locomotor system of a more widespread non-neuronal cholinergic system than previously expected will be discussed in relation to possible new treatment strategies. The conditions discussed are painful and degenerative tendon disease (tendinopathy/tendinosis, rheumatoid arthritis, and osteoarthritis.

  20. Lesions of cholinergic pedunculopontine tegmental nucleus neurons fail to affect cocaine or heroin self-administration or conditioned place preference in rats.

    Directory of Open Access Journals (Sweden)

    Stephan Steidl

    Full Text Available Cholinergic input to the ventral tegmental area (VTA is known to contribute to reward. Although it is known that the pedunculopontine tegmental nucleus (PPTg provides an important source of excitatory input to the dopamine system, the specific role of PPTg cholinergic input to the VTA in cocaine reward has not been previously determined. We used a diphtheria toxin conjugated to urotensin-II (Dtx::UII, the endogenous ligand for urotensin-II receptors expressed by PPTg cholinergic but not glutamatergic or GABAergic cells, to lesion cholinergic PPTg neurons. Dtx::UII toxin infusion resulted in the loss of 95.78 (±0.65% of PPTg cholinergic cells but did not significantly alter either cocaine or heroin self-administration or the development of cocaine or heroin conditioned place preferences. Thus, cholinergic cells originating in PPTg do not appear to be critical for the rewarding effects of cocaine or of heroin.

  1. Improvements in glucose metabolism early after gastric bypass surgery are not explained by increases in total bile acids and fibroblast growth factor 19 concentrations

    DEFF Research Database (Denmark)

    Jørgensen, Nils B; Dirksen, Carsten; Bojsen-Møller, Kirstine N;

    2015-01-01

    Context: Bile acids and fibroblast growth factor 19 (FGF19) have been suggested as key mediators of the improvements in glucose metabolism after Roux-en-Y gastric bypass (RYGB). Objective: To describe fasting and postprandial state total bile acid (TBA) and FGF19 concentrations before and after...

  2. [Bowel obstruction-induced cholinergic crisis with progressive respiratory failure following distigmine bromide treatment].

    Science.gov (United States)

    Kobayashi, Kazuki; Sekiguchi, Hiroshi; Sato, Nobuhiro; Hirose, Yasuo

    2016-03-01

    A 54-year-old female experienced rapid respiratory failure while being transported in an ambulance to our emergency department for evaluation and management of constipation and abdominal pain. The patient was on treatment with distigmine bromide for postoperative urination disorder and magnesium oxide for constipation. Increased salivary secretions, diminished respiratory excursion, type 2 respiratory failure (PaCO2 : 65 mmHg), low serum cholinesterase, and hypermagnesemia were detected. Imaging studies revealed that the patient had bilateral aspiration pneumonia, fecal impaction in the rectum, and a distended colon causing ileus. The patient was mechanically ventilated and was weaned off the ventilator on day 3. Therapeutic drug monitoring after discharge revealed that the serum level of distigmine bromide on admission was markedly elevated (377.8 ng/mL vs. the normal therapeutic level of 5-10 ng/mL). Distigmine bromide induced a cholinergic crisis with a resultant increase in airway secretions and respiratory failure. In this particular case, orally administered distigmine bromide was excessively absorbed because of prolonged intestinal transit time secondary to fecal impaction and sluggish bowel movement; this caused a cholinergic crisis and hypermagnesemia contributing to respiratory failure. Clinicians should be aware that bowel obstruction in a patient treated with distigmine bromide can increase the risk of a cholinergic crisis. PMID:27255021

  3. ROLE OF CHOLINERGIC SYSTEM ON THE CONSTRUCTION OF MEMORY AND ITS INTERACTION WITH DOPAMINERGIC SYSTEM

    Directory of Open Access Journals (Sweden)

    F. Z. Zangeneh

    2006-07-01

    Full Text Available The central cholinergic system has been associated with cognitive function and memory and acetylcholine plays an important role during the early stages of memory consolidation. In this study, after training mice were tested with one way active avoidance procedure and retention were tested at 4, 8, 12, 16 and 24 hours of training and compared with non-shocked mice, in which it took 24 hours, a suitable time for retention test. Low dose administration of arecoline and physostigmine pre-training, immediate post-training and before retrieval showed that muscarinic agonist arecoline can potentiated memory in post trained and retrieval phases and reversible cholinesterase inhibitor physostigmine potentiated memory only in retrieval phase. Scopolamine disrupted acetylcholine potentiation only in retrieval phase. In the second part of this study, the effect of dopaminergic system was investigated. Low dose of apomorphine and D2 agonist bromocriptine potentiated memory when administered immediately post-training, and D2 antagonist sulpiride impaired memory. When the cholinergic system was blocked by scopolamine immediately post-training, apomorphine and bromocriptine potentiated memory and sulpiride impaired it. In conclusion, these results suggest that, cholinergic system in retrieval phase is very critical and there was no interaction between the two systems in the post-training phase.

  4. Naltrexone pretreatment blocks microwave-induced changes in central cholinergic receptors

    Energy Technology Data Exchange (ETDEWEB)

    Lai, H.; Carino, M.A.; Wen, Y.F.; Horita, A.; Guy, A.W. (Univ. of Washington School of Medicine, Seattle (USA))

    1991-01-01

    Repeated exposure of rats to pulsed, circularly polarized microwaves (2,450-MHz, 2-microseconds pulses at 500 pps, power density 1 mW/cm2, at an averaged, whole-body SAR of 0.6 W/kg) induced biphasic changes in the concentration of muscarinic cholinergic receptors in the central nervous system. An increase in receptor concentration occurred in the hippocampus of rats subjected to ten 45-min sessions of microwave exposure, whereas a decrease in concentration was observed in the frontal cortex and hippocampus of rats exposed to ten 20-min sessions. These findings, which confirm earlier work in the authors' laboratory, were extended to include pretreatment of rats with the narcotic antagonist naltrexone (1 mg/kg, IP) before each session of exposure. The drug treatment blocked the microwave-induced changes in cholinergic receptors in the brain. These data further support the authors' hypothesis that endogenous opioids play a role in the effects of microwaves on central cholinergic systems.

  5. Pharmacological identification of cholinergic receptor subtypes on Drosophila melanogaster larval heart.

    Science.gov (United States)

    Malloy, Cole A; Ritter, Kyle; Robinson, Jonathan; English, Connor; Cooper, Robin L

    2016-01-01

    The Drosophila melanogaster heart is a popular model in which to study cardiac physiology and development. Progress has been made in understanding the role of endogenous compounds in regulating cardiac function in this model. It is well characterized that common neurotransmitters act on many peripheral and non-neuronal tissues as they flow through the hemolymph of insects. Many of these neuromodulators, including acetylcholine (ACh), have been shown to act directly on the D. melanogaster larval heart. ACh is a primary neurotransmitter in the central nervous system (CNS) of vertebrates and at the neuromuscular junctions on skeletal and cardiac tissue. In insects, ACh is the primary excitatory neurotransmitter of sensory neurons and is also prominent in the CNS. A full understanding regarding the regulation of the Drosophila cardiac physiology by the cholinergic system remains poorly understood. Here we use semi-intact D. melanogaster larvae to study the pharmacological profile of cholinergic receptor subtypes, nicotinic acetylcholine receptors (nAChRs) and muscarinic acetylcholine receptors (mAChRs), in modulating heart rate (HR). Cholinergic receptor agonists, nicotine and muscarine both increase HR, while nAChR agonist clothianidin exhibits no significant effect when exposed to an open preparation at concentrations as low as 100 nM. In addition, both nAChR and mAChR antagonists increase HR as well but also display capabilities of blocking agonist actions. These results provide evidence that both of these receptor subtypes display functional significance in regulating the larval heart's pacemaker activity.

  6. Somatostatin inhibits cANP-mediated cholinergic transmission in the myenteric plexus

    International Nuclear Information System (INIS)

    The mechanism by which somatostatin acts to modulate cholinergic transmission is not clear. In this study the authors investigated the role of the adenosine 3',5'-cyclic monophosphate (cAMP) system in mediating cholinergic transmission in the guinea pig myenteric plexus and examined the ability of somatostatin to alter acetylcholine (ACh) release stimulated by various cAMP agonists. Forskolin, 8-bromo-cAMP, vasoactive intestinal peptide (VIP), and cholera toxin each stimulated the release of [3H]ACh in a dose-related manner. Addition of theophylline enhanced the release of [3H]ACh stimulated by these cAMP agonists. The observations suggest that cAMP may serve as a physiological mediator for ACh release from myenteric neurons. Somatostatin inhibited release of [3H]ACh evoked by various cAMP agonists in a dose-related manner. Pretreatment with pertussis toxin antagonized the inhibitory effect of somatostatin on the release of [3H]ACh evoked by forskolin, VIP, or cholera toxin but had no effect on the inhibitory action of somatostatin on the release of [3H]ACh evoked by 8-bromo-cAMP. This suggests that the principal mechanism by which somatostatin inhibits cAMP-mediated cholinergic transmission is via activation of the inhibitory regulatory protein (Ni subunit) of adenyalte cyclase

  7. Surface colonization by Azospirillum brasilense SM in the indole-3-acetic acid dependent growth improvement of sorghum.

    Science.gov (United States)

    Kochar, Mandira; Srivastava, Sheela

    2012-04-01

    The key to improving plant productivity is successful bacterial-plant interaction in the rhizosphere that can be maintained in the environment. The results presented here confirm Azospirillum brasilense strain SM as a competent plant growth promoting bacterium over mid- and long-term associations with sorghum. This study establishes that plant growth can be directly correlated with the associated bacterium's indole-3-acetic acid (IAA) production capability as IAA over-expressing variants, SMp30 and SMΔi3-6 fared better than the wild type strain. The auxin antagonist, p-chlorophenoxy isobutyric acid confirmed the role of bacterial IAA in plant growth promotion and verified the presence of larger amount of IAA available to the seeds on inoculation with IAA over-expressing mutants. Microscopic analysis identified the bacterial association at root tips, root-shoot junction and elongation zone and their surface colonizing nature. Scanning electron microscopy identified larger number of root hairs and extensive exopolysaccharide covering in comparison to untreated ones. In addition, vibroid-shaped Azospirilla attached by means of fibrillar material were dispersed along the elongation zone. The notable difference with IAA over-expressing variants was enhanced number of root hairs. Thus, the variant strains may be more efficient surface colonizers of the sorghum root and used as superior bio-inoculants for improving plant productivity.

  8. Multiple-unit tablet of probiotic bacteria for improved storage stability, acid tolerability, and in vivo intestinal protective effect.

    Science.gov (United States)

    Park, Hee Jun; Lee, Ga Hyeon; Jun, Joonho; Son, Miwon; Kang, Myung Joo

    2016-01-01

    The aim of this study was to formulate probiotics-loaded pellets in a tablet form to improve storage stability, acid tolerability, and in vivo intestinal protective effect. Bacteria-loaded pellets primarily prepared with hydroxypropyl methylcellulose acetate succinate were compressed into tablets with highly compressible excipients and optimized for flow properties, hardness, and disintegration time. The optimized probiotic tablet consisted of enteric-coated pellets (335 mg), microcrystalline cellulose (Avicel PH102, 37.5 mg), and porous calcium silicate (25 mg) and allowed whole survival of living bacteria during the compaction process with sufficient tablet hardness (13 kp) and disintegration time (14 minutes). The multiple-unit tablet showed remarkably higher storage stability under ambient conditions (25°C/60% relative humidity) over 6 months and resistance to acidic medium compared to uncoated strains or pellets. Repeated intake of this multiple-unit tablet significantly lowered plasma level of endotoxin, a pathogenic material, compared to repeated intake of bare probiotics or marketed products in rats. These results, therefore, suggest that the multiple-unit tablet is advantageous to better bacterial viability and gain the beneficial effects on the gut flora, including the improvement of intestinal barrier function. PMID:27103789

  9. The anticoagulant ability of ferulic acid and its applications for improving the blood compatibility of silk fibroin

    Energy Technology Data Exchange (ETDEWEB)

    Wang Song; Gao Zhen; Chen Xiaomeng; Lian Xiaojie; Zhu Hesun [School of Material Science and Engineering, Beijing Institute of Technology, Beijing 100081 (China); Zheng Jun; Sun Lizhong [Department of Cardiac Surgery, Cardiovascular Institute and Fu Wai Hospital, CAMS and PUMC, Beijing 100037 (China)], E-mail: wangsongbit@hotmail.com

    2008-12-15

    The hemocompatibility of silk fibroin (SF) was improved with ferulic acid (FA) by graft polymerization. Ferulic acid is an active ingredient of many Chinese herbal medicines, such as Chuanxiong (Rhizoma ligustici wallichii), Danggui (Angelica sinensis) and Awei (Asafoetida giantfennel), which have been used to treat cardiovascular diseases by Chinese physicians for thousands of years. The inhibitory functions of FA on blood coagulation and erythrocyte agglutination were first characterized by a Lee-White test tube method and a micropipette technique, respectively. Then, FA was immobilized on SF by graft polymerization and the surface composition of modified SF was characterized by attenuated total reflectance Fourier-transform infrared (ATR-FTIR), x-ray photoelectron spectroscopy (XPS) and optical microscopy. The anticoagulant activity of modified SF was assessed, respectively, by in vitro clotting time measurements on a photo-optical clot detection instrument and with the Lee-White test tube method. The test results indicated that in comparison to untreated SF, the anticoagulant activity of modified SF has been improved significantly. Moreover, the SF surface composition is altered by FA but its {beta}-sheet conformation is not disturbed.

  10. Multiple-unit tablet of probiotic bacteria for improved storage stability, acid tolerability, and in vivo intestinal protective effect

    Science.gov (United States)

    Park, Hee Jun; Lee, Ga Hyeon; Jun, Joonho; Son, Miwon; Kang, Myung Joo

    2016-01-01

    The aim of this study was to formulate probiotics-loaded pellets in a tablet form to improve storage stability, acid tolerability, and in vivo intestinal protective effect. Bacteria-loaded pellets primarily prepared with hydroxypropyl methylcellulose acetate succinate were compressed into tablets with highly compressible excipients and optimized for flow properties, hardness, and disintegration time. The optimized probiotic tablet consisted of enteric-coated pellets (335 mg), microcrystalline cellulose (Avicel PH102, 37.5 mg), and porous calcium silicate (25 mg) and allowed whole survival of living bacteria during the compaction process with sufficient tablet hardness (13 kp) and disintegration time (14 minutes). The multiple-unit tablet showed remarkably higher storage stability under ambient conditions (25°C/60% relative humidity) over 6 months and resistance to acidic medium compared to uncoated strains or pellets. Repeated intake of this multiple-unit tablet significantly lowered plasma level of endotoxin, a pathogenic material, compared to repeated intake of bare probiotics or marketed products in rats. These results, therefore, suggest that the multiple-unit tablet is advantageous to better bacterial viability and gain the beneficial effects on the gut flora, including the improvement of intestinal barrier function. PMID:27103789

  11. Multiple-unit tablet of probiotic bacteria for improved storage stability, acid tolerability, and in vivo intestinal protective effect

    Directory of Open Access Journals (Sweden)

    Park HJ

    2016-04-01

    Full Text Available Hee Jun Park,1 Ga Hyeon Lee,1 Joonho Jun,1 Miwon Son,1 Myung Joo Kang2 1Dong-A Pharmaceutical Co. Ltd., Yongin, Gyeonggi, 2College of Pharmacy, Dankook University, Cheonan, Chungnam, Korea Abstract: The aim of this study was to formulate probiotics-loaded pellets in a tablet form to improve storage stability, acid tolerability, and in vivo intestinal protective effect. Bacteria-loaded pellets primarily prepared with hydroxypropyl methylcellulose acetate succinate were compressed into tablets with highly compressible excipients and optimized for flow properties, hardness, and disintegration time. The optimized probiotic tablet consisted of enteric-coated pellets (335 mg, microcrystalline cellulose (Avicel PH102, 37.5 mg, and porous calcium silicate (25 mg and allowed whole survival of living bacteria during the compaction process with sufficient tablet hardness (13 kp and disintegration time (14 minutes. The multiple-unit tablet showed remarkably higher storage stability under ambient conditions (25°C/60% relative humidity over 6 months and resistance to acidic medium compared to uncoated strains or pellets. Repeated intake of this multiple-unit tablet significantly lowered plasma level of endotoxin, a pathogenic material, compared to repeated intake of bare probiotics or marketed products in rats. These results, therefore, suggest that the multiple-unit tablet is advantageous to better bacterial viability and gain the beneficial effects on the gut flora, including the improvement of intestinal barrier function. Keywords: probiotics, multiple-unit tablet, bacterial viability, acid resistance, intestinal barrier function

  12. Improved ethyl caproate production of Chinese liquor yeast by overexpressing fatty acid synthesis genes with OPI1 deletion.

    Science.gov (United States)

    Chen, Yefu; Luo, Weiwei; Gong, Rui; Xue, Xingxiang; Guan, Xiangyu; Song, Lulu; Guo, Xuewu; Xiao, Dongguang

    2016-09-01

    During yeast fermentation, ethyl esters play a key role in the development of the flavor profiles of Chinese liquor. Ethyl caproate, an ethyl ester eliciting apple-like flavor, is the characteristic flavor of strong aromatic liquor, which is the best selling liquor in China. In the traditional fermentation process, ethyl caproate is mainly produced at the later fermentation stage by aroma-producing yeast, bacteria, and mold in a mud pit instead of Saccharomyces cerevisiae at the expense of grains and fermentation time. To improve the production of ethyl caproate by Chinese liquor yeast (S. cerevisiae) with less food consumption and shorter fermentation time, we constructed three recombinant strains, namely, α5-ACC1ΔOPI1, α5-FAS1ΔOPI1, and α5-FAS2ΔOPI1 by overexpressing acetyl-CoA carboxylase (ACC1), fatty acid synthase 1 (FAS1), and fatty acid synthase 2 (FAS2) with OPI1 (an inositol/choline-mediated negative regulatory gene) deletion, respectively. In the liquid fermentation of corn hydrolysate, the contents of ethyl caproate produced by α5-ACC1ΔOPI1, α5-FAS1ΔOPI1, and α5-FAS2ΔOPI1 increased by 0.40-, 1.75-, and 0.31-fold, correspondingly, compared with the initial strain α5. The contents of other fatty acid ethyl esters (FAEEs) (C8:0, C10:0, C12:0) also increased. In comparison, the content of FAEEs produced by α5-FAS1ΔOPI1 significantly improved. Meanwhile, the contents of acetyl-CoA and ethyl acetate were enhanced by α5-FAS1ΔOPI1. Overall, this study offers a promising platform for the development of pure yeast culture fermentation of Chinese strong aromatic liquor without the use of a mud pit. PMID:27344573

  13. β-Cyclodextrin Inclusion Complex to Improve Physicochemical Properties of Pipemidic Acid: Characterization and Bioactivity Evaluation

    Directory of Open Access Journals (Sweden)

    Gaetano Malgieri

    2013-06-01

    Full Text Available The aptitude of cyclodextrins (CDs to form host-guest complexes has prompted an increase in the development of new drug formulations. In this study, the inclusion complexes of pipemidic acid (HPPA, a therapeutic agent for urinary tract infections, with native β-CD were prepared in solid state by kneading method and confirmed by FT-IR and 1H NMR. The inclusion complex formation was also characterized in aqueous solution at different pH via UV-Vis titration and phase solubility studies obtaining the stability constant. The 1:1 stoichiometry was established by a Job plot and the inclusion mechanism was clarified using docking experiments. Finally, the antibacterial activity of HPPA and its inclusion complex was tested on P. aeruginosa, E. coli and S. aureus to determine the respective EC50s and EC90s. The results showed that the antibacterial activity of HPPA:β-CD against E. coli and S. aureus is higher than that of HPPA. Furthermore, HPPA and HPPA:β-CD, tested on human hepatoblastoma HepG2 and MCF-7 cell lines by MTT assay, exhibited, for the first time, antitumor activities, and the complex revealed a higher activity than that of HPPA. The use of β-CD allows an increase in the aqueous solubility of the drug, its bioavailability and then its bioactivity.

  14. Improved Free Fatty Acid Production in Cyanobacteria with Synechococcus sp. PCC 7002 as Host

    Directory of Open Access Journals (Sweden)

    Anne M Ruffing

    2014-05-01

    Full Text Available Microbial free fatty acids (FFAs have been proposed as a potential feedstock for renewable energy. The ability to directly convert carbon dioxide into FFAs makes cyanobacteria ideal hosts for renewable FFA production. Previous metabolic engineering efforts using the cyanobacterial hosts Synechocystis sp. PCC 6803 and Synechococcus elongatus PCC 7942 have demonstrated this direct conversion of carbon dioxide into FFAs; however, FFA yields in these hosts are limited by the negative impact of FFA production on the host cell physiology. This work investigates the use of Synechococcus sp. PCC 7002 as a cyanobacterial host for FFA production. In comparison to S. elongatus PCC 7942, Synechococcus sp. PCC 7002 strains produced and excreted FFAs at similar concentrations but without the detrimental effects on host physiology. The enhanced tolerance to FFA production with Synechococcus sp. PCC 7002 was found to be temperature dependent, with physiological effects such as reduced photosynthetic yield and decreased photosynthetic pigments observed at higher temperatures. Additional genetic manipulations were targeted for increased FFA production, including thioesterases and RuBisCO. Overexpression of non-native RuBisCO subunits (rbcLS from a psbAI promoter resulted in more than a 3-fold increase in FFA production, with excreted FFA concentrations reaching greater than 130 mg/L. This work illustrates the importance of host strain selection for cyanobacterial biofuel production and demonstrates that the FFA tolerance of Synechococcus sp. PCC 7002 can allow for high yields of excreted FFA.

  15. Improvement of the photo stabilization of PVC films in the presence of thioacetic acid benzothiazole complexes

    International Nuclear Information System (INIS)

    The photo stabilization of poly(vinyl chloride) (PVC) films by 2-thioacetic acid benzothiazole with Sn (II), Cd (II), Ni (II), Zn (II) and Cu (II) complexes was investigated. The PVC films containing concentration of complexes 0.5 % by weight were produced by the same casting method from tetrahydrofuran (THF) solvent. The photo stabilization activities of these compounds were determined by monitoring the carbonyl, polyene and hydroxyl indices with irradiation time. The changes in viscosity average molecular weight of PVC with irradiation time were also tracked (using THF as a solvent). The quantum yield of the chain scission (φcs) of these complexes in PVC films was evaluated and found to range between 4.71 x 10-8 and 8.98 x 10-8. Results obtained showed that the rate of photo stabilization of PVC in the presence of the additive follows the trend: Sn(L)2 > Cd(L)2 > Ni(L)2 > Zn(L)2 > Cu(L)2. According to the experimental results obtained, several mechanisms were suggested depending on the structure of the additive. Among them HCl scavenging, UV absorption, peroxide decomposer and radical scavenger for photo stabilizer additives mechanisms were suggested. (author)

  16. Improving arachidonic acid fermentation by Mortierella alpina through multistage temperature and aeration rate control in bioreactor.

    Science.gov (United States)

    Gao, Min-Jie; Wang, Cheng; Zheng, Zhi-Yong; Zhu, Li; Zhan, Xiao-Bei; Lin, Chi-Chung

    2016-05-18

    Effective production of arachidonic acid (ARA) using Mortierella alpina was conducted in a 30-L airlift bioreactor. Varying the aeration rate and temperature significantly influenced cell morphology, cell growth, and ARA production, while the optimal aeration rate and temperature for cell growth and product formation were quite different. As a result, a two-stage aeration rate control strategy was constructed based on monitoring of cell morphology and ARA production under various aeration rate control levels (0.6-1.8 vvm). Using this strategy, ARA yield reached 4.7 g/L, an increase of 38.2% compared with the control (constant aeration rate control at 1.0 vvm). Dynamic temperature-control strategy was implemented based on the fermentation performance at various temperatures (13-28°C), with ARA level in total cellular lipid increased by 37.1% comparing to a constant-temperature control (25°C). On that basis, the combinatorial fermentation strategy of two-stage aeration rate control and dynamic temperature control was applied and ARA production achieved the highest level of 5.8 g/L.

  17. Influence of surface modified cellulose microfibrils on the improved mechanical properties of poly (lactic acid).

    Science.gov (United States)

    Johari, Atul P; Kurmvanshi, S K; Mohanty, S; Nayak, S K

    2016-03-01

    Cellulose microfibrils (CMF) were extracted from sisal fiber and characterized. Biocomposites of PLA reinforced with CMF were fabricated employing melt blending technique followed by injection moulding. The biocomposites were subjected to various characterization studies to investigate the effect of CMF within the PLA matrix. Differential scanning calorimetry (DSC) measurements confirmed that the addition of CMF accelerates the crystallization process of PLA matrix. Addition of 5 wt.% of CMF with and without compatibilizers and plasticizers such as maleic anhydride, polyethylene glycol and acetyltributyl citrate in PLA improved the crystallization of PLA up to 100 °C. MA grafting gave moderate effects on both the stiffness and ductility, exhibiting optimum properties. PMID:26708431

  18. Nanoamphiphilic Chitosan Dispersed Poly(lactic acid) Bionanocomposite Films with Improved Thermal, Mechanical, and Gas Barrier Properties.

    Science.gov (United States)

    Pal, Akhilesh Kumar; Katiyar, Vimal

    2016-08-01

    This article demonstrates the synthesis of lactic acid oligomer-grafted-chitosan (OLLA-g-CH), a nanoamphiphilic molecule, by in situ condensation polymerization and its effective use as a nanofiller for improvement in multiple properties of poly(lactic acid) (PLA) films, essential for stringent food packaging applications. Fourier transform infrared spectroscopy (FTIR) analysis shows the presence of amide-ester bond at 1539 cm(-1), which confirms the structural grafting of OLLA chains with chitosan molecules. This nanoamphiphilic OLLA-g-CH molecule act as surfactant containing hydrophilic chitosan head and hydrophobic OLLA tails with average size in the range of ∼2-4 nm. Prepared PLA/OLLA-g-CH bionanocomposite films appear with uniform dispersion of nanoamphiphilic OLLA-g-CH molecules with self-assembled micelles having size as low as ∼20 nm and as high as ∼150 nm with core-shell morphology in PLA matrix. This nanofiller is found very effective toward significant reduction in oxygen permeability (OP) by ∼10-fold due to the reduction in solubility of oxygen molecules and improvement in crystal nucleation density due to availability of nanonucleating sites. Ultimate tensile strength (UTS) of PLA/OLLA-g-CH bionanocomposite films are relatively comparable to that of PLA, however, elongation at break is improved significantly. The onset of thermal degradation of PLA/(OLLA-g-CH) films is also found comparable to that of PLA film. The glass transition temperature (Tg) of bionanocomposites is decreased by more than 18 °C with increase in OLLA-g-CH loading, which indicates the improved plasticization characteristics of PLA matrix. The crystallization kinetics suggest nonthree dimensional truncated spherical structures, which is controlled by the combination of thermal and athermal instantaneous nucleations. POM analysis suggested that the spherulite growth of PLA is improved significantly with the addition of OLLA-g-CH. The reduction in Tg of PLA with improvement

  19. Improving volatile fatty acid yield from sludge anaerobic fermentation through self-forming dynamic membrane separation.

    Science.gov (United States)

    Liu, Hongbo; Wang, Yuanyuan; Yin, Bo; Zhu, Yanfang; Fu, Bo; Liu, He

    2016-10-01

    Self-forming dynamic membrane (SFDM) separation was applied to the conventional sludge fermenter for improving VFA yields. Results indicated SFDM presented good performance in transferring products, retaining substrates, and enriching useful bacteria. The retention ratios of suspended solids, soluble COD, proteins, and polysaccharides reached 99%, 30%, 70%, and 40%, respectively, and more than 90% of the VFAs and ammonia could be transferred in a timely manner. The structure of the microbial community was optimized, which led to enhanced releases of hydrolytic enzymes and accelerated enrichments of functional bacteria. Protease and β-glucosidase activities increased from 1.0 to 5.0U/mL and 15.0 to 23.0μmol/L·h, respectively. VFA yield and sludge conversion ratio increased by 233.3% and 227.9%, respectively. Moreover, SFDM had good operation stability, including a short formation time, a long operation period, and a low transmembrane pressure. These results show VFA yield from sludge fermentation can be greatly improved by SFDM separation. PMID:27347803

  20. Sodium Tanshinone IIA Sulfonate Attenuates Scopolamine-Induced Cognitive Dysfunctions via Improving Cholinergic System.

    Science.gov (United States)

    Xu, Qing-Qing; Xu, Yi-Jun; Yang, Cong; Tang, Ying; Li, Lin; Cai, Hao-Bin; Hou, Bo-Nan; Chen, Hui-Fang; Wang, Qi; Shi, Xu-Guang; Zhang, Shi-Jie

    2016-01-01

    Sodium Tanshinone IIA sulfonate (STS) is a derivative of Tanshinone IIA (Tan IIA). Tan IIA has been reported to possess neuroprotective effects against Alzheimer's disease (AD). However, whether STS possesses effect on AD remains unclear. This study aims to estimate whether STS could protect against scopolamine- (SCOP-) induced learning and memory deficit in Kunming mice. Morris water maze results showed that oral administration of STS (10 mg/kg and 20 mg/kg) and Donepezil shortened escape latency, increased crossing times of the original position of the platform, and increased the time spent in the target quadrant. STS decreased the activity of acetylcholinesterase (AChE) and increased the activity of choline acetyltransferase (ChAT) in the hippocampus and cortex of SCOP-treated mice. Oxidative stress results showed that STS increased the activity of superoxide dismutase (SOD) and decreased the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) in hippocampus and cortex. In addition, western blot was carried out to detect the expression of apoptosis related proteins (Bcl-2, Bax, and Caspase-3). STS upregulated the protein expression of Bcl-2 and downregulated the proteins expression of Bax and Caspase-3. These results indicated that STS might become a promising therapeutic candidate for attenuating AD-like pathological dysfunction. PMID:27556046

  1. Sodium Tanshinone IIA Sulfonate Attenuates Scopolamine-Induced Cognitive Dysfunctions via Improving Cholinergic System

    Directory of Open Access Journals (Sweden)

    Qing-Qing Xu

    2016-01-01

    Full Text Available Sodium Tanshinone IIA sulfonate (STS is a derivative of Tanshinone IIA (Tan IIA. Tan IIA has been reported to possess neuroprotective effects against Alzheimer’s disease (AD. However, whether STS possesses effect on AD remains unclear. This study aims to estimate whether STS could protect against scopolamine- (SCOP- induced learning and memory deficit in Kunming mice. Morris water maze results showed that oral administration of STS (10 mg/kg and 20 mg/kg and Donepezil shortened escape latency, increased crossing times of the original position of the platform, and increased the time spent in the target quadrant. STS decreased the activity of acetylcholinesterase (AChE and increased the activity of choline acetyltransferase (ChAT in the hippocampus and cortex of SCOP-treated mice. Oxidative stress results showed that STS increased the activity of superoxide dismutase (SOD and decreased the levels of malondialdehyde (MDA and reactive oxygen species (ROS in hippocampus and cortex. In addition, western blot was carried out to detect the expression of apoptosis related proteins (Bcl-2, Bax, and Caspase-3. STS upregulated the protein expression of Bcl-2 and downregulated the proteins expression of Bax and Caspase-3. These results indicated that STS might become a promising therapeutic candidate for attenuating AD-like pathological dysfunction.

  2. Cholinergic basis of memory improving effect of Ocimum tenuiflorum linn

    OpenAIRE

    Joshi H; Parle M

    2006-01-01

    Dementia is one of the age-related mental problems and a characteristic symptom of Alzheimer′s disease. Nootropic agents are used in situations where there is organic disorder in learning abilities. The present work was undertaken to assess the potential of Ocimum tenuiflorum Linn. as a nootropic and anticholinesterase agent in mice. Ethanol extract of dried whole plant of O. tenuiflorum Linn. ameliorated the amnesic effect of scopolamine (0.4 mg/kg) and aging-induced memory defici...

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

    Science.gov (United States)

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

    2016-01-01

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

  4. An antiaging skin care system containing alpha hydroxy acids and vitamins improves the biomechanical parameters of facial skin

    Directory of Open Access Journals (Sweden)

    Tran D

    2014-12-01

    Full Text Available Diana Tran, Joshua P Townley, Tanya M Barnes, Kerryn A Greive Ego Pharmaceuticals, Braeside, Victoria, Australia Background: The demand for antiaging products has dramatically increased in recent years, driven by an aging population seeking to maintain the appearance of youth. This study investigates the effects of an antiaging skin care system containing alpha hydroxy acids (AHAs in conjunction with vitamins B3, C, and E on the biomechanical parameters of facial skin. Methods: Fifty two volunteers followed an antiaging skin care regimen comprising of cleanser, eye cream, day moisturizer, and night moisturizer for 21 days. Wrinkle depth (Ry and skin roughness (Ra were measured by skin surface profilometry of the crow's feet area, and skin elasticity parameters R2 (gross elasticity, R5 (net elasticity, R6 (viscoelastic portion, and R7 (recovery after deformation were determined for facial skin by cutometer, preapplication and after 7, 14, and 21 days. Volunteers also completed a self-assessment questionnaire. Results: Compared to baseline, Ry and Ra significantly improved by 32.5% (P<0.0001 and 42.9% (P<0.0001, respectively, after 21 days of antiaging skin care treatment. These results were observed by the volunteers with 9 out of 10 discerning an improvement in skin texture and smoothness. Compared to baseline, R2 and R5 significantly increased by 15.2% (P<0.0001 and 12.5% (P=0.0449, respectively, while R6 significantly decreased by 17.7% (P<0.0001 after 21 days. R7 increased by 9.7% after 21 days compared to baseline but this was not significant over this time period. Conclusion: An antiaging skin care system containing AHAs and vitamins significantly improves the biomechanical parameters of the skin including wrinkles and skin texture, as well as elasticity without significant adverse effects. Keywords: alpha hydroxy acids, antiaging, nicotinamide, vitamin C, vitamin E, profilometry, cutometer

  5. Non-adrenergic non-cholinergic (NANC) excitatory response of the channel catfish intestine.

    Science.gov (United States)

    Venugopalan, C S; Holmes, E P; Jarboe, H H; Kleinow, K M

    1994-06-01

    1. Optimal parameters for electrical field stimulation (EFS) of catfish pyloric and middle intestinal segments were determined (15 Hz, 60 V) from a range of frequencies (5-45 Hz) and voltages (40-120 V) using a modified Magnus' method. Contractile responses were produced by EFS which were reproducible and showed no significant difference between the tissues. 2. The contractile cholinergic responses of the tissues to carbachol and acetylcholine (ACh) were blocked by atropine on an equimolar concentration, whereas, these responses were enhanced in the presence of neostigmine, and acetylcholinesterase inhibitor. 3. Adrenergic responses were examined with noradrenaline (NA). NA produced contraction of the segments only, at a concentration of 10(-4) M. Among the various adrenoceptors, beta-adrenoceptor stimulation produced a weak relaxation whereas, both alpha 1- and alpha 2-adrenoceptor stimulation produced contractions, of which alpha 2-induced contraction was of greater magnitude. The beta, alpha 1 and alpha 2 responses were blocked by their respective blocking agents propranolol, prazosin and yohimbine. 4. The autonomic components of the response to EFS were determined by using selected cholinergic and adrenergic antagonists separately or collectively. Cholinergic blockade with atropine did not produce a significant blockade of the EFS-induced response. Similarly, blockade of beta-adrenoceptors with propranolol did not modulate the contractile response to EFS to any significant level. Blockade by prazosin or yohimbine did not significantly change the contractile response to EFS. After a complete blockade of the adrenergic and cholinergic divisions, the intestinal segments still showed a contractile response to EFS which was not significantly different from the control response. This indicated the presence of a non-adrenergic non-cholinergic (NANC) response. 5. Tetrodotoxin, at 10(-6) M, significantly blocked the EFS-induced NANC response suggesting a neurogenic

  6. Approaches to improve the oral bioavailability and effects of novel anticancer drugs berberine and betulinic acid.

    Directory of Open Access Journals (Sweden)

    Chandraiah Godugu

    Full Text Available The poor bioavailability of Berberine (BBR and Betulinic acid (BA limits the development of these promising anticancer agents for clinical use. In the current study, BBR and BA in spray dried (SD mucoadhesive microparticle formulations were prepared.A patented dual channel spray gun technology established in our laboratory was used for both formulations. Gastrointestinal (GI permeability studies were carried out using Caco-2 cell monolayer grown in in-vitro system. The oral bioavailability and pharmacokinetic profile of SD formulations were studied in Sprague Dawley rats. A549 orthotopic and H1650 metastatic NSCLC models were utilized for the anticancer evaluations.Pharmacokinetic studies demonstrated that BBR and BA SD formulations resulted in 3.46 and 3.90 fold respectively, significant increase in plasma Cmax concentrations. AUC levels were increased by 6.98 and 7.41 fold in BBR and BA SD formulations, respectively. Compared to untreated controls groups, 49.8 & 53.4% decrease in the tumor volumes was observed in SD formulation groups of BBR and BA, respectively. Molecular studies done on excised tumor (A549 tissue suggested that BBR in SD form resulted in a significant decrease in the survivin, Bcl-2, cyclin D1, MMP-9, HIF-1α, VEGF and CD31 expressions. Cleaved caspase 3, p53 and TUNEL expressions were increased in SD formulations. The RT-PCR analysis on H1650 tumor tissue suggested that p38, Phospho-JNK, Bax, BAD, cleaved caspase 3&8 mRNA expressions were significantly increased in BA SD formulations. Chronic administration of BBR and BA SD formulations did not show any toxicity.Due to significant increase in oral bioavailability and superior anticancer effects, our results suggest that spray drying is a superior alternative formulation approach for oral delivery of BBR and BA.

  7. Development of a lauric acid/albumin hybrid iron oxide nanoparticle system with improved biocompatibility.

    Science.gov (United States)

    Zaloga, Jan; Janko, Christina; Nowak, Johannes; Matuszak, Jasmin; Knaup, Sabine; Eberbeck, Dietmar; Tietze, Rainer; Unterweger, Harald; Friedrich, Ralf P; Duerr, Stephan; Heimke-Brinck, Ralph; Baum, Eva; Cicha, Iwona; Dörje, Frank; Odenbach, Stefan; Lyer, Stefan; Lee, Geoffrey; Alexiou, Christoph

    2014-01-01

    The promising potential of superparamagnetic iron oxide nanoparticles (SPIONs) in various nanomedical applications has been frequently reported. However, although many different synthesis methods, coatings, and functionalization techniques have been described, not many core-shell SPION drug delivery systems are available for clinicians at the moment. Here, bovine serum albumin was adsorbed onto lauric acid-stabilized SPIONs. The agglomeration behavior, zeta potential, and their dependence on the synthesis conditions were characterized with dynamic light scattering. The existence and composition of the core-shell-matrix structure was investigated by transmission electron microscopy, Fourier transform infrared spectroscopy, and zeta potential measurements. We showed that the iron oxide cores form agglomerates in the range of 80 nm. Moreover, despite their remarkably low tendency to aggregate even in a complex media like whole blood, the SPIONs still maintained their magnetic properties and were well attractable with a magnet. The magnetic properties were quantified by vibrating sample magnetometry and a superconducting quantum interference device. Using flow cytometry, we further investigated the effects of the different types of nanoparticle coating on morphology, viability, and DNA integrity of Jurkat cells. We showed that by addition of bovine serum albumin, the toxicity of nanoparticles is greatly reduced. We also investigated the effect of the particles on the growth of primary human endothelial cells to further demonstrate the biocompatibility of the particles. As proof of principle, we showed that the hybrid-coated particles are able to carry payloads of up to 800 μg/mL of the cytostatic drug mitoxantrone while still staying colloidally stable. The drug-loaded system exhibited excellent therapeutic potential in vitro, exceeding that of free mitoxantrone. In conclusion, we have synthesized a biocompatible ferrofluid that shows great potential for clinical

  8. Improving the Thermostability of Acidic Pullulanase from Bacillus naganoensis by Rational Design

    Science.gov (United States)

    Lv, Jinzhi; Li, Qingbin; Tian, Jian; Wu, Ningfeng

    2016-01-01

    Pullulanase (EC 3.2.1.41) plays an important role in the specific hydrolysis of branch points in amylopectin. Enhancing its thermostability is required for its industrial application. In this study, rational protein design was used to improve the thermostability of PulB from Bacillus naganoensis (AB231790.1), which has strong enzymatic properties. Three positive single-site mutants (PulB-D328H, PulB-N387D, and PulB-A414P) were selected from six mutants. After incubation at 65°C for 5 min, the residual activities of PulB-D328H, PulB-N387D, and PulB-A414P were 4.5-, 1.7-, and 1.47-fold higher than PulB-WT, and their Tm values (the temperature at which half protein molecule denature) were 1.8°C, 0.4°C, and 0.9°C higher than PulB-WT, respectively. Then the final combined mutant PulB-328/387/414 was constructed. The t1/2 of it was 12.9-fold longer than that of PulB-WT at 65°C and the total increase in Tm of it (5.0°C) was almost 60% greater than the sum of individual increases (3.1°C). In addition, kinetic studies revealed that the kcat and the kcat/Km of PulB-328/387/414 increased by 38.8% and 12.9%. The remarkable improvement in thermostability and the high catalytic efficiency of PulB-328/387/414 make it suitable for industrial applications. PMID:27764201

  9. Electroacupuncture at Zusanli Prevents Severe Scalds-Induced Gut Ischemia and Paralysis by Activating the Cholinergic Pathway

    Directory of Open Access Journals (Sweden)

    Huan Wang

    2015-01-01

    Full Text Available Severe burn injuries may result in gastrointestinal paralysis, and barrier dysfunction due to gut ischemia and lowered vagus excitability. In this study we investigate whether electroacupuncture (EA at Zusanli (ST36 could prevent severe scalds-induced gut ischemia, paralysis, and barrier dysfunction and whether the protective role of EA at ST36 is related to the vagus nerve. 35% burn area rats were divided into six groups: (a EAN: EA nonchannel acupoints followed by scald injury; (b EA: EA at ST36 after scald injury; (c VGX/EA: vagotomy (VGX before EA at ST36 and scald injury; (d VGX/EAN: VGX before EAN and scald injury; (e atropine/EA: applying atropine before scald injury and then EA at ST36; (f atropine/EAN: applying atropine before scald injury and then EA at nonchannel acupoints. EA at the Zusanli point significantly promoted the intestinal impelling ratio and increased the amount of mucosal blood flow after scald injury. The plasma diamine oxidase (DAO and intestinal permeability decreased significantly after scald injury in the EA group compared with others. However, EA after atropine injection or cervical vagotomy failed to improve intestinal motility and mucosa blood flow suggesting that the mechanism of EA may be related to the activation of the cholinergic nerve pathway.

  10. Cross-talk between oxidative stress and modifications of cholinergic and glutaminergic receptors in the pathogenesis of Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Zhi-zhong GUAN

    2008-01-01

    Alzheimer's disease (AD) is the most common neurodegenerative disorder, and its pathogenesis is likely to be associated with multiple etiologies and mechanisms in which oxidative stress and deficits of neurotransmitter receptors may play impor-tant roles. It has been indicated that a high level of free radicals can influence the expressions of nicotinic receptors (nAChRs), muscarinic receptors (mAChRs), and N-methyl-D-aspartate (NMDA) receptors, exhibiting disturbances of cellular mem-brane by lipid peroxidation, damages of the protein receptors by protein oxidation, and possible modified gene expressions of these receptors by DNA oxidation. nAChRs have shown an antioxidative effect by a direct or an indirect pathway; mAChR stimulation may generate reactive oxygen species, which might be a physi-ological compensative reaction, or improve oxidative stress; and high stimulation to NMDA receptors can increase the sensitivity of oxidative stress of neurons. This review may provide complemental information" for understanding the correla-tion between oxidative stress and changed cholinergic and glutaminergic recep-tors in AD processing, and for revealing the underlying molecular mechanisms of these factors in the multiple etiologies and pathophysiology of the disorder.

  11. NO-flurbiprofen reduces amyloid β, is neuroprotective in cell culture, and enhances cognition in response to cholinergic blockade

    Science.gov (United States)

    Abdul-Hay, Samer O.; Luo, Jia; Ashghodom, Rezene T.; Thatcher, Gregory R.J.

    2009-01-01

    The nonsteroidal anti-inflamatory drug (NSAID) flurbiprofen is a selective amyloid lowering agent (SALA) which has been studied clinically in Alzheimer’s disease. HCT-1026 is an ester prodrug of flurbiprofen incorporating a nitrate carrier moiety that in vivo provides NO bioactivity and an improved safety profile. In vitro, HCT-1026 retained the COX inhibitory and NSAID activity of flurbiprofen, but at concentrations at which levels of Aβ1–42 were lowered by flurbiprofen, Aβ1–42 levels were elevated 200% by HCT-1026. Conversely, at lower concentrations, HCT-1026 behaved as a SALA with greater potency than flurbiprofen. The difference in concentration responses between flurbiprofen and HCT-1026 in vitro suggests different cellular targets; and in no case did a combination of nitrate drug with flurbiprofen provide similar actions. In vivo, HCT-1026 was observed to reverse cognitive deficits induced by scopolamine in two behavioral assays; activity that was also shown by a classical nitrate drug, but not by flurbiprofen. The ability to restore aversive memory and spatial working and reference memory after cholinergic blockade has been demonstrated by other agents that stimulate NO/cGMP signaling. These observations add positively to the preclinical profile of HCT-1026 and NO chimeras in Alzheimer’s disease. PMID:19702655

  12. Development of a lauric acid/albumin hybrid iron oxide nanoparticle system with improved biocompatibility

    Directory of Open Access Journals (Sweden)

    Zaloga J

    2014-10-01

    Full Text Available Jan Zaloga,1 Christina Janko,1 Johannes Nowak,2 Jasmin Matuszak,1 Sabine Knaup,1 Dietmar Eberbeck,3 Rainer Tietze,1 Harald Unterweger,1 Ralf P Friedrich,1 Stephan Duerr,1 Ralph Heimke-Brinck,4 Eva Baum,4 Iwona Cicha,1 Frank Dörje,4 Stefan Odenbach,2 Stefan Lyer,1 Geoffrey Lee,5 Christoph Alexiou1 1Department of Otorhinolaryngology, Head and Neck Surgery, Section for Experimental Oncology and Nanomedicine (SEON, Else Kröner-Fresenius-Stiftung-Professorship, University Hospital Erlangen, Erlangen, Germany; 2Measuring and Automation Technology, Technical University Dresden, Dresden, Germany; 3Physikalisch-Technische-Bundesanstalt, Berlin, Germany; 4Pharmacy Department, University Hospital Erlangen, Erlangen, Germany; 5Division of Pharmaceutics, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany Abstract: The promising potential of superparamagnetic iron oxide nanoparticles (SPIONs in various nanomedical applications has been frequently reported. However, although many different synthesis methods, coatings, and functionalization techniques have been described, not many core-shell SPION drug delivery systems are available for clinicians at the moment. Here, bovine serum albumin was adsorbed onto lauric acid-stabilized SPIONs. The agglomeration behavior, zeta potential, and their dependence on the synthesis conditions were characterized with dynamic light scattering. The existence and composition of the core-shell-matrix structure was investigated by transmission electron microscopy, Fourier transform infrared spectroscopy, and zeta potential measurements. We showed that the iron oxide cores form agglomerates in the range of 80 nm. Moreover, despite their remarkably low tendency to aggregate even in a complex media like whole blood, the SPIONs still maintained their magnetic properties and were well attractable with a magnet. The magnetic properties were quantified by vibrating sample magnetometry and a superconducting quantum

  13. Improvement of multicrystalline silicon wafer solar cells by post-fabrication wet-chemical etching in phosphoric acid

    Indian Academy of Sciences (India)

    A Mefoued; M Fathi; J Bhatt; A Messaoud; B Palahouane; N Benrekaa

    2011-12-01

    In this study, we have improved electrical characteristics such as the efficiency () and the fill factor (FF) of finished multicrystalline silicon (-Si) solar cells by using a new chemical treatment with a hot phosphoric (H3PO4) acidic solution. These -Si solar cells were made by a standard industrial process with screen-printed contacts and a silicon nitride (SiN) antireflection coating. We have deposited SiN thin layer (80 nm) on -type -Si substrate by the mean of plasma enhanced chemical vapour deposition (PECVD) technique. The reactive gases used as precursors inside PECVD chamber are a mixture of silane (SiH4) and ammonia (NH3) at a temperature of 380°C. The developed H3PO4 chemical surface treatment has improved from 5.4 to 7.7% and FF from 50.4 to 70.8%, this means a relative increase of up to 40% from the initial values of and FF. In order to explain these improvements, physical (AFM, EDX), chemical (FTIR) and optical (spectrophotometer) analyses were done.

  14. Overexpression of AtABCG25 enhances the abscisic acid signal in guard cells and improves plant water use efficiency.

    Science.gov (United States)

    Kuromori, Takashi; Fujita, Miki; Urano, Kaoru; Tanabata, Takanari; Sugimoto, Eriko; Shinozaki, Kazuo

    2016-10-01

    In addition to improving drought tolerance, improvement of water use efficiency is a major challenge in plant physiology. Due to their trade-off relationships, it is generally considered that achieving stress tolerance is incompatible with maintaining stable growth. Abscisic acid (ABA) is a key phytohormone that regulates the balance between intrinsic growth and environmental responses. Previously, we identified AtABCG25 as a cell-membrane ABA transporter that export ABA from the inside to the outside of cells. AtABCG25-overexpressing plants showed a lower transpiration phenotype without any growth retardation. Here, we dissected this useful trait using precise phenotyping approaches. AtABCG25 overexpression stimulated a local ABA response in guard cells. Furthermore, AtABCG25 overexpression enhanced drought tolerance, probably resulting from maintenance of water contents over the common threshold for survival after drought stress treatment. Finally, we observed enhanced water use efficiency by overexpression of AtABCG25, in addition to drought tolerance. These results were consistent with the function of AtABCG25 as an ABA efflux transporter. This unique trait may be generally useful for improving the water use efficiency and drought tolerance of plants. PMID:27593465

  15. Improving enzymatic hydrolysis of corn stover pretreated by ethylene glycol-perchloric acid-water mixture.

    Science.gov (United States)

    He, Yu-Cai; Liu, Feng; Gong, Lei; Lu, Ting; Ding, Yun; Zhang, Dan-Ping; Qing, Qing; Zhang, Yue

    2015-02-01

    To improve the enzymatic saccharification of lignocellulosic biomass, a mixture of ethylene glycol-HClO4-water (88.8:1.2:10, w/w/w) was used for pretreating corn stover in this study. After the optimization in oil-bath system, the optimum pretreatment temperature and time were 130 °C and 30 min, respectively. After the saccharification of 10 g/L pretreated corn stover for 48 h, the saccharification rate was obtained in the yield of 77.4 %. To decrease pretreatment temperature and shorten pretreatment time, ethylene glycol-HClO4-water (88.8:1.2:10, w/w/w) media under microwave irradiation was employed to pretreat corn stover effectively at 100 °C and 200 W for 5 min. Finally, the recovered hydrolyzates containing glucose obtained from the enzymatic hydrolysis of pretreated corn stovers could be fermented into ethanol efficiently. These results would be helpful for developing a cost-effective pretreatment combined with enzymatic saccharification of cellulosic materials for the production of lignocellulosic ethanol.

  16. Gallic acid ameliorates hyperglycemia and improves hepatic carbohydrate metabolism in rats fed a high-fructose diet.

    Science.gov (United States)

    Huang, Da-Wei; Chang, Wen-Chang; Wu, James Swi-Bea; Shih, Rui-Wen; Shen, Szu-Chuan

    2016-02-01

    Herein, we investigated the hypoglycemic effect of plant gallic acid (GA) on glucose uptake in an insulin-resistant cell culture model and on hepatic carbohydrate metabolism in rats with a high-fructose diet (HFD)-induced diabetes. Our hypothesis is that GA ameliorates hyperglycemia via alleviating hepatic insulin resistance by suppressing hepatic inflammation and improves abnormal hepatic carbohydrate metabolism by suppressing hepatic gluconeogenesis and enhancing the hepatic glycogenesis and glycolysis pathways in HFD-induced diabetic rats. Gallic acid increased glucose uptake activity by 19.2% at a concentration of 6.25 μg/mL in insulin-resistant FL83B mouse hepatocytes. In HFD-induced diabetic rats, GA significantly alleviated hyperglycemia, reduced the values of the area under the curve for glucose in an oral glucose tolerance test, and reduced the scores of the homeostasis model assessment of insulin resistance index. The levels of serum C-peptide and fructosamine and cardiovascular risk index scores were also significantly decreased in HFD rats treated with GA. Moreover, GA up-regulated the expression of hepatic insulin signal transduction-related proteins, including insulin receptor, insulin receptor substrate 1, phosphatidylinositol-3 kinase, Akt/protein kinase B, and glucose transporter 2, in HFD rats. Gallic acid also down-regulated the expression of hepatic gluconeogenesis-related proteins, such as fructose-1,6-bisphosphatase, and up-regulated expression of hepatic glycogen synthase and glycolysis-related proteins, including hexokinase, phosphofructokinase, and aldolase, in HFD rats. Our findings indicate that GA has potential as a health food ingredient to prevent diabetes mellitus. PMID:26547672

  17. A pilot study of folic acid supplementation for improving homocysteine levels, cognitive and depressive status in eating disorders

    Directory of Open Access Journals (Sweden)

    Viviana Loria-Kohen

    2013-06-01

    Full Text Available Background & aims: Several authors have reported low folate intake in patients with eating disorders (ED. This vitamin plays an essential role in synthesis reactions for neurotransmitters and structural elements of neurons, and therefore its deficiency has been associated with the presence of different disorders linked to mental function. The aim of this study was to determine the effect of folic acid supplementation on homocysteine levels and the cognitive and depressive status of a group of patients with eating disorders with low folate intake. Subjects/methods: The study was designed as a randomised, prospective clinical trial, which included 24 participants assigned to two treatment groups for six months: supplemented group (SG (10 mg/day of folic acid [ACFOL®] and a placebo group (PG. Both groups maintained their medical, dietary and psychological treatment. At baseline and end of the intervention, anthropometric, dietary and biochemical parameters (plasma homocysteine [Hcy], serum and red blood cell folate were recorded. Cognitive and depressive status questionnaires were administered (Stroop Test, Trail Making Test and Beck Depression Inventory. Results: Twenty-two patients completed the study (SG: 12, PG: 10, mean age: 24.2 ± 8.8 years, BMI 18, ± 3.5 kg/m². The SG significantly increased their serum and red blood cell folate levels and lowered Hcy levels (9.4 ± 2.4 µmol/l vs. 7.5 ± 1.7 µmol/l, P < 0.01. The SG also significantly improved most of their test scores for cognitive and depressive status. The PG showed no significant changes in any of the evaluated variables. Conclusions: The results show that folic acid supplementation may be used as another tool within the comprehensive and multidisciplinary treatment applied to patients with ED.

  18. An Amino Acids Mixture Improves the Hepatotoxicity Induced by Acetaminophen in Mice

    Directory of Open Access Journals (Sweden)

    Francesco Di Pierro

    2013-01-01

    Full Text Available Acetaminophen (APAP is a widely used analgesic and antipyretic drug, but at high dose it leads to undesirable side effects, such as hepatotoxicity and nephrotoxicity. The aim of this study was to evaluate the protective role of DDM-GSH, a mixture of L-cysteine, L-methionine, and L-serine in a weight ratio of 2 : 1 : 1, in comparison to N-acetylcysteine (NAC, against acetaminophen- (APAP- induced hepatotoxicity in mice. Toxicity was induced in mice by the intraperitoneal (ip administration of low dose (2 mmol/kg or high dose (8 mmol/kg of APAP. DDM-GSH (0.4 to 1.6 mmol/kg was given ip to mice 1 h before the APAP administration. The same was done with NAC (0.9 to 3.6 mmol/kg, the standard antidote of APAP toxicity. Mice were sacrificed 8 h after the APAP injection to determine liver weight, serum alanine aminotransferase (ALT, and total glutathione (GSH depletion and malondialdehyde (MDA accumulation in liver tissues. DDM-GSH improved mouse survival rates better than NAC against a high dose of APAP. Moreover, DDM-GSH significantly reduced in a dose-dependent manner not only APAP-induced increases of ALT but also APAP-induced hepatic GSH depletion and MDA accumulation. Our results suggest that DDM-GSH may be more potent than NAC in protecting the liver from APAP-induced liver injury.

  19. Improvement in the behavior of bromelain coupled to pNIPAm polymers containing acrylamide or acrylic acid

    Directory of Open Access Journals (Sweden)

    Rubab Mahmood

    2014-08-01

    Full Text Available Bromelain was coupled to N-isopropyl acrylamide (NIPAmpolymers, synthesized using NIPAm and various concentrations of acrylamide (Ac or acrylic acid (AAc. Incorporation of Ac/AAcinto the polymer increased the LCST (lower critical solutiontemperature in a concentration dependent manner but AAc wasmore effective in this regard; the LCST rose to 40°C when 6 percent AAc was used. Incorporation of Ac/AAc increased the coupling of enzyme to the polymer and the η (effectiveness factor of the coupled enzyme, moderately. Various studies indicate that such incorporation of hydrophilic monomers into the polymer does not impair its capacity to couple enzyme or expression of the activity of bound enzyme but seems to actually improve the stability of the enzyme against heat induced inactivation and alkaline pH.

  20. Butter blend containing fish oil improves the level of n-3 fatty acids in biological tissues of hamster

    DEFF Research Database (Denmark)

    Porsgaard, Trine; Overgaard, Jesper; Krogh, Anne Louise;

    2007-01-01

    into food. In the present study, fish oil was incorporated into butter blends by enzymatic interesterification. The aim of the study was to investigate the effects of this butter product in comparison with a commercial butter blend and a product produced by interesterification but without fish oil. Golden...... Syrian hamsters received hamster feed blended with one of the three butter products. After 6 weeks of feeding, the fatty acid compositions of plasma, erythrocytes, liver, brain, and visceral fat were determined. The intake of butter product with fish oil resulted in a higher level of n-3 PUFA in plasma......, erythrocytes, and liver. The incorporation of n-3 PUFA was significantly higher in phospholipids than in triacylglycerols. The results suggest that enriching butter blends with small amounts of fish oil can be used as an alternative method for improving the level of n-3 PUFA in biological tissues....

  1. Improvement of glyphosate resistance through concurrent mutations in three amino acids of the Ochrobactrum 5-enopyruvylshikimate-3-phosphate synthase.

    Science.gov (United States)

    Tian, Yong-Sheng; Xu, Jing; Xiong, Ai-Sheng; Zhao, Wei; Fu, Xiao-Yan; Peng, Ri-He; Yao, Quan-Hong

    2011-12-01

    A mutant of 5-enopyruvylshikimate-3-phosphate synthase from Ochrobactrum anthropi was identified after four rounds of DNA shuffling and screening. Its ability to restore the growth of the mutant ER2799 cell on an M9 minimal medium containing 300 mM glyphosate led to its identification. The mutant had mutations in seven amino acids: E145G, N163H, N267S, P318R, M377V, M425T, and P438L. Among these mutations, N267S, P318R, and M425T have never been previously reported as important residues for glyphosate resistance. However, in the present study they were found by site-directed mutagenesis to collectively contribute to the improvement of glyphosate tolerance. Kinetic analyses of these three mutants demonstrated that the effectiveness of these three individual amino acid alterations on glyphosate tolerance was in the order P318R > M425T > N267S. The results of the kinetic analyses combined with a three-dimensional structure modeling of the location of P318R and M425T demonstrate that the lower hemisphere's upper surface is possibly another important region for glyphosate resistance. Furthermore, the transgenic Arabidopsis was obtained to confirm the potential of the mutant in developing glyphosate-resistant crops.

  2. Biochar Application in Malaysian Sandy and Acid Sulfate Soils: Soil Amelioration Effects and Improved Crop Production over Two Cropping Seasons

    Directory of Open Access Journals (Sweden)

    Theeba Manickam

    2015-12-01

    Full Text Available The use of biochar as an agricultural soil improvement was tested in acid sulfate and sandy soils from Malaysia, cropped with rice and corn. Malaysia has an abundance of waste rice husks that could be used to produce biochar. Rice husk biochar was produced in a gasifier at a local mill in Kelantan as well as in the laboratory using a controlled, specially designed, top lift up draft system (Belonio unit. Rice husk biochar was applied once to both soils at two doses (2% and 5%, in a pot set up that was carried out for two cropping seasons. Positive and significant crop yield effects were observed for both soils, biochars and crops. The yield effects varied with biochar type and dosage, with soil type and over the cropping seasons. The yield increases observed for the sandy soil were tentatively attributed to significant increases in plant-available water contents (from 4%–5% to 7%–8%. The yield effects in the acid sulfate soil were likely a consequence of a combination of (i alleviation of plant root stress by aluminum (Ca/Al molar ratios significantly increased, from around 1 to 3–5 and (ii increases in CEC. The agricultural benefits of rice husk biochar application to Malaysian soils holds promise for its future use.

  3. Electrochemical gas sensors based on paper-supported room-temperature ionic liquids for improved analysis of acid vapours.

    Science.gov (United States)

    Toniolo, Rosanna; Dossi, Nicolò; Pizzariello, Andrea; Casagrande, Alice; Bontempelli, Gino

    2013-04-01

    A prototype of a fast-response task-specific amperometric gas sensor based on paper-supported room-temperature ionic liquids (RTILs) is proposed here for improved analysis of volatile acid species. It consists of a small filter paper foil soaked with a RTIL mixture containing an ionic liquid whose anion (acetate) displays a basic character, upon which three electrodes are screen printed by carbon ink profiting from a suitable mask. It takes advantage of the high electrical conductivity and negligible vapour pressure of RTILs and of their easy immobilization into a porous and inexpensive supporting material such as paper. The performance of this device, used as a wall-jet amperometric detector for flow injection analyses of headspace samples in equilibrium with aqueous solutions at controlled concentrations, was evaluated for phenol and 1-butanethiol vapours which were adopted as model acid gaseous analytes. The results obtained showed that the quite high potentials required for the detection of these analytes are lowered significantly, thanks to the addition of the basic acetate RTIL. In such a way, overlap with the medium discharge is avoided, and the possible adverse effect of interfering species is minimised. The sensor performance was quite satisfactory (detection limits, ca. 0.3 μM; dynamic range, ca. 1-200 μM, both referred to solution concentrations; correlation coefficients in the range 0.993-0.997; repeatability, ± 6% RSD; long-term stability, 9%); thus suggesting the possible use of this device for manifold applications.

  4. Shikimic acid production in Escherichia coli: From classical metabolic engineering strategies to omics applied to improve its production

    Directory of Open Access Journals (Sweden)

    Juan Andrés Martínez

    2015-09-01

    Full Text Available Shikimic acid (SA is an intermediate of the SA pathway that is present in bacteria and plants. SA has gained great interest because it is a precursor in the synthesis of the drug oseltamivir phosphate (OSF, an efficient inhibitor of the neuraminidase enzyme of diverse seasonal influenza viruses, the avian influenza virus H5N1, and the human influenza virus H1N1. For the purposes of OSF production, SA is extracted from the pods of Chinese star anise plants (Illicium spp., yielding up to 17% of SA (dry basis content. The high demand for OSF necessary to manage a major influenza outbreak is not adequately met by industrial production using SA from plants sources. As the SA pathway is present in the model bacteria Escherichia coli, several intuitive metabolically engineered strains have been applied for its successful overproduction by biotechnological processes, resulting in strains producing up to 71 g/L of SA, with high conversion yields of up to 0.42 (mol SA/mol Glc, in both batch and fed-batch cultures using complex fermentation broths, including glucose as a carbon source and yeast extract. Global transcriptomic analyses have been performed in SA producing strains, resulting in the identification of possible key target genes for the design of a rational strain improvement strategy. Because possible target genes are involved in the transport, catabolism and interconversion of different carbon sources and metabolic intermediates outside the central carbon metabolism and SA pathways, as genes involved in diverse cellular stress responses, the development of rational cellular strain improvement strategies based on omics data constitutes a challenging task to improve SA production in currently overproducing engineered strains. In this review, we discuss the main metabolic engineering strategies that have been applied for the development of efficient SA producing strains, as the perspective of omics analysis has focused on further strain improvement

  5. Histaminergic modulation of cholinergic release from the nucleus basalis magnocellularis into insular cortex during taste aversive memory formation.

    Directory of Open Access Journals (Sweden)

    Liliana Purón-Sierra

    Full Text Available The ability of acetylcholine (ACh to alter specific functional properties of the cortex endows the cholinergic system with an important modulatory role in memory formation. For example, an increase in ACh release occurs during novel stimulus processing, indicating that ACh activity is critical during early stages of memory processing. During novel taste presentation, there is an increase in ACh release in the insular cortex (IC, a major structure for taste memory recognition. There is extensive evidence implicating the cholinergic efferents of the nucleus basalis magnocellularis (NBM in cortical activity changes during learning processes, and new evidence suggests that the histaminergic system may interact with the cholinergic system in important ways. However, there is little information as to whether changes in cholinergic activity in the IC are modulated during taste memory formation. Therefore, in the present study, we evaluated the influence of two histamine receptor subtypes, H1 in the NBM and H3 in the IC, on ACh release in the IC during conditioned taste aversion (CTA. Injection of the H3 receptor agonist R-α-methylhistamine (RAMH into the IC or of the H1 receptor antagonist pyrilamine into the NBM during CTA training impaired subsequent CTA memory, and simultaneously resulted in a reduction of ACh release in the IC. This study demonstrated that basal and cortical cholinergic pathways are finely tuned by histaminergic activity during CTA, since dual actions of histamine receptor subtypes on ACh modulation release each have a significant impact during taste memory formation.

  6. Decrease of a Current Mediated by Kv1.3 Channels Causes Striatal Cholinergic Interneuron Hyperexcitability in Experimental Parkinsonism

    Directory of Open Access Journals (Sweden)

    Cecilia Tubert

    2016-09-01

    Full Text Available The mechanism underlying a hypercholinergic state in Parkinson’s disease (PD remains uncertain. Here, we show that disruption of the Kv1 channel-mediated function causes hyperexcitability of striatal cholinergic interneurons in a mouse model of PD. Specifically, our data reveal that Kv1 channels containing Kv1.3 subunits contribute significantly to the orphan potassium current known as IsAHP in striatal cholinergic interneurons. Typically, this Kv1 current provides negative feedback to depolarization that limits burst firing and slows the tonic activity of cholinergic interneurons. However, such inhibitory control of cholinergic interneuron excitability by Kv1.3-mediated current is markedly diminished in the parkinsonian striatum, suggesting that targeting Kv1.3 subunits and their regulatory pathways may have therapeutic potential in PD therapy. These studies reveal unexpected roles of Kv1.3 subunit-containing channels in the regulation of firing patterns of striatal cholinergic interneurons, which were thought to be largely dependent on KCa channels.

  7. Elimination of the vesicular acetylcholine transporter in the striatum reveals regulation of behaviour by cholinergic-glutamatergic co-transmission.

    Science.gov (United States)

    Guzman, Monica S; De Jaeger, Xavier; Raulic, Sanda; Souza, Ivana A; Li, Alex X; Schmid, Susanne; Menon, Ravi S; Gainetdinov, Raul R; Caron, Marc G; Bartha, Robert; Prado, Vania F; Prado, Marco A M

    2011-11-01

    Cholinergic neurons in the striatum are thought to play major regulatory functions in motor behaviour and reward. These neurons express two vesicular transporters that can load either acetylcholine or glutamate into synaptic vesicles. Consequently cholinergic neurons can release both neurotransmitters, making it difficult to discern their individual contributions for the regulation of striatal functions. Here we have dissected the specific roles of acetylcholine release for striatal-dependent behaviour in mice by selective elimination of the vesicular acetylcholine transporter (VAChT) from striatal cholinergic neurons. Analysis of several behavioural parameters indicates that elimination of VAChT had only marginal consequences in striatum-related tasks and did not affect spontaneous locomotion, cocaine-induced hyperactivity, or its reward properties. However, dopaminergic sensitivity of medium spiny neurons (MSN) and the behavioural outputs in response to direct dopaminergic agonists were enhanced, likely due to increased expression/function of dopamine receptors in the striatum. These observations indicate that previous functions attributed to striatal cholinergic neurons in spontaneous locomotor activity and in the rewarding responses to cocaine are mediated by glutamate and not by acetylcholine release. Our experiments demonstrate how one population of neurons can use two distinct neurotransmitters to differentially regulate a given circuitry. The data also raise the possibility of using VAChT as a target to boost dopaminergic function and decrease high striatal cholinergic activity, common neurochemical alterations in individuals affected with Parkinson's disease. PMID:22087075

  8. Elimination of the vesicular acetylcholine transporter in the striatum reveals regulation of behaviour by cholinergic-glutamatergic co-transmission.

    Directory of Open Access Journals (Sweden)

    Monica S Guzman

    2011-11-01

    Full Text Available Cholinergic neurons in the striatum are thought to play major regulatory functions in motor behaviour and reward. These neurons express two vesicular transporters that can load either acetylcholine or glutamate into synaptic vesicles. Consequently cholinergic neurons can release both neurotransmitters, making it difficult to discern their individual contributions for the regulation of striatal functions. Here we have dissected the specific roles of acetylcholine release for striatal-dependent behaviour in mice by selective elimination of the vesicular acetylcholine transporter (VAChT from striatal cholinergic neurons. Analysis of several behavioural parameters indicates that elimination of VAChT had only marginal consequences in striatum-related tasks and did not affect spontaneous locomotion, cocaine-induced hyperactivity, or its reward properties. However, dopaminergic sensitivity of medium spiny neurons (MSN and the behavioural outputs in response to direct dopaminergic agonists were enhanced, likely due to increased expression/function of dopamine receptors in the striatum. These observations indicate that previous functions attributed to striatal cholinergic neurons in spontaneous locomotor activity and in the rewarding responses to cocaine are mediated by glutamate and not by acetylcholine release. Our experiments demonstrate how one population of neurons can use two distinct neurotransmitters to differentially regulate a given circuitry. The data also raise the possibility of using VAChT as a target to boost dopaminergic function and decrease high striatal cholinergic activity, common neurochemical alterations in individuals affected with Parkinson's disease.

  9. Improved biocompatibility of poly(lactic-co-glycolic acid) orv and poly-L-lactic acid blended with nanoparticulate amorphous calcium phosphate in vascular stent applications.

    Science.gov (United States)

    Zheng, Xiaoxin; Wang, Yujue; Lan, Zhiyuan; Lyu, Yongnan; Feng, Gaoke; Zhang, Yipei; Tagusari, Shizu; Kislauskis, Edward; Robich, Michael P; McCarthy, Stephen; Sellke, Frank W; Laham, Roger; Jiang, Xuejun; Gu, Wei Wang; Wu, Tim

    2014-06-01

    Biodegradable polymers used as vascular stent coatings and stent platforms encounter a major challenge: biocompatibility in vivo, which plays an important role in in-stent restenosis (ISR). Co-formulating amorphous calcium phosphate (ACP) into poly(lactic-co-glycolic acid) (PLGA) or poly-L-lactic acid (PLLA) was investigated to address the issue. For stent coating applications, metal stents were coated with polyethylene-co-vinyl acetate/poly-n-butyl methacrylate (PEVA/PBMA), PLGA or PLGA/ACP composites, and implanted into rat aortas for one and three months. Comparing with both PEVA/PBMA and PLGA groups after one month, the results showed that stents coated with PLGA/ACP had significantly reduced restenosis (PLGA/ACP vs. PEVA/PBMA vs. PLGA: 21.24 +/- 2.59% vs. 27.54 +/- 1.19% vs. 32.12 +/- 3.93%, P < 0.05), reduced inflammation (1.25 +/- 0.35 vs. 1.77 +/- 0.38 vs. 2.30 +/- 0.21, P < 0.05) and increased speed of re-endothelialization (1.78 +/- 0.46 vs. 1.17 +/- 0.18 vs. 1.20 +/- 0.18, P < 0.05). After three months, the PLGA/ACP group still displayed lower inflammation score (1.33 +/- 0.33 vs. 2.27 +/- 0.55, P < 0.05) and higher endothelial scores (2.33 +/- 0.33 vs. 1.20 +/- 0.18, P < 0.05) as compared with the PEVA/PBMA group. Moreover, for stent platform applications, PLLA/ACP stent tube significantly reduced the inflammatory cells infiltration in the vessel walls of rabbit iliac arteries relative to their PLLA cohort (NF-kappaB-positive cells: 23.31 +/- 2.33/mm2 vs. 9.34 +/- 1.35/mm2, P < 0.05). No systemic biochemical or pathological evidence of toxicity was found in either PLGA/ACP or PLLA/ACP. The co-formulation of ACP into PLGA and PLLA resulted in improved biocompatibility without systemic toxicity.

  10. Maternal exposure to hexachlorophene targets intermediate-stage progenitor cells in the hippocampal neurogenesis involving myelin vacuolation of cholinergic and glutamatergic inputs in mice.

    Science.gov (United States)

    Kato, Mizuho; Abe, Hajime; Itahashi, Megu; Kikuchihara, Yoh; Kimura, Masayuki; Mizukami, Sayaka; Yoshida, Toshinori; Shibutani, Makoto

    2016-02-01

    Hexachlorophene (HCP) has been shown to induce myelin vacuolation due to intramyelinic edema of the nerve fibers in animal neural tissue. We investigated the maternal exposure effect of HCP on hippocampal neurogenesis in the offspring of pregnant mice supplemented with 0 (control), 33 or 100 ppm HCP in diet from gestational day 6 to day 21 after delivery. On postnatal day (PND) 21, offspring as examined in males exhibited decreased granule cell lineage populations expressing paired box 6, sex-determining region Y-box 2 and eomesodermin in the hippocampal subgranular zone (SGZ) accompanied by myelin vacuolation involving white matter tracts of the hippocampal fimbria at ≥ 33 ppm. However, SGZ cellular populations expressing brain lipid binding protein and doublecortin were unchanged at any dose. Transcript expression of cholinergic receptor genes, Chrna4 and Chrnb2, and glutamate receptor genes, Grm1 and Grin2d, examined at 100 ppm, decreased in the dentate gyrus. HCP exposure did not alter the number of proliferating or apoptotic cells in the SGZ, or reelin- or calcium-binding protein-expressing γ-aminobutyric acid (GABA)ergic interneurons in the dentate hilus, on PND 21 and PND 77. All neurogenesis-related changes observed in HCP-exposed offspring on PND 21 disappeared on PND 77, suggesting that maternal HCP exposure at ≥ 33 ppm reversibly decreased type 2 intermediate-stage progenitor cells in the hippocampal neurogenesis. Myelin vacuolation might be responsible for changes in neurogenesis possibly by reducing nerve conduction velocity of cholinergic inputs from the septal-hippocampal pathway to granule cell lineages and/or GABAergic interneurons, and of glutamatergic inputs to granule cell lineages.

  11. Improvement of foaming properties of cuttlefish skin gelatin by modification with N-hydroxysuccinimide esters of fatty acid

    NARCIS (Netherlands)

    Aewsiri, T.; Benjakul, S.; Visessanguan, W.; Wierenga, P.A.; Gruppen, H.

    2011-01-01

    Conformation and foaming properties of cuttlefish skin gelatin modified by N-hydroxysuccinimide esters of different saturated fatty acids including capric acid (C10:0), lauric acid (C12:0) and myristic acid (C14:0) at different molar ratios (0.25, 0.50, 1.00 and 2.00) were investigated. Covalent att

  12. Biocompatibility Assessment of Novel Collagen-Sericin Scaffolds Improved with Hyaluronic Acid and Chondroitin Sulfate for Cartilage Regeneration

    Directory of Open Access Journals (Sweden)

    Sorina Dinescu

    2013-01-01

    Full Text Available Cartilage tissue engineering (CTE applications are focused towards the use of implantable biohybrids consisting of biodegradable scaffolds combined with in vitro cultured cells. Hyaluronic acid (HA and chondroitin sulfate (CS were identified as the most potent prochondrogenic factors used to design new biomaterials for CTE, while human adipose-derived stem cells (ASCs were proved to display high chondrogenic potential. In this context, our aim was not only to build novel 3D porous scaffolds based on natural compounds but also to evaluate their in vitro biological performances. Therefore, for prospective CTE, collagen-sericin (Coll-SS scaffolds improved with HA (5% or 10% and CS (5% or 10% were used as temporary physical supports for ASCs and were analyzed in terms of structural, thermal, morphological, and swelling properties and cytotoxic potential. To complete biocompatibility data, ASCs viability and proliferation potential were also assessed. Our studies revealed that Coll-SS hydrogels improved with 10% HA and 5% CS displayed the best biological performances in terms of cell viability, proliferation, morphology, and distribution. Thus, further work will address a novel 3D system including both HA 10% and CS 5% glycoproteins, which will probably be exposed to prochondrogenic conditions in order to assess its potential use in CTE applications.

  13. Improving solubility, stability, and cellular uptake of resveratrol by nanoencapsulation with chitosan and γ-poly (glutamic acid).

    Science.gov (United States)

    Jeon, Young Ok; Lee, Ji-Soo; Lee, Hyeon Gyu

    2016-11-01

    Resveratrol (RES), a polyphenolic compound found in grape skins, is a potent antioxidant with broad health benefits. However, its utilization in food has been limited by its poor water solubility, instability, and low bioavailability. The purpose of this study is to improve the solubility, stability, and cellular uptake of RES by nanoencapsulation using chitosan (CS) and γ-poly (glutamic acid) (γ-PGA). The size of nanoparticles significantly decreases with a decrease in the CS/γ-PGA ratio (p<0.05). The nanoparticle size with CS/γ-PGA ratio of 5 was 100-150nm. The entrapment efficiency and UV-light protection effect significantly increases (p<0.05), with an increase in the CS and γ-PGA concentration. The solubility of RES increases 3.2 and 4.2 times before and after lyophilization by nanoencapsulation, respectively. Compared with non-nanoencapsulated RES, the nanoencapsulated RES tends to maintain its solubility and antioxidant activity during storage. CS/γ-PGA nanoencapsulation was able to significantly enhance the transport of RES across a Caco-2 cell monolayer (p<0.05). The highest cellular uptake was found for nanoparticles prepared with 0.5mg/mL CS and 0.1mg/mL γ-PGA, which showed the highest solubility and antioxidant activity during storage. Therefore, CS/γ-PGA nanoencapsulation is found to be a potentially valuable technique for improving the solubility, stability, and cellular uptake of RES. PMID:27518454

  14. Improving volatile fatty acids production by exploiting the residual substrates in post-fermented sludge: Protease catalysis of refractory protein.

    Science.gov (United States)

    Yin, Bo; Liu, Hongbo; Wang, Yuanyuan; Bai, Jie; Liu, He; Fu, Bo

    2016-03-01

    The real cause to the low yield of volatile fatty acids (VFAs), from inhibition or low biodegradation, is uncertain in sludge anaerobic fermentation. In this study, poor biodegradability of proteins and fast decrease of the indigenous hydrolase activity in the residual post-fermented sludge were found to be the major reasons. With the addition of trypsin or alkaline protease in residual post-fermented sludge after primary alkaline fermentation, degradation efficiency of refractory protein increased by 33.6% and 34.8%, respectively. Accordingly, the VFAs yields were improved by 69.7% and 106.1%, respectively. Furthermore, the activities of added trypsin and alkaline protease could maintain at 13.52 U/mL and 19.11 U/mL in the alkaline fermentation process. This study demonstrated that exploiting the refractory proteins in residual post-fermented sludge by protease addition seems to be a very promising way for improving VFAs yield of conventional alkaline fermentations with waste activated sludge. PMID:26722812

  15. Quinic Acid Could Be a Potential Rejuvenating Natural Compound by Improving Survival of Caenorhabditis elegans under Deleterious Conditions

    Science.gov (United States)

    Zhang, Longze; Zhang, Junjing

    2012-01-01

    Abstract Quinic acid (QA) is an active ingredient of Cat's Claw (Uncaria tomentosa), which is found to be active in enhancing DNA repair and immunity in model systems and able to generate neuroprotective effects in neurons. However, QA's role in improving survival is not well studied. Here we report that QA can provide protection in Caenorhabidits elegans and improve worm survival under stress. Under heat stress and oxidative stress, QA-treated wild-type C. elegans N2 (N2) survived 17.8% and 29.7% longer, respectively, than the control worms. Our data suggest that under heat stress, QA can upregulate the expression of the small heat shock protein hsp-16.2 gene, which could help the worms survive a longer time. We also found that QA extended the C. elegans mutant VC475 [hsp-16.2 (gk249)] life span by 15.7% under normal culture conditions. However, under normal culture conditions, QA did not affect hsp-16.2 expression, but upregulated the expression of daf-16 and sod-3 in a DAF-16–dependent manner, and downregulated the level of reactive oxygen species (ROS), suggesting that under normal conditions QA acts in different pathways. As a natural product, QA demonstrates great potential as a rejuvenating compound. PMID:22950425

  16. Salicylic acid restrains nickel toxicity, improves antioxidant defence system and enhances the production of anticancer alkaloids in Catharanthus roseus (L.).

    Science.gov (United States)

    Idrees, Mohd; Naeem, M; Aftab, Tariq; Khan, M Masroor A; Moinuddin

    2013-05-15

    Salicylic acid (SA) has been reported to ameliorate various stresses in plants. In order to explore the role of SA under nickel (Ni) stress, thirty-days old plants of periwinkle (Catharanthus roseus L.) were supplied with eight treatments comprising basal application of Ni (0, 50, 100 and 150 mg kg(-1)) and foliar application of SA (0 and 10(-5)M) under net house conditions. Ni application significantly reduced the growth attributes including plant height, leaf-area index and fresh and dry weights of shoot and root. Increasing Ni concentration led to a gradual decrease in photosynthetic parameters and activities of nitrate reductase and carbonic anhydrase. The plants, undergoing Ni stress, exhibited a significant increase in the activity of superoxide dismutase, catalase and peroxidase together with an increase in electrolyte leakage and proline content. Total alkaloid content was also declined in Ni-treated plants. Foliar application of SA (10(-5)M) reduced the deleterious effects of Ni on plant growth, accelerating the restoration of growth processes. SA also improved the total alkaloid content under normal as well as adverse conditions. Foliar spray of SA significantly improved the content of anticancer alkaloids vincristine (by 22.2%) and vinblastine (by 50.0%) in plants treated with 150 mg kg(-1) of Ni. PMID:23597961

  17. Activation of bile acid signaling improves metabolic phenotypes in high-fat diet-induced obese mice.

    Science.gov (United States)

    Pierre, Joseph F; Martinez, Kristina B; Ye, Honggang; Nadimpalli, Anuradha; Morton, Timothy C; Yang, Jinghui; Wang, Qiang; Patno, Noelle; Chang, Eugene B; Yin, Deng Ping

    2016-08-01

    The metabolic benefits induced by gastric bypass, currently the most effective treatment for morbid obesity, are associated with bile acid (BA) delivery to the distal intestine. However, mechanistic insights into BA signaling in the mediation of metabolic benefits remain an area of study. The bile diversion () mouse model, in which the gallbladder is anastomosed to the distal jejunum, was used to test the specific role of BA in the regulation of glucose and lipid homeostasis. Metabolic phenotype, including body weight and composition, glucose tolerance, energy expenditure, thermogenesis genes, total BA and BA composition in the circulation and portal vein, and gut microbiota were examined. BD improves the metabolic phenotype, which is in accord with increased circulating primary BAs and regulation of enterohormones. BD-induced hypertrophy of the proximal intestine in the absence of BA was reversed by BA oral gavage, but without influencing BD metabolic benefits. BD-enhanced energy expenditure was associated with elevated TGR5, D2, and thermogenic genes, including UCP1, PRDM16, PGC-1α, PGC-1β, and PDGFRα in epididymal white adipose tissue (WAT) and inguinal WAT, but not in brown adipose tissue. BD resulted in an altered gut microbiota profile (i.e., Firmicutes bacteria were decreased, Bacteroidetes were increased, and Akkermansia was positively correlated with higher levels of circulating primary BAs). Our study demonstrates that enhancement of BA signaling regulates glucose and lipid homeostasis, promotes thermogenesis, and modulates the gut microbiota, which collectively resulted in an improved metabolic phenotype. PMID:27340128

  18. Biocompatibility Assessment of Novel Collagen-Sericin Scaffolds Improved with Hyaluronic Acid and Chondroitin Sulfate for Cartilage Regeneration

    Science.gov (United States)

    Gălăţeanu, Bianca; Albu, Mădălina

    2013-01-01

    Cartilage tissue engineering (CTE) applications are focused towards the use of implantable biohybrids consisting of biodegradable scaffolds combined with in vitro cultured cells. Hyaluronic acid (HA) and chondroitin sulfate (CS) were identified as the most potent prochondrogenic factors used to design new biomaterials for CTE, while human adipose-derived stem cells (ASCs) were proved to display high chondrogenic potential. In this context, our aim was not only to build novel 3D porous scaffolds based on natural compounds but also to evaluate their in vitro biological performances. Therefore, for prospective CTE, collagen-sericin (Coll-SS) scaffolds improved with HA (5% or 10%) and CS (5% or 10%) were used as temporary physical supports for ASCs and were analyzed in terms of structural, thermal, morphological, and swelling properties and cytotoxic potential. To complete biocompatibility data, ASCs viability and proliferation potential were also assessed. Our studies revealed that Coll-SS hydrogels improved with 10% HA and 5% CS displayed the best biological performances in terms of cell viability, proliferation, morphology, and distribution. Thus, further work will address a novel 3D system including both HA 10% and CS 5% glycoproteins, which will probably be exposed to prochondrogenic conditions in order to assess its potential use in CTE applications. PMID:24308001

  19. Feeding a Diet Enriched in Docosahexaenoic Acid to Lactating Dams Improves the Tolerance Response to Egg Protein in Suckled Pups

    Directory of Open Access Journals (Sweden)

    Caroline Richard

    2016-02-01

    Full Text Available The objective of this study was to determine the effect of feeding a maternal diet supplemented with docosahexaenoic acid (DHA during the suckling period on the development of the immune system and oral tolerance (OT in offspring. Dams were randomized to consume one of two nutritionally adequate diets throughout the suckling period: control (N = 12, 0% DHA or DHA (N = 8, 0.9% DHA diet. At 11 days, pups from each dam were randomly assigned to a mucosal OT challenge: the placebo or the ovalbumin (OVA treatment. At three weeks, plasma immunoglobulins and splenocyte cytokine production ex vivo were measured. OVA-tolerized pups had a lower Th2 (IL-13 response to OVA despite the presence of more activated T cells and memory cells (CD27+, all p < 0.05. Feeding a high DHA diet improved the ability of splenocytes to respond to mitogens toward a skewed Th1 response and led to a higher IL-10 and a lower TGF-β production after stimulation with OVA (all p < 0.05. Untolerized DHA-fed pups had lower plasma concentrations of OVA-specific immunoglobulin E (p for interaction < 0.05. Overall, feeding a high DHA maternal diet improves the tolerance response in untolerized suckled pups in a direction that is thought to be beneficial for the establishment of OT.

  20. Feeding a Diet Enriched in Docosahexaenoic Acid to Lactating Dams Improves the Tolerance Response to Egg Protein in Suckled Pups.

    Science.gov (United States)

    Richard, Caroline; Lewis, Erin D; Goruk, Susan; Field, Catherine J

    2016-02-01

    The objective of this study was to determine the effect of feeding a maternal diet supplemented with docosahexaenoic acid (DHA) during the suckling period on the development of the immune system and oral tolerance (OT) in offspring. Dams were randomized to consume one of two nutritionally adequate diets throughout the suckling period: control (N = 12, 0% DHA) or DHA (N = 8, 0.9% DHA) diet. At 11 days, pups from each dam were randomly assigned to a mucosal OT challenge: the placebo or the ovalbumin (OVA) treatment. At three weeks, plasma immunoglobulins and splenocyte cytokine production ex vivo were measured. OVA-tolerized pups had a lower Th2 (IL-13) response to OVA despite the presence of more activated T cells and memory cells (CD27+, all p < 0.05). Feeding a high DHA diet improved the ability of splenocytes to respond to mitogens toward a skewed Th1 response and led to a higher IL-10 and a lower TGF-β production after stimulation with OVA (all p < 0.05). Untolerized DHA-fed pups had lower plasma concentrations of OVA-specific immunoglobulin E (p for interaction < 0.05). Overall, feeding a high DHA maternal diet improves the tolerance response in untolerized suckled pups in a direction that is thought to be beneficial for the establishment of OT. PMID:26907333