Persistent fibrosis in the liver of choline-deficient and iron-supplemented L-amino acid-defined diet-induced nonalcoholic steatohepatitis rat due to continuing oxidative stress after choline supplementation

Energy Technology Data Exchange (ETDEWEB)

Takeuchi-Yorimoto, Ayano, E-mail: ayano.takeuchi@astellas.com [Drug Safety Research Labs, Astellas Pharma Inc., Osaka 532-8514 (Japan); Noto, Takahisa [Drug Safety Research Labs, Astellas Pharma Inc., Osaka 532-8514 (Japan); Yamada, Atsushi [Drug Safety Research Division, Astellas Research Technologies Co., Ltd., Osaka 532-8514 (Japan); Miyamae, Yoichi; Oishi, Yuji; Matsumoto, Masahiro [Drug Safety Research Labs, Astellas Pharma Inc., Osaka 532-8514 (Japan)

2013-05-01

Nonalcoholic steatohepatitis (NASH) is characterized by combined pathology of steatosis, lobular inflammation, fibrosis, and hepatocellular degeneration, with systemic symptoms of diabetes or hyperlipidemia, all in the absence of alcohol abuse. Given the therapeutic importance and conflicting findings regarding the potential for healing the histopathologic features of NASH in humans, particularly fibrosis, we investigated the reversibility of NASH-related findings in Wistar rats fed a choline-deficient and iron-supplemented L-amino acid-defined (CDAA) diet for 12 weeks, with a recovery period of 7 weeks, during which the diets were switched to a choline-sufficient and iron-supplemented L-amino acid-defined (CSAA) one. Analysis showed that steatosis and inflammation were significantly resolved by the end of the recovery period, along with decreases in AST and ALT activities within 4 weeks. In contrast, fibrosis remained even after the recovery period, to an extent similar to that in continuously CDAA-fed animals. Real-time reverse transcriptase-polymerase chain reaction, Western blot, and immunohistochemical investigations revealed that expression of some factors indicating oxidative stress (CYP2E1, 4-HNE, and iNOS) were elevated, whereas catalase and SOD1 were decreased, and a hypoxic state and CD34-positive neovascularization were evident even after the recovery period, although the fibrogenesis pathway by activated α-SMA-positive hepatic stellate cells via TGF-β and TIMPs decreased to the CSAA group level. In conclusion, persistent fibrosis was noted after the recovery period of 7 weeks, possibly due to sustained hypoxia and oxidative stress supposedly caused by capillarization. Otherwise, histopathological features of steatosis and inflammation, as well as serum AST and ALT activities, were recovered. - Highlights: ► NASH-like liver lesions are induced in rats by feeding a CDAA diet. ► Steatosis and lobular inflammation are resolved after switching to a

Spatial memory and hippocampal plasticity are differentially sensitive to the availability of choline in adulthood as a function of choline supply in utero

OpenAIRE

Wong-Goodrich, Sarah J.E.; Glenn, Melissa J.; Mellott, Tiffany J.; Blusztajn, Jan K.; Meck, Warren H.; Williams, Christina L.

2008-01-01

Altered dietary choline availability early in life leads to persistent changes in spatial memory and hippocampal plasticity in adulthood. Developmental programming by early choline nutrition may determine the range of adult choline intake that is optimal for the types of neural plasticity involved in cognitive function. To test this, male Sprague-Dawley rats were exposed to a choline chloride deficient (DEF), sufficient (CON), or supplemented (SUP) diet during embryonic days 12-17 and then re...

Role of Choline-Docosahexaenoic acid and Trigonella foenum graecum Seed Extract on Ovariectomy Induced Dyslipidemia and Oxidative Stress in Rat Model

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Nagamma Takkella

2018-01-01

Full Text Available Background: Menopause is characterized by the deficiency of ovarian hormones, mainly estrogen. The decline in estrogen hormone is contributing the cardiovascular disorders in women. Hormone replacement therapy has disadvantages especially a higher risk of breast, ovarian and endometrial cancers upon chronic use. Phytoestrogens may be used as an alternative to hormone replacement therapy. Aim and Objectives: This study was designed to scientifically evaluate the role of Choline- Docosahexaenoic Acid (DHA and Trigonella foenum graecum (TFG seed extract on Ovariectomy (OVX induced dyslipidemia and oxidative stress in rat model. Material and Methods: Female Wistar rats were allocated into four groups (n=6:1 Sham control, 2 ovariectomized, 3 ovariectomized+ choline-DHA and 4 ovariectomized + choline-DHA+TFG. After 30 days of treatment, fasting blood samples and liver tissues were collected. Serum was analyzed for lipid profile and liver homogenates were used for assessment of oxidative stress and antioxidant activity. Results: Ovariectomized rats showed significantly increased (P<0.05 Total Cholesterol (TC, Low Density Lipoprotein (LDL levels and decreased High Density Lipoprotein (HDL levels. Treating ovariectomized rats with choline-DHA and TFG seed extract significantly lowered (P<0.05 total cholesterol, LDL and markedly increased the HDL. Significantly increased (P≤0.01 Thiobarbituric Acid Reactive Substances (TBARS and reduced (P<0.05 glutathione levels were observed in OVX group. The synergetic effect of choline-DHA and fenugreek showed a significant reduction ((P≤0.01 in TBARS levels. Conclusion: These results showed that choline-DHA with TFG supplementation have a favorable effect on OVX induced hyperlipidemia and oxidative stress. Therefore, these components may be a therapeutic agent for treating the menopause induced hyperlipidemia or oxidative stress.

Choline-Deficient-Diet-Induced Fatty Liver Is a Metastasis-Resistant Microenvironment.

Science.gov (United States)

Nakamura, Miki; Suetsugu, Atsushi; Hasegawa, Kosuke; Matsumoto, Takuro; Aoki, Hitomi; Kunisada, Takahiro; Shimizu, Masahito; Saji, Shigetoyo; Moriwaki, Hisataka; Hoffman, Robert M

2017-07-01

Fatty liver disease is increasing in the developed and developing world. Liver metastasis from malignant lymphoma in the fatty liver is poorly understood. In a previous report, we developed color-coded imaging of the tumor microenvironment (TME) of the murine EL4-RFP malignant lymphoma during metastasis, including the lung. In the present report, we investigated the potential and microenvironment of the fatty liver induced by a choline-deficient diet as a metastatic site in this mouse lymphoma model. C57BL/6-GFP transgenic mice were fed with a choline-deficient diet in order to establish a fatty liver model. EL4-RFP cells were injected in the spleen of normal mice and fatty-liver mice. Metastases in mice with fatty liver or normal liver were imaged with the Olympus SZX7 microscope and the Olympus FV1000 confocal microscope. Metastases of EL4-RFP were observed in the liver, ascites and bone marrow. Primary tumors were imaged in the spleen at the injection site. The fewest metastases were observed in the fatty liver. In addition, the fewest cancer-associated fibroblasts (CAFs) were observed in the fatty liver. The relative metastatic resistance of the fatty liver may be due to the reduced number of CAFs in the fatty livers. The mechanism of the effect of the choline-deficient diet is discussed. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Multi-Vitamin B Supplementation Reverses Hypoxia-Induced Tau Hyperphosphorylation and Improves Memory Function in Adult Mice.

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Yu, Lixia; Chen, Yuan; Wang, Weiguang; Xiao, Zhonghai; Hong, Yan

2016-08-04

Hypobaric hypoxia (HH) leads to reduced oxygen delivery to brain. It could trigger cognitive dysfunction and increase the risk of dementia including Alzheimer's disease (AD). The present study was undertaken in order to examine whether B vitamins (B6, B12, folate, and choline) could exert protective effects on hypoxia-induced memory deficit and AD related molecular events in mice. Adult male Kunming mice were assigned to five groups: normoxic control, hypoxic model (HH), hypoxia+vitamin B6/B12/folate (HB), hypoxia+choline (HC), hypoxia+vitamin B6/B12/folate+choline (HBC). Mice in the hypoxia, HB, HC, and HBC groups were exposed to hypobaric hypoxia for 8 h/day for 28 days in a decompression chamber mimicking 5500 meters of high altitude. Spatial and passive memories were assessed by radial arm and step-through passive test, respectively. Levels of tau and glycogen synthase kinase (GSK)-3β phosphorylation were detected by western blot. Homocysteine (Hcy) concentrations were determined using enzymatic cycling assay. Mice in the HH group exhibited significant spatial working and passive memory impairment, increased tau phosphorylation at Thr181, Ser262, Ser202/Thr205, and Ser396 in the cortex and hippocampus, and elevated Hcy levels compared with controls. Concomitantly, the levels of Ser9-phosphorylated GSK-3β were significantly decreased in brain after hypoxic treatment. Supplementations of vitamin B6/B12/folate+choline could significantly ameliorate the hypoxia-induced memory deficits, observably decreased Hcy concentrations in serum, and markedly attenuated tau hyperphosphorylation at multiple AD-related sites through upregulating inhibitory Ser9-phosphorylated GSK-3β. Our finding give further insight into combined neuroprotective effects of vitamin B6, B12, folate, and choline on brain against hypoxia.

Genetic Variation in Choline-Metabolizing Enzymes Alters Choline Metabolism in Young Women Consuming Choline Intakes Meeting Current Recommendations

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Ariel B. Ganz

2017-01-01

Full Text Available Single nucleotide polymorphisms (SNPs in choline metabolizing genes are associated with disease risk and greater susceptibility to organ dysfunction under conditions of dietary choline restriction. However, the underlying metabolic signatures of these variants are not well characterized and it is unknown whether genotypic differences persist at recommended choline intakes. Thus, we sought to determine if common genetic risk factors alter choline dynamics in pregnant, lactating, and non-pregnant women consuming choline intakes meeting and exceeding current recommendations. Women (n = 75 consumed 480 or 930 mg choline/day (22% as a metabolic tracer, choline-d9 for 10–12 weeks in a controlled feeding study. Genotyping was performed for eight variant SNPs and genetic differences in metabolic flux and partitioning of plasma choline metabolites were evaluated using stable isotope methodology. CHKA rs10791957, CHDH rs9001, CHDH rs12676, PEMT rs4646343, PEMT rs7946, FMO3 rs2266782, SLC44A1 rs7873937, and SLC44A1 rs3199966 altered the use of choline as a methyl donor; CHDH rs9001 and BHMT rs3733890 altered the partitioning of dietary choline between betaine and phosphatidylcholine synthesis via the cytidine diphosphate (CDP-choline pathway; and CHKA rs10791957, CHDH rs12676, PEMT rs4646343, PEMT rs7946 and SLC44A1 rs7873937 altered the distribution of dietary choline between the CDP-choline and phosphatidylethanolamine N-methyltransferase (PEMT denovo pathway. Such metabolic differences may contribute to disease pathogenesis and prognosis over the long-term.

Highly reversible lead-carbon battery anode with lead grafting on the carbon surface

KAUST Repository

Yin, Jian; Lin, Nan; Zhang, Wenli; Lin, Zheqi; Zhang, Ziqing; Wang, Yue; Shi, Jun; Bao, Jinpeng; Lin, Haibo

2018-01-01

A novel C/Pb composite has been successfully prepared by electroless plating to reduce the hydrogen evolution and achieve the high reversibility of the anode of lead-carbon battery (LCB). The deposited lead on the surface of C/Pb composite was found to be uniform and adherent to carbon surface. Because lead has been stuck on the surface of C/Pb composite, the embedded structure suppresses the hydrogen evolution of lead-carbon anode and strengthens the connection between carbon additive and sponge lead. Compared with the blank anode, the lead-carbon anode with C/Pb composite displays excellent charge–discharge reversibility, which is attributed to the good connection between carbon additives and lead that has been stuck on the surface of C/Pb composite during the preparation process. The addition of C/Pb composite maintains a solid anode structure with high specific surface area and power volume, and thereby, it plays a significant role in the highly reversible lead-carbon anode.

Highly reversible lead-carbon battery anode with lead grafting on the carbon surface

KAUST Repository

Yin, Jian

2018-03-27

A novel C/Pb composite has been successfully prepared by electroless plating to reduce the hydrogen evolution and achieve the high reversibility of the anode of lead-carbon battery (LCB). The deposited lead on the surface of C/Pb composite was found to be uniform and adherent to carbon surface. Because lead has been stuck on the surface of C/Pb composite, the embedded structure suppresses the hydrogen evolution of lead-carbon anode and strengthens the connection between carbon additive and sponge lead. Compared with the blank anode, the lead-carbon anode with C/Pb composite displays excellent charge–discharge reversibility, which is attributed to the good connection between carbon additives and lead that has been stuck on the surface of C/Pb composite during the preparation process. The addition of C/Pb composite maintains a solid anode structure with high specific surface area and power volume, and thereby, it plays a significant role in the highly reversible lead-carbon anode.

Opioid receptor subtypes mediating the noise-induced decreases in high-affinity choline uptake in the rat brain.

Science.gov (United States)

Lai, H; Carino, M A

1992-07-01

Acute (20 min) exposure to 100-dB white noise elicits a naltrexone-sensitive decrease in sodium-dependent high-affinity choline uptake in the frontal cortex and hippocampus of the rat. In the present study, the subtypes of opioid receptors involved were investigated by pretreating rats with microinjection of specific opioid-receptor antagonists into the lateral cerebroventricle before noise exposure. We found that the noise-induced decrease in high-affinity choline uptake in the hippocampus was blocked by pretreatment with either mu-, delta-, or kappa-opioid-receptor antagonists, whereas the effect of noise on frontal cortical high-affinity choline uptake was blocked by a mu- and delta- but not by a kappa-antagonist. These data further confirm the role of endogenous opioids in mediating the effects of noise on central cholinergic activity and indicate that different neural mechanisms are involved in the effects of noise on the frontal cortical and hippocampal cholinergic systems.

Selective Inducible Nitric Oxide Synthase Inhibitor Reversed Zinc Chloride-Induced Spatial Memory Impairment via Increasing Cholinergic Marker Expression.

Science.gov (United States)

Tabrizian, Kaveh; Azami, Kian; Belaran, Maryam; Soodi, Maliheh; Abdi, Khosrou; Fanoudi, Sahar; Sanati, Mehdi; Mottaghi Dastjerdi, Negar; Soltany Rezaee-Rad, Mohammad; Sharifzadeh, Mohammad

2016-10-01

Zinc, an essential micronutrient and biochemical element of the human body, plays structural, catalytic, and regulatory roles in numerous physiological functions. In the current study, the effects of a pretraining oral administration of zinc chloride (10, 25, and 50 mg/kg) for 14 consecutive days and post-training bilateral intra-hippocampal infusion of 1400W as a selective inducible nitric oxide synthase (iNOS) inhibitor (10, 50, and 100 μM/side), alone and in combination, on the spatial memory retention in Morris water maze (MWM) were investigated. Animals were trained for 4 days and tested 48 h after completion of training. Also, the molecular effects of these compounds on the expression of choline acetyltransferase (ChAT), as a cholinergic marker in the CA1 region of the hippocampus and medial septal area (MSA), were evaluated. Behavioral and molecular findings of this study showed that a 2-week oral administration of zinc chloride (50 mg/kg) impaired spatial memory retention in MWM and decreased ChAT expression. Immunohistochemical analysis of post-training bilateral intra-hippocampal infusion of 1400W revealed a significant increase in ChAT immunoreactivity. Furthermore, post-training bilateral intra-hippocampal infusion of 1400W into the CA1 region of the hippocampus reversed zinc chloride-induced spatial memory impairment in MWM and significantly increased ChAT expression in comparison with zinc chloride-treated animals. Taken together, these results emphasize the role of selective iNOS inhibitors in reversing zinc chloride-induced spatial memory deficits via modulation of cholinergic marker expression.

Photoreactivation reverses ultraviolet radition induced premutagenic lesions leading to frameshift mutations in Escherichia coli

International Nuclear Information System (INIS)

Yamamoto, Kazuo

1985-01-01

The effect of photoreactivation of the ultraviolet radiation induced reversion of a trpE9777 frameshift mutation was studied in a uvr A6 derivative of Escherichia coli K12. Two different photoreactivation treatments were used, one providing a single flash of photoreactivating light and another providing 10 min of light from fluorescent lamps. The reversion frequency of the trpE9777 frameshift mutation was strongly reduced when subsueqently exposed to visible light. The dose modification factor (the ratio of equally effective doses), for cells challenged with single-flash photoreactivation, for survival and induction of reversion to Trp + was 3.6 and 3.4, respectively. UV induction of RecA protein synthesis was not reversed by a single flash of photoreactivation. The dose modification factor for 10 min of fluorescent lamp photoreactivation for survival and for induction of reversion to Trp + was 6.5 and 6.3, respectively. The dose modification factor for 10 min of photoreactivation for induction of RecA protein was 1.7-2.5. Photoreactivation decreased the reversion of trpE9777 and increased survival to the same extent. We concluded that cyclobutyl pyrimidine dimers are the premutagenic lesions of UV mutagenesis of the trpE9777 allele in a uvr A6 background. (orig.)

Choline evokes fluid secretion by perfused rat mandibular gland without desensitization

DEFF Research Database (Denmark)

Murakami, M; Novak, I; Young, J A

1986-01-01

M and evoked secretory responses comparable with those of acetylcholine (0.05-1.0 microM) administered at similar Na concentrations. Continuous infusion of choline, in contrast to acetylcholine, did not lead to a fall off in the secretory response (desensitization or tachyphylaxis) until the choline...

Choline and Working Memory Training Improve Cognitive Deficits Caused by Prenatal Exposure to Ethanol

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Jaylyn Waddell

2017-09-01

Full Text Available Prenatal ethanol exposure is associated with deficits in executive function such as working memory, reversal learning and attentional set shifting in humans and animals. These behaviors are dependent on normal structure and function in cholinergic brain regions. Supplementation with choline can improve many behaviors in rodent models of fetal alcohol spectrum disorders and also improves working memory function in normal rats. We tested the hypothesis that supplementation with choline in the postnatal period will improve working memory during adolescence in normal and ethanol-exposed animals, and that working memory engagement during adolescence will transfer to other cognitive domains and have lasting effects on executive function in adulthood. Male and female offspring of rats fed an ethanol-containing liquid diet (ET; 3% v/v or control dams given a non-ethanol liquid diet (CT were injected with choline (Cho; 100 mg/kg or saline (Sal once per day from postnatal day (P 16–P30. Animals were trained/tested on a working memory test in adolescence and then underwent attentional set shifting and reversal learning in young adulthood. In adolescence, ET rats required more training to reach criterion than CT-Sal. Choline improved working memory performance for both CT and ET animals. In young adulthood, ET animals also performed poorly on the set shifting and reversal tasks. Deficits were more robust in ET male rats than female ET rats, but Cho improved performance in both sexes. ET male rats given a combination of Cho and working memory training in adolescence required significantly fewer trials to achieve criterion than any other ET group, suggesting that early interventions can cause a persistent improvement.

Case report: an electrocardiogram of spontaneous pneumothorax mimicking arm lead reversal.

Science.gov (United States)

Wieters, J Scott; Carlin, Joseph P; Morris, Andrew

2014-05-01

There are several previously documented findings for electrocardiograms (ECGs) of spontaneous pneumothorax. These findings include axis deviation, T-wave inversion, and right bundle branch block. When an ECG has the arm leads incorrectly placed, the ECG will display right axis deviation and inversion of the P waves in lead I. There have been no previously published ECGs of spontaneous pneumothorax that have shown the same findings as reversal of the limb leads of an ECG. A possible finding of spontaneous pneumothorax is an identical finding to that of an ECG that has been flagged for limb lead reversal. A patient presented in the emergency setting with acute chest pain and shortness of breath caused by a tension pneumothorax. An ECG was administered; findings indicated reversal of the arm leads (right axis deviation and inverted P waves in lead I), but there was no actual limb lead reversal present. ECG findings resolved upon resolution of the pneumothorax. If a patient presents with chest pain and shortness of breath, and the patient's ECG is flagged for limb lead reversal despite being set up correctly, the physician should raise clinical suspicion for a possible spontaneous pneumothorax. Copyright © 2014 Elsevier Inc. All rights reserved.

Anaerobic choline metabolism in microcompartments promotes growth and swarming of Proteus mirabilis.

Science.gov (United States)

Jameson, Eleanor; Fu, Tiantian; Brown, Ian R; Paszkiewicz, Konrad; Purdy, Kevin J; Frank, Stefanie; Chen, Yin

2016-09-01

Gammaproteobacteria are important gut microbes but only persist at low levels in the healthy gut. The ecology of Gammaproteobacteria in the gut environment is poorly understood. Here, we demonstrate that choline is an important growth substrate for representatives of Gammaproteobacteria. Using Proteus mirabilis as a model, we investigate the role of choline metabolism and demonstrate that the cutC gene, encoding a choline-trimethylamine lyase, is essential for choline degradation to trimethylamine by targeted mutagenesis of cutC and subsequent complementation experiments. Proteus mirabilis can rapidly utilize choline to enhance growth rate and cell yield in broth culture. Importantly, choline also enhances swarming-associated colony expansion of P. mirabilis under anaerobic conditions on a solid surface. Comparative transcriptomics demonstrated that choline not only induces choline-trimethylamine lyase but also genes encoding shell proteins for the formation of bacterial microcompartments. Subsequent analyses by transmission electron microscopy confirmed the presence of such novel microcompartments in cells cultivated in liquid broth and hyper-flagellated swarmer cells from solid medium. Together, our study reveals choline metabolism as an adaptation strategy for P. mirabilis and contributes to better understand the ecology of this bacterium in health and disease. © 2015 The Authors. Environmental Microbiology published by Society for Applied Microbiology and John Wiley & Sons Ltd.

Evaluation of the choline status in mink fed different levels and sources of choline

DEFF Research Database (Denmark)

Hedemann, Mette Skou; Damgaard, Birthe Marie; Clausen, T.N.

2012-01-01

Choline is an essential nutrient but the daily need for choline in mink has never been determined. Two experiments were performed to evalutate the choline status in mink kits and full-grown mink fed different levels of choline. In the first experiment mink kits were fed a synthetic diet with chol...

Choline-mediated modulation of hippocampal sharp wave-ripple complexes in vitro.

Science.gov (United States)

Fischer, Viktoria; Both, Martin; Draguhn, Andreas; Egorov, Alexei V

2014-06-01

The cholinergic system is critically involved in the modulation of cognitive functions, including learning and memory. Acetylcholine acts through muscarinic (mAChRs) and nicotinic receptors (nAChRs), which are both abundantly expressed in the hippocampus. Previous evidence indicates that choline, the precursor and degradation product of Acetylcholine, can itself activate nAChRs and thereby affects intrinsic and synaptic neuronal functions. Here, we asked whether the cellular actions of choline directly affect hippocampal network activity. Using mouse hippocampal slices we found that choline efficiently suppresses spontaneously occurring sharp wave-ripple complexes (SPW-R) and can induce gamma oscillations. In addition, choline reduces synaptic transmission between hippocampal subfields CA3 and CA1. Surprisingly, these effects are mediated by activation of both mAChRs and α7-containing nAChRs. Most nicotinic effects became only apparent after local, fast application of choline, indicating rapid desensitization kinetics of nAChRs. Effects were still present following block of choline uptake and are, therefore, likely because of direct actions of choline at the respective receptors. Together, choline turns out to be a potent regulator of patterned network activity within the hippocampus. These actions may be of importance for understanding state transitions in normal and pathologically altered neuronal networks. In this study we asked whether choline, the precursor and degradation product of acetylcholine, directly affects hippocampal network activity. Using mouse hippocampal slices we found that choline efficiently suppresses spontaneously occurring sharp wave-ripple complexes (SPW-R). In addition, choline reduces synaptic transmission between hippocampal subfields. These effects are mediated by direct activation of muscarinic as well as nicotinic cholinergic pathways. Together, choline turns out to be a potent regulator of patterned activity within hippocampal

Editor's Highlight: Perfluorooctane Sulfonate-Choline Ion Pair Formation: A Potential Mechanism Modulating Hepatic Steatosis and Oxidative Stress in Mice.

Science.gov (United States)

Zhang, Limin; Krishnan, Prasad; Ehresman, David J; Smith, Philip B; Dutta, Mainak; Bagley, Bradford D; Chang, Shu-Ching; Butenhoff, John L; Patterson, Andrew D; Peters, Jeffrey M

2016-09-01

The mechanisms underlying perfluorooctane sulfonate (PFOS)-induced steatosis remain unclear. The hypothesis that PFOS causes steatosis and other hepatic effects by forming an ion pair with choline was examined. C57BL/6 mice were fed either a control diet or a marginal methionine/choline-deficient (mMCD) diet, with and without 0.003, 0.006, or 0.012% potassium PFOS. Dietary PFOS caused a dose-dependent decrease in body weight, and increases in the relative liver weight, hepatic triglyceride concentration and serum markers of liver toxicity and oxidative stress. Some of these effects were exacerbated in mice fed the mMCD diet supplemented with 0.012% PFOS compared with those fed the control diet supplemented with 0.012% PFOS. Surprisingly, serum PFOS concentrations were higher while liver PFOS concentrations were lower in mMCD-fed mice compared with corresponding control-fed mice. To determine if supplemental dietary choline could prevent PFOS-induced hepatic effects, C57BL/6 mice were fed a control diet, or a choline supplemental diet (1.2%) with or without 0.003% PFOS. Lipidomic analysis demonstrated that PFOS caused alterations in hepatic lipid metabolism in the PFOS-fed mice compared with controls, and supplemental dietary choline prevented these PFOS-induced changes. Interestingly, dietary choline supplementation also prevented PFOS-induced oxidative damage. These studies are the first to suggest that PFOS may cause hepatic steatosis and oxidative stress by effectively reducing the choline required for hepatic VLDL production and export by forming an ion pair with choline, and suggest that choline supplementation may prevent and/or treat PFOS-induced hepatic steatosis and oxidative stress. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Selective retrograde labeling of cholinergic neurons with [3H]choline

International Nuclear Information System (INIS)

Bagnoli, P.; Beaudet, A.; Stella, M.; Cuenod, M.

1981-01-01

Evidence is presented which is consistent with a specific retrograde labeling of cholinergic neurons following [ 3 H]choline application in their zone of termination. [ 3 H]Choline injection in the rat hippocampus leads to perikaryal retrograde labeling in the ipsilateral medial septal nuclease and nucleus of the diagonal band, thus delineating an established cholinergic pathway, while only diffuse presumably anterograde labeling was observed in the lateral septum, the entorhinal cortex, and the opposite hippocampus. After [ 3 H]choline injection in the pigeon visual Wulst, only the ipsilateral thalamic relay, of all inputs, showed similar perikaryal retrograde labeling, an observation supporting the suggestion that at least some thalamo-Wulst neurons are cholinergic

Resveratrol reverses morphine-induced neuroinflammation in morphine-tolerant rats by reversal HDAC1 expression

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Ru-Yin Tsai

2016-06-01

Conclusion: Resveratrol restores the antinociceptive effect of morphine by reversing morphine infusion-induced spinal cord neuroinflammation and increase in TNFR1 expression. The reversal of the morphine-induced increase in TNFR1 expression by resveratrol is partially due to reversal of the morphine infusion-induced increase in HDAC1 expression. Resveratrol pretreatment can be used as an adjuvant in clinical pain management for patients who need long-term morphine treatment or with neuropathic pain.

A comparison of choline:urea and choline:oxalic acid deep eutectic solvents at 338 K

Science.gov (United States)

Gilmore, Mark; Moura, Leila M.; Turner, Adam H.; Swadźba-Kwaśny, Małgorzata; Callear, Samantha K.; McCune, Jade A.; Scherman, Oren A.; Holbrey, John D.

2018-05-01

1:2 choline chloride:urea and 1:1 choline chloride:oxalic acid deep eutectic solvents are compared at 338 K using liquid-phase neutron diffraction with H/D isotopic substitution to obtain differential neutron scattering cross sections and fitting of models to the experimental data using Empirical Potential Structure Refinement. In comparison to the previously reported study of choline chloride:urea at 303 K, we observed significant weakening and lengthening of choline-OH⋯Cl- and choline-OH⋯hydrogen-bond acceptor correlations.

Free radical scavenging reverses fructose-induced salt-sensitive hypertension

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Zenner ZP

2017-12-01

Full Text Available Zachary P Zenner, Kevin L Gordish, William H Beierwaltes Department of Internal Medicine, Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, MI, USA Abstract: We have previously reported that a moderate dietary supplementation of 20% fructose but not glucose leads to a salt-sensitive hypertension related to increased proximal sodium–hydrogen exchanger activity and increased renal sodium retention. We also found that while high salt increased renal nitric oxide formation, this was retarded in the presence of fructose intake. We hypothesized that at least part of the pathway leading to fructose-induced salt-sensitive hypertension could be due to fructose-induced formation of reactive oxygen species and inappropriate stimulation of renin secretion, all of which would contribute to an increase in blood pressure. We found that both 20% fructose intake and a high-salt diet stimulated 8-isoprostane excretion. The superoxide dismutase (SOD mimetic tempol significantly reduced this elevated excretion. Next, we placed rats on a high-salt diet (4% for 1 week in combination with normal rat chow or 20% fructose with or without chronic tempol administration. A fructose plus high-salt diet induced a rapid increase (15 mmHg in systolic blood pressure and reversed high salt suppression of plasma renin activity. Tempol treatment reversed the pressor response and restored high salt suppression of renin. We conclude that fructose-induced salt-sensitive hypertension is driven by increased renal reactive oxygen species formation associated with salt retention and an enhanced renin–angiotensin system. Keywords: reactive oxygen species, tempol, sodium, renin, oxidative stress

Choline Magnesium Trisalicylate

Science.gov (United States)

Choline magnesium trisalicylate is used to relieve the pain, tenderness, inflammation (swelling), and stiffness caused by arthritis and painful ... used to relieve pain and lower fever. Choline magnesium trisalicylate is in a class of nonsteroidal anti- ...

The effect of cytidine-diphosphate choline (CDP-choline) on brain lipid changes during aging

International Nuclear Information System (INIS)

De Medio, G.E.; Trovarelli, G.; Piccinin, G.L.; Porcellati, G.

1984-01-01

Lipid synthesis has been tested in vivo in different brain areas of 12-month-old male rats. Cortex, striatum, brainstem, and subcortex of brain have been examined. The cerebellum was discarded. Mixtures of (2- 3 H)glycerol and (Me- 14 C)choline were injected into the lateral ventricle of the brain as lipid precursors, and their incorporation into total lipid, water-soluble intermediates and choline-containing phospholipids was examined 1 hr after isotope injection. In another series of experiments cytidine-5'-diphosphate choline (CDP-choline) was injected intraventricularly to the aged rats 10 min before sacrifice with a simultaneous injection, and radioactivity assays were performed as above. Distribution of radioactivity content of CDP-choline among brain areas 10 min after its administration showed a noticeable enrichment of the nucleotide and water-soluble-related compounds in the examined areas, but to a lesser degree in the cerebral cortex. The incorporation of labelled glycerol, which is severely depressed in aged rats in all four areas [Gaiti et al, 1982, 1983], was increased only in the cortex, and apparently decreased in the other areas. This last result is probably due to a dilution effect brought about by the administered cold CDP-choline upon the ( 14 C)-containing water-soluble metabolites. As a consequence, the ( 3 H)/( 14 C) ratio in total lipid and in isolated phosphatidylcholine and choline plasmalogen increased after CDP-choline treatment

The efflux of choline from nerve cells: mediation by ionic gradients and functional exchange of choline from glia to neurons

International Nuclear Information System (INIS)

Hoffmann, D.; Ferret, B.; Massarelli, R.; Mykita, S.

1986-01-01

This paper analyzes the relationship between ions and the efflux of choline, and suggests the possibility of a balance effect for choline fluxes which is produced and maintained by ioinic gradients. It is also suggested that glial cells may actively exchange choline with neurons during nerve actively exchange choline with neurons during nerve activity, and that they may function as a choline reservoir for neuronal needs. The study shows that neurons and glial cells spontaneously discharge choline into the incubation medium. The exiting choline is essentially of free origin, as can be seen in an illustration provided. Neurons and glial cells had been prelabelled with ( 14 C) choline overnight, and labelled for 15 min with tritium-choline. The higher amount of tritium-choline exiting the cells indicates that it is the freshly labelled choline which is preferentially released. The remaining of ( 14 C) - choline exiting the cells corresponds to the free choline of phospholipid origin which amounts to about one third of the total free choline content

Reversible cold-induced abnormalities in myocardial perfusion and function in systemic sclerosis

International Nuclear Information System (INIS)

Alexander, E.L.; Firestein, G.S.; Weiss, J.L.; Heuser, R.R.; Leitl, G.; Wagner, H.N. Jr.; Brinker, J.A.; Ciuffo, A.A.; Becker, L.C.

1986-01-01

The effects of peripheral cold exposure on myocardial perfusion and function were studied in 13 patients with scleroderma without clinically evident myocardial disease. Ten patients had at least one transient, cold-induced, myocardial perfusion defect visualized by thallium-201 scintigraphy, and 12 had reversible, cold-induced, segmental left ventricular hypokinesis by two-dimensional echocardiography. The 10 patients with transient perfusion defects all had anatomically corresponding ventricular wall motion abnormalities. No one in either of two control groups (9 normal volunteers and 7 patients with chest pain and normal coronary arteriograms) had cold-induced abnormalities. This study is the first to show the simultaneous occurrence of cold-induced abnormalities in myocardial perfusion and function in patients with scleroderma. The results suggest that cold exposure in such patients may elicit transient reflex coronary vasoconstriction resulting in reversible myocardial ischemia and dysfunction. Chronic recurrent episodes of coronary spasm may lead to focal myocardial fibrosis

Dietary Reference Values for choline

DEFF Research Database (Denmark)

Sjödin, Anders Mikael

2016-01-01

Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) derives Dietary Reference Values (DRVs) for choline. In this Opinion, the Panel considers dietary choline including choline compounds (e.g. glycerophosphocholine, phosphocholine...

Choline transport via choline transporter-like protein 1 in conditionally immortalized rat syncytiotrophoblast cell lines TR-TBT.

Science.gov (United States)

Lee, N-Y; Choi, H-M; Kang, Y-S

2009-04-01

Choline is an essential nutrient for phospholipids and acetylcholine biosynthesis in normal development of fetus. In the present study, we investigated the functional characteristics of choline transport system and inhibitory effect of cationic drugs on choline transport in rat conditionally immortalized syncytiotrophoblast cell line (TR-TBT). Choline transport was weakly Na(+) dependent and significantly influenced by extracellular pH and by membrane depolarization. The transport process of choline is saturable with Michaelis-Menten constants (K(m)) of 68microM and 130microM in TR-TBT 18d-1 and TR-TBT 18d-2 respectively. Choline uptake in the cells was inhibited by unlabeled choline and hemicholinium-3 as well as various organic cations including guanidine, amiloride and acetylcholine. However, the prototypical organic cation tetraethylammonium and cimetidine showed very little inhibitory effect of choline uptake in TR-TBT cells. RT-PCR revealed that choline transporter-like protein 1 (CTL1) and organic cation transporter 2 (OCT2) are expressed in TR-TBT cells. The transport properties of choline in TR-TBT cells were similar or identical to that of CTL1 but not OCT2. CTL1 was also detected in human placenta. In addition, several cationic drugs such as diphenhydramine and verapamil competitively inhibited choline uptake in TR-TBT 18d-1 with K(i) of 115microM and 55microM, respectively. Our results suggest that choline transport system, which has intermediate affinity and weakly Na(+) dependent, in TR-TBT seems to occur through a CTL1 and this system may have relevance with the uptake of pharmacologically important organic cation drugs.

Reversible air-induced optical and electrical modulation of methylammonium lead bromide (MAPbBr3) single crystals

Science.gov (United States)

Zhang, Huotian; Liu, Yiting; Lu, Haizhou; Deng, Wan; Yang, Kang; Deng, Zunyi; Zhang, Xingmin; Yuan, Sijian; Wang, Jiao; Niu, Jiaxin; Zhang, Xiaolei; Jin, Qingyuan; Feng, Hongjian; Zhan, Yiqiang; Zheng, Lirong

2017-09-01

The photoluminescence (PL) variations of organic-inorganic hybrid lead halide perovskites in different atmospheres are well documented, while the fundamental mechanism still lacks comprehensive understandings. This study reports the reversible optical and electrical properties of methylammonium lead bromide (MAPbBr3 or CH3NH3PbBr3) single crystals caused by air infiltration. With the change in the surrounding atmosphere from air to vacuum, the PL intensity of perovskite single crystals decreases, while the conductivity increases. By means of first-principles computational studies, the shallow trap states are considered as key elements in PL and conductivity changes. These results have important implications for the characterization and application of organic-inorganic hybrid lead halide perovskites in vacuum.

Plasma immune protein analysis in the orange-spotted grouper Epinephelus coioides: Evidence for altered expressions of immune factors associated with a choline-supplemented diet.

Science.gov (United States)

Shiu, Ya-Li; Chiu, Kuo-Hsun; Huynh, Truong-Giang; Liu, Ping-Chung; Liu, Chun-Hung

2017-06-01

This study aimed to unravel the regulatory roles of choline in activating immune responses and disease resistance of the orange-spotted grouper Epinephelus coioides. Fish were fed a choline-supplemented diet at 1 g kg -1 of feed for 30 days. Fish fed a fish meal basal diet without choline-supplement served as controls. At the end of the feeding trial, fish were challenged with Vibrio alginolyticus. Meanwhile, plasma proteomics of fish in each group were also evaluated by two-dimensional gel electrophoresis (2-DE), and differentially expressed proteins were identified by tandem mass spectrophotometry (MS/MS), then a Western blot analysis or real-time polymerase chain reaction was used to confirm differential expressions of immune-enhancing proteins. Results showed that choline significantly increased survival of E. coioides 48 days after being injected with V. alginolyticus. From maps of plasma proteins, a comparative analysis between the control and choline groups revealed that 111 spots matched, with 26 altered expression spots in the choline group. Of these 26 spots, 16 were upregulated and 10 downregulated. After protein identification by reverse-phase nano-high-performance liquid chromatography-electrospray ionization MS/MS analysis, eight of 26 proteins were found to be immune-related proteins, all of which were upregulated, including complement 3 (C3), alpha-2-macroglobulin-P-like isoform (A2M), fibrinogen beta chain precursor (FBG), and immunoglobulin heavy constant mu (Ighm) proteins. Expression of the A2M protein and A2M enzyme activity in plasma of fish fed choline significantly increased compared to the control group. Additionally, A2M messenger (m)RNA transcripts were also upregulated in the liver and kidneys. Significantly higher C3 expressions at both the mRNA and protein levels were detected in the liver of fish in the choline group. Moreover, FBG gene expressions in the liver and kidneys significantly increased, while Ighm increased in the

A brief history of choline

Science.gov (United States)

Zeisel, Steven H.

2015-01-01

In 1850, Theodore Gobley, working in Paris, described a substance “lecithine”, which he named after the Greek “lekithos” for egg yolk. Adolph Strecker noted in 1862 that when lecithin from bile was heated, it generated a new nitrogenous chemical that he named “choline”. Three years later, Oscar Liebreich identified a new substance, “neurine”, in the brain. After a period of confusion, neurine and choline were found to be the same molecule, and the name choline was adapted. Lecithin was eventually characterized chemically as being phosphatidylcholine. In 1954, Eugene Kennedy described the cytidine 5-dihphosphocholine pathway by which choline is incorporated into phosphatidylcholine. A second route, the phosphatidylethanolamine-N-methyltransferase pathway, was identified by Jon Bremer and David Greenberg in 1960. The role of choline as part of the neurotransmitter acetylcholine was established by Otto Loewi and Henry Dale. Working in the 1930s at the University of Toronto, Charles Best showed that choline prevented fatty liver in dogs and rats. The importance of choline as an essential nutrient for human health was determined in the 1990s through controlled feeding studies in humans. Recently, an understanding of the role of genetic variation in setting the dietary requirement for choline in people is being unraveled. PMID:23183298

Molecular Effects of Doxorubicin on Choline Metabolism in Breast Cancer

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Menglin Cheng

2017-08-01

Full Text Available Abnormal choline phospholipid metabolism is a hallmark of cancer. The magnetic resonance spectroscopy (MRS detected total choline (tCho signal can serve as an early noninvasive imaging biomarker of chemotherapy response in breast cancer. We have quantified the individual components of the tCho signal, glycerophosphocholine (GPC, phosphocholine (PC and free choline (Cho, before and after treatment with the commonly used chemotherapeutic drug doxorubicin in weakly metastatic human MCF7 and triple-negative human MDA-MB-231 breast cancer cells. While the tCho concentration did not change following doxorubicin treatment, GPC significantly increased and PC decreased. Of the two phosphatidylcholine-specific PLD enzymes, only PLD1, but not PLD2, mRNA was down-regulated by doxorubicin treatment. For the two reported genes encoding GPC phosphodiesterase, the mRNA of GDPD6, but not GDPD5, decreased following doxorubicin treatment. mRNA levels of choline kinase α (ChKα, which converts Cho to PC, were reduced following doxorubicin treatment. PLD1 and ChKα protein levels decreased following doxorubicin treatment in a concentration dependent manner. Treatment with the PLD1 specific inhibitor VU0155069 sensitized MCF7 and MDA-MB-231 breast cancer cells to doxorubicin-induced cytotoxicity. Low concentrations of 100 nM of doxorubicin increased MDA-MB-231 cell migration. GDPD6, but not PLD1 or ChKα, silencing by siRNA abolished doxorubicin-induced breast cancer cell migration. Doxorubicin induced GPC increase and PC decrease are caused by reductions in PLD1, GDPD6, and ChKα mRNA and protein expression. We have shown that silencing or inhibiting these genes/proteins can promote drug effectiveness and reduce adverse drug effects. Our findings emphasize the importance of detecting PC and GPC individually.

Choline-PET/CT for imaging prostate cancer; Cholin-PET/CT zur Bildgebung des Prostatakarzinoms

Energy Technology Data Exchange (ETDEWEB)

Krause, Bernd Joachim [Klinik- und Poliklinik fuer Nuklearmedizin, Klinikum rechts der Isar, Technische Univ. Muenchen (Germany); Treiber, U.; Schwarzenboeck, S.; Souvatzoglou, M. [Klinik fuer Urologie, Klinikum rechts der Isar, Technische Univ. Muenchen (Germany)

2010-09-15

PET and PET/CT using [{sup 11}C]- and [{sup 18}F]-labelled choline derivatives are increasingly being used for imaging of prostate cancer. The value of PET and PET/CT with [{sup 11}C]- and [{sup 18}F]-labelled choline derivates in biochemical recurrence of prostate cancer has been examined in many studies and demonstrates an increasing importance. Primary prostate cancer can be detected with moderate sensitivity using PET and PET/CT using [{sup 11}C]- and [{sup 18}F]-labelled choline derivatives - the differentiation between benign prostatic hyperplasia, prostatitis or high-grade intraepithelial neoplasia (HGPIN) is not always possible. At the present time [{sup 11}C]choline PET/CT is not recommended in the primary setting but may be utilized in clinically suspected prostate cancer with repeatedly negative prostate biopsies, in preparation of a focused re-biopsy. Promising results have been obtained for the use of PET and PET/CT with [{sup 11}C]- and [{sup 18}F]-labelled choline derivates in patients with biochemical recurrence. The detection rate of choline PET and PET/CT for local, regional, and distant recurrence in patients with a biochemical recurrence shows a linear correlation with PSA values at the time of imaging and reaches about 75% in patients with PSA > 3 ng/mL. At PSA values below 1 ng/mL, the recurrence can be diagnosed with choline PET/CT in approximately 1/3 of the patients. PET and PET/CT with [{sup 11}C]- and [{sup 18}F]choline derivates can be helpful for choosing a therapeutic strategy in the sense of an individualized treatment: since an early diagnosis of recurrence is crucial to the choice of optimal treatment. The localization of the site of recurrence - local recurrence, lymph node metastasis or systemic dissemination - has important influence on the therapy regimen. (orig.)

Over-expressing the soluble gp130-Fc does not ameliorate methionine and choline deficient diet-induced non alcoholic steatohepatitis in mice.

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Helene L Kammoun

Full Text Available Non-alcoholic steatohepatitis (NASH is a liver disease with the potential to lead to cirrhosis and hepatocellular carcinoma. Interleukin-6 (IL-6 has been implicated in the pathogenesis of NASH, with the so-called IL-6 'trans-signaling' cascade being responsible for the pro-inflammatory actions of this cytokine. We aimed to block IL-6 'trans-signaling', using a transgenic mouse that overexpresses human soluble glycoprotein130 (sgp130Fc Tg mice fed a commonly used dietary model of inducing NASH (methionine and choline deficient-diet; MCD diet and hypothesized that markers of NASH would be ameliorated in such mice. Sgp130Fc Tg and littermate control mice were fed a MCD or control diet for 4 weeks. The MCD diet induced many hallmarks of NASH including hepatomegaly, steatosis, and liver inflammation. However, in contrast with other mouse models and, indeed, human NASH, the MCD diet model did not increase the mRNA or protein expression of IL-6. Not surprisingly, therefore, markers of MCD diet-induced NASH were unaffected by sgp130Fc transgenic expression. While the MCD diet model induces many pathophysiological markers of NASH, it does not induce increased IL-6 expression in the liver, a key hallmark of human NASH. We, therefore, caution the use of the MCD diet as a viable mouse model of NASH.

Effects of CDP-choline on neurologic deficits and cerebral glucose metabolism in a rat model of cerebral ischemia

Energy Technology Data Exchange (ETDEWEB)

Kakihana, M.; Fukuda, N.; Suno, M.; Nagaoka, A.

1988-02-01

The effects of cytidine 5'-diphosphocholine (CDP-choline) on neurologic deficits and cerebral glucose metabolism were studied in a rat model of transient cerebral ischemia. Cerebral ischemia was induced by occluding both common carotid arteries for 20 or 30 minutes 24 hours after the vertebral arteries were permanently occluded by electrocautery. CDP-choline was administered intraperitoneally twice daily for 4 days after reestablishing carotid blood flow. CDP-choline at two dosages (50 and 250 mg/kg) shortened the time required for recovery of spontaneous motor activity in a dose-related manner; recovery time was measured early after reperfusion. Neurologic signs were observed for 10 days. High-dose CDP-choline improved neurologic signs in the rats within 20-30 minutes of ischemia. When cerebral glucose metabolism was assessed on Day 4, increases in the levels of glucose and pyruvate were accompanied by decreases in the synthesis of labeled acetylcholine from uniformly labeled (/sup 14/C)glucose measured in the cerebral cortex of rats with 30 minutes of ischemia. High-dose CDP-choline also attenuated changes in these variables. CDP-(1,2-/sup 14/C)choline injected intravenously 10 minutes after reperfusion was used for membrane lipid biosynthesis. These results indicate that CDP-choline has beneficial effects on brain dysfunction induced by cerebral ischemia, which may be due in part to the restorative effects of CDP-choline on disturbed cerebral glucose metabolism, probably by stimulating phospholipid biosynthesis.

Effects of CDP-choline on neurologic deficits and cerebral glucose metabolism in a rat model of cerebral ischemia

International Nuclear Information System (INIS)

Kakihana, M.; Fukuda, N.; Suno, M.; Nagaoka, A.

1988-01-01

The effects of cytidine 5'-diphosphocholine (CDP-choline) on neurologic deficits and cerebral glucose metabolism were studied in a rat model of transient cerebral ischemia. Cerebral ischemia was induced by occluding both common carotid arteries for 20 or 30 minutes 24 hours after the vertebral arteries were permanently occluded by electrocautery. CDP-choline was administered intraperitoneally twice daily for 4 days after reestablishing carotid blood flow. CDP-choline at two dosages (50 and 250 mg/kg) shortened the time required for recovery of spontaneous motor activity in a dose-related manner; recovery time was measured early after reperfusion. Neurologic signs were observed for 10 days. High-dose CDP-choline improved neurologic signs in the rats within 20-30 minutes of ischemia. When cerebral glucose metabolism was assessed on Day 4, increases in the levels of glucose and pyruvate were accompanied by decreases in the synthesis of labeled acetylcholine from uniformly labeled [ 14 C]glucose measured in the cerebral cortex of rats with 30 minutes of ischemia. High-dose CDP-choline also attenuated changes in these variables. CDP-[1,2- 14 C]choline injected intravenously 10 minutes after reperfusion was used for membrane lipid biosynthesis. These results indicate that CDP-choline has beneficial effects on brain dysfunction induced by cerebral ischemia, which may be due in part to the restorative effects of CDP-choline on disturbed cerebral glucose metabolism, probably by stimulating phospholipid biosynthesis

A modified choline-deficient, ethionine-supplemented diet reduces morbidity and retains a liver progenitor cell response in mice

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Adam M. Passman

2015-12-01

Full Text Available The choline-deficient, ethionine-supplemented (CDE dietary model induces chronic liver damage, and stimulates liver progenitor cell (LPC-mediated repair. Long-term CDE administration leads to hepatocellular carcinoma in rodents and lineage-tracing studies show that LPCs differentiate into functional hepatocytes in this model. The CDE diet was first modified for mice by our laboratory by separately administering choline-deficient chow and ethionine in the drinking water (CD+E diet. Although this CD+E diet is widely used, concerns with variability in weight loss, morbidity, mortality and LPC response have been raised by researchers who have adopted this model. We propose that these inconsistencies are due to differential consumption of chow and ethionine in the drinking water, and that incorporating ethionine in the choline-deficient chow, and altering the strength, will achieve better outcomes. Therefore, C57Bl/6 mice, 5 and 6 weeks of age, were fed an all-inclusive CDE diet of various strengths (67% to 100% for 3 weeks. The LPC response was quantitated and cell lines were derived. We found that animal survival, LPC response and liver damage are correlated with CDE diet strength. The 67% and 75% CDE diet administered to mice older than 5 weeks and greater than 18 g provides a consistent and acceptable level of animal welfare and induces a substantial LPC response, permitting their isolation and establishment of cell lines. This study shows that an all-inclusive CDE diet for mice reproducibly induces an LPC response conducive to in vivo studies and isolation, whilst minimizing morbidity and mortality.

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.

Teucrium polium reversed the MCD diet-induced liver injury in rats.

Science.gov (United States)

Amini, Rahim; Yazdanparast, Razieh; Aghazadeh, Safiyeh; Ghaffari, Seyed H

2011-09-01

In the present study, we evaluated the ability of Teucrium polium ethyl acetate fraction, with high antioxidant activity, in the treatment of nonalcoholic steatohepatitis (NASH) in rats and its possible effect on factors involved in pathogenesis of the disease. To induce NASH, a methionine and choline deficient (MCD) diet was given to N-Mary rats for 8 weeks. After NASH development, MCD-fed rats were divided into 2 groups: NASH group that received MCD diet and NASH + T group which was fed MCD diet plus ethyl acetate fraction of T. polium orally for 3 weeks. Histopathological evaluations revealed that treatment with the extract has abated the severity of NASH among the MCD-fed rats. In addition, the fraction reduced the elevated levels of hepatic tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β) gene expression and also the elevated level of malondialdehyde (MDA). In addition, the extract increased the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and enhanced the level of hepatic glutathione (GSH). Moreover, the fraction treatments lowered caspase-3 level and the phosphorylated form of C-Jun N-terminal kinase (JNK) and augmented the phosphorylated level of extracellular regulated kinase1/2 (ERK1/2). These results indicate that the ethyl acetate fraction of T. poium effectively reversed NASH, mainly due to its strong antioxidant and anti-inflammatory properties.

21 CFR 582.5252 - Choline chloride.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Choline chloride. 582.5252 Section 582.5252 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5252 Choline chloride. (a) Product. Choline chloride. (b) Conditions of use. This...

Light-induced defects in hybrid lead halide perovskite

Science.gov (United States)

Sharia, Onise; Schneider, William

One of the main challenges facing organohalide perovskites for solar application is stability. Solar cells must last decades to be economically viable alternatives to traditional energy sources. While some causes of instability can be avoided through engineering, light-induced defects can be fundamentally limiting factor for practical application of the material. Light creates large numbers of electron and hole pairs that can contribute to degradation processes. Using ab initio theoretical methods, we systematically explore first steps of light induced defect formation in methyl ammonium lead iodide, MAPbI3. In particular, we study charged and neutral Frenkel pair formation involving Pb and I atoms. We find that most of the defects, except negatively charged Pb Frenkel pairs, are reversible, and thus most do not lead to degradation. Negative Pb defects create a mid-gap state and localize the conduction band electron. A minimum energy path study shows that, once the first defect is created, Pb atoms migrate relatively fast. The defects have two detrimental effects on the material. First, they create charge traps below the conduction band. Second, they can lead to degradation of the material by forming Pb clusters.

Combinational chelation therapy abrogates lead-induced neurodegeneration in rats

International Nuclear Information System (INIS)

Pachauri, Vidhu; Saxena, Geetu; Mehta, Ashish; Mishra, Deepshikha; Flora, Swaran J.S.

2009-01-01

Lead, a ubiquitous and potent neurotoxicant causes oxidative stress which leads to numerous neurobehavioral and physiological alterations. The ability of lead to bind sulfhydryl groups or compete with calcium could be one of the reasons for its debilitating effects. In the present study, we addressed: i) if chelation therapy could circumvent the altered oxidative stress and prevent neuronal apoptosis in chronic lead-intoxicated rats, ii) whether chelation therapy could reverse biochemical and behavioral changes, and iii) if mono or combinational therapy with captopril (an antioxidant) and thiol chelating agents (DMSA/MiADMSA) is more effective than individual thiol chelator in lead-exposed rats. Results indicated that lead caused a significant increase in reactive oxygen species, nitric oxide, and intracellular free calcium levels along with altered behavioral abnormalities in locomotor activity, exploratory behavior, learning, and memory that were supported by changes in neurotransmitter levels. A fall in membrane potential, release of cytochrome c, and DNA damage indicated mitochondrial-dependent apoptosis. Most of these alterations showed significant recovery following combined therapy with captopril with MiADMSA and to a smaller extend with captopril + DMSA over monotherapy with these chelators. It could be concluded from our present results that co-administration of a potent antioxidant (like captopril) might be a better treatment protocol than monotherapy to counter lead-induced oxidative stress. The major highlight of the work is an interesting experimental evidence of the efficacy of combinational therapy using an antioxidant with a thiol chelator in reversing neurological dystrophy caused due to chronic lead exposure in rats.

A choline-deficient diet exacerbates fatty liver but attenuates insulin resistance and glucose intolerance in mice fed a high-fat diet.

Science.gov (United States)

Raubenheimer, Peter J; Nyirenda, Moffat J; Walker, Brian R

2006-07-01

Liver fat accumulation is proposed to link obesity and insulin resistance. To dissect the role of liver fat in the insulin resistance of diet-induced obesity, we altered liver fat using a choline-deficient diet. C57Bl/6 mice were fed a low-fat (10% of calories) or high-fat (45% of calories) diet for 8 weeks; during the final 4 weeks, diets were either choline deficient or choline supplemented. In choline replete animals, high-fat feeding induced weight gain, elevated liver triglycerides (171%), hyperinsulinemia, and glucose intolerance. Choline deficiency did not affect body or adipose depot weights but amplified liver fat accumulation with high-fat diet (281%, P insulin (from 983 +/- 175 to 433 +/- 36 pmol/l, P phosphatidylcholine synthesis and of enzymes involved in free fatty acid esterification, without affecting those of de novo lipogenesis or fatty acid oxidation. We conclude that liver fat accumulation per se does not cause insulin resistance during high-fat feeding and that choline deficiency may shunt potentially toxic free fatty acids toward innocuous storage triglyceride in the liver.

Restoration of hippocampal growth hormone reverses stress-induced hippocampal impairment

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Caitlin M. Vander Weele

2013-06-01

Full Text Available Though growth hormone (GH is synthesized by hippocampal neurons, where its expression is influenced by stress exposure, its function is poorly characterized. Here, we show that a regimen of chronic stress that impairs hippocampal function in rats also leads to a profound decrease in hippocampal GH levels. Restoration of hippocampal GH in the dorsal hippocampus via viral-mediated gene transfer completely reversed stress-related impairment of two hippocampus-dependent behavioral tasks, auditory trace fear conditioning and contextual fear conditioning, without affecting hippocampal function in unstressed control rats. GH overexpression reversed stress-induced decrements in both fear acquisition and long-term fear memory. These results suggest that loss of hippocampal GH contributes to hippocampal dysfunction following prolonged stress and demonstrate that restoring hippocampal GH levels following stress can promote stress resilience.

Choline Deficiency Causes Colonic Type II Natural Killer T (NKT) Cell Loss and Alleviates Murine Colitis under Type I NKT Cell Deficiency.

Science.gov (United States)

Sagami, Shintaro; Ueno, Yoshitaka; Tanaka, Shinji; Fujita, Akira; Niitsu, Hiroaki; Hayashi, Ryohei; Hyogo, Hideyuki; Hinoi, Takao; Kitadai, Yasuhiko; Chayama, Kazuaki

2017-01-01

Serum levels of choline and its derivatives are lower in patients with inflammatory bowel disease (IBD) than in healthy individuals. However, the effect of choline deficiency on the severity of colitis has not been investigated. In the present study, we investigated the role of choline deficiency in dextran sulfate sodium (DSS)-induced colitis in mice. Methionine-choline-deficient (MCD) diet lowered the levels of type II natural killer T (NKT) cells in the colonic lamina propria, peritoneal cavity, and mesenteric lymph nodes, and increased the levels of type II NKT cells in the livers of wild-type B6 mice compared with that in mice fed a control (CTR) diet. The gene expression pattern of the chemokine receptor CXCR6, which promotes NKT cell accumulation, varied between colon and liver in a manner dependent on the changes in the type II NKT cell levels. To examine the role of type II NKT cells in colitis under choline-deficient conditions, we assessed the severity of DSS-induced colitis in type I NKT cell-deficient (Jα18-/-) or type I and type II NKT cell-deficient (CD1d-/-) mice fed the MCD or CTR diets. The MCD diet led to amelioration of inflammation, decreases in interferon (IFN)-γ and interleukin (IL)-4 secretion, and a decrease in the number of IFN-γ and IL-4-producing NKT cells in Jα18-/- mice but not in CD1d-/- mice. Finally, adaptive transfer of lymphocytes with type II NKT cells exacerbated DSS-induced colitis in Jα18-/- mice with MCD diet. These results suggest that choline deficiency causes proinflammatory type II NKT cell loss and alleviates DSS-induced colitis. Thus, inflammation in DSS-induced colitis under choline deficiency is caused by type II NKT cell-dependent mechanisms, including decreased type II NKT cell and proinflammatory cytokine levels.

A modified choline-deficient, ethionine-supplemented diet reduces morbidity and retains a liver progenitor cell response in mice.

Science.gov (United States)

Passman, Adam M; Strauss, Robyn P; McSpadden, Sarah B; Finch-Edmondson, Megan L; Woo, Ken H; Diepeveen, Luke A; London, Roslyn; Callus, Bernard A; Yeoh, George C

2015-12-01

The choline-deficient, ethionine-supplemented (CDE) dietary model induces chronic liver damage, and stimulates liver progenitor cell (LPC)-mediated repair. Long-term CDE administration leads to hepatocellular carcinoma in rodents and lineage-tracing studies show that LPCs differentiate into functional hepatocytes in this model. The CDE diet was first modified for mice by our laboratory by separately administering choline-deficient chow and ethionine in the drinking water (CD+E diet). Although this CD+E diet is widely used, concerns with variability in weight loss, morbidity, mortality and LPC response have been raised by researchers who have adopted this model. We propose that these inconsistencies are due to differential consumption of chow and ethionine in the drinking water, and that incorporating ethionine in the choline-deficient chow, and altering the strength, will achieve better outcomes. Therefore, C57Bl/6 mice, 5 and 6 weeks of age, were fed an all-inclusive CDE diet of various strengths (67% to 100%) for 3 weeks. The LPC response was quantitated and cell lines were derived. We found that animal survival, LPC response and liver damage are correlated with CDE diet strength. The 67% and 75% CDE diet administered to mice older than 5 weeks and greater than 18 g provides a consistent and acceptable level of animal welfare and induces a substantial LPC response, permitting their isolation and establishment of cell lines. This study shows that an all-inclusive CDE diet for mice reproducibly induces an LPC response conducive to in vivo studies and isolation, whilst minimizing morbidity and mortality. © 2015. Published by The Company of Biologists Ltd.

Choline and Choline Metabolite Patterns and Associations in Blood and Milk during Lactation in Dairy Cows

Science.gov (United States)

Artegoitia, Virginia M.; Middleton, Jesse L.; Harte, Federico M.; Campagna, Shawn R.; de Veth, Michael J.

2014-01-01

Milk and dairy products are an important source of choline, a nutrient essential for human health. Infant formula derived from bovine milk contains a number of metabolic forms of choline, all contribute to the growth and development of the newborn. At present, little is known about the factors that influence the concentrations of choline metabolites in milk. The objectives of this study were to characterize and then evaluate associations for choline and its metabolites in blood and milk through the first 37 weeks of lactation in the dairy cow. Milk and blood samples from twelve Holstein cows were collected in early, mid and late lactation and analyzed for acetylcholine, free choline, betaine, glycerophosphocholine, lysophosphatidylcholine, phosphatidylcholine, phosphocholine and sphingomyelin using hydrophilic interaction liquid chromatography-tandem mass spectrometry, and quantified using stable isotope-labeled internal standards. Total choline concentration in plasma, which was almost entirely phosphatidylcholine, increased 10-times from early to late lactation (1305 to 13,535 µmol/L). In milk, phosphocholine was the main metabolite in early lactation (492 µmol/L), which is a similar concentration to that found in human milk, however, phosphocholine concentration decreased exponentially through lactation to 43 µmol/L in late lactation. In contrast, phosphatidylcholine was the main metabolite in mid and late lactation (188 µmol/L and 659 µmol/L, respectively), with the increase through lactation positively correlated with phosphatidylcholine in plasma (R 2 = 0.78). Unlike previously reported with human milk we found no correlation between plasma free choline concentration and milk choline metabolites. The changes in pattern of phosphocholine and phosphatidylcholine in milk through lactation observed in the bovine suggests that it is possible to manufacture infant formula that more closely matches these metabolites profile in human milk. PMID:25157578

Choline and choline metabolite patterns and associations in blood and milk during lactation in dairy cows.

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Virginia M Artegoitia

Full Text Available Milk and dairy products are an important source of choline, a nutrient essential for human health. Infant formula derived from bovine milk contains a number of metabolic forms of choline, all contribute to the growth and development of the newborn. At present, little is known about the factors that influence the concentrations of choline metabolites in milk. The objectives of this study were to characterize and then evaluate associations for choline and its metabolites in blood and milk through the first 37 weeks of lactation in the dairy cow. Milk and blood samples from twelve Holstein cows were collected in early, mid and late lactation and analyzed for acetylcholine, free choline, betaine, glycerophosphocholine, lysophosphatidylcholine, phosphatidylcholine, phosphocholine and sphingomyelin using hydrophilic interaction liquid chromatography-tandem mass spectrometry, and quantified using stable isotope-labeled internal standards. Total choline concentration in plasma, which was almost entirely phosphatidylcholine, increased 10-times from early to late lactation (1305 to 13,535 µmol/L. In milk, phosphocholine was the main metabolite in early lactation (492 µmol/L, which is a similar concentration to that found in human milk, however, phosphocholine concentration decreased exponentially through lactation to 43 µmol/L in late lactation. In contrast, phosphatidylcholine was the main metabolite in mid and late lactation (188 µmol/L and 659 µmol/L, respectively, with the increase through lactation positively correlated with phosphatidylcholine in plasma (R2 = 0.78. Unlike previously reported with human milk we found no correlation between plasma free choline concentration and milk choline metabolites. The changes in pattern of phosphocholine and phosphatidylcholine in milk through lactation observed in the bovine suggests that it is possible to manufacture infant formula that more closely matches these metabolites profile in human milk.

Lipoic acid in combination with a chelator ameliorates lead-induced peroxidative damages in rat kidney

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Sivaprasad, R.; Nagaraj, M.; Varalakshmi, P. [Department of Medical Biochemistry, University of Madras (Taramani), Chennai 600 113 (India)

2002-08-01

The deleterious effect of lead has been attributed to lead-induced oxidative stress with the consequence of lipid peroxidation. The present study was designed to investigate the combined effect of DL-{alpha}-lipoic acid (LA) and meso-2,3-dimercaptosuccinic acid (DMSA) on lead-induced peroxidative damages in rat kidney. The increase in peroxidated lipids in lead-poisoned rats was accompanied by alterations in antioxidant defence systems. Lead acetate (Pb, 0.2%) was administered in drinking water for 5 weeks to induce lead toxicity. LA (25 mg/kg body weight per day i.p) and DMSA (20 mg/kg body weight per day i.p) were administered individually and also in combination during the sixth week. Nephrotoxic damage was evident from decreases in the activities of {gamma}-glutamyl transferase and N-acetyl {beta}-D-glucosaminidase, which were reversed upon combined treatment with LA and DMSA. Rats subjected to lead intoxication showed a decline in the thiol capacity of the cell, accompanied by high malondialdehyde levels along with lowered activities of catalase, superoxide dismutase, glutathione peroxidase and glutathione metabolizing enzymes (glutathione reductase, glucose-6-phosphate dehydrogenase, glutathione-S-transferase). Supplementation with LA as a sole agent showed considerable changes over oxidative stress parameters. The study has highlighted the combined effect of both drugs as being more effective in reversing oxidative damage by bringing about an improvement in the reductive status of the cell. (orig.)

Choline acetyltransferase expression during periods of behavioral activity and across natural sleep-wake states in the basal forebrain.

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Greco, M A; McCarley, R W; Shiromani, P J

1999-01-01

The present study examined whether the expression of the messenger RNA encoding the protein responsible for acetylcholine synthesis is associated with sleep-wakefulness. Choline acetyltransferase messenger RNA levels were analysed using a semi-quantitative assay in which reverse transcription was coupled to complementary DNA amplification using the polymerase chain reaction. To examine the relationship between steady-state messenger RNA and behavioral activity, rats were killed during the day (4.00 p.m.) or night (4.00 a.m.), and tissue from the vertical and horizontal limbs of the diagonal bands of Broca was analysed. Choline acetyltransferase messenger RNA levels were higher during the day than during the night. The second study examined more closely the association between choline acetyltransferase messenger RNA levels and individual bouts of wakefulness, slow-wave sleep or rapid eye movement sleep. Choline acetyltransferase messenger RNA levels were low during wakefulness, intermediate in slow-wave sleep and high during rapid eye movement sleep. In contrast, protein activity, measured at a projection site of cholinergic neurons of the basal forebrain, was higher during wakefulness than during sleep. These findings suggest that choline acetyltransferase protein and messenger RNA levels exhibit an inverse relationship during sleep and wakefulness. The increased messenger RNA expression during sleep is consistent with a restorative function of sleep.

Risperidone-induced reversible neutropenia.

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Kattalai Kailasam, Vasanth; Chima, Victoria; Nnamdi, Uchechukwu; Sharma, Kavita; Shah, Kairav

2017-01-01

This case report presents a 44-year-old man with a history of schizophrenia who developed neutropenia on risperidone therapy. The patient's laboratory reports showed a gradual decline of leukocytes and neutrophils after resolution and rechallenging. This was reversed with the discontinuation of risperidone and by switching to olanzapine. In this case report, we also discuss the updated evidence base for management of risperidone-induced neutropenia.

No evidence for role of extracellular choline-acetyltransferase in generation of gamma oscillations in rat hippocampal slices in vitro.

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Hollnagel, J O; ul Haq, R; Behrens, C J; Maslarova, A; Mody, I; Heinemann, U

2015-01-22

Acetylcholine (ACh) is well known to induce persistent γ-oscillations in the hippocampus when applied together with physostigmine, an inhibitor of the ACh degrading enzyme acetylcholinesterase (AChE). Here we report that physostigmine alone can also dose-dependently induce γ-oscillations in rat hippocampal slices. We hypothesized that this effect was due to the presence of choline in the extracellular space and that this choline is taken up into cholinergic fibers where it is converted to ACh by the enzyme choline-acetyltransferase (ChAT). Release of ACh from cholinergic fibers in turn may then induce γ-oscillations. We therefore tested the effects of the choline uptake inhibitor hemicholinium-3 (HC-3) on persistent γ-oscillations either induced by physostigmine alone or by co-application of ACh and physostigmine. We found that HC-3 itself did not induce γ-oscillations and also did not prevent physostigmine-induced γ-oscillation while washout of physostigmine and ACh-induced γ-oscillations was accelerated. It was recently reported that ChAT might also be present in the extracellular space (Vijayaraghavan et al., 2013). Here we show that the effect of physostigmine was prevented by the ChAT inhibitor (2-benzoylethyl)-trimethylammonium iodide (BETA) which could indicate extracellular synthesis of ACh. However, when we tested for effects of extracellularly applied acetyl-CoA, a substrate of ChAT for synthesis of ACh, physostigmine-induced γ-oscillations were attenuated. Together, these findings do not support the idea that ACh can be synthesized by an extracellularly located ChAT. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Prenatal choline supplementation mitigates behavioral alterations associated with prenatal alcohol exposure in rats.

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Thomas, Jennifer D; Idrus, Nirelia M; Monk, Bradley R; Dominguez, Hector D

2010-10-01

Prenatal alcohol exposure can alter physical and behavioral development, leading to a range of fetal alcohol spectrum disorders. Despite warning labels, pregnant women continue to drink alcohol, creating a need to identify effective interventions to reduce the severity of alcohol's teratogenic effects. Choline is an essential nutrient that influences brain and behavioral development. Recent studies indicate that choline supplementation can reduce the teratogenic effects of developmental alcohol exposure. The present study examined whether choline supplementation during prenatal ethanol treatment could mitigate the adverse effects of ethanol on behavioral development. Pregnant Sprague-Dawley rats were intubated with 6 g/kg/day ethanol in a binge-like manner from gestational days 5-20; pair-fed and ad libitum chow controls were included. During treatment, subjects from each group were intubated with either 250 mg/kg/day choline chloride or vehicle. Spontaneous alternation, parallel bar motor coordination, Morris water maze, and spatial working memory were assessed in male and female offspring. Subjects prenatally exposed to alcohol exhibited delayed development of spontaneous alternation behavior and deficits on the working memory version of the Morris water maze during adulthood, effects that were mitigated with prenatal choline supplementation. Neither alcohol nor choline influenced performance on the motor coordination task. These data indicate that choline supplementation during prenatal alcohol exposure may reduce the severity of fetal alcohol effects, particularly on alterations in tasks that require behavioral flexibility. These findings have important implications for children of women who drink alcohol during pregnancy. © 2010 Wiley-Liss, Inc.

Aminocaproic Acid and Tranexamic Acid Fail to Reverse Dabigatran-Induced Coagulopathy.

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Levine, Michael; Huang, Margaret; Henderson, Sean O; Carmelli, Guy; Thomas, Stephen H

In recent years, dabigatran has emerged as a popular alternative to warfarin for treatment of atrial fibrillation. If rapid reversal is required, however, no reversal agent has clearly been established. The primary purpose of this manuscript was to evaluate the efficacy of tranexamic acid and aminocaproic acid as agents to reverse dabigatran-induced coagulopathy. Rats were randomly assigned to 6 groups. Each rat received either dabigatran or oral placebo, followed by saline, tranexamic acid, or aminocaproic acid. An activated clotting test was used to measure the coagulopathy. Neither tranexamic acid nor aminocaproic acid successfully reversed dabigatran-induced coagulopathy. In this rodent model of dabigatran-induced coagulopathy, neither tranexamic acid nor aminocaproic acid were able to reverse the coagulopathy.

RBC-choline: changes by lithium and relation to prophylactic response

International Nuclear Information System (INIS)

Haag, M.; Haag, H.; Eisenried, F.; Greil, W.

1984-01-01

Red blod cell (RBC)- and plasma-choline levels were measured in patients on lithium (n=96), antidepressants (n=32) and neuroleptics (n=51) and in 25 healthy drug-free controls. Lithium patients exhibited highly increased RBC- and slightly increased plasma-choline levels compared with controls (P<0.001 and P<0.05, respectively); the choline ratio (RBC-/plasma-choline) was elevated almost to the same extent as RBC-choline (P<0.001). With antidepressants RBC-choline and choline ratios were slightly reduced (P<0.05), whereas neuroleptics showed no effect on choline levels. 79% of lithium patients were responders (reduction in hospitalizations with lithium) 21% were non-responders (no reduction or increase in hospitalizations). Choline ratio exhibited a significant relation to prophylactic lithium response, but lithium ratio did not. The percentage of non-responders was significantly higher in patients with a choline ratio exceeding 100 than in patients with a choline ratio below this cut-off (P<0.01). Thus, the increase of RBC-choline and choline ratios appears to be an effect specific for lithium and might be related to the outcome of lithium prophylaxis. (author)

TNF α is involved in neuropathic pain induced by nucleoside reverse transcriptase inhibitor in rats

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Zheng, Xuexing; Ouyang, Handong; Liu, Shue; Mata, Marina; Fink, David J.; Hao, Shuanglin

2011-01-01

In patients with HIV/AIDS, neuropathic pain is a common neurological complication. Infection with the HIV itself may lead to neuropathic pain, and painful symptoms are enhanced when patients are treated with nucleoside reverse transcriptase inhibitors (NRTI). The mechanisms by which NRTIs contribute to the development of neuropathic pain are not known. In the current studies, we tested the role of TNFα in antiretroviral drug-induced neuropathic pain. We administered 2′,3′-dideoxycytidine (ddC, one of the NRTIs) systemically to induce mechanical allodynia. We found that ddC induced overexpression of both mRNA and proteins of GFAP and TNFα in the spinal dorsal horn. TNFα was colocalized with GFAP in the spinal dorsal horn and with NeuN in the DRG. Knockdown of TNFα with siRNA blocked the mechanical allodynia induced by ddC. Intrathecal administration of glial inhibitor or recombinant TNF soluble receptor, reversed mechanical allodynia induced by ddC. These results suggest that TNFα is involved in NRTI-induced neuropathic pain. PMID:21741472

Interaction between cytotoxic effects of γ-radiation and folate deficiency in relation to choline reserves

International Nuclear Information System (INIS)

Batra, Vipen; Devasagayam, Thomas Paul Asir

2009-01-01

The search for non-toxic radio-protective drugs has yielded many potential agents but most of these compounds have certain amount of toxicity. Recent studies have indicated that bio-molecules such as folate and choline might be of radio-protective value as they are, within broad dose ranges, non-toxic to humans and experimental animals. The objective of the present study was to investigate choline dependent adaptive response to potential synergistic cytotoxic effect of folate deficiency and γ-radiation. Male Swiss mice maintained on folate sufficient diet (FSD) and folate free diet (FFD) based on AIN-93 M formula, were subjected to 1-4 Gy total body γ-irradiation. To investigate liver DNA damage, apurinic/apyrimidinic sites (AP sites) were quantified. A significant increase in liver DNA AP sites with concomitant depletion of liver choline reserves was observed when γ-radiation was combined with folate deficiency. Further work in this direction suggested that cytotoxic interaction between folate deficiency and gamma radiation might induce utilization of choline and choline containing moieties by modifying levels of key regulatory enzymes dihydrofolate reductase (DHFR) and choline oxidase (ChoOx). Another major finding of these studies is that significant liver damage at higher doses of radiation (3-4 Gy), might release considerable amounts of choline reserves to serum. In conclusion, a plausible interpretation of the present studies is that folate deprivation and γ-radiation interact to mobilize additional choline reserves of hepatic tissue, for redistribution to other organs, which could not be utilized by folate deficiency alone. Present results clearly indicated a distinct choline pool in liver and kidney tissues that could be utilized by folate deficient animals only under radiation stress conditions

Choline Phospholipid Metabolites of Human Vascular Endothelial Cells Altered by Cyclooxygenase Inhibition, Growth Factor Depletion, and Paracrine Factors Secreted by Cancer Cells

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Noriko Mori

2003-04-01

Full Text Available Magnetic resonance studies have previously shown that solid tumors and cancer cells in culture typically exhibit high phosphocholine and total choline. Treatment of cancer cells with the anti-inflammatory agent, indomethacin (INDO, reverted the phenotype of choline phospholipid metabolites in cancer cells towards a less malignant phenotype. Since endothelial cells form a key component of tumor vasculature, in this study, we used MR spectroscopy to characterize the phenotype of choline phospholipid metabolites in human umbilical vein endothelial cells (HUVECs. We determined the effect of growth factors, the anti-inflammatory agent INDO, and conditioned media obtained from a malignant cell line, on choline phospholipid metabolites. Growth factor depletion or treatment with INDO induced similar changes in the choline phospholipid metabolites of HUVECs. Treatment with conditioned medium obtained from MDA-MB-231 cancer cells induced changes similar to the presence of growth factor supplements. These results suggest that cancer cells secrete growth factors and/or other molecules that influence the choline phospholipid metabolism of HUVECs. The ability of INDO to alter choline phospholipid metabolism in the presence of growth factor supplements suggests that the inflammatory response pathways of HUVECs may play a role in cancer cell-HUVEC interaction and in the response of HUVECs to growth factors.

Adolescent, but not adult, binge ethanol exposure leads to persistent global reductions of choline acetyltransferase expressing neurons in brain.

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Ryan P Vetreno

Full Text Available During the adolescent transition from childhood to adulthood, notable maturational changes occur in brain neurotransmitter systems. The cholinergic system is composed of several distinct nuclei that exert neuromodulatory control over cognition, arousal, and reward. Binge drinking and alcohol abuse are common during this stage, which might alter the developmental trajectory of this system leading to long-term changes in adult neurobiology. In Experiment 1, adolescent intermittent ethanol (AIE; 5.0 g/kg, i.g., 2-day on/2-day off from postnatal day [P] 25 to P55 treatment led to persistent, global reductions of choline acetyltransferase (ChAT expression. Administration of the Toll-like receptor 4 agonist lipopolysaccharide to young adult rats (P70 produced a reduction in ChAT+IR that mimicked AIE. To determine if the binge ethanol-induced ChAT decline was unique to the adolescent, Experiment 2 examined ChAT+IR in the basal forebrain following adolescent (P28-P48 and adult (P70-P90 binge ethanol exposure. Twenty-five days later, ChAT expression was reduced in adolescent, but not adult, binge ethanol-exposed animals. In Experiment 3, expression of ChAT and vesicular acetylcholine transporter expression was found to be significantly reduced in the alcoholic basal forebrain relative to moderate drinking controls. Together, these data suggest that adolescent binge ethanol decreases adult ChAT expression, possibly through neuroimmune mechanisms, which might impact adult cognition, arousal, or reward sensitivity.

Different behaviors of single and multi wall carbon nanotubes for studying electrochemistry and electrocatalysis of choline oxidase

International Nuclear Information System (INIS)

Sajjadi, Sharareh; Ghourchian, Hedayatollah; Rahimi, Parvaneh

2011-01-01

Highlights: → In the presence of a typical room temperature ionic liquid (RTIL), Choline oxidase (ChOx) as a model enzyme was uniformly immobilized on either single or multi wall carbon nanotubes (SWCNTs or MWCNTs) covered on glassy carbon (GC) electrode, and the electron transfer and electroanalytical response of enzyme toward choline was evaluated. → ChOx on RTIL/MWCNTs/GC electrode showed higher electrical conductivity, better reversibility of redox reaction and higher electron transfer rate indicating more facile and rapid rate of electron transfer. → On the other hand, RTIL/SWCNTs/GC electrode showed higher amount of enzyme loading, higher enzyme-substrate affinity, lower detection limit, better sensitivity and wider linear range. → Consequently, MWCNTs are preferable for kinetic study of ChOx, while SWCNTs are more convenient for biosensing applications. - Abstract: This work presents a detailed comparison between single and multi wall carbon nanotubes (SWCNTs and MWCNTs) in an effort to understand which could be a better supporting material for studying the electrochemistry and electrocatalysis of enzymes. Choline oxidase (ChOx) was chosen as a model enzyme for evaluation of the electrodes' performance. The enzyme was adsorbed on either SWCNT or MWCNT modified electrode, in the presence of a typical room temperature ionic liquid (RTIL), and its electron transfer and electroanalytical response toward choline was investigated. RTIL/MWCNTs/GC electrode was uniformly covered by ChOx. Besides, higher electrical conductivity, better reversibility of the ChOx redox reaction and higher electron transfer rate of the enzyme indicated more facile and rapid rate of electron transfer. On the other hand, RTIL/SWCNTs/GC electrodes showed higher amount of enzyme loading, higher enzyme-substrate affinity, lower detection limit, better sensitivity and wider linear range. Consequently, MWCNTs are preferable for kinetic study of ChOx, while SWCNTs are more convenient

Postnatal choline supplementation selectively attenuates hippocampal microRNA alterations associated with developmental alcohol exposure.

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Balaraman, Sridevi; Idrus, Nirelia M; Miranda, Rajesh C; Thomas, Jennifer D

2017-05-01

Prenatal alcohol exposure can result in a range of physical, neuropathological, and behavioral alterations, collectively termed fetal alcohol spectrum disorders (FASD). We have shown that supplementation with the nutrient choline reduces the severity of developmental alcohol-associated deficits in hippocampal-dependent behaviors and normalizes some aspects of hippocampal cholinergic development and DNA methylation patterns. Alcohol's developmental effects may also be mediated, in part, by altering microRNAs (miRNAs) that serve as negative regulators of gene translation. To determine whether choline supplementation alters ethanol's long-lasting effects on miRNAs, Sprague-Dawley rats were exposed to 5.25 g/kg/day ethanol from postnatal days (PD) 4-9 via intubation; controls received sham intubations. Subjects were treated with choline chloride (100 mg/kg/day) or saline vehicle subcutaneously (s.c.) from PD 4-21. On PD 22, subjects were sacrificed, and RNA was isolated from the hippocampus. MiRNA expression was assessed with TaqMan Human MicroRNA Panel Low-Density Arrays. Ethanol significantly increased miRNA expression variance, an effect that was attenuated with choline supplementation. Cluster analysis of stably expressed miRNAs that exceeded an ANOVA p < 0.05 criterion indicated that for both male and female offspring, control and ethanol-exposed groups were most dissimilar from each other, with choline-supplemented groups in between. MiRNAs that expressed an average 2-fold change due to ethanol exposure were further analyzed to identify which ethanol-sensitive miRNAs were protected by choline supplementation. We found that at a false discovery rate (FDR)-adjusted criterion of p < 0.05, miR-200c was induced by ethanol exposure and that choline prevented this effect. Collectively, our data show that choline supplementation can normalize disturbances in miRNA expression following developmental alcohol exposure and can protect specific miRNAs from induction by

Neuroprotective Actions of Dietary Choline

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Jan Krzysztof Blusztajn

2017-07-01

Full Text Available Choline is an essential nutrient for humans. It is a precursor of membrane phospholipids (e.g., phosphatidylcholine (PC, the neurotransmitter acetylcholine, and via betaine, the methyl group donor S-adenosylmethionine. High choline intake during gestation and early postnatal development in rat and mouse models improves cognitive function in adulthood, prevents age-related memory decline, and protects the brain from the neuropathological changes associated with Alzheimer’s disease (AD, and neurological damage associated with epilepsy, fetal alcohol syndrome, and inherited conditions such as Down and Rett syndromes. These effects of choline are correlated with modifications in histone and DNA methylation in brain, and with alterations in the expression of genes that encode proteins important for learning and memory processing, suggesting a possible epigenomic mechanism of action. Dietary choline intake in the adult may also influence cognitive function via an effect on PC containing eicosapentaenoic and docosahexaenoic acids; polyunsaturated species of PC whose levels are reduced in brains from AD patients, and is associated with higher memory performance, and resistance to cognitive decline.

Relationship Between Organophosphate Toxicity and Choline Metabolism

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1986-06-06

Results from studies on the actions of the organophosphates on the central nervus system have suggested that these compounds, through an action on...Grganophosphates alter the disposition and metabolism of choline and choline-containing compounds in the nervous system , the relationshi ý of these changes to...mechanisms regulating the metabolism of choline, as well as the specific interactions of the organophospha:es with biochemical systems , may differ

Characterization and detection of a widely distributed gene cluster that predicts anaerobic choline utilization by human gut bacteria.

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Martínez-del Campo, Ana; Bodea, Smaranda; Hamer, Hilary A; Marks, Jonathan A; Haiser, Henry J; Turnbaugh, Peter J; Balskus, Emily P

2015-04-14

Elucidation of the molecular mechanisms underlying the human gut microbiota's effects on health and disease has been complicated by difficulties in linking metabolic functions associated with the gut community as a whole to individual microorganisms and activities. Anaerobic microbial choline metabolism, a disease-associated metabolic pathway, exemplifies this challenge, as the specific human gut microorganisms responsible for this transformation have not yet been clearly identified. In this study, we established the link between a bacterial gene cluster, the choline utilization (cut) cluster, and anaerobic choline metabolism in human gut isolates by combining transcriptional, biochemical, bioinformatic, and cultivation-based approaches. Quantitative reverse transcription-PCR analysis and in vitro biochemical characterization of two cut gene products linked the entire cluster to growth on choline and supported a model for this pathway. Analyses of sequenced bacterial genomes revealed that the cut cluster is present in many human gut bacteria, is predictive of choline utilization in sequenced isolates, and is widely but discontinuously distributed across multiple bacterial phyla. Given that bacterial phylogeny is a poor marker for choline utilization, we were prompted to develop a degenerate PCR-based method for detecting the key functional gene choline TMA-lyase (cutC) in genomic and metagenomic DNA. Using this tool, we found that new choline-metabolizing gut isolates universally possessed cutC. We also demonstrated that this gene is widespread in stool metagenomic data sets. Overall, this work represents a crucial step toward understanding anaerobic choline metabolism in the human gut microbiota and underscores the importance of examining this microbial community from a function-oriented perspective. Anaerobic choline utilization is a bacterial metabolic activity that occurs in the human gut and is linked to multiple diseases. While bacterial genes responsible for

Choline Theft-An Inside Job.

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Mora-Ortiz, Marina; Claus, Sandrine Paule

2017-09-13

Choline is a crucial methyl donor necessary for epigenetic regulation. In this issue of Cell Host & Microbe, Romano et al. (2017) demonstrate that choline-utilizing gut bacteria compete with their host for this essential resource, calling for a systematic consideration of gut microbial composition for personalized diet recommendations. Copyright © 2017. Published by Elsevier Inc.

Reversible surface binding of cadmium and lead by lactic acid and bifidobacteria.

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Teemu, Halttunen; Seppo, Salminen; Jussi, Meriluoto; Raija, Tahvonen; Kalle, Lertola

2008-07-15

Extensive cadmium and lead contamination of water has been reported to occur locally as a result of human activities. Lactic acid bacteria have been reported to remove cadmium and lead from water. The aim of this work was to clarify the mechanisms of cadmium and lead removal from water. In addition, the effect of other metals, reversibility of binding and recyclability of the biomass was assessed. Based on our earlier data, the two most promising lactic acid bacteria, Lactobacillus fermentum ME3 and Bifidobacterium longum 46, were selected for these experiments. The results showed that the presence of other cationic metals and blocking of carboxyl and phosphoryl groups reduced cadmium and lead removal. These results suggest involvement of electrostatic interactions in cadmium and lead removal, and support our earlier findings. Transmission electron micrographs showed large deposits of lead on the bacterial surface suggesting formation of metallic lead precipitates. Both cadmium and lead removal were reversible processes established by full recovery of removed metal after desorption with dilute solutions of EDTA and HNO(3). Resorption capacity of both biomasses tested was reduced after regeneration with 10 mM EDTA and 15 mM HNO(3). Taken together, the results suggest involvement of several reversible mechanisms such as ion exchange and precipitation in cadmium and lead binding by lactic acid bacteria. The results show that specific lactic acid bacteria have the potential for removal of cadmium and lead from water although reduction in resorption capacity after regeneration of the biomass may form a problem. Since the studies so far have mainly focused on removal of single metals from pure water, metal removal in conditions of natural waters should be assessed in further experiments.

Biocompatible choline based ionic salts: Solubility in short-chain alcohols

International Nuclear Information System (INIS)

Lopes, Joana M.; Paninho, Ana B.; Môlho, Marta F.; Nunes, Ana V.M.; Rocha, Angelo; Lourenço, Nuno M.T.; Najdanovic-Visak, Vesna

2013-01-01

Highlights: • Biocompatible ionic liquids based on choline esters were synthesized in this work. • Solubility of choline and choline esters based ionic salt in alcohols were measured. • Activity coefficients were calculated. • Experimental data were correlated by means of the semi-empirical Grant equation. -- Abstract: In this work, we report data on solubility of choline chloride and choline acetate in short-chain linear alcohols (ethanol, 1-propanol and 1-butanol) at various temperatures. Furthermore, we synthesize two choline derivatives: hydrogen choline chloride glutarate ([CholGlut][Cl]) and hydrogen choline chloride succinate ([CholSucc][Cl]). Their characterization and solubility in short-chain alcohols as a function of temperature are also included. Activity coefficients were calculated and their comparisons with ideal solutions were discussed. The experimental data were correlated successfully by means of the semi-empirical Grant equation

Light-induced reversible expansion of individual gold nanoplates

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Jinsheng Lu

2017-10-01

Full Text Available Light-induced mechanical response of materials has been extensively investigated and widely utilized to convert light energy into mechanical energy directly. The metallic nanomaterials have excellent photothermal properties and show enormous potential in micromechanical actuators, etc. However, the photo-thermo-mechanical properties of individual metallic nanostructures have yet to be well investigated. Here, we experimentally demonstrate a way to realize light-induced reversible expansion of individual gold nanoplates on optical microfibers. The light-induced thermal expansion coefficient is obtained as 21.4 ± 4.6 ∼ 31.5 ± 4.2 μ·K-1 when the light-induced heating temperature of the gold nanoplates is 240 ∼ 490 °C. The photo-thermo-mechanical response time of the gold nanoplates is about 0.3 ± 0.1 s. This insight into the photo-thermo-mechanical properties of the gold nanoplates could deepen the understanding of the light-induced reversible expansion behavior in nanoscale and pave the way for applications based on this piezoelectric-like response, such as light-driven metallic micromotors.

21 CFR 182.8252 - Choline chloride.

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2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Choline chloride. 182.8252 Section 182.8252 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR... chloride. (a) Product. Choline chloride. (b) Conditions of use. This substance is generally recognized as...

Uptake of 3H-choline and synthesis of 3H-acetylcholine by human penile corpus cavernosum

International Nuclear Information System (INIS)

Blanco, R.; Saenz de Tejada, I.; Azadzoi, K.; Goldstein, I.; Krane, R.J.; Wotiz, H.H.; Cohen, R.A.

1986-01-01

The neuroeffectors which relax penile smooth muscle and lead to erection are unknown; physiological studies of human corpus cavernosum, in vitro, have suggested a significant role of cholinergic neurotransmission. To further characterize the importance of cholinergic nerves, biopsies of human corpus cavernosum were obtained at the time of penile prosthesis implantation. Tissues were incubated in 3 H-choline (10 -5 M, 80 Ci/mmol) in oxygenated physiological salt solution at 37 0 C, pH 7.4 for 1 hour. Radiolabelled compounds were extracted with perchloric acid (0.4 M) and acetylcholine and choline were separated by HPLC; 14 C-acetylcholine was used as internal standard. 3 H-choline was accumulated by the tissues (20 +/- 1.9 fmol/mg), and 3 H-acetylcholine was synthesized (4.0 +/- 1.1 fmol/mg). In control experiments, heating of the tissue blocked synthesis of 3 H-acetylcholine. Inhibition of high affinity choline transport by hemicholinium-3 (10 -5 M) diminished tissue accumulation of 3 H-choline and significantly reduced the synthesis of 3 H-acetylcholine (0.5 +/ 0.2 fmol/mg, p < 0.05). These results provide direct evidence of neuronal accumulation of choline and enzymatic conversion to acetylcholine in human corpus cavernosum. Taken together with the physiological studies, it can be concluded that cholinergic neurotransmission in human corpus cavernosum plays a role in penile erection

CDP-choline modulates matrix metalloproteinases in rat sciatic injury.

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Gundogdu, Elif Basaran; Bekar, Ahmet; Turkyilmaz, Mesut; Gumus, Abdullah; Kafa, Ilker Mustafa; Cansev, Mehmet

2016-02-01

CDP-choline (cytidine-5'-diphosphocholine) improves functional recovery, promotes nerve regeneration, and decreases perineural scarring in rat peripheral nerve injury. The aim of the present study was to investigate the mechanism of action of CDP-choline with regard to matrix metalloproteinase (MMP) activity in the rat-transected sciatic nerve injury model. Male Wistar rats were randomized into Sham, Saline, and CDP-choline groups. Rats in Sham group received Sham surgery, whereas rats in Saline and CDP-choline groups underwent right sciatic nerve transection followed by immediate primary saturation and injected intraperitoneally with 0.9% NaCl (1 mL/kg) and CDP-choline (600 μg/kg), respectively. Sciatic nerve samples were obtained 1, 3, and 7 d after the surgery and analyzed for levels and activities of MMP-2 and MMP-9, levels of tissue inhibitor of metalloproteinases-1 (TIMP-1) and TIMP-3, and axonal regeneration. CDP-choline treatment decreased the levels and activities of MMP-2 and MMP-9, whereas increasing levels of TIMP-1 and TIMP-3 significantly on the third and seventh day after injury compared to Saline group. In addition, CDP-choline administration resulted in new axon formation and formation and advancement of myelination on newly formed islets (compartments) of axonal regrowth. Our data show, for the first time, that CDP-choline modulates MMP activity and promotes the expression of TIMPs to stimulate axonal regeneration. These data help to explain one mechanism by which CDP-choline provides neuroprotection in peripheral nerve injury. Copyright © 2016 Elsevier Inc. All rights reserved.

Human neural stem cells over-expressing choline acetyltransferase restore cognition in rat model of cognitive dysfunction.

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Park, Dongsun; Lee, Hong Jun; Joo, Seong Soo; Bae, Dae-Kwon; Yang, Goeun; Yang, Yun-Hui; Lim, Inja; Matsuo, Akinori; Tooyama, Ikuo; Kim, Yun-Bae; Kim, Seung U

2012-04-01

A human neural stem cell (NSC) line over-expressing human choline acetyltransferase (ChAT) gene was generated and these F3.ChAT NSCs were transplanted into the brain of rat Alzheimer disease (AD) model which was induced by application of ethylcholine mustard aziridinium ion (AF64A) that specifically denatures cholinergic nerves and thereby leads to memory deficit as a salient feature of AD. Transplantation of F3.ChAT human NSCs fully recovered the learning and memory function of AF64A animals, and induced elevated levels of acetylcholine (ACh) in cerebrospinal fluid (CSF). Transplanted F3.ChAT human NSCs were found to migrate to various brain regions including cerebral cortex, hippocampus, striatum and septum, and differentiated into neurons and astrocytes. The present study demonstrates that brain transplantation of human NSCs over-expressing ChAT ameliorates complex learning and memory deficits in AF64A-cholinotoxin-induced AD rat model. Copyright © 2012 Elsevier Inc. All rights reserved.

In vivo 19F-MRS observation of 5-FU metabolism in fatty liver induced by choline-deficient diet

International Nuclear Information System (INIS)

Otsuka, Hideki; Harada, Masafumi; Nishitani, Hiromu; Koga, Keiko.

1996-01-01

Using 19 F-MRS, 5-FU metabolism was investigated in rat fatty liver. Fatty liver was induced by choline-deficient diet (CD diet). This study showed differences in 5-FU metabolism between normal and fatty liver. After laparotomy, a surface coil was placed directly on the liver surface. Spectra were continuously obtained after injection of 5-FU 100 mg/kg body weight via a catheter inserted into femoral vein. We made MRI and 1 H-MRS study to examine the lipid accumulation. Histological study was also performed using HE (hematoxylin-eosin) and oil red stain. The livers of rats fed a CD diet showed very high intensity on T 1 -WI. 1 H-MRS was very useful in deteminating the fat content because the fat ratio demonstrated by 1 H-MRS is well correlated to histological findings. In 19 F-MRS, we recognized the following four peaks: 5-FU, FBAL, Fnct (fluoronucleotide) and FUPA. The decrease of 5-FU was not very apparent, but compared to the normal liver, the formation of Fnct increased and the formation of FBAL was suppressed in fatty liver. The rats fed a CD diet for four weeks showed a higher Fnct peak and lower FBAL peak compared with the results of rats fed a CD diet for two weeks. In a CD diet group, liver cell degeneration and necrotic changes were observed histologically. It is reported that cell degeneration is followed by cell proliferation in fatty liver induced by a choline deficient diet, and the high Fnct peak found in our study may reflect this phenomenon. The high Fnct peak on 19 F-MRS may correspond to recovering reaction from liver injury like fatty liver. (author)

New approaches to the synthesis of diclofenac choline

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Elżbieta Dąbrowska-Maś

2017-07-01

Full Text Available The process described herein proceeds to obtaining diclofenac choline from choline bicarbonate and diclofenac acid in mild conditions, using non-toxic solvent, with the same impurity profile deriving from diclofenac particle as for diclofenac sodium EP. The substance is also substantially free from impurities deriving from choline and free from inorganic by-products, what means that the quality may be accepted for use as an active substance in medicine.

Reversible Posterior Leukoencephalopathy Syndrome Induced by Pazopanib

International Nuclear Information System (INIS)

Chelis, Leonidas; Kakolyris, Stylianos; Souftas, Vasilios; Amarantidis, Kiriakos; Xenidis, Nikolaos; Chamalidou, Eleni; Dimopoulos, Prokopios; Michailidis, Prodromos; Christakidis, Evagelos; Prassopoulos, Panagiotis

2012-01-01

The reversible posterior leukoencephalopathy syndrome is a clinical/radiological syndrome characterized by headache, seizures, impaired vision, acute hypertension, and typical magnetic resonance imaging findings. There are several reports in the literature that depict its occurrence in cancer patients. The list of common anticancer and supportive care drugs that predispose to reversible posterior leukoencephalopathy syndrome is expanding and includes not only a large number of chemotherapeutic agents but also an increased number of new targeted drugs, particularly angiogenesis inhibitors such as bevacizumab,sorefenib and sunitinib. Pazopanib is an oral tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-Kit which after a positive phase III randomized clinical trial in patients with advanced renal cell cancer received FDA approval for the treatment of advanced renal cell carcinoma. Until now no cases of reversible posterior leukoencephalopathy syndrome induced by pazopanib have been reported. We present the case of a 40 years old female patient with heavily pre-treated metastatic renal cell carcinoma who received pazopanib as salvage treatment. After 21 days of pazopanib therapy the patient referred to the emergency department with epileptic seizure, impaired vision at both eyes and headache. MRI of the brain revealed subcortical oedema at the occipital and parietal lobes bilaterally. She was treated with anticonvulsants, i.v. administration of mannitol and antihypertensives and she recovered completely from her symptoms and was discharged on the tenth hospital day. A brain MRI performed 3 weeks after showed that the subcortical oedema had been subsided. In conclusion this is the first case of pazopanib induced reversible posterior leukoencephalopathy syndrome. Although usually reversible, this syndrome is a serious and potentially life threatening adverse effect, if untreated, that should

Reversible Posterior Leukoencephalopathy Syndrome Induced by Pazopanib

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Chelis Leonidas

2012-10-01

Full Text Available Abstract Background The reversible posterior leukoencephalopathy syndrome is a clinical/radiological syndrome characterized by headache, seizures, impaired vision, acute hypertension, and typical magnetic resonance imaging findings. There are several reports in the literature that depict its occurrence in cancer patients. The list of common anticancer and supportive care drugs that predispose to reversible posterior leukoencephalopathy syndrome is expanding and includes not only a large number of chemotherapeutic agents but also an increased number of new targeted drugs, particularly angiogenesis inhibitors such as bevacizumab,sorefenib and sunitinib. Pazopanib is an oral tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-Kit which after a positive phase III randomized clinical trial in patients with advanced renal cell cancer received FDA approval for the treatment of advanced renal cell carcinoma. Until now no cases of reversible posterior leukoencephalopathy syndrome induced by pazopanib have been reported. Case report We present the case of a 40 years old female patient with heavily pre-treated metastatic renal cell carcinoma who received pazopanib as salvage treatment. After 21 days of pazopanib therapy the patient referred to the emergency department with epileptic seizure, impaired vision at both eyes and headache. MRI of the brain revealed subcortical oedema at the occipital and parietal lobes bilaterally. She was treated with anticonvulsants, i.v. administration of mannitol and antihypertensives and she recovered completely from her symptoms and was discharged on the tenth hospital day. A brain MRI performed 3 weeks after showed that the subcortical oedema had been subsided. Conclusion In conclusion this is the first case of pazopanib induced reversible posterior leukoencephalopathy syndrome. Although usually reversible, this syndrome is a serious and

Comparison between the efficacies of curcumin and puerarin in C57BL/6 mice with steatohepatitis induced by a methionine- and choline-deficient diet

OpenAIRE

WANG, YUNLIANG; LI, JIAN; ZHUGE, LI; SU, DONGMEI; YANG, MEIJUAN; TAO, SHIYING; LI, JUNXIANG

2013-01-01

Non-alcoholic fatty liver disease (NAFLD) is a prevalent disease, which features an abnormal accumulation of lipids inside hepatocytes. Steatohepatitis plays a critical role in the process resulting in liver fibrosis and cirrhosis. Curcumin and puerarin are herbal products widely used in Asia, which are believed to have therapeutic benefits for alleviating the symptoms of steatohepatitis. In this study, mice models of steatohepatitis induced by a methionine- and choline-deficient diet (MCD) w...

{sup 18}F-Choline, {sup 11}C-choline and {sup 11}C-acetate PET/CT: comparative analysis for imaging prostate cancer patients

Energy Technology Data Exchange (ETDEWEB)

Brogsitter, Claudia; Zoephel, Klaus; Kotzerke, Joerg [Carl Gustav Carus Medical School, University of Dresden, Department of Nuclear Medicine, Dresden (Germany)

2013-07-15

Prostate cancer (PCA) is the second most common tumour in men worldwide. Whereas prostate specific antigen (PSA) is an established biochemical marker, the optimal imaging method for all clinical scenarios has not yet been found. With the rising number of PET centres there is an increasing availability and use of {sup 18}F-/{sup 11}C-choline or {sup 11}C-acetate for staging of PCA. However, to date no final conclusion has been reached as to whether acetate or choline tracers should be preferred. In this review we provide an overview of the performance of choline and acetate PET for staging the primary and recurrent disease and lymph nodes in PCA, based on the literature of the last 10 years. Although predominantly choline has been used rather than acetate, both tracers performed in a similar manner in published studies. Choline as well as acetate have insufficient diagnostic accuracy for the staging of the primary tumour, due to a minimum detectable tumour size of 5 mm and inability to differentiate PCA from benign prostate hyperplasia, chronic prostatitis and high-grade intraepithelial neoplasia. Regarding lymph node staging, choline tracers have demonstrated a high specificity. Unfortunately, the sensitivity is only moderate. For staging recurrent disease, sensitivity depends on the level of serum PSA (PSA should be >2 ng/ml). This applies to both choline and acetate. However, despite these limitations, a significant number of patients with recurrent disease can benefit from PET imaging by a change in treatment planning. (orig.)

Inactivation of Ca2+-induced ciliary reversal by high-salt extraction in the cilia of Paramecium.

Science.gov (United States)

Kutomi, Osamu; Seki, Makoto; Nakamura, Shogo; Kamachi, Hiroyuki; Noguchi, Munenori

2013-10-01

Intracellular Ca(2+) induces ciliary reversal and backward swimming in Paramecium. However, it is not known how the Ca(2+) signal controls the motor machinery to induce ciliary reversal. We found that demembranated cilia on the ciliated cortical sheets from Paramecium caudatum lost the ability to undergo ciliary reversal after brief extraction with a solution containing 0.5 M KCl. KNO(3), which is similar to KCl with respect to chaotropic effect; it had the same effect as that of KCl on ciliary response. Cyclic AMP antagonizes Ca(2+)-induced ciliary reversal. Limited trypsin digestion prevents endogenous A-kinase and cAMP-dependent phosphorylation of an outer arm dynein light chain and induces ciliary reversal. However, the trypsin digestion prior to the high-salt extraction did not affect the inhibition of Ca(2+)-induced ciliary reversal caused by the high-salt extraction. Furthermore, during the course of the high-salt extraction, some axonemal proteins were extracted from ciliary axonemes, suggesting that they may be responsible for Ca(2+)-induced ciliary reversal.

Reversal of rocuronium-induced profound neuromuscular block by sugammadex in Duchenne muscular dystrophy.

NARCIS (Netherlands)

Boer, H.D. de; Egmond, J. van; Booij, L.H.D.J.; Driessen, J.J.

2009-01-01

A case is reported in which a child with Duchenne muscular dystrophy received a dose of sugammadex to reverse a rocuronium-induced profound neuromuscular block. Sugammadex is the first selective relaxant binding agent and reverses rocuronium- and vecuronium-induced neuromuscular block. A fast and

Hall magnetohydrodynamics simulations of end-shorting induced rotation in field-reversed configurations

International Nuclear Information System (INIS)

Macnab, A. I. D.; Milroy, R. D.; Kim, C. C.; Sovinec, C. R.

2007-01-01

End-shorting of the open field lines that surround a field-reversed configuration (FRC) is believed to contribute to its observed rotation. In this study, nonlinear extended magnetohydrodynamics (MHD) simulations were performed that detail the end-shorting process and the resulting spin-up of the FRC. The tangential component of the electric field E T is set to zero at the axial boundaries in an extended MHD model that includes the Hall and ∇P e terms. This shorting of the electric field leads to the generation of toroidal fields on the open field lines, which apply a torque leading to a rotation of the ions on the open field lines. The FRC then gains angular momentum through a viscous transfer from the open field line region. In addition, it is shown that spin-up is still induced when insulating boundaries are assumed

Idarucizumab for Reversing Dabigatran-Induced Anticoagulation: A Systematic Review.

Science.gov (United States)

Thibault, Nathan; Morrill, Amanda M; Willett, Kristine C

The approval of the oral direct thrombin inhibitor, dabigatran etexilate, gave patients an alternative to oral anticoagulation with warfarin. Like all anticoagulants, the primary adverse event (AE) associated with dabigatran is bleeding. Until the FDA approval of idarucizumab, there had been no reversal agent for dabigatran-induced anticoagulation in patients with life-threatening or uncontrollable bleeding, or those requiring emergent procedures. The primary purpose of this review is to summarize the safety and efficacy of idarucizumab, a monoclonal antibody fragment, and its use as a reversal agent for dabigatran. A literature search was conducted through MEDLINE (1946 to November week 1 2015) and Embase (1980-2015 week 46) using the search term idarucizumab. Clinicaltrials.gov was consulted for a comprehensive list of ongoing and completed studies. Additional studies were identified through bibliographical citations. Clinical trials in animals and humans published in English evaluating the safety and efficacy of idarucizumab for reversal of anticoagulant treatment with dabigatran were included for review. Idarucizumab has been shown to significantly reverse the anticoagulant effects of dabigatran in both healthy volunteers and patients requiring a reversal agent because of either overt bleeding or an emergency surgery or invasive procedure. The most common AEs were headache, nasopharyngitis, back pain, skin irritation, hypokalemia, delirium, constipation, pyrexia, and pneumonia. Deaths reported in idarucizumab studies were attributed to either the index event or a preexisting comorbidity. Most adverse effects were minor, but 21 serious AEs have been reported in the published data including thrombotic events. Given the increased use of direct oral anticoagulants, such as dabigatran, a need for specific reversal agents exists. Idarucizumab has been shown to be safe and effective in the reversal of dabigatran-induced anticoagulation in patients requiring emergent

A highly reversible anthraquinone-based anolyte for alkaline aqueous redox flow batteries

Science.gov (United States)

Cao, Jianyu; Tao, Meng; Chen, Hongping; Xu, Juan; Chen, Zhidong

2018-05-01

The development of electroactive organic materials for use in aqueous redox flow battery (RFB) electrolytes is highly attractive because of their structural flexibility, low cost and sustainability. Here, we report on a highly reversible anthraquinone-based anolyte (1,8-dihydroxyanthraquinone, 1,8-DHAQ) for alkaline aqueous RFB applications. Electrochemical measurements reveal the substituent position of hydroxyl groups for DHAQ isomers has a significant impact on the redox potential, electrochemical reversibility and water-solubility. 1,8-DHAQ shows the highest redox reversibility and rapidest mass diffusion among five isomeric DHAQs. The alkaline aqueous RFB using 1,8-DHAQ as the anolyte and potassium ferrocyanide as the catholyte yields open-circuit voltage approaching 1.1 V and current efficiency and capacity retention exceeding 99.3% and 99.88% per cycle, respectively. This aqueous RFB produces a maximum power density of 152 mW cm-2 at 100% SOC and 45 °C. Choline hydroxide was used as a hydrotropic agent to enhance the water-solubility of 1,8-DHAQ. 1,8-DHAQ has a maximum solubility of 3 M in 1 M KOH with 4 M choline hydroxide.

Role of choline deficiency in the Fatty liver phenotype of mice fed a low protein, very low carbohydrate ketogenic diet.

Science.gov (United States)

Schugar, Rebecca C; Huang, Xiaojing; Moll, Ashley R; Brunt, Elizabeth M; Crawford, Peter A

2013-01-01

Though widely employed for clinical intervention in obesity, metabolic syndrome, seizure disorders and other neurodegenerative diseases, the mechanisms through which low carbohydrate ketogenic diets exert their ameliorative effects still remain to be elucidated. Rodent models have been used to identify the metabolic and physiologic alterations provoked by ketogenic diets. A commonly used rodent ketogenic diet (Bio-Serv F3666) that is very high in fat (~94% kcal), very low in carbohydrate (~1% kcal), low in protein (~5% kcal), and choline restricted (~300 mg/kg) provokes robust ketosis and weight loss in mice, but through unknown mechanisms, also causes significant hepatic steatosis, inflammation, and cellular injury. To understand the independent and synergistic roles of protein restriction and choline deficiency on the pleiotropic effects of rodent ketogenic diets, we studied four custom diets that differ only in protein (5% kcal vs. 10% kcal) and choline contents (300 mg/kg vs. 5 g/kg). C57BL/6J mice maintained on the two 5% kcal protein diets induced the most significant ketoses, which was only partially diminished by choline replacement. Choline restriction in the setting of 10% kcal protein also caused moderate ketosis and hepatic fat accumulation, which were again attenuated when choline was replete. Key effects of the 5% kcal protein diet - weight loss, hepatic fat accumulation, and mitochondrial ultrastructural disarray and bioenergetic dysfunction - were mitigated by choline repletion. These studies indicate that synergistic effects of protein restriction and choline deficiency influence integrated metabolism and hepatic pathology in mice when nutritional fat content is very high, and support the consideration of dietary choline content in ketogenic diet studies in rodents to limit hepatic mitochondrial dysfunction and fat accumulation.

Electric-Field-Induced Magnetization Reversal in a Ferromagnet-Multiferroic Heterostructure

Science.gov (United States)

Heron, J. T.; Trassin, M.; Ashraf, K.; Gajek, M.; He, Q.; Yang, S. Y.; Nikonov, D. E.; Chu, Y.-H.; Salahuddin, S.; Ramesh, R.

2011-11-01

A reversal of magnetization requiring only the application of an electric field can lead to low-power spintronic devices by eliminating conventional magnetic switching methods. Here we show a nonvolatile, room temperature magnetization reversal determined by an electric field in a ferromagnet-multiferroic system. The effect is reversible and mediated by an interfacial magnetic coupling dictated by the multiferroic. Such electric-field control of a magnetoelectric device demonstrates an avenue for next-generation, low-energy consumption spintronics.

Rumen-protected choline: A significance effect on dairy cattle nutrition.

Science.gov (United States)

Jayaprakash, G; Sathiyabarathi, M; Robert, M Arokia; Tamilmani, T

2016-08-01

Choline is a vitamin-like substance it has multi-function in animal production, reproduction, and health. The transition period is most crucial stage in lactation cycle of dairy cows due to its association with negative hormonal and energy balances. Unfortunately, unprotected choline easily degrades in the rumen; therefore, choline added to the diet in a rumen-protected form. The use of rumen-protected choline (RPC) is a preventive measurement for the fatty liver syndrome and ketosis; may improve milk production as well as milk composition and reproduction parameters. This review summarizes the effectiveness of RPC on animal production, health, and reproduction.

21 CFR 172.370 - Iron-choline citrate complex.

Science.gov (United States)

2010-04-01

....370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Special Dietary and Nutritional Additives § 172.370 Iron-choline citrate complex. Iron-choline...

Pentoxifylline Attenuates Methionine- and Choline-Deficient-Diet-Induced Steatohepatitis by Suppressing TNF-α Expression and Endoplasmic Reticulum Stress

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Min Kyung Chae

2012-01-01

Full Text Available Background. Pentoxifylline (PTX anti-TNF properties are known to exert hepatoprotective effects in various liver injury models. The aim of this study was to investigate whether PTX has beneficial roles in the development of methionine- and choline-deficient-(MCD- diet-induced NAFLD SD rats in vivo and TNF-α-induced Hep3B cells in vitro. Methods. SD Rats were classified according to diet (chow or MCD diet and treatment (normal saline or PTX injection over a period of 4 weeks: group I (chow + saline, n=4, group II (chow + PTX, group III (MCD + saline, and group IV (MCD + PTX. Hep3B cells were treated with 100 ng/ml TNF-α (24 h in the absence or presence of PTX (1 mM. Results. PTX attenuated MCD-diet-induced serum ALT levels and hepatic steatosis. In real-time PCR and western blotting analysis, PTX decreased MCD-diet-induced TNF-alpha mRNA expression and proapoptotic unfolded protein response by ER stress (GRP78, p-eIF2, ATF4, IRE1α, CHOP, and p-JNK activation in vivo. PTX (1 mM reduced TNF-α-induced activation of GRP78, p-eIF2, ATF4, IRE1α, and CHOP in vitro. Conclusion. PTX has beneficial roles in the development of MCD-diet-induced steatohepatitis through partial suppression of TNF-α and ER stress.

Nutrition in pregnancy: the argument for including a source of choline

OpenAIRE

Zeisel, Steven H

2013-01-01

Steven H Zeisel Nutrition Research Institute at Kannapolis, Department of Nutrition, University of North Carolina at Chapel Hill, Kannapolis, NC, USA Abstract: Women, during pregnancy and lactation, should eat foods that contain adequate amounts of choline. A mother delivers large amounts of choline across the placenta to the fetus, and after birth she delivers large amounts of choline in milk to the infant; this greatly increases the demand on the choline stores of the mother. Adequate inta...

Synergistic effects of ginseng stem and leaf-extracted ginsenoside and choline on improving learning and memory in rats Association verification experiment in animals with multiple learning and memory Disorders

Institute of Scientific and Technical Information of China (English)

Xiaomin Zhao; Hongxia Gu; Qing Li; Xianglin Xie; Zuoli Xia; Hongxin Cai; Ling Zhang; Dawei Li; Xinnong Wang

2008-01-01

BACKGROUND:Ginsenoside extracted from the stem and leaf of ginseng(GSL)and choline have both been shown to improve learning and memory functions; however,further studies are needed to understand the synergistic effects of a combination of both.OBJECTIVE:To verify the combined improved synergistic effects of GSL and choline on learning and memory disorders in rats.DESIGN:Control observation.SETTING:Taishan Medical College.MATERIALS:A total of 150 male Kunming mice weighing(20±2)g and 40 healthy male Wistar rats weighing(220±20)g were provided by the Experimental Animal Department of Jilin University.Animal experimentation received confirmed consent from the local ethic committee.GSL was provided by the Department of Chemistry,Norman Bethune Medical University,and choline was provided by the Third Experiment Factory,Shanghai.METHODS:This study was performed at the Life Science Institute,Taishan Medical College from October 2006 to February 2007.①Scopolamine-induced learning and memory disorders in rats:Forty rats were randomly divided into control group,model group,combination group(400 mg/kg GSL + 200 mg/kg choline),GSL(400 mg/kg)group,and choline(200 mg/kg)group,8 rats/group.Rats were perfused and administrated in the morning,once a day for 14 successive days.Rats in the control group and model group were perfused with 20 mL/kg distilled water and underwent Morris water maze spatial resolution test 1 hour after perfusion on the 10th,11th,and 12th days after administration.Rats also underwent passive step-down avoidance test 1 hour after reperfusion on the 13th and 14th days after administration.Thirty minutes prior to experimentation,rats in the remaining three groups were intraperitoneally(I.p)injected with 2 mg/kg scopolamine,and rats in the control group were I.p.injected with 2 mL/kg saline.②Scopolamine-induced learning disorder and memory acquired disorder in mice:Fifty mice were randomly divided into control group,model group,combination group(400 mg

Intergenic sequence between Arabidopsis caseinolytic protease B-cytoplasmic/heat shock protein100 and choline kinase genes functions as a heat-inducible bidirectional promoter.

Science.gov (United States)

Mishra, Ratnesh Chandra; Grover, Anil

2014-11-01

In Arabidopsis (Arabidopsis thaliana), the At1g74310 locus encodes for caseinolytic protease B-cytoplasmic (ClpB-C)/heat shock protein100 protein (AtClpB-C), which is critical for the acquisition of thermotolerance, and At1g74320 encodes for choline kinase (AtCK2) that catalyzes the first reaction in the Kennedy pathway for phosphatidylcholine biosynthesis. Previous work has established that the knockout mutants of these genes display heat-sensitive phenotypes. While analyzing the AtClpB-C promoter and upstream genomic regions in this study, we noted that AtClpB-C and AtCK2 genes are head-to-head oriented on chromosome 1 of the Arabidopsis genome. Expression analysis showed that transcripts of these genes are rapidly induced in response to heat stress treatment. In stably transformed Arabidopsis plants harboring this intergenic sequence between head-to-head oriented green fluorescent protein and β-glucuronidase reporter genes, both transcripts and proteins of the two reporters were up-regulated upon heat stress. Four heat shock elements were noted in the intergenic region by in silico analysis. In the homozygous transfer DNA insertion mutant Salk_014505, 4,393-bp transfer DNA is inserted at position -517 upstream of ATG of the AtClpB-C gene. As a result, AtCk2 loses proximity to three of the four heat shock elements in the mutant line. Heat-inducible expression of the AtCK2 transcript was completely lost, whereas the expression of AtClpB-C was not affected in the mutant plants. Our results suggest that the 1,329-bp intergenic fragment functions as a heat-inducible bidirectional promoter and the region governing the heat inducibility is possibly shared between the two genes. We propose a model in which AtClpB-C shares its regulatory region with heat-induced choline kinase, which has a possible role in heat signaling. © 2014 American Society of Plant Biologists. All Rights Reserved.

Multimodal elucidation of choline metabolism in a murine glioma model using magnetic resonance spectroscopy and 11C-choline positron emission tomography

NARCIS (Netherlands)

Wehrl, H.F.; Schwab, J.; Hasenbach, K.; Reischl, G.; Tabatabai, G.; Quintanilla-Martinez, L.; Jiru, F.; Chughtai, K; Kiss, A.; Cay, F.; Bukala, D.; Heeren, R.M.A.; Pichler, B.J.; Sauter, A.W.

2013-01-01

The metabolites, transporters, and enzymes involved in choline metabolism are regarded as biomarkers for disease progression in a variety of cancers, but their in vivo detection is not ideal. Both magnetic resonance spectroscopy [MRS using chemical shift imaging (CSI) total choline (tCho)] and

Choline transport in the isolated rabbit corneal epithelium

International Nuclear Information System (INIS)

Faust, R.L.

1988-01-01

In the present study, isolated epithelial sheets were obtained by performing two sequential anterior keratectomies, three weeks apart, on rabbit corneas. Light microscopy of the isolated sheets revealed a multilayered epithelium with an intact basal cell layer without contamination from other cell types. The accumulation of [ 3 H]choline into the epithelial sheets was studied at substrate concentrations varying from 1 to 100 μMoles with and without the addition of specific metabolic and stereochemical inhibitors. Accumulation of [ 3 H]choline into these sheets was saturable. Kinetic analysis, performed by estimation from double-reciprocal plots, revealed a single component system with a K m of 24.9 μM. The metabolic inhibitors potassium cyanide and ouabain showed no effect on the uptake of [ 3 H]choline; however, the stereochemical inhibitor hemicholinium-3 significantly reduced the accumulation of radiolabel at both high and low substrate concentrations. The results suggest a non-energy dependent yet a highly specific transport system for the accumulation of choline into the rabbit epithelium

Phosphorylation of the Yeast Choline Kinase by Protein Kinase C

Science.gov (United States)

Choi, Mal-Gi; Kurnov, Vladlen; Kersting, Michael C.; Sreenivas, Avula; Carman, George M.

2005-01-01

The Saccharomyces cerevisiae CKI1-encoded choline kinase catalyzes the committed step in phosphatidylcholine synthesis via the Kennedy pathway. The enzyme is phosphorylated on multiple serine residues, and some of this phosphorylation is mediated by protein kinase A. In this work, we examined the hypothesis that choline kinase is also phosphorylated by protein kinase C. Using choline kinase as a substrate, protein kinase C activity was dose- and time-dependent, and dependent on the concentrations of choline kinase (Km = 27 μg/ml) and ATP (Km = 15 μM). This phosphorylation, which occurred on a serine residue, was accompanied by a 1.6-fold stimulation of choline kinase activity. The synthetic peptide SRSSS25QRRHS (Vmax/Km = 17.5 mM-1 μmol min-1 mg-1) that contains the protein kinase C motif for Ser25 was a substrate for protein kinase C. A Ser25 to Ala (S25A) mutation in choline kinase resulted in a 60% decrease in protein kinase C phosphorylation of the enzyme. Phosphopeptide mapping analysis of the S25A mutant enzyme confirmed that Ser25 was a protein kinase C target site. In vivo, the S25A mutation correlated with a decrease (55%) in phosphatidylcholine synthesis via the Kennedy pathway whereas an S25D phosphorylation site mimic correlated with an increase (44%) in phosphatidylcholine synthesis. Whereas the S25A (protein kinase C site) mutation did not affect the phosphorylation of choline kinase by protein kinase A, the S30A (protein kinase A site) mutation caused a 46% reduction in enzyme phosphorylation by protein kinase C. A choline kinase synthetic peptide (SQRRHS30LTRQ) containing Ser30 was a substrate (Vmax/Km = 3.0 mM−1 μmol min−1 mg−1) for protein kinase C. Comparison of phosphopeptide maps of the wild type and S30A mutant choline kinase enzymes phosphorylated by protein kinase C confirmed that Ser30 was also a target site for protein kinase C. PMID:15919656

Distinct choline metabolic profiles are associated with differences in gene expression for basal-like and luminal-like breast cancer xenograft models

International Nuclear Information System (INIS)

Moestue, Siver A; Borgan, Eldrid; Huuse, Else M; Lindholm, Evita M; Sitter, Beathe; Børresen-Dale, Anne-Lise; Engebraaten, Olav; Mælandsmo, Gunhild M; Gribbestad, Ingrid S

2010-01-01

Increased concentrations of choline-containing compounds are frequently observed in breast carcinomas, and may serve as biomarkers for both diagnostic and treatment monitoring purposes. However, underlying mechanisms for the abnormal choline metabolism are poorly understood. The concentrations of choline-derived metabolites were determined in xenografted primary human breast carcinomas, representing basal-like and luminal-like subtypes. Quantification of metabolites in fresh frozen tissue was performed using high-resolution magic angle spinning magnetic resonance spectroscopy (HR MAS MRS). The expression of genes involved in phosphatidylcholine (PtdCho) metabolism was retrieved from whole genome expression microarray analyses. The metabolite profiles from xenografts were compared with profiles from human breast cancer, sampled from patients with estrogen/progesterone receptor positive (ER+/PgR+) or triple negative (ER-/PgR-/HER2-) breast cancer. In basal-like xenografts, glycerophosphocholine (GPC) concentrations were higher than phosphocholine (PCho) concentrations, whereas this pattern was reversed in luminal-like xenografts. These differences may be explained by lower choline kinase (CHKA, CHKB) expression as well as higher PtdCho degradation mediated by higher expression of phospholipase A2 group 4A (PLA2G4A) and phospholipase B1 (PLB1) in the basal-like model. The glycine concentration was higher in the basal-like model. Although glycine could be derived from energy metabolism pathways, the gene expression data suggested a metabolic shift from PtdCho synthesis to glycine formation in basal-like xenografts. In agreement with results from the xenograft models, tissue samples from triple negative breast carcinomas had higher GPC/PCho ratio than samples from ER+/PgR+ carcinomas, suggesting that the choline metabolism in the experimental models is representative for luminal-like and basal-like human breast cancer. The differences in choline metabolite

Role of choline deficiency in the Fatty liver phenotype of mice fed a low protein, very low carbohydrate ketogenic diet.

Directory of Open Access Journals (Sweden)

Rebecca C Schugar

Full Text Available Though widely employed for clinical intervention in obesity, metabolic syndrome, seizure disorders and other neurodegenerative diseases, the mechanisms through which low carbohydrate ketogenic diets exert their ameliorative effects still remain to be elucidated. Rodent models have been used to identify the metabolic and physiologic alterations provoked by ketogenic diets. A commonly used rodent ketogenic diet (Bio-Serv F3666 that is very high in fat (~94% kcal, very low in carbohydrate (~1% kcal, low in protein (~5% kcal, and choline restricted (~300 mg/kg provokes robust ketosis and weight loss in mice, but through unknown mechanisms, also causes significant hepatic steatosis, inflammation, and cellular injury. To understand the independent and synergistic roles of protein restriction and choline deficiency on the pleiotropic effects of rodent ketogenic diets, we studied four custom diets that differ only in protein (5% kcal vs. 10% kcal and choline contents (300 mg/kg vs. 5 g/kg. C57BL/6J mice maintained on the two 5% kcal protein diets induced the most significant ketoses, which was only partially diminished by choline replacement. Choline restriction in the setting of 10% kcal protein also caused moderate ketosis and hepatic fat accumulation, which were again attenuated when choline was replete. Key effects of the 5% kcal protein diet - weight loss, hepatic fat accumulation, and mitochondrial ultrastructural disarray and bioenergetic dysfunction - were mitigated by choline repletion. These studies indicate that synergistic effects of protein restriction and choline deficiency influence integrated metabolism and hepatic pathology in mice when nutritional fat content is very high, and support the consideration of dietary choline content in ketogenic diet studies in rodents to limit hepatic mitochondrial dysfunction and fat accumulation.

Effect of hypoxia on the uptake of [methyl-3H]choline, [1-14C] acetate and [18F]FDG in cultured prostate cancer cells

International Nuclear Information System (INIS)

Hara, Toshihiko; Bansal, Aditya; DeGrado, Timothy R.

2006-01-01

Introduction: Choline, acetate and glucose ([2- 18 F]fluoro-2-deoxyglucose, [ 18 F]FDG) analogs are under investigation as positron emission tomography (PET) tracers for the imaging of prostate cancer; however, their response to tumor hypoxia has not been clarified. Methods: The uptake of [methyl- 3 H]choline, [1- 14 C]acetate and [ 18 F]FDG was monitored in androgen-independent PC-3 cells and androgen-sensitive LNCaP cells under aerobic or anoxic conditions. The effect of androgen depletion was also examined. Results: PC-3 cells exhibited aerobic choline and acetate uptake five to six times higher than FDG uptake, whereas LNCaP cells showed choline uptake 2.2-fold higher than acetate uptake and 10-fold higher than FDG uptake. After 4 h of anoxia, PC-3 cells showed an 85% increase in FDG uptake, a 15% decrease in choline uptake and a 36% increase in acetate uptake, whereas LNCaP cells showed a 212% increase in FDG uptake, a 28% decrease in choline uptake and no change in acetate uptake. Androgen depletion resulted in a marked decrease in the uptake of all tracers in LNCaP cells but no changes in PC-3 cells. Conclusion: In aerobic conditions, both PC-3 and LNCaP cells exhibited an order of uptake preference as follows: choline>acetate>FDG. In hypoxic cells, the order is reversed, reflecting diverse biochemical responses to hypoxia. These findings may help to explain PET imaging findings of the diverse responses of these tracers in different stages and locations of prostate cancer. Androgen depletion markedly suppressed the uptake of all three tracers in LNCaP cells, which suggests the potential for underestimation of the disease state when PET imaging is performed subsequent to antiandrogen therapy

Sex Reversal in Birds.

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Major, Andrew T; Smith, Craig A

2016-01-01

Sexual differentiation in birds is controlled genetically as in mammals, although the sex chromosomes are different. Males have a ZZ sex chromosome constitution, while females are ZW. Gene(s) on the sex chromosomes must initiate gonadal sex differentiation during embryonic life, inducing paired testes in ZZ individuals and unilateral ovaries in ZW individuals. The traditional view of avian sexual differentiation aligns with that expounded for other vertebrates; upon sexual differentiation, the gonads secrete sex steroid hormones that masculinise or feminise the rest of the body. However, recent studies on naturally occurring or experimentally induced avian sex reversal suggest a significant role for direct genetic factors, in addition to sex hormones, in regulating sexual differentiation of the soma in birds. This review will provide an overview of sex determination in birds and both naturally and experimentally induced sex reversal, with emphasis on the key role of oestrogen. We then consider how recent studies on sex reversal and gynandromorphic birds (half male:half female) are shaping our understanding of sexual differentiation in avians and in vertebrates more broadly. Current evidence shows that sexual differentiation in birds is a mix of direct genetic and hormonal mechanisms. Perturbation of either of these components may lead to sex reversal. © 2016 S. Karger AG, Basel.

A silk peptide fraction restores cognitive function in AF64A-induced Alzheimer disease model rats by increasing expression of choline acetyltransferase gene

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Cha, Yeseul [College of Veterinary Medicine, Veterinary Medical Center, Chungbuk National University, Cheongju (Korea, Republic of); Lee, Sang Hoon [Department of Food Science and Technology, Chungbuk National University, Cheongju (Korea, Republic of); Jang, Su Kil [Division of Marine Molecular Biotechnology, Gangneung-Wonju National University, Gangneung (Korea, Republic of); Guo, Haiyu; Ban, Young-Hwan; Park, Dongsun [College of Veterinary Medicine, Veterinary Medical Center, Chungbuk National University, Cheongju (Korea, Republic of); Jang, Gwi Yeong; Yeon, Sungho [Department of Food Science and Technology, Chungbuk National University, Cheongju (Korea, Republic of); Lee, Jeong-Yong [Worldway Co., Ltd., Sejong (Korea, Republic of); Choi, Ehn-Kyoung [College of Veterinary Medicine, Veterinary Medical Center, Chungbuk National University, Cheongju (Korea, Republic of); Joo, Seong Soo [Division of Marine Molecular Biotechnology, Gangneung-Wonju National University, Gangneung (Korea, Republic of); Jeong, Heon-Sang, E-mail: hsjeong@cbu.ac.kr [Department of Food Science and Technology, Chungbuk National University, Cheongju (Korea, Republic of); Kim, Yun-Bae, E-mail: solar93@cbu.ac.kr [College of Veterinary Medicine, Veterinary Medical Center, Chungbuk National University, Cheongju (Korea, Republic of)

2017-01-01

This study investigated the effects of a silk peptide fraction obtained by incubating silk proteins with Protease N and Neutrase (SP-NN) on cognitive dysfunction of Alzheimer disease model rats. In order to elucidate underlying mechanisms, the effect of SP-NN on the expression of choline acetyltransferase (ChAT) mRNA was assessed in F3.ChAT neural stem cells and Neuro2a neuroblastoma cells; active amino acid sequence was identified using HPLC-MS. The expression of ChAT mRNA in F3.ChAT cells increased by 3.79-fold of the control level by treatment with SP-NN fraction. The active peptide in SP-NN was identified as tyrosine-glycine with 238.1 of molecular weight. Male rats were orally administered with SP-NN (50 or 300 mg/kg) and challenged with a cholinotoxin AF64A. As a result of brain injury and decreased brain acetylcholine level, AF64A induced astrocytic activation, resulting in impairment of learning and memory function. Treatment with SP-NN exerted recovering activities on acetylcholine depletion and brain injury, as well as cognitive deficit induced by AF64A. The results indicate that, in addition to a neuroprotective activity, the SP-NN preparation restores cognitive function of Alzheimer disease model rats by increasing the release of acetylcholine. - Highlights: • Cognition-enhancing effects of SP-NN, a silk peptide preparation, were investigated. • SP-NN enhanced ChAT mRNA expression in F3.ChAT neural stem cells and Neuro-2a neuroblastoma cells. • Active molecule was identified as a dipeptide composed of tyrosine-glycine. • SP-NN reversed cognitive dysfunction elicited by AF64A. • Neuroprotection followed by increased acetylcholine level was achieved with SP-NN.

Importance of Choline as Essential Nutrient and Its Role in Prevention of Various Toxicities

Directory of Open Access Journals (Sweden)

Somava Biswas

2015-01-01

Full Text Available Choline is a water-soluble essential nutrient included as a member of the vitamin B12 group owing to its structural similarities with that of the other members of the group. Its roles and functions, however, extend much wider than that of the vitamins with which it is grouped. Choline is vital for maintenance of various key metabolic processes which play a role in the prevention or progression of various health impairments. The occurrence of diseases like neural tube defect (NTD and Alzheimer’s is prevented by the metabolic role of choline. It is also indispensable for mitigation of various forms of toxic contamination. While adequate level of choline in the body is essential, an excess of choline can result in various forms of disorder. To maintain the optimal level of choline in the body can be a challenge. The vital roles played by choline together with the range of contradictions and problems that choline presents make choline an interesting area of study. This paper attempts to summarize and review some recent publications on choline that have opened up new prospect in understanding the multiple role played by choline and in throwing light on the role played by this wonder essential nutrient in mitigating various forms of toxic contamination.

Formulation and utilization of choline based samples for dissolution dynamic nuclear polarization

DEFF Research Database (Denmark)

Bowen, Sean; Ardenkjær-Larsen, Jan Henrik

2013-01-01

their performance to more traditional sample formulations. Choline yields stable samples with exceptional polarization performance while simultaneously offering the capability to easily remove the choline after dissolution, perform experiments with the hyperpolarized choline, or anything in between....

Multilayer Choline Phosphate Molecule Modified Surface with Enhanced Cell Adhesion but Resistance to Protein Adsorption.

Science.gov (United States)

Chen, Xingyu; Yang, Ming; Liu, Botao; Li, Zhiqiang; Tan, Hong; Li, Jianshu

2017-08-22

Choline phosphate (CP), which is a new zwitterionic molecule, and has the reverse order of phosphate choline (PC) and could bind to the cell membrane though the unique CP-PC interaction. Here we modified a glass surface with multilayer CP molecules using surface-initiated atom-transfer radical polymerization (SI-ATRP) and the ring-opening method. Polymeric brushes of (dimethylamino)ethyl methacrylate (DMAEMA) were synthesized by SI-ATRP from the glass surface. Then the grafted PDMAEMA brushes were used to introduce CP groups to fabricate the multilayer CP molecule modified surface. The protein adsorption experiment and cell culture test were used to evaluate the biocompatibility of the modified surfaces by using human umbilical veinendothelial cells (HUVECs). The protein adsorption results demonstrated that the multilayer CP molecule decorated surface could prevent the adsorption of fibrinogen and serum protein. The adhesion and proliferation of cells were improved significantly on the multilayer CP molecule modified surface. Therefore, the biocompatibility of the material surface could be improved by the modified multilayer CP molecule, which exhibits great potential for biomedical applications, e.g., scaffolds in tissue engineering.

N-Acetylcysteine Reverses Cocaine Induced Metaplasticity

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Moussawi, Khaled; Pacchioni, Alejandra; Moran, Megan; Olive, M. Foster; Gass, Justin T.; Lavin, Antonieta; Kalivas, Peter W

2009-01-01

Cocaine addiction is characterized by an impaired ability to develop adaptive behaviors that can compete with cocaine seeking, implying a deficit in the ability to induce plasticity in cortico-accumbens circuitry critical for regulating motivated behavior. RWe found that rats withdrawn from cocaine self-administration had a marked in vivo deficit in the ability to develop long-term potentation (LTP) and depression (LTD) in the nucleus accumbens core subregion following stimulation of prefrontal cortex. N-acetylcysteine treatment prevents relapse in animal models and craving in humans by activating cystine-glutamate exchange and thereby stimulating extrasynaptic metabotropic glutamate receptors (mGluR). N-acetylcysteine treatment restored the ability to induce LTP and LTD by indirectly stimulating mGluR2/3 and mGluR5, respectively. Cocaine self-administration induces metaplasticity that inhibits the further induction of synaptic plasticity, and this impairment can be reversed by N-acetylcysteine, a drug that also prevents relapse. PMID:19136971

N-Acetylcysteine reverses cocaine-induced metaplasticity.

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Moussawi, Khaled; Pacchioni, Alejandra; Moran, Megan; Olive, M Foster; Gass, Justin T; Lavin, Antonieta; Kalivas, Peter W

2009-02-01

Cocaine addiction is characterized by an impaired ability to develop adaptive behaviors that can compete with cocaine seeking, implying a deficit in the ability to induce plasticity in cortico-accumbens circuitry crucial for regulating motivated behavior. We found that rats withdrawn from cocaine self-administration had a marked in vivo deficit in the ability to develop long-term potentiation (LTP) and long-term depression (LTD) in the nucleus accumbens core subregion after stimulation of the prefrontal cortex. N-acetylcysteine (NAC) treatment prevents relapse in animal models and craving in humans by activating cystine-glutamate exchange and thereby stimulating extrasynaptic metabotropic glutamate receptors (mGluR). NAC treatment of rats restored the ability to induce LTP and LTD by indirectly stimulating mGluR2/3 and mGluR5, respectively. Our findings show that cocaine self-administration induces metaplasticity that inhibits further induction of synaptic plasticity, and this impairment can be reversed by NAC, a drug that also prevents relapse.

Evaluation of the PET component of simultaneous [18F]choline PET/MRI in prostate cancer: comparison with [18F]choline PET/CT

International Nuclear Information System (INIS)

Wetter, Axel; Lipponer, Christine; Nensa, Felix; Altenbernd, Jens-Christian; Schlosser, Thomas; Lauenstein, Thomas; Heusch, Philipp; Ruebben, Herbert; Bockisch, Andreas; Poeppel, Thorsten; Nagarajah, James

2014-01-01

The aim of this study was to evaluate the positron emission tomography (PET) component of [ 18 F]choline PET/MRI and compare it with the PET component of [ 18 F]choline PET/CT in patients with histologically proven prostate cancer and suspected recurrent prostate cancer. Thirty-six patients were examined with simultaneous [ 18 F]choline PET/MRI following combined [ 18 F]choline PET/CT. Fifty-eight PET-positive lesions in PET/CT and PET/MRI were evaluated by measuring the maximum and mean standardized uptake values (SUV max and SUV mean ) using volume of interest (VOI) analysis. A scoring system was applied to determine the quality of the PET images of both PET/CT and PET/MRI. Agreement between PET/CT and PET/MRI regarding SUV max and SUV mean was tested using Pearson's product-moment correlation and Bland-Altman analysis. All PET-positive lesions that were visible on PET/CT were also detectable on PET/MRI. The quality of the PET images was comparable in both groups. Median SUV max and SUV mean of all lesions were significantly lower in PET/MRI than in PET/CT (5.2 vs 6.1, p max of PET/CT and PET/MRI (R = 0.86, p mean of PET/CT and PET/MRI (R = 0.81, p max of PET/CT vs PET/MRI and -1.12 to +2.23 between SUV mean of PET/CT vs PET/MRI. PET image quality of PET/MRI was comparable to that of PET/CT. A highly significant correlation between SUV max and SUV mean was found. Both SUV max and SUV mean were significantly lower in [ 18 F]choline PET/MRI than in [ 18 F]choline PET/CT. Differences of SUV max and SUV mean might be caused by different techniques of attenuation correction. Furthermore, differences in biodistribution and biokinetics of [ 18 F]choline between the subsequent examinations and in the respective organ systems have to be taken into account. (orig.)

Intestinal absorption of cytidine diphosphate choline and its changes in the digestive tract

International Nuclear Information System (INIS)

Yashima, Keisuke; Takamatsu, Masatoshi; Okuda, Kunio

1975-01-01

Intestinal absorption of cytidine diphosphate choline (CDP-choline), its structural changes in the digestive tract, and hepatic uptake have been investigated in rats using 14 C-labeled ( 14 CH 3 attached to N of choline) and 3 H-labeled (at C 5 of pyrimidine) compounds. The results indicate that: 1) CDP-choline is relatively stable in the stomach, but is quickly degraded into cytidine and choline in the intestine; 2) The hepatic uptakes of 14 C and 3 H reach the maximum in two to three hours after oral administration; 3) Whereas the amount of 14 C remaining in the gut is inversely related to the hepatic uptake, no similar correlation is seen with 3 H-labeled CDP-choline, and 4) Extrahepatic uptake of 14 C and 3 H is very small. The possibility of phosphorylation in the mucosa of choline and cytidine has been discussed, based on the differences in relative amount of radioactivity in individual broken-down products in the intestinal lumen and mucosa. (auth.)

Chunggan extract (CGX), methionine-and choline-deficient (MCD) diet-induced hepatosteatosis and oxidative stress in C57BL/6 mice.

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Park, H-J; Han, J-M; Kim, H-G; Choi, M-K; Lee, J-S; Lee, H-W; Son, C-G

2013-12-01

In the present study, we aimed to evaluate the hepatoprotective and antioxidant effects of Chunggan extract (CGX) in an animal model of hepatosteatosis. The C57BL/6N mice were fed either methionine- and choline-sufficient (MCS) diet (n = 10) or a methionine- and choline-deficient (MCD) diet (n = 50) for 4 weeks, and then they were treated orally with CGX (100 or 200 mg/kg), ursodeoxycholic acid (80 mg/kg, as a positive control), or distilled water (DW, MCS diet group, and MCD diet group) for the final 2 weeks (once per day). The MCD diet induced severe hepatic injury with the typical features of hepatosteatosis in both serum and hepatic tissues. CGX treatment significantly attenuated these alterations in the serum levels including triglyceride (TG), aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and total bilirubin. Moreover, CGX also efficiently prevented from the hepatic TG accumulation in the hepatic tissue, evidenced by histopathological findings, compared with the MCD diet. In addition, CGX treatment significantly ameliorated the excessive oxidative stress and antioxidant markers in the serum as well as the hepatic levels of reactive oxygen species, the levels of malondialdehyde, the protein carbonyl, and total antioxidant capacity, and the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. In conclusion, our results indicate the experimental relevance of CGX for potential clinical application in patients with hepatosteatotic disorders and a possible mechanism related to its antioxidant properties.

A comparison between endogenous acetylcholiner release and (3H) choline outflow from guinea-pig brain slices

International Nuclear Information System (INIS)

Beani, L.; Bianchi, C.; Siniscalchi, A.; Sivilotti, L.; Tanganelli, S.; Veratti, E.

1986-01-01

The measure of tritium-choline efflux from preloaded brain slices is considered a valid method for studying cholinergic functiton. At variance with th say of endogenous acetylcholine this procedure gives andindex of the release process in the absence of esterase inhibition, thus excluding the dampening of the autoreceptor-mediated negative feedback. In order to establish the equivalence of these approaches the tow methods have been compared on electrically=stimulated guinea-pig brain slices, kept under the ame experimental conditions. The results show that only a partial equivalence of the two methods can be recognized. A drawback of the tritium-choline approach is the exhaustion or dilution of tritium stores, so that drug-induced increases of evoked efflux are minimized

Branched-chain amino acids alleviate hepatic steatosis and liver injury in choline-deficient high-fat diet induced NASH mice.

Science.gov (United States)

Honda, Takashi; Ishigami, Masatoshi; Luo, Fangqiong; Lingyun, Ma; Ishizu, Yoji; Kuzuya, Teiji; Hayashi, Kazuhiko; Nakano, Isao; Ishikawa, Tetsuya; Feng, Guo-Gang; Katano, Yoshiaki; Kohama, Tomoya; Kitaura, Yasuyuki; Shimomura, Yoshiharu; Goto, Hidemi; Hirooka, Yoshiki

2017-04-01

For successful treatment for nonalcoholic steatohepatitis (NASH), it may be important to treat the individual causative factors. At present, however, there is no established treatment for this disease. Branched-chain amino acids (BCAAs) have been used to treat patients with decompensated cirrhosis. In order to elucidate the mechanisms responsible for the effects of BCAAs on hepatic steatosis and disease progression, we investigated the effects of BCAA supplementation in mice fed a choline-deficient high-fat diet (CDHF), which induces NASH. Male mice were divided into four groups that received (1) choline-sufficient high fat (HF) diet (HF-control), (2) HF plus 2% BCAA in drinking water (HF-BCAA), (3) CDHF diet (CDHF-control), or (4) CDHF-BCAA for 8weeks. We monitored liver injury, hepatic steatosis and cholesterol, gene expression related to lipid metabolism, and hepatic fat accumulation. Serum alanine aminotransferase (ALT) levels and hepatic triglyceride (TG) were significantly elevated in CDHF-control relative to HF-control. Liver histopathology revealed severe steatosis, inflammation, and pericellular fibrosis in CDHF-control, confirming the NASH findings. Serum ALT levels and hepatic TG and lipid droplet areas were significantly lower in CDHF-BCAA than in CDHF-control. Gene expression and protein level of fatty acid synthase (FAS), which catalyzes the final step in fatty acid biosynthesis, was significantly decreased in CDHF-BCAA than in CDHF-control (PBCAA was significantly lower than those of CDHF-control. BCAA can alleviate hepatic steatosis and liver injury associated with NASH by suppressing FAS gene expression and protein levels. Copyright © 2017 Elsevier Inc. All rights reserved.

Choline concentrations are lower in postnatal plasma of preterm infants than in cord plasma.

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Bernhard, Wolfgang; Raith, Marco; Kunze, Rebecca; Koch, Vera; Heni, Martin; Maas, Christoph; Abele, Harald; Poets, Christian F; Franz, Axel R

2015-08-01

Choline is essential to human development, particularly of the brain in the form of phosphatidylcholine, sphingomyelin and acetylcholine, for bile and lipoprotein formation, and as a methyl group donator. Choline is actively transported into the fetus, and maternal supply correlates with cognitive outcome. Interruption of placental supply may therefore impair choline homeostasis in preterm infants. Determination of postnatal plasma concentrations of choline and its derivatives betaine and dimethylglycine (DMG) in preterm infants compared to cord and maternal blood matched for postmenstrual age (PMA). We collected plasma of very low-birth-weight infants undergoing neonatal intensive care (n = 162), cord plasma of term and preterm infants (n = 176, 24-42-week PMA), serum of parturients (n = 36), and plasma of healthy premenopausal women (n = 40). Target metabolites were analyzed with tandem mass spectrometry and reported as median (25th/75th percentiles). Cord plasma choline concentration was 41.4 (31.8-51.2) µmol/L and inversely correlated with PMA. In term but not in preterm infants, cord plasma choline was lower in girls than in boys. Prenatal glucocorticoid treatment did not affect choline levels in cord plasma, whereas betaine was decreased and DMG increased. In parturients and non-pregnant women, choline concentrations were 14.1 (10.3-16.9) and 8.8 (5.7-11.2) µmol/L, respectively, whereas betaine was lowest in parturients. After delivery, preterm infant plasma choline decreased to 20.8 (16.0-27.6) µmol/L within 48 h. Betaine and DMG correlated with plasma choline in all groups. In preterm infants, plasma choline decreases to 50 % of cord plasma concentrations, reflecting choline undernourishment and postnatal metabolic adaptation, and potentially contributing to impaired outcome.

Seizure-induced brain lesions: A wide spectrum of variably reversible MRI abnormalities

International Nuclear Information System (INIS)

Cianfoni, A.; Caulo, M.; Cerase, A.; Della Marca, G.; Falcone, C.; Di Lella, G.M.; Gaudino, S.; Edwards, J.; Colosimo, C.

2013-01-01

Introduction MRI abnormalities in the postictal period might represent the effect of the seizure activity, rather than its structural cause. Material and Methods Retrospective review of clinical and neuroimaging charts of 26 patients diagnosed with seizure-related MR-signal changes. All patients underwent brain-MRI (1.5-Tesla, standard pre- and post-contrast brain imaging, including DWI-ADC in 19/26) within 7 days from a seizure and at least one follow-up MRI, showing partial or complete reversibility of the MR-signal changes. Extensive clinical work-up and follow-up, ranging from 3 months to 5 years, ruled out infection or other possible causes of brain damage. Seizure-induced brain-MRI abnormalities remained a diagnosis of exclusion. Site, characteristics and reversibility of MRI changes, and association with characteristics of seizures were determined. Results MRI showed unilateral (13/26) and bilateral abnormalities, with high (24/26) and low (2/26) T2-signal, leptomeningeal contrast-enhancement (2/26), restricted diffusion (9/19). Location of abnormality was cortical/subcortical, basal ganglia, white matter, corpus callosum, cerebellum. Hippocampus was involved in 10/26 patients. Reversibility of MRI changes was complete in 15, and with residual gliosis or focal atrophy in 11 patients. Reversibility was noted between 15 and 150 days (average, 62 days). Partial simple and complex seizures were associated with hippocampal involvement (p = 0.015), status epilepticus with incomplete reversibility of MRI abnormalities (p = 0.041). Conclusions Seizure or epileptic status can induce transient, variably reversible MRI brain abnormalities. Partial seizures are frequently associated with hippocampal involvement and status epilepticus with incompletely reversible lesions. These seizure-induced MRI abnormalities pose a broad differential diagnosis; increased awareness may reduce the risk of misdiagnosis and unnecessary intervention

Seizure-induced brain lesions: A wide spectrum of variably reversible MRI abnormalities

Energy Technology Data Exchange (ETDEWEB)

Cianfoni, A., E-mail: acianfoni@hotmail.com [Neuroradiology, Neurocenter of Italian Switzerland–Ospedale regionale Lugano, Via Tesserete 46, Lugano, 6900, CH (Switzerland); Caulo, M., E-mail: caulo@unich.it [Department of Neuroscience and Imaging, University of Chieti, Via dei Vestini 33, 6610 Chieti. Italy (Italy); Cerase, A., E-mail: alfonsocerase@gmail.com [Unit of Neuroimaging and Neurointervention NINT, Department of Neurological and Sensorineural Sciences, Azienda Ospedaliera Universitaria Senese, Policlinico “Santa Maria alle Scotte”, V.le Bracci 16, Siena (Italy); Della Marca, G., E-mail: dellamarca@rm.unicatt.it [Neurology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy); Falcone, C., E-mail: carlo_falc@libero.it [Radiology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy); Di Lella, G.M., E-mail: gdilella@rm.unicatt.it [Radiology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy); Gaudino, S., E-mail: sgaudino@sirm.org [Radiology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy); Edwards, J., E-mail: edwardjc@musc.edu [Neuroscience Dept., Medical University of South Carolina, 96J Lucas st, 29425, Charleston, SC (United States); Colosimo, C., E-mail: colosimo@rm.unicatt.it [Radiology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy)

2013-11-01

Introduction MRI abnormalities in the postictal period might represent the effect of the seizure activity, rather than its structural cause. Material and Methods Retrospective review of clinical and neuroimaging charts of 26 patients diagnosed with seizure-related MR-signal changes. All patients underwent brain-MRI (1.5-Tesla, standard pre- and post-contrast brain imaging, including DWI-ADC in 19/26) within 7 days from a seizure and at least one follow-up MRI, showing partial or complete reversibility of the MR-signal changes. Extensive clinical work-up and follow-up, ranging from 3 months to 5 years, ruled out infection or other possible causes of brain damage. Seizure-induced brain-MRI abnormalities remained a diagnosis of exclusion. Site, characteristics and reversibility of MRI changes, and association with characteristics of seizures were determined. Results MRI showed unilateral (13/26) and bilateral abnormalities, with high (24/26) and low (2/26) T2-signal, leptomeningeal contrast-enhancement (2/26), restricted diffusion (9/19). Location of abnormality was cortical/subcortical, basal ganglia, white matter, corpus callosum, cerebellum. Hippocampus was involved in 10/26 patients. Reversibility of MRI changes was complete in 15, and with residual gliosis or focal atrophy in 11 patients. Reversibility was noted between 15 and 150 days (average, 62 days). Partial simple and complex seizures were associated with hippocampal involvement (p = 0.015), status epilepticus with incomplete reversibility of MRI abnormalities (p = 0.041). Conclusions Seizure or epileptic status can induce transient, variably reversible MRI brain abnormalities. Partial seizures are frequently associated with hippocampal involvement and status epilepticus with incompletely reversible lesions. These seizure-induced MRI abnormalities pose a broad differential diagnosis; increased awareness may reduce the risk of misdiagnosis and unnecessary intervention.

Reversible Age-Related Phenotypes Induced during Larval Quiescence in C. elegans

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Roux, Antoine E.; Langhans, Kelley; Huynh, Walter; Kenyon, Cynthia

2017-01-01

Summary Cells can enter quiescent states in which cell cycling and growth are suspended. We find that during a long developmental arrest (quiescence) induced by starvation, newly-hatched C. elegans acquire features associated with impaired proteostasis and aging: mitochondrial fission, ROS production, protein aggregation, decreased proteotoxic-stress resistance, and at the organismal level, decline of mobility and high mortality. All signs of aging but one, the presence of protein aggregates, were reversed upon return to development induced by feeding. The endoplasmic reticulum receptor IRE-1 is completely required for recovery, and the downstream transcription factor XBP-1, as well as a protein kinase, KGB-1, are partially required. Interestingly, kgb-1(−) mutants that do recover fail to reverse aging-like mitochondrial phenotypes and have a short adult lifespan. Our study describes the first pathway that reverses phenotypes of aging at the exit of prolonged quiescence. PMID:27304510

Choline requirements of White Pekin ducks from hatch to 21 days of age.

Science.gov (United States)

Wen, Z G; Tang, J; Hou, S S; Guo, Y M; Huang, W; Xie, M

2014-12-01

A dose-response experiment with 8 dietary choline levels (302, 496, 778, 990, 1,182, 1,414, 1,625, and 1,832 mg/kg) was conducted with male White Pekin ducks to estimate the choline requirement from hatch to 21 d of age. Three hundred eighty-four 1-d-old male White Pekin ducks were randomly assigned to 8 dietary treatments, each containing 6 replicate pens with 8 birds per pen. At 21 d of age, weight gain, feed intake, and feed/gain from each pen were calculated for feeding period, and 2 ducks selected randomly from each pen were euthanized and the liver was collected to determine total lipids, triglycerides, and phospholipids. In our study, perosis, poor growth, and high liver fat were all observed in choline-deficient ducks and incidence of perosis was zero when dietary choline was 1,182 mg/kg. As dietary choline increased, the weight gain and feed intake increased linearly or quadratically (P < 0.05). On the other hand, as dietary choline increased, the total lipid and triglyceride in liver decreased linearly and liver phospholipid increased linearly (P < 0.05), and the lipotropic activity of choline may be associated with increasing phospholipid at a high dietary choline level. According to broken-line regression, the choline requirements for weight gain and feed intake were 810 and 823 mg/kg, respectively, but higher requirement should be considered to prevent perosis and excess liver lipid deposition completely. ©2014 Poultry Science Association Inc.

First interactions between hydrogen and stress-induced reverse transformation of Ni-Ti superelastic alloy

Science.gov (United States)

Yokoyama, Ken'ichi; Hashimoto, Tatsuki; Sakai, Jun'ichi

2017-11-01

The first dynamic interactions between hydrogen and the stress-induced reverse transformation have been investigated by performing an unloading test on a Ni-Ti superelastic alloy subjected to hydrogen charging under a constant applied strain in the elastic deformation region of the martensite phase. Upon unloading the specimen, charged with a small amount of hydrogen, no change in the behaviour of the stress-induced reverse transformation is observed in the stress-strain curve, although the behaviour of the stress-induced martensite transformation changes. With increasing amount of hydrogen charging, the critical stress for the reverse transformation markedly decreases. Eventually, for a larger amount of hydrogen charging, the reverse transformation does not occur, i.e. there is no recovery of the superelastic strain. The residual martensite phase on the side surface of the unloaded specimen is confirmed by X-ray diffraction. Upon training before the unloading test, the properties of the reverse transformation slightly recover after ageing in air at room temperature. The present study indicates that to change the behaviour of the reverse transformation a larger amount of hydrogen than that for the martensite transformation is necessary. In addition, it is likely that a substantial amount of hydrogen in solid solution more strongly suppresses the reverse transformation than hydrogen trapped at defects, thereby stabilising the martensite phase.

Metformin prevents and reverses inflammation in a non-diabetic mouse model of nonalcoholic steatohepatitis.

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Yuki Kita

Full Text Available BACKGROUND: Optimal treatment for nonalcoholic steatohepatitis (NASH has not yet been established, particularly for individuals without diabetes. We examined the effects of metformin, commonly used to treat patients with type 2 diabetes, on liver pathology in a non-diabetic NASH mouse model. METHODOLOGY/PRINCIPAL FINDINGS: Eight-week-old C57BL/6 mice were fed a methionine- and choline-deficient plus high fat (MCD+HF diet with or without 0.1% metformin for 8 weeks. Co-administration of metformin significantly decreased fasting plasma glucose levels, but did not affect glucose tolerance or peripheral insulin sensitivity. Metformin ameliorated MCD+HF diet-induced hepatic steatosis, inflammation, and fibrosis. Furthermore, metformin significantly reversed hepatic steatosis and inflammation when administered after the development of experimental NASH. CONCLUSIONS/SIGNIFICANCE: These histological changes were accompanied by reduced hepatic triglyceride content, suppressed hepatic stellate cell activation, and the downregulation of genes involved in fatty acid metabolism, inflammation, and fibrogenesis. Metformin prevented and reversed steatosis and inflammation of NASH in an experimental non-diabetic model without affecting peripheral insulin resistance.

Transport and phosphorylation of choline in higher plant cells. Phosphorus-31 nuclear magnetic resonance studies

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Bligny, R.; Foray, M.F.; Roby, C.; Douce, R.

1989-03-25

When sycamore cells were suspended in basal medium containing choline, the latter was taken up by the cells very rapidly. A facilitated diffusion system appertained at low concentrations of choline and exhibited Michaelis-Menten kinetics. At higher choline concentrations simple diffusion appeared to be the principal mode of uptake. Addition of choline to the perfusate of compressed sycamore cells monitored by /sup 31/P NMR spectroscopy resulted in a dramatic accumulation of P-choline in the cytoplasmic compartment containing choline kinase and not in the vacuole. The total accumulation of P-choline over a 10-h period exhibited Michaelis-Menten kinetics. During this period, in the absence of Pi in the perfusion medium there was a marked depletion of glucose-6-P, and the cytoplasmic Pi resonance disappeared almost completely. When a threshold of cytoplasmic Pi was attained, the phosphorylation of choline was sustained by the continuous release of Pi from the vacuole although at a much lower rate. However, when 100 microM inorganic phosphate was present in the perfusion medium, externally added Pi was preferentially used to sustain P-choline synthesis. It is clear, therefore, that cytosolic choline kinase associated with a carrier-mediated transport system for choline uptake appeared as effective systems for continuously trapping cytoplasmic Pi including vacuolar Pi entering the cytoplasm.

The Investigation of Strain-Induced Martensite Reverse Transformation in AISI 304 Austenitic Stainless Steel

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Cios, G.; Tokarski, T.; Żywczak, A.; Dziurka, R.; Stępień, M.; Gondek, Ł.; Marciszko, M.; Pawłowski, B.; Wieczerzak, K.; Bała, P.

2017-10-01

This paper presents a comprehensive study on the strain-induced martensitic transformation and reversion transformation of the strain-induced martensite in AISI 304 stainless steel using a number of complementary techniques such as dilatometry, calorimetry, magnetometry, and in-situ X-ray diffraction, coupled with high-resolution microstructural transmission Kikuchi diffraction analysis. Tensile deformation was applied at temperatures between room temperature and 213 K (-60 °C) in order to obtain a different volume fraction of strain-induced martensite (up to 70 pct). The volume fraction of the strain-induced martensite, measured by the magnetometric method, was correlated with the total elongation, hardness, and linear thermal expansion coefficient. The thermal expansion coefficient, as well as the hardness of the strain-induced martensitic phase was evaluated. The in-situ thermal treatment experiments showed unusual changes in the kinetics of the reverse transformation (α' → γ). The X-ray diffraction analysis revealed that the reverse transformation may be stress assisted—strains inherited from the martensitic transformation may increase its kinetics at the lower annealing temperature range. More importantly, the transmission Kikuchi diffraction measurements showed that the reverse transformation of the strain-induced martensite proceeds through a displacive, diffusionless mechanism, maintaining the Kurdjumov-Sachs crystallographic relationship between the martensite and the reverted austenite. This finding is in contradiction to the results reported by other researchers for a similar alloy composition.

Influence of dietary protein and excess methionine on choline needs for young bobwhite quail

Science.gov (United States)

Serafin, J.A.

1982-01-01

Experiments were conducted with young Bobwhite quail (Colinus virginianus) to investigate the effect of differing dietary protein levels and nondetrimental amounts of excess methionine on choline needs. Growth and feed consumption of quail fed an adequate (27.3%) protein purified diet supplemented with 2000 mg/kg of choline were unaffected by increasing the level of excess methionine to 1.75%; however, greater amounts (2.0%, 2.25%) of excess methionine depressed growth (P less than .01), reduced feed consumption (P less than .01), and decreased feed utilization (P less than .05). Quail fed a purified diet containing 13.85% protein and 515 mg/kg of choline grew poorly. Growth was unaffected by additional choline in this diet. Growth was suboptimal among quail fed purified diets containing adequate or high (41.55%) levels of protein in which choline was limiting; however, a high level of protein did not in itself affect performance. Growth was improved by supplemental choline in these diets. Growth of quail fed purified diets with up to 1.35% excess methionine which were limiting (531 mg/kg) in choline was less than that of groups fed 2000 mg/kg of added dietary choline (P less than .01); however, excess methionine did not significantly influence growth of quail fed choline-deficient diets. These experiments indicate that neither high dietary protein nor excess methionine, fed at non-growth-depressing levels, increases dietary choline needs for young Bobwhite quail.

Exercise reverses metabolic syndrome in high-fat diet-induced obese rats.

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Touati, Sabeur; Meziri, Fayçal; Devaux, Sylvie; Berthelot, Alain; Touyz, Rhian M; Laurant, Pascal

2011-03-01

Chronic consumption of a high-fat diet induces obesity. We investigated whether exercise would reverse the cardiometabolic disorders associated with obesity without it being necessary to change from a high- to normal-fat diet. Sprague-Dawley rats were placed on a high-fat (HFD) or control diet (CD) for 12 wk. HFD rats were then divided into four groups: sedentary HFD (HFD-S), exercise trained (motor treadmill for 12 wk) HFD (HFD-Ex), modified diet (HFD to CD; HF/CD-S), and exercise trained with modified diet (HF/CD-Ex). Cardiovascular risk parameters associated with metabolic syndrome were measured, and contents of aortic Akt, phospho-Akt at Ser (473), total endothelial nitric oxide synthase (eNOS), and phospho-eNOS at Ser (1177) were determined by Western blotting. Chronic consumption of HFD induced a metabolic syndrome. Exercise and dietary modifications reduced adiposity, improved glucose and insulin levels and plasma lipid profile, and exerted an antihypertensive effect. Exercise was more effective than dietary modification in improving plasma levels of thiobarbituric acid-reacting substance and in correcting the endothelium-dependent relaxation to acetylcholine and insulin. Furthermore, independent of the diet used, exercise increased Akt and eNOS phosphorylation. Metabolic syndrome induced by HFD is reversed by exercise and diet modification. It is demonstrated that exercise training induces these beneficial effects without the requirement for dietary modification, and these beneficial effects may be mediated by shear stress-induced Akt/eNOS pathway activation. Thus, exercise may be an effective strategy to reverse almost all the atherosclerotic risk factors linked to obesity, particularly in the vasculature.

The nutrigenetics and nutrigenomics of the dietary requirement for choline.

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Corbin, Karen D; Zeisel, Steven H

2012-01-01

Advances in nutrigenetics and nutrigenomics have been instrumental in demonstrating that nutrient requirements vary among individuals. This is exemplified by studies of the nutrient choline, in which gender, single-nucleotide polymorphisms, estrogen status, and gut microbiome composition have been shown to influence its optimal intake level. Choline is an essential nutrient with a wide range of biological functions, and current studies are aimed at refining our understanding of its requirements and, importantly, on defining the molecular mechanisms that mediate its effects in instances of suboptimal dietary intake. This chapter introduces the reader to challenges in developing individual nutrition recommendations, the biological function of choline, current and future research paradigms to fully understand the consequences of inadequate choline nutrition, and some forward thinking about the potential for individualized nutrition recommendations to become a tangible application for improved health. Copyright © 2012 Elsevier Inc. All rights reserved.

Therapeutic Efficacy of Fenugreek Extract or/and Choline with Docosahexaenoic Acid in Attenuating Learning and Memory Deficits in Ovariectomized Rats

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Anjaneyulu K

2018-04-01

Full Text Available Background: Studies have demonstrated that estradiol influences cognitive functions. Phytoestrogens and many other estrogen-like compounds in plants have beneficial effects on cognitive performance in postmenopausal women. However, there is no evident report of fenugreek and choline-Docosahexaenoic Acid (DHA on cognition in ovariectomized rats. Aim and Objectives: The present study was aimed to evaluate the therapeutic efficacy of fenugreek extract or/and choline- DHA in attenuating ovariectomy-induced memory impairment, brain antioxidant status and hippocampal neural cell deficits in the rat model. Material and Methods: Female Wistar 9-10 months old rats were grouped (n=12/group as - (1 Normal Control (NC, (2 Ovariectomized (OVX, (3 OVX+FG (hydroalcoholic seed extract of fenugreek, (4 OVX+C-DHA,(5 OVX+FG+C-DHA and (6 OVX+Estradiol. Groups 2- 6 were bilaterally OVX. FG, C-DHA was supplemented orally for 30 days, 14 days after ovariectomy. Assessment of learning and memory was performed by passive avoidance test. Oxidative stress and antioxidant markers were assessed by standard methods. Nissl stained hippocampal sections were analyzed to determine alterations in neural cell numbers in CA1, CA3 and dentate gyrus. Results: Supplementation of FG or/and choline with DHA to OVX rats, caused significant improvement in learning and memory as well as decreased neural cell deficits compared to the same in OVX rats. Further, significantly reduced levels of brain Malondialdehyde (MDA and increased levels of Glutathione (GSH were observed. Conclusion: Therapeutic supplementation of FG with choline-DHA significantly attenuates ovariectomy-induced neurocognitive deficits in rats.

From the Cover: 7,8-Dihydroxyflavone Rescues Lead-Induced Impairment of Vesicular Release: A Novel Therapeutic Approach for Lead Intoxicated Children.

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Zhang, Xiao-Lei; McGlothan, Jennifer L; Miry, Omid; Stansfield, Kirstie H; Loth, Meredith K; Stanton, Patric K; Guilarte, Tomás R

2018-01-01

Childhood lead (Pb2+) intoxication is a public health problem of global proportion. Lead exposure during development produces multiple effects on the central nervous system including impaired synapse formation, altered synaptic plasticity, and learning deficits. In primary hippocampal neurons in culture and hippocampal slices, Pb2+ exposure inhibits vesicular release and reduces the number of fast-releasing sites, an effect associated with Pb2+ inhibition of NMDA receptor-mediated trans-synaptic Brain-Derived Neurotrophic Factor (BDNF) signaling. The objective of this study was to determine if activation of TrkB, the cognate receptor for BDNF, would rescue Pb2+-induced impairments of vesicular release. Rats were chronically exposed to Pb2+ prenatally and postnatally until 50 days of age. This chronic Pb2+ exposure paradigm enhanced paired-pulse facilitation of synaptic potentials in Schaffer collateral-CA1 synapses in the hippocampus, a phenomenon indicative of reduced vesicular release probability. Decreased vesicular release probability was confirmed by both mean-variance analysis and direct 2-photon imaging of vesicular release from hippocampal slices of rats exposed to Pb2+in vivo. We also found a Pb2+-induced impairment of calcium influx in Schaffer collateral-CA1 synaptic terminals. Intraperitoneal injections of Pb2+ rats with the TrkB receptor agonist 7,8-dihydroxyflavone (5 mg/kg) for 14-15 days starting at postnatal day 35, reversed all Pb2+-induced impairments of presynaptic transmitter release at Schaffer collateral-CA1 synapses. This study demonstrates for the first time that in vivo pharmacological activation of TrkB receptors by small molecules such as 7,8-dihydroxyflavone can reverse long-term effects of chronic Pb2+ exposure on presynaptic terminals, pointing to TrkB receptor activation as a promising therapeutic intervention in Pb2+-intoxicated children. © The Author 2017. Published by Oxford University Press on behalf of the Society of

Age-Dependent Cellular and Behavioral Deficits Induced by Molecularly Targeted Drugs Are Reversible.

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Scafidi, Joseph; Ritter, Jonathan; Talbot, Brooke M; Edwards, Jorge; Chew, Li-Jin; Gallo, Vittorio

2018-04-15

Newly developed targeted anticancer drugs inhibit signaling pathways commonly altered in adult and pediatric cancers. However, as these pathways are also essential for normal brain development, concerns have emerged of neurologic sequelae resulting specifically from their application in pediatric cancers. The neural substrates and age dependency of these drug-induced effects in vivo are unknown, and their long-term behavioral consequences have not been characterized. This study defines the age-dependent cellular and behavioral effects of these drugs on normally developing brains and determines their reversibility with post-drug intervention. Mice at different postnatal ages received short courses of molecularly targeted drugs in regimens analagous to clinical treatment. Analysis of rapidly developing brain structures important for sensorimotor and cognitive function showed that, while adult administration was without effect, earlier neonatal administration of targeted therapies attenuated white matter oligodendroglia and hippocampal neuronal development more profoundly than later administration, leading to long-lasting behavioral deficits. This functional impairment was reversed by rehabilitation with physical and cognitive enrichment. Our findings demonstrate age-dependent, reversible effects of these drugs on brain development, which are important considerations as treatment options expand for pediatric cancers. Significance: Targeted therapeutics elicit age-dependent long-term consequences on the developing brain that can be ameliorated with environmental enrichment. Cancer Res; 78(8); 2081-95. ©2018 AACR . ©2018 American Association for Cancer Research.

DSS colitis promotes tumorigenesis and fibrogenesis in a choline-deficient high-fat diet-induced NASH mouse model.

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Achiwa, Koichi; Ishigami, Masatoshi; Ishizu, Yoji; Kuzuya, Teiji; Honda, Takashi; Hayashi, Kazuhiko; Hirooka, Yoshiki; Katano, Yoshiaki; Goto, Hidemi

2016-01-29

Nonalcoholic steatohepatitis (NASH) patients progress to liver cirrhosis and even hepatocellular carcinoma (HCC). Several lines of evidence indicate that accumulation of lipopolysaccharide (LPS) and disruption of gut microbiota play contributory roles in HCC. Moreover, in a dextran sodium sulfate (DSS)-induced colitis model in mice, a high-fat diet increases portal LPS level and promotes hepatic inflammation and fibrosis. However, this diet-induced NASH model requires at least 50 weeks for carcinogenesis. In this study, we sought to determine whether increased intestinal permeability would aggravate liver inflammation and fibrosis and accelerate tumorigenesis in a diet-induced NASH model. Mice were fed a choline-deficient high-fat (CDHF) diet for 4 or 12 weeks. The DSS group was fed CDHF and intermittently received 1% DSS in the drinking water. Exposure to DSS promoted mucosal changes such as crypt loss and increased the number of inflammatory cells in the colon. In the DSS group, portal LPS levels were elevated at 4 weeks, and the proportions of Clostridium cluster XI in the fecal microbiota were elevated. In addition, levels of serum transaminase, number of lobular inflammatory cells, F4/80 staining-positive area, and levels of inflammatory cytokines were all elevated in the DSS group. Liver histology in the DSS group revealed severe fibrosis at 12 weeks. Liver tumors were detected in the DSS group at 12 weeks, but not in the other groups. Thus, DSS administration promoted liver tumors in a CDHF diet-induced NASH mouse over the short term, suggesting that the induction of intestinal inflammation and gut disruption of microbiota in NASH promote hepatic tumorigenesis. Copyright © 2015 Elsevier Inc. All rights reserved.

Phospholipid biosynthesis in Candida albicans: Regulation by the precursors inositol and choline

International Nuclear Information System (INIS)

Klig, L.S.; Friedli, L.; Schmid, E.

1990-01-01

Phospholipid metabolism in the pathogenic fungus Candida albicans was examined. The phospholipid biosynthetic pathways of C. albicans were elucidated and were shown to be similar to those of Saccharomyces cerevisiae. However, marked differences were seen between these two fungi in the regulation of the pathways in response to exogenously provided precursors inositol and choline. In S. cerevisiae, the biosynthesis of phosphatidylcholine via methylation of phosphatidylethanolamine appears to be regulated in response to inositol and choline; provision of choline alone does not repress the activity of this pathway. The same pathway in C. albicans responds to the exogenous provision of choline. Possible explanations for the observed differences in regulation are discussed

Choline transporter mutations in severe congenital myasthenic syndrome disrupt transporter localization.

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Wang, Haicui; Salter, Claire G; Refai, Osama; Hardy, Holly; Barwick, Katy E S; Akpulat, Ugur; Kvarnung, Malin; Chioza, Barry A; Harlalka, Gaurav; Taylan, Fulya; Sejersen, Thomas; Wright, Jane; Zimmerman, Holly H; Karakaya, Mert; Stüve, Burkhardt; Weis, Joachim; Schara, Ulrike; Russell, Mark A; Abdul-Rahman, Omar A; Chilton, John; Blakely, Randy D; Baple, Emma L; Cirak, Sebahattin; Crosby, Andrew H

2017-11-01

The presynaptic, high-affinity choline transporter is a critical determinant of signalling by the neurotransmitter acetylcholine at both central and peripheral cholinergic synapses, including the neuromuscular junction. Here we describe an autosomal recessive presynaptic congenital myasthenic syndrome presenting with a broad clinical phenotype due to homozygous choline transporter missense mutations. The clinical phenotype ranges from the classical presentation of a congenital myasthenic syndrome in one patient (p.Pro210Leu), to severe neurodevelopmental delay with brain atrophy (p.Ser94Arg) and extend the clinical outcomes to a more severe spectrum with infantile lethality (p.Val112Glu). Cells transfected with mutant transporter construct revealed a virtually complete loss of transport activity that was paralleled by a reduction in transporter cell surface expression. Consistent with these findings, studies to determine the impact of gene mutations on the trafficking of the Caenorhabditis elegans choline transporter orthologue revealed deficits in transporter export to axons and nerve terminals. These findings contrast with our previous findings in autosomal dominant distal hereditary motor neuropathy of a dominant-negative frameshift mutation at the C-terminus of choline transporter that was associated with significantly reduced, but not completely abrogated choline transporter function. Together our findings define divergent neuropathological outcomes arising from different classes of choline transporter mutation with distinct disease processes and modes of inheritance. These findings underscore the essential role played by the choline transporter in sustaining acetylcholine neurotransmission at both central and neuromuscular synapses, with important implications for treatment and drug selection. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Chronic lead exposure induces cochlear oxidative stress and potentiates noise-induced hearing loss.

Science.gov (United States)

Jamesdaniel, Samson; Rosati, Rita; Westrick, Judy; Ruden, Douglas M

2018-08-01

Acquired hearing loss is caused by complex interactions of multiple environmental risk factors, such as elevated levels of lead and noise, which are prevalent in urban communities. This study delineates the mechanism underlying lead-induced auditory dysfunction and its potential interaction with noise exposure. Young-adult C57BL/6 mice were exposed to: 1) control conditions; 2) 2 mM lead acetate in drinking water for 28 days; 3) 90 dB broadband noise 2 h/day for two weeks; and 4) both lead and noise. Blood lead levels were measured by inductively coupled plasma mass spectrometry analysis (ICP-MS) lead-induced cochlear oxidative stress signaling was assessed using targeted gene arrays, and the hearing thresholds were assessed by recording auditory brainstem responses. Chronic lead exposure downregulated cochlear Sod1, Gpx1, and Gstk1, which encode critical antioxidant enzymes, and upregulated ApoE, Hspa1a, Ercc2, Prnp, Ccl5, and Sqstm1, which are indicative of cellular apoptosis. Isolated exposure to lead or noise induced 8-12 dB and 11-25 dB shifts in hearing thresholds, respectively. Combined exposure induced 18-30 dB shifts, which was significantly higher than that observed with isolated exposures. This study suggests that chronic exposure to lead induces cochlear oxidative stress and potentiates noise-induced hearing impairment, possibly through parallel pathways. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Comparison of the computational NMR chemical shifts of choline with the experimental data

International Nuclear Information System (INIS)

Alcorn, C; Cuperlovic-Culf, M; Ghandi, K

2012-01-01

One of the main biological markers of the presence of cancer in living patients is an over-expression of total choline (tCho), which is the sum of free choline and its derivatives. 1 H Magnetic Resonance Spectroscopy, or H-MRS, enables the quantification of tCho via its proton spectra, and thus has the potential to be a diagnostic tool for the presence of cancer and an accurate early indicator of the response of cancer to treatment. However, it remains difficult to quantify individual choline derivatives, since they share a large structural similarity ((CH 3 ) 3 -N + -CH 2 -CH 2 -O-), of which the strongest signal detectable by MRS is that of the choline h ead group : the three methyl groups bonded to the nitrogen. This work used ACENet, a high performance computing system, to attempt to model the NMR parameters of choline derivatives, with the focus of this report being free choline. Optimized structures were determined using Density Functional Theory and the B3LYP electron correlation functional. The Polarizable Continuum Model was used to evaluate solvent effects. The Gauge-Invariant Atomic Orbital method was found to be the superior method for calculating the NMR parameters of cholines.

Injection-induced gluteus muscle contractures: diagnosis with the "reverse Ober test" and surgical management.

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Scully, William F; White, Klane K; Song, Kit M; Mosca, Vincent S

2015-03-01

, such as Russia and China, injection-induced gluteus muscle contractures are seldom seen in the United States and other developed countries. Diagnosis of this condition can be difficult leading to inappropriate treatment. Knowledge of the clinical presentation typical of a gluteus contracture and of the pathognomonic finding of a "reverse Ober test" can facilitate an effective surgical procedure to correct the associated functional impairment. Level IV: retrospective case series.

Are dietary choline and betaine intakes determinants of total homocysteine concentration?

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Elevated homocysteine concentrations are associated with an increased risk of cardiovascular disease and a decline in cognitive function. Intakes of choline and betaine, as methyl donors, may affect homocysteine concentrations. The objective was to examine whether choline and betaine intakes, assess...

Reversible Heat-Induced Inactivation of Chimeric β-Glucuronidase in Transgenic Plants1

Science.gov (United States)

Almoguera, Concepción; Rojas, Anabel; Jordano, Juan

2002-01-01

We compared the expression patterns in transgenic tobacco (Nicotiana tabacum) of two chimeric genes: a translational fusion to β-glucuronidase (GUS) and a transcriptional fusion, both with the same promoter and 5′-flanking sequences of Ha hsp17.7 G4, a small heat shock protein (sHSP) gene from sunflower (Helianthus annuus). We found that immediately after heat shock, the induced expression from the two fusions in seedlings was similar, considering chimeric mRNA or GUS protein accumulation. Surprisingly, we discovered that the chimeric GUS protein encoded by the translational fusion was mostly inactive in such conditions. We also found that this inactivation was fully reversible. Thus, after returning to control temperature, the GUS activity was fully recovered without substantial changes in GUS protein accumulation. In contrast, we did not find differences in the in vitro heat inactivation of the respective GUS proteins. Insolubilization of the chimeric GUS protein correlated with its inactivation, as indicated by immunoprecipitation analyses. The inclusion in another chimeric gene of the 21 amino-terminal amino acids from a different sHSP lead to a comparable reversible inactivation. That effect not only illustrates unexpected post-translational problems, but may also point to sequences involved in interactions specific to sHSPs and in vivo heat stress conditions. PMID:12011363

Population pharmacokinetic–pharmacodynamic analysis for sugammadex-mediated reversal of rocuronium-induced neuromuscular blockade

Science.gov (United States)

Kleijn, Huub J; Zollinger, Daniel P; van den Heuvel, Michiel W; Kerbusch, Thomas

2011-01-01

AIMS An integrated population pharmacokinetic–pharmacodynamic model was developed with the following aims: to simultaneously describe pharmacokinetic behaviour of sugammadex and rocuronium; to establish the pharmacokinetic–pharmacodynamic model for rocuronium-induced neuromuscular blockade and reversal by sugammadex; to evaluate covariate effects; and to explore, by simulation, typical covariate effects on reversal time. METHODS Data (n = 446) from eight sugammadex clinical studies covering men, women, non-Asians, Asians, paediatrics, adults and the elderly, with various degrees of renal impairment, were used. Modelling and simulation techniques based on physiological principles were applied to capture rocuronium and sugammadex pharmacokinetics and pharmacodynamics and to identify and quantify covariate effects. RESULTS Sugammadex pharmacokinetics were affected by renal function, bodyweight and race, and rocuronium pharmacokinetics were affected by age, renal function and race. Sevoflurane potentiated rocuronium-induced neuromuscular blockade. Posterior predictive checks and bootstrapping illustrated the accuracy and robustness of the model. External validation showed concordance between observed and predicted reversal times, but interindividual variability in reversal time was pronounced. Simulated reversal times in typical adults were 0.8, 1.5 and 1.4 min upon reversal with sugammadex 16 mg kg−1 3 min after rocuronium, sugammadex 4 mg kg−1 during deep neuromuscular blockade and sugammadex 2 mg kg−1 during moderate blockade, respectively. Simulations indicated that reversal times were faster in paediatric patients and slightly slower in elderly patients compared with adults. Renal function did not affect reversal time. CONCLUSIONS Simulations of the therapeutic dosing regimens demonstrated limited impact of age, renal function and sevoflurane use, as predicted reversal time in typical subjects was always <2 min. PMID:21535448

Clinically Relevant Pharmacological Strategies That Reverse MDMA-Induced Brain Hyperthermia Potentiated by Social Interaction.

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Kiyatkin, Eugene A; Ren, Suelynn; Wakabayashi, Ken T; Baumann, Michael H; Shaham, Yavin

2016-01-01

MDMA-induced hyperthermia is highly variable, unpredictable, and greatly potentiated by the social and environmental conditions of recreational drug use. Current strategies to treat pathological MDMA-induced hyperthermia in humans are palliative and marginally effective, and there are no specific pharmacological treatments to counteract this potentially life-threatening condition. Here, we tested the efficacy of mixed adrenoceptor blockers carvedilol and labetalol, and the atypical antipsychotic clozapine, in reversing MDMA-induced brain and body hyperthermia. We injected rats with a moderate non-toxic dose of MDMA (9 mg/kg) during social interaction, and we administered potential treatment drugs after the development of robust hyperthermia (>2.5 °C), thus mimicking the clinical situation of acute MDMA intoxication. Brain temperature was our primary focus, but we also simultaneously recorded temperatures from the deep temporal muscle and skin, allowing us to determine the basic physiological mechanisms of the treatment drug action. Carvedilol was modestly effective in attenuating MDMA-induced hyperthermia by moderately inhibiting skin vasoconstriction, and labetalol was ineffective. In contrast, clozapine induced a marked and immediate reversal of MDMA-induced hyperthermia via inhibition of brain metabolic activation and blockade of skin vasoconstriction. Our findings suggest that clozapine, and related centrally acting drugs, might be highly effective for reversing MDMA-induced brain and body hyperthermia in emergency clinical situations, with possible life-saving results.

Ocular lesions and experimental choline deficiency Lesiones oculares y deficiencia experimental de colina

Directory of Open Access Journals (Sweden)

Georgina P. Ossani

2006-10-01

Full Text Available Previous studies have shown ocular haemorrhages in choline-deficient rats. The aim of this paper is to study further the relationship between ocular and renal lesions and biochemical alterations in rats fed a choline-deficient diet. Fifty one weanling male Wistar rats, were divided into two groups. Thirty one of them were fed a choline-deficient diet and the rest was fed a choline-supplemented diet ad libitum. Animals from both groups were killed between the fifth and the eighth day. Urea, creatinine and homocysteine concentrations in blood were determined. Eyes were used for light microscopy study; high resolution light microscopy and the study of the retina as "rétine a plat". Kidneys were studied by light microscopy. Choline-supplemented rats did not show ocular or renal lesion. Choline-deficient rats that showed renal lesions, tubular or cortical necrosis, did not always have ocular changes. There were no ocular changes in the only choline-deficient rat without renal lesion. The ocular changes consisted mainly in haemorrhage in both cameras and ciliary and vitreous bodies. Correlations between ocular and renal lesion (r=0.72, pEstudios previos han demostrado hemorragia ocular en ratas deficientes en colina. El objetivo de este trabajo es profundizar en la relación entre las alteraciones oculares, renales y bioquímicas en ratas deficientes en colina. Cincuenta y una ratas Wistar macho recién destetadas fueron divididas en dos grupos: treinta y una fueron alimentadas con una dieta colino deficiente y el resto con colina suplementada ad-libitum. Los animales de ambos grupos fueron sacrificados entre el quinto y el octavo día. Se midió la concentración de urea, creatinina y homocisteína en sangre. Los ojos fueron estudiados por microscopía de luz, microscopía óptica de alta resolución y para el estudio de la retina como retina plana. Los riñones fueron estudiados por microscopía de luz. Las ratas suplementadas con colina no

Dietary restriction of choline reduces hippocampal acetylcholine release in rats: in vivo microdialysis study.

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Nakamura, A; Suzuki, Y; Umegaki, H; Ikari, H; Tajima, T; Endo, H; Iguchi, A

2001-12-01

We fed rats with a diet deficient in choline for 12 weeks and studied how dietary choline deficiency affected their behavior and their ability to release acetylcholine in discrete regions of rat brain using step-through passive avoidance task and in vivo microdialysis. In comparison with the control, rats fed the choline-deficient diet showed poorer retention of nociceptive memory in the passive avoidance task. Average choline level in cerebrospinal fluid in the choline-deficient group was significantly less (33.1%) than that of control rats. In vivo microdialysis showed no difference in the pattern of acetylcholine release enhanced by intraperitoneal administration of scopolamine hydrochloride (2 mg/kg) in the striatum between the two groups, whereas in the hippocampus, the maximum and subsequent increase of acetylcholine from the baseline by scopolamine injection was significantly lower in the choline-deficient group than in the control. From the results of our study, we speculate that long-term dietary restriction of choline can affect extra- and intracellular sources of substrates required for acetylcholine synthesis, and eventually limit the ability to release acetylcholine in the hippocampus. Reduced capacity to release acetylcholine in the hippocampus implies that the mechanism, maintaining acetylcholine synthesis on increased neuronal demand, may vary in discrete regions of the brain in response to dietary manipulation. The vulnerability of the mechanism in the hippocampus to dietary choline restriction is indicated by impaired mnemonic performance we observed.

Reversal of rocuronium-induced neuromuscular block by the selective relaxant binding agent sugammadex: a dose-finding and safety study

DEFF Research Database (Denmark)

Sorgenfrei, Iben F; Norrild, Kathrine; Larsen, Per Bo

2006-01-01

Sugammadex (Org 25969) forms a complex with steroidal neuromuscular blocking agents, thereby reversing neuromuscular block. This study investigated the dose-response relation, safety, and pharmacokinetics of sugammadex to reverse rocuronium-induced block.......Sugammadex (Org 25969) forms a complex with steroidal neuromuscular blocking agents, thereby reversing neuromuscular block. This study investigated the dose-response relation, safety, and pharmacokinetics of sugammadex to reverse rocuronium-induced block....

Role of choline PET/CT in guiding target volume delineation for irradiation of prostate cancer

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Schwarzenboeck, S.M.; Kurth, J. [University Medical Centre Rostock, Department of Nuclear Medicine, Rostock (Germany); Gocke, C.; Kuhnt, T.; Hildebrandt, G. [University Medical Centre Rostock, Department of Radiotherapy, Rostock (Germany); Krause, B.J. [University Medical Centre Rostock, Department of Nuclear Medicine, Rostock (Germany); Universitaet Rostock, Department of Nuclear Medicine, Universitaetsmedizin Rostock, Rostock (Germany)

2013-07-15

Choline PET/CT has shown limitations for the detection of primary prostate cancer and nodal metastatic disease, mainly due to limited sensitivity and specificity. Conversely in the restaging of prostate cancer recurrence, choline PET/CT is a promising imaging modality for the detection of local regional and nodal recurrence with an impact on therapy management. This review highlights current literature on choline PET/CT for radiation treatment planning in primary and recurrent prostate cancer. Due to limited sensitivity and specificity in differentiating between benign and malignant prostatic tissues in primary prostate cancer, there is little enthusiasm for target volume delineation based on choline PET/CT. Irradiation planning for the treatment of single lymph node metastases on the basis of choline PET/CT is controversial due to its limited lesion-based sensitivity in primary nodal staging. In high-risk prostate cancer, choline PET/CT might diagnose lymph node metastases, which potentially can be included in the conventional irradiation field. Prior to radiation treatment of recurrent prostate cancer, choline PET/CT may prove useful for patient stratification by excluding distant disease which would require systemic therapy. In patients with local recurrence, choline PET/CT can be used to delineate local sites of recurrence within the prostatic resection bed allowing a boost to PET-positive sites. In patients with lymph node metastases outside the prostatic fossa and regional metastatic lymph nodes, choline PET/CT might influence radiation treatment planning by enabling extension of the target volume to lymphatic drainage sites with or without a boost to PET-positive lymph nodes. Further clinical randomized trials are required to assess treatment outcomes following choline-based biological radiation treatment planning in comparison with conventional radiation treatment planning. (orig.)

Core--strategy leading to high reversible hydrogen storage capacity for NaBH4.

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Christian, Meganne L; Aguey-Zinsou, Kondo-François

2012-09-25

Owing to its high storage capacity (10.8 mass %), sodium borohydride (NaBH(4)) is a promising hydrogen storage material. However, the temperature for hydrogen release is high (>500 °C), and reversibility of the release is unachievable under reasonable conditions. Herein, we demonstrate the potential of a novel strategy leading to high and stable hydrogen absorption/desorption cycling for NaBH(4) under mild pressure conditions (4 MPa). By an antisolvent precipitation method, the size of NaBH(4) particles was restricted to a few nanometers (hydrogen at 400 °C. Further encapsulation of these nanoparticles upon reaction of nickel chloride at their surface allowed the synthesis of a core--shell nanostructure, NaBH(4)@Ni, and this provided a route for (a) the effective nanoconfinement of the melted NaBH(4) core and its dehydrogenation products, and (b) reversibility and fast kinetics owing to short diffusion lengths, the unstable nature of nickel borohydride, and possible modification of reaction paths. Hence at 350 °C, a reversible and steady hydrogen capacity of 5 mass % was achieved for NaBH(4)@Ni; 80% of the hydrogen could be desorbed or absorbed in less than 60 min, and full capacity was reached within 5 h. To the best of our knowledge, this is the first time that such performances have been achieved with NaBH(4). This demonstrates the potential of the strategy in leading to major advancements in the design of effective hydrogen storage materials from pristine borohydrides.

Choline and betaine intake and colorectal cancer risk in Chinese population: a case-control study.

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Min-Shan Lu

Full Text Available Few studies have examined the association of choline and betaine intake with colorectal cancer risk, although they might play an important role in colorectal cancer development because of their role as methyl donors. The aim of this study was to examine the relationship between consumption of choline and betaine and colorectal cancer risk in a Chinese population.A case-control study was conducted between July 2010 and December 2013 in Guangzhou, China. Eight hundred and ninety consecutively recruited colorectal cancer cases were frequency matched to 890 controls by age (5-year interval and sex. Dietary information was assessed with a validated food frequency questionnaire by face-to-face interviews. The logistic regression model was used to estimate multivariate odds ratios (ORs and 95% confidence intervals (CIs. Total choline intake was inversely associated with colorectal cancer risk after adjustment for various lifestyle and dietary factors. The multivariate-adjusted OR was 0.54 (95%CI = 0.37-0.80, Ptrend <0.01 comparing the highest with the lowest quartile. No significant associations were observed for betaine or total choline+betaine intakes. For choline-containing compounds, lower colorectal cancer risk was associated with higher intakes of choline from phosphatidylcholine, glycerophosphocholine and sphingomyelin but not for free choline and phosphocholine. The inverse association of total choline intake with colorectal cancer risk was observed in both men and women, colon and rectal cancer. These inverse associations were not modified by folate intake.These results indicate that high intake of total choline is associated with a lower risk of colorectal cancer.

Inhibition of protein kinase A and GIRK channel reverses fentanyl-induced respiratory depression.

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Liang, Xiaonan; Yong, Zheng; Su, Ruibin

2018-06-11

Opioid-induced respiratory depression is a major obstacle to improving the clinical management of moderate to severe chronic pain. Opioids inhibit neuronal activity via various pathways, including calcium channels, adenylyl cyclase, and potassium channels. Currently, the underlying molecular pathway of opioid-induced respiratory depression is only partially understood. This study aimed to investigate the mechanisms of opioid-induced respiratory depression in vivo by examining the effects of different pharmacological agents on fentanyl-induced respiratory depression. Respiratory parameters were detected using whole body plethysmography in conscious rats. We show that pre-treatment with the protein kinase A (PKA) inhibitor H89 reversed the fentanyl-related effects on respiratory rate, inspiratory time, and expiratory time. Pre-treatment with the G protein-gated inwardly rectifying potassium (GIRK) channel blocker Tertiapin-Q dose-dependently reversed the fentanyl-related effects on respiratory rate and inspiratory time. A phosphodiesterase 4 (PDE4) inhibitor and cyclic adenosine monophosphate (cAMP) analogs did not affect fentanyl-induced respiratory depression. These findings suggest that PKA and GIRK may be involved in fentanyl-induced respiratory depression and could represent useful therapeutic targets for the treatment of fentanyl-induced ventilatory depression. Copyright © 2018 Elsevier B.V. All rights reserved.

Radiosynthesis and pre-clinical evaluation of [{sup 18}F]fluoro-[1,2-{sup 2}H{sub 4}]choline

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Smith, Graham [Comprehensive Cancer Imaging Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN (United Kingdom); Zhao Yongjun [MDx Discovery (part of GE Healthcare) at Hammersmith Imanet, Ltd., Hammersmith Hospital, Du Cane Road, London W12 0NN (United Kingdom); Leyton, Julius [Comprehensive Cancer Imaging Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN (United Kingdom); Shan Bo [MDx Discovery (part of GE Healthcare) at Hammersmith Imanet, Ltd., Hammersmith Hospital, Du Cane Road, London W12 0NN (United Kingdom); Nguyen, Quang-de; Perumal, Meg [Comprehensive Cancer Imaging Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN (United Kingdom); Turton, David [GE-Imanet, Hammersmith Hospital, Du Cane Road, London, W12 0NN (United Kingdom); Arstad, Erik; Luthra, Sajinder K.; Robins, Edward G. [MDx Discovery (part of GE Healthcare) at Hammersmith Imanet, Ltd., Hammersmith Hospital, Du Cane Road, London W12 0NN (United Kingdom); Aboagye, Eric O., E-mail: eric.aboagye@imperial.ac.u [Comprehensive Cancer Imaging Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN (United Kingdom)

2011-01-15

Introduction: Choline radiotracers are widely used for clinical PET diagnosis in oncology. [{sup 11}C]Choline finds particular utility in the imaging of brain and prostate tumor metabolic status, where 2-[{sup 18}F]fluoro-2-deoxy-D-glucose ('FDG') shows high background uptake. More recently we have extended the clinical utility of [{sup 11}C]choline to breast cancer where radiotracer uptake correlates with tumor aggressiveness (grade). In the present study, a new choline analog, [{sup 18}F]fluoro-[1,2-{sup 2}H{sub 4}]choline, was synthesized and evaluated as a potential PET imaging probe. Methods: [{sup 18}F]Fluorocholine, [{sup 18}F]fluoro-[1-{sup 2}H{sub 2}]choline and [{sup 18}F]fluoro-[1,2-{sup 2}H{sub 4}]choline were synthesized by alkylation of the relevant precursor with [{sup 18}F]fluorobromomethane or [{sup 18}F]fluoromethyl tosylate. Radiosynthesis of [{sup 18}F]fluoromethyl tosylate required extensive modification of the existing method. [{sup 18}F]Fluorocholine and [{sup 18}F]fluoro-[1,2-{sup 2}H{sub 4}]choline were then subjected to in vitro oxidative stability analysis in a chemical oxidation model using potassium permanganate and an enzymatic model using choline oxidase. The two radiotracers, together with the corresponding di-deuterated compound, [{sup 18}F]fluoro-[1-{sup 2}H{sub 2}]choline, were then evaluated in vivo in a time-course biodistribution study in HCT-116 tumor-bearing mice. Results: Alkylation with [{sup 18}F]fluoromethyl tosylate proved to be the most reliable radiosynthetic route. Stability models indicate that [{sup 18}F]fluoro-[1,2-{sup 2}H{sub 4}]choline possesses increased chemical and enzymatic (choline oxidase) oxidative stability relative to [{sup 18}F]fluorocholine. The distribution of the three radiotracers, [{sup 18}F]fluorocholine, [{sup 18}F]fluoro-[1-{sup 2}H{sub 2}]choline and [{sup 18}F]fluoro-[1,2-{sup 2}H{sub 4}]choline, showed a similar uptake profile in most organs. Crucially, tumor uptake of [{sup 18}F

No Acute Effects of Choline Bitartrate Food Supplements on Memory in Healthy, Young, Human Adults.

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Lippelt, D P; van der Kint, S; van Herk, K; Naber, M

2016-01-01

Choline is a dietary component and precursor of acetylcholine, a crucial neurotransmitter for memory-related brain functions. In two double-blind, placebo-controlled cross-over experiments, we investigated whether the food supplement choline bitartrate improved declarative memory and working memory in healthy, young students one to two hours after supplementation. In experiment 1, 28 participants performed a visuospatial working memory task. In experiment 2, 26 participants performed a declarative picture memorization task. In experiment 3, 40 participants performed a verbal working memory task in addition to the visuospatial working memory and declarative picture task. All tasks were conducted approximately 60 minutes after the ingestion of 2.0-2.5g of either choline bitartrate or placebo. We found that choline did not significantly enhance memory performance during any of the tasks. The null hypothesis that choline does not improve memory performance as compared to placebo was strongly supported by Bayesian statistics. These results are in contrast with animal studies suggesting that choline supplementation boosts memory performance and learning. We conclude that choline likely has no acute effects on cholinergic memory functions in healthy human participants.

Synthesis of acetylcholine from choline derived from phosphatidylcholine in a human neuronal cell line

International Nuclear Information System (INIS)

Blusztajn, J.K.; Liscovitch, M.; Richardson, U.I.

1987-01-01

Cholinergic neurons are unique among cells since they alone utilize choline not only as a component of major membrane phospholipids, such as phosphatidylcholine (Ptd-Cho), but also as a precursor of their neurotransmitter acetylcholine (AcCho). It has been hypothesized that choline-phospholipids might serve as a storage pool of choline for AcCho synthesis. The selective vulnerability of cholinergic neurons in certain neurodegenerative diseases (e.g., Alzheimer disease, motor neuron disorders) might result from the abnormally accelerated liberation of choline (to be used a precursor of AcCho) from membrane phospholipids, resulting in altered membrane composition and function and compromised neuronal viability. However, the proposed metabolic link between membrane turnover and AcCho synthesis has been difficult to demonstrate because of the heterogeneity of the preparations used. Here the authors used a population of purely cholinergic cells (human neuroblastomas, LA-N-2), incubated in the presence of [methyl- 3 H]methionine to selectively label PtdCho synthesized by methylation of phosphatidylethanolamine, the only pathway of de novo choline synthesis. Three peaks of radioactive material that cochromatographed with authentic AcCho, choline, and phosphocholine were observed when the water-soluble metabolites of the [ 3 H]PtdCho were purified by high-performance liquid chromatography. The results demonstrate that AcCho can be synthesized from choline derived from the degradation of endogenous PtdCho formed de novo by methylation of phosphatidylethanolamine

Autolyse the cell in order to save it? Inducing, then blocking, autolysis as a strategy for delaying cell death in the probiotic Lactobacillus reuteri.

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Zimmerman, Tahl; Gyawali, Rabin; Ibrahim, Salam

2017-10-01

To examine whether choline and its derivatives can be used to preserve viable cells of Lactobacillus reuteri in autolytic models. A phosphate-induced autolytic model in de Man, Rogosa and Sharpe medium (MRS) was used. Viable cell counts were determined by plated on MRS-agar. Choline and hemicholinium-3 (HC-3) significantly blocked autolysis of L. reuteri at 360 mM and 4 mM, respectively. Viable cell counts corroborated these observations. Importantly, autolytically induced cells treated with choline and hemicholinium-3 were significantly more viable then even non-induced cells. Over-production of a known autolytic protein, spirosin, was not attenuated in the presence of choline and hemicholinium-3. Inducing autolysis and then blocking it with choline and its analogs is a promising approach for retaining the viability of L. reuteri cells.

Serial plasma choline measurements after cardiac arrest in patients undergoing mild therapeutic hypothermia: a prospective observational pilot trial.

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Christian Storm

Full Text Available OBJECTIVE: Choline is related to phospholipid metabolism and is a marker for global ischaemia with a small reference range in healthy volunteers. The aim of our study was to characterize the early kinetics of plasma free choline in patients after cardiac arrest. Additionally, we investigated the potential of plasma free choline to predict neurological outcome. METHODS: Twenty patients admitted to our medical intensive care unit were included in this prospective, observational trial. All patients were enrolled between May 2010 and May 2011. They received post cardiac arrest treatment including mild therapeutic hypothermia which was initiated with a combination of cold fluid and a feedback surface cooling device according to current guidelines. Sixteen blood samples per patient were analysed for plasma free choline levels within the first week after resuscitation. Choline was detected by liquid chromatography-tandem mass spectrometry. RESULTS: Most patients showed elevated choline levels on admission (median 14.8 µmol/L; interquartile range; IQR 9.9-20.1 which subsequently decreased. 48 hours after cardiac arrest choline levels in all patients reached subnormal levels at a median of 4.0 µmol/L (IQR 3-4.9; p = 0.001. Subsequently, choline levels normalized within seven days. There was no significant difference in choline levels when groups were analyzed in relation to neurological outcome. CONCLUSIONS: Our data indicate a choline deficiency in the early postresucitation phase. This could potentially result in impaired cell membrane recovery. The detailed characterization of the early choline time course may aid in planning of choline supplementation trials. In a limited number of patients, choline was not promising as a biomarker for outcome prediction.

Mouth reversal extinguishes mismatch negativity induced by the McGurk illusion

DEFF Research Database (Denmark)

Eskelund, Kasper; Andersen, Tobias

2013-01-01

The sight of articulatory mouth movements (visual speech) influences auditory speech perception. This is demonstrated by the McGurk illusion in which incongruent visual speech alters the auditory phonetic percept. In behavioral studies, reversal of the vertical mouth direction has been reported...... by visual speech with either upright (unaltered) or vertically reversed mouth area. In a preliminary analysis, we found a Mismatch Negativity component induced by the McGurk illusion for 6 of 17 participants at electrode Cz when the mouth area was upright. In comparison, these participants produced...

An electrochemiluminescence-based fibre optic biosensor for choline flow injection analysis.

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Tsafack, V C; Marquette, C A; Leca, B; Blum, L J

2000-01-01

A fibre optic biosensor based on luminol electrochemiluminescence (ECL) integrated in a flow injection analysis (FIA) system was developed for the detection of choline. The electrochemiluminescence of luminol was generated by a glassy carbon electrode polarised at +425 mV vs. a platinum pseudo-reference electrode. Choline oxidase (Chx) was immobilised either covalently on polyamide (ABC type) or on UltraBind preactivated membranes, or by physical entrapment in a photo-cross-linkable poly(vinyl alcohol) polymer (PVA-SbQ) alone or after absorption on a weak anion exchanger, DEAE (diethylaminoethyl) Sepharose. The optimisation of the reaction conditions and physicochemical parameters influencing the FIA biosensor response demonstrated that the choline biosensor exhibited the best performances in a 30 mM veronal buffer containing 30 mM KCl and 1.5 mM MgCl2, at pH 9. The use of a 0.5 ml min-1 flow rate enabled the measurement of choline by the membrane-based ECL biosensors in 8 or 5 min, with ABC or UltraBind membranes, respectively, whereas the measurement required only 3 min with the DEAE-PVA system. For comparison, the detection of choline was performed with Chx immobilised using the four different supports. The best performances were obtained with the DEAE-PVA-Chx sensing layer, which allowed a detection limit of 10 pmol, whereas with the ABC, the UltraBind and the PVA systems, the detection limits were 300 pmol, 75 pmol and 220 pmol, respectively. The DEAE-based system also exhibited a good operational stability since 160 repeated measurements of 3 nmol of choline could be performed with an RSD of 4.5% whereas the stability under the best conditions was 45 assays with the other supports.

X-ray diffraction study of choline chloride's β form

International Nuclear Information System (INIS)

Petrouleas, V.; Lemmon, R.M.; Christensen, A.

1978-01-01

The organic salt choline chloride exists in two crystalline polymorphs. One (the α form) is extraordinarily sensitive to ionizing radiation, the other (the β form) is not. The present report describes an x-ray diffraction study of the β form. The structure has been found to be highly disordered face centered cubic. A reasonable least-square refinement of the intensity data has been achieved in the centrosymmetric space group Fm3 or Fm3m by use of a molecular model with restrained bond lengths. The results show that in the β form the electronic density due to the choline cation is closely spaced around the N, so that hydrogen bonding to the chloride is unlikely. Comparison with infrared and NMR data indicates that the disordering is dynamic and can be ascribed to rotations of the choline ion around crystallographic symmetry axes. Possible connections of these results with the radiation stability of the β form are discussed

Dietary choline levels modify the effects of prenatal alcohol exposure in rats.

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Idrus, Nirelia M; Breit, Kristen R; Thomas, Jennifer D

Prenatal alcohol exposure can cause a range of physical and behavioral alterations; however, the outcome among children exposed to alcohol during pregnancy varies widely. Some of this variation may be due to nutritional factors. Indeed, higher rates of fetal alcohol spectrum disorders (FASD) are observed in countries where malnutrition is prevalent. Epidemiological studies have shown that many pregnant women throughout the world may not be consuming adequate levels of choline, an essential nutrient critical for brain development, and a methyl donor. In this study, we examined the influence of dietary choline deficiency on the severity of fetal alcohol effects. Pregnant Sprague-Dawley rats were randomly assigned to receive diets containing 40, 70, or 100% recommended choline levels. A group from each diet condition was exposed to ethanol (6.0g/kg/day) from gestational day 5 to 20 via intubation. Pair-fed and ad lib lab chow control groups were also included. Physical and behavioral development was measured in the offspring. Prenatal alcohol exposure delayed motor development, and 40% choline altered performance on the cliff avoidance task, independent of one another. However, the combination of low choline and prenatal alcohol produced the most severe impairments in development. Subjects exposed to ethanol and fed the 40% choline diet exhibited delayed eye openings, significantly fewer successes in hindlimb coordination, and were significantly overactive compared to all other groups. These data suggest that suboptimal intake of a single nutrient can exacerbate some of ethanol's teratogenic effects, a finding with important implications for the prevention of FASD. Copyright © 2016. Published by Elsevier Inc.

Lead Exposure Induces Telomere Instability in Human Cells.

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Géraldine Pottier

Full Text Available Lead (Pb is an important environmental contaminant due to its widespread use over many centuries. While it affects primarily every organ system of the body, the most pernicious effects of Pb are on the central nervous system leading to cognitive and behavioral modification. Despite decades of research, the mechanisms responsible for Pb toxicity remain poorly understood. Recent work has suggested that Pb exposure may have consequences on chromosomal integrity as it was shown that Pb exposure leads to the generation of γH2Ax foci, a well-established biomarker for DNA double stranded break (DSB formation. As the chromosomal localization of γH2Ax foci plays an important role in determining the molecular mechanism responsible for their formation, we examined the localization of Pb-induced foci with respect to telomeres. Indeed, short or dysfunctional telomeres (uncapped or damaged telomeres may be recognized as DSB by the DNA repair machinery, leading to "telomere-Induced Foci" (TIFs. In the current study, we show that while Pb exposure did not increase intra-chromosomal foci, it significantly induced TIFs, leading in some cases, to chromosomal abnormalities including telomere loss. The evidence suggests that these chromosomal abnormalities are likely due to perturbation of telomere replication, in particular on the lagging DNA strand. We propose a mechanism by which Pb exposure leads to the loss of telomere maintenance. As numerous studies have demonstrated a role for telomere maintenance in brain development and tissue homeostasis, our results suggest a possible mechanism for lead-induced neurotoxicity.

Structure of choline oxidase in complex with the reaction product glycine betaine.

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Salvi, Francesca; Wang, Yuan-Fang; Weber, Irene T; Gadda, Giovanni

2014-02-01

Choline oxidase from Arthrobacter globiformis, which is involved in the biosynthesis of glycine betaine from choline, has been extensively characterized in its mechanistic and structural properties. Despite the knowledge gained on the enzyme, the details of substrate access to the active site are not fully understood. The `loop-and-lid' mechanism described for the glucose-methanol-choline enzyme superfamily has not been confirmed for choline oxidase. Instead, a hydrophobic cluster on the solvent-accessible surface of the enzyme has been proposed by molecular dynamics to control substrate access to the active site. Here, the crystal structure of the enzyme was solved in complex with glycine betaine at pH 6.0 at 1.95 Å resolution, allowing a structural description of the ligand-enzyme interactions in the active site. This structure is the first of choline oxidase in complex with a physiologically relevant ligand. The protein structures with and without ligand are virtually identical, with the exception of a loop at the dimer interface, which assumes two distinct conformations. The different conformations of loop 250-255 define different accessibilities of the proposed active-site entrance delimited by the hydrophobic cluster on the other subunit of the dimer, suggesting a role in regulating substrate access to the active site.

Value of bimodal (18)F-choline-PET/MRI and trimodal (18)F-choline-PET/MRI/TRUS for the assessment of prostate cancer recurrence after radiation therapy and radical prostatectomy.

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Paparo, Francesco; Piccardo, Arnoldo; Bacigalupo, Lorenzo; Romagnoli, Andrea; Piccazzo, Riccardo; Monticone, Michela; Cevasco, Luca; Campodonico, Fabio; Conzi, Giuseppe Maria; Carmignani, Giorgio; Rollandi, Gian Andrea

2015-08-01

Between 27% and 53% of all patients who undergo radical prostatectomy (RP) or radiation therapy (RT) as the first-line treatment of prostate cancer (PCa) develop a biochemical recurrence. Imaging plays a pivotal role in restaging by helping to distinguish between local relapse and metastatic disease (i.e., lymph-node and skeletal metastases). At present, the most promising tools for assessing PCa patients with biochemical recurrence are multiparametric magnetic resonance imaging (mpMRI) and positron emission tomography (PET)/computed tomography (CT) with radio-labeled choline derivatives. The main advantage of mpMRI is its high diagnostic accuracy in detecting local recurrence, while choline-PET/CT is able to identify lymph-node metastases when they are not suspicious on morphological imaging. The most recent advances in the field of fusion imaging have shown that multimodal co-registration, synchronized navigation, and combined interpretation are more valuable than the individual; separate assessment offered by different diagnostic techniques. The objective of the present essay was to describe the value of bimodal choline-PET/mpMRI fusion imaging and trimodal choline-PET/mpMRI/transrectal ultrasound (TRUS) in the assessment of PCa recurrence after RP and RT. Bimodal choline-PET/mpMRI fusion imaging allows morphological, functional, and metabolic information to be combined, thereby overcoming the limitations of each separate imaging modality. In addition, trimodal real-time choline-PET/mpMRI/TRUS fusion imaging may be useful for the planning and real-time guidance of biopsy procedures in order to obtain histological confirmation of the local recurrence.

Feeding a diet devoid of choline to lactating rodents restricts growth and lymphocyte development in offspring.

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Lewis, E D; Goruk, S; Richard, C; Dellschaft, N S; Curtis, J M; Jacobs, R L; Field, C J

2016-09-01

The nutrient choline is necessary for membrane synthesis and methyl donation, with increased requirements during lactation. The majority of immune development occurs postnatally, but the importance of choline supply for immune development during this critical period is unknown. The objective of this study was to determine the importance of maternal supply of choline during suckling on immune function in their offspring among rodents. At parturition, Sprague-Dawley dams were randomised to either a choline-devoid (ChD; n 7) or choline-sufficient (ChS, 1 g/kg choline; n 10) diet with their offspring euthanised at 3 weeks of age. In a second experiment, offspring were weaned to a ChS diet until 10 weeks of age (ChD-ChS, n 5 and ChS-ChS, n 9). Splenocytes were isolated, and parameters of immune function were measured. The ChD offspring received less choline in breast milk and had lower final body and organ weight compared with ChS offspring (P<0·05), but this effect disappeared by week 10 with choline supplementation from weaning. ChD offspring had a higher proportion of T cells expressing activation markers (CD71 or CD28) and a lower proportion of total B cells (CD45RA+) and responded less to T cell stimulation (lower stimulation index and less IFN-γ production) ex vivo (P<0·05). ChD-ChS offspring had a lower proportion of total and activated CD4+ T cells, and produced less IL-6 after mitogen stimulation compared with cells from ChS-ChS (P<0·05). Our study suggests that choline is required in the suckling diet to facilitate immune development, and choline deprivation during this critical period has lasting effects on T cell function later in life.

Quaternary naltrexone reverses radiogenic and morphine-induced locomotor hyperactivity

Energy Technology Data Exchange (ETDEWEB)

Mickley, G.A.; Stevens, K.E.; Galbraith, J.A.; White, G.A.; Gibbs, G.L.

1984-04-01

The present study attempted to determine the relative role of the peripheral and central nervous system in the production of morphine-induced or radiation-induced locomotor hyperactivity of the mouse. Toward this end, we used a quaternary derivative of an opiate antagonist (naltrexone methobromide), which presumably does not cross the blood-brain barrier. Quaternary naltrexone was used to challenge the stereotypic locomotor response observed in these mice after either an i.p. injection of morphine or exposure to 1500 rads /sup 60/Co. The quaternary derivative of naltrexone reversed the locomotor hyperactivity normally observed in the C57BL/6J mouse after an injection of morphine. It also significantly attenuated radiation-induced locomotion. The data reported here support the hypothesis of endorphin involvement in radiation-induced and radiogenic behaviors. However, these conclusions are contingent upon further research which more fully evaluates naltrexone methobromide's capacity to cross the blood-brain barrier.

Reversal of haloperidol-induced tardive vacuous chewing movements and supersensitive somatodendritic serotonergic response by imipramine in rats

International Nuclear Information System (INIS)

Samad, N.; Haleem, D.J.

2013-01-01

The study was designed to test the hypothesis that a decrease in the responsiveness of somatodendritic 5-HT-1A receptors by co- administration of imipramine could reverse the induction of VCMs and supersensitivity at 5-HT-IA receptors by haloperidol. Rats treated with haloperidol 0.2mg/rat/day for 2 weeks induced VCMs with twitching of facial musculature that increased in a time dependent manner as the treatment continued to 5 weeks. Co administration of imipramine (5mg/kg/m1) attenuated haloperidol-induced VCMs after 2 weeks and completely reversed it after 5 weeks. The intensity of 8-hydroxy -2-di(n-propyleamino)tetraline (8-OH-DPAT)-induced locomotion and forepaw treading were greater in saline+haloperidol injected but not in imipramine+haloperidol injected animals. 8-OH-DPAT induced decreases of 5-HT metabolism were greater in saline+haloperidol injected animals but not in imipramine+haloperidol injected animals. The mechanism involved in reversal/attenuation of haloperidol-induced tardive dyskinesia by imipramine is discussed. (author)

X-ray irradiation induced reversible resistance change in Pt/TiO2/Pt cells.

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Chang, Seo Hyoung; Kim, Jungho; Phatak, Charudatta; D'Aquila, Kenneth; Kim, Seong Keun; Kim, Jiyoon; Song, Seul Ji; Hwang, Cheol Seong; Eastman, Jeffrey A; Freeland, John W; Hong, Seungbum

2014-02-25

The interaction between X-rays and matter is an intriguing topic for both fundamental science and possible applications. In particular, synchrotron-based brilliant X-ray beams have been used as a powerful diagnostic tool to unveil nanoscale phenomena in functional materials. However, it has not been widely investigated how functional materials respond to the brilliant X-rays. Here, we report the X-ray-induced reversible resistance change in 40-nm-thick TiO2 films sandwiched by Pt top and bottom electrodes, and propose the physical mechanism behind the emergent phenomenon. Our findings indicate that there exists a photovoltaic-like effect, which modulates the resistance reversibly by a few orders of magnitude, depending on the intensity of impinging X-rays. We found that this effect, combined with the X-ray irradiation induced phase transition confirmed by transmission electron microscopy, triggers a nonvolatile reversible resistance change. Understanding X-ray-controlled reversible resistance changes can provide possibilities to control initial resistance states of functional materials, which could be useful for future information and energy storage devices.

Uptake of [N-Me-3H]-choline by synaptosomes from the central nervous system of Locusta migratoria

International Nuclear Information System (INIS)

Breer, H.

1982-01-01

The accumulation of 3H-choline by isolated synaptosomes from the central nervous system of locust was studied at concentrations varying from 0.05 to 40 microM. Kinetic analysis of the saturable process revealed a high-affinity and a low-affinity system. The high-affinity uptake was competitively inhibited by hemicholinium-3 and was absolutely dependent on external sodium. Elevated potassium concentrations inhibited choline uptake. The choline uptake by insect synaptosomes was found to be remarkably resistant to a variety of metabolic inhibitors. The reduced choline uptake under depolarizing conditions (high potassium concentration or veratridine) in the absence of calcium implies that electrochemical gradients are important for high-affinity choline uptake. Depolarization of preloaded synaptosomes under appropriate conditions resulted in a significant release of newly accumulated choline radioactivity

Carbon Nanotubes/Gold Nanoparticles Composite Film for the Construction of a Novel Amperometric Choline Biosensor

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Baoyan Wu

2011-01-01

Full Text Available This study develops a facile method to fabricate a novel choline biosensor based on multiwalled carbon nanotubes (MWCNTs and gold nanoparticles (AuNPs. Chitosan, a natural biocompatible polymer, was used to solubilize MWCNTs for constructing the aqueous Chit-MWCNTs solution. Then Chit-MWCNTs were first dropped on the surface of a cleaned platinum electrode. Finally, a thiolated silica sol containing AuNPs and choline oxidase (ChOx was immobilized on the surface of the Chit-MWCNTs-modified electrode. The MWCNTs/AuNPs/Pt electrode showed excellent electrocatalytic activity for choline. The resulting choline biosensor showed high sensitivity of choline (3.56 μA/mM, and wide linear range from 0.05 to 0.8 mM with the detection limit of 15 μM. In addition, good reproducibility and stability were obtained.

Dietary Intake and Plasma Levels of Choline and Betaine in Children with Autism Spectrum Disorders

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Joanna C. Hamlin

2013-01-01

Full Text Available Abnormalities in folate-dependent one-carbon metabolism have been reported in many children with autism. Because inadequate choline and betaine can negatively affect folate metabolism and in turn downstream methylation and antioxidant capacity, we sought to determine whether dietary intake of choline and betaine in children with autism was adequate to meet nutritional needs based on national recommendations. Three-day food records were analyzed for 288 children with autism (ASDs who participated in the national Autism Intervention Research Network for Physical Health (AIR-P Study on Diet and Nutrition in children with autism. Plasma concentrations of choline and betaine were measured in a subgroup of 35 children with ASDs and 32 age-matched control children. The results indicated that 60–93% of children with ASDs were consuming less than the recommended Adequate Intake (AI for choline. Strong positive correlations were found between dietary intake and plasma concentrations of choline and betaine in autistic children as well as lower plasma concentrations compared to the control group. We conclude that choline and betaine intake is inadequate in a significant subgroup of children with ASDs and is reflected in lower plasma levels. Inadequate intake of choline and betaine may contribute to the metabolic abnormalities observed in many children with autism and warrants attention in nutritional counseling.

Choline and betaine intake and colorectal cancer risk in Chinese population: a case-control study.

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Lu, Min-Shan; Fang, Yu-Jing; Pan, Zhi-Zhong; Zhong, Xiao; Zheng, Mei-Chun; Chen, Yu-Ming; Zhang, Cai-Xia

2015-01-01

Few studies have examined the association of choline and betaine intake with colorectal cancer risk, although they might play an important role in colorectal cancer development because of their role as methyl donors. The aim of this study was to examine the relationship between consumption of choline and betaine and colorectal cancer risk in a Chinese population. A case-control study was conducted between July 2010 and December 2013 in Guangzhou, China. Eight hundred and ninety consecutively recruited colorectal cancer cases were frequency matched to 890 controls by age (5-year interval) and sex. Dietary information was assessed with a validated food frequency questionnaire by face-to-face interviews. The logistic regression model was used to estimate multivariate odds ratios (ORs) and 95% confidence intervals (CIs). Total choline intake was inversely associated with colorectal cancer risk after adjustment for various lifestyle and dietary factors. The multivariate-adjusted OR was 0.54 (95%CI = 0.37-0.80, Ptrend colorectal cancer risk was associated with higher intakes of choline from phosphatidylcholine, glycerophosphocholine and sphingomyelin but not for free choline and phosphocholine. The inverse association of total choline intake with colorectal cancer risk was observed in both men and women, colon and rectal cancer. These inverse associations were not modified by folate intake. These results indicate that high intake of total choline is associated with a lower risk of colorectal cancer.

Reversal of CRF- and stress-induced anorexia by an ayurvedic formulation

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V. S. Kulkarni

2012-04-01

Full Text Available Trikatu churna is one of the commonly used Ayurvedic formulations in the traditional system of medicine in India for the treatment of agnimandya, i.e. anorexia. Trikatu contains equal amounts of finely powdered rhizomes of Zingiber officinale Roscoe (Zingiberaceae and fruits of Piper longum L. and Piper nigrum L. (Piperaceae. The chief objective of the study was to determine the antianorectic effects of three drugs individually and to compare these effects with the effect of Trikatu. The activity of the drugs was studied after anorexia was induced in rats by (1 physical stress arising from immobilization for 60 min; (2 intraperitoneal injection of Escherichia coli lipopolysaccharide (LPS, 100 μg/kg body weight; and (3 intraperitoneal administration of fluoxetine (8 mg/kg body weight. Similar doses of the extracts were tested on freely feeding rats and on rats that had been deprived of food for 20 h. Corticotrophin-releasing factor (CRF, 0.3 μg/rat can induce anxiogenic-like behavior and reduced food intake. This model was also studied, and the results were compared. The components of Trikatu churna failed to individually reverse the inhibition of feeding. In contrast, Trikatu churna pretreatment reversed stress-, fluoxetine- and CRF-induced anorexia. The study provides strong evidence of the synergistic action of Ayurvedic formulas and also proves the ability of Trikatu churna to reduce stress and CRF-induced anorexia.

Reversal of CRF- and stress-induced anorexia by an ayurvedic formulation

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V. S. Kulkarni

2011-09-01

Full Text Available Trikatu churna is one of the commonly used Ayurvedic formulations in the traditional system of medicine in India for the treatment of agnimandya, i.e. anorexia. Trikatu contains equal amounts of finely powdered rhizomes of Zingiber officinale Roscoe (Zingiberaceae and fruits of Piper longum L. and Piper nigrum L. (Piperaceae. The chief objective of the study was to determine the antianorectic effects of three drugs individually and to compare these effects with the effect of Trikatu. The activity of the drugs was studied after anorexia was induced in rats by (1 physical stress arising from immobilization for 60 min; (2 intraperitoneal injection of Escherichia coli lipopolysaccharide (LPS, 100 μg/kg body weight; and (3 intraperitoneal administration of fluoxetine (8 mg/kg body weight. Similar doses of the extracts were tested on freely feeding rats and on rats that had been deprived of food for 20 h. Corticotrophin-releasing factor (CRF, 0.3 μg/rat can induce anxiogenic-like behavior and reduced food intake. This model was also studied, and the results were compared. The components of Trikatu churna failed to individually reverse the inhibition of feeding. In contrast, Trikatu churna pretreatment reversed stress-, fluoxetine- and CRF-induced anorexia. The study provides strong evidence of the synergistic action of Ayurvedic formulas and also proves the ability of Trikatu churna to reduce stress and CRF-induced anorexia.

PET/CT with 18F-choline: Physiological whole bio-distribution in male and female subjects and diagnostic pitfalls on 1000 prostate cancer patients: 18F-choline PET/CT bio-distribution and pitfalls. A southern Italian experience.

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Calabria, Ferdinando; Chiaravalloti, Agostino; Cicciò, Carmelo; Gangemi, Vincenzo; Gullà, Domenico; Rocca, Federico; Gallo, Gianpasquale; Cascini, Giuseppe Lucio; Schillaci, Orazio

2017-08-01

The 11 C/ 18 F-choline is a PET/CT radiopharmaceutical useful in detecting tumors with high lipogenesis. 11 C/ 18 F-choline uptake can occur in physiological conditions or tumors. The knowledge of its bio-distribution is essential to recognize physiologic variants or diagnostic pitfalls. Moreover, few information are available on the bio-distribution of this tracer in female patients. Our aim was to discuss some documented 18 F-choline PET/CT pitfalls in prostate cancer patients. Our secondary aim was to describe the 18 F-choline bio-distribution in the female body. We collected diagnostic pitfalls in three PET centers examining 1000 prostate cancer by 18 F-choline PET/CT. All pitfalls were ensured by follow-up, imaging and/or histology. We also performed whole body 18 F-choline PET/CT in 5 female patients. 169/1000 (16.9%) patients showed pitfalls not owing to prostate cancer. These findings were due to inflammation, benign tumors while, in 1% of examined patients, a concomitant neoplasm was found. In the female body, the breast showed low physiological uptake. The accurate knowledge of 18 F-choline PET/CT bio-distribution and diagnostic pitfalls is essential. Correlative imaging and histological exam are often necessary to depict pitfalls. In women, the uptake in the breast is due to the physiological gradient of 18 F-choline uptake in the exocrine glands. Our results confirm the possibility of 18 F-choline uptake in several diseases other than prostate cancer. However, our experience was acquired on a large population and shows that a conspicuous amount of 18 F-choline diagnostic pitfalls are easily recognizable and attributable to inflammation. A new advance in knowledge is the minimal difference in terms of physiological tracer bio-distribution between male and female patients. The knowledge of the physiological bio-distribution and of the potential pitfalls linked of a tracer could help physicians to choose the best diagnostic and therapeutic approaches for a

Specific and Reversible Immobilization of Proteins Tagged to the Affinity Polypeptide C-LytA on Functionalized Graphite Electrodes

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Bello-Gil, Daniel; Maestro, Beatriz; Fonseca, Jennifer; Feliu, Juan M.; Climent, Víctor; Sanz, Jesús M.

2014-01-01

We have developed a general method for the specific and reversible immobilization of proteins fused to the choline-binding module C-LytA on functionalized graphite electrodes. Graphite electrode surfaces were modified by diazonium chemistry to introduce carboxylic groups that were subsequently used to anchor mixed self-assembled monolayers consisting of N,N-diethylethylenediamine groups, acting as choline analogs, and ethanolamine groups as spacers. The ability of the prepared electrodes to specifically bind C-LytA-tagged recombinant proteins was tested with a C-LytA-β-galactosidase fusion protein. The binding, activity and stability of the immobilized protein was evaluated by electrochemically monitoring the formation of an electroactive product in the enzymatic hydrolysis of the synthetic substrate 4-aminophenyl β-D-galactopyranoside. The hybrid protein was immobilized in an specific and reversible way, while retaining the catalytic activity. Moreover, these functionalized electrodes were shown to be highly stable and reusable. The method developed here can be envisaged as a general, immobilization procedure on the protein biosensor field. PMID:24498237

Specific and reversible immobilization of proteins tagged to the affinity polypeptide C-LytA on functionalized graphite electrodes.

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Daniel Bello-Gil

Full Text Available We have developed a general method for the specific and reversible immobilization of proteins fused to the choline-binding module C-LytA on functionalized graphite electrodes. Graphite electrode surfaces were modified by diazonium chemistry to introduce carboxylic groups that were subsequently used to anchor mixed self-assembled monolayers consisting of N,N-diethylethylenediamine groups, acting as choline analogs, and ethanolamine groups as spacers. The ability of the prepared electrodes to specifically bind C-LytA-tagged recombinant proteins was tested with a C-LytA-β-galactosidase fusion protein. The binding, activity and stability of the immobilized protein was evaluated by electrochemically monitoring the formation of an electroactive product in the enzymatic hydrolysis of the synthetic substrate 4-aminophenyl β-D-galactopyranoside. The hybrid protein was immobilized in an specific and reversible way, while retaining the catalytic activity. Moreover, these functionalized electrodes were shown to be highly stable and reusable. The method developed here can be envisaged as a general, immobilization procedure on the protein biosensor field.

Usual Choline Intakes Are Associated with Egg and Protein Food Consumption in the United States

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Taylor C. Wallace

2017-08-01

Full Text Available Choline is an essential nutrient with critical roles in several biological processes including neuronal development, cell signaling, nerve impulse transmission, and lipid transport and metabolism. The National Cancer Institute method was used to assess usual intakes of choline from foods according to data for participants enrolled in the National Health and Nutrition Examination Survey 2009–2014 datasets and pregnant women in the 2005–2014 datasets. Suboptimal intakes of choline are present across many gender and life-stage subpopulations, as well as pregnant women in the U.S. Only 8.03 ± 0.56% of adults and 8.51 ± 2.89% pregnant women meet the AI for choline. Children 2–3 years were the most likely to meet their gender and life-stage specific AI, followed by children 4–8 years. Adults 19+ years who consume eggs were more likely to meet their gender and life-stage AI as compared to non-consumers (57.3 ± 1.45% and 2.43 ± 0.28%. Consumers of eggs had almost double the usual intake of choline as compared to non-consumers (525 ± 5.17 mg/d and 294 ± 1.98; p < 0.0001. Protein food (meat, poultry and seafood consumption also increased usual choline intakes compared to non-consumers (345 ± 2.21 mg/day and 235 ± 8.81; p < 0.0001 to a lesser degree, but did not result in substantial increases in the percent of individuals meeting the AI. No subpopulation exceeded the UL for choline. This research illustrates that it is extremely difficult to achieve the AI for choline without consuming eggs or taking a dietary supplement.

Genetic impairments in folate enzymes increase dependence on dietary choline for phosphatidylcholine production at the expense of betaine synthesis.

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Ganz, Ariel B; Shields, Kelsey; Fomin, Vlad G; Lopez, Yusnier S; Mohan, Sanjay; Lovesky, Jessica; Chuang, Jasmine C; Ganti, Anita; Carrier, Bradley; Yan, Jian; Taeswuan, Siraphat; Cohen, Vanessa V; Swersky, Camille C; Stover, Julie A; Vitiello, Gerardo A; Malysheva, Olga V; Mudrak, Erika; Caudill, Marie A

2016-10-01

Although single nucleotide polymorphisms (SNPs) in folate-mediated pathways predict susceptibility to choline deficiency during severe choline deprivation, it is unknown if effects persist at recommended intakes. Thus, we used stable isotope liquid chromatography-mass spectrometry (LC-MS) methodology to examine the impact of candidate SNPs on choline metabolism in a long-term, randomized, controlled feeding trial among pregnant, lactating, and nonpregnant (NP) women consuming 480 or 930 mg/d choline (22% as choline-d 9 , with d 9 indicating a deuterated trimethyl amine group) and meeting folate-intake recommendations. Variants impairing folate metabolism, methylenetetrahydrofolate reductase (MTHFR) rs1801133, methionine synthase (MTR) rs1805087 [wild-type (WT)], MTR reductase (MTRR) rs1801394, and methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase (MTHFD1) rs2236225, influenced choline dynamics, frequently through interactions with reproductive state and choline intake, with fewer genotypic alterations observed among pregnant women. Women with these variants partitioned more dietary choline toward phosphatidylcholine (PC) biosynthesis via the cytidine diphosphate (CDP)-choline pathway at the expense of betaine synthesis even when use of betaine as a methyl donor was increased. Choline intakes of 930 mg/d restored partitioning of dietary choline between betaine and CDP-PC among NP (MTHFR rs1801133 and MTR rs1805087 WT) and lactating (MTHFD1 rs2236225) women with risk genotypes. Overall, our findings indicate that loss-of-function variants in folate-metabolizing enzymes strain cellular PC production, possibly via impaired folate-dependent phosphatidylethanolamine-N-methyltransferase (PEMT)-PC synthesis, and suggest that women with these risk genotypes may benefit from choline intakes exceeding current recommendations.-Ganz, A. B., Shields, K., Fomin, V. G., Lopez, Y. S., Mohan, S., Lovesky, J., Chuang, J

Four-week dietary supplementation with 10- and/or 15-fold basal choline caused decreased body weight in Sprague Dawley rats.

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Bagley, Bradford D; Chang, Shu-Ching; Ehresman, David J; Eveland, Alan; Parker, George A; Peters, Jeffrey M; Butenhoff, John L

2017-10-01

Choline is an essential nutrient utilized for phosphatidylcholine biosynthesis and lipoprotein packaging and secretion. Recently, choline supplementation has been used by athletes and the public for weight loss. However, the potential toxicological impact of choline dietary supplementation requires further investigation. This study examined the effects of choline dietary supplementation in Sprague Dawley rats for 4 weeks. Rats were fed diets containing basal choline levels (control) or 5-, 10-, or 15-fold (5×, 10×, or 15×) basal diet concentration. In groups fed choline-supplemented diets, there were no toxicologically relevant findings in clinical observations, food intake, clinical chemistry, liver weights, or liver histopathology. However, decreased mean body weights (8.5-10.2%) and body weight gains (24-31%) were noted for the 10× choline-supplemented (females only) and 15× choline-supplemented (both sexes) groups relative to the control groups from day 3 onward. These body weight effects were not related to a persistent reduction in average food intake. Serum cholesterol was increased in the 15× choline-supplemented male rats relative to the controls, an expected effect of choline supplementation; however, there were no changes in the serum cholesterol of female rats. Serum choline concentrations were increased in female rats relative to the male rats across all treatment groups. The maximum tolerated dose for male and female rats were the 15× and 10× choline supplements, respectively, based on decreased mean body weight and body weight gains. This study supported the conclusions of a clinical trial that showed a high choline diet can decrease body weight in humans.

Electrodeposition of copper composites from deep eutectic solvents based on choline chloride.

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Abbott, Andrew P; El Ttaib, Khalid; Frisch, Gero; McKenzie, Katy J; Ryder, Karl S

2009-06-07

Here we describe for the first time the electrolytic deposition of copper and copper composites from a solution of the metal chloride salt in either urea-choline chloride, or ethylene glycol-choline chloride based eutectics. We show that the deposition kinetics and thermodynamics are quite unlike those in aqueous solution under comparable conditions and that the copper ion complexation is also different. The mechanism of copper nucleation is studied using chronoamperometry and it is shown that progressive nucleation leads to a bright nano-structured deposit. In contrast, instantaneous nucleation, at lower concentrations of copper ions, leads to a dull deposit. This work also pioneers the use of the electrochemical quartz crystal microbalance (EQCM) to monitor both current efficiency and the inclusion of inert particulates into the copper coatings. This technique allows the first in situ quantification or particulate inclusion. It was found that the composition of composite material was strongly dependent on the amount of species suspended in solution. It was also shown that the majority of material was dragged onto the surface rather than settling on to it. The distribution of the composite material was found to be even throughout the coating. This technology is important because it facilitates deposition of bright copper coatings without co-ligands such as cyanide. The incorporation of micron-sized particulates into ionic liquids has resulted, in one case, in a decrease in viscosity. This observation is both unusual and surprising; we explain this here in terms of an increase in the free volume of the liquid and local solvent perturbation.

Incorporation of radioactive labelled cholin and palmitate into lung lecithin of rabbits treated with high doses of bromcarbamides, barbiturates and diazepam

International Nuclear Information System (INIS)

Wichert, P. von; Schmidt, C.; Pomraenke, K.; Wiegers, U.

1977-01-01

Severe intoxications with bromcarbamides often show respiratory complications. To answer the question if there is a direct effect of the drug on lung tissue the incorporation of radioactive labelled choline and palmitate into lung lecithin was investigated. The phospholipid metabolism is in close relation to the surfactant system of the lung. Secondly the influence of bromcarbamides was compared with other hypnotic drugs. There was a reduction of palmitate incorporation into lung lecithin down to 40%, whereas the incorporation of choline increases in bromcarbamide intoxication. The relation between palmitate and choline incorporation was 6.77 in the controls and it decreases to 2-3 in the bromcarbamide group. The total phospholipid content in the lung/g wet weight remained unchanged in all experiments. From this data it is concluded, that these drugs cause a reduction of fatty acid exchange of the lecithin molecules of the lung. This might lead to the production of non surface active lecithin. The clinical and the morphological aspects of severe bromcarbamide intoxication are consistent with a perturbation of the surfactant function. (orig./MG) [de

Umbilical choline and related methylamines betaine and dimethylglycine in relation to birth weight

NARCIS (Netherlands)

Hogeveen, M.; Heijer, M. den; Semmekrot, B.A.; Sporken, J.M.J.; Ueland, P.M.; Blom, H.J.

2013-01-01

Background:Low birth weight (LBW) is associated with increased morbidity and mortality for the newborn and risk of chronic disease in adulthood. Choline plays an essential role in the integrity of cell membranes, methylation reactions, and memory development. We examined whether choline, betaine,

Reversal of aflatoxin induced liver damage by turmeric and curcumin.

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Soni, K B; Rajan, A; Kuttan, R

1992-09-30

The effect of certain food additives on aflatoxin production by Aspergillus parasiticus has been studied in vitro. Extracts of turmeric (Curcuma longa), garlic (Allium sativum) and asafoetida (Ferula asafoetida) inhibited the aflatoxin production considerably (more than 90%) at concentrations of 5-10 mg/ml. Similar results were also seen using butylated hydroxytoluene, butylated hydroxyanisole and ellagic acid at concentration 0.1 mM. Curcumin, the antioxidant principle from Curcuma longa did not have any effect on aflatoxin production. Turmeric and curcumin were also found to reverse the aflatoxin induced liver damage produced by feeding aflatoxin B1 (AFB1) (5 micrograms/day per 14 days) to ducklings. Fatty changes, necrosis and biliary hyperplasia produced by AFB1 were considerably reversed by these food additives.

Surviving bacterial sibling rivalry: inducible and reversible phenotypic switching in Paenibacillus dendritiformis.

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Be'er, Avraham; Florin, E-L; Fisher, Carolyn R; Swinney, Harry L; Payne, Shelley M

2011-01-01

Natural habitats vary in available nutrients and room for bacteria to grow, but successful colonization can lead to overcrowding and stress. Here we show that competing sibling colonies of Paenibacillus dendritiformis bacteria survive overcrowding by switching between two distinct vegetative phenotypes, motile rods and immotile cocci. Growing colonies of the rod-shaped bacteria produce a toxic protein, Slf, which kills cells of encroaching sibling colonies. However, sublethal concentrations of Slf induce some of the rods to switch to Slf-resistant cocci, which have distinct metabolic and resistance profiles, including resistance to cell wall antibiotics. Unlike dormant spores of P. dendritiformis, the cocci replicate. If cocci encounter conditions that favor rods, they secrete a signaling molecule that induces a switch to rods. Thus, in contrast to persister cells, P. dendritiformis bacteria adapt to changing environmental conditions by inducible and reversible phenotypic switching. In favorable environments, species may face space and nutrient limits due to overcrowding. Bacteria provide an excellent model for analyzing principles underlying overcrowding and regulation of density in nature, since their population dynamics can be easily and accurately assessed under controlled conditions. We describe a newly discovered mechanism for survival of a bacterial population during overcrowding. When competing with sibling colonies, Paenibacillus dendritiformis produces a lethal protein (Slf) that kills cells at the interface of encroaching colonies. Slf also induces a small proportion of the cells to switch from motile, rod-shaped cells to nonmotile, Slf-resistant, vegetative cocci. When crowding is reduced and nutrients are no longer limiting, the bacteria produce a signal that induces cocci to switch back to motile rods, allowing the population to spread. Genes encoding components of this phenotypic switching pathway are widespread among bacterial species, suggesting

Galvanostatic bottom-up filling of TSV-like trenches: Choline-based leveler containing two quaternary ammoniums

International Nuclear Information System (INIS)

Kim, Myung Jun; Seo, Youngran; Kim, Hoe Chul; Lee, Yoonjae; Choe, Seunghoe; Kim, Young Gyu; Cho, Sung Ki; Kim, Jae Jeong

2015-01-01

Highlights: • The choline-based leveler having two quaternary ammoniums was synthesized. • The adsorption of this leveler with suppressor and accelerator was examined. • Galvanostatic Cu bottom-up filling was achieved with three-additive system. • The mechanism of gap-filling was elucidated based on the additive adsorption. - Abstract: Through Silicon Via (TSV) technology is essential to accomplish 3-dimensional packaging of electronics. Hence, more reliable and faster TSV filling by Cu electrodeposition is required. Our approach to improve Cu gap-filling in TSV is based on the development of new organic additives for feature filling. Here, we introduce our achievements from the synthesis of choline-based leveler to the feature filling using a synthesized leveler. The choline-based leveler, which includes two quaternary ammoniums at both ends of the molecule, is synthesized from glutaric acid. The characteristics of the choline-based additive are examined by the electrochemical analyses, and it is confirmed that the choline-based leveler shows a convection dependent adsorption behavior, which is essential for leveling. The interactions between the polymeric suppressor, accelerator, and the choline-based leveler are also investigated by changing the convection condition. Using the combination of suppressor, accelerator, and the choline-based leveler, the extreme bottom-up filling of Cu at trenches with dimensions similar to TSV are fulfilled. The mechanism of Cu gap-filling is demonstrated based on the results of electrochemical analyses and feature filling

Cerium(terbium, erbium)chloride-choline chloride aqueous systems

International Nuclear Information System (INIS)

Gajfutdinova, R.K.; Zhuravlev, E.F.; Bikbaeva, G.G.; Domrachev, V.N.; Vanskova, G.I.

1985-01-01

To clarify the effect of rare earth nature on mutual solubility of rare earth salts and amines the solubility of solid phases in the systems, consisting of choline chloride, water and cerium, terbium, erbium chlorides, has been studied. It is established, that solubility isotherms of all the systems, testify to the formation of new solid phases of the composition: Ce(Tb, Er)xCl 3 x2C 5 H 14 ONClx3H 2 O. Individuality of new solid phases is proved by DTA method, the composition is confirmed by chemical analysis and data of PMR spectra, for choline chloride and its complexes with rare earth chlorides of the given composition PMR and IR spectra are studied

Reversal of rocuronium-induced (1.2 mg/kg) profound neuromuscular block by sugammadex: a multicenter, dose-finding and safety study.

NARCIS (Netherlands)

Boer, H.D. de; Driessen, J.J.; Marcus, M.A.; Kerkkamp, H.E.M.; Heeringa, M.; Klimek, M.

2007-01-01

BACKGROUND: Reversal of rocuronium-induced neuromuscular blockade can be accomplished by chemical encapsulation of rocuronium by sugammadex, a modified gamma-cyclodextrin derivative. This study investigated the efficacy and safety of sugammadex in reversing rocuronium-induced profound neuromuscular

Chronic choline supplementation improves cognitive and motor performance via modulating oxidative and neurochemical status in rats.

Science.gov (United States)

Tabassum, Saiqa; Haider, Saida; Ahmad, Saara; Madiha, Syeda; Parveen, Tahira

2017-08-01

Choline, an essential nutrient, accounts for multiple functions in the body and brain. While its beneficial effects on healthy adults are not clear, choline supplementation is important during pregnancy for brain development, in elderly patients for support of cognitive performance and in patients with neurological disorders to reduce memory deficits. Thus, the aim of this study is to investigate whether choline administration in healthy adult rats beneficially impacts cognitive and locomotor performance, and associated oxidative and neurochemical outcomes. Two groups, control and choline, received tap water and choline bitartrate, respectively at the dose equivalent to adequate intake for five weeks. Food intake and body weight were monitored daily. Behavioral analysis comprising assessment of cognitive performance (by novel object recognition, passive avoidance and Morris Water Maze test) and locomotor performance (by Open field, Kondziela's inverted screen and beam walking test) were performed. Following testing, rats were decapitated and brain samples were collected for estimation of acetylcholine, redox profile and monoamine measurements. The results showed that chronic choline administration significantly improves cognitive and locomotor performance accompanied by a reduction in oxidative stress, enhanced cholinergic neurotransmission and monoamine levels in the brain of healthy adult rats. Hence, chronic choline intake was found to improve behavioral, oxidative and neurochemical outcomes in the normal population, so it can be suggested that choline tablets can be used as a safe and effective supplement for improving the neurological health of normal individuals and that they might also be beneficial in preventing cognitive and motor disorders later in life. Copyright © 2017 Elsevier Inc. All rights reserved.

Higher Dietary Choline and Betaine Intakes Are Associated with Better Body Composition in the Adult Population of Newfoundland, Canada.

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Xiang Gao

Full Text Available Choline is an essential nutrient and betaine is an osmolyte and methyl donor. Both are important to maintain health including adequate lipid metabolism. Supplementation of dietary choline and betaine increase muscle mass and reduce body fat in animals. However, little data is available regarding the role of dietary choline and betaine on body composition in humans.To investigate the association between dietary choline and betaine intakes with body composition in a large population based cross-sectional study.A total of 3214 subjects from the CODING (Complex Disease in Newfoundland population: Environment and Genetics study were assessed. Dietary choline and betaine intakes were computed from the Willett Food Frequency questionnaire. Body composition was measured using dual-energy X-ray absorptiometry following a 12-hour fast. Major confounding factors including age, sex, total calorie intake and physical activity level were controlled in all analyses.Significantly inverse correlations were found between dietary choline and betaine intakes, with all obesity measurements: total percent body fat (%BF, percent trunk fat (%TF, percent android fat (%AF, percent gynoid fat (%GF and anthropometrics: weight, body mass index, waist circumference, waist-to-hip ratio in both women and men (r range from -0.13 to -0.47 for choline and -0.09 to -0.26 for betaine, p<0.001 for all. Dietary choline intake had stronger association than betaine. Moreover, obese subjects had the lowest dietary choline and betaine intakes, with overweight subjects in the middle, and normal weight subjects consumed the highest dietary choline and betaine (p<0.001. Vice versa, when subjects were ranked according to dietary choline and betaine intakes, subjects with the highest intake of both had the lowest %TF, %AF, %GF, %BF and highest %LM among the groups in both sexes.Our findings indicate that high dietary choline and betaine intakes are significantly associated with favorable body

Lecithin: a by-product of biodiesel production and a source of choline for dairy cows

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Igino Andrighetto

2012-04-01

Full Text Available The aim of the present study was to compare the effects of soy lecithins (L, a by-product of the biodiesel production process, and choline chloride microencapsulated with hydrogenated vegetable oils (C on dry matter intake, milk yield,  milk quality traits, milk choline and haematological profile of dairy cows. A total of 12 mid-lactating Holstein Friesian cows were assigned to one of two experimental groups and fed according to cross-over design (2 diets x 2 periods. Diets were isoenergetic, isofibrous and isonitrogenous and had the same content of choline. Dry matter intake was not affected by the diet, but L led to lower milk choline (P

The Protective Effect of Gangliosides on Lead (Pb)-Induced Neurotoxicity Is Mediated by Autophagic Pathways.

Science.gov (United States)

Meng, Hongtao; Wang, Lan; He, Junhong; Wang, Zhufeng

2016-03-25

Lead (Pb) is a ubiquitous environmental and industrial pollutant and can affect intelligence development and the learning ability and memory of children. Therefore, necessary measures should be taken to protect the central nervous system (CNS) from Pb toxicity. Gangliosides are sialic acid-containing glycosphingolipids that are constituents of mammalian cell membranes and are more abundantly expressed in the CNS. Studies have shown that gangliosides constitute a useful tool in the attempt to promote functional recovery of CNS and can reverse Pb-induced impairments of synaptic plasticity in rats. However, the detailed mechanisms have yet to be fully understood. In our present study, we tried to investigate the role of gangliosides in Pb-induced injury in hippocampus neurons and to further confirm the detailed mechanism. Our results show that Pb-induced injuries in the spatial reference memory were associated with a reduction of cell viability and cell apoptosis, and treatment with gangliosides markedly ameliorated the Pb-induced injury by inhibition of apoptosis action. Gangliosides further attenuated Pb-induced the abnormal autophagic process by regulation of mTOR pathways. In summary, our study establishes the efficacy of gangliosides as neuroprotective agents and provides a strong rationale for further studies on the underlying mechanisms of their neuroprotective functions.

The Protective Effect of Gangliosides on Lead (Pb-Induced Neurotoxicity Is Mediated by Autophagic Pathways

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Hongtao Meng

2016-03-01

Full Text Available Lead (Pb is a ubiquitous environmental and industrial pollutant and can affect intelligence development and the learning ability and memory of children. Therefore, necessary measures should be taken to protect the central nervous system (CNS from Pb toxicity. Gangliosides are sialic acid-containing glycosphingolipids that are constituents of mammalian cell membranes and are more abundantly expressed in the CNS. Studies have shown that gangliosides constitute a useful tool in the attempt to promote functional recovery of CNS and can reverse Pb-induced impairments of synaptic plasticity in rats. However, the detailed mechanisms have yet to be fully understood. In our present study, we tried to investigate the role of gangliosides in Pb-induced injury in hippocampus neurons and to further confirm the detailed mechanism. Our results show that Pb-induced injuries in the spatial reference memory were associated with a reduction of cell viability and cell apoptosis, and treatment with gangliosides markedly ameliorated the Pb-induced injury by inhibition of apoptosis action. Gangliosides further attenuated Pb-induced the abnormal autophagic process by regulation of mTOR pathways. In summary, our study establishes the efficacy of gangliosides as neuroprotective agents and provides a strong rationale for further studies on the underlying mechanisms of their neuroprotective functions.

Nicotine Prevents and Reverses Paclitaxel-Induced Mechanical Allodynia in a Mouse Model of CIPN.

Science.gov (United States)

Kyte, S Lauren; Toma, Wisam; Bagdas, Deniz; Meade, Julie A; Schurman, Lesley D; Lichtman, Aron H; Chen, Zhi-Jian; Del Fabbro, Egidio; Fang, Xianjun; Bigbee, John W; Damaj, M Imad; Gewirtz, David A

2018-01-01

Chemotherapy-induced peripheral neuropathy (CIPN), a consequence of peripheral nerve fiber dysfunction or degeneration, continues to be a dose-limiting and debilitating side effect during and/or after cancer chemotherapy. Paclitaxel, a taxane commonly used to treat breast, lung, and ovarian cancers, causes CIPN in 59-78% of cancer patients. Novel interventions are needed due to the current lack of effective CIPN treatments. Our studies were designed to investigate whether nicotine can prevent and/or reverse paclitaxel-induced peripheral neuropathy in a mouse model of CIPN, while ensuring that nicotine will not stimulate lung tumor cell proliferation or interfere with the antitumor properties of paclitaxel. Male C57BL/6J mice received paclitaxel every other day for a total of four injections (8 mg/kg, i.p.). Acute (0.3-0.9 mg/kg, i.p.) and chronic (24 mg/kg per day, s.c.) administration of nicotine respectively reversed and prevented paclitaxel-induced mechanical allodynia. Blockade of the antinociceptive effect of nicotine with mecamylamine and methyllycaconitine suggests that the reversal of paclitaxel-induced mechanical allodynia is primarily mediated by the α 7 nicotinic acetylcholine receptor subtype. Chronic nicotine treatment also prevented paclitaxel-induced intraepidermal nerve fiber loss. Notably, nicotine neither promoted proliferation of A549 and H460 non-small cell lung cancer cells nor interfered with paclitaxel-induced antitumor effects, including apoptosis. Most importantly, chronic nicotine administration did not enhance Lewis lung carcinoma tumor growth in C57BL/6J mice. These data suggest that the nicotinic acetylcholine receptor-mediated pathways may be promising drug targets for the prevention and treatment of CIPN. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Effect of choline supplementation on rapid weight loss and biochemical variables among female taekwondo and judo athletes.

Science.gov (United States)

Elsawy, Gehan; Abdelrahman, Osama; Hamza, Amr

2014-03-27

Taekwondo and judo competitions are divided into weight categories. Many athletes reduce their body mass a few days before competition in order to obtain a competitive advantage over lighter opponents. To achieve fast body mass reduction, athletes use a number of nutritional strategies, including choline supplementation. The goal of this study was to identify the effects of choline supplementation on body mass reduction and leptin levels among female taekwondo and judo athletes. Twenty-two female athletes (15 taekwondo and 7 judo athletes) were selected from different weight categories and divided into two groups, according to weight. The players in the experimental group took choline tablets for one week before a competition. The results revealed significant differences between pre- and post-competition measurements of leptin, free plasma choline, urine choline and urine malondialdehyde levels; body mass was also reduced in the post-competition measurements. In conclusion, choline supplementation could rapidly reduce body mass without any side effects on biochemical levels or static strength.

Metabolism of choline in brain of the aged CBF-1 mouse

International Nuclear Information System (INIS)

Saito, M.; Kindel, G.; Karczmar, A.G.; Rosenberg, A.

1986-01-01

In order to quantify the changes that occur in the cholinergic central nervous system with aging, we have compared acetylcholine (Ach) formation in brain cortex slice preparations from 2-year-old aged CBF-1 mouse brains and compared the findings with those in 2-4-month-old young adult mouse brain slices. Incorporation of exogenous radioactively labelled choline (31 nM [ 3 H] choline) into acetyl choline in incubated brain slices was linear with time for 90 min. Percentage of total choline label distributed into Ach remained constant from 5 min after starting the incubation to 90 min. In contrast, distribution of label into intracellular free choline (Ch) and phosphorylcholine (Pch) changed continuously over this period suggesting that the Ch pool for Ach synthesis in brain cortex is different from that for Pch synthesis. Incorporation of radioactivity into Ach was not influenced by administration of 10 microM eserine, showing that the increment of radioactivity in Ach reflects rate of Ach formation, independently from degradation by acetylcholine esterases. Under our experimental conditions, slices from cortices of aged 24-month-old mouse brain showed a significantly greater (27%) incorporation of radioactivity into intracellular Ach than those from young, 2-4-month-old, brain cortices. Inhibitors of Ach release, 1 mM ATP or GABA, had no effect. Since concentration of radioactive precursor in the incubation medium was very low (31 nM), the Ch pool for Ach synthesis in slices was labelled without measurably changing the size of the endogenous pool. These data suggest a compensatory acceleration of Ach synthesis or else a smaller precursor pool specific for Ach synthesis into which labelled Ch migrated in aged brain

Sugammadex, a new reversal agent for neuromuscular block induced by rocuronium in the anaesthetized Rhesus monkey.

NARCIS (Netherlands)

Boer, H.D. de; Egmond, J. van; Pol, F. van de; Bom, A.; Booij, L.H.D.J.

2006-01-01

BACKGROUND: Binding of the steroidal molecule of rocuronium by a cyclodextrin is a new concept for reversal of neuromuscular block. The present study evaluated the ability of Sugammadex Org 25969, a synthetic gamma-cyclodextrin derivative, to reverse constant neuromuscular block of about 90% induced

Inhibition of high affinity choline uptake by N-allyl-3-quinuclidinol

International Nuclear Information System (INIS)

Asermely, K.E.; O'Neill, J.J.

1986-01-01

The peripheral actions of N-allyl-3-quinuclidinol (N-Al-3-OHQ) on high affinity choline uptake (HAChU) on rat phrenic nerve diaphragm are described. Endplate regions (EPA) identified by the Koelle histochemical techniques for acetylcholinesterase, were dissected from adult rat hemidiaphragms and placed in cold Krebs solution (pH-7.35). All measurements of HAChU were at 37 0 C in buffers containing tritium choline (5 μM 0.124 μC/mmole) at intervals of 1, 2, 4, 8, 15 and 30 min. Tissues were washed 3x, digested in 1N NaOH and counted for tritium in Chaikoff's solution. All data are expressed as pmole Ch/g wet weight. Comparison between EPA and non-EPA tissue demonstrate HAChU and slow choline diffusion, respectively. Steady state is observed in 15 min. N-Al-3-OHQ produces 15% inhibition at 5 x 10 -5 M compared with 50% inhibition on brain synaptosomes. At 5 x 10 -4 M N-Al-3-OHQ, 30% inhibition is observed. Attempts to deplete ACh by pre-stimulation with high K + -ion (25 mM) were unsuccessful; tissue 3 H-choline uptake appeared to oscillate over a 30 min period

Inhibition of high affinity choline uptake by N-allyl-3-quinuclidinol

Energy Technology Data Exchange (ETDEWEB)

Asermely, K.E.; O' Neill, J.J.

1986-03-01

The peripheral actions of N-allyl-3-quinuclidinol (N-Al-3-OHQ) on high affinity choline uptake (HAChU) on rat phrenic nerve diaphragm are described. Endplate regions (EPA) identified by the Koelle histochemical techniques for acetylcholinesterase, were dissected from adult rat hemidiaphragms and placed in cold Krebs solution (pH-7.35). All measurements of HAChU were at 37/sup 0/C in buffers containing tritium choline (5 ..mu..M 0.124 ..mu..C/mmole) at intervals of 1, 2, 4, 8, 15 and 30 min. Tissues were washed 3x, digested in 1N NaOH and counted for tritium in Chaikoff's solution. All data are expressed as pmole Ch/g wet weight. Comparison between EPA and non-EPA tissue demonstrate HAChU and slow choline diffusion, respectively. Steady state is observed in 15 min. N-Al-3-OHQ produces 15% inhibition at 5 x 10/sup -5/ M compared with 50% inhibition on brain synaptosomes. At 5 x 10/sup -4/ M N-Al-3-OHQ, 30% inhibition is observed. Attempts to deplete ACh by pre-stimulation with high K/sup +/-ion (25 mM) were unsuccessful; tissue /sup 3/H-choline uptake appeared to oscillate over a 30 min period.

Effects of spin-polarized current on pulse field-induced precessional magnetization reversal

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Guang-fu Zhang

2012-12-01

Full Text Available We investigate effects of a small DC spin-polarized current on the pulse field-induced precessional magnetization reversal in a thin elliptic magnetic element by micromagnetic simulations. We find that the spin-polarized current not only broadens the time window of the pulse duration, in which a successful precessional reversal is achievable, but also significantly suppresses the magnetization ringing after the reversal. The pulse time window as well as the decay rate of the ringing increase with increasing the current density. When a spin-polarized current with 5 MA/cm2 is applied, the time window increases from 80 ps to 112 ps, and the relaxation time of the ringing decreases from 1.1 ns to 0.32 ns. Our results provide useful information to achieve magnetic nanodevices based on precessional switching.

Reversal of haloperidol induced motor deficits in rats exposed to repeated immobilization stress.

Science.gov (United States)

Shireen, Erum; Pervez, Sidra; Masroor, Maria; Ali, Wafa Binte; Rais, Qudsia; Khalil, Samira; Tariq, Anum; Haleem, Darakshan Jabeen

2014-09-01

Stress is defined as a non specific response of body to any physiological and psychological demand. Preclinical studies have shown that an uncontrollable stress condition produces neurochemical and behavioral deficits. The present study was conducted to test the hypothesis that a decrease in the responsiveness of somatodendritic 5-hydroxytryptamine (5-HT)-1A receptors following adaptation to stress could attenuate haloperidol induced acute parkinsonian like effect. Results showed that single exposure (2h) to immobilization stress markedly decreased food intake, growth rate and locomotor activity but these stress-induced behavioral deficits were not observed following repeated (2h/day for 5 days) exposure of immobilization stress suggesting behavioral tolerance occurs to similar stress. An important finding of present study is a reversal of haloperidol-induced motor deficits in animals exposed to repeated immobilization stress than respective control animals. It is suggested that stress induced possible desensitization of somatodendritic 5-HT-1A as well as 5-HT-2C receptors could release dopamine system from the inhibitory influence of serotonin. On the other hand, an increase in the effectiveness of postsynaptic 5-HT-1A receptors elicits a direct stimulatory influence on the activity of dopaminergic neuron and is possibly involved in the reversal of haloperidol-induced parkinsonian like symptoms in repeatedly immobilized rats.

Treatment with pioglitazone induced significant, reversible mitral regurgitation.

Science.gov (United States)

Dorkhan, Mozhgan; Dencker, Magnus; Frid, Anders

2008-04-30

There has in recent years been great concern about possible cardiac side effects of thiazolidinediones (TZDs). We present a case-report of a 60 year-old male who developed significant mitral regurgitation during six months treatment with pioglitazone in parallel with laboratory indications of fluid retention. Echocardiography six months after discontinuation of medication showed regression of mitral regurgitation and the laboratory parameters were also normalized. It is noteworthy that six months treatment with pioglitazone could induce significant valve dysfunction, which was reversible, and this underlines the importance of carefully monitoring patients when placing them on treatment with TZDs.

Treatment with pioglitazone induced significant, reversible mitral regurgitation

Directory of Open Access Journals (Sweden)

Frid Anders

2008-04-01

Full Text Available Abstract There has in recent years been great concern about possible cardiac side effects of thiazolidinediones (TZDs. We present a case-report of a 60 year-old male who developed significant mitral regurgitation during six months treatment with pioglitazone in parallel with laboratory indications of fluid retention. Echocardiography six months after discontinuation of medication showed regression of mitral regurgitation and the laboratory parameters were also normalized. It is noteworthy that six months treatment with pioglitazone could induce significant valve dysfunction, which was reversible, and this underlines the importance of carefully monitoring patients when placing them on treatment with TZDs.

AMPK Activation Prevents and Reverses Drug-Induced Mitochondrial and Hepatocyte Injury by Promoting Mitochondrial Fusion and Function.

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Sun Woo Sophie Kang

Full Text Available Mitochondrial damage is the major factor underlying drug-induced liver disease but whether conditions that thwart mitochondrial injury can prevent or reverse drug-induced liver damage is unclear. A key molecule regulating mitochondria quality control is AMP activated kinase (AMPK. When activated, AMPK causes mitochondria to elongate/fuse and proliferate, with mitochondria now producing more ATP and less reactive oxygen species. Autophagy is also triggered, a process capable of removing damaged/defective mitochondria. To explore whether AMPK activation could potentially prevent or reverse the effects of drug-induced mitochondrial and hepatocellular damage, we added an AMPK activator to collagen sandwich cultures of rat and human hepatocytes exposed to the hepatotoxic drugs, acetaminophen or diclofenac. In the absence of AMPK activation, the drugs caused hepatocytes to lose polarized morphology and have significantly decreased ATP levels and viability. At the subcellular level, mitochondria underwent fragmentation and had decreased membrane potential due to decreased expression of the mitochondrial fusion proteins Mfn1, 2 and/or Opa1. Adding AICAR, a specific AMPK activator, at the time of drug exposure prevented and reversed these effects. The mitochondria became highly fused and ATP production increased, and hepatocytes maintained polarized morphology. In exploring the mechanism responsible for this preventive and reversal effect, we found that AMPK activation prevented drug-mediated decreases in Mfn1, 2 and Opa1. AMPK activation also stimulated autophagy/mitophagy, most significantly in acetaminophen-treated cells. These results suggest that activation of AMPK prevents/reverses drug-induced mitochondrial and hepatocellular damage through regulation of mitochondrial fusion and autophagy, making it a potentially valuable approach for treatment of drug-induced liver injury.

AMPK Activation Prevents and Reverses Drug-Induced Mitochondrial and Hepatocyte Injury by Promoting Mitochondrial Fusion and Function

Science.gov (United States)

Taniane, Caitlin; Farrell, Geoffrey; Arias, Irwin M.; Lippincott-Schwartz, Jennifer; Fu, Dong

2016-01-01

Mitochondrial damage is the major factor underlying drug-induced liver disease but whether conditions that thwart mitochondrial injury can prevent or reverse drug-induced liver damage is unclear. A key molecule regulating mitochondria quality control is AMP activated kinase (AMPK). When activated, AMPK causes mitochondria to elongate/fuse and proliferate, with mitochondria now producing more ATP and less reactive oxygen species. Autophagy is also triggered, a process capable of removing damaged/defective mitochondria. To explore whether AMPK activation could potentially prevent or reverse the effects of drug-induced mitochondrial and hepatocellular damage, we added an AMPK activator to collagen sandwich cultures of rat and human hepatocytes exposed to the hepatotoxic drugs, acetaminophen or diclofenac. In the absence of AMPK activation, the drugs caused hepatocytes to lose polarized morphology and have significantly decreased ATP levels and viability. At the subcellular level, mitochondria underwent fragmentation and had decreased membrane potential due to decreased expression of the mitochondrial fusion proteins Mfn1, 2 and/or Opa1. Adding AICAR, a specific AMPK activator, at the time of drug exposure prevented and reversed these effects. The mitochondria became highly fused and ATP production increased, and hepatocytes maintained polarized morphology. In exploring the mechanism responsible for this preventive and reversal effect, we found that AMPK activation prevented drug-mediated decreases in Mfn1, 2 and Opa1. AMPK activation also stimulated autophagy/mitophagy, most significantly in acetaminophen-treated cells. These results suggest that activation of AMPK prevents/reverses drug-induced mitochondrial and hepatocellular damage through regulation of mitochondrial fusion and autophagy, making it a potentially valuable approach for treatment of drug-induced liver injury. PMID:27792760

Intrinsic torque reversals induced by magnetic shear effects on the turbulence spectrum in tokamak plasmas

Energy Technology Data Exchange (ETDEWEB)

Lu, Z. X.; Tynan, G. [Center for Energy Research and Department of Mechanical and Aerospace Engineering, University of California at San Diego, San Diego, California 92093 (United States); Center for Momentum Transport and Flow Organization and Center for Astrophysics and Space Science, University of California, San Diego, California 92093 (United States); Wang, W. X.; Ethier, S. [Princeton Plasma Physics Laboratory, Princeton, New Jersey 08540 (United States); Diamond, P. H. [Center for Momentum Transport and Flow Organization and Center for Astrophysics and Space Science, University of California, San Diego, California 92093 (United States); Gao, C.; Rice, J. [Plasma Science and Fusion Center, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 (United States)

2015-05-15

Intrinsic torque, which can be generated by turbulent stresses, can induce toroidal rotation in a tokamak plasma at rest without direct momentum injection. Reversals in intrinsic torque have been inferred from the observation of toroidal velocity changes in recent lower hybrid current drive (LHCD) experiments. This work focuses on understanding the cause of LHCD-induced intrinsic torque reversal using gyrokinetic simulations and theoretical analyses. A new mechanism for the intrinsic torque reversal linked to magnetic shear (s{sup ^}) effects on the turbulence spectrum is identified. This reversal is a consequence of the ballooning structure at weak s{sup ^}. Based on realistic profiles from the Alcator C-Mod LHCD experiments, simulations demonstrate that the intrinsic torque reverses for weak s{sup ^} discharges and that the value of s{sup ^}{sub crit} is consistent with the experimental results s{sup ^}{sub crit}{sup exp}≈0.2∼0.3 [Rice et al., Phys. Rev. Lett. 111, 125003 (2013)]. The consideration of this intrinsic torque feature in our work is important for the understanding of rotation profile generation at weak s{sup ^} and its consequent impact on macro-instability stabilization and micro-turbulence reduction, which is crucial for ITER. It is also relevant to internal transport barrier formation at negative or weakly positive s{sup ^}.

A mechanism for suppression of the CDP-choline pathway during apoptosis

OpenAIRE

Morton, Craig C.; Aitchison, Adam J.; Gehrig, Karsten; Ridgway, Neale D.

2013-01-01

Inhibition of the CDP-choline pathway during apoptosis restricts the availability of phosphatidylcholine (PtdCho) for assembly of membranes and synthesis of signaling factors. The N-terminal nuclear localization signal (NLS) in CTP:phosphocholine cytidylyltransferase (CCT)α is removed during apoptosis but the caspase(s) involved and the contribution to suppression of the CDP-choline pathway is unresolved. In this study we utilized siRNA silencing of caspases in HEK293 cells and caspase 3-defi...

Studies of antimony telluride and copper telluride films electrodeposition from choline chloride containing ionic liquids

Energy Technology Data Exchange (ETDEWEB)

Catrangiu, Adriana-Simona; Sin, Ion [Department of Inorganic Chemistry, Physical Chemistry and Electrochemistry, POLITEHNICA University of Bucharest, Calea Grivitei 132, Bucharest (Romania); Prioteasa, Paula [INCDIE ICPE-Advanced Research, Splaiul Unirii 313, Bucharest (Romania); Cotarta, Adina [Department of Inorganic Chemistry, Physical Chemistry and Electrochemistry, POLITEHNICA University of Bucharest, Calea Grivitei 132, Bucharest (Romania); Cojocaru, Anca, E-mail: a_cojocaru@chim.upb.ro [Department of Inorganic Chemistry, Physical Chemistry and Electrochemistry, POLITEHNICA University of Bucharest, Calea Grivitei 132, Bucharest (Romania); Anicai, Liana [Center of Surface Science and Nanotechnology, University POLITEHNICA of Bucharest, Splaiul Independentei 313, Bucharest (Romania); Visan, Teodor [Department of Inorganic Chemistry, Physical Chemistry and Electrochemistry, POLITEHNICA University of Bucharest, Calea Grivitei 132, Bucharest (Romania)

2016-07-29

Cyclic voltammetry and electrochemical impedance spectroscopy were used to investigate the deposition of antimony telluride or copper telluride from ionic liquid consisting in mixture of choline chloride with oxalic acid. In addition, the cathodic process during copper telluride formation was studied in the mixture of choline chloride with ethylene glycol. The results indicate that the Pt electrode is first covered with a Te layer, and then the more negative polarisation leads to the deposition of Sb{sub x}Te{sub y} or Cu{sub x}Te{sub y} semiconductor compounds. Thin films were deposited on copper and carbon steel at 60–70 °C and were characterised by scanning electron microscopy, energy X-ray dispersive spectroscopy (EDS), and X-ray diffraction (XRD). Their stoichiometry depends on the bath composition and applied potential. EDS and XRD patterns indicate the possible synthesis of stoichiometric Sb{sub 2}Te{sub 3} phase and Cu{sub 2}Te, Cu{sub 5}Te{sub 3}, and Cu{sub 2.8}Te{sub 2} phases, respectively, by controlling the ratio of ion concentrations in ionic liquid electrolytes and deposition potential. - Highlights: • Sb{sub x}Te{sub y} and Cu{sub x}Te{sub y} films electrodeposited from choline-chloride-based ionic liquids. • The stoichiometry of film depends on the bath composition and deposition potential. • Sb{sub 2}Te{sub 3}, Cu{sub 2}Te, Cu{sub 5}Te{sub 3}, Cu{sub 2.8}Te{sub 2} phases were identified in X-ray diffraction patterns.

Involvement of microglia activation in the lead induced long-term potentiation impairment.

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Ming-Chao Liu

Full Text Available Exposure of Lead (Pb, a known neurotoxicant, can impair spatial learning and memory probably via impairing the hippocampal long-term potentiation (LTP as well as hippocampal neuronal injury. Activation of hippocampal microglia also impairs spatial learning and memory. Thus, we raised the hypothesis that activation of microglia is involved in the Pb exposure induced hippocampal LTP impairment and neuronal injury. To test this hypothesis and clarify its underlying mechanisms, we investigated the Pb-exposure on the microglia activation, cytokine release, hippocampal LTP level as well as neuronal injury in in vivo or in vitro model. The changes of these parameters were also observed after pretreatment with minocycline, a microglia activation inhibitor. Long-term low dose Pb exposure (100 ppm for 8 weeks caused significant reduction of LTP in acute slice preparations, meanwhile, such treatment also significantly increased hippocampal microglia activation as well as neuronal injury. In vitro Pb-exposure also induced significantly increase of microglia activation, up-regulate the release of cytokines including tumor necrosis factor-alpha (TNF-α, interleukin-1β (IL-1β and inducible nitric oxide synthase (iNOS in microglia culture alone as well as neuronal injury in the co-culture with hippocampal neurons. Inhibiting the microglia activation with minocycline significantly reversed the above-mentioned Pb-exposure induced changes. Our results showed that Pb can cause microglia activation, which can up-regulate the level of IL-1β, TNF-α and iNOS, these proinflammatory factors may cause hippocampal neuronal injury as well as LTP deficits.

Dietary Reversal Ameliorates Short- and Long-Term Memory Deficits Induced by High-fat Diet Early in Life.

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Catrina Sims-Robinson

Full Text Available A high-fat diet (HFD, one of the major factors contributing to metabolic syndrome, which is associated with an increased risk of neurodegenerative diseases, leads to insulin resistance and cognitive impairment. It is not known whether these alterations are improved with dietary intervention. To investigate the long-term impact of a HFD on hippocampal insulin signaling and memory, C57BL6 mice were placed into one of three groups based on the diet: a standard diet (control, a HFD, or a HFD for 16 weeks and then the standard diet for 8 weeks (HF16. HFD-induced impairments in glucose tolerance and hippocampal insulin signaling occurred concurrently with deficits in both short- and long-term memory. Furthermore, these conditions were improved with dietary intervention; however, the HFD-induced decrease in insulin receptor expression in the hippocampus was not altered with dietary intervention. Our results demonstrate that memory deficits due to the consumption of a HFD at an early age are reversible.

Usefulness of Choline-PET for the detection of residual hemangiopericytoma in the skull base: comparison with FDG-PET

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Ito Shin

2012-02-01

Full Text Available Abstract Background Choline is a new PET tracer that is useful for the detection of malignant tumor. Choline is a precursor of the biosynthesis of phosphatidylcholine, a major phospholipid in the cell membrane of eukaryotic cells. Malignant tumors have an elevated level of phosphatidylcholine in cell membrane. Thus, choline is a marker of tumor malignancy. Method The patient was a 51-year-old man with repeated recurrent hemangiopericytoma in the skull base. We performed Choline-PET in this patient after various treatments and compared findings with those of FDG-PET. Results Choline accumulated in this tumor, but FDG did not accumulate. We diagnosed this tumor as residual hemangiopericytoma and performed the resection of the residual tumor. FDG-PET is not appropriate for skull base tumor detection because uptake in the brain is very strong. Conclusion We emphasize the usefulness of Choline-PET for the detection of residual hemangiopericytoma in the skull base after various treatments, compared with FDG-PET.

PET and PET/CT with radiolabeled choline in prostate cancer: a critical reappraisal of 20 years of clinical studies

Energy Technology Data Exchange (ETDEWEB)

Giovacchini, Giampiero; Giovannini, Elisabetta; Leoncini, Rossella; Riondato, Mattia; Ciarmiello, Andrea [S. Andrea Hospital, Nuclear Medicine Department, La Spezia (Italy)

2017-09-15

We here aim to provide a comprehensive and critical review of the literature concerning the clinical applications of positron emission tomography/computed tomography (PET/CT) with radiolabeled choline in patients with prostate cancer (PCa). We will initially briefly summarize the historical context that brought to the synthesis of [{sup 11}C]choline, which occurred exactly 20 years ago. We have arbitrarily grouped the clinical studies in three different periods, according to the year in which they were published and according to their relation with their applications in urology, radiotherapy and oncology. Studies at initial staging and, more extensively, studies in patients with biochemical failure, as well as factors predicting positive PET/CT will be reviewed. The capability of PET/CT with radiolabeled choline to provide prognostic information on PCa-specific survival will also be examined. The last sections will be devoted to the use of radiolabeled choline for monitoring the response to androgen deprivation therapy, radiotherapy, and chemotherapy. The accuracy and the limits of the technique will be discussed according to the information available from standard validation processes, including biopsy or histology. The clinical impact of the technique will be discussed on the basis of changes induced in the management of patients and in the evaluation of the response to therapy. Current indications to PET/CT, as officially endorsed by guidelines, or as routinely performed in the clinical practice will be illustrated. Emphasis will be made on methodological factors that might have influenced the results of the studies or their interpretation. Finally, we will briefly highlight the potential role of positron emission tomography/magnetic resonance and of new radiotracers for PCa imaging. (orig.)

Lead induced oxidative stress: beneficial effects of Kombucha tea.

Science.gov (United States)

Dipti, P; Yogesh, B; Kain, A K; Pauline, T; Anju, B; Sairam, M; Singh, B; Mongia, S S; Kumar, G Ilavazhagan Devendra; Selvamurthy, W

2003-09-01

To evaluate the effect of oral administration of Kombucha tea (K-tea) on lead induced oxidative stress. Sprague Dawley rats were administered 1 mL of 3.8% lead acetate solution daily alone or in combination with K-tea orally for 45 d, and the antioxidant status and lipid peroxidation were evaluated. Oral administration of lead acetate to rats enhanced lipid peroxidation and release of creatine phosphokinase and decreased levels of reduced glutathione (GSH) and antioxidant enzymes (superoxide dismutase, SOD and glutathione peroxidase, GPx). Lead treatment did not alter humoral immunity, but inhibited DTH response when compared to the control. Lead administration also increased DNA fragmentation in liver. Oral administration of Kombucha tea to rats exposed to lead decreased lipid peroxidation and DNA damage with a concomitant increase in the reduced glutathione level and GPx activity. Kombucha tea supplementation relieved the lead induced immunosuppression to appreciable levels. The results suggest that K-tea has potent antioxidant and immunomodulating properties.

Modulatory role of Co-enzyme Q10 on methionine and choline deficient diet-induced non-alcoholic steatohepatitis (NASH) in albino rats.

Science.gov (United States)

Saleh, Dalia O; Ahmed, Rania F; Amin, Mohamed M

2017-03-01

The present study aimed to evaluate the hepato-protective and neuro-protective activity of Co-enzyme Q10 (CoQ10) on non-alcoholic steatohepatitis (NASH) in albino rats induced by methionine and choline-deficient (MCD) diet. Rats were fed an MCD diet for 8 weeks to induce non-alcoholic steatohepatitis. CoQ10 (10 mg/(kg·day) -1 ) was orally administered for 2 consecutive weeks. Twenty-four hours after the last dose of the drug, the behavioral test, namely the activity cage test, was performed and the activity counts were recorded. Serum alanine transaminase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, total/direct bilirubin, and albumin were valued to assess liver function. Moreover, hepatic cytokines interleukin-6 as well as its modulator nuclear factor kappa-light-chain-enhancer of activated B cells were determined. In addition, brain biomarkers, viz ammonia, nitric oxide, and brain-derived neurotrophic factor (BDNF), were measured as they are reliable indices to assess brain damage. Histopathological and immunohistochemical examination of brain proliferating cell nuclear antigen in brain and liver tissues were also evaluated. Results revealed that MCD-induced NASH showed impairment in the liver functions with an increase in the liver inflammatory markers. Moreover, NASH resulted in pronounced brain dysfunction as evidenced by hyper-locomotor activity, a decrease in the BDNF level, as well as an increase in the brain nitric oxide and ammonia contents. Oral treatment of MCD-diet-fed rats with CoQ10 for 14 days showed a marked improvement in all the assigned parameters. Finally, it can be concluded that CoQ10 has a hepatoprotective and neuroprotective role in MCD-diet-induced NASH in rats.

Effect of dimethylaminoethanol, an inhibitor of betaine production, on the disposition of choline in the rat kidney

International Nuclear Information System (INIS)

Lohr, J.; Acara, M.

1990-01-01

The choline metabolite betaine has been shown to be an important organic osmoregulatory solute in the kidney. The isolated perfused rat kidney and kidney slice incubations were used to investigate the effect of 2-dimethylaminoethanol (DMAE), a choline oxidase inhibitor, on the renal excretion and metabolism of choline. In the isolated perfused kidney, [ 14 C]choline, at an initial perfusate concentration of 300 microM, was effectively removed from the perfusate over 25 min, with nearly all the 14 C in the perfusate accounted for by betaine during the remainder of the 90-min perfusion. DMAE at concentrations of 3.0 or 5.0 mM significantly decreased the rate of removal of [ 14 C]choline from the perfusate and the rate of addition of [ 14 C]betaine to the perfusate, yet [14C]betaine remained the only metabolite of choline in perfusate and urine. In kidney tissue slice experiments, conversion of [ 14 C]choline to [ 14 C]betaine was found in cortical, outer medullary and inner medullary regions of rat kidney. DMAE at 5.0 mM significantly inhibited [ 14 C]betaine production in each of the three regions studied. These data show that DMAE is an effective inhibitor of betaine production by the kidney and, as such, may be an important agent for the study of osmoregulation by the kidney

Reversal of profound vecuronium-induced neuromuscular block under sevoflurane anesthesia: sugammadex versus neostigmine.

Directory of Open Access Journals (Sweden)

Lemmens Hendrikus JM

2010-09-01

Full Text Available Abstract Background Acetylcholinesterase inhibitors cannot rapidly reverse profound neuromuscular block. Sugammadex, a selective relaxant binding agent, reverses the effects of rocuronium and vecuronium by encapsulation. This study assessed the efficacy of sugammadex compared with neostigmine in reversal of profound vecuronium-induced neuromuscular block under sevoflurane anesthesia. Methods Patients aged ≥18 years, American Society of Anesthesiologists class 1-4, scheduled to undergo surgery under general anesthesia were enrolled in this phase III, multicenter, randomized, safety-assessor blinded study. Sevoflurane anesthetized patients received vecuronium 0.1 mg/kg for intubation, with maintenance doses of 0.015 mg/kg as required. Patients were randomized to receive sugammadex 4 mg/kg or neostigmine 70 μg/kg with glycopyrrolate 14 μg/kg at 1-2 post-tetanic counts. The primary efficacy variable was time from start of study drug administration to recovery of the train-of-four ratio to 0.9. Safety assessments included physical examination, laboratory data, vital signs, and adverse events. Results Eighty three patients were included in the intent-to-treat population (sugammadex, n = 47; neostigmine, n = 36. Geometric mean time to recovery of the train-of-four ratio to 0.9 was 15-fold faster with sugammadex (4.5 minutes compared with neostigmine (66.2 minutes; p Conclusions Recovery from profound vecuronium-induced block is significantly faster with sugammadex, compared with neostigmine. Neostigmine did not rapidly reverse profound neuromuscular block (Trial registration number: NCT00473694.

Magnetic field induced flow pattern reversal in a ferrofluidic Taylor-Couette system.

Science.gov (United States)

Altmeyer, Sebastian; Do, Younghae; Lai, Ying-Cheng

2015-12-21

We investigate the dynamics of ferrofluidic wavy vortex flows in the counter-rotating Taylor-Couette system, with a focus on wavy flows with a mixture of the dominant azimuthal modes. Without external magnetic field flows are stable and pro-grade with respect to the rotation of the inner cylinder. More complex behaviors can arise when an axial or a transverse magnetic field is applied. Depending on the direction and strength of the field, multi-stable wavy states and bifurcations can occur. We uncover the phenomenon of flow pattern reversal as the strength of the magnetic field is increased through a critical value. In between the regimes of pro-grade and retrograde flow rotations, standing waves with zero angular velocities can emerge. A striking finding is that, under a transverse magnetic field, a second reversal in the flow pattern direction can occur, where the flow pattern evolves into pro-grade rotation again from a retrograde state. Flow reversal is relevant to intriguing phenomena in nature such as geomagnetic reversal. Our results suggest that, in ferrofluids, flow pattern reversal can be induced by varying a magnetic field in a controlled manner, which can be realized in laboratory experiments with potential applications in the development of modern fluid devices.

Plasma microRNAs are sensitive indicators of inter-strain differences in the severity of liver injury induced in mice by a choline- and folate-deficient diet

International Nuclear Information System (INIS)

Tryndyak, Volodymyr P.; Latendresse, John R.; Montgomery, Beverly; Ross, Sharon A.; Beland, Frederick A.; Rusyn, Ivan; Pogribny, Igor P.

2012-01-01

MicroRNAs (miRNAs) are a class of small, conserved, tissue-specific regulatory non-coding RNAs that modulate a variety of biological processes and play a fundamental role in the pathogenesis of major human diseases, including nonalcoholic fatty liver disease (NAFLD). However, the association between inter-individual differences in susceptibility to NAFLD and altered miRNA expression is largely unknown. In view of this, the goals of the present study were (i) to determine whether or not individual differences in the extent of NAFLD-induced liver injury are associated with altered miRNA expression, and (ii) assess if circulating blood miRNAs may be used as potential biomarkers for the noninvasive evaluation of the severity of NAFLD. A panel of seven genetically diverse strains of inbred male mice (A/J, C57BL/6J, C3H/HeJ, 129S/SvImJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ) were fed a choline- and folate-deficient (CFD) diet for 12 weeks. This diet induced liver injury in all mouse strains; however, the extent of NAFLD-associated pathomorphological changes in the livers was strain-specific, with A/J, C57BL/6J, and C3H/HeJ mice being the least sensitive and WSB/EiJ mice being the most sensitive. The morphological changes in the livers were accompanied by differences in the levels of hepatic and plasma miRNAs. The levels of circulating miR-34a, miR-122, miR-181a, miR-192, and miR-200b miRNAs were significantly correlated with a severity of NAFLD-specific liver pathomorphological features, with the strongest correlation occurring with miR-34a. These observations suggest that the plasma levels of miRNAs may be used as biomarkers for noninvasive monitoring the extent of NAFLD-associated liver injury and susceptibility to NAFLD. -- Highlights: ► Choline- and folate-deficiency induces a strain-specific fatty liver injury in mice. ► The extent of liver pathology was accompanied by the changes in microRNA expression. ► The levels of circulating microRNAs mirror the magnitude of

Reversible catecholamine-induced cardiomyopathy due to pheochromocytoma: case report.

Science.gov (United States)

Satendra, Milan; de Jesus, Cláudia; Bordalo e Sá, Armando L; Rosário, Luís; Rocha, José; Bicha Castelo, Henrique; Correia, Maria José; Nunes Diogo, António

2014-03-01

Pheochromocytoma is a tumor originating from chromaffin tissue. It commonly presents with symptoms and signs of catecholamine excess, such as hypertension, tachycardia, headache and sweating. Cardiovascular manifestations include catecholamine-induced cardiomyopathy, which may present as severe left ventricular dysfunction and congestive heart failure. We report a case of pheochromocytoma which was diagnosed following investigation of dilated cardiomyopathy. We highlight the dramatic symptomatic improvement and reversal of cardiomyopathy, with recovery of left ventricular function after treatment. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Superhydrophobic TiO2-polymer nanocomposite surface with UV-induced reversible wettability and self-cleaning properties.

Science.gov (United States)

Xu, Qian Feng; Liu, Yang; Lin, Fang-Ju; Mondal, Bikash; Lyons, Alan M

2013-09-25

Multifunctional superhydrophobic nanocomposite surfaces based on photocatalytic materials, such as fluorosilane modified TiO2, have generated significant research interest. However, there are two challenges to forming such multifunctional surfaces with stable superhydrophobic properties: the photocatalytic oxidation of the hydrophobic functional groups, which leads to the permanent loss of superhydrophobicity, as well as the photoinduced reversible hydrolysis of the catalytic particle surface. Herein, we report a simple and inexpensive template lamination method to fabricate multifunctional TiO2-high-density polyethylene (HDPE) nanocomposite surfaces exhibiting superhydrophobicity, UV-induced reversible wettability, and self-cleaning properties. The laminated surface possesses a hierarchical roughness spanning the micro- to nanoscale range. This was achieved by using a wire mesh template to emboss the HDPE surface creating an array of polymeric posts while partially embedding untreated TiO2 nanoparticles selectively into the top surface of these features. The surface exhibits excellent superhydrophobic properties immediately after lamination without any chemical surface modification to the TiO2 nanoparticles. Exposure to UV light causes the surface to become hydrophilic. This change in wettability can be reversed by heating the surface to restore superhydrophobicity. The effect of TiO2 nanoparticle surface coverage and chemical composition on the mechanism and magnitude of wettability changes was studied by EDX and XPS. In addition, the ability of the surface to shed impacting water droplets as well as the ability of such droplets to clean away particulate contaminants was demonstrated.

Olanzapine Reverses MK-801-Induced Cognitive Deficits and Region-Specific Alterations of NMDA Receptor Subunits

Science.gov (United States)

Liu, Xiao; Li, Jitao; Guo, Chunmei; Wang, Hongli; Sun, Yaxin; Wang, Han; Su, Yun-Ai; Li, Keqing; Si, Tianmei

2018-01-01

Cognitive dysfunction constitutes an essential component in schizophrenia for its early presence in the pathophysiology of the disease and close relatedness to life quality of patients. To develop effective treatment of cognitive deficits, it is important to understand their neurobiological causes and to identify potential therapeutic targets. In this study, adopting repeated MK-801 treatment as an animal model of schizophrenia, we investigated whether antipsychotic drugs, olanzapine and haloperidol, can reverse MK-801-induced cognitive deficits and how the reversal processes recruited proteins involved in glutamate neurotransmission in rat medial prefrontal cortex (mPFC) and hippocampus. We found that low-dose chronic MK-801 treatment impaired object-in-context recognition memory and reversal learning in the Morris water maze, leaving reference memory relatively unaffected, and that these cognitive deficits can be partially reversed by olanzapine, not haloperidol, treatment. At the molecular level, chronic MK-801 treatment resulted in the reduction of multiple N-methyl-D-aspartate (NMDA) receptor subunits in rat mPFC and olanzapine, not haloperidol, treatment restored the levels of GluN1 and phosphorylated GluN2B in this region. Taken together, MK-801-induced cognitive deficits may be associated with region-specific changes in NMDA receptor subunits and the reversal of specific NMDA receptor subunits may underlie the cognition-enhancing effects of olanzapine. PMID:29375333

Effect of choline chloride supplementation on milk production and milk composition of Etawah grade goats

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Supriyati

2016-08-01

Full Text Available Abstract Background The effect of choline chloride supplementation through forced drinking combined with concentrate diets containing Ca-fish oil on milk production and milk composition of Etawah Grade goats was evaluated. Choline chloride is an essential component in ruminant diets as it is required for fat metabolism. Method The experiment was conducted in a completely randomized block design with three types of treatments and eight replications. The trial had two successive experimental periods; the first, during the eight weeks of late pregnancy, and the second, during the first 12 weeks of lactation. Twenty-four Etawah Grade does in the second gestation period were divided into three treatment groups. Commercial choline chloride 60 % in corncobs-based powder was used as a source of choline chloride. The treatments were no supplementation (control and supplemented with either 4 g or 8 g/2days of choline chloride. Choline chloride was given to the animals through a forced drinking technique, after dissolving it in 60 ml drinking water. The initial body weight of does was 38.81 ± 3.66 kg. The does were penned individually, and were given fresh chopped King Grass ad libitum and 700 g/day of concentrate diets containing Ca-fish oil, starting eight weeks prior to expecting kidding and continuing for 12 weeks of parturition. Results All nutrient intakes were not significantly different (p > 0.05 among the treatments during the late pregnancy and the lactation periods. Supplementation did not affect (p > 0.05 the average daily gains and feed conversion ratio during pregnancy but gave effects (p < 0.05 on the average daily gains, feed conversion ratio and income over feed cost during lactation. The highest average daily milk yields and 4 % fat corrected milk yields were found in goats supplemented with 4 g/2days of choline chloride and increased by 17.00 % and 24.67 %, respectively, compared to the control. Moreover, milk

Structural studies on choline-carboxylate bio-ionic liquids by x-ray scattering and molecular dynamics.

Science.gov (United States)

Tanzi, Luana; Ramondo, Fabio; Caminiti, Ruggero; Campetella, Marco; Di Luca, Andrea; Gontrani, Lorenzo

2015-09-21

We report a X-ray diffraction and molecular dynamics study on three choline-based bio-ionic liquids, choline formate, [Ch] [For], choline propanoate, [Ch][Pro], and choline butanoate, [Ch][But]. For the first time, this class of ionic liquids has been investigated by X-ray diffraction. Experimental and theoretical structure factors have been compared for each term of the series. Local structural organization has been obtained from ab initio calculations through static models of isolated ion pairs and dynamic simulations of small portions of liquids through twelve, ten, and nine ion pairs for [Ch][For], [Ch][Pro], and [Ch][But], respectively. All the theoretical models indicate that cations and anions are connected by strong hydrogen bonding and form stable ion pairs in the liquid that are reminiscent of the static ab initio ion pairs. Different structural aspects may affect the radial distribution function, like the local structure of ion pairs and the conformation of choline. When small portions of liquids have been simulated by dynamic quantum chemical methods, some key structural features of the X-ray radial distribution function were well reproduced whereas the classical force fields here applied did not entirely reproduce all the observed structural features.

Structural studies on choline-carboxylate bio-ionic liquids by x-ray scattering and molecular dynamics

International Nuclear Information System (INIS)

Tanzi, Luana; Ramondo, Fabio; Caminiti, Ruggero; Campetella, Marco; Di Luca, Andrea; Gontrani, Lorenzo

2015-01-01

We report a X-ray diffraction and molecular dynamics study on three choline-based bio-ionic liquids, choline formate, [Ch] [For], choline propanoate, [Ch][Pro], and choline butanoate, [Ch][But]. For the first time, this class of ionic liquids has been investigated by X-ray diffraction. Experimental and theoretical structure factors have been compared for each term of the series. Local structural organization has been obtained from ab initio calculations through static models of isolated ion pairs and dynamic simulations of small portions of liquids through twelve, ten, and nine ion pairs for [Ch][For], [Ch][Pro], and [Ch][But], respectively. All the theoretical models indicate that cations and anions are connected by strong hydrogen bonding and form stable ion pairs in the liquid that are reminiscent of the static ab initio ion pairs. Different structural aspects may affect the radial distribution function, like the local structure of ion pairs and the conformation of choline. When small portions of liquids have been simulated by dynamic quantum chemical methods, some key structural features of the X-ray radial distribution function were well reproduced whereas the classical force fields here applied did not entirely reproduce all the observed structural features

Structural studies on choline-carboxylate bio-ionic liquids by x-ray scattering and molecular dynamics

Energy Technology Data Exchange (ETDEWEB)

Tanzi, Luana; Ramondo, Fabio, E-mail: fabio.ramondo@univaq.it [Department of Physical and Chemical Sciences, University of L’Aquila, Via Vetoio, L’Aquila I-67100 (Italy); Caminiti, Ruggero; Campetella, Marco; Di Luca, Andrea; Gontrani, Lorenzo, E-mail: lorenzo.gontrani@uniroma1.it [Department of Chemistry, University of Rome ‘La Sapienza’, P.le Aldo Moro 5, I-00185 Rome (Italy)

2015-09-21

We report a X-ray diffraction and molecular dynamics study on three choline-based bio-ionic liquids, choline formate, [Ch] [For], choline propanoate, [Ch][Pro], and choline butanoate, [Ch][But]. For the first time, this class of ionic liquids has been investigated by X-ray diffraction. Experimental and theoretical structure factors have been compared for each term of the series. Local structural organization has been obtained from ab initio calculations through static models of isolated ion pairs and dynamic simulations of small portions of liquids through twelve, ten, and nine ion pairs for [Ch][For], [Ch][Pro], and [Ch][But], respectively. All the theoretical models indicate that cations and anions are connected by strong hydrogen bonding and form stable ion pairs in the liquid that are reminiscent of the static ab initio ion pairs. Different structural aspects may affect the radial distribution function, like the local structure of ion pairs and the conformation of choline. When small portions of liquids have been simulated by dynamic quantum chemical methods, some key structural features of the X-ray radial distribution function were well reproduced whereas the classical force fields here applied did not entirely reproduce all the observed structural features.

Dexamethasone Does Not Inhibit Sugammadex Reversal After Rocuronium-Induced Neuromuscular Block.

Science.gov (United States)

Buonanno, Pasquale; Laiola, Anna; Palumbo, Chiara; Spinelli, Gianmario; Servillo, Giuseppe; Di Minno, Raffaele Maria; Cafiero, Tullio; Di Iorio, Carlo

2016-06-01

Sugammadex is a relatively new molecule that reverses neuromuscular block induced by rocuronium. The particular structure of sugammadex traps the cyclopentanoperhydrophenanthrene ring of rocuronium in its hydrophobic cavity. Dexamethasone shares the same steroidal structure with rocuronium. Studies in vitro have demonstrated that dexamethasone interacts with sugammadex, reducing its efficacy. In this study, we investigated the clinical relevance of this interaction and its influence on neuromuscular reversal. In this retrospective case-control study, we analyzed data from 45 patients divided into 3 groups: dexamethasone after induction group (15 patients) treated with 8 mg dexamethasone as an antiemetic drug shortly after induction of anesthesia; dexamethasone before reversal group (15 patients) treated with dexamethasone just before sugammadex injection; and control group (15 patients) treated with 8 mg ondansetron. All groups received 0.6 mg/kg rocuronium at induction, 0.15 mg/kg rocuronium at train-of-four ratio (TOF) 2 for neuromuscular relaxation, and 2 mg/kg sugammadex for reversal at the end of the procedure at TOF2. Neuromuscular relaxation was monitored with a TOF-Watch® system. The control group had a recovery time of 154 ± 54 seconds (mean ± SD), the dexamethasone after induction group 134 ± 55 seconds, and the dexamethasone before reversal group 131 ± 68 seconds. The differences among groups were not statistically significant (P = 0.5141). Our results show that the use of dexamethasone as an antiemetic drug for the prevention of postoperative nausea and vomiting does not interfere with reversal of neuromuscular blockade with sugammadex in patients undergoing elective surgery with general anesthesia in contrast to in vitro studies that support this hypothesis.

[11C]Choline PET/CT predicts survival in hormone-naive prostate cancer patients with biochemical failure after radical prostatectomy

International Nuclear Information System (INIS)

Giovacchini, Giampiero; Incerti, Elena; Mapelli, Paola; Gianolli, Luigi; Picchio, Maria; Kirienko, Margarita; Briganti, Alberto; Gandaglia, Giorgio; Montorsi, Francesco

2015-01-01

Over the last decade, PET/CT with radiolabelled choline has been shown to be useful for restaging patients with prostate cancer (PCa) who develop biochemical failure. The limitations of most clinical studies have been poor validation of [ 11 C]choline PET/CT-positive findings and lack of survival analysis. The aim of this study was to assess whether [ 11 C]choline PET/CT can predict survival in hormone-naive PCa patients with biochemical failure. This retrospective study included 302 hormone-naive PCa patients treated with radical prostatectomy who underwent [ 11 C]choline PET/CT from 1 December 2004 to 31 July 2007 because of biochemical failure (prostate-specific antigen, PSA, >0.2 ng/mL). Median PSA was 1.02 ng/mL. PCa-specific survival was estimated using Kaplan-Meier curves. Cox regression analysis was used to evaluate the association between clinicopathological variables and PCa-specific survival. The coefficients of the covariates included in the Cox regression analysis were used to develop a novel nomogram. Median follow-up was 7.2 years (1.4 - 18.9 years). [ 11 C]Choline PET/CT was positive in 101 of 302 patients (33 %). Median PCa-specific survival after prostatectomy was 14.9 years (95 % CI 9.7 - 20.1 years) in patients with positive [ 11 C]choline PET/CT. Median survival was not achieved in patients with negative [ 11 C]choline PET/CT. The 15-year PCa-specific survival probability was 42.4 % (95 % CI 31.7 - 53.1 %) in patients with positive [ 11 C]choline PET/CT and 95.5 % (95 % CI 93.5 - 97.5 %) in patients with negative [ 11 C]choline PET/CT. In multivariate analysis, [ 11 C]choline PET/CT (hazard ratio 6.36, 95 % CI 2.14 - 18.94, P < 0.001) and Gleason score >7 (hazard ratio 3.11, 95 % CI 1.11 - 8.66, P = 0.030) predicted PCa-specific survival. An internally validated nomogram predicted 15-year PCa-specific survival probability with an accuracy of 80 %. Positive [ 11 C]choline PET/CT after biochemical failure predicts PCa-specific survival in hormone

Gold nanoparticle–choline complexes can block nicotinic acetylcholine receptors

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Chur Chin

2010-04-01

Full Text Available Chur Chin1, In Kyeom Kim2, Dong Yoon Lim3, Ki Suk Kim4, Hyang Ae Lee4, Eun Joo Kim41Department of Pediatrics, Fatima Hospital, Daegu, Korea; 2Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu, Korea; 3Department of Pharmacology, School of Medicine, Chosun University, Gwangju, Korea; 4Korea Institute of Toxicology, Daejeon, KoreaAbstract: We identified a novel class of direct ion-channel blockers of ligand-gated ion channels called the gold nanoparticle–choline complex. Negatively charged gold nanoparticles (1.4 nm block ion pores by binding to the sulfur group of the cysteine loop of nicotinic acetylcholine receptors (nAChRs, and currents evoked by acetylcholine (Ach can break these bonds. The current evoked by ACh in nAChRs was blocked directly in ion pores by the gold nanoparticle–choline complex. In adrenal-gland perfusion studies, the complex also blocked nAChRs by diminishing catecholamine release by about 75%. An in vivo study showed muscle relaxation in rats after injection of the complex. These results will foster the application of gold nanoparticles as a direct ion-channel blocker. Keywords: negatively charged gold nanoparticle, choline, gold–sulfur bond, nicotinic acetylcholine receptor, direct ion-channel blocker

Review on Carbon Dioxide Absorption by Choline Chloride/Urea Deep Eutectic Solvents

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Rima J. Isaifan

2018-01-01

Full Text Available In the recent past few years, deep eutectic solvents (DESs were developed sharing similar characteristics to ionic liquids but with more advantageous features related to preparation cost, environmental impact, and efficiency for gas separation processes. Amongst many combinations of DES solvents that have been prepared, reline (choline chloride as the hydrogen bond acceptor mixed with urea as the hydrogen bond donor was the first DES synthesized and is still the one with the lowest melting point. Choline chloride/urea DES has proven to be a promising solvent as an efficient medium for carbon dioxide capture when compared with amine alone or ionic liquids under the same conditions. This review sheds light on the preparation method, physical and chemical characteristics, and the CO2 absorption capacity of choline chloride/urea DES under different temperatures and pressures reported up to date.

11C-choline vs. 18F-FDG PET/CT in assessing bone involvement in patients with multiple myeloma

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Ambrosini Valentina

2007-06-01

Full Text Available Abstract Background Multiple Myeloma (MM is a B cell neoplasm causing lytic or osteopenic bone abnormalities. Whole body skeletal survey (WBSS, Magnetic resonance (MR and 18F-FDG PET/CT are imaging techniques routinely used for the evaluation of bone involvement in MM patients. Aim As MM bone lesions may present low 18F-FDG uptake; the aim of this study was to assess the possible added value and limitations of 11C-Choline to that of 18F-FDG PET/CT in patients affected with MM. Methods Ten patients affected with MM underwent a standard 11C-Choline PET/CT and an 18F-FDG PET/CT within one week. The results of the two scans were compared in terms of number, sites and SUVmax of lesions. Results Four patients (40% had a negative concordant 11C-Choline and 18F-FDG PET/CT scans. Two patients (20% had a positive 11C-Choline and 18F-FDG PET/CT scans that identified the same number and sites of bone lesions. The remaining four patients (40% had a positive 11C-Choline and 18F-FDG PET/CT scan, but the two exams identified different number of lesions. Choline showed a mean SUVmax of 5 while FDG showed a mean SUVmax of 3.8 (P = 0.042. Overall, 11C-Choline PET/CT scans detected 37 bone lesions and 18F-FDG PET/CT scans detected 22 bone lesions but the difference was not significant (P = 0.8. Conclusion According to these preliminary data, 11C-Choline PET/CT appears to be more sensitive than 18F-FDG PET/CT for the detection of bony myelomatous lesions. If these data are confirmed in larger series of patients, 11C-Choline may be considered a more appropriate functional imaging in association with MRI for MM bone staging.

No Acute Effects of Choline Bitartrate Food Supplements on Memory in Healthy, Young, Human Adults

NARCIS (Netherlands)

Lippelt, Dominique; van der Kint, Sander; van Herk, Kevin; Naber, M.

2016-01-01

Choline is a dietary component and precursor of acetylcholine, a crucial neurotransmitter for memory-related brain functions. In two double-blind, placebo-controlled cross-over experiments, we investigated whether the food supplement choline bitartrate improved declarative memory and working memory

Sugammadex 4.0 mg kg-1 reversal of deep rocuronium-induced neuromuscular blockade

DEFF Research Database (Denmark)

Yu, Buwei; Wang, Xiangrui; Hansen, Søren Helbo

2014-01-01

Objective: Maintenance of deep Neuro Muscular Blockade (NMB) until the end of surgery may be beneficial in some surgical procedures. The selective relaxant binding agent sugammadex rapidly reverses deep levels of rocuronium-induced NMB. The purpose of this study was to evaluate the efficacy...... and safety of sugammadex 4.0 mg kg-1 for reversal of deep rocuronium-induced NMB in Chinese and Caucasian patients. Methods: This was an open-label, multicenter, prospective Phase III efficacy study in adult American Society of Anesthesiologists Class 1-3 patients scheduled for surgery under general...... anesthesia and requiring deep NMB. All patients received intravenous propofol and opioids for induction and maintenance of anesthesia, and a single intubation dose of rocuronium 0.6 mg/kg, with maintenance doses of 0.1-0.2 mg/kg as required. Sugammadex 4.0 mg/kg was administered after the last dose...

Arsenite binding-induced zinc loss from PARP-1 is equivalent to zinc deficiency in reducing PARP-1 activity, leading to inhibition of DNA repair

Energy Technology Data Exchange (ETDEWEB)

Sun, Xi; Zhou, Xixi [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Du, Libo [Center for Molecular Science, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190 (China); Liu, Wenlan [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Liu, Yang [Center for Molecular Science, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190 (China); Hudson, Laurie G. [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Liu, Ke Jian, E-mail: kliu@salud.unm.edu [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States)

2014-01-15

Inhibition of DNA repair is a recognized mechanism for arsenic enhancement of ultraviolet radiation-induced DNA damage and carcinogenesis. Poly(ADP-ribose) polymerase-1 (PARP-1), a zinc finger DNA repair protein, has been identified as a sensitive molecular target for arsenic. The zinc finger domains of PARP-1 protein function as a critical structure in DNA recognition and binding. Since cellular poly(ADP-ribosyl)ation capacity has been positively correlated with zinc status in cells, we hypothesize that arsenite binding-induced zinc loss from PARP-1 is equivalent to zinc deficiency in reducing PARP-1 activity, leading to inhibition of DNA repair. To test this hypothesis, we compared the effects of arsenite exposure with zinc deficiency, created by using the membrane-permeable zinc chelator TPEN, on 8-OHdG formation, PARP-1 activity and zinc binding to PARP-1 in HaCat cells. Our results show that arsenite exposure and zinc deficiency had similar effects on PARP-1 protein, whereas supplemental zinc reversed these effects. To investigate the molecular mechanism of zinc loss induced by arsenite, ICP-AES, near UV spectroscopy, fluorescence, and circular dichroism spectroscopy were utilized to examine arsenite binding and occupation of a peptide representing the first zinc finger of PARP-1. We found that arsenite binding as well as zinc loss altered the conformation of zinc finger structure which functionally leads to PARP-1 inhibition. These findings suggest that arsenite binding to PARP-1 protein created similar adverse biological effects as zinc deficiency, which establishes the molecular mechanism for zinc supplementation as a potentially effective treatment to reverse the detrimental outcomes of arsenic exposure. - Highlights: • Arsenite binding is equivalent to zinc deficiency in reducing PARP-1 function. • Zinc reverses arsenic inhibition of PARP-1 activity and enhancement of DNA damage. • Arsenite binding and zinc loss alter the conformation of zinc finger

Arsenite binding-induced zinc loss from PARP-1 is equivalent to zinc deficiency in reducing PARP-1 activity, leading to inhibition of DNA repair

International Nuclear Information System (INIS)

Sun, Xi; Zhou, Xixi; Du, Libo; Liu, Wenlan; Liu, Yang; Hudson, Laurie G.; Liu, Ke Jian

2014-01-01

Inhibition of DNA repair is a recognized mechanism for arsenic enhancement of ultraviolet radiation-induced DNA damage and carcinogenesis. Poly(ADP-ribose) polymerase-1 (PARP-1), a zinc finger DNA repair protein, has been identified as a sensitive molecular target for arsenic. The zinc finger domains of PARP-1 protein function as a critical structure in DNA recognition and binding. Since cellular poly(ADP-ribosyl)ation capacity has been positively correlated with zinc status in cells, we hypothesize that arsenite binding-induced zinc loss from PARP-1 is equivalent to zinc deficiency in reducing PARP-1 activity, leading to inhibition of DNA repair. To test this hypothesis, we compared the effects of arsenite exposure with zinc deficiency, created by using the membrane-permeable zinc chelator TPEN, on 8-OHdG formation, PARP-1 activity and zinc binding to PARP-1 in HaCat cells. Our results show that arsenite exposure and zinc deficiency had similar effects on PARP-1 protein, whereas supplemental zinc reversed these effects. To investigate the molecular mechanism of zinc loss induced by arsenite, ICP-AES, near UV spectroscopy, fluorescence, and circular dichroism spectroscopy were utilized to examine arsenite binding and occupation of a peptide representing the first zinc finger of PARP-1. We found that arsenite binding as well as zinc loss altered the conformation of zinc finger structure which functionally leads to PARP-1 inhibition. These findings suggest that arsenite binding to PARP-1 protein created similar adverse biological effects as zinc deficiency, which establishes the molecular mechanism for zinc supplementation as a potentially effective treatment to reverse the detrimental outcomes of arsenic exposure. - Highlights: • Arsenite binding is equivalent to zinc deficiency in reducing PARP-1 function. • Zinc reverses arsenic inhibition of PARP-1 activity and enhancement of DNA damage. • Arsenite binding and zinc loss alter the conformation of zinc finger

Synthesis and preclinical evaluation of the choline transport tracer deshydroxy-[18F]fluorocholine ([18F]dOC)

International Nuclear Information System (INIS)

Henriksen, G.; Herz, M.; Hauser, A.; Schwaiger, M.; Wester, H.-J.

2004-01-01

11 C-labeled choline ([ 11 C]CHO) and 18 F-fluorinated choline analogues have been demonstrated to be valuable tracers for in vivo imaging of neoplasms by means of positron emission tomography (PET). The objective of the present study was to evaluate whether deshydroxy-[ 18 F]fluorocholine, ([ 18 F]dOC), a non-metabolizable [ 18 F]fluorinated choline analogue, can serve as a surrogate for cholines that are able to be phosphorylated and thus allow PET-imaging solely by addressing the choline transport system. The specificity of uptake of [ 18 F]dOC was compared with that of [ 11 C]choline ([ 11 C]CHO) in cultured rat pancreatic carcinoma and PC-3 human prostate cancer cells in vitro. In addition, biodistribution of [ 18 F]dOC and [ 11 C]CHO was compared in AR42J- and PC-3 tumor bearing mice. The in vitro studies revealed that membrane transport of both compounds can be inhibited in a concentration dependent manner by similar concentrations of cold choline (IC 50 [ 18 F]dOC= 11 μM; IC 50 [ 11 C]CHO=13 μM. In vitro studies with PC-3 and AR42J cells revealed that the internalized fraction of [ 18 F]dOC after 5 min incubation time is comparable to that of [ 11 C]CHO, whereas the uptake of [ 11 C]CHO was superior after 20 min incubation time. As for [ 11 C]CHO, kidney and liver were also the primary sites of uptake for [ 18 F]dOC in vivo. Biodistribution data after simultaneous injection of both tracers into AR42J tumor bearing mice revealed slightly higher tumor uptake for [ 18 F]dOC at 10 min post-injection, whereas [ 11 C]CHO uptake was higher at later time points. In conclusion, [ 18 F]dOC is taken up into AR42J rat pancreatic carcinoma and PC-3 human prostate cancer cells by a choline specific transport system. Similar transport rates of [ 18 F]dOC and [ 11 C]CHO result in comparable cellular uptake levels at early time points. In contrast to [ 18 F]dOC, which is transported but not intracellularily trapped, the choline kinase substrate [ 11 C]CHO is transported

Reversible photo-induced trap formation in mixed-halide hybrid perovskites for photovoltaics.

Science.gov (United States)

Hoke, Eric T; Slotcavage, Daniel J; Dohner, Emma R; Bowring, Andrea R; Karunadasa, Hemamala I; McGehee, Michael D

2015-01-01

We report on reversible, light-induced transformations in (CH 3 NH 3 )Pb(Br x I 1- x ) 3 . Photoluminescence (PL) spectra of these perovskites develop a new, red-shifted peak at 1.68 eV that grows in intensity under constant, 1-sun illumination in less than a minute. This is accompanied by an increase in sub-bandgap absorption at ∼1.7 eV, indicating the formation of luminescent trap states. Light soaking causes a splitting of X-ray diffraction (XRD) peaks, suggesting segregation into two crystalline phases. Surprisingly, these photo-induced changes are fully reversible; the XRD patterns and the PL and absorption spectra revert to their initial states after the materials are left for a few minutes in the dark. We speculate that photoexcitation may cause halide segregation into iodide-rich minority and bromide-enriched majority domains, the former acting as a recombination center trap. This instability may limit achievable voltages from some mixed-halide perovskite solar cells and could have implications for the photostability of halide perovskites used in optoelectronics.

Role of carbon-11 choline PET/CT in the management of uterine carcinoma. Initial experience

International Nuclear Information System (INIS)

Sofue, Keitaro; Sawada, Morio; Arai, Yasuaki; Tateishi, Ukihide; Inoue, Tomio; Maeda, Tetsuo; Sugimura, Kazuro; Terauchi, Takashi; Kano, Daisuke

2009-01-01

The present study was conducted to clarify the role of carbon-11 choline ( 11 C-choline) positron emission tomography (PET)/computed tomography (CT) in the management of uterine carcinoma. Twenty-two patients who underwent 11 C-choline PET/CT and pelvic MRI were evaluated retrospectively. The images were reviewed by a board-certified radiologist and a nuclear medicine specialist who were unaware of any clinical information, and a consensus was reached. Diagnostic accuracy of PET/CT was evaluated for staging. The reference standard consisted of histological examination (n=17) and follow-up conventional CT (n=5). In five patients with cervical carcinoma, 11 C-choline PET/CT was performed before and after treatment that consisted of cisplatin infusion and subsequent radiotherapy. Standardized uptake value (SUV) was compared with unidimensional and volumetric measurements that were made on magnetic resonance images (MRI) before and after treatment. Based on PET/CT interpretations, the reviewers correctly classified tumor (T) stage in 8 patients (47%), nodes (N) stage in 21 patients (96%), metastasis (M) stage in 20 patients (91%), and tumor, nodes and metastasis (TNM) stage in 15 patients (88%). Tumor size, volume, and SUV decreased after treatment in five patients with cervical carcinoma. Using the Pearson correlation test, a significant correlation was found between the reduction rate of SUV and reduction rate of tumor volume. 11 C-choline PET/CT is an accurate means for the management of patients with uterine carcinoma. The combination of 11 C-choline PET/CT and MRI increases the accuracy of staging in patients with uterine carcinoma. (author)

Measurement of concentrations of whole blood levels of choline, betaine, and dimethylglycine and their relations to plasma levels.

Science.gov (United States)

Awwad, Hussain Mohamad; Kirsch, Susanne H; Geisel, Juergen; Obeid, Rima

2014-04-15

We aimed at developing a method for the measurement of choline and its metabolites in whole blood (WB). After an extraction step, quantification of choline, betaine, and dimethylglycine (DMG) was performed using ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Plasma and WB metabolites were evaluated in a group of 61 elderly people. The calibration curves were linear (r(2)>0.997) for all compounds. The inter- and intra-assay coefficients of variation for all analytes were 90% and the relative matrix effect were ≤4.0%. The median concentrations of choline, betaine, and DMG were 11.3, 27.8, and 5.9μmol/L in plasma and 66.6, 165, and 13.7μmol/L in WB, respectively. There were positive correlations between WB and plasma markers; for choline (r=0.42), betaine (r=0.61), and DMG (r=0.56) (all p≤0.001). The concentrations of betaine in WB and plasma were significantly higher in men than in women. The concentrations of WB choline and DMG did not differ significantly according to sex. In conclusion, we have established a reliable method for measuring choline metabolites in WB. The concentrations of WB choline, betaine, and DMG seem to reflect intracellular concentrations of these metabolites. Copyright © 2014 Elsevier B.V. All rights reserved.

Pressure-induced reversal between thermal contraction and expansion in ferroelectric PbTiO3.

Science.gov (United States)

Zhu, Jinlong; Zhang, Jianzhong; Xu, Hongwu; Vogel, Sven C; Jin, Changqing; Frantti, Johannes; Zhao, Yusheng

2014-01-15

Materials with zero/near zero thermal expansion coefficients are technologically important for applications in thermal management and engineering. To date, this class of materials can only be produced by chemical routes, either by changing chemical compositions or by composting materials with positive and negative thermal expansion. Here, we report for the first time a physical route to achieve near zero thermal expansion through application of pressure. In the stability field of tetragonal PbTiO3 we observed pressure-induced reversals between thermal contraction and expansion between ambient pressure and 0.9 GPa. This hybrid behavior leads to a mathematically infinite number of crossover points in the pressure-volume-temperature space and near-zero thermal expansion coefficients comparable to or even smaller than those attained by chemical routes. The observed pressures for this unusual phenomenon are within a small range of 0.1-0.9 GPa, potentially feasible for designing stress-engineered materials, such as thin films and nano-crystals, for thermal management applications.

Monoamines stimulate sex reversal in the saddleback wrasse.

Science.gov (United States)

Larson, Earl T; Norris, David O; Gordon Grau, E; Summers, Cliff H

2003-02-15

Monoamine neurotransmitters (norepinephrine, dopamine, and serotonin) play an important role in reproduction and sexual behavior throughout the vertebrates. They are the first endogenous chemical signals in the regulation of the hypothalamo-pituitary-gonadal (HPG) axis. In teleosts with behavioral sex determination, much is known about behavioral cues that induce sex reversal. The cues are social, processed via the visual system and depend on the ratio of females to males in the population. The mechanisms by which these external behavioral cues are converted to an internal chemical regulatory process are largely unknown. The protogynous Hawaiian saddleback wrasse, Thalassoma duperrey, was used to investigate the biological pathway mediating the conversion of a social cue into neuroendocrine events regulating sex reversal. Because monoamines play an important role in the regulation of the HPG axis, they were selected as likely candidates for such a conversion. To determine if monoamines could affect sex reversal, drugs affecting monoamines were used in an attempt to either induce sex reversal under non-permissive conditions, or prevent sex reversal under permissive conditions. Increasing norepinephrine or blocking dopamine or serotonin lead to sex reversal in experimental animals under non-permissive conditions. Increasing serotonin blocked sex reversal under permissive conditions, while blocking dopamine or norepinephrine retarded the process. The results presented here demonstrate that monoamines contribute significantly to the control sex reversal. Norepinephrine stimulates initiation and completion of gonadal sex of reversal as well as color change perhaps directly via its effects on the HPG axis. Dopamine exercises inhibitory action on the initiation of sex reversal while 5-HT inhibits both initiation and completion of sex reversal. The serotonergic system appears to be an integral part of the pathway mediating the conversion of a social cue into a

Progressive myopia or hyperopia can be induced in chicks and reversed by manipulation of the chromaticity of ambient light.

Science.gov (United States)

Foulds, Wallace S; Barathi, Veluchamy A; Luu, Chi D

2013-12-09

To determine whether progressive ametropia can be induced in chicks and reversed by manipulation of the chromaticity of ambient light. One-day-old chicks were raised in red light (90% red, 10% yellow-green) or in blue light (85% blue, 15% green) with a 12 hour on/off cycle for 14 to 42 days. Refraction was determined by streak retinoscopy, and by automated infrared photoretinoscopy and ocular biometry by A-scan ultrasonography. Red light induced progressive myopia (mean refraction ± SD at 28 days, -2.83 ± 0.25 diopters [D]). Progressive hyperopia was induced by blue light (mean refraction at 28 days, +4.55 ± 0.21 D). The difference in refraction between the groups was highly significant at P light (-2.21 ± 0.21 D) was reversed to hyperopia (+2.50 ± 0.29 D) by subsequent 21 days of blue light. Hyperopia induced by 21 days of blue light (+4.21 ± 0.19 D) was reversed to myopia (-1.23 ± 0.12 D) by 21 days of red light. Rearing chicks in red light caused progressive myopia, while rearing in blue light caused progressive hyperopia. Light-induced myopia or hyperopia in chicks can be reversed to hyperopia or myopia, respectively, by an alteration in the chromaticity of ambient light. Manipulation of chromaticity may be applicable to the management of human childhood myopia.

Prostate cancer: concordance between "1"8F-choline PET and CT in biochemical relapse

International Nuclear Information System (INIS)

Herández Pinzón, J.; Ferrarotti, C.; Ferrari, L.; Larrañaga, N.; Gallo, J.C.; Mena, D.; Bastianello, M.

2016-01-01

Objective: To establish the concordance between 18-fluor choline positron emission tomography (PET) and computed tomography (CT) for re-staging patients with biochemical relapse of prostate cancer according to the TNM system. Materials and methods: The medical records of the Molecular Imaging Section were retrospectively reviewed. The TNM classification was established by us for each method, and the Kappa concordance statistic was used to classify the results according to the Landis and Koch proposal. Results: The PET-choline reported 19 (59.4%) patients N0 and 13 (40.6%) N1, while CT reported 28 (87.5%) N0 and 4 (12.5%) N1. In metastasis classification PET-choline established M0 in 17 (53.1%) patients, M1a in 1 (3.1%), M1b in 5 (15.6%), M1c in 1 (3.1%), M1a + M1b in 7 (21.9%), and M1b + M1c in 1 (3.1%). On the other hand, CT was M0 in 23 (71.9%) patients, M1a in 2 (6.25%), M1a + M1b in 2 (6.25%), and M1b + M1c in 5 (15.6%). The correlation between PET-choline and CT in the TNM lymph node and metastasis classifications was 71.88%, with a Kappa of 0.3455 (standard error 0.1336; P=.0049) and 62.5% with Kappa 0.3725 (standard error 0.0847; P=.0001), respectively. Discussion: Several studies have shown a high diagnostic accuracy of PET-choline detecting the spread of the disease compared to conventional methods. Conclusion: There is poor concordance for metastatic and lymph node classifications according to the TNM system between choline-PET and CT. (authors) [es

Expression of human choline kinase in NIH 3T3 fibroblasts increases the mitogenic potential of insulin and insulin-like growth factor I.

Science.gov (United States)

Chung, T; Huang, J S; Mukherjee, J J; Crilly, K S; Kiss, Z

2000-05-01

In mammalian cells, growth factors, oncogenes, and carcinogens stimulate phosphocholine (PCho) synthesis by choline kinase (CK), suggesting that PCho may regulate cell growth. To validate the role of PCho in mitogenesis, we determined the effects of insulin, insulin-like growth factor I (IGF-I), and other growth factors on DNA synthesis in NIH 3T3 fibroblast sublines highly expressing human choline kinase (CK) without increasing phosphatidylcholine synthesis. In serum-starved CK expressor cells, insulin and IGF-I stimulated DNA synthesis, p70 S6 kinase (p70 S6K) activity, phosphatidylinositol 3-kinase (PI3K) activity, and activating phosphorylation of p42/p44 mitogen-activated protein kinases (MAPK) to greater extents than in the corresponding vector control cells. Furthermore, the CK inhibitor hemicholinium-3 (HC-3) inhibited insulin- and IGF-I-induced DNA synthesis in the CK overexpressors, but not in the vector control cells. The results indicate that high cellular levels of PCho potentiate insulin- and IGF-I-induced DNA synthesis by MAPK- and p70 S6K-regulated mechanisms.

Inositol induces mesenchymal-epithelial reversion in breast cancer cells through cytoskeleton rearrangement.

Science.gov (United States)

Dinicola, Simona; Fabrizi, Gianmarco; Masiello, Maria Grazia; Proietti, Sara; Palombo, Alessandro; Minini, Mirko; Harrath, Abdel Halim; Alwasel, Saleh H; Ricci, Giulia; Catizone, Angela; Cucina, Alessandra; Bizzarri, Mariano

2016-07-01

Inositol displays multi-targeted effects on many biochemical pathways involved in epithelial-mesenchymal transition (EMT). As Akt activation is inhibited by inositol, we investigated if such effect could hamper EMT in MDA-MB-231 breast cancer cells. In cancer cells treated with pharmacological doses of inositol E-cadherin was increased, β-catenin was redistributed behind cell membrane, and metalloproteinase-9 was significantly reduced, while motility and invading capacity were severely inhibited. Those changes were associated with a significant down-regulation of PI3K/Akt activity, leading to a decrease in downstream signaling effectors: NF-kB, COX-2, and SNAI1. Inositol-mediated inhibition of PS1 leads to lowered Notch 1 release, thus contributing in decreasing SNAI1 levels. Overall, these data indicated that inositol inhibits the principal molecular pathway supporting EMT. Similar results were obtained in ZR-75, a highly metastatic breast cancer line. These findings are coupled with significant changes on cytoskeleton. Inositol slowed-down vimentin expression in cells placed behind the wound-healing edge and stabilized cortical F-actin. Moreover, lamellipodia and filopodia, two specific membrane extensions enabling cell migration and invasiveness, were no longer detectable after inositol addiction. Additionally, fascin and cofilin, two mandatory required components for F-actin assembling within cell protrusions, were highly reduced. These data suggest that inositol may induce an EMT reversion in breast cancer cells, suppressing motility and invasiveness through cytoskeleton modifications. Copyright © 2016 Elsevier Inc. All rights reserved.

Proanthocyanidins Attenuation of Chronic Lead-Induced Liver Oxidative Damage in Kunming Mice via the Nrf2/ARE Pathway

Directory of Open Access Journals (Sweden)

Miao Long

2016-10-01

Full Text Available Lead is harmful for human health and animals. Proanthocyanidins (PCs, a natural antioxidant, possess a broad spectrum of pharmacological and medicinal properties. However, its protective effects against lead-induced liver damage have not been clarified. This study was aimed to evaluate the protective effect of PCs on the hepatotoxicity of male Kunming mice induced by chronic lead exposure. A total of 70 healthy male Kunming mice were averagely divided into four groups: control group, i.e., the group exposed to lead, the group treated with PCs, and the group co-treated with lead and PCs. The mice exposed to lead were given water containing 0.2% lead acetate. Mice treated in the PCs and PCs lead co-treated groups were given PC (100 mg/kg in 0.9% saline by oral gavage. Lead exposure caused a significant elevation in the liver function parameters, lead level, lipid peroxidation, and inhibition of antioxidant enzyme activities. The induction of oxidative stress and histological alterations in the liver were minimized by co-treatment with PCs. Meanwhile, the number of Transferase-Mediated Deoxyuridine Triphosphate-Biotin Nick End Labeling (TUNEL-positive cells was significantly reduced in the PCs/lead co-treated group compared to the lead group. In addition, the lead group showed an increase in the expression level of Bax, while the expression of Bcl-2 was decreased. Furthermore, the lead group showed an increase in the expression level of endoplasmic reticulum (ER stress-related genes and protein (GRP78 and CHOP. Co-treated with PCs significantly reversed these expressions in the liver. PCs were, therefore, demonstrated to have protective, antioxidant, and anti-ER stress and anti-apoptotic activities in liver damage caused by chronic lead exposure in the Kunming mouse. This may be due to the ability of PCs to enhance the ability of liver tissue to protect against oxidative stress via the Nrf2/ARE signaling pathway, resulting in decreasing ER stress

Catalytic Conversion of Carbohydrates to Furanic Derivatives in the Presence of Choline Chloride

Directory of Open Access Journals (Sweden)

François Jérôme

2017-07-01

Full Text Available The synthesis of furanic derivatives (5-hydroxymethylfurfural (HMF, furfural… from carbohydrates is of high interest for a wide range of applications. These reactions are carried out in the presence of various solvents, and among them choline chloride can be used. It is a salt that can form a low melting mixture with a carbohydrate (fructose, glucose… or a deep eutectic mixture with carboxylic acid. A review of the studies performed in the conversion of carbohydrates to furanic derivatives in the presence of choline chloride is presented here with the advantages and drawbacks of this solvent. Choline chloride can enhance the selectivity to HMF by stabilizing effect and allows the conversion of highly concentrated feed. However, the extraction of the products from these solvents still needs improvement.

Leptin reverses corticosterone-induced inhibition of neural stem cell proliferation through activating the NR2B subunits of NMDA receptors

Energy Technology Data Exchange (ETDEWEB)

Shi, Wen-Zhu [Anesthesia and Operation Center, Hainan Branch of Chinese PLA General Hospital, Hainan 572013 (China); Anesthesia and Operation Center, Chinese PLA General Hospital, Beijing 100853 (China); Miao, Yu-Liang [Department of Anesthesiology, PLA No. 306 Hospital, Beijing 100101 (China); Guo, Wen-Zhi [Department of Anesthesiology, Beijing Military General Hospital of Chinese People’s Liberation Army, Beijing 100700 (China); Wu, Wei, E-mail: wwzwgk@163.com [Department of Head and Neck Surgery of Otolaryngology, PLA No. 306 Hospital, Beijing 100101 (China); Li, Bao-Wei [Department of Head and Neck Surgery of Otolaryngology, PLA No. 306 Hospital, Beijing 100101 (China); An, Li-Na [Department of Anesthesiology, Armed Police General Hospital, Beijing 100039 (China); Fang, Wei-Wu [Department of Anesthesiology, PLA No. 306 Hospital, Beijing 100101 (China); Mi, Wei-Dong, E-mail: elite2005gg@163.com [Anesthesia and Operation Center, Chinese PLA General Hospital, Beijing 100853 (China)

2014-04-25

Highlights: • Leptin promotes the proliferation of neural stem cells isolated from embryonic mouse hippocampus. • Leptin reverses corticosterone-induced inhibition of neural stem cell proliferation. • The effects of leptin are partially mediated by upregulating NR2B subunits. - Abstract: Corticosterone inhibits the proliferation of hippocampal neural stem cells (NSCs). The removal of corticosterone-induced inhibition of NSCs proliferation has been reported to contribute to neural regeneration. Leptin has been shown to regulate brain development, improve angiogenesis, and promote neural regeneration; however, its effects on corticosterone-induced inhibition of NSCs proliferation remain unclear. Here we reported that leptin significantly promoted the proliferation of hippocampal NSCs in a concentration-dependent pattern. Also, leptin efficiently reversed the inhibition of NSCs proliferation induced by corticosterone. Interestingly, pre-treatment with non-specific NMDA antagonist MK-801, specific NR2B antagonist Ro 25-6981, or small interfering RNA (siRNA) targeting NR2B, significantly blocked the effect of leptin on corticosterone-induced inhibition of NSCs proliferation. Furthermore, corticosterone significantly reduced the protein expression of NR2B, whereas pre-treatment with leptin greatly reversed the attenuation of NR2B expression caused by corticosterone in cultured hippocampal NSCs. Our findings demonstrate that leptin reverses the corticosterone-induced inhibition of NSCs proliferation. This process is, at least partially mediated by increased expression of NR2B subunits of NMDA receptors.

Factors influencing erythrocyte choline concentrations.

Science.gov (United States)

Miller, B L; Jenden, D J; Tang, C; Read, S

1989-01-01

Choline concentrations in human erythrocytes increase after freezing and thawing, during incubation in Krebs-phosphate for 30 min or on storage at 0 degrees C for 3-24 hr. The increase is prevented by protein precipitation by 10% perchloric acid, 10% zinc hydroxide, 10% sodium tungstate or boiling in water. It is not prevented by EDTA (10 mM) and is increased by oleate (5 mM). We suggest that the increase is due to the action of phospholipase D on erythrocyte phospholipids.

Effect of CDP-choline on the biosynthesis of phospholipids in brain regions during hypoxic treatment

International Nuclear Information System (INIS)

Alberghina, M.; Viola, M.; Serra, I.; Mistretta, A.; Giuffrida, A.M.

1981-01-01

Acute administration of CDP-choline (i.p. 100 mg/Kg b.w.), 10 min before the intraventricular injection of labeled precursors, [2-3H] glycerol and [1-14C]-palmitate, was able to correct the impairment caused by hypoxic treatment of lipid metabolism in some brain regions, ie, cerebral hemispheres, cerebellum, and brainstem. After CDP-choline treatment, an increase of the specific radioactivity of total lipids and of phospholipids was observed in mitochondria purified from the three above-mentioned brain regions of the hypoxic animals, while no effect on the other subcellular fractions was found. CDP-Choline had a stimulating effect particularly on the incorporation of both precursors into mitochondrial PC, PE, and polyglycerophosphatides isolated form the three brain regions examined. The results obtained show that the action of CDP-choline in restoring lipid metabolism was more pronounced in brain mitochondria, which, among subcellular fractions, were the most affected by the hypoxic treatment

Comparable stability of Hoogsteen and Watson-Crick base pairs in ionic liquid choline dihydrogen phosphate.

Science.gov (United States)

Tateishi-Karimata, Hisae; Nakano, Miki; Sugimoto, Naoki

2014-01-08

The instability of Hoogsteen base pairs relative to Watson-Crick base pairs has limited biological applications of triplex-forming oligonucleotides. Hydrated ionic liquids (ILs) provide favourable environments for a wide range of chemical reactions and are known to impact the stabilities of Watson-Crick base pairs. We found that DNA triplex formation was significantly stabilized in hydrated choline dihydrogen phosphate as compared with an aqueous buffer at neutral pH. Interestingly, the stability of Hoogsteen base pairs was found to be comparable with that of Watson-Crick base pairs in the hydrated IL. Molecular dynamics simulations of a DNA triplex in the presence of choline ions revealed that the DNA triplex was stabilized because of the binding of choline ion around the third strand in the grooves. Our finding will facilitate the development of new DNA materials. Our data also indicate that triplex formation may be stabilized inside cells where choline ions and their derivatives are abundant in vivo.

Comparable Stability of Hoogsteen and Watson–Crick Base Pairs in Ionic Liquid Choline Dihydrogen Phosphate

Science.gov (United States)

Tateishi-Karimata, Hisae; Nakano, Miki; Sugimoto, Naoki

2014-01-01

The instability of Hoogsteen base pairs relative to Watson–Crick base pairs has limited biological applications of triplex-forming oligonucleotides. Hydrated ionic liquids (ILs) provide favourable environments for a wide range of chemical reactions and are known to impact the stabilities of Watson–Crick base pairs. We found that DNA triplex formation was significantly stabilized in hydrated choline dihydrogen phosphate as compared with an aqueous buffer at neutral pH. Interestingly, the stability of Hoogsteen base pairs was found to be comparable with that of Watson–Crick base pairs in the hydrated IL. Molecular dynamics simulations of a DNA triplex in the presence of choline ions revealed that the DNA triplex was stabilized because of the binding of choline ion around the third strand in the grooves. Our finding will facilitate the development of new DNA materials. Our data also indicate that triplex formation may be stabilized inside cells where choline ions and their derivatives are abundant in vivo. PMID:24399194

Studies on the riboflavin, pantothenic acid, nicotinic acid and choline requirements of young Embden geese

Science.gov (United States)

Serafin, J.A.

1981-01-01

Four experiments were conducted to examine the riboflavin, pantothenic acid, nicotinic acid, and choline requirements of young Embden geese fed purified diets. Goslings fed diets deficient in either riboflavin, pantothenic acid, nicotinic acid, or choline grew poorly. Feeding a pantothenic acid-deficient diet resulted in 100% mortality. Goslings fed diets containing 530 mg/kg of choline or less developed perosis. Under the conditions of these experiments it was found that: 1) goslings require no more than 3.84 mg/kg of riboflavin and 31.2 mg/kg of nicotinic acid in the diet for rapid growth and normal development, 2) the pantothenic acid requirement of goslings is no more than 12.6 mg/kg of diet, and 3) a dietary choline level of 1530 mg/kg is adequate for both the prevention of perosis and rapid growth of goslings. The levels of vitamins found to support normal growth and development of goslings appear to be similar to requirements of other species that have been examined.

Value of {sup 11}C-choline PET and PET/CT in patients with suspected prostate cancer

Energy Technology Data Exchange (ETDEWEB)

Scher, Bernhard; Albinger, Wolfram; Tiling, Reinhold; Gildehaus, Franz-Josef; Dresel, Stefan [University of Munich, Department of Nuclear Medicine, Munich (Germany); Seitz, Michael [University of Munich, Department of Urology, Munich (Germany); Scherr, Michael; Becker, Hans-Christoph [University of Munich, Department of Radiology, Munich (Germany); Souvatzogluou, Michael; Wester, Hans-Juergen [Technical University of Munich, Department of Nuclear Medicine, Munich (Germany)

2007-01-15

The value and limitations of {sup 11}C-choline PET and PET/CT for the detection of prostate cancer remain controversial. The aim of this study was to investigate the diagnostic efficacy of {sup 11}C-choline PET and PET/CT in a large group of patients with suspected prostate cancer. Fifty-eight patients with clinical suspicion of prostate cancer underwent {sup 11}C-choline PET (25/58, Siemens ECAT Exact HR+) or PET/CT (33/58, Philips Gemini) scanning. On average, 500 MBq of {sup 11}C-choline was administered intravenously. Studies were interpreted by raters blinded to clinical information and other diagnostic procedures. Qualitative image analysis as well as semiquantitative SUV measurement was carried out. The reference standard was histopathological examination of resection specimens or biopsy. Prevalence of prostate cancer in this selected patient population was 63.8% (37/58). {sup 11}C-choline PET and PET/CT showed a sensitivity of 86.5% (32/37) and a specificity of 61.9% (13/21) in the detection of the primary malignancy. With regard to metastatic spread, PET showed a per-patient sensitivity of 81.8% (9/11) and produced no false positive findings. Based on our findings, differentiation between benign prostatic changes, such as benign prostatic hyperplasia or prostatitis, and prostate cancer is feasible in the majority of cases when image interpretation is primarily based on qualitative characteristics. SUV{sub max} may serve as guidance. False positive findings may occur due to an overlap of {sup 11}C-choline uptake between benign and malignant processes. By providing functional information regarding both the primary malignancy and its metastases, {sup 11}C-choline PET may prove to be a useful method for staging prostate cancer. (orig.)

Reversal with sugammadex for rocuronium-induced deep neuromuscular block after pretreatment of magnesium sulfate in rabbits.

Science.gov (United States)

Kang, Woon Seok; Kim, Kyo Sang; Song, Shin Mi

2017-04-01

Magnesium sulfate (MgSO 4 ) has been used in the treatment of pre-eclampsia, hypertension and arrhythmia. Magnesium enhances the neuromuscular block of rocuronium. This study has been conducted to evaluate the reversal efficacy of sugammadex from deep rocuronium-induced neuromuscular block (NMB) during consistent pretreatment of MgSO 4 in rabbits. Twenty-eight rabbits were randomly assigned to four groups, a control group or study groups (50% MgSO 4 150-200 mg/kg and 25 mg/kg/h IV), and received rocuronium 0.6 mg/kg. When post-tetanic count 1-2 appeared, sugammadex 2, 4, and 8 mg/kg was administered in the 2-mg group, control and 4-mg group, and 8-mg group, respectively. The recovery course after reversal of sugammadex administration was evaluated in each group. The mean serum concentration of magnesium was maintained at more than 2 mmol/L in the study groups, and the total dose of MgSO 4 was more than 590 mg. The reversal effect of sugammadex on rocuronium-induced NMB in pretreated MgSO 4 was not different from that in the group without MgSO 4 . The recovery time to train-of-four ratio 0.9 after sugammadex administration in the 2-mg group was longer than in the other groups (P rocuronium-induced NMB during large pretreatment of MgSO 4 was not affected. However, we should consider that the reversal effect of sugammadex varied depending on the dose.

Crystal structure of CbpF, a bifunctional choline-binding protein and autolysis regulator from Streptococcus pneumoniae.

Science.gov (United States)

Molina, Rafael; González, Ana; Stelter, Meike; Pérez-Dorado, Inmaculada; Kahn, Richard; Morales, María; Moscoso, Miriam; Campuzano, Susana; Campillo, Nuria E; Mobashery, Shahriar; García, José L; García, Pedro; Hermoso, Juan A

2009-03-01

Phosphorylcholine, a crucial component of the pneumococcal cell wall, is essential in bacterial physiology and in human pathogenesis because it binds to serum components of the immune system and acts as a docking station for the family of surface choline-binding proteins. The three-dimensional structure of choline-binding protein F (CbpF), one of the most abundant proteins in the pneumococcal cell wall, has been solved in complex with choline. CbpF shows a new modular structure composed both of consensus and non-consensus choline-binding repeats, distributed along its length, which markedly alter its shape, charge distribution and binding ability, and organizing the protein into two well-defined modules. The carboxy-terminal module is involved in cell wall binding and the amino-terminal module is crucial for inhibition of the autolytic LytC muramidase, providing a regulatory function for pneumococcal autolysis.

Loss of P53 Function in Colon Cancer Cells Results in Increased Phosphocholine and Total Choline

Directory of Open Access Journals (Sweden)

Noriko Mori

2004-10-01

Full Text Available Mutations in the p53 gene are the most frequently observed genetic lesions in human cancers. Human cancers that contain a p53 mutation are more aggressive, more apt to metastasize, and more often fatal. p53 controls numerous downstream targets that can influence various outcomes such as apoptosis, growth arrest, and DNA repair. Based on previous observations using 1H magnetic resonance spectroscopy (MRS, we have identified choline phospholipid metabolite intensities typical of increased malignancy. Here we have used 1H MRS to characterize the choline phospholipid metabolite levels of p53+/+ and p53−/– cells, and demonstrated that loss of p53 function results in increased phosphocholine and total choline. These data suggest that the increased malignancy of cancer cells resulting from loss of p53 may be mediated, in part, through the choline phospholipid pathway.

Choline-based biodegradable ionic liquid catalyst for Mannich-type

Indian Academy of Sciences (India)

Choline-based biodegradable ionic liquid catalyst for Mannich-type reaction ... Abstract. A three-component Mannich-type reaction of aromatic aldehydes, ketones, and amines was catalyzed by a novel ... Journal of Chemical Sciences | News.

Early reversal of profound rocuronium-induced neuromuscular blockade by sugammadex in a randomized multicenter study - Efficacy, safety, and pharmacokinetics

NARCIS (Netherlands)

Sparr, Harald J.; Vermeyen, Karel M.; Beaufort, Anton M.; Rietbergen, Henk; Proost, Johannes H.; Saldien, Vera; Velik-Salchner, Corinna; Wierda, J. Mark K. H.

Background: Sugammadex reverses the neuromuscular blocking effects of rocuronium by chemical encapsulation. The efficacy, safety, and pharmacokinetics of sugammadex for reversal of profound rocuronium-induced neuromuscular blockade were evaluated. Methods: Ninety-eight male adult patients were

Roux-en-Y gastric bypass reverses the effects of diet-induced obesity to inhibit the responsiveness of central vagal motoneurones.

Science.gov (United States)

Browning, Kirsteen N; Fortna, Samuel R; Hajnal, Andras

2013-05-01

Diet-induced obesity (DIO) has been shown to alter the biophysical properties and pharmacological responsiveness of vagal afferent neurones and fibres, although the effects of DIO on central vagal neurones or vagal efferent functions have never been investigated. The aims of this study were to investigate whether high-fat diet-induced DIO also affects the properties of vagal efferent motoneurones, and to investigate whether these effects were reversed following weight loss induced by Roux-en-Y gastric bypass (RYGB) surgery. Whole-cell patch-clamp recordings were made from rat dorsal motor nucleus of the vagus (DMV) neurones in thin brainstem slices. The DMV neurones from rats exposed to high-fat diet for 12-14 weeks were less excitable, with a decreased membrane input resistance and decreased ability to fire action potentials in response to direct current pulse injection. The DMV neurones were also less responsive to superfusion with the satiety neuropeptides cholecystokinin and glucagon-like peptide 1. Roux-en-Y gastric bypass reversed all of these DIO-induced effects. Diet-induced obesity also affected the morphological properties of DMV neurones, increasing their size and dendritic arborization; RYGB did not reverse these morphological alterations. Remarkably, independent of diet, RYGB also reversed age-related changes of membrane properties and occurrence of charybdotoxin-sensitive (BK) calcium-dependent potassium current. These results demonstrate that DIO also affects the properties of central autonomic neurones by decreasing the membrane excitability and pharmacological responsiveness of central vagal motoneurones and that these changes were reversed following RYGB. In contrast, DIO-induced changes in morphological properties of DMV neurones were not reversed following gastric bypass surgery, suggesting that they may be due to diet, rather than obesity. These findings represent the first direct evidence for the plausible effect of RYGB to improve vagal

Choline status and neurodevelopmental outcomes at 5 years of age in the Seychelles Child Development Nutrition Study.

Science.gov (United States)

Strain, J J; McSorley, Emeir M; van Wijngaarden, Edwin; Kobrosly, Roni W; Bonham, Maxine P; Mulhern, Maria S; McAfee, Alison J; Davidson, Philip W; Shamlaye, Conrad F; Henderson, Juliette; Watson, Gene E; Thurston, Sally W; Wallace, Julie M W; Ueland, Per M; Myers, Gary J

2013-07-28

Choline is an essential nutrient that is found in many food sources and plays a critical role in the development of the central nervous system. Animal studies have shown that choline status pre- and postnatally can have long-lasting effects on attention and memory; however, effects in human subjects have not been well studied. The aim of the present study was to examine the association between plasma concentrations of free choline and its related metabolites in children and their neurodevelopment in the Seychelles Child Development Nutrition Study, an ongoing longitudinal study assessing the development of children born to mothers with high fish consumption during pregnancy. Plasma concentrations of free choline, betaine, dimethylglycine (DMG), methionine and homocysteine and specific measures of neurodevelopment were measured in 210 children aged 5 years. The children's plasma free choline concentration (9·17 (sd 2·09) μmol/l) was moderately, but significantly, correlated with betaine (r 0·24; P= 0·0006), DMG (r 0·15; P= 0·03), methionine (r 0·24; P= 0·0005) and homocysteine (r 0·19; P= 0·006) concentrations. Adjusted multiple linear regression revealed that betaine concentrations were positively associated with Preschool Language Scale – total language scores (β = 0·066; P= 0·04), but no other associations were evident. We found no indication that free choline concentration or its metabolites, within the normal physiological range, are associated with neurodevelopmental outcomes in children at 5 years of age. As there is considerable animal evidence suggesting that choline status during development is associated with cognitive outcome, the issue deserves further study in other cohorts.

Choline kinase-alpha by regulating cell aggressiveness and drug sensitivity is a potential druggable target for ovarian cancer

OpenAIRE

Granata, A; Nicoletti, R; Tinaglia, V; De Cecco, L; Pisanu, M E; Ricci, A; Podo, F; Canevari, S; Iorio, E; Bagnoli, M; Mezzanzanica, D

2013-01-01

Background: Aberrant choline metabolism has been proposed as a novel cancer hallmark. We recently showed that epithelial ovarian cancer (EOC) possesses an altered MRS-choline profile, characterised by increased phosphocholine (PCho) content to which mainly contribute over-expression and activation of choline kinase-alpha (ChoK-alpha). Methods: To assess its biological relevance, ChoK-alpha expression was downmodulated by transient RNA interference in EOC in vitro models. Gene expression profi...

A Facile, Choline Chloride/Urea Catalyzed Solid Phase Synthesis of Coumarins via Knoevenagel Condensation

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Hosanagara N. Harishkumar

2011-01-01

Full Text Available The influence of choline chloride/urea ionic liquid in solid phase on the Knoevenagel condensation is demonstrated. The active methylene compounds such as meldrum’s acid, diethylmalonate, ethyl cyanoacetate, dimethylmalonate, were efficiently condensed with various salicylaldehydes in presence of choline chloride/urea ionic liquid without using any solvents or additional catalyst. The reaction is remarkably facile because of the air and water stability of the catalyst, and needs no special precautions. The reactions were completed within 1hr with excellent yields (95%. The products formed were sufficiently pure, and can be easily recovered. The use of ionic liquid choline chloride/urea in solid phase offered several significant advantages such as low cost, greater selectivity and easy isolation of products.

Choline and its metabolites are differently associated with cardiometabolic risk factors, cardiovascular history and MRI documented cerebrovascular disease in older adults

Science.gov (United States)

Background: There is a potential role of choline in cardiovascular and cerebrovascular disease through its involvement in lipid and one-carbon metabolism. Objective: We evaluated the associations of plasma choline and choline-related compounds with cardiometabolic risk factors, history of cardiovas...

Local Peltier-effect-induced reversible metal–insulator transition in VO2 nanowires

International Nuclear Information System (INIS)

Takami, Hidefumi; Kanki, Teruo; Tanaka, Hidekazu

2016-01-01

We report anomalous resistance leaps and drops in VO 2 nanowires with operating current density and direction, showing reversible and nonvolatile switching. This event is associated with the metal–insulator phase transition (MIT) of local nanodomains with coexistence states of metallic and insulating phases induced by thermoelectric cooling and heating effects. Because the interface of metal and insulator domains has much different Peltier coefficient, it is possible that a significant Peltier effect would be a source of the local MIT. This operation can be realized by one-dimensional domain configuration in VO 2 nanowires because one straight current path through the electronic domain-interface enables theoretical control of thermoelectric effects. This result will open a new method of reversible control of electronic states in correlated electron materials.

Reversal of rocuronium-induced (1.2 mg kg-1) profound neuromuscular block by accidental high dose of sugammadex (40 mg kg-1).

NARCIS (Netherlands)

Molina, A.L.; Boer, H.D. de; Klimek, M.; Heeringa, M.; Klein, J.

2007-01-01

Sugammadex is the first selective relaxant binding agent and reverses rocuronium-induced neuromuscular block. A case is reported in which a patient accidentally received a high dose of sugammadex (40 mg kg-1) to reverse a rocuronium-induced (1.2 mg kg-1) profound neuromuscular block. A fast and

Bronsted acid-functionalized choline chloride-butane sultone for the ...

Indian Academy of Sciences (India)

M P PADMA PRIYA

2018-03-21

Mar 21, 2018 ... Choline chloride and 1,4-butane sultone were combined to obtain a sulphonic acid-functionalized ..... Knifton J F and Sanderson J R 1990 Method for produc- ... alkenes via the Knoevenagel condensation Tetrahedron. Lett.

Pituitary Adenylate Cyclase-Activating Polypeptide Reverses Ammonium Metavanadate-Induced Airway Hyperresponsiveness in Rats

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Mounira Tlili

2015-01-01

Full Text Available The rate of atmospheric vanadium is constantly increasing due to fossil fuel combustion. This environmental pollution favours vanadium exposure in particular to its vanadate form, causing occupational bronchial asthma and bronchitis. Based on the well admitted bronchodilator properties of the pituitary adenylate cyclase-activating polypeptide (PACAP, we investigated the ability of this neuropeptide to reverse the vanadate-induced airway hyperresponsiveness in rats. Exposure to ammonium metavanadate aerosols (5 mg/m3/h for 15 minutes induced 4 hours later an array of pathophysiological events, including increase of bronchial resistance and histological alterations, activation of proinflammatory alveolar macrophages, and increased oxidative stress status. Powerfully, PACAP inhalation (0.1 mM for 10 minutes alleviated many of these deleterious effects as demonstrated by a decrease of bronchial resistance and histological restoration. PACAP reduced the level of expression of mRNA encoding inflammatory chemokines (MIP-1α, MIP-2, and KC and cytokines (IL-1α and TNF-α in alveolar macrophages and improved the antioxidant status. PACAP reverses the vanadate-induced airway hyperresponsiveness not only through its bronchodilator activity but also by counteracting the proinflammatory and prooxidative effects of the metal. Then, the development of stable analogs of PACAP could represent a promising therapeutic alternative for the treatment of inflammatory respiratory disorders.

Choline PET based dose-painting in prostate cancer - Modelling of dose effects

International Nuclear Information System (INIS)

Niyazi, Maximilian; Bartenstein, Peter; Belka, Claus; Ganswindt, Ute

2010-01-01

Several randomized trials have documented the value of radiation dose escalation in patients with prostate cancer, especially in patients with intermediate risk profile. Up to now dose escalation is usually applied to the whole prostate. IMRT and related techniques currently allow for dose escalation in sub-volumes of the organ. However, the sensitivity of the imaging modality and the fact that small islands of cancer are often dispersed within the whole organ may limit these approaches with regard to a clear clinical benefit. In order to assess potential effects of a dose escalation in certain sub-volumes based on choline PET imaging a mathematical dose-response model was developed. Based on different assumptions for α/β, γ50, sensitivity and specificity of choline PET, the influence of the whole prostate and simultaneous integrated boost (SIB) dose on tumor control probability (TCP) was calculated. Based on the given heterogeneity of all potential variables certain representative permutations of the parameters were chosen and, subsequently, the influence on TCP was assessed. Using schedules with 74 Gy within the whole prostate and a SIB dose of 90 Gy the TCP increase ranged from 23.1% (high detection rate of choline PET, low whole prostate dose, high γ50/ASTRO definition for tumor control) to 1.4% TCP gain (low sensitivity of PET, high whole prostate dose, CN + 2 definition for tumor control) or even 0% in selected cases. The corresponding initial TCP values without integrated boost ranged from 67.3% to 100%. According to a large data set of intermediate-risk prostate cancer patients the resulting TCP gains ranged from 22.2% to 10.1% (ASTRO definition) or from 13.2% to 6.0% (CN + 2 definition). Although a simplified mathematical model was employed, the presented model allows for an estimation in how far given schedules are relevant for clinical practice. However, the benefit of a SIB based on choline PET seems less than intuitively expected. Only under the

Dietary folate and choline status differentially affect lipid metabolism and behavior-mediated neurotransmitters in young rats

Science.gov (United States)

The relationship between choline and folate metabolisms is an important issue due to the essential role of these nutrients in brain plasticity and cognitive functions. Present study was designed to investigate whether modification of the dietary folate-choline status in young rats would affect brain...

Isoflurane reversibly destabilizes hippocampal dendritic spines by an actin-dependent mechanism.

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Jimcy Platholi

Full Text Available General anesthetics produce a reversible coma-like state through modulation of excitatory and inhibitory synaptic transmission. Recent evidence suggests that anesthetic exposure can also lead to sustained cognitive dysfunction. However, the subcellular effects of anesthetics on the structure of established synapses are not known. We investigated effects of the widely used volatile anesthetic isoflurane on the structural stability of hippocampal dendritic spines, a postsynaptic structure critical to excitatory synaptic transmission in learning and memory. Exposure to clinical concentrations of isoflurane induced rapid and non-uniform shrinkage and loss of dendritic spines in mature cultured rat hippocampal neurons. Spine shrinkage was associated with a reduction in spine F-actin concentration. Spine loss was prevented by either jasplakinolide or cytochalasin D, drugs that prevent F-actin disassembly. Isoflurane-induced spine shrinkage and loss were reversible upon isoflurane elimination. Thus, isoflurane destabilizes spine F-actin, resulting in changes to dendritic spine morphology and number. These findings support an actin-based mechanism for isoflurane-induced alterations of synaptic structure in the hippocampus. These reversible alterations in dendritic spine structure have important implications for acute anesthetic effects on excitatory synaptic transmission and synaptic stability in the hippocampus, a locus for anesthetic-induced amnesia, and have important implications for anesthetic effects on synaptic plasticity.

Effect of addition of Proline, ionic liquid [Choline][Pro] on CO2 separation properties of poly(amidoamine) dendrimer / poly(ethylene glycol) hybrid membranes

Science.gov (United States)

Duan, S. H.; Kai, T.; Chowdhury, F. A.; Taniguchi, I.; Kazama, S.

2018-01-01

Poly(amidoamine) (PAMAM) dendrimers were incorporated into cross-linked poly(ethylene glycol) (PEGDMA) matrix to improve carbon dioxide (CO2) separation performance at elevated pressures. In our previous studies, PAMAM/PEGDMA hybrid membranes showed high CO2 separation properties from CO2/H2 mixed gases. In this study, proline, choline and ionic liquid [Choline][Pro] compounds were selected as rate promoters that were used to prepare PAMAM/PEGDMA hybrid membranes. The effect of addition of proline, choline, IL [Choline][Pro] on separation performance of PAMAM/PEGDMA) hybrid membranes for CO2/H2 separation was investigated. Amino acid proline, choline, and IL [Choline][Pro] were used to promote CO2 and amine reaction. With the addition of [Choline][Pro] into PAMAM/PEG membrane, CO2 permeance of PAMAM/PEG hybrid membranes are increased up to 46% without any change of selectivity of membrane for CO2.

Synthesis and study of thiocarbonate derivatives of choline as potential inhibitors of acetylcholinesterase.

Science.gov (United States)

Boyle, N A; Talesa, V; Giovannini, E; Rosi, G; Norton, S J

1997-09-12

Fourteen alkyl and aryl thiocarbonate derivatives of choline were synthesized and studied as potential inhibitors of acetylcholinesterase (AChE). Twelve of the compounds inhibited AChEs derived from calf forebrain, human red blood cells, and octopus brain ranging from low to moderately high inhibition potency. The concentration of each inhibitory compound giving 50% inhibition of enzyme activity (IC50 values, which ranged from 1 x 10(-2) to 8 x 10(-7) M) was determined and is reported; inhibitor constants (Ki values) for the most inhibitory compounds, (1-pentylthiocarbonyl)choline chloride and (1-heptylthiocarbonyl)choline chloride, were calculated from kinetic data and are also reported. The inhibitors are competitive with substrate, and they are not hydrolyzed by the AChE activities. Certain of these new compounds may provide direction for the development of new drugs that have anticholinesterase activity and may be used for the treatment of Alzheimer's disease.

Novel Small Molecule Inhibitors of Choline Kinase Identified by Fragment-Based Drug Discovery.

Science.gov (United States)

Zech, Stephan G; Kohlmann, Anna; Zhou, Tianjun; Li, Feng; Squillace, Rachel M; Parillon, Lois E; Greenfield, Matthew T; Miller, David P; Qi, Jiwei; Thomas, R Mathew; Wang, Yihan; Xu, Yongjin; Miret, Juan J; Shakespeare, William C; Zhu, Xiaotian; Dalgarno, David C

2016-01-28

Choline kinase α (ChoKα) is an enzyme involved in the synthesis of phospholipids and thereby plays key roles in regulation of cell proliferation, oncogenic transformation, and human carcinogenesis. Since several inhibitors of ChoKα display antiproliferative activity in both cellular and animal models, this novel oncogene has recently gained interest as a promising small molecule target for cancer therapy. Here we summarize our efforts to further validate ChoKα as an oncogenic target and explore the activity of novel small molecule inhibitors of ChoKα. Starting from weakly binding fragments, we describe a structure based lead discovery approach, which resulted in novel highly potent inhibitors of ChoKα. In cancer cell lines, our lead compounds exhibit a dose-dependent decrease of phosphocholine, inhibition of cell growth, and induction of apoptosis at low micromolar concentrations. The druglike lead series presented here is optimizable for improvements in cellular potency, drug target residence time, and pharmacokinetic parameters. These inhibitors may be utilized not only to further validate ChoKα as antioncogenic target but also as novel chemical matter that may lead to antitumor agents that specifically interfere with cancer cell metabolism.

Evaluation of a reverse-hybridization StripAssay for the detection of genetic polymorphisms leading to acenocoumarol sensitivity.

Science.gov (United States)

Gialeraki, Argyri; Markatos, Christos; Grouzi, Elisabeth; Merkouri, Efrosyni; Travlou, Anthi; Politou, Marianna

2010-04-01

Acenocoumarol is mainly catabolized by CYP2C9 isoform of cytochrome P450 (CYP) liver complex and exerts its anticoagulant effect through the inhibition of Vitamin K Epoxide Reductase (VKOR). The most important genetic polymorphisms which lead to an impaired enzymatic activity and therefore predispose to acenocoumarol sensitivity, are considered to be CYP2C9*2 (Arg144Cys), CYP2C9*3 (Ile359Leu) and VKORC1-1639G>A, respectively. In this study we compared the results of the PGXThrombo StripAssay kit (ViennaLab Diagnostics,Vienna, Austria) with direct DNA sequencing and in house Restriction Fragment Length Polymorphisms (RFLP) for the detection of the aforementioned Single Nucleotide Polymorphisms (SNPs). The reverse hybridization StripAssay was found to be equally effective with RFLP and direct DNA sequencing for the detection of CYP2C9*2 and CYP2C9*3 polymorphisms, respectively. The comparison of the RFLP reference method with the reverse hybridization StripAssay for the detection of VKORC1-1639 G>A polymorphism showed that the reverse hybridization StripAsssay might misclassify some A/A homozygotes as heterozygotes. Optimization of the hybridization procedures may eliminate the extra low signal band observed in some samples at the reverse hybridization StripAssay and improve its diagnostic value.

Naringin Reverses Hepatocyte Apoptosis and Oxidative Stress Associated with HIV-1 Nucleotide Reverse Transcriptase Inhibitors-Induced Metabolic Complications

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Oluwafeyisetan O. Adebiyi

2015-12-01

Full Text Available Nucleoside Reverse Transcriptase Inhibitors (NRTIs have not only improved therapeutic outcomes in the treatment of HIV infection but have also led to an increase in associated metabolic complications of NRTIs. Naringin’s effects in mitigating NRTI-induced complications were investigated in this study. Wistar rats, randomly allotted into seven groups (n = 7 were orally treated daily for 56 days with 100 mg/kg zidovudine (AZT (groups I, II III, 50 mg/kg stavudine (d4T (groups IV, V, VI and 3 mL/kg of distilled water (group VII. Additionally, rats in groups II and V were similarly treated with 50 mg/kg naringin, while groups III and VI were treated with 45 mg/kg vitamin E. AZT or d4T treatment significantly reduced body weight and plasma high density lipoprotein concentrations but increased liver weights, plasma triglycerides and total cholesterol compared to controls, respectively. Furthermore, AZT or d4T treatment significantly increased oxidative stress, adiposity index and expression of Bax protein, but reduced Bcl-2 protein expression compared to controls, respectively. However, either naringin or vitamin E significantly mitigated AZT- or d4T-induced weight loss, dyslipidemia, oxidative stress and hepatocyte apoptosis compared to AZT- or d4T-only treated rats. Our results suggest that naringin reverses metabolic complications associated with NRTIs by ameliorating oxidative stress and apoptosis. This implies that naringin supplements could mitigate lipodystrophy and dyslipidemia associated with NRTI therapy.

[Comparison of neostigmine induced reversal of rocuronium in different age children].

Science.gov (United States)

Liu, Jinzhu; Cheng, Zhaoyu

2016-03-15

To compare the effectiveness of neostigmine induced reversal of rocuronium in neonates, infants, young children and children. One hundred and sixty ASA I or II pediatric patients undergoings elective surgical procedures under total intravenous anesthesia were enrolled during July 2014 to April 2015 in Tianjin Children's Hospital. The patients were divided into four groups according to ages: neonate group, infant group, young children group and children group.Then control subgroup and neostigmine reversal subgroup including twenty patients were randomly selected from every different age groups by the method of random number table. After induction of anesthesia, 0.6 mg/kg rocuronium was administered, and 0.2 mg/kg maintenance doses given as required during period of operation. Neuromuscular block was monitored using acceleromyographic train of four (TOF). When T1/control returned to 15%, 0.03 mg/kg neostigmine and 0.01 mg/kg atropine were given to patients of reversal subgroups, and saline 0.1 ml/kg was given to patients of control subgroups. The recovery time of T25, T75, TR0.7, recovery index, blood pressure, heart rate and adverse reactions were observed and recorded. In control subgroups, the recovery time of T75 for neonates, infants, young children and children were (27.10±8.72), (16.70±6.35), (13.05±1.96), (14.40±3.08) min, respectively (F=25.052, P0.05). But the recovery time of T75, TR0.7 and recovery index in neonate group were longer than other age groups (all Procuronium are comparable in infant, young children and children. There are obviously reversal effects in all of age groups when neostigmine is given to antagonize rocuronium. Either spontaneous recovery time or reversal recovery time of neostigmine to rocuronium is longer for neonates than other age's children.

3D-segmentation of the 18F-choline PET signal for target volume definition in radiation therapy of the prostate.

Science.gov (United States)

Ciernik, I Frank; Brown, Derek W; Schmid, Daniel; Hany, Thomas; Egli, Peter; Davis, J Bernard

2007-02-01

Volumetric assessment of PET signals becomes increasingly relevant for radiotherapy (RT) planning. Here, we investigate the utility of 18F-choline PET signals to serve as a structure for semi-automatic segmentation for forward treatment planning of prostate cancer. 18F-choline PET and CT scans of ten patients with histologically proven prostate cancer without extracapsular growth were acquired using a combined PET/CT scanner. Target volumes were manually delineated on CT images using standard software. Volumes were also obtained from 18F-choline PET images using an asymmetrical segmentation algorithm. PTVs were derived from CT 18F-choline PET based clinical target volumes (CTVs) by automatic expansion and comparative planning was performed. As a read-out for dose given to non-target structures, dose to the rectal wall was assessed. Planning target volumes (PTVs) derived from CT and 18F-choline PET yielded comparable results. Optimal matching of CT and 18F-choline PET derived volumes in the lateral and cranial-caudal directions was obtained using a background-subtracted signal thresholds of 23.0+/-2.6%. In antero-posterior direction, where adaptation compensating for rectal signal overflow was required, optimal matching was achieved with a threshold of 49.5+/-4.6%. 3D-conformal planning with CT or 18F-choline PET resulted in comparable doses to the rectal wall. Choline PET signals of the prostate provide adequate spatial information amendable to standardized asymmetrical region growing algorithms for PET-based target volume definition for external beam RT.

Correlation between 11C-choline or 18F-FDG uptake and tumor proliferation: a rabbit bearing lung cancer model study

International Nuclear Information System (INIS)

Li Yajun; Bai Renju; Gao Shuo; Li Yansheng; Liu Lei; Jia Wei; Cai Li; Xing Xiling

2009-01-01

Objective: Tumor proliferative activity has been recognized as an indicator of malignant degree in lung cancer and related to prognosis. The purpose of this study was to evaluate the feasibility of assessing proliferative activity with 11 C-choline and 18 F-fluorodeoxyglucose (FDG) PET on a rabbit bearing lung VX2 tumor model. Methods: About 0.5 ml of viable VX2 tumor cell suspension was slowly injected into the right lungs of 54 New Zealand white rabbits through a transthoracical needle insertion. 11 C-choline and 18 F-FDG PET scan were performed 10-11 d after tumor implantation. One ear vein was cannulated for administration of the tracers, 11 C-choline PET scan (with Discovery LS PET/CT scanner, GE) was performed 5 rain after intravenously injection of 37 MBq 11 C-choline. Then 18.7 MBq 18 F-FDG was infused at 60 min after 11 C-choline administration and 18 F-FDG PET scan was performed at 60 min after 18 F-FDG administration. The maximal standardized uptake value of tumor was calculated. The animals were euthanized after examination. Histochemical stain with proliferating cell nuclear antigen (PCNA) was performed and PCNA index was obtained to assess tumor proliferation. The difference of 11 C-choline and 18 F-FDG was analyzed using paired student t-test. The correlation of 11 C-choline 18 F-FDG and tumor cell density and PCNA index was analyzed using Pearson linear regression. Results: Of the 54 rabbits, 36 had a solitary pulmonary tumor. The rate of successful generation of a solitary VX2 tumor was 66.7% (36/54). Only 33 rabbits underwent both 11 C-choline and 18 F-FDG PET, and enrolled in this study. The mean cellular density was (547.36 ± 64.78) cells/field and the mean PCNA index was (42.34 ± 15.26)%. 18 F-FDG was higher than 11 C-choline (5.70 ± 3.45 vs 4.02 ± 3.07, t=-3.188, P=0.003). 11 C-choline significantly and positively correlated with PCNA index (r=0.786, P 11 C-choline and tumor cellular density (r=-0.176, P=0.327). 18 F-FDG significantly and

Enhancing the biodegradation of oil in sandy sediments with choline: A naturally methylated nitrogen compound

International Nuclear Information System (INIS)

Mortazavi, Behzad; Horel, Agota; Anders, Jennifer S.; Mirjafari, Arsalan; Beazley, Melanie J.; Sobecky, Patricia A.

2013-01-01

We investigated how additions of choline, a naturally occurring methylated nitrogen-containing compound, accelerated hydrocarbon degradation in sandy sediments contaminated with moderately weathered crude oil (4000 mg kg −1 sediment). Addition of lauroylcholine chloride (LCC) and tricholine citrate (TCC) to oil contaminated sediments resulted in 1.6 times higher hydrocarbon degradation rates compared to treatments without added choline derivatives. However, the degradation rate constant for the oil contaminated sediments amended with LCC was similar to that in contaminated sediments amended with inorganic nitrogen, phosphorus, and glucose. Additions of LLC and TCC to sediments containing extensively weathered oil also resulted in enhanced mineralization rates. Cultivation-free 16S rRNA analysis revealed the presence of an extant microbial community with clones closely related to known hydrocarbon degraders from the Gammaproteobacteria, Alphaproteobacteria, and Firmicutes phyla. The results demonstrate that the addition of minimal amounts of organic compounds to oil contaminated sediments enhances the degradation of hydrocarbons. -- Highlights: •Aerobic degradation of weathered crude oil in sandy sediments was determined. •The effect of input of choline on degradation rates was determined. •16S rRNA clone library analyses were used to examine the microbial phylogeny. •The bacterial community was consisted of clones related to hydrocarbon degraders. •Hydrocarbon degradation in sandy sediments was accelerated by addition of choline. -- Choline, a naturally occurring methylated nitrogen-containing compound, accelerated hydrocarbon degradation in sandy sediments by an extant microbial community

Application of 11C-choline PET/CT imaging for differentiating malignant from benign prostate lesions

International Nuclear Information System (INIS)

Li Xin; Wang Muwen; Liu Qingwei; Zhu Renjuan; Liu Lihui; Yuan Xianshun; Yao Shuzhan; Liu Songtao

2006-01-01

Objective: To investigate the potential of 11 C-choline PET/CT imaging for differentiating prostate cancer from benign prostate hyperplasia. Methods: A total of 45 patients with prostate lesions under- went 11 C-choline PET/CT imaging before transrectal needle biopsy. PET/CT imaging was performed 5 min after injection of 7.4 MBq/kg 11 C-choline in supine position over lower abdomen (3 min per bed with 2 beds), including the pelvis, and the whole body with 6 beds when necessary. After attenuation correction and iterative reconstruction, PET data were analyzed semi-quantitatively by measuring maximum standardized uptake values (SUV max ) in prostate lesions (P, target) and the muscles (M, non-target) and then P/M ratios were calculated. Also visual analysis was performed in different transverse, sagittal views and slices as well as three-dimensional images. Results: Eighteen prostate cancer and 27 benign prostate hyperplasia [and(or) chronic prostatitis] were all confirmed by pathology. The mean P/M ratio of prostate cancer was 4.02± 1.88, while in benign lesions was 1.87±1.21. The statistical differences of P/M ratios between them were significant (t=2.07, P 11 C-choline PET/CT imaging were 88.89%, 88.89% and 92.31% respectively. Conclusions: 11 C-choline PET/CT imaging is a valuable non-invasive technology in the diagnosis of pros- tate cancer. The P/M ratio can differentiate prostate cancer from benign lesions better than SUV. (authors)

Lactobacillus rhamnosus strain JB-1 reverses restraint stress-induced gut dysmotility.

Science.gov (United States)

West, C; Wu, R Y; Wong, A; Stanisz, A M; Yan, R; Min, K K; Pasyk, M; McVey Neufeld, K-A; Karamat, M I; Foster, J A; Bienenstock, J; Forsythe, P; Kunze, W A

2017-01-01

Environmental stress affects the gut with dysmotility being a common consequence. Although a variety of microbes or molecules may prevent the dysmotility, none reverse the dysmotility. We have used a 1 hour restraint stress mouse model to test for treatment effects of the neuroactive microbe, L. rhamnosus JB-1 ™ . Motility of fluid-filled ex vivo gut segments in a perfusion organ bath was recorded by video and migrating motor complexes measured using spatiotemporal maps of diameter changes. Stress reduced jejunal and increased colonic propagating contractile cluster velocities and frequencies, while increasing contraction amplitudes for both. Luminal application of 10E8 cfu/mL JB-1 restored motor complex variables to unstressed levels within minutes of application. L. salivarius or Na.acetate had no treatment effects, while Na.butyrate partially reversed stress effects on colonic frequency and amplitude. Na.propionate reversed the stress effects for jejunum and colon except on jejunal amplitude. Our findings demonstrate, for the first time, a potential for certain beneficial microbes as treatment of stress-induced intestinal dysmotility and that the mechanism for restoration of function occurs within the intestine via a rapid drug-like action on the enteric nervous system. © 2016 John Wiley & Sons Ltd.

Protective Effect of Morocco Carob Honey Against Lead-Induced Anemia and Hepato-Renal Toxicity

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Aicha Fassi Fihri

2016-06-01

Full Text Available Background/Aims: Natural honey has many biological activities including protective effect against toxic materials. The aim of this study was to evaluate the protective effect of carob honey against lead-induced hepato-renal toxicity and lead-induced anemia in rabbits. Methods: Twenty four male rabbits were allocated into four groups six rabbits each; group 1: control group, received distilled water (0.1 ml / kg.b.wt /daily; group 2: received oral lead acetate (2 g/kg.b.wt/daily; group 3: treated with oral honey (1g /kg.b.wt/daily and oral lead (2 g/kg.b.wt/daily, and group 4: received oral honey (1 g/kg.b.wt/daily. Honey and lead were given daily during 24 days of experimentation. Laboratory tests and histopathological evaluations of kidneys were done. Results: Oral administration of lead induced hepatic and kidney injury and caused anemia during three weeks of the exposure. Treatment with honey prevented hepato-renal lead toxicity and ameliorated lead-induced anemia when honey was given to animals during lead exposure. Conclusion: It might be concluded that honey has a protective effect against lead-induced blood, hepatic and renal toxic effects.

Protective Effect of Morocco Carob Honey Against Lead-Induced Anemia and Hepato-Renal Toxicity.

Science.gov (United States)

Fihri, Aicha Fassi; Al-Waili, Noori S; El-Haskoury, Redouan; Bakour, Meryem; Amarti, Afaf; Ansari, Mohammad J; Lyoussi, Badiaa

2016-01-01

Natural honey has many biological activities including protective effect against toxic materials. The aim of this study was to evaluate the protective effect of carob honey against lead-induced hepato-renal toxicity and lead-induced anemia in rabbits. Twenty four male rabbits were allocated into four groups six rabbits each; group 1: control group, received distilled water (0.1 ml / kg.b.wt /daily); group 2: received oral lead acetate (2 g/kg.b.wt/daily); group 3: treated with oral honey (1g /kg.b.wt/daily) and oral lead (2 g/kg.b.wt/daily), and group 4: received oral honey (1 g/kg.b.wt/daily). Honey and lead were given daily during 24 days of experimentation. Laboratory tests and histopathological evaluations of kidneys were done. Oral administration of lead induced hepatic and kidney injury and caused anemia during three weeks of the exposure. Treatment with honey prevented hepato-renal lead toxicity and ameliorated lead-induced anemia when honey was given to animals during lead exposure. It might be concluded that honey has a protective effect against lead-induced blood, hepatic and renal toxic effects. © 2016 The Author(s) Published by S. Karger AG, Basel.

Effects of vitamin E on lead-induced impairments in hippocampal synaptic plasticity.

Science.gov (United States)

Salehi, Iraj; Karamian, Ruhollah; Komaki, Alireza; Tahmasebi, Lida; Taheri, Masoumeh; Nazari, Masoumeh; Shahidi, Siamak; Sarihi, Abdolrahman

2015-12-10

Lead (Pb) exposure during development is associated with impaired cognitive function and long-term potentiation (LTP). Vitamin E (VE) is an antioxidant that could have protective effects against Pb intoxication. In this study, we examined the protective effects of vitamin E against Pb-induced LTP impairments. Forty-six adult male Wistar rats were randomly divided into 6 treatment groups: (1) control; (2) Pb exposure; (3) VE; (4) Pb +VE; (5) Pb exposure followed by VE 2 months after exposure; (6) VE followed by Pb exposure 1 month after treatment. Rats were exposed to Pb through daily consumption of Pb-contaminated distilled water; VE was administered by daily gavage for 3 months. After this period, the population spike (PS) amplitudes and the slopes of excitatory postsynaptic potentials (EPSPs) were measured in the dentate gyrus (DG) area of the hippocampus in adult rats in response to electrical stimulation applied to the perforant pathway in vivo. Blood samples were also collected to evaluate malondialdehyde (MDA) levels, total antioxidant capacity (TAC), and total oxidant status (TOS). Biochemical analyses demonstrated significant increases in plasma MDA and TOS levels in the Pb-exposed group compared to the control group. VE-protected groups revealed significant increases in TAC levels. Our results demonstrate that Pb decreased EPSP slopes and PS amplitudes compared to the control group, whereas VE increased these parameters compared to the control group. Co-administration of VE with Pb exposure inhibited Pb-induced effects. These findings suggest that VE via its antioxidant activity reverses Pb-induced impairments of synaptic plasticity in the DG. Copyright © 2015 Elsevier B.V. All rights reserved.

Whole brain radiation-induced impairments in learning and memory are time-sensitive and reversible by systemic hypoxia.

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Junie P Warrington

Full Text Available Whole brain radiation therapy (WBRT is commonly used for treatment of primary and metastatic brain tumors; however, cognitive impairment occurs in 40-50% of brain tumor survivors. The etiology of the cognitive impairment following WBRT remains elusive. We recently reported that radiation-induced cerebrovascular rarefaction within hippocampal subregions could be completely reversed by systemic hypoxia. However, the effects of this intervention on learning and memory have not been reported. In this study, we assessed the time-course for WBRT-induced impairments in contextual and spatial learning and the capacity of systemic hypoxia to reverse WBRT-induced deficits in spatial memory. A clinical fractionated series of 4.5Gy WBRT was administered to mice twice weekly for 4 weeks, and after various periods of recovery, behavioral analyses were performed. To study the effects of systemic hypoxia, mice were subjected to 11% (hypoxia or 21% oxygen (normoxia for 28 days, initiated 1 month after the completion of WBRT. Our results indicate that WBRT induces a transient deficit in contextual learning, disruption of working memory, and progressive impairment of spatial learning. Additionally, systemic hypoxia completely reversed WBRT-induced impairments in learning and these behavioral effects as well as increased vessel density persisted for at least 2 months following hypoxia treatment. Our results provide critical support for the hypothesis that cerebrovascular rarefaction is a key component of cognitive impairment post-WBRT and indicate that processes of learning and memory, once thought to be permanently impaired after WBRT, can be restored.

Current Reversal Due to Coupling Between Asymmetrical Driving Force and Ratchet Potential

International Nuclear Information System (INIS)

Ai Baoquan; Xie Huizhang; Liu Lianggang

2006-01-01

Transport of a Brownian particle moving in a periodic potential is investigated in the presence of an asymmetric unbiased external force. The asymmetry of the external force and the asymmetry of the potential are the two ways of inducing a net current. It is found that the competition of the spatial asymmetry of potential with the temporal asymmetry of the external force leads to the phenomena like current reversal. The competition between the two opposite driving factors is a necessary but not a sufficient condition for current reversals.

Change of choline compounds in sodium selenite-induced apoptosis of rats used as quantitative analysis by in vitro 9.4T MR spectroscopy

DEFF Research Database (Denmark)

Cao, Zhen; Wu, Lin-Ping; Li, Yun-Xia

2008-01-01

staining was employed to detect and confirm the change of liver cells. RESULTS: Good (1)H-MR spectra of perchloric acid extract from liver tissue of rats were obtained. The conventional metabolites were detected and assigned. Concentrations of different ingredient choline compounds in treatment group vs...

Standardized Salvia miltiorrhiza Extract Suppresses Hepatic Stellate Cell Activation and Attenuates Steatohepatitis Induced by a Methionine-Choline Deficient Diet in Mice

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Hak Sung Lee

2014-06-01

Full Text Available The aim of this study was to examine the effect of standardized extract of Salvia miltiorrhiza (SME on gene and protein expression of non-alcoholic steatohepatitis (NASH-related factors in activated human hepatic stellate cells (HSC, and in mice with steatohepatitis induced by a methionine-choline deficient (MCD diet. Male C57BL/6J mice were placed on an MCD or control diet for 8 weeks and SME (0, 0.1, 0.5 and 1 mg/kg body weight was administered orally every other day for 4 or 6 weeks. HSCs from the LX-2 cell line were treated with transforming growth factor β-1 (TGF-β1 or TGF-β1 plus SME (0.1–10 μg/mL. To investigate the effect of SME on reactive oxygen species (ROS-induced condition, LX-2 cells were treated with hydrogen peroxide (H2O2 or H2O2 plus SME (0.1–100 μg/mL. MCD administration for 12 weeks increased mRNA expression of tumor necrosis factor (TNF-α, TGF-β1, interleukin-1β (IL-1β, C-reactive protein (CRP, α-smooth muscle actin (α-SMA, type I collagen, matrix metalloproteinase-2 (MMP-2 and MMP-9. TGF-β1-induced LX-2 cells exhibited similar gene expression patterns. SME treatment significantly reduced the mRNA and protein expression of NASH-related factors in the mouse model and HSCs. Histopathological liver analysis showed improved non-alcoholic fatty liver disease (NAFLD activity and fibrosis score in SME-treated mice. The in vivo studies showed that SME had a significant effect at low doses. These results suggest that SME might be a potential therapeutic candidate for NAFLD treatment.

The effect of sodium ions on the light-induced 86Rb release from the isolated crayfish retina

International Nuclear Information System (INIS)

Hartung, K.; Stieve, H.

1980-01-01

The effect of low external Na + concentrations on the light-induced K + release from crayfish photoreceptor cells was tested by labelling intracellular K + with the isotope 86 Rb. The amount of isotope released per light, stimulus is roughly proportional to the external Na + concentration if the osmolarity is kept constant by replacing Na + with Tris, choline or sucrose. When sucrose is used to replace the depleted Na + the light-induced K + release is a linear function of the external Na + concentration and is reduced by approx. 95% at an external Na + concentration of 5 mmol/l. For choline and Tris substitutions the relationships are less clear but at Na + concentrations + release is smaller in a Tris solution and larger in a choline solution. It is suggested that the light-induced K + release is due mainly to an activation of voltage sensitive K + channels. (orig.)

Speman®, A Proprietary Ayurvedic Formulation, Reverses Cyclophosphamide-Induced Oligospermia In Rats.

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Mohd. Azeemuddin Mukram

2013-04-01

Full Text Available Background: This investigation was aimed to evaluate the effect of Speman®, a well known ayurvedic proprietary preparation, in an experimental model of cyclophosphamide-(CP induced oligospermia in rats.Materials and Methods: Thirty male rats were randomized in to five, equally-sized groups. Rats in group 1 served as a normal control; group 2 served as an untreated positive control; groups 3, 4, 5 received  Speman® granules  at doses of 300, 600, and 900mg/kg body weight p.o. respectively, once daily for 13 days. On day four, one hour after the respective treatment, oligospermia was induced by administering a single dose of CP (100mg/kg body weight p.o.  to all the groups except group1. At the end of the study period the rats were euthanised and accessory reproductive organs were weighed and subjected to histopathological examination. The semen samples were subject to enumeration of sperms.  Weight of the reproductive organs, histopathological examination of the tissues, and sperm count were the parameters studied to understand the effect of Speman® on rats with CP-induced oligospermia.Results: Changes that occurred due to the administration of CP at a dose of 100 mg/kg body weight were dose dependently reversed with Speman® at a dose of 300, 600, and 900 mg/kg body weight. There was a statistically significant increase in sperm count and the weight of the seminal vesicle, epididymis, and prostate.Conclusion: Findings of this investigation indicate that Speman® dose dependently reversed the CP-induced derangement of various parameters pertaining to the reproductive system.  This could explain the total beneficial actions of Speman® reported in several other clinical trials.

Lead phytotoxicity in soils and nutrient solutions is related to lead induced phosphorus deficiency

International Nuclear Information System (INIS)

Cheyns, Karlien; Peeters, Sofie; Delcourt, Dorien; Smolders, Erik

2012-01-01

This study was set up to relate lead (Pb) bioavailability with its toxicity to plants in soils. Tomato and barley seedlings were grown in six different PbCl 2 spiked soils (pH: 4.7–7.4; eCEC: 4.2–41.7 cmol c /kg). Soils were leached and pH corrected after spiking to exclude confounding factors. Plant growth was halved at 1600–6500 mg Pb/kg soil for tomato and at 1900–8300 mg Pb/kg soil for barley. These soil Pb threshold were unrelated to soil pH, organic carbon, texture or eCEC and neither soil solution Pb nor Pb 2+ ion activity adequately explained Pb toxicity among soils. Shoot phosphorus (P) concentrations significantly decreased with increasing soil Pb concentrations. Tomato grown in hydroponics at either varying P supply or at increasing Pb (equal initial P) illustrated that shoot P explained growth response in both scenarios. The results suggest that Pb toxicity is partially related to Pb induced P deficiency, likely due to lead phosphate precipitation. - Highlights: ► Tomato and barley shoot growth was affected by Pb toxicity in six different soils. ► Soil properties did not explain differences in plant Pb toxicity among soils. ► Neither soil solution Pb nor Pb 2+ ion activity explained Pb toxicity among soils. ► Shoot phosphorus concentration decreased with increasing soil Pb concentrations. ► Lead induced a P deficiency in plants, likely due to lead phosphate precipitation. - Soil properties did not explain differences in plant lead toxicity among different soils. Shoot phosphorus concentration decreased with increasing soil lead concentrations.

The Investigation of Electrochemistry Behaviors of Tyrosinase Based on Directly-Electrodeposited Grapheneon Choline-Gold Nanoparticles.

Science.gov (United States)

He, Yaping; Yang, Xiaohui; Han, Quan; Zheng, Jianbin

2017-06-23

A novel catechol (CA) biosensor was developed by embedding tyrosinase (Tyr) onto in situ electrochemical reduction graphene (EGR) on choline-functionalized gold nanoparticle (AuNPs-Ch) film. The results of UV-Vis spectra indicated that Tyr retained its original structure in the film, and an electrochemical investigation of the biosensor showed a pair of well-defined, quasi-reversible redox peaks with E pa = -0.0744 V and E pc = -0.114 V (vs. SCE) in 0.1 M, pH 7.0 sodium phosphate-buffered saline at a scan rate of 100 mV/s. The transfer rate constant k s is 0.66 s -1 . The Tyr-EGR/AuNPs-Ch showed a good electrochemical catalytic response for the reduction of CA, with the linear range from 0.2 to 270 μM and a detection limit of 0.1 μM (S/N = 3). The apparent Michaelis-Menten constant was estimated to be 109 μM.

Reversal of sodium pump inhibitor induced vascular smooth muscle contraction with digibind. Stoichiometry and its implications.

Science.gov (United States)

Krep, H H; Graves, S W; Price, D A; Lazarus, M; Ensign, A; Soszynski, P A; Hollenberg, N K

1996-01-01

The possibility that a circulating sodium pump inhibitor contributes to the pathogenesis of volume-dependent hypertension via an action on vascular smooth muscle (VSM) is supported by multiple lines of investigation, but remains controversial. We had two goals in this study. The first was to compare the pattern of contractile response of rabbit aorta induced by two candidates, ouabain and a labile sodium pump inhibitor that we have identified in the peritoneal dialysate of volume-expanded hypertensive patients with chronic renal failure. Our second goal was to examine the ability of Digibind, a Fab fragment of antisera directed against digoxin, to reverse VSM contraction induced by both agents. Ouabain induced a concentration-dependent contraction, which was delayed in onset, was gradual, and reached a stable plateau after many hours. The labile sodium pump inhibitor induced a qualitatively similar series of responses. Digibind rapidly reversed the contractile responses to both sodium pump inhibitors, with a rate of relaxation that matched that induced by physical removal of the pump inhibitor from the bath. For ouabain, the Digibind:ouabain stoichiometry was highly predictable. When Digibind was present in a molar concentration equivalent to that of ouabain, or less, it had no effect. When the Digibind concentration was twice that of ouabain, complete relaxation occurred. Although the concentration:VSM response relationship for ouabain was steep, the concentration:effect interaction with Digibind was even more steep. The molar concentration of Digibind required to reverse the effects of the labile endogenous inhibitor from peritoneal dialysate was consistently lower than that for ouabain, which is compatible with either greater potency of the labile factor in VSM or greater affinity for Digibind. These findings are compatible with a role for one or more endogenous sodium pump inhibitors as the determinant of vascular smooth muscle tone in the volume

PET imaging of hepatocellular carcinoma with {sup 18}F-fluoroethylcholine and {sup 11}C-choline

Energy Technology Data Exchange (ETDEWEB)

Kolthammer, Jeffrey A.; Tenley, Nathan [Case Western Reserve University, Department of Biomedical Engineering, Cleveland, OH (United States); Corn, David J.; Wu, Chunying; Tian, Haibin; Wang, Yanming [University Hospitals Case Medical Center, Nuclear Medicine Division, Department of Radiology, Cleveland, OH (United States); Lee, Zhenghong [Case Western Reserve University, Department of Biomedical Engineering, Cleveland, OH (United States); University Hospitals Case Medical Center, Nuclear Medicine Division, Department of Radiology, Cleveland, OH (United States)

2011-07-15

Choline-based radiotracers have been studied for PET imaging of hepatocellular carcinoma (HCC). Using an {sup 18}F-labeled choline analog, instead of the {sup 11}C-labeled native choline, would facilitate its widespread use in the clinic. In this study, PET with {sup 18}F-fluoroethylcholine (FEC) and {sup 11}C-choline (CHOL) were compared using an animal model of HCC. The effects of fasting on the performance of choline-based tracers were also investigated. A woodchuck model of HCC was used to compare the two tracers, which were administered and imaged in sequence during the same imaging session. Dynamic PET images were generated spanning 50 min starting from tracer injection. Time-activity curves and tracer contrast were calculated in liver regions with tracer accumulation, and the contrast at a late time-point with the two tracers, and between fasted and nonfasted states, were compared. Foci of HCC with increased uptake ranged in size from 1.0 to 1.6 cm, with mean tumor-to-background contrast of 1.3 with FEC and 1.5 with CHOL at 50 min after injection. The tracers show similar patterns of uptake immediately following administration, and both activities plateaued at 10 min after injection. No significant differences in uptake dynamics or final contrast were observed between the fasted and nonfasted states. PET imaging of HCC is possible with both CHOL and FEC. Fasting was not found to affect accumulation of either tracer. These results encourage further investigation into the clinical utility of FEC for HCC imaging. (orig.)

Seawater feed reverse osmosis preheating appraisal, Part I: leading element performance

International Nuclear Information System (INIS)

Karameldin, A.; Saadawy, M.S.

2006-01-01

This paper is concerned with the seawater reverse osmosis preheating process, and presents a parametric study of the process. The basic transport equations describing the leading element are exhibited and appraised. The leading element, which governs the whole system performance, is studied and analysed. The incorporated and investigated operating parameters are the feed pressure and the temperature for different feed salt concentrations. In addition, different feed flow rates, effects on permeate flux and permeator salt rejection, together with the permeator recovery, are studied. A seawater membrane of a well-known data, for instance FT30SW380HR, is used to perform the study. The membrane water permeability coefficient K w is determined and correlated. Furthermore, the membrane salt permeability coefficient K s from the manufacturer system analysis program (ROSA) is given and discussed. The transport governing equations are programmed in a way that facilitates the achievement of a realistic parametric study. The results showed that the permeate flux increases significantly as the feed pressure increases. Also, it increases significantly as the feed salt concentration decreases, and also as the feed temperature and pressure increase. Meanwhile, the permeator salt rejection increases significantly as the feed pressure increases, and decreases significantly as the feed temperature increases. The study of the leading element of the array showed that there are constraints that must be considered, such as maximum membrane flux, maximum applied feed pressure, maximum feed flow rate and maximum feed temperature. Therefore, to attain the maximum membrane flux, the applied feed pressure must be lowered when the feed temperature is increased. In the case where the feed temperature is increased from 18 deg.. C to 45 deg.. C, a pressure saving of between 7% and 26% is achieved, according to the feed salt concentration and feed flow rate. (author)

Maternal Choline Supplementation: A Potential Prenatal Treatment for Down Syndrome and Alzheimer's Disease.

Science.gov (United States)

Strupp, Barbara J; Powers, Brian E; Velazquez, Ramon; Ash, Jessica A; Kelley, Christy M; Alldred, Melissa J; Strawderman, Myla; Caudill, Marie A; Mufson, Elliott J; Ginsberg, Stephen D

2016-01-01

Although Down syndrome (DS) can be diagnosed prenatally, currently there are no effective treatments to lessen the intellectual disability (ID) which is a hallmark of this disorder. Furthermore, starting as early as the third decade of life, DS individuals exhibit the neuropathological hallmarks of Alzheimer's disease (AD) with subsequent dementia, adding substantial emotional and financial burden to their families and society at large. A potential therapeutic strategy emerging from the study of trisomic mouse models of DS is to supplement the maternal diet with additional choline during pregnancy and lactation. Studies demonstrate that maternal choline supplementation (MCS) markedly improves spatial cognition and attentional function, as well as normalizes adult hippocampal neurogenesis and offers protection to basal forebrain cholinergic neurons (BFCNs) in the Ts65Dn mouse model of DS. These effects on neurogenesis and BFCNs correlate significantly with spatial cognition, suggesting functional relationships. In this review, we highlight some of these provocative findings, which suggest that supplementing the maternal diet with additional choline may serve as an effective and safe prenatal strategy for improving cognitive, affective, and neural functioning in DS. In light of growing evidence that all pregnancies would benefit from increased maternal choline intake, this type of recommendation could be given to all pregnant women, thereby providing a very early intervention for individuals with DS, and include babies born to mothers unaware that they are carrying a fetus with DS.

Arginase Inhibition Reverses Monocrotaline-Induced Pulmonary Hypertension

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Christian Jung

2017-07-01

Full Text Available Pulmonary hypertension (PH is a heterogeneous disorder associated with a poor prognosis. Thus, the development of novel treatment strategies is of great interest. The enzyme arginase (Arg is emerging as important player in PH development. The aim of the current study was to determine the expression of ArgI and ArgII as well as the effects of Arg inhibition in a rat model of PH. PH was induced in 35 Sprague–Dawley rats by monocrotaline (MCT, 60 mg/kg as single-dose. There were three experimental groups: sham-treated controls (control group, n = 11, MCT-induced PH (MCT group, n = 11 and MCT-induced PH treated with the Arg inhibitor Nω-hydroxy-nor-l-arginine (nor-NOHA; MCT/NorNoha group, n = 13. ArgI and ArgII expression was determined by immunohistochemistry and Western blot. Right ventricular systolic pressure (RVPsys was measured and lung tissue remodeling was determined. Induction of PH resulted in an increase in RVPsys (81 ± 16 mmHg compared to the control group (41 ± 15 mmHg, p = 0.002 accompanied by a significant elevation of histological sum-score (8.2 ± 2.4 in the MCT compared to 1.6 ± 1.6 in the control group, p < 0.001. Both, ArgI and ArgII were relevantly expressed in lung tissue and there was a significant increase in the MCT compared to the control group (p < 0.01. Arg inhibition resulted in a significant reduction of RVPsys to 52 ± 19 mmHg (p = 0.006 and histological sum-score to 5.8 ± 1.4 compared to the MCT group (p = 0.022. PH leads to increased expression of Arg. Arg inhibition leads to reduction of RVPsys and diminished lung tissue remodeling and therefore represents a potential treatment strategy in PH.

Antivenom reversal of biochemical alterations induced by black scorpion Heterometrus fastigiousus Couzijn venom in mice

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MK Chaubey

2009-01-01

Full Text Available In the present study, Heterometrus fastigiousus venom (HFV was employed as antigen to produce species-specific scorpion antivenom (SAV in albino mice (NIH strain. To determine SAV efficacy, it was pre-incubated with 10 LD50 of HFV and then injected subcutaneously into mice. Subsequently, mortality was observed after 24 hours. Minimum effective dose (MED was 12.5 LD50 of HFV/mL of SAV. SAV effectiveness to reverse HFV-induced biochemical alterations in mice was analyzed by challenge method. Simultaneously, mice received subcutaneously 40% of 24-hour-LD50 of HFV and intravenously SAV. After four hours, changes in serum glucose, free amino acids, uric acids, pyruvic acid, cholesterol, total protein, alkaline phosphatase, acid phosphatase, lactic dehydrogenase and glutamate-pyruvate transaminase enzyme level were determined. Treatment with species-specific SAV resulted in the reversal of HFV-induced biochemical alterations.

Thymoquinone ameliorates lead-induced brain damage in Sprague Dawley rats.

Science.gov (United States)

Radad, Khaled; Hassanein, Khaled; Al-Shraim, Mubarak; Moldzio, Rudolf; Rausch, Wolf-Dieter

2014-01-01

The present study aims to investigate the protective effects of thymoquinone, the major active ingredient of Nigella sativa seeds, against lead-induced brain damage in Sprague-Dawley rats. In which, 40 rats were divided into four groups (10 rats each). The first group served as control. The second, third and fourth groups received lead acetate, lead acetate and thymoquinone, and thymoquinone only, respectively, for one month. Lead acetate was given in drinking water at a concentration of 0.5 g/l (500 ppm). Thymoquinone was given daily at a dose of 20mg/kg b.w. in corn oil by gastric tube. Control and thymoquinone-treated rats showed normal brain histology. Treatment of rats with lead acetate was shown to produce degeneration of endothelial lining of brain blood vessels with peri-vascular cuffing of mononuclear cells consistent to lymphocytes, congestion of choroid plexus blood vessels, ischemic brain infarction, chromatolysis and neuronal degeneration, microglial reaction and neuronophagia, degeneration of hippocampal and cerebellar neurons, and axonal demyelination. On the other hand, co-administration of thymoquinone with lead acetate markedly decreased the incidence of lead acetate-induced pathological lesions. Thus the current study shed some light on the beneficial effects of thymoquinone against neurotoxic effects of lead in rats. Copyright © 2013 Elsevier GmbH. All rights reserved.

Metalloproteinase Inhibition Protects against Reductions in Circulating Adrenomedullin during Lead-induced Acute Hypertension.

Science.gov (United States)

Nascimento, Regina A; Mendes, Gabryella; Possomato-Vieira, Jose S; Gonçalves-Rizzi, Victor Hugo; Kushima, Hélio; Delella, Flavia K; Dias-Junior, Carlos A

2015-06-01

Intoxication with lead (Pb) results in increased blood pressure by mechanisms involving matrix metalloproteinases (MMPs). Recent findings have revealed that MMP type two (MMP-2) seems to cleave vasoactive peptides. This study examined whether MMP-2 and MMP-9 levels/activities increase after acute intoxication with low lead concentrations and whether these changes were associated with increases in blood pressure and circulating endothelin-1 or with reductions in circulating adrenomedullin and calcitonin gene-related peptide (CGRP). Here, we expand previous findings and examine whether doxycycline (a MMPs inhibitor) affects these alterations. Wistar rats received intraperitoneally (i.p.) 1st dose 8 μg/100 g of lead (or sodium) acetate, a subsequent dose of 0.1 μg/100 g to cover daily loss and treatment with doxycycline (30 mg/kg/day) or water by gavage for 7 days. Similar whole-blood lead levels (9 μg/dL) were found in lead-exposed rats treated with either doxycycline or water. Lead-induced increases in systolic blood pressure (from 143 ± 2 to 167 ± 3 mmHg) and gelatin zymography of plasma samples showed that lead increased MMP-9 (but not MMP-2) levels. Both lead-induced increased MMP-9 activity and hypertension were blunted by doxycycline. Doxycycline also prevented lead-induced reductions in circulating adrenomedullin. No significant changes in plasma levels of endothelin-1 or CGRP were found. Lead-induced decreases in nitric oxide markers and antioxidant status were not prevented by doxycycline. In conclusion, acute lead exposure increases blood pressure and MMP-9 activity, which were blunted by doxycycline. These findings suggest that MMP-9 may contribute with lead-induced hypertension by cleaving the vasodilatory peptide adrenomedullin, thereby inhibiting adrenomedullin-dependent lowering of blood pressure. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Sugammadex for reversal of rocuronium-induced neuromuscular blockade in pediatric patients

Science.gov (United States)

Won, Young Ju; Lim, Byung Gun; Lee, Dong Kyu; Kim, Heezoo; Kong, Myoung Hoon; Lee, Il Ok

2016-01-01

Abstract Background: Previous studies have shown that sugammadex, a modified γ-cyclodextrin, is a well-tolerated agent for the reversal of neuromuscular blockade (NMB) induced by a steroidal neuromuscular blocking drug in adult patients. However, its use has not been reviewed in pediatric patients. The aim of this meta-analysis was to evaluate the efficacy and safety of sugammadex in the reversal of rocuronium-induced NMB during surgery under general anesthesia in pediatric patients. Methods: A literature search was performed using the Pubmed, EMBASE: Drugs and pharmacology, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. Analysis was conducted using RevMan 5.3. Data collected from different trials were pooled; the weighted mean difference or the pooled risk ratio and the corresponding 95% confidence interval (CI) were used for analysis, and heterogeneity (I2) assessment was performed. Results: Six randomized controlled trials comparing 253 pediatric patients (age range, 2–18 years) were included in the final analysis. The mean time taken to reach a train-of-four ratio of ≥0.9 was significantly shorter in the sugammadex groups (2 and 4 mg/kg) than in the control group (neostigmine or placebo), although the heterogeneity was high. The weighted mean differences of the 2 and 4 mg/kg sugammadex groups were −7.15 (95% CI: −10.77 to −3.54; I2 = 96%; P = 0.0001) and −17.32 (95% CI: −29.31 to −5.32; I2 = 98%; P = 0.005), respectively. The extubation time in the sugammadex group was shorter than that in the control group; the weighted mean difference of the sugammadex group was −6.00 (95% CI: −11.46 to −0.53; I2 = 99%; P = 0.03). There was no significant difference between the groups in terms of the incidence of postanesthetic adverse events; the pooled risk ratio was 0.67 (95% CI: 0.27–1.71; I2 = 59%; P = 0.41). Conclusion: We suggest that sugammadex is fast and

Inducing sex reversal of the urogenital system of marsupials.

Science.gov (United States)

Renfree, Marilyn B; Chew, Keng Yih; Shaw, Geoff

2014-01-01

Marsupials differ from eutherian mammals in their reproductive strategy of delivering a highly altricial young after a short gestation. The young, with its undeveloped organ systems completes its development post-natally, usually within a pouch. The young is dependent on milk with a composition that varies through lactation to support its growth and changing needs as it matures over a lengthy period. Gonadal differentiation occurs after birth, providing a unique opportunity to examine the effects of hormonal manipulations on its sexual differentiation of the highly accessible young. In marsupials a difference in the migration of the urinary ducts around the genital ducts from eutherian mammals results in the unique tammar reproductive tract which has three vaginae and two cervices, and two distinctly separate uteri. In the tammar wallaby, a small member of the kangaroo family, we showed that virilisation of the Wolffian duct, prostate and phallus depends on an alternate androgen pathway, which has now been shown to be important for virilisation in humans. Through hormonal manipulations over differing time periods we have achieved sex reversal of both ovaries and testes, germ cells, genital ducts, prostate and phallus. Whilst we understand many of the mechanisms behind sexual differentiation there are still many lessons to be learned from understanding how sex reversal is achieved by using a model such as the tammar wallaby. This will help guide investigations into the major questions of how and why sex determination is achieved in other species. This review discusses the control and development of the marsupial urogenital system, largely drawn from our studies in the tammar wallaby and our ability to manipulate this system to induce sex reversal. Copyright © 2013 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

Choline and/or folic acid deficiency is associated with genomic damage and cell death in human lymphocytes in vitro.

Science.gov (United States)

Lu, Lin; Ni, Juan; Zhou, Tao; Xu, Weijiang; Fenech, Michael; Wang, Xu

2012-04-01

Choline and folate are interrelated methyl donors. Previous studies showed that folate prevents genomic damage in human lymphocytes in vitro; however, the association between choline and human genomic stability is uncertain. To explore the genotoxicity, cytotoxicity, and cytostatic effects and possible interactions of choline and/or folate deficiency on the human genome, lymphocytes from 6 volunteers were cultured in 18 combinations of choline (CC) and folic acid (FA) media for 9 days. The genotoxicity was evaluated by micronuclei, nucleoplasmic bridges, and nuclear buds in the binucleated cell; the cytotoxicity indices included apoptosis and necrosis, and the cytostatic effects were indicated by nuclear division index (NDI). Across all choline concentrations, the frequencies of all biomarkers except NDI were diminished when FA concentration was more than or equal to 120 nmol/L. The frequencies of micronuclei, buds, and necrosis were significantly higher at lower levels of CC (0-6 μmol/L) compared with higher concentrations of CC (12-21.5 μmol/L) while maintaining the same FA concentration. We concluded that both choline and folate significantly impact genomic stability and cell death, although effects of folate were 2.5- to 6.2-fold greater, depending on the biomarker and dose. A combination of 12 μmol/L CC and 120 nmol/L FA appears to be optimal for genomic integrity in vitro.

The detection rate of [11C]Choline-PET/CT depends on the serum PSA-value in patients with biochemical recurrence of prostate cancer

International Nuclear Information System (INIS)

Krause, B.J.; Souvatzoglou, M.; Tuncel, M.; Herrmann, K.; Buck, A.K.; Praus, C.; Schwaiger, M.; Schuster, T.; Geinitz, H.; Treiber, U.

2008-01-01

An increase of the serum PSA-level is a sensitive in vitro marker for recurrent prostate cancer. However, it remains difficult to differentiate between local, regional or distant recurrent disease. The aim of this study was to assess the relationship between the detection rate of [ 11 C]Choline-PET/CT and the serum PSA-level in patients with a biochemical recurrence of prostate cancer with the view towards localisation of recurrent disease. Sixty-three patients (mean age, 68.8 ± 6.9; range, 45-83 years) with biochemical recurrence after primary therapy for prostate cancer were included in the analysis. Mean PSA-levels were 5.9 ± 9.7 ng/ml (range, 0.2-39 ng/ml; median, 2.15). Of the 63 patients, 17 were under anti-androgen therapy at the time of [ 11 C]Choline PET/CT. Patients underwent a [ 11 C]Choline-PET/CT study after injection of 656 ± 119 MBq [ 11 C]Choline on a Sensation 16 Biograph PET/CT scanner. Of the 63 patients, 35 (56%) showed a pathological [ 11 C]Choline uptake. The detection rate of [ 11 C]Choline-PET/CT showed a relationship with the serum PSA-level: The detection rate was 36% for a PSA-value 11 C]Choline-PET/CT (p = 0.374). As an important result our study shows that even for PSA-values 11 C]Choline-PET/CT is 36%. Furthermore, the detection rate of [ 11 C]Choline-PET/CT shows a positive relationship with serum PSA-levels in patients with biochemical recurrence of prostate cancer after primary therapy. Therefore, in these patients, [ 11 C]Choline PET/CT allows not only to diagnose but also to localise recurrent disease with implications on disease management (localised vs systemic therapy). (orig.)

Early deprivation leads to long-term reductions in motivation for reward and 5-HT1A binding and both effects are reversed by fluoxetine.

Science.gov (United States)

Leventopoulos, Michail; Russig, Holger; Feldon, Joram; Pryce, Christopher R; Opacka-Juffry, Jolanta

2009-03-01

Early life stress is a risk factor in aetiology of depression. In rats, early life stress can lead to pro-depressive biomarkers in adulthood. The present study in male Wistar rats investigated the effects of early life deprivation and fluoxetine on motivation for reward, activity in the forced swim test, and brain monoamine receptors, in adulthood. P1-14 pups were isolated for 4 h/day (early deprivation, ED) or were handled for 1 min (CON). They were weaned at PND21 and left undisturbed until 4-6 months old. The ED and CON groups were halved to receive either vehicle or fluoxetine (FLX, 10 mg/kg, 31 days). Thus, four treatment groups were studied: CON-VEH, CON-FLX, ED-VEH and ED-FLX, n = 8 each. On a progressive ratio schedule, ED-VEH animals showed significantly reduced motivation to obtain sucrose versus CON-VEH, and this reward-motivation deficit was reversed by FLX. Activity in the forced swim test was unaffected by ED and increased by FLX. Quantitative autoradiography was used to determine 5-HT1A and 5-HT2C receptor binding with [O-methyl-(3)H]WAY 100635 and [(3)H]mesulergine (added spiperone and 8-OH-DPAT), respectively. In ED-VEH versus CON-VEH, 5-HT1A receptor binding was significantly reduced in anterior cingulate, motor cortex, ventral hippocampal CA1 and dorsal raphé; this was reversed by chronic FLX. Concomitant ED-dependent reductions observed in 5-HT2C (motor and frontal cortices, ventral CA1 and dorsal raphé) and D2 (dorsolateral striatum and accumbens) binding were not reversed by FLX. Because chronic FLX treatment reversed the ED-induced behavioural and 5-HT1A binding deficits, the 5-HT1A receptor is implicated as a selective therapeutic target.

Ex vivo analysis identifies effective HIV-1 latency–reversing drug combinations

Science.gov (United States)

Laird, Gregory M.; Bullen, C. Korin; Rosenbloom, Daniel I.S.; Martin, Alyssa R.; Hill, Alison L.; Durand, Christine M.; Siliciano, Janet D.; Siliciano, Robert F.

2015-01-01

Reversal of HIV-1 latency by small molecules is a potential cure strategy. This approach will likely require effective drug combinations to achieve high levels of latency reversal. Using resting CD4+ T cells (rCD4s) from infected individuals, we developed an experimental and theoretical framework to identify effective latency-reversing agent (LRA) combinations. Utilizing ex vivo assays for intracellular HIV-1 mRNA and virion production, we compared 2-drug combinations of leading candidate LRAs and identified multiple combinations that effectively reverse latency. We showed that protein kinase C agonists in combination with bromodomain inhibitor JQ1 or histone deacetylase inhibitors robustly induce HIV-1 transcription and virus production when directly compared with maximum reactivation by T cell activation. Using the Bliss independence model to quantitate combined drug effects, we demonstrated that these combinations synergize to induce HIV-1 transcription. This robust latency reversal occurred without release of proinflammatory cytokines by rCD4s. To extend the clinical utility of our findings, we applied a mathematical model that estimates in vivo changes in plasma HIV-1 RNA from ex vivo measurements of virus production. Our study reconciles diverse findings from previous studies, establishes a quantitative experimental approach to evaluate combinatorial LRA efficacy, and presents a model to predict in vivo responses to LRAs. PMID:25822022

Studies on the riboflavin, niacin, pantothenic acid and choline requirements of young bobwhite quail

Science.gov (United States)

Serafin, J.A.

1974-01-01

Four experiments were conducted to examine the riboflavin, niacin, pantothenic acid and choline requirements of young Bobwhite quail. Quail fed purified diets deficient in either riboflavin, niacin, pantothenic acid or choline grew poorly and high mortality occurred by 5 weeks of age. Under the conditions of these experiments, it was found that: (1) young quail require approximately 3.8 mg. riboflavin/kg. diet for satisfactory growth and survival; (2) no more than 31 mg. niacin/kg. diet are required for normal growth and survival of young quail; (3) the requirement for pantothenic acid is higher than has previously been reported, quail in these studies requiring 12.6 mg. pantothenic acid/kg. feed for growth and survival; and (4) the requirement for choline for reducing mortality is approximately 1000 mg./kg., while the amount necessary for normal growth of young quail is no greater than 1500 mg./kg. when the diet contains ample amounts of methionine. Quail fed a niacin-deficient diet developed stiff, shortened feathers and an erythema about the head; those receiving a riboflavin-deficient ration developed enlarged hocks and bowed legs, as did quail fed diets low or devoid of choline. Aside from slow growth, poor feathering was the only other indication that a deficient diet was being fed when quail were placed on a basal ration without pantothenic acid for five weeks.

Efficacy of anti-inflammatory, antibiotic and pleiotropic agents in reversing nitrogen mustard-induced injury in ex vivo cultured rabbit cornea.

Science.gov (United States)

Goswami, Dinesh G; Kant, Rama; Tewari-Singh, Neera; Agarwal, Rajesh

2018-09-01

Vesicating agent, Sulfur mustard (SM), causes devastating eye injury; however, there are no effective antidotes available. Using nitrogen mustard (NM), a bi-functional analog of SM, we have earlier reported that NM-induced corneal injury in ex vivo rabbit cornea organ culture model parallels corneal injury reported with SM. Using this model, we have demonstrated the therapeutic efficacy of dexamethasone (DEX), doxycycline (DOX) and silibinin (SB) in reversing NM (2h exposure)-induced corneal injuries when added immediately after washing NM. In the present study, we further examined the efficacy of similar/higher doses of these agents when added immediately, 2, or 4h after washing NM following its 2h exposure. All three treatment agents caused a reversal in established NM-induced injury biomarkers when added immediately or 2h after washing NM following its 2h exposure; however, when treatments were carried out 4h after washing NM, there was no significant effect. Together, our results further show the beneficial effect of these agents in reversing NM-induced corneal injury and indicate the time window for effective treatment. This could be useful towards future development of targeted therapeutics against vesicant-induced ocular injury. Copyright © 2017 Elsevier B.V. All rights reserved.

Extremely low-frequency magnetic fields can impair spermatogenesis recovery after reversible testicular damage induced by heat.

Science.gov (United States)

Tenorio, Bruno Mendes; Ferreira Filho, Moisés Bonifacio Alves; Jimenez, George Chaves; de Morais, Rosana Nogueira; Peixoto, Christina Alves; Nogueira, Romildo de Albuquerque; da Silva Junior, Valdemiro Amaro

2014-06-01

Male infertility is often related to reproductive age couples experiencing fertility-related issues. Men may have fertility problems associated with reversible testicular damage. Considering that men have been increasingly exposed to extremely low-frequency magnetic fields generated by the production, distribution and use of electricity, this study analyzed whether 60 Hz and 1 mT magnetic field exposure may impair spermatogenesis recovery after reversible testicular damage induced by heat shock using rats as an experimental model. Adult male rats were subjected to a single testicular heat shock (HS, 43 °C for 12 min) and then exposed to the magnetic field for 15, 30 and 60 d after HS. Magnetic field exposure during the spermatogenesis recovery induced changes in testis components volume, cell ultrastructure and histomorphometrical parameters. Control animals had a reestablished and active spermatogenesis at 60 d after heat shock, while animals exposed to magnetic field still showed extensive testicular degeneration. Magnetic field exposure did not change the plasma testosterone. In conclusion, extremely low-frequency magnetic field may be harmful to fertility recovery in males affected by reversible testicular damage.

Electric Field-Induced Large Strain in Ni/Sb-co Doped (Bi0.5Na0.5) TiO3-Based Lead-Free Ceramics

Science.gov (United States)

Li, Liangliang; Hao, Jigong; Xu, Zhijun; Li, Wei; Chu, Ruiqing

2018-02-01

Lead-free piezoelectric ceramics (Bi0.5Na0.5)0.935Ba0.065Ti1- x (Ni0.5Sb0.5) x O3 (BNBT6.5- xNS) have been fabricated using conventional solid sintering technique. The effect of (Ni, Sb) doping on the phase structure and electrical properties of BNBT6.5 ceramics were systematically investigated. Results show that the addition of (Ni, Sb) destroyed the ferroelectric long-range order of BNBT6.5 and shifted the ferroelectric-relaxor transition temperature ( T F-R) down to room temperature. Thus, this process induced an ergodic relaxor phase at zero field in samples with x = 0.005. Under the electric field, the ergodic relaxor phase could reversibly transform to ferroelectric phase, which promotes the strain response with peak value of 0.38% (at 80 kV/cm, corresponding to d 33 * = 479 pm/V) at x = 0.005. Temperature-dependent measurements of both polarization and strain confirmed that the large strain originated from a reversible field-induced ergodic relaxor to ferroelectric phase transformation. The proposed material exhibits potential for nonlinear actuators.

Selective activation of M4 muscarinic acetylcholine receptors reverses MK-801-induced behavioral impairments and enhances associative learning in rodents

DEFF Research Database (Denmark)

Bubser, Michael; Bridges, Thomas M; Dencker, Ditte

2014-01-01

PAMs, enabling a more extensive characterization of M4 actions in rodent models. We used VU0467154 to test the hypothesis that selective potentiation of M4 receptor signaling could ameliorate the behavioral, cognitive, and neurochemical impairments induced by the noncompetitive NMDAR antagonist MK-801....... VU0467154 produced a robust dose-dependent reversal of MK-801-induced hyperlocomotion and deficits in preclinical models of associative learning and memory functions, including the touchscreen pairwise visual discrimination task in wild-type mice, but failed to reverse these stimulant...

Negative Pressure Pulmonary Edema after Reversing Rocuronium-Induced Neuromuscular Blockade by Sugammadex

Directory of Open Access Journals (Sweden)

Manzo Suzuki

2014-01-01

Full Text Available Negative pressure pulmonary edema (NPPE is a rare complication that accompanies general anesthesia, especially after extubation. We experienced a case of negative pressure pulmonary edema after tracheal extubation following reversal of rocuronium-induced neuromuscular blockade by sugammadex. In this case, the contribution of residual muscular block on the upper airway muscle as well as large inspiratory forces created by the respiratory muscle which has a low response to muscle relaxants, is suspected as the cause.

Permanent pacemaker lead induced severe tricuspid regurgitation in patient undergoing multiple valve surgery.

Science.gov (United States)

Lee, Jung Hee; Kim, Tae Ho; Kim, Wook Sung

2015-04-01

Severe and permanent tricuspid regurgitation induced by pacemaker leads is rarely reported in the literature. The mechanism of pacemaker-induced tricuspid regurgitation has been identified, but its management has not been well established. Furthermore, debate still exists regarding the proper surgical approach. We present the case of a patient with severe tricuspid regurgitation induced by a pacemaker lead, accompanied by triple valve disease. The patient underwent double valve replacement and tricuspid valve repair without removal of the pre-existing pacemaker lead. The operation was successful and the surgical procedure is discussed in detail.

Variability of Gross Tumor Volume in Nasopharyngeal Carcinoma Using 11C-Choline and 18F-FDG PET/CT.

Directory of Open Access Journals (Sweden)

Jun Jiang

Full Text Available This study was conducted to evaluate the variability of gross tumor volume (GTV using 11C-Choline and 18F-FDG PET/CT images for nasopharyngeal carcinomas boundary definition. Assessment consisted of inter-observer and inter-modality variation analysis. Four radiation oncologists were invited to manually contour GTV by using PET/CT fusion obtained from a cohort of 12 patients with nasopharyngeal carcinoma (NPC and who underwent both 11C-Choline and 18F-FDG scans. Student's paired-sample t-test was performed for analyzing inter-observer and inter-modality variability. Semi-automatic segmentation methods, including thresholding and region growing, were also validated against the manual contouring of the two types of PET images. We observed no significant variation in the results obtained by different oncologists in terms of the same type of PET/CT volumes. Choline fusion volumes were significantly larger than the FDG volumes (p < 0.0001, mean ± SD = 18.21 ± 8.19. While significantly consistent results were obtained between the oncologists and the standard references in Choline volumes compared with those in FDG volumes (p = 0.0025. Simple semi-automatic delineation methods indicated that 11C-Choline PET images could provide better results than FDG volumes (p = 0.076, CI = [-0.29, 0.025]. 11C-Choline PET/CT may be more advantageous in GTV delineation for the radiotherapy of NPC than 18F-FDG. Phantom simulations and clinical trials should be conducted to prove the possible improvement of the treatment outcome.

Choline chloride-based deep eutectic solvents as additives for optimizing chromatographic behavior of caffeic acid

International Nuclear Information System (INIS)

Li, Guizhen; Zhu, Tao; Lei, Yingjie

2015-01-01

A series of deep eutectic solvents (DESs) were prepared using glycerol and choline chloride (ChCl), and Fourier transform infrared spectrometer (FT-IR) was used to analyze the spectra of glycerol, choline chloride and DESs based on glycerol and choline chloride. Then DESs were used as the additives of mobile phase to optimize chromatographic behavior of caffeic acid in high performance liquid chromatography (HPLC). A 17-run Box-Behnken design (BBD) was employed to evaluate effect of DESs as additives by analyzing the maximum theoretical plate number. Three factors, reaction temperature (60 .deg. C, 80 .deg. C, 100 .deg. C), molar ratio of glycerol and choline chloride (2 : 1, 3 : 1, 4 : 1, n/n), and volume percent of additives (0.05%, 0.10%, 0.15%, v/v), were investigated in BBD. The optimum experiment condition was that of reaction temperature (80 .deg. C), molar ratio of glycerol and ChCl (3 : 1, n/n), and volume percent of additive (0.10%, v/v). The mean chromatographic theoretical plate number of the caffeic acid this condition was 1567.5, and DESs as additives shorten the retention time and modify the chromatogram shape, proving DESs as additives for effective theoretical plate number and column efficiency in HPLC.

Choline chloride-based deep eutectic solvents as additives for optimizing chromatographic behavior of caffeic acid

Energy Technology Data Exchange (ETDEWEB)

Li, Guizhen; Zhu, Tao; Lei, Yingjie [Tianjin University of Technology, Tianjin (China)

2015-10-15

A series of deep eutectic solvents (DESs) were prepared using glycerol and choline chloride (ChCl), and Fourier transform infrared spectrometer (FT-IR) was used to analyze the spectra of glycerol, choline chloride and DESs based on glycerol and choline chloride. Then DESs were used as the additives of mobile phase to optimize chromatographic behavior of caffeic acid in high performance liquid chromatography (HPLC). A 17-run Box-Behnken design (BBD) was employed to evaluate effect of DESs as additives by analyzing the maximum theoretical plate number. Three factors, reaction temperature (60 .deg. C, 80 .deg. C, 100 .deg. C), molar ratio of glycerol and choline chloride (2 : 1, 3 : 1, 4 : 1, n/n), and volume percent of additives (0.05%, 0.10%, 0.15%, v/v), were investigated in BBD. The optimum experiment condition was that of reaction temperature (80 .deg. C), molar ratio of glycerol and ChCl (3 : 1, n/n), and volume percent of additive (0.10%, v/v). The mean chromatographic theoretical plate number of the caffeic acid this condition was 1567.5, and DESs as additives shorten the retention time and modify the chromatogram shape, proving DESs as additives for effective theoretical plate number and column efficiency in HPLC.

Protective effects of piperine on lead acetate induced-nephrotoxicity in rats

Directory of Open Access Journals (Sweden)

Sri Agus Sudjarwo

2017-11-01

Full Text Available Objective(s: In this study, we investigated the protective effects of piperine on lead acetate-induced renal damage in rat kidney tissue. Materials and Methods: Forty male rats were divided into 5 groups: negative control (rats were given aquadest daily, positive control (rats were given lead acetate 30 mg/kg BW orally once a day for 60 days, and the treatment group (rats were given piperine 50 mg; 100 mg and 200 mg/kg BW orally once a day for 65 days, and on 5th day, were given lead acetate 30 mg/kg BW one hr after piperine administration for 60 days. On day 65 levels of blood urea nitrogen (BUN, creatinine, malondialdehyde (MDA, Superoxide Dismutase (SOD, and Glutathione Peroxidase (GPx were measured. Also, kidney samples were collected for histopathological studies. Results: The results revealed that lead acetate toxicity induced a significant increase in the levels of BUN, creatinine, and MDA; moreover, a significant decrease in SOD and GPx. Lead acetate also altered kidney histopathology (kidney damage, necrosis of tubules compared to the negative control. However, administration of piperine significantly improved the kidney histopathology, decreased the levels of BUN, creatinine, and MDA, and also significantly increased the SOD and GPx in the kidney of lead acetate-treated rats. Conclusion: From the results of this study it was concluded that piperine could be a potent natural herbal product exhibiting nephroprotective effect against lead acetate induced nephrotoxicity in rats.

Parkinson’s disease managing reversible neurodegeneration

Science.gov (United States)

Hinz, Marty; Stein, Alvin; Cole, Ted; McDougall, Beth; Westaway, Mark

2016-01-01

Traditionally, the Parkinson’s disease (PD) symptom course has been classified as an irreversible progressive neurodegenerative disease. This paper documents 29 PD and treatment-induced systemic depletion etiologies which cause and/or exacerbate the seven novel primary relative nutritional deficiencies associated with PD. These reversible relative nutritional deficiencies (RNDs) may facilitate and accelerate irreversible progressive neurodegeneration, while other reversible RNDs may induce previously undocumented reversible pseudo-neurodegeneration that is hiding in plain sight since the symptoms are identical to the symptoms being experienced by the PD patient. Documented herein is a novel nutritional approach for reversible processes management which may slow or halt irreversible progressive neurodegenerative disease and correct reversible RNDs whose symptoms are identical to the patient’s PD symptoms. PMID:27103805

Reversal of dexamethasone induced insulin resistance in 3T3L1 adipocytes by 3β-taraxerol of Mangifera indica.

Science.gov (United States)

Sangeetha, K N; Shilpa, K; Jyothi Kumari, P; Lakshmi, B S

2013-02-15

The present study investigates the efficacy of Mangifera indica ethyl acetate extract (MIEE) and its bioactive compound, 3β-taraxerol in the reversal of dexamethasone (DEX) induced insulin resistance in 3T3L1 adipocytes. MIEE and 3β-taraxerol were evaluated for their ability to restore impaired glucose uptake and, expression of molecular markers in the insulin signaling pathway induced by DEX in 3T3L1 adipocytes using 2-deoxy-D-[1-(3)H] glucose uptake assay and ELISA. An insulin resistant model has been developed using a glucocorticoid, DEX on 3T3L1 adipocytes. Insulin resistant condition was observed at 24h of DEX induction wherein a maximum degree of resistance of about 50% was measured based on inhibition of glucose uptake, which was confirmed using cytotoxicity analysis. The developed model of insulin resistance was studied in comparison to positive control rosiglitazone. DEX induced inhibition of glucose uptake and the expression of insulin signaling markers GLUT4 and PI3K were found to be restored by 3β-taraxerol and MIEE, thus delineating its mechanism of action in the reversal of insulin resistance. 3β-Taraxerol effectively restored DEX induced desensitization via restoration of PI3K and GLUT4 expression. To conclude, since 3β-taraxerol exhibits significant effect in reversing insulin resistance it can be further investigated as an insulin resistance reversal agent. Copyright © 2012 Elsevier GmbH. All rights reserved.

Choline Catabolism in Burkholderia thailandensis Is Regulated by Multiple Glutamine Amidotransferase 1-Containing AraC Family Transcriptional Regulators.

Science.gov (United States)

Nock, Adam M; Wargo, Matthew J

2016-09-15

Burkholderia thailandensis is a soil-dwelling bacterium that shares many metabolic pathways with the ecologically similar, but evolutionarily distant, Pseudomonas aeruginosa Among the diverse nutrients it can utilize is choline, metabolizable to the osmoprotectant glycine betaine and subsequently catabolized as a source of carbon and nitrogen, similar to P. aeruginosa Orthologs of genes in the choline catabolic pathway in these two bacteria showed distinct differences in gene arrangement as well as an additional orthologous transcriptional regulator in B. thailandensis In this study, we showed that multiple glutamine amidotransferase 1 (GATase 1)-containing AraC family transcription regulators (GATRs) are involved in regulation of the B. thailandensis choline catabolic pathway (gbdR1, gbdR2, and souR). Using genetic analyses and sequencing the transcriptome in the presence and absence of choline, we identified the likely regulons of gbdR1 (BTH_II1869) and gbdR2 (BTH_II0968). We also identified a functional ortholog for P. aeruginosa souR, a GATR that regulates the metabolism of sarcosine to glycine. GbdR1 is absolutely required for expression of the choline catabolic locus, similar to P. aeruginosa GbdR, while GbdR2 is important to increase expression of the catabolic locus. Additionally, the B. thailandensis SouR ortholog (BTH_II0994) is required for catabolism of choline and its metabolites as carbon sources, whereas in P. aeruginosa, SouR function can by bypassed by GbdR. The strategy employed by B. thailandensis represents a distinct regulatory solution to control choline catabolism and thus provides both an evolutionary counterpoint and an experimental system to analyze the acquisition and regulation of this pathway during environmental growth and infection. Many proteobacteria that occupy similar environmental niches have horizontally acquired orthologous genes for metabolism of compounds useful in their shared environment. The arrangement and differential

Local Peltier-effect-induced reversible metal–insulator transition in VO{sub 2} nanowires

Energy Technology Data Exchange (ETDEWEB)

Takami, Hidefumi; Kanki, Teruo, E-mail: kanki@sanken.osaka-u.ac.jp, E-mail: h-tanaka@sanken.osaka-u.ac.jp; Tanaka, Hidekazu, E-mail: kanki@sanken.osaka-u.ac.jp, E-mail: h-tanaka@sanken.osaka-u.ac.jp [Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka 567-0047 (Japan)

2016-06-15

We report anomalous resistance leaps and drops in VO{sub 2} nanowires with operating current density and direction, showing reversible and nonvolatile switching. This event is associated with the metal–insulator phase transition (MIT) of local nanodomains with coexistence states of metallic and insulating phases induced by thermoelectric cooling and heating effects. Because the interface of metal and insulator domains has much different Peltier coefficient, it is possible that a significant Peltier effect would be a source of the local MIT. This operation can be realized by one-dimensional domain configuration in VO{sub 2} nanowires because one straight current path through the electronic domain-interface enables theoretical control of thermoelectric effects. This result will open a new method of reversible control of electronic states in correlated electron materials.

Effect of herbal choline and rumen-protected methionine on lamb ...

African Journals Online (AJOL)

Elizabeth A Mendoza B MD

2018-01-30

Jan 30, 2018 ... oral doses of rumen-protected methionine (RPM) (0 and 1.5 g/day) and ... and stimulating glucose and cholesterol synthesis. .... The in vitro gas production indicates that half of herbal choline is fermented at 18 hours (Table 2),.

Thujone inhibits the function of α7-nicotinic acetylcholine receptors and impairs nicotine-induced memory enhancement in one-trial passive avoidance paradigm.

Science.gov (United States)

Sultan, Ahmed; Yang, Keun-Hang Susan; Isaev, Dmitro; Nebrisi, Eslam El; Syed, Nurulain; Khan, Nadia; Howarth, Christopher F; Sadek, Bassem; Oz, Murat

2017-06-01

Effects of thujone, a major ingredient of absinthe, wormwood oil and some herbal medicines, were tested on the function of α 7 subunit of the human nicotinic acetylcholine (α 7 nACh) receptor expressed in Xenopus oocytes using the two-electrode voltage-clamp technique. Thujone reversibly inhibited ACh (100μM)-induced currents with an IC 50 value of 24.7μM. The effect of thujone was not dependent on the membrane potential and did not involve Ca 2+ -dependent Cl - channels expressed endogenously in oocytes. Inhibition by thujone was not reversed by increasing ACh concentrations. Moreover, specific binding of [ 125 I] α-bungarotoxin was not altered by thujone. Further experiments in SH-EP1 cells expressing human α 7 nACh receptor indicated that thujone suppressed choline induced Ca 2+ transients in a concentration-dependent manner. In rat hippocampal CA3-dentate gyrus synapses, nicotine-induced enhancement of long-term potentiation was also inhibited by thujone. Furthermore, the results observed in in-vivo one-trial passive avoidance paradigm show that thujone (1.25mg/kg, i.p.) significantly impaired nicotine-induced enhancement of learning and memory in Wistar rats. Collectively, our results indicate that thujone inhibits the function of the α7-nACh receptor and impairs cellular and behavioral correlates of cholinergic modulation of learning and memory. Copyright © 2017 Elsevier B.V. All rights reserved.

Thujone inhibits the function of α7-nicotinic acetylcholine receptors and impairs nicotine-induced memory enhancement in one-trial passive avoidance paradigm

International Nuclear Information System (INIS)

Sultan, Ahmed; Yang, Keun-Hang Susan; Isaev, Dmitro; Nebrisi, Eslam El; Syed, Nurulain; Khan, Nadia; Howarth, Christopher F.; Sadek, Bassem; Oz, Murat

2017-01-01

Effects of thujone, a major ingredient of absinthe, wormwood oil and some herbal medicines, were tested on the function of α 7 subunit of the human nicotinic acetylcholine (α 7 nACh) receptor expressed in Xenopus oocytes using the two-electrode voltage-clamp technique. Thujone reversibly inhibited ACh (100 μM)-induced currents with an IC 50 value of 24.7 μM. The effect of thujone was not dependent on the membrane potential and did not involve Ca 2+ -dependent Cl − channels expressed endogenously in oocytes. Inhibition by thujone was not reversed by increasing ACh concentrations. Moreover, specific binding of [ 125 I] α-bungarotoxin was not altered by thujone. Further experiments in SH-EP1 cells expressing human α 7 nACh receptor indicated that thujone suppressed choline induced Ca 2+ transients in a concentration-dependent manner. In rat hippocampal CA3-dentate gyrus synapses, nicotine-induced enhancement of long-term potentiation was also inhibited by thujone. Furthermore, the results observed in in-vivo one-trial passive avoidance paradigm show that thujone (1.25 mg/kg, i.p.) significantly impaired nicotine-induced enhancement of learning and memory in Wistar rats. Collectively, our results indicate that thujone inhibits the function of the α7-nACh receptor and impairs cellular and behavioral correlates of cholinergic modulation of learning and memory.

Memory-induced sign reversals of the spatial cross-correlation for particles in viscoelastic shear flows

International Nuclear Information System (INIS)

Sauga, Ako; Laas, Katrin; Mankin, Romi

2015-01-01

Highlights: • Cross-correlation (CC) of coordinates of particles in viscoelastic shear flows is discussed. • Expressions for CC functions subjected to both internal and external noises are presented. • Impact of internal and external noises on CC functions are compared. • Memory-induced reentrant sign reversals of the spatial cross-moment are established. - Abstract: The behavior of shear-induced cross-correlation functions between particle fluctuations along orthogonal directions in the shear plane for harmonically trapped Brownian particles in a viscoelastic shear flow is studied. A generalized Langevin equation with a power-law-type memory kernel is used to model the complex structure of the viscoelastic media. Interaction with fluctuations of environmental parameters is modeled by a multiplicative white Gaussian noise, by an internal fractional Gaussian noise, and by an additive external white noise. It is shown that the presence of a memory has a profound effect on the behavior of the cross-correlation functions. Particularly, memory-induced reentrant sign reversals of the spatial cross-moment between orthogonal random displacements of a particle are established, i.e., an increase of the memory exponent can cause the sign reversal from positive to negative, but by a further increase of the memory exponent a reentrant transition from negative to positive values appears. Similarities and differences between the behavior of the models with additive internal and external noises are considered. It is shown that additive external and internal noises cause qualitatively different dependencies of the cross-correlation functions on the time lag. The occurrence of energetic instability due to the influence of multiplicative noise is also discussed.

MRI-induced heating of deep brain stimulation leads

International Nuclear Information System (INIS)

Mohsin, Syed A; Sheikh, Noor M; Saeed, Usman

2008-01-01

The radiofrequency (RF) field used in magnetic resonance imaging is scattered by medical implants. The scattered field of a deep brain stimulation lead can be very intense near the electrodes stimulating the brain. The effect is more pronounced if the lead behaves as a resonant antenna. In this paper, we examine the resonant length effect. We also use the finite element method to compute the near field for (i) the lead immersed in inhomogeneous tissue (fat, muscle, and brain tissues) and (ii) the lead connected to an implantable pulse generator. Electric field, specific absorption rate and induced temperature rise distributions have been obtained in the brain tissue surrounding the electrodes. The worst-case scenario has been evaluated by neglecting the effect of blood perfusion. The computed values are in good agreement with in vitro measurements made in the laboratory.

Oscillatory bands, neuronal synchrony and hippocampal function: implications of the effects of prenatal choline supplementation for sleep-dependent memory consolidation.

Science.gov (United States)

Cheng, Ruey-Kuang; Williams, Christina L; Meck, Warren H

2008-10-27

Choline supplementation of the maternal diet has long-term facilitative effects on spatial and temporal memory processes in the offspring. To further delineate the impact of early nutritional status on brain and behavior, we examined effects of prenatal-choline availability on hippocampal oscillatory frequency bands in 12 month-old male and female rats. Adult offspring of time-pregnant dams that were given a deficient level of choline (DEF=0.0 g/kg), sufficient choline (CON=1.1 g/kg) or supplemental choline (SUP=3.5 g/kg) in their chow during embryonic days (ED) 12-17 were implanted with an electroencephalograph (EEG) electrode in the hippocampal dentate gyrus in combination with an electromyograph (EMG) electrode patch implanted in the nuchal muscle. Five consecutive 8-h recording sessions revealed differential patterns of EEG activity as a function of awake, slow-wave sleep (SWS) and rapid-eye movement (REM) sleep states and prenatal choline status. The main finding was that SUP rats displayed increased power levels of gamma (30-100 Hz) band oscillations during all phases of the sleep/wake cycle. These findings are discussed within the context of a general review of neuronal oscillations (e.g., delta, theta, and gamma bands) and synchronization across multiple brain regions in relation to sleep-dependent memory consolidation in the hippocampus.

Permanent Pacemaker Lead Induced Severe Tricuspid Regurgitation in Patient Undergoing Multiple Valve Surgery

Directory of Open Access Journals (Sweden)

Jung Hee Lee

2015-04-01

Full Text Available Severe and permanent tricuspid regurgitation induced by pacemaker leads is rarely reported in the literature. The mechanism of pacemaker-induced tricuspid regurgitation has been identified, but its management has not been well established. Furthermore, debate still exists regarding the proper surgical approach. We present the case of a patient with severe tricuspid regurgitation induced by a pacemaker lead, accompanied by triple valve disease. The patient underwent double valve replacement and tricuspid valve repair without removal of the pre-existing pacemaker lead. The operation was successful and the surgical procedure is discussed in detail.

Rapid and reversible epigenome editing by endogenous chromatin regulators.

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Braun, Simon M G; Kirkland, Jacob G; Chory, Emma J; Husmann, Dylan; Calarco, Joseph P; Crabtree, Gerald R

2017-09-15

Understanding the causal link between epigenetic marks and gene regulation remains a central question in chromatin biology. To edit the epigenome we developed the FIRE-Cas9 system for rapid and reversible recruitment of endogenous chromatin regulators to specific genomic loci. We enhanced the dCas9-MS2 anchor for genome targeting with Fkbp/Frb dimerizing fusion proteins to allow chemical-induced proximity of a desired chromatin regulator. We find that mSWI/SNF (BAF) complex recruitment is sufficient to oppose Polycomb within minutes, leading to activation of bivalent gene transcription in mouse embryonic stem cells. Furthermore, Hp1/Suv39h1 heterochromatin complex recruitment to active promoters deposits H3K9me3 domains, resulting in gene silencing that can be reversed upon washout of the chemical dimerizer. This inducible recruitment strategy provides precise kinetic information to model epigenetic memory and plasticity. It is broadly applicable to mechanistic studies of chromatin in mammalian cells and is particularly suited to the analysis of endogenous multi-subunit chromatin regulator complexes.Understanding the link between epigenetic marks and gene regulation requires the development of new tools to directly manipulate chromatin. Here the authors demonstrate a Cas9-based system to recruit chromatin remodelers to loci of interest, allowing rapid, reversible manipulation of epigenetic states.

Protective Effect of Vitamin E Against Lead-induced Memory and Learning Impairment in Male Rats

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Salehi

2015-02-01

Full Text Available Background Lead (Pb2+ is a neurotoxin substance that has been known for its adverse effects on central nervous system and memory. Previous studies reported the potential effect of vitamin E as a memory enhancer. Objectives The purpose of the present study was to assess the protective effects of vitamin E against Pb-induced amnesia. Materials and Methods Forty-eight male Wistar rats (200-250 g were divided equally into the saline, Pb, Pb + vitamin E, and vitamin E alone groups. To induce Pb toxicity, rats received water that contained 0.2% Pb instead of regular water for 1 month. Rats pretreated, treated or post treated with vitamin E (150 mg/kg for 2 months. Passive avoidance learning was assessed using Shuttle-Box after two months. Retention was tested 24 and 48 hours after training. Results The results showed that Pb caused impairment in acquisition and retrieval processes in passive avoidance learning. Vitamin E reversed learning and memory deficits in pre, post or co- exposure with Pb (P < 0.001. Conclusions According to the results of this study, administration of vitamin E to rats counteracts the negative effects of Pb on learning and memory. To more precisely extrapolate these findings to humans, future clinical studies are warranted.

Human Neural Stem Cells Overexpressing Choline Acetyltransferase Restore Unconditioned Fear in Rats with Amygdala Injury

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Kyungha Shin

2016-01-01

Full Text Available Amygdala is involved in the fear memory that recognizes certain environmental cues predicting threatening events. Manipulation of neurotransmission within the amygdala affects the expression of conditioned and unconditioned emotional memories such as fear freezing behaviour. We previously demonstrated that F3.ChAT human neural stem cells (NSCs overexpressing choline acetyltransferase (ChAT improve cognitive function of Alzheimer’s disease model rats with hippocampal or cholinergic nerve injuries by increasing acetylcholine (ACh level. In the present study, we examined the effect of F3.ChAT cells on the deficit of unconditioned fear freezing. Rats given N-methyl-d-aspartate (NMDA in their amygdala 2 weeks prior to cat odor exposure displayed very short resting (freezing time compared to normal animals. NMDA induced neuronal degeneration in the amygdala, leading to a decreased ACh concentration in cerebrospinal fluid. However, intracerebroventricular transplantation of F3.ChAT cells attenuated amygdala lesions 4 weeks after transplantation. The transplanted cells were found in the NMDA-injury sites and produced ChAT protein. In addition, F3.ChAT-receiving rats recuperated freezing time staying remote from the cat odor source, according to the recovery of brain ACh concentration. The results indicate that human NSCs overexpressing ChAT may facilitate retrieval of unconditioned fear memory by increasing ACh level.

Effects of L-cysteine on lead acetate induced neurotoxicity in albino mice.

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Mahmoud, Y I; Sayed, S S

2016-07-01

Lead is a toxic heavy metal that adversely affects nervous tissues; it often occurs as an environmental pollutant. We investigated histological changes in the cerebral cortex, hippocampus and cerebellum of adult albino mice following exposure to lead acetate. We also studied the possible ameliorative effect of the chelating agent, L-cysteine, on lead-induced neurotoxicity. We divided albino mice into six groups: 1) vehicle-only control, 2) L-cysteine control, 3 and 4) treated for 7 days with 20 and 40 mg/kg lead acetate, respectively, and 5 and 6) treated for 7 days with 20 and 40 mg/kg lead acetate, respectively, followed by 50 mg/kg L-cysteine for 7 days. Lead acetate administration caused disorganization of cell layers, neuronal loss and degeneration, and neuropil vacuolization. Brain sections from lead-intoxicated mice treated with L-cysteine showed fewer pathological changes; the neuropil showed less vacuolization and the neurons appeared less damaged. L-cysteine at the dose we used only marginally alleviated lead-induced toxicity.

Hormonal regulation of phosphatidylcholine synthesis by reversible modulation of cytidylyltransferase.

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Kelly, K L; Gutierrez, G; Martin, A

1988-01-01

The effect of both lipolytic and antilipolytic hormones on the turnover of phosphatidylcholine in freshly isolated rat adipocytes was investigated. Treatment of adipocytes with agonists such as glucagon or isoprenaline that stimulate lipolysis through a cyclic AMP-dependent mechanism caused an increase in the incorporation of [Me-3H]choline into phosphatidylcholine. Pulse-chase studies indicated that the stimulation was due to an increase in the conversion of choline into phosphatidylcholine, which was both time- and dose-dependent. The stimulatory effect of isoprenaline was inhibited in a dose-dependent manner by oxytocin or insulin. Oxytocin inhibited the incorporation of [Me-3H]choline into phosphatidylcholine in both the presence and the absence of isoprenaline, whereas in the absence of isoprenaline insulin increased the incorporation of [Me-3H]choline into phosphatidylcholine. The effects of isoprenaline, oxytocin and insulin on the incorporation of [3H]choline into phosphatidylcholine were paralleled by changes in the activity of CTP:phosphocholine cytidylyltransferase. PMID:2849424

Choline kinase-alpha by regulating cell aggressiveness and drug sensitivity is a potential druggable target for ovarian cancer.

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Granata, A; Nicoletti, R; Tinaglia, V; De Cecco, L; Pisanu, M E; Ricci, A; Podo, F; Canevari, S; Iorio, E; Bagnoli, M; Mezzanzanica, D

2014-01-21

Aberrant choline metabolism has been proposed as a novel cancer hallmark. We recently showed that epithelial ovarian cancer (EOC) possesses an altered MRS-choline profile, characterised by increased phosphocholine (PCho) content to which mainly contribute over-expression and activation of choline kinase-alpha (ChoK-alpha). To assess its biological relevance, ChoK-alpha expression was downmodulated by transient RNA interference in EOC in vitro models. Gene expression profiling by microarray analysis and functional analysis was performed to identify the pathway/functions perturbed in ChoK-alpha-silenced cells, then validated by in vitro experiments. In silenced cells, compared with control, we observed: (I) a significant reduction of both CHKA transcript and ChoK-alpha protein expression; (II) a dramatic, proportional drop in PCho content ranging from 60 to 71%, as revealed by (1)H-magnetic spectroscopy analysis; (III) a 35-36% of cell growth inhibition, with no evidences of apoptosis or modification of the main cellular survival signalling pathways; (IV) 476 differentially expressed genes, including genes related to lipid metabolism. Ingenuity pathway analysis identified cellular functions related to cell death and cellular proliferation and movement as the most perturbed. Accordingly, CHKA-silenced cells displayed a significant delay in wound repair, a reduced migration and invasion capability were also observed. Furthermore, although CHKA silencing did not directly induce cell death, a significant increase of sensitivity to platinum, paclitaxel and doxorubicin was observed even in a drug-resistant context. We showed for the first time in EOC that CHKA downregulation significantly decreased the aggressive EOC cell behaviour also affecting cells' sensitivity to drug treatment. These observations open the way to further analysis for ChoK-alpha validation as a new EOC therapeutic target to be used alone or in combination with conventional drugs.

Biochemical adaptations of mammalian hibernation: exploring squirrels as a perspective model for naturally induced reversible insulin resistance

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Wu, C-W.; Biggar, K.K.; Storey, K.B. [Carleton University, Department of Biology, Institute of Biochemistry, Ottawa, ON (Canada)

2013-01-28

An important disease among human metabolic disorders is type 2 diabetes mellitus. This disorder involves multiple physiological defects that result from high blood glucose content and eventually lead to the onset of insulin resistance. The combination of insulin resistance, increased glucose production, and decreased insulin secretion creates a diabetic metabolic environment that leads to a lifetime of management. Appropriate models are critical for the success of research. As such, a unique model providing insight into the mechanisms of reversible insulin resistance is mammalian hibernation. Hibernators, such as ground squirrels and bats, are excellent examples of animals exhibiting reversible insulin resistance, for which a rapid increase in body weight is required prior to entry into dormancy. Hibernator studies have shown differential regulation of specific molecular pathways involved in reversible resistance to insulin. The present review focuses on this growing area of research and the molecular mechanisms that regulate glucose homeostasis, and explores the roles of the Akt signaling pathway during hibernation. Here, we propose a link between hibernation, a well-documented response to periods of environmental stress, and reversible insulin resistance, potentially facilitated by key alterations in the Akt signaling network, PPAR-γ/PGC-1α regulation, and non-coding RNA expression. Coincidentally, many of the same pathways are frequently found to be dysregulated during insulin resistance in human type 2 diabetes. Hence, the molecular networks that may regulate reversible insulin resistance in hibernating mammals represent a novel approach by providing insight into medical treatment of insulin resistance in humans.

Biochemical adaptations of mammalian hibernation: exploring squirrels as a perspective model for naturally induced reversible insulin resistance

International Nuclear Information System (INIS)

Wu, C-W.; Biggar, K.K.; Storey, K.B.

2013-01-01

An important disease among human metabolic disorders is type 2 diabetes mellitus. This disorder involves multiple physiological defects that result from high blood glucose content and eventually lead to the onset of insulin resistance. The combination of insulin resistance, increased glucose production, and decreased insulin secretion creates a diabetic metabolic environment that leads to a lifetime of management. Appropriate models are critical for the success of research. As such, a unique model providing insight into the mechanisms of reversible insulin resistance is mammalian hibernation. Hibernators, such as ground squirrels and bats, are excellent examples of animals exhibiting reversible insulin resistance, for which a rapid increase in body weight is required prior to entry into dormancy. Hibernator studies have shown differential regulation of specific molecular pathways involved in reversible resistance to insulin. The present review focuses on this growing area of research and the molecular mechanisms that regulate glucose homeostasis, and explores the roles of the Akt signaling pathway during hibernation. Here, we propose a link between hibernation, a well-documented response to periods of environmental stress, and reversible insulin resistance, potentially facilitated by key alterations in the Akt signaling network, PPAR-γ/PGC-1α regulation, and non-coding RNA expression. Coincidentally, many of the same pathways are frequently found to be dysregulated during insulin resistance in human type 2 diabetes. Hence, the molecular networks that may regulate reversible insulin resistance in hibernating mammals represent a novel approach by providing insight into medical treatment of insulin resistance in humans

Long-term improvements in sensory inhibition with gestational choline supplementation linked to α7 nicotinic receptors through studies in Chrna7 null mutation mice.

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Stevens, Karen E; Choo, Kevin S; Stitzel, Jerry A; Marks, Michael J; Adams, Catherine E

2014-03-13

Perinatal choline supplementation has produced several benefits in rodent models, from improved learning and memory to protection from the behavioral effects of fetal alcohol exposure. We have shown that supplemented choline through gestation and lactation produces long-term improvement in deficient sensory inhibition in DBA/2 mice which models a similar deficit in schizophrenia patients. The present study extends that research by feeding normal or supplemented choline diets to DBA/2 mice carrying the null mutation for the α7 nicotinic receptor gene (Chrna7). DBA/2 mice heterozygotic for Chrna7 were bred together. Dams were placed on supplemented (5 gm/kg diet) or normal (1.1 gm/kg diet) choline at mating and remained on the specific diet until offspring weaning. Thereafter, offspring were fed standard rodent chow. Adult offspring were assessed for sensory inhibition. Brains were obtained to ascertain hippocampal α7 nicotinic receptor levels. Choline-supplemented mice heterozygotic or null-mutant for Chrna7 failed to show improvement in sensory inhibition. Only wildtype choline-supplemented mice showed improvement with the effect solely through a decrease in test amplitude. This supports the hypothesis that gestational-choline supplementation is acting through the α7 nicotinic receptor to improve sensory inhibition. Although there was a significant gene-dose-related change in hippocampal α7 receptor numbers, binding studies did not reveal any choline-dose-related change in binding in any hippocampal region, the interaction being driven by a significant genotype main effect (wildtype>heterozygote>null mutant). These data parallel a human study wherein the offspring of pregnant women receiving choline supplementation during gestation, showed better sensory inhibition than offspring of women on placebo. Published by Elsevier B.V.

Antioxidant effects of Spirulina supplement against lead acetate-induced hepatic injury in rats

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Walid Hamdy El-Tantawy

2016-10-01

Full Text Available Lead is a toxic metal that induces a wide range of behavioral, biochemical and physiological effects in humans. Oxidative damage has been proposed as a possible mechanism involved in lead toxicity. The current study was carried out to evaluate the antioxidant activities of Spirulina supplement against lead acetate -induced hepatic injury in rats. Five groups of rats were used in this study, Control, Lead acetate (100 mg/kg, Lead acetate (100 mg/kg + 0.5 g/kg Spirulina, Lead acetate (100 mg/kg + 1 g/kg Spirulina and Lead acetate + 25 mg/100 g Vitamin C (reference drug. All experimental groups received the oral treatment by stomach tube once daily for 4 weeks. Lead intoxication resulted in a significant increase in serum alanine transaminae (ALT, aspartate transaminae (AST activities, liver homogenate tumor necrosis factor-α (TNF-α, caspase-3, malondialdehyde (MDA, nitric oxide (NO levels and a significant decline of total serum protein, liver homogenate reduced glutathione (GSH level and superoxide dismutase (SOD activity. Both doses of Spirulina supplement as well as Vitamin C succeeded to improve the biochemical parameters of serum and liver and prevented the lead acetate-induced significant changes on plasma and antioxidant status of the liver. Both doses of Spirulina supplement had the same anti-apoptotic activity and high dose exhibited more antioxidant activity than that of low dose. In conclusion, the results of the present work revealed that Spirulina supplement had protective, antioxidant and anti-apoptotic effects on lead acetate-induced hepatic damage.

Choline chloride based ionic liquid analogues as tool for the fabrication of agar films with improved mechanical properties

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In the present paper, we test the suitability of Choline-Cl/urea (DES-U) and Choline-Cl/glycerol (DES-G) eutectic mixtures at 1:2 molar ratios for the production of agar biodegradable films. A three-step process is proposed: pre-solubilization of polymer in DES followed by compression-molding and s...

Genetic signatures in choline and 1-carbon metabolism are associated with the severity of hepatic steatosis

Science.gov (United States)

Corbin, Karen D.; Abdelmalek, Manal F.; Spencer, Melanie D.; da Costa, Kerry-Ann; Galanko, Joseph A.; Sha, Wei; Suzuki, Ayako; Guy, Cynthia D.; Cardona, Diana M.; Torquati, Alfonso; Diehl, Anna Mae; Zeisel, Steven H.

2013-01-01

Choline metabolism is important for very low-density lipoprotein secretion, making this nutritional pathway an important contributor to hepatic lipid balance. The purpose of this study was to assess whether the cumulative effects of multiple single nucleotide polymorphisms (SNPs) across genes of choline/1-carbon metabolism and functionally related pathways increase susceptibility to developing hepatic steatosis. In biopsy-characterized cases of nonalcoholic fatty liver disease and controls, we assessed 260 SNPs across 21 genes in choline/1-carbon metabolism. When SNPs were examined individually, using logistic regression, we only identified a single SNP (PNPLA3 rs738409) that was significantly associated with severity of hepatic steatosis after adjusting for confounders and multiple comparisons (P=0.02). However, when groupings of SNPs in similar metabolic pathways were defined using unsupervised hierarchical clustering, we identified groups of subjects with shared SNP signatures that were significantly correlated with steatosis burden (P=0.0002). The lowest and highest steatosis clusters could also be differentiated by ethnicity. However, unique SNP patterns defined steatosis burden irrespective of ethnicity. Our results suggest that analysis of SNP patterns in genes of choline/1-carbon metabolism may be useful for prediction of severity of steatosis in specific subsets of people, and the metabolic inefficiencies caused by these SNPs should be examined further.—Corbin, K. D., Abdelmalek, M. F., Spencer, M. D., da Costa, K.-A., Galanko, J. A., Sha, W., Suzuki, A., Guy, C. D., Cardona, D. M., Torquati, A., Diehl, A. M., Zeisel, S. H. Genetic signatures in choline and 1-carbon metabolism are associated with the severity of hepatic steatosis. PMID:23292069

Reversal or protection by light of the ethidium bromide induced petite mutation in yeast

International Nuclear Information System (INIS)

Hixon, S.C.; Burnham, A.D.; Irons, R.L.

1979-01-01

An intermediate in the ethidium bromide (EB) induced petite mutation pathway may be destabilized by daylight light to cause a reversion to the normal grande phenotype. Starved cells preincubated in the dark for up to 6 h with 100μg/ml EB could be reverted to grandes after one hour of light exposure, whereas similarly treated cells maintained in the dark expresse the petite mutation in more than 80 percent of the population. In addition, the production of petite mutants by EB in buffer could be prevented if cell suspensions were exposed to light immediately upon the addition of EB. Photoreversal of the EB-derived petite mutation in growing cells as less efficient presumably because the availability of an energy source caused a continuation of mutation events beyond the light revertible step to a non-reversible fixation of the mutation. Cells treated with EB in growth and reversal of the mutation. This may be due to the cold inhibition of an enzyme which comes into play beyond the light sensitive step in the mutation pathway. (orig.) [de

Lactobacillus salivarius reverse diabetes-induced intestinal defense impairment in mice through non-defensin protein.

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Chung, Pei-Hsuan; Wu, Ying-Ying; Chen, Pei-Hsuan; Fung, Chang-Phone; Hsu, Ching-Mei; Chen, Lee-Wei

2016-09-01

Altered intestinal microbiota and subsequent endotoxemia play pathogenic roles in diabetes. We aimed to study the mechanisms of intestinal defense impairment in type 1 diabetes and the effects of Lactobacillus salivarius as well as fructooligosaccharides (FOS) supplementation on diabetes-induced bacterial translocation. Alterations in the enteric microbiome, expression of mucosal antibacterial proteins and bacteria-killing activity of the intestinal mucosa in streptozotocin (STZ)-induced diabetic mice and Ins2(Akita) mice were investigated. The effects of dead L. salivarius (2×10(8)CFU/ml) and FOS (250 mg per day) supplementation for 1 week on endotoxin levels and Klebsiella pneumoniae translocation were also examined. Finally, germ-free mice were cohoused with wild-type or Ins2(Akita) mice for 2 weeks to examine the contribution of microbiota on the antibacterial protein expression. STZ-induced diabetic mice developed intestinal defense impairment as demonstrated by decreased mucosal bacteria-killing activity; reduction of non-defensin family proteins, such as Reg3β, Reg3γ, CRP-ductin and RELMβ, but not the defensin family proteins; and increased bacterial translocation. Intestinal bacteria overgrowth, enteric dysbiosis and increased intestinal bacterial translocation, particularly pathogenic K. pneumoniae in STZ-induced diabetic mice and Ins2(Akita) mice, were noted. Treating diabetic mice with dead L. salivarius or FOS reversed enteric dysbiosis, restored mucosal antibacterial protein and lessened endotoxin levels as well as K. pneumoniae translocation. Moreover, germ-free mice cohoused with wild-type mice demonstrated more intestinal Reg3β and RELMβ expression than those cohoused with Ins2(Akita) mice. These results indicate that hyperglycemia induces enteric dysbiosis, reduction of non-defensin proteins as well as bacteria-killing activity of the intestinal mucosa and intestinal defense impairment. Reversal of enteric dysbiosis with dead L. salivarius or

A randomized, dose-response study of sugammadex given for the reversal of deep rocuronium- or vecuronium-induced neuromuscular blockade under sevoflurane anesthesia

DEFF Research Database (Denmark)

Duvaldestin, Philippe; Kuizenga, Karel; Saldien, Vera

2010-01-01

Sugammadex is the first of a new class of selective muscle relaxant binding drugs developed for the rapid and complete reversal of neuromuscular blockade induced by rocuronium and vecuronium. Many studies have demonstrated a dose-response relationship with sugammadex for reversal of neuromuscular...

A Randomized, Dose-Response Study of Sugammadex Given for the Reversal of Deep Rocuronium- or Vecuronium-Induced Neuromuscular Blockade Under Sevoflurane Anesthesia

NARCIS (Netherlands)

Duvaldestin, Philippe; Kuizenga, Karel; Saldien, Vera; Claudius, Casper; Servin, Frederique; Klein, Jan; Debaene, Bertrand; Heeringa, Marten

BACKGROUND: Sugammadex is the first of a new class of selective muscle relaxant binding drugs developed for the rapid and complete reversal of neuromuscular blockade induced by rocuronium and vecuronium. Many studies have demonstrated a close-response relationship with sugammadex for reversal of

Quetiapine reverse paclitaxel-induced neuropathic pain in mice: Role of Alpha2- adrenergic receptors

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Alireza Abed

2017-11-01

Full Text Available Objective(s: Paclitaxel-induced peripheral neuropathy is a common adverse effect of cancer chemo -therapy. This neuropathy has a profound impact on quality of life and patient’s survival. Preventing and treating paclitaxel-induced peripheral neuropathy is a major concern. First- and second-generation antipsychotics have shown analgesic effects both in humans and animals. Quetiapine is a novel atypical antipsychotic with low propensity to induce extrapyramidal or hyperprolactinemia side effects. The present study was designed to investigate the effects of quetiapine on the development and expression of neuropathic pain induced by paclitaxel in mice and the role of α2-adrenoceptors on its antinociception. Materials and Methods: Paclitaxel (2 mg/kg IP was injected for five consecutive days which resulted in thermal hyperalgesia and mechanical and cold allodynia. Results: Early administration of quetiapine from the 1st day until the 5th day (5, 10, and 15 mg/kg PO did not affect thermal, mechanical, and cold stimuli and could not prevent the development of neuropathic pain. In contrast, when quetiapine (10 and 15 mg/kg PO administration was started on the 6th day after the first paclitaxel injections, once the model had been established, and given daily until the 10th day, heat hyperalgesia and mechanical and cold allodynia were significantly attenuated. Also, the effect of quetiapine on heat hyperalgesia was reversed by pretreatment with yohimbine, as an alpha-2 adrenergic receptor antagonist. Conclusion: These results indicate that quetiapine, when administered after nerve injury can reverse the expression of neuropathic pain. Also, we conclude that α2-adrenoceptors participate in the antinociceptive effects of quetiapine.

Glioprotective Effects of Ashwagandha Leaf Extract against Lead Induced Toxicity

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Praveen Kumar

2014-01-01

Full Text Available Withania somnifera (Ashwagandha, also known as Indian Ginseng, is a well-known Indian medicinal plant due to its antioxidative, antistress, antigenotoxic, and immunomodulatory properties. The present study was designed to assess and establish the cytoprotective potential of Ashwagandha leaf aqueous extract against lead induced toxicity. Pretreatment of C6 cells with 0.1% Ashwagandha extract showed cytoprotection against 25 μM to 400 μM concentration of lead nitrate. Further pretreatment with Ashwagandha extract to lead nitrate exposed cells (200 μM resulted in normalization of glial fibrillary acidic protein (GFAP expression as well as heat shock protein (HSP70, mortalin, and neural cell adhesion molecule (NCAM expression. Further, the cytoprotective efficacy of Ashwagandha extract was studied in vivo. Administration of Ashwagandha extract provided significant protection to lead induced altered antioxidant defense that may significantly compromise normal cellular function. Ashwagandha also provided a significant protection to lipid peroxidation (LPx levels, catalase, and superoxide dismutase (SOD but not reduced glutathione (GSH contents in brain tissue as well as peripheral organs, liver and kidney, suggesting its ability to act as a free radical scavenger protecting cells against toxic insult. These results, thus, suggest that Ashwagandha water extract may have the potential therapeutic implication against lead poisoning.

Vitamin C and Vitamin E in Prevention of Nonalcoholic Fatty Liver Disease (NAFLD in Choline Deficient Diet Fed Rats

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Lopasso Fabio P

2003-10-01

Full Text Available Abstract Aim Oxidative stress has been implicated in the pathogenesis of Nonalcoholic Fatty Liver Disease (NAFLD. Vitamin C and vitamin E are known to react with reactive oxygen species (ROS blocking the propagation of radical reactions in a wide range of oxidative stress situations. The potential therapeutic efficacy of antioxidants in NAFLD is unknown. The aim of this study was to evaluate the role of antioxidant drugs (vitamin C or vitamin E in its prevention. Methods Fatty liver disease was induced in Wistar rats by choline-deficient diet for four weeks. The rats were randomly assigned to receive vitamin E (n = 6 – (200 mg/day, vitamin C (n = 6 (30 mg/Kg/day or vehicle orally. Results In the vehicle and vitamin E-treated rats, there were moderate macro and microvesicular fatty changes in periportal area without inflammatory infiltrate or fibrosis. Scharlach stain that used for a more precise identification of fatty change was strong positive. With vitamin C, there was marked decrease in histological alterations. Essentially, there was no liver steatosis, only hepatocellular ballooning. Scharlach stain was negative. The lucigenin-enhanced luminescence was reduced with vitamin C (1080 ± 330 cpm/mg/minx103 as compared to those Vitamin E and control (2247 ± 790; 2020 ± 407 cpm/mg/minx103, respectively (p Conclusions 1 Vitamin C reduced oxidative stress and markedly inhibited the development of experimental liver steatosis induced by choline-deficient diet ; 2Vitamin E neither prevented the development of fatty liver nor reduced the oxidative stress in this model.

Effect of quinolinic acid in the nucleus basalis magnocellularis on cortical high-affinity choline uptake

Energy Technology Data Exchange (ETDEWEB)

Metcalf, R.H.; Boegman, R.J.; Quirion, R.; Riopelle, R.J.; Ludwin, S.K.

1987-08-01

A transient 45% increase in cortical high-affinity choline uptake (HACU) was observed after an injection of quinolinic acid (QUIN) into the nucleus basalis magnocellularis (nbM) of the rat. This was followed by a steady decline in choline uptake, which resulted in a 46% decrease by day 7. Specific (/sup 3/H)hemicholinium-3 binding to coronal brain sections showed a similar pattern following injections of QUIN into the nbM. The increase in cortical HACU elicited by QUIN appeared to be dose dependent.

Eggs early in complementary feeding increase choline pathway biomarkers and DHA: a randomized controlled trial in Ecuador.

Science.gov (United States)

Iannotti, Lora L; Lutter, Chessa K; Waters, William F; Gallegos Riofrío, Carlos Andres; Malo, Carla; Reinhart, Gregory; Palacios, Ana; Karp, Celia; Chapnick, Melissa; Cox, Katherine; Aguirre, Santiago; Narvaez, Luis; López, Fernando; Sidhu, Rohini; Kell, Pamela; Jiang, Xuntian; Fujiwara, Hideji; Ory, Daniel S; Young, Rebecca; Stewart, Christine P

2017-12-01

Background: Choline status has been associated with stunting among young children. Findings from this study showed that an egg intervention improved linear growth by a length-for-age z score of 0.63. Objective: We aimed to test the efficacy of eggs introduced early in complementary feeding on plasma concentrations of biomarkers in choline pathways, vitamins B-12 and A, and essential fatty acids. Design: A randomized controlled trial, the Lulun ("egg" in Kichwa) Project, was conducted in a rural indigenous population of Ecuador. Infants aged 6-9 mo were randomly assigned to treatment (1 egg/d for 6 mo; n = 80) and control (no intervention; n = 83) groups. Socioeconomic data, anthropometric measures, and blood samples were collected at baseline and endline. Household visits were made weekly for morbidity surveillance. We tested vitamin B-12 plasma concentrations by using chemiluminescent competitive immunoassay and plasma concentrations of choline, betaine, dimethylglycine, retinol, essential fatty acids, methionine, dimethylamine (DMA), trimethylamine, and trimethylamine- N -oxide (TMAO) with the use of liquid chromatography-tandem mass spectrometry. Results: Socioeconomic factors and biomarker concentrations were comparable at baseline. Of infants, 11.4% were vitamin B-12 deficient and 31.7% marginally deficient at baseline. In adjusted generalized linear regression modeling, the egg intervention increased plasma concentrations compared with control by the following effect sizes: choline, 0.35 (95% CI: 0.12, 0.57); betaine, 0.29 (95% CI: 0.01, 0.58); methionine, 0.31 (95% CI: 0.03, 0.60); docosahexaenoic acid, 0.43 (95% CI: 0.13, 0.73); DMA, 0.37 (95% CI: 0.37, 0.69); and TMAO, 0.33 (95% CI: 0.08, 0.58). No significant group differences were found for vitamin B-12, retinol, linoleic acid (LA), α-linolenic acid (ALA), or ratios of betaine to choline and LA to ALA. Conclusion: The findings supported our hypothesis that early introduction of eggs significantly

Blockage of High-Affinity Choline Transporter Increases Visceral Hypersensitivity in Rats with Chronic Stress

Science.gov (United States)

2018-01-01

Background Visceral hypersensitivity is a common feature of irritable bowel syndrome. Cholinergic system involves in the development of visceral hypersensitivity, and high-affinity choline transporter (CHT1) is of crucial importance in choline uptake system. However, involvement of CHT1 in visceral hypersensitivity remains unknown. The research aimed to study the CHT1 expression in dorsal root ganglions (DRGs) and the role of CHT1 in visceral hypersensitivity. Methods Repetitive water avoidance stress (WAS) was used to induce visceral hypersensitivity in rats. Colorectal distension (CRD) was determined, and the abdominal withdrawal reflex (AWR) and threshold intensity data were recorded to measure the visceral sensitivity. After intraperitoneal injection of hemicholinium-3 (HC-3), the specific inhibitor of CHT1, CRD data were also recorded. The CHT1 expression of DRGs was investigated by Western blotting, immunohistochemistry, and quantitative RT-PCR. Acetylcholine levels in the DRGs were detected by the assay kit. Results Repetitive WAS increased the AWR score of CRD at high distension pressure and decreased the mean threshold of rats. The CHT1 expression and acetylcholine concentration of DRG were significantly increased in WAS rats. After the administration of HC-3, the AWR score in WAS group was significantly increased at higher distension pressure while the threshold intensity was significantly reduced compared to the normal saline group. Acetylcholine concentration was significantly lower than the normal saline rats. Conclusion Our research firstly reports that CHT1 is overexpressed in noninflammatory visceral hypersensitivity, and blockage of CHT1 can enhance the visceral hypersensitivity. CHT1 may play an inhibitory role in visceral hypersensitivity. PMID:29849603

A transient ischemic environment induces reversible compaction of chromatin.

Science.gov (United States)

Kirmes, Ina; Szczurek, Aleksander; Prakash, Kirti; Charapitsa, Iryna; Heiser, Christina; Musheev, Michael; Schock, Florian; Fornalczyk, Karolina; Ma, Dongyu; Birk, Udo; Cremer, Christoph; Reid, George

2015-11-05

Cells detect and adapt to hypoxic and nutritional stress through immediate transcriptional, translational and metabolic responses. The environmental effects of ischemia on chromatin nanostructure were investigated using single molecule localization microscopy of DNA binding dyes and of acetylated histones, by the sensitivity of chromatin to digestion with DNAseI, and by fluorescence recovery after photobleaching (FRAP) of core and linker histones. Short-term oxygen and nutrient deprivation of the cardiomyocyte cell line HL-1 induces a previously undescribed chromatin architecture, consisting of large, chromatin-sparse voids interspersed between DNA-dense hollow helicoid structures 40-700 nm in dimension. The chromatin compaction is reversible, and upon restitution of normoxia and nutrients, chromatin transiently adopts a more open structure than in untreated cells. The compacted state of chromatin reduces transcription, while the open chromatin structure induced upon recovery provokes a transitory increase in transcription. Digestion of chromatin with DNAseI confirms that oxygen and nutrient deprivation induces compaction of chromatin. Chromatin compaction is associated with depletion of ATP and redistribution of the polyamine pool into the nucleus. FRAP demonstrates that core histones are not displaced from compacted chromatin; however, the mobility of linker histone H1 is considerably reduced, to an extent that far exceeds the difference in histone H1 mobility between heterochromatin and euchromatin. These studies exemplify the dynamic capacity of chromatin architecture to physically respond to environmental conditions, directly link cellular energy status to chromatin compaction and provide insight into the effect ischemia has on the nuclear architecture of cells.

Cladribine and Fludarabine Nucleotides Induce Distinct Hexamers Defining a Common Mode of Reversible RNR Inhibition.

Science.gov (United States)

Wisitpitthaya, Somsinee; Zhao, Yi; Long, Marcus J C; Li, Minxing; Fletcher, Elaine A; Blessing, William A; Weiss, Robert S; Aye, Yimon

2016-07-15

The enzyme ribonucleotide reductase (RNR) is a major target of anticancer drugs. Until recently, suicide inactivation in which synthetic substrate analogs (nucleoside diphosphates) irreversibly inactivate the RNR-α2β2 heterodimeric complex was the only clinically proven inhibition pathway. For instance, this mechanism is deployed by the multifactorial anticancer agent gemcitabine diphosphate. Recently reversible targeting of RNR-α-alone coupled with ligand-induced RNR-α-persistent hexamerization has emerged to be of clinical significance. To date, clofarabine nucleotides are the only known example of this mechanism. Herein, chemoenzymatic syntheses of the active forms of two other drugs, phosphorylated cladribine (ClA) and fludarabine (FlU), allow us to establish that reversible inhibition is common to numerous drugs in clinical use. Enzyme inhibition and fluorescence anisotropy assays show that the di- and triphosphates of the two nucleosides function as reversible (i.e., nonmechanism-based) inhibitors of RNR and interact with the catalytic (C site) and the allosteric activity (A site) sites of RNR-α, respectively. Gel filtration, protease digestion, and FRET assays demonstrate that inhibition is coupled with formation of conformationally diverse hexamers. Studies in 293T cells capable of selectively inducing either wild-type or oligomerization-defective mutant RNR-α overexpression delineate the central role of RNR-α oligomerization in drug activity, and highlight a potential resistance mechanism to these drugs. These data set the stage for new interventions targeting RNR oligomeric regulation.

Comparison between the efficacies of curcumin and puerarin in C57BL/6 mice with steatohepatitis induced by a methionine- and choline-deficient diet.

Science.gov (United States)

Wang, Yunliang; Li, Jian; Zhuge, Li; Su, Dongmei; Yang, Meijuan; Tao, Shiying; Li, Junxiang

2014-03-01

Non-alcoholic fatty liver disease (NAFLD) is a prevalent disease, which features an abnormal accumulation of lipids inside hepatocytes. Steatohepatitis plays a critical role in the process resulting in liver fibrosis and cirrhosis. Curcumin and puerarin are herbal products widely used in Asia, which are believed to have therapeutic benefits for alleviating the symptoms of steatohepatitis. In this study, mice models of steatohepatitis induced by a methionine- and choline-deficient diet (MCD) were established to compare the pharmacological actions of curcumin and puerarin. The results showed that curcumin and puerarin exerted inhibitory effects against MCD-induced steatohepatitis in mice. Briefly, curcumin and puerarin significantly downregulated the levels of tumor necrosis factor-α in the blood serum of mice (PMCD group). In addition, the levels of triglycerides, total cholesterol and low density lipoproteins in the serum were significantly reduced by puerarin treatment (PMCD group). The concentration of interleukin-6 was downregulated by curcumin only (PMCD group). Curcumin and puerarin significantly increased the levels of peroxisome proliferator-activated receptor-γ (PPARγ; PMCD group). Moreover, increased nuclear factor-κB (NF-κB) was markedly attenuated by curcumin (PMCD group). In conclusion, curcumin and puerarin appear to exert different actions against steatohepatitis. It is possible that puerarin regulated lipid metabolism in the 'first hit' stage through the PPARγ pathway, while curcumin inhibited the inflammatory response in the 'second hit' stage through the NF-κB pathway.

Role of bone marrow cells in the development of pancreatic fibrosis in a rat model of pancreatitis induced by a choline-deficient/ethionine-supplemented diet

Energy Technology Data Exchange (ETDEWEB)

Akita, Shingo; Kubota, Koji [Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621 (Japan); Kobayashi, Akira, E-mail: kbys@shinshu-u.ac.jp [Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621 (Japan); Misawa, Ryosuke; Shimizu, Akira; Nakata, Takenari; Yokoyama, Takahide [Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621 (Japan); Takahashi, Masafumi [Center for Molecular Medicine Division of Bioimaging Sciences, Jichi Medical University, 3311-1 Yakushiji, Shimono, Tochigi 329-0498 (Japan); Miyagawa, Shinichi [Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621 (Japan)

2012-04-20

Highlights: Black-Right-Pointing-Pointer BMC-derived PSCs play a role in a rat CDE diet-induced pancreatitis model. Black-Right-Pointing-Pointer BMC-derived PSCs contribute mainly to the early stage of pancreatic fibrosis. Black-Right-Pointing-Pointer BMC-derived activated PSCs can produce PDGF and TGF {beta}1. -- Abstract: Bone marrow cell (BMC)-derived myofibroblast-like cells have been reported in various organs, including the pancreas. However, the contribution of these cells to pancreatic fibrosis has not been fully discussed. The present study examined the possible involvement of pancreatic stellate cells (PSCs) originating from BMCs in the development of pancreatic fibrosis in a clinically relevant rat model of acute pancreatitis induced by a choline-deficient/ethionine-supplemented (CDE) diet. BMCs from female transgenic mice ubiquitously expressing green fluorescent protein (GFP) were transplanted into lethally irradiated male rats. Once chimerism was established, acute pancreatitis was induced by a CDE diet. Chronological changes in the number of PSCs originating from the donor BMCs were examined using double immunofluorescence for GFP and markers for PSCs, such as desmin and alpha smooth muscle actin ({alpha}SMA), 1, 3 and 8 weeks after the initiation of CDE feeding. We also used immunohistochemical staining to evaluate whether the PSCs from the BMCs produce growth factors, such as platelet-derived growth factor (PDGF) and transforming growth factor (TGF) {beta}1. The percentage of BMC-derived activated PSCs increased significantly, peaking after 1 week of CDE treatment (accounting for 23.3 {+-} 0.9% of the total population of activated PSCs) and then decreasing. These cells produced both PDGF and TGF{beta}1 during the early stage of pancreatic fibrosis. Our results suggest that PSCs originating from BMCs contribute mainly to the early stage of pancreatic injury, at least in part, by producing growth factors in a rat CDE diet-induced pancreatitis model.

Role of bone marrow cells in the development of pancreatic fibrosis in a rat model of pancreatitis induced by a choline-deficient/ethionine-supplemented diet

International Nuclear Information System (INIS)

Akita, Shingo; Kubota, Koji; Kobayashi, Akira; Misawa, Ryosuke; Shimizu, Akira; Nakata, Takenari; Yokoyama, Takahide; Takahashi, Masafumi; Miyagawa, Shinichi

2012-01-01

Highlights: ► BMC-derived PSCs play a role in a rat CDE diet-induced pancreatitis model. ► BMC-derived PSCs contribute mainly to the early stage of pancreatic fibrosis. ► BMC-derived activated PSCs can produce PDGF and TGF β1. -- Abstract: Bone marrow cell (BMC)-derived myofibroblast-like cells have been reported in various organs, including the pancreas. However, the contribution of these cells to pancreatic fibrosis has not been fully discussed. The present study examined the possible involvement of pancreatic stellate cells (PSCs) originating from BMCs in the development of pancreatic fibrosis in a clinically relevant rat model of acute pancreatitis induced by a choline-deficient/ethionine-supplemented (CDE) diet. BMCs from female transgenic mice ubiquitously expressing green fluorescent protein (GFP) were transplanted into lethally irradiated male rats. Once chimerism was established, acute pancreatitis was induced by a CDE diet. Chronological changes in the number of PSCs originating from the donor BMCs were examined using double immunofluorescence for GFP and markers for PSCs, such as desmin and alpha smooth muscle actin (αSMA), 1, 3 and 8 weeks after the initiation of CDE feeding. We also used immunohistochemical staining to evaluate whether the PSCs from the BMCs produce growth factors, such as platelet-derived growth factor (PDGF) and transforming growth factor (TGF) β1. The percentage of BMC-derived activated PSCs increased significantly, peaking after 1 week of CDE treatment (accounting for 23.3 ± 0.9% of the total population of activated PSCs) and then decreasing. These cells produced both PDGF and TGFβ1 during the early stage of pancreatic fibrosis. Our results suggest that PSCs originating from BMCs contribute mainly to the early stage of pancreatic injury, at least in part, by producing growth factors in a rat CDE diet-induced pancreatitis model.

MiADMSA reverses impaired mitochondrial energy metabolism and neuronal apoptotic cell death after arsenic exposure in rats

Energy Technology Data Exchange (ETDEWEB)

Dwivedi, Nidhi; Mehta, Ashish; Yadav, Abhishek [Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior-474 002 (India); Binukumar, B.K.; Gill, Kiran Dip [Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh-160 012 (India); Flora, Swaran J.S., E-mail: sjsflora@hotmail.com [Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior-474 002 (India)

2011-11-15

Arsenicosis, due to contaminated drinking water, is a serious health hazard in terms of morbidity and mortality. Arsenic induced free radicals generated are known to cause cellular apoptosis through mitochondrial driven pathway. In the present study, we investigated the effect of arsenic interactions with various complexes of the electron transport chain and attempted to evaluate if there was any complex preference of arsenic that could trigger apoptosis. We also evaluated if chelation with monoisoamyl dimercaptosuccinic acid (MiADMSA) could reverse these detrimental effects. Our results indicate that arsenic exposure induced free radical generation in rat neuronal cells, which diminished mitochondrial potential and enzyme activities of all the complexes of the electron transport chain. Moreover, these complexes showed differential responses towards arsenic. These early events along with diminished ATP levels could be co-related with the later events of cytosolic migration of cytochrome c, altered bax/bcl{sub 2} ratio, and increased caspase 3 activity. Although MiADMSA could reverse most of these arsenic-induced altered variables to various extents, DNA damage remained unaffected. Our study for the first time demonstrates the differential effect of arsenic on the complexes leading to deficits in bioenergetics leading to apoptosis in rat brain. However, more in depth studies are warranted for better understanding of arsenic interactions with the mitochondria. -- Research highlights: Black-Right-Pointing-Pointer Arsenic impairs mitochondrial energy metabolism leading to neuronal apoptosis. Black-Right-Pointing-Pointer Arsenic differentially affects mitochondrial complexes, I - III and IV being more sensitive than complex II. Black-Right-Pointing-Pointer Arsenic-induced apoptosis initiates through ROS generation or impaired [Ca{sup 2+}]i homeostasis. Black-Right-Pointing-Pointer MiADMSA reverses arsenic toxicity via intracellular arsenic- chelation, antioxidant

Detection of choline transporter-like 1 protein CTL1 in neuroblastoma × glioma cells and in the CNS, and its role in choline uptake

Czech Academy of Sciences Publication Activity Database

Machová, Eva; O´Regan, S.; Newcombe, J.; Meunier, F. M.; Prentice, J.; Dove, R.; Lisá, Věra; Doležal, Vladimír

2009-01-01

Roč. 110, č. 4 (2009), s. 1297-1309 ISSN 0022-3042 R&D Projects: GA MŠk(CZ) LC554; GA AV ČR(CZ) IAA500110703 Institutional research plan: CEZ:AV0Z50110509 Keywords : CTL1 * choline * cell growth Subject RIV: ED - Physiology Impact factor: 3.999, year: 2009

Strain-assisted current-induced magnetization reversal in magnetic tunnel junctions: A micromagnetic study with phase-field microelasticity

International Nuclear Information System (INIS)

Huang, H. B.; Hu, J. M.; Yang, T. N.; Chen, L. Q.; Ma, X. Q.

2014-01-01

Effect of substrate misfit strain on current-induced in-plane magnetization reversal in CoFeB-MgO based magnetic tunnel junctions is investigated by combining micromagnetic simulations with phase-field microelasticity theory. It is found that the critical current density for in-plane magnetization reversal decreases dramatically with an increasing substrate strain, since the effective elastic field can drag the magnetization to one of the four in-plane diagonal directions. A potential strain-assisted multilevel bit spin transfer magnetization switching device using substrate misfit strain is also proposed.

Evaluation of Positron Emission Tomographic Tracers for Imaging of Papillomavirus-Induced Tumors in Rabbits

Directory of Open Access Journals (Sweden)

Sonja Probst

2014-01-01

Full Text Available In this study, simultaneous positron emission tomography (PET/magnetic resonance (MR imaging was employed to evaluate the feasibility of the PET tracers 2-deoxy-2-18F-fluoro-D-glucose (18F-FDG, 11C-choline, and 18F-fluorothymidine (18F-FLT to detect papillomavirus-induced tumors in an established rabbit model system. The combined PET/MR allowed the analysis of tracer uptake of the tumors using the morphologic information acquired by MR. New Zealand White rabbits were infected with cottontail rabbit papillomavirus genomes and were imaged for up to 10 months with a simultaneous PET/MR system during the course of infection. The uptake characteristics of the PET tracers 11C-choline and 18F-FLT of tumors and reference tissues were examined relative to the clinical standard, 18F-FDG. Tracer biodistribution of various organs was measured by gamma-counting after the last PET scan and compared to the in vivo PET/MR 18F-FDG uptake. Increased tracer uptake was found 2 months postinfection in primary tumors with 18F-FDG and 11C-choline, whereas 18F-FLT failed to detect the tumors at all measured time points. Our data show that the PET tracer 18F-FDG is superior for imaging papillomavirus-induced tumors in rabbits compared to 11C-choline and 18F-FLT. However, 11C-choline imaging, which has previously been applied to detect various tumor entities in patients, appears to be an alternative to 18F-FDG.

11C-Choline PET/pathology image coregistration in primary localized prostate cancer

International Nuclear Information System (INIS)

Grosu, Anca-Ligia; Prokic, Vesna; Weirich, Gregor; Wendl, Christina; Geinitz, Hans; Molls, Michael; Kirste, Simon; Souvatzoglou, Michael; Schwaiger, Markus; Gschwend, Juergen E.; Treiber, Uwe; Weber, Wolfgang A.; Krause, Bernd Joachim

2014-01-01

The aim of this study was to develop a methodology for the comparison of pathology specimens after prostatectomy (post-S) with PET images obtained before surgery (pre-S). This method was used to evaluate the merit of 11 C-choline PET/CT for delineation of gross tumour volume (GTV) in prostate cancer (PC). In 28 PC patients, 11 C-choline PET/CT was performed before surgery. PET/CT data were coregistered with the pathology specimens. GTV on PET images (GTV-PET) was outlined automatically and corrected manually. Tumour volume in the prostate (TVP) was delineated manually on the pathology specimens. Based on the coregistered PET/pathology images, the following parameters were assessed: SUVmax and SUVmean in the tumoral and nontumoral prostate (NP), GTV-PET (millilitres) and TVP (millilitres). PET/pathology image coregistration was satisfactory. Mean SUVmax in the TVP was lower than in the NP: 5.0 and 5.5, respectively (p = 0.093). Considering the entire prostate, SUVmax was located in the TVP in two patients, in the TVP and NP in 12 patients and exclusively in NP in 14 patients. Partial overlap the TVP and GTV-PET was seen in 71 % of patients, and complete overlap in 4 %. PET/pathology image coregistration can be used for evaluation of different imaging modalities. 11 C-Choline PET failed to distinguish tumour from nontumour tissue. (orig.)

Interplay between autophagy and apoptosis in lead(II)-induced cytotoxicity of primary rat proximal tubular cells.

Science.gov (United States)

Chu, Bing-Xin; Fan, Rui-Feng; Lin, Shu-Qian; Yang, Du-Bao; Wang, Zhen-Yong; Wang, Lin

2018-05-01

Autophagy and apoptosis are two different biological processes that determine cell fates. We previously reported that autophagy inhibition and apoptosis induction are involved in lead(II)-induced cytotoxicity in primary rat proximal tubular (rPT) cells, but the interplay between them remains to be elucidated. Firstly, data showed that lead(II)-induced elevation of LC3-II protein levels can be significantly modulated by 3-methyladenine or rapamycin; moreover, protein levels of Autophagy-related protein 5 (Atg5) and Beclin-1 were markedly up-regulated by lead(II) treatment, demonstrating that lead(II) could promote the autophagosomes formation in rPT cells. Next, we applied three pharmacological agents and genetic method targeting the early stage of autophagy to validate that enhancement of autophagosomes formation can inhibit lead(II)-induced apoptotic cell death in rPT cells. Simultaneously, lead(II) inhibited the autophagic degradation of rPT cells, while the addition of autophagic degradation inhibitor bafilomycin A1 aggravated lead(II)-induced apoptotic death in rPT cells. Collectively, this study provided us a good model to know about the dynamic process of lead(II)-induced autophagy in rPT cells, and the interplay between autophagy and apoptosis highlights a new sight into the mechanism of lead(II)-induced nephrotoxicity. Copyright © 2018. Published by Elsevier Inc.

An efficient and green method for regio- and chemo-selective Friedel–Crafts acylations using a deep eutectic mixture ([CholineCl][ZnCl2]3)

DEFF Research Database (Denmark)

Hoang, Tran Phuong; Nguyen, Hai Truong; Hansen, Poul Erik

2016-01-01

[CholineCl][ZnCl2]3, a deep eutectic solvent between choline chloride and ZnCl2, has been used as a dual function catalyst and green solvent for the Friedel–Crafts acylation of aromatic compounds instead of using the moisture-sensitive Lewis acids and volatile organic solvents. The reactions...... are performed with high yields under microwave irradiation with short reaction times for the synthesis of ketones. Interestingly, indole derivatives are regioselectively acylated in the 3-position under mild conditions with high yields without NH protection. Three new ketone products are synthesized. [Choline......Cl][ZnCl2]3 is easily synthesized from choline chloride and zinc chloride at a low cost, with easy purification and environmentally benign compounds. [CholineCl][ZnCl2]3 can be reused up to five times without loss of catalytic activity, making it ideal in industrial processes....

Dose-dependency and reversibility of radiation-induced injury in cardiac explant-derived cells of mice

Science.gov (United States)

Luo, Lan; Yan, Chen; Urata, Yoshishige; Hasan, Al Shaimaa; Goto, Shinji; Guo, Chang-Ying; Zhang, Shouhua; Li, Tao-Sheng

2017-01-01

We evaluated the dose-dependency and reversibility of radiation-induced injury in cardiac explant-derived cells (CDCs), a mixed cell population grown from heart tissues. Adult C57BL/6 mice were exposed to 0, 10, 50 and 250 mGy γ-rays for 7 days and atrial tissues were collected for experiments 24 hours after last exposure. The number of CDCs was significantly decreased by daily exposure to over 250 mGy. Interestingly, daily exposure to over 50 mGy significantly decreased the c-kit expression and telomerase activity, increased 53BP1 foci in the nuclei of CDCs. However, CD90 expression and growth factors production in CDCs were not significantly changed even after daily exposure to 250 mGy. We further evaluated the reversibility of radiation-induced injury in CDCs at 1 week and 3 weeks after a single exposure to 3 Gy γ-rays. The number and growth factors production of CDCs were soon recovered at 1 week. However, the increased expression of CD90 were retained at 1 week, but recovered at 3 weeks. Moreover, the decreased expression of c-kit, impaired telomerase activity, and increased 53BP1 foci were poorly recovered even at 3 weeks. These data may help us to find the most sensitive and reliable bio-parameter(s) for evaluating radiation-induced injury in CDCs. PMID:28098222

Acute agmatine administration, similar to ketamine, reverses depressive-like behavior induced by chronic unpredictable stress in mice.

Science.gov (United States)

Neis, Vivian B; Bettio, Luis E B; Moretti, Morgana; Rosa, Priscila B; Ribeiro, Camille M; Freitas, Andiara E; Gonçalves, Filipe M; Leal, Rodrigo B; Rodrigues, Ana Lúcia S

Agmatine is an endogenous neuromodulator that has been shown to have antidepressant-like properties. We have previously demonstrated that it can induce a rapid increase in BDNF levels after acute administration, suggesting that agmatine may be a fast-acting antidepressant. To investigate this hypothesis, the present study evaluated the effects of a single administration of agmatine in mice subjected to chronic unpredictable stress (CUS), a model of depression responsive only to chronic treatment with conventional antidepressants. The ability of agmatine to reverse CUS-induced behavioral and biochemical alterations was evaluated and compared with those elicited by the fast-acting antidepressant (ketamine) and the conventional antidepressant (fluoxetine). After exposed to CUS for 14days, mice received a single oral dose of agmatine (0.1mg/kg), ketamine (1mg/kg) or fluoxetine (10mg/kg), and were submitted to behavioral evaluation after 24h. The exposure to CUS caused an increased immobility time in the tail suspension test (TST) but did not change anhedonic-related parameters in the splash test. Our findings provided evidence that, similarly to ketamine, agmatine is able to reverse CUS-induced depressive-like behavior in the TST. Western blot analyses of prefrontal cortex (PFC) demonstrated that mice exposed to CUS and/or treated with agmatine, fluoxetine or ketamine did not present alterations in the immunocontent of synaptic proteins [i.e. GluA1, postsynaptic density protein 95 (PSD-95) and synapsin]. Altogether, our findings indicate that a single administration of agmatine is able to reverse behavioral alterations induced by CUS in the TST, suggesting that this compound may have fast-acting antidepressant-like properties. However, there was no alteration in the levels of synaptic proteins in the PFC, a result that need to be further investigated in other time points. Copyright © 2016 Elsevier Inc. All rights reserved.

Glutamine/glutamate (Glx) concentration in prefrontal cortex predicts reversal learning performance in the marmoset.

Science.gov (United States)

Lacreuse, Agnès; Moore, Constance M; LaClair, Matthew; Payne, Laurellee; King, Jean A

2018-07-02

This study used Magnetic Resonance Spectroscopy (MRS) to identify potential neurometabolitic markers of cognitive performance in male (n = 7) and female (n = 8) middle-aged (∼5 years old) common marmosets (Callithrix jacchus). Anesthetized marmosets were scanned with a 4.7 T/40 cm horizontal magnet equipped with 450 mT/m magnetic field gradients and a 20 G/cm magnetic field gradient insert, within 3 months of completing the CANTAB serial Reversal Learning task. Neurometabolite concentrations of N-Acetyl Asparate, Myo-Inositol, Choline, Phosphocreatine + creatine, Glutamate and Glutamine were acquired from a 3 mm 3 voxel positioned in the Prefrontal Cortex (PFC). Males acquired the reversals (but not simple discriminations) faster than the females. Higher PFC Glx (glutamate + glutamine) concentration was associated with faster acquisition of the reversals. Interestingly, the correlation between cognitive performance and Glx was significant in males, but not in females. These results suggest that MRS is a useful tool to identify biochemical markers of cognitive performance in the healthy nonhuman primate brain and that biological sex modulates the relationship between neurochemical composition and cognition. Copyright © 2018 Elsevier B.V. All rights reserved.

[{sup 11}C]Choline PET/CT detection of bone metastases in patients with PSA progression after primary treatment for prostate cancer: comparison with bone scintigraphy

Energy Technology Data Exchange (ETDEWEB)

Picchio, Maria [San Raffaele Scientific Institute, Nuclear Medicine Department, Milan (Italy); National Research Council (IBFM-CNR), Institute for Bioimaging and Molecular Physiology, Milan (Italy); Spinapolice, Elena Giulia; Crivellaro, Cinzia [University of Milano-Bicocca, Center for Molecular Bioimaging, Milan (Italy); Fallanca, Federico; Gianolli, Luigi [San Raffaele Scientific Institute, Nuclear Medicine Department, Milan (Italy); Giovacchini, Giampiero [University of Milano-Bicocca, Center for Molecular Bioimaging, Milan (Italy); University Hospital Basel, Institute of Nuclear Medicine, Basel (Switzerland); Messa, Cristina [National Research Council (IBFM-CNR), Institute for Bioimaging and Molecular Physiology, Milan (Italy); University of Milano-Bicocca, Center for Molecular Bioimaging, Milan (Italy); San Gerardo Hospital, Department of Nuclear Medicine, Monza (Italy)

2012-01-15

The aim of this study was to evaluate the clinical usefulness of [{sup 11}C]choline positron emission tomography (PET)/CT in comparison with bone scintigraphy (BS) in detecting bone metastases (BM) of patients with biochemical progression after radical treatment for prostate cancer (PCa). Seventy-eight consecutive patients with biochemical progression of PCa (mean prostate-specific antigen 21.1 ng/ml, range 0.2-500.0 ng/ml) referred for both [{sup 11}C]choline PET/CT and BS for restaging purposes were retrospectively analysed. The diagnostic accuracy of [{sup 11}C]choline PET/CT and BS was assessed by using morphological imaging and/or follow-up as standards of reference. As equivocal findings were found, the accuracy analysis was performed twice, once including them as positive and once as negative. A separate analysis was also performed in hormone-resistant patients and data compared with those of patients who did not receive anti-androgenic treatment. Equivocal findings occurred in 1 of 78 (1%) cases in [{sup 11}C]choline PET/CT and in 21 of 78 (27%) cases in BS. Depending on their attribution as either positive or negative, the ranges of sensitivity, specificity, positive predictive value, negative predictive value and accuracy for [{sup 11}C]choline PET/CT were 89-89%, 98-100%, 96-100%, 94-96% and 95-96%, respectively. For BS they were 100-70%, 75-100%, 68-100%, 100-86% and 83-90%, respectively. Concordant findings between [{sup 11}C]choline PET/CT and BS occurred in 55 of 78 (71%) cases. The accuracy of [{sup 11}C]choline PET/CT did not significantly (p = 0.30) differ between hormone-resistant patients (97%) and those who did not receive anti-androgenic treatment (95%). In clinical practice, [{sup 11}C]choline PET/CT may not replace BS because of its lower sensitivity. However, for its high specificity, [{sup 11}C]choline PET/CT positive findings may accurately predict the presence of BM. Equivocal findings are more frequent in BS than [{sup 11}C]choline PET

Airway remodeling and its reversibility in equine asthma

Directory of Open Access Journals (Sweden)

Jean-Pierre Lavoie

2017-06-01

Full Text Available Despite effective therapies for controlling its clinical manifestations, human asthma remains an incurable disease. It is now recognized that inflammation induced structural changes (remodeling of the airways are responsible for the progressive loss of lung function in asthmatic patients. However, the peripheral airways, where most of the remodeling occurs in severe asthmatic patients, cannot be safely sampled in humans, and therefore, little is known of the effects of current therapies at reversing the established asthmatic remodeling, especially those occurring in the peripheral airways. Animal models have been studied to unravel etiological, immunopathological, and genetic attributes leading to asthma. However, experiments in which the disease is artificially induced have been shown to have limited translational potential for humans. To the contrary, horses naturally suffer from an asthma-like condition which shares marked similarities with human asthma making this model unique to investigate the kinetics, reversibility, as well as the physiological consequences of tissue remodeling (Bullone and Lavoie 2015. We reported an increased deposition of smooth muscle, collagen and elastic fibers in the peripheral airways of affected horses, which was correlated with the lung function (Herszberg et al., 2006; Setlakwe et al., 2014. The airway subepithelial collagen depositions were almost completely reversed with 6 to 12 months of treatment with either antigen avoidance or inhaled corticosteroids (ICS administration, and there was a modest (30% on average decrease in airway smooth muscle (Leclere et al., 2011. A recent study also found that ICS combined with long-acting ß2-agonists drugs (LABA and ICS monotherapy similarly induced a 30% decrease of the airway smooth muscle mass at 3 months (Buollone, 2017. However, only ICS/LABA and antigen avoidance decreased airway luminal neutrophilia. The findings indicate the enhance therapeutic effect of ICS

The value of 18F-choline PET/CT in patients with elevated PSA-level and negative prostate needle biopsy for localisation of prostate cancer

International Nuclear Information System (INIS)

Igerc, I.; Kohlfuerst, S.; Gallowitsch, H.J.; Matschnig, S.; Kresnik, E.; Gomez-Segovia, I.; Lind, P.

2008-01-01

Patients with persistent elevated PSA and repeated negative prostate biopsy, that means having the prostate biopsied at multiple times, were investigated with 18F-choline PET/CT to delineate prostate cancer and guide renewed prostate biopsy. Twenty patients with elevated PSA and negative prostate biopsies underwent 18F-choline PET/CT. We performed an early examination of the pelvic region 3-5 min after application. After 30 minutes a whole body PET/CT examination was performed. Image analysis was performed visually and by semi-quantitative analysis calculating the maximum standardised uptake value (SUVmax). 18F-choline uptake was defined as focal, multifocal or inhomogeneous. After the 18F-choline PET/CT, all patients underwent a repeated prostate biopsy, and in the cases where a focal or multifocal uptake was found, the biopsy was guided by the result of the examination. Qualitative image analysis revealed focal 18F-choline uptake in 13 out of 20 patients. In five patients, prostate cancer was revealed by repeated aspiration biopsy. None of the patients with a multifocal or inhomogeneous 18F-choline uptake had a malignant neoplasm in the prostate. Semiquantitative analysis performed with SUVmax was not helpful in the discrimination of malignancy but showed high values also in benign prostate diseases, as well as in normal prostate tissue. The dual-phase protocol delivered no clear benefit in discriminating malignancy from benign alterations. The use of 18F-choline cannot be generally recommended for localising prostate cancer; however, in highly selected patients, we found useful additional information. In 25% of patients, 18F-choline PET/CT allowed the identification of neoplastic prostatic zones. (orig.)

Prostate cancer: a comparative study of {sup 11}C-choline PET and MR imaging combined with proton MR spectroscopy

Energy Technology Data Exchange (ETDEWEB)

Yamaguchi, Takako; Lee, Jin; Takahashi, Nobukazu; Oka, Takashi; Shizukuishi, Kazuya; Inoue, Tomio [Yokohama City University School of Medicine, Department of Radiology, Yokohama (Japan); Uemura, Hiroji; Kubota, Yoshinobu [Yokohama City University School of Medicine, Department of Urology, Kanagawa (Japan); Sasaki, Takeshi [Yokohama City University School of Medicine, Department of Pathology, Kanagawa (Japan); Endou, Hisashi [Yokohama City University School of Medicine, Department of Pharmacy, Kanagawa (Japan)

2005-07-01

Prostate cancer is difficult to visualise in its early stages using current imaging technology. The present study aimed to clarify the utility of {sup 11}C-choline PET for localising and evaluating cancer lesions in patients with prostate cancer by conducting a prospective comparison with magnetic resonance (MR) imaging combined with proton MR spectroscopy. PET and MR imaging combined with proton MR spectroscopy were performed in 20 patients with prostate cancer. Correlations among the metabolite ratio of choline + creatine to citrate (Cho+Cr/Ci) on MR spectroscopy, serum PSA and maximum standardised uptake value (SUV{sub max}) of {sup 11}C-choline were assessed. The location of the primary lesion was assessed by the site of SUV{sub max} and the laterality of the highest Cho+Cr/Ci ratio and confirmed by examination of surgical pathology specimens (n=16). PET exhibited a diagnostic sensitivity of 100% (20/20) for primary lesions, while the sensitivities of MR imaging and MR spectroscopy were 60% (12/20) and 65% (13/20), respectively. Weak linear correlations were observed between SUV{sub max} and serum PSA (r=0.52, p<0.05), and between SUV{sub max} and Cho+Cr/Ci ratio (r=0.49, p<0.05). Regarding the localisation of main primary lesions, PET results agreed with pathological findings in 13 patients (81%) ({kappa}=0.59), while MR spectroscopy results were in accordance with pathological findings in eight patients (50%) ({kappa}=0.11). This preliminary study suggests that {sup 11}C-choline PET may provide more accurate information regarding the localisation of main primary prostate cancer lesions than MR imaging/MR spectroscopy. A further clinical study of {sup 11}C-choline PET in a large number of patients suspected of prostate cancer will be necessary to determine the clinical utility of {sup 11}C-choline PET in patients who clinically require biopsy. (orig.)

Reverse electron flow-induced ROS production is attenuated by activation of mitochondrial Ca2+-sensitive K+ channels

NARCIS (Netherlands)

Heinen, André; Aldakkak, Mohammed; Stowe, David F.; Rhodes, Samhita S.; Riess, Matthias L.; Varadarajan, Srinivasan G.; Camara, Amadou K. S.

2007-01-01

Mitochondria generate reactive oxygen species (ROS) dependent on substrate conditions, O(2) concentration, redox state, and activity of the mitochondrial complexes. It is well known that the FADH(2)-linked substrate succinate induces reverse electron flow to complex I of the electron transport chain

Gallic Acid Ameliorated Impaired Glucose and Lipid Homeostasis in High Fat Diet-Induced NAFLD Mice

Science.gov (United States)

Chao, Jung; Huo, Teh-Ia; Cheng, Hao-Yuan; Tsai, Jen-Chieh; Liao, Jiunn-Wang; Lee, Meng-Shiou; Qin, Xue-Mei; Hsieh, Ming-Tsuen; Pao, Li-Heng; Peng, Wen-Huang

2014-01-01

Gallic acid (GA), a naturally abundant plant phenolic compound in vegetables and fruits, has been shown to have potent anti-oxidative and anti-obesity activity. However, the effects of GA on nonalcoholic fatty liver disease (NAFLD) are poorly understood. In this study, we investigated the beneficial effects of GA administration on nutritional hepatosteatosis model by a more “holistic view” approach, namely 1H NMR-based metabolomics, in order to prove efficacy and to obtain information that might lead to a better understanding of the mode of action of GA. Male C57BL/6 mice were placed for 16 weeks on either a normal chow diet, a high fat diet (HFD, 60%), or a high fat diet supplemented with GA (50 and 100 mg/kg/day, orally). Liver histopathology and serum biochemical examinations indicated that the daily administration of GA protects against hepatic steatosis, obesity, hypercholesterolemia, and insulin resistance among the HFD-induced NAFLD mice. In addition, partial least squares discriminant analysis scores plots demonstrated that the cluster of HFD fed mice is clearly separated from the normal group mice plots, indicating that the metabolic characteristics of these two groups are distinctively different. Specifically, the GA-treated mice are located closer to the normal group of mice, indicating that the HFD-induced disturbances to the metabolic profile were partially reversed by GA treatment. Our results show that the hepatoprotective effect of GA occurs in part through a reversing of the HFD caused disturbances to a range of metabolic pathways, including lipid metabolism, glucose metabolism (glycolysis and gluconeogenesis), amino acids metabolism, choline metabolism and gut-microbiota-associated metabolism. Taken together, this study suggested that a 1H NMR-based metabolomics approach is a useful platform for natural product functional evaluation. The selected metabolites are potentially useful as preventive action biomarkers and could also be used to help

Crystallization and preliminary X-ray diffraction studies of choline-binding protein F from Streptococcus pneumoniae

Energy Technology Data Exchange (ETDEWEB)

Molina, Rafael [Grupo de Cristalografía Macromolecular y Biología Estructural, Instituto Química Física Rocasolano, CSIC, Serrano 119, 28006 Madrid (Spain); González, Ana; Moscoso, Miriam; García, Pedro [Departamento de Microbiología Molecular, Centro de Investigaciones Biológicas, CSIC, Ramiro de Maeztu 9, 28040 Madrid (Spain); Stelter, Meike; Kahn, Richard [Institut de Biologie Structurale J.-P. Ebel CEA CNRS UJF, Laboratoire de Cristallographie Macromoléculaire, 41 Rue Jules Horowitz, 38027 Grenoble CEDEX 1 (France); Hermoso, Juan A., E-mail: xjuan@iqfr.csic.es [Grupo de Cristalografía Macromolecular y Biología Estructural, Instituto Química Física Rocasolano, CSIC, Serrano 119, 28006 Madrid (Spain)

2007-09-01

The modular choline-binding protein F (CbpF) from S. pneumoniae has been crystallized by the hanging-drop vapour-diffusion method. A SAD data set from a gadolinium-complex derivative has been collected to 2.1 Å resolution. Choline-binding protein F (CbpF) is a modular protein that is bound to the pneumococcal cell wall through noncovalent interactions with choline moieties of the bacterial teichoic and lipoteichoic acids. Despite being one of the more abundant proteins on the surface, along with the murein hydrolases LytA, LytB, LytC and Pce, its function is still unknown. CbpF has been crystallized using the hanging-drop vapour-diffusion method at 291 K. Diffraction-quality orthorhombic crystals belong to space group P2{sub 1}2{sub 1}2, with unit-cell parameters a = 49.13, b = 114.94, c = 75.69 Å. A SAD data set from a Gd-HPDO3A-derivatized CbpF crystal was collected to 2.1 Å resolution at the gadolinium L{sub III} absorption edge using synchrotron radiation.

Crystallization and preliminary X-ray diffraction studies of choline-binding protein F from Streptococcus pneumoniae

International Nuclear Information System (INIS)

Molina, Rafael; González, Ana; Moscoso, Miriam; García, Pedro; Stelter, Meike; Kahn, Richard; Hermoso, Juan A.

2007-01-01

The modular choline-binding protein F (CbpF) from S. pneumoniae has been crystallized by the hanging-drop vapour-diffusion method. A SAD data set from a gadolinium-complex derivative has been collected to 2.1 Å resolution. Choline-binding protein F (CbpF) is a modular protein that is bound to the pneumococcal cell wall through noncovalent interactions with choline moieties of the bacterial teichoic and lipoteichoic acids. Despite being one of the more abundant proteins on the surface, along with the murein hydrolases LytA, LytB, LytC and Pce, its function is still unknown. CbpF has been crystallized using the hanging-drop vapour-diffusion method at 291 K. Diffraction-quality orthorhombic crystals belong to space group P2 1 2 1 2, with unit-cell parameters a = 49.13, b = 114.94, c = 75.69 Å. A SAD data set from a Gd-HPDO3A-derivatized CbpF crystal was collected to 2.1 Å resolution at the gadolinium L III absorption edge using synchrotron radiation

The use of choline in association with the Bangerter filters for the treatment of amblyopia

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Lelio Sabetti

2017-11-01

Full Text Available The study investigated the effects of choline combined with Bangerter filter in the treatment of amblyopia. All amblyopic subjects used a Bangerter filter on the corrective spectacle lens (1d over the left eye, 1d over the right eye. Choline was then administered orally to 39 patients once daily, five days per week for the entire study period. Subjects treated with the Bangerter filter showed a mean visual acuity of 0.27 logMAR; at 12mo of treatment, the mean visual acuity reached 0.09 logMAR. Patients treated with the Bangerter filter and citicoline showed a mean visual acuity of 0.35 logMAR; at 12mo of treatment, the mean visual acuity reached 0.01 logMAR. No significant changes in the angle of deviation were observed in both groups. Subjects in both forms of amblyopia therapies demonstrated an increase in visual acuity. However, these effects were markedly enhanced when coupled with the administration of choline. Findings suggest that the effects are particularly relevant in the more severe amblyopic cases.

Lithium attenuates lead induced toxicity on mouse non-adherent bone marrow cells.

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Banijamali, Mahsan; Rabbani-Chadegani, Azra; Shahhoseini, Maryam

2016-07-01

Lead is a poisonous heavy metal that occurs in all parts of environment and causes serious health problems in humans. The aim of the present study was to investigate the possible protective effect of lithium against lead nitrate induced toxicity in non-adherent bone marrow stem cells. Trypan blue and MTT assays represented that exposure of the cells to different concentrations of lead nitrate decreased viability in a dose dependent manner, whereas, pretreatment of the cells with lithium protected the cells against lead toxicity. Lead reduced the number and differentiation status of bone marrow-derived precursors when cultured in the presence of colony stimulating factor (CSF), while the effect was attenuated by lithium. The cells treated with lead nitrate exhibited cell shrinkage, DNA fragmentation, anion superoxide production, but lithium prevented lead action. Moreover, apoptotic indexes such as PARP cleavage and release of HMGB1 induced by lead, were protected by lithium, suggesting anti-apoptotic effect of lithium. Immunoblot analysis of histone H3K9 acetylation indicated that lithium overcame lead effect on acetylation. In conclusion, lithium efficiently reduces lead toxicity suggesting new insight into lithium action which may contribute to increased cell survival. It also provides a potentially new therapeutic strategy for lithium and a cost-effective approach to minimize destructive effects of lead on bone marrow stem cells. Copyright © 2016 Elsevier GmbH. All rights reserved.

Quantification of acetylcholine, choline, betaine, and dimethylglycine in human plasma and urine using stable-isotope dilution ultra performance liquid chromatography-tandem mass spectrometry.

Science.gov (United States)

Kirsch, Susanne H; Herrmann, Wolfgang; Rabagny, Yannick; Obeid, Rima

2010-12-15

Disorders in choline metabolism are related to disease conditions. We developed a stable-isotope dilution ultra performance liquid chromatography-mass spectrometry (UPLC-MS/MS) method for the simultaneous quantification of acetylcholine (ACh), betaine, choline, and dimethylglycine (DMG). We used this method to measure concentrations of the analytes in plasma and urine in addition to other biological fluids after a protein precipitation by acetonitrile. The detection limits were between 0.35 nmol/L (for ACh in urine) and 0.34 μmol/L (for betaine in urine). ACh concentrations were not detectable in plasma. Intraassay and interassay coefficient of variation (CVs) were all DMG in cerebrospinal fluid (CV=12.44%). Mean recoveries in urine pool samples were between 99.2% and 103.9%. The urinary excretion of betaine, choline, and DMG was low, with approximately 50.0% higher excretion of choline in females compared to males. Median urinary excretion of ACh were 3.44 and 3.92 μmol/mol creatinine in males and females, respectively (p=0.689). Plasma betaine concentrations correlated significantly with urinary excretions of betaine (r=0.495, p=0.027) and choline (r=0.502, p=0.024) in females. Plasma choline concentrations correlated significantly with urinary excretion of ACh in males (r=0.419, p=0.041) and females (r=0.621, p=0.003). The new method for the simultaneous determination of ACh, betaine, choline, and DMG is sensitive, precise, and fast enough to be used in clinical investigations related to the methylation pathway. Copyright © 2010 Elsevier B.V. All rights reserved.

In silico-designed novel non-peptidic ABAD LD hot spot mimetics reverse Aβ-induced mitochondrial impairments in vitro.

Science.gov (United States)

Viswanath, Ambily Nath Indu; Kim, TaeHun; Jung, Seo Yun; Lim, Sang Min; Pae, Ae Nim

2017-12-01

Present work aimed to introduce non-peptidic ABAD loop D (L D ) hot spot mimetics as ABAD-Aβ inhibitors. A full-length atomistic model of ABAD-Aβ complex was built as a scaffold to launch the lead design and its topology later verified by cross-checking the computational mutagenesis results with that of in vitro data. Thereafter, the interactions of prime Aβ-binding L D residues-Tyr101, Thr108, and Thr110-were translated into specific pharmacophore features and this hypothesis subsequently used as a virtual screen query. ELISA-based screening of 20 hits identified two promising lead candidates, VC15 and VC19 with an IC 50 of 4.4 ± 0.3 and 9.6 ± 0.1 μm, respectively. They productively reversed Aβ-induced mitochondrial dysfunctions such as mitochondrial membrane potential loss (JC-1 assay), toxicity (MTT assay), and ATP reduction (ATP assay) in addition to increased cell viabilities. This is the first reporting of L D hot spot-centric in silico scheme to discover novel compounds with promising ABAD-Aβ inhibitory potential. These chemotypes are proposed for further structural optimization to derive novel Alzheimer's disease (AD) therapeutics. © 2017 John Wiley & Sons A/S.

Complexity of MRI induced heating on metallic leads: Experimental measurements of 374 configurations

Directory of Open Access Journals (Sweden)

Mendoza Gonzalo

2008-03-01

Full Text Available Abstract Background MRI induced heating on PM leads is a very complex issue. The widely varying results described in literature suggest that there are many factors that influence the degree of heating and that not always are adequately addressed by existing testing methods. Methods We present a wide database of experimental measurements of the heating of metallic wires and PM leads in a 1.5 T RF coil. The aim of these measurements is to systematically quantify the contribution of some potential factors involved in the MRI induced heating: the length and the geometric structure of the lead; the implant location within the body and the lead path; the shape of the phantom used to simulate the human trunk and its relative position inside the RF coil. Results We found that the several factors are the primary influence on heating at the tip. Closer locations of the leads to the edge of the phantom and to the edge of the coil produce maximum heating. The lead length is the other crucial factor, whereas the implant area does not seem to have a major role in the induced temperature increase. Also the lead structure and the geometry of the phantom revealed to be elements that can significantly modify the amount of heating. Conclusion Our findings highlight the factors that have significant effects on MRI induced heating of implanted wires and leads. These factors must be taken into account by those who plan to study or model MRI heating of implants. Also our data should help those who wish to develop guidelines for defining safe medical implants for MRI patients. In addition, our database of the entire set of measurements can help those who wish to validate their numerical models of implants that may be exposed to MRI systems.

Bacterial lipoprotein-induced tolerance is reversed by overexpression of IRAK-1.

LENUS (Irish Health Repository)

Li, Chong Hui

2012-03-01

Tolerance to bacterial cell wall components including bacterial lipoprotein (BLP) represents an essential regulatory mechanism during bacterial infection. Reduced Toll-like receptor 2 (TLR2) and IL-1 receptor-associated kinase 1 (IRAK-1) expression is a characteristic of the downregulated TLR signaling pathway observed in BLP-tolerised cells. In this study, we attempted to clarify whether TLR2 and\\/or IRAK-1 are the key molecules responsible for BLP-induced tolerance. Transfection of HEK293 cells and THP-1 cells with the plasmid encoding TLR2 affected neither BLP tolerisation-induced NF-κB deactivation nor BLP tolerisation-attenuated pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α) production, indicating that BLP tolerance develops despite overexpression of TLR2 in these cells. In contrast, overexpression of IRAK-1 reversed BLP-induced tolerance, as transfection of IRAK-1 expressing vector resulted in a dose-dependent NF-κB activation and TNF-α release in BLP-tolerised cells. Furthermore, BLP-tolerised cells exhibited markedly repressed NF-κB p65 phosphorylation and impaired binding of p65 to several pro-inflammatory cytokine gene promoters including TNF-α and interleukin-6 (IL-6). Overexpression of IRAK-1 restored the nuclear transactivation of p65 at both TNF-α and IL-6 promoters. These results indicate a crucial role for IRAK-1 in BLP-induced tolerance, and suggest IRAK-1 as a potential target for manipulation of the TLR-mediated inflammatory response during microbial sepsis.

Metabolomic Analysis of N-acetylcysteine Protection of Injury from Gadolinium-DTPA Contrast Agent in Rats with Chronic Renal Failure.

Science.gov (United States)

Wan, Chuanling; Xue, Rong; Zhan, Youyang; Wu, Yijie; Li, Xiaojing; Pei, Fengkui

2017-09-01

Gadolinium-based contrast agents (GBCAs) are frequently used to enhance the diagnostic efficacy of magnetic resonance imaging. On the other hand, the association between GBCA administration in patients with advanced renal disease and nephrogenic systemic fibrosis (NSF) was also noted. NSF is a systemic disorder characterized by widespread tissue fibrosis that may lead to death. N-acetylcysteine (NAC) protects rats from injury induced by gadolinium-based contrast agents, but the underlying mechanisms remain unclear. In this study, a nuclear magnetic resonance-based metabolomic approach was used to systematically investigate the protective effects of NAC on Gd-DTPA-induced injury. Thirty-two male Sprague-Dawley rats were given adenine (200 mg·kg -1 body weight) by oral gavage once a day for 3 weeks to induce chronic renal failure (CRF). NAC (600 mg/L in drinking water for 9 days) pretreatment was initiated 2 days before Gd-DTPA injection (a single tail vein injection, 2 mmol/kg body weight). Serum and liver samples were collected on day 7 after Gd-DTPA injection. By study design, the serum and hepatic metabolic changes of rats were measured in four groups of eight each: CRF, CRF-Gd, CRF-Gd-NAC, and CRF-NAC. Gd-DTPA administration to rats with CRF resulted in disturbances of several metabolic pathways, including glucose, lipid, glutamate, choline, gut microbiota, one-carbon, and purine metabolism. NAC pretreatment reversed the abundance changes of high-density lipoprotein, low-density lipoprotein, very low-density lipoprotein, glutamate, glutamine, oxidized glutathione, choline, phosphocholine, glycerophosphocholine, trimethylamine, and trimethylamine-N-oxide induced by Gd-DTPA. It is noteworthy, however, that the ameliorating effects of NAC on the disturbance of glutamate, choline, and gut microbiota metabolism may be specific to Gd-DTPA. In all, these findings could be potentially useful to decipher the underlying mechanisms of NAC protective effects from the

Prospective head-to-head comparison of 11C-choline-PET/MR and 11C-choline-PET/CT for restaging of biochemical recurrent prostate cancer

International Nuclear Information System (INIS)

Eiber, Matthias; Rauscher, Isabel; Souvatzoglou, Michael; Schwaiger, Markus; Maurer, Tobias; Holzapfel, Konstantin; Beer, Ambros J.

2017-01-01

Whole-body integrated 11 C-choline PET/MR might provide advantages compared to 11 C-choline PET/CT for restaging of prostate cancer (PC) due to the high soft-tissue contrast and the use of multiparametric MRI, especially for detection of local recurrence and bone metastases. Ninety-four patients with recurrent PC underwent a single-injection/dual-imaging protocol with contrast-enhanced PET/CT followed by fully diagnostic PET/MR. Imaging datasets were read separately by two reader teams (team 1 and 2) assessing the presence of local recurrence, lymph node and bone metastases in predefined regions using a five-point scale. Detection rates were calculated. The diagnostic performance of PET/CT vs. PET/MR was compared using ROC analysis. Inter-observer and inter-modality variability, radiation exposure, and mean imaging time were evaluated. Clinical follow-up, imaging, and/or histopathology served as standard of reference (SOR). Seventy-five patients qualified for the final image analysis. A total of 188 regions were regarded as positive: local recurrence in 37 patients, 87 regions with lymph node metastases, and 64 regions with bone metastases. Mean detection rate between both readers teams for PET/MR was 84.7% compared to 77.3% for PET/CT (p > 0.05). Local recurrence was identified significantly more often in PET/MR compared to PET/CT by team 1. Lymph node and bone metastases were identified significantly more often in PET/CT compared to PET/MR by both teams. However, this difference was not present in the subgroup of patients with PSA values ≤2 ng/ml. Inter-modality and inter-observer agreement (K > 0.6) was moderate to substantial for nearly all categories. Mean reduction of radiation exposure for PET/MR compared to PET/CT was 79.7% (range, 72.6-86.2%). Mean imaging time for PET/CT was substantially lower (18.4 ± 0.7 min) compared to PET/MR (50.4 ± 7.9 min). 11 C-choline PET/MR is a robust imaging modality for restaging biochemical recurrent PC and

Urtica dioica leaves modulates muscarinic cholinergic system in the hippocampus of streptozotocin-induced diabetic mice.

Science.gov (United States)

Patel, Sita Sharan; Parashar, Arun; Udayabanu, Malairaman

2015-06-01

Diabetes mellitus is a chronic metabolic disorder and has been associated with cognitive dysfunction. In our earlier study, chronic Urtica dioica (UD) treatment significantly ameliorated diabetes induced associative and spatial memory deficit in mice. The present study was designed to explore the effect of UD leaves extract on muscarinic cholinergic system, which has long been known to be involved in cognition. Streptozotocin (STZ) (50 mg/kg, i.p., consecutively for 5 days) was used to induce diabetes followed by treatment with UD extract (50 mg/kg, oral) or rosiglitazone (5 mg/kg, oral) for 8 weeks. STZ-induced diabetic mice showed significant reduction in hippocampal muscarinic acetylcholine receptor-1 and choline acetyltransferase expressions. Chronic diabetes significantly up-regulated the protein expression of acetylcholinesterase associated with oxidative stress in hippocampus. Besides, STZ-induced diabetic mice showed hypolocomotion with up-regulation of muscarinic acetylcholine receptor-4 expression in striatum. Chronic UD treatment significantly attenuated the cholinergic dysfunction and oxidative stress in the hippocampus of diabetic mice. UD had no effect on locomotor activity and muscarinic acetylcholine receptor-4 expression in striatum. In conclusion, UD leaves extract has potential to reverse diabetes mediated alteration in muscarinic cholinergic system in hippocampus and thereby improve memory functions.

(p-ClPhSe)2 stimulates carbohydrate metabolism and reverses the metabolic alterations induced by high fructose load in rats.

Science.gov (United States)

Quines, Caroline B; Rosa, Suzan G; Chagas, Pietro M; Velasquez, Daniela; Prado, Vinicius C; Nogueira, Cristina W

2017-09-01

The modern life leads to excess consumption of food rich in fructose; however, the long-term changes in carbohydrate and lipid metabolism could lead to metabolic dysfunction in humans. The present study evaluated the in vitro insulin-mimetic action of p-chloro-diphenyl diselenide (p-ClPhSe) 2 . The second aim of this study was to investigate if (p-ClPhSe) 2 reverses metabolic dysfunction induced by fructose load in Wistar rats. The insulin-mimetic action of (p-ClPhSe) 2  at concentrations of 50 and 100 μM was determined in slices of rat skeletal muscle. (p-ClPhSe) 2  at a concentration of 50 μM stimulated the glucose uptake by 40% in skeletal muscle. A dose-response curve revealed that (p-ClPhSe) 2  at a dose of 25 mg/kg reduced (∼20%) glycemia in rats treated with fructose (5 g/kg, i.g.). The administration of fructose impaired the liver homeostasis and (p-ClPhSe) 2 (25 mg/kg) protected against the increase (∼25%) in the G-6-Pase and isocitrate dehydrogenase activities and reduced the triglyceride content (∼25%) in the liver. (p-ClPhSe) 2 regulated the liver homeostasis by stimulating hexokinase activity (∼27%), regulating the TCA cycle activity (increased the ATP and citrate synthase activity (∼15%)) and increasing the glycogen levels (∼67%). In conclusion, (p-ClPhSe) 2 stimulated carbohydrate metabolism and reversed metabolic dysfunction in rats fed with fructose. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of dimethyl sulfoxide (DMSO) on radiation-induced heteroallelic reversion in diploid yeast

International Nuclear Information System (INIS)

Singh, D.R.; Mahajan, J.M.; Krishnan, D.

1976-01-01

Dimethyl sulfoxide has cryoprotective and radioprotective properties. It is also an efficient scavenger of radicals produced by radiolysis of water. Gamma-induced reversion of diploid yeast in the presence of this chemical during irradiation have been studied. The dose-modifying factor was in the same range as for survival. When the yeast was irradiated in the frozen state, the observed protection by DMSO disappeared. The results are discussed in terms of direct and indirect actions of radiations and the radical-scavenging ability of this chemical

Light-induced lattice expansion leads to high-efficiency perovskite solar cells

Science.gov (United States)

Tsai, Hsinhan; Asadpour, Reza; Blancon, Jean-Christophe; Stoumpos, Constantinos C.; Durand, Olivier; Strzalka, Joseph W.; Chen, Bo; Verduzco, Rafael; Ajayan, Pulickel M.; Tretiak, Sergei; Even, Jacky; Alam, Muhammad Ashraf; Kanatzidis, Mercouri G.; Nie, Wanyi; Mohite, Aditya D.

2018-04-01

Light-induced structural dynamics plays a vital role in the physical properties, device performance, and stability of hybrid perovskite–based optoelectronic devices. We report that continuous light illumination leads to a uniform lattice expansion in hybrid perovskite thin films, which is critical for obtaining high-efficiency photovoltaic devices. Correlated, in situ structural and device characterizations reveal that light-induced lattice expansion benefits the performances of a mixed-cation pure-halide planar device, boosting the power conversion efficiency from 18.5 to 20.5%. The lattice expansion leads to the relaxation of local lattice strain, which lowers the energetic barriers at the perovskite-contact interfaces, thus improving the open circuit voltage and fill factor. The light-induced lattice expansion did not compromise the stability of these high-efficiency photovoltaic devices under continuous operation at full-spectrum 1-sun (100 milliwatts per square centimeter) illumination for more than 1500 hours.

Pregnancy induces transcriptional activation of the peripheral innate immune system and increases oxidative DNA damage among healthy third trimester pregnant women.

Directory of Open Access Journals (Sweden)

Xinyin Jiang

Full Text Available BACKGROUND: Pregnancy induces physiological adaptations that may involve, or contribute to, alterations in the genomic landscape. Pregnancy also increases the nutritional demand for choline, an essential nutrient that can modulate epigenomic and transcriptomic readouts secondary to its role as a methyl donor. Nevertheless, the interplay between human pregnancy, choline and the human genome is largely unexplored. METHODOLOGY/PRINCIPAL FINDINGS: As part of a controlled feeding study, we assessed the influence of pregnancy and choline intake on maternal genomic markers. Healthy third trimester pregnant (n = 26, wk 26-29 gestation and nonpregnant (n = 21 women were randomized to choline intakes of 480 mg/day, approximating the Adequate Intake level, or 930 mg/day for 12-weeks. Blood leukocytes were acquired at study week 0 and study week 12 for microarray, DNA damage and global DNA/histone methylation measurements. A main effect of pregnancy that was independent of choline intake was detected on several of the maternal leukocyte genomic markers. Compared to nonpregnant women, third trimester pregnant women exhibited higher (P<0.05 transcript abundance of defense response genes associated with the innate immune system including pattern recognition molecules, neutrophil granule proteins and oxidases, complement proteins, cytokines and chemokines. Pregnant women also exhibited higher (P<0.001 levels of DNA damage in blood leukocytes, a genomic marker of oxidative stress. No effect of choline intake was detected on the maternal leukocyte genomic markers with the exception of histone 3 lysine 4 di-methylation which was lower among pregnant women in the 930 versus 480 mg/d choline intake group. CONCLUSIONS: Pregnancy induces transcriptional activation of the peripheral innate immune system and increases oxidative DNA damage among healthy third trimester pregnant women.

Reversible metronidazole-induced neurotoxicity after 10 weeks of therapy.

Science.gov (United States)

AlDhaleei, Wafa; AlMarzooqi, Ayesha; Gaber, Nouran

2018-04-20

Metronidazole is a commonly used antimicrobial worldwide. The most common side effects that have been reported are nausea, vomiting and hypersensitivity reactions. However, neurotoxicity has been reported with the use of metronidazole but rather rare. The most common neurological manifestation is peripheral neuropathy involvement in the form of sensory loss. It is worth mentioning that central neurotoxicity is a rare side effect of metronidazole use but reversible. The manifestations vary from a headache, altered mental status to focal neurological deficits. The diagnosis is mainly by neuroimaging in the setting of acute neurological change in the patient status. Here, we report a case of metronidazole-induced neurotoxicity in a 38-year-old male patient who was admitted with a brain abscess and was started on metronidazole for more than 10 weeks. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Brain antioxidant effect of mirtazapine and reversal of sedation by its combination with alpha-lipoic acid in a model of depression induced by corticosterone.

Science.gov (United States)

Oliveira, Tatiana de Queiroz; de Sousa, Caren Nádia Soares; Vasconcelos, Germana Silva; de Sousa, Luciene Costa; de Oliveira, Anneheydi Araújo; Patrocínio, Cláudio Felipe Vasconcelos; Medeiros, Ingridy da Silva; Honório Júnior, José Eduardo Ribeiro; Maes, Michael; Macedo, Danielle; Vasconcelos, Silvânia Maria Mendes

2017-09-01

Depression is accompanied by activated neuro-oxidative and neuro-nitrosative pathways, while targeting these pathways has clinical efficacy in depression. This study aimed to investigate the effects of mirtazapine (MIRT) alone and combined with alpha-lipoic acid (ALA) against corticosterone (CORT) induced behavioral and oxidative alterations. Male mice received vehicle or CORT 20mg/kg during 14 days. From the 15th to 21st days they were divided in groups administered: vehicle, MIRT 3mg/kg or the combinations MIRT+ALA100 or MIRT+ALA200. On the 21st day of treatment, the animals were subjected to behavioral tests. Twenty-four hours after the last drug administration hippocampus (HC) and striatum (ST) were dissected for the determination reduced glutathione (GSH), lipid peroxidation (LP) and nitrite levels. CORT induced anxiety- and depressive-like behaviors as observed by increased immobility time in the tail suspension test and decreased sucrose consumption. MIRT or MIRT+ALA are effective in reversing anxiety- and depressive-like behaviors induced by CORT. CORT and MIRT alone prolonged sleeping time and this effect was reversed by MIRT+ALA. CORT significantly increased LP, which was reversed by MIRT or MIRT+ALA. Nitrite levels were increased in CORT-treated animals and reversed by MIRT+ALA200 (HC), MIRT or MIRT+ALA (ST). A relative small sample size and lack of a washout period between drug administration and behavioral testing. MIRT or MIRT+ALA reverse CORT-induced anxiety- and depressive-like behaviors probably via their central antioxidant effects. Augmentation of MIRT with ALA may reverse sedation, an important side effect of MIRT. Randomized controlled studies are needed to examine the clinical efficacy of this combination in human depression. Copyright © 2017 Elsevier B.V. All rights reserved.

Improved Diagnostic Accuracy in Characterization of Adnexal Masses by Detection of Choline Peak Using 1H MR Spectroscopy in Comparison to Internal Reference at 3 Tesla.

Science.gov (United States)

Malek, Mahrooz; Pourashraf, Maryam; Gilani, Mitra Modares; Gity, Masoumeh

2015-01-01

The aim of this study was to assess the role of the presence of a choline peak in 3 Tesla 1H magnetic resonance spectroscopy (MRS) for differentiating benign from malignant adnexal masses. A total of 46 adnexal masses (23 malignant and 23 benign) underwent 1H MRS study prior to surgery to assess the presence of choline peak. A choline peak was detected in 16 malignant masses (69.5%) and was absent in the other 7 (30.5%). A choline peak was only detected in 6 (26%) of the benign adnexal masses. The presence of an MRS choline peak had a sensitivity of 69.5%, a specificity of 74%, a positive predictive value (PPV) of 72.7%, and a negative predictive value (NPV) of 71% for diagnosing malignant adnexal masses. A significant difference between the frequency of mean choline peaks in benign and malignant adnexal masses was observed (P valuepeak is seen in malignant adnexal masses more frequently than the benign masses, and may be helpful for diagnosing malignant adnexal masses.

Blockage of High-Affinity Choline Transporter Increases Visceral Hypersensitivity in Rats with Chronic Stress

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Chen Zhao

2018-01-01

Full Text Available Background. Visceral hypersensitivity is a common feature of irritable bowel syndrome. Cholinergic system involves in the development of visceral hypersensitivity, and high-affinity choline transporter (CHT1 is of crucial importance in choline uptake system. However, involvement of CHT1 in visceral hypersensitivity remains unknown. The research aimed to study the CHT1 expression in dorsal root ganglions (DRGs and the role of CHT1 in visceral hypersensitivity. Methods. Repetitive water avoidance stress (WAS was used to induce visceral hypersensitivity in rats. Colorectal distension (CRD was determined, and the abdominal withdrawal reflex (AWR and threshold intensity data were recorded to measure the visceral sensitivity. After intraperitoneal injection of hemicholinium-3 (HC-3, the specific inhibitor of CHT1, CRD data were also recorded. The CHT1 expression of DRGs was investigated by Western blotting, immunohistochemistry, and quantitative RT-PCR. Acetylcholine levels in the DRGs were detected by the assay kit. Results. Repetitive WAS increased the AWR score of CRD at high distension pressure and decreased the mean threshold of rats. The CHT1 expression and acetylcholine concentration of DRG were significantly increased in WAS rats. After the administration of HC-3, the AWR score in WAS group was significantly increased at higher distension pressure while the threshold intensity was significantly reduced compared to the normal saline group. Acetylcholine concentration was significantly lower than the normal saline rats. Conclusion. Our research firstly reports that CHT1 is overexpressed in noninflammatory visceral hypersensitivity, and blockage of CHT1 can enhance the visceral hypersensitivity. CHT1 may play an inhibitory role in visceral hypersensitivity.

How decision reversibility affects motivation.

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Bullens, Lottie; van Harreveld, Frenk; Förster, Jens; Higgins, Tory E

2014-04-01

The present research examined how decision reversibility can affect motivation. On the basis of extant findings, it was suggested that 1 way it could affect motivation would be to strengthen different regulatory foci, with reversible decision making, compared to irreversible decision making, strengthening prevention-related motivation relatively more than promotion-related motivation. If so, then decision reversibility should have effects associated with the relative differences between prevention and promotion motivation. In 5 studies, we manipulated the reversibility of a decision and used different indicators of regulatory focus motivation to test these predictions. Specifically, Study 1 tested for differences in participants' preference for approach versus avoidance strategies toward a desired end state. In Study 2, we used speed and accuracy performance as indicators of participants' regulatory motivation, and in Study 3, we measured global versus local reaction time performance. In Study 4, we approached the research question in a different way, making use of the value-from-fit hypothesis (Higgins, 2000, 2002). We tested whether a fit between chronic regulatory focus and focus induced by the reversibility of the decision increased participants' subjective positive feelings about the decision outcome. Finally, in Study 5, we tested whether regulatory motivation, induced by decision reversibility, also influenced participants' preference in specific product features. The results generally support our hypothesis showing that, compared to irreversible decisions, reversible decisions strengthen a prevention focus more than a promotion focus. Implications for research on decision making are discussed.

Effect of choline on antioxidant defenses and gene expressions of Nrf2 signaling molecule in the spleen and head kidney of juvenile Jian carp (Cyprinus carpio var. Jian).

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Wu, Pei; Jiang, Wei-Dan; Liu, Yang; Chen, Gang-Fu; Jiang, Jun; Li, Shu-Hong; Feng, Lin; Zhou, Xiao-Qiu

2014-06-01

The present work evaluates the effects of various levels of dietary choline on antioxidant defenses and gene expressions of Nrf2 signaling molecule in spleen and head kidney of juvenile Jian carp (Cyprinus carpio var. Jian). Fish were fed with six different experimental diets containing graded levels of choline at 165 (choline-deficient control), 310, 607, 896, 1167 and 1820 mg kg(-1) diet for 65 days. At the end of the feeding trail, fish were challenged with Aeromonas hydrophila and mortalities were recorded over 17 days. Dietary choline significantly decreased malondialdehyde and protein carbonyl contents in spleen and head kidney. However, anti-superoxide anion and anti-hydroxyl radical activities in spleen and head kidney also decreased. Interestingly, activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR) in spleen, GPx activity in head kidney, and glutathione contents in spleen and head kidney were decreased with increase of dietary choline levels up to a certain point, whereas, activities of SOD, GST and GR in head kidney showed no significantly differences among groups. Similarly, expression levels of CuZnSOD, MnSOD, CAT, GPx1a, GPx1b and GR gene in spleen and head kidney were significantly lower in group with choline level of 607 mg kg(-1) diet than those in the choline-deficient group. The relative gene expressions of Nrf2 in head kidney and Keap1a in spleen and head kidney were decreased with increasing of dietary choline up to a certain point. However, the relative gene expression of Nrf2 in spleen were not significantly affected by dietary choline. In conclusion, dietary choline decreased the oxidant damage and regulated the antioxidant system in immune organs of juvenile Jian carp. Copyright © 2014 Elsevier Ltd. All rights reserved.

Evaluation of 11C-choline PET/CT for primary diagnosis and staging of urothelial carcinoma of the upper urinary tract: a pilot study

International Nuclear Information System (INIS)

Sassa, Naoto; Yamamoto, Tokunori; Gotoh, Momokazu; Kato, Katsuhiko; Ikeda, Mitsuru; Shimamoto, Kazuhiro; Yamamoto, Seiichi; Abe, Shinji; Iwano, Shingo; Ito, Shinji; Naganawa, Shinji

2014-01-01

We conducted a pilot study to prospectively evaluate the efficacy of PET/CT with 11 C-choline (choline PET/CT) for primary diagnosis and staging of urothelial carcinoma of the upper urinary tract (UUT-UC). Enrolled in this study were 16 patients (9 men, 7 women; age range 51 - 83 years, mean ± SD 69 ± 10.8 years) with suspected UUT-UC. The patients were examined by choline PET/CT, and 13 underwent laparoscopic nephroureterectomy and partial cystectomy. Lymphadenectomy and chemotherapy were also performed as necessary in some of the patients. Of the 16 patients, 12 were confirmed to have UUT-UC (7 renal pelvis carcinoma and 5 ureteral carcinoma), 1 had malignant lymphoma (ureter), 1 had IgG4-related disease (ureter), and 2 had other benign diseases (ureter). Of the 16 study patients, 13 showed definite choline uptake in urothelial lesions, and of these, 11 had UUT-UC, 1 had malignant lymphoma, and 1 had IgG4-related disease. Three patients without choline uptake comprised one with UUT-UC and two with benign diseases. Of the 12 patients with UUT-UC, 3 had distant metastases, 2 had metastases only in the regional lymph nodes, and 7 had no metastases. Distant metastases and metastases in the regional lymph nodes showed definite choline uptake. The outcome in patients with UUT-UC, which was evaluated 592 - 1,530 days after surgery, corresponded to the patient classification based on the presence or absence of metastases and locoregional or distant metastases. Choline uptake determined as SUVmax 10 min after administration was significantly higher than at 20 min in metastatic tumours of UUT-UC (p < 0.05), whereas there was no statistically significant difference between the SUVmax values at 10 and those at 20 min in primary tumours of UUT-UC. This study suggests that choline PET/CT is a promising tool for the primary diagnosis and staging of UUT-UC. (orig.)

The change of β-adrenergic system after cessation of lead exposure

International Nuclear Information System (INIS)

Chang, H.-R.; Tsao, D.-A.; Yu, H.-S.; Ho, C.-K.

2005-01-01

For understanding a reversible or irreversible harm of β-adrenergic system in lead induced cardiovascular disease (hypertension), We set up animal model to estimate the change of blood pressure and sympathetic nervous system after lead exposure withdrawn in the study. We address three topics in this study: (a) the relationship between withdrawal time of lead exposure and β-adrenergic receptor, plasma catecholamine level, blood pressure, and lead level in heart, aorta, and kidney in lead-induced hypertensive rats after lead exposure stopped; (b) the relationship between blood pressure and β-adrenergic receptor in heart, aorta, and kidney; (c) the estimation of relationship between lead withdrawn and the variation of β-adrenergic system. Wistar rats were chronically fed with 2% lead acetate (experimental group) and water (control group) for 2 months. The rats were divided into 8 groups by withdrawal time of lead exposure stopped. Plasma catecholamine level was measured by high-performance liquid chromatography. Radioligand binding assay was measured by a method that fulfilled strict criteria of β-adrenergic receptor using the ligand [ 125 I]iodocyanopindolol. The levels of lead were determined by electrothermal atomic absorption spectrometry. The results showed that a close relation between reduced lead level and the plasma catecholamine level decreased, aorta β-adrenergic receptor increased, kidney β-adrenergic receptor diminished, heart β-adrenergic receptor increased, and blood pressure dropped after lead exposure withdrawn. The study on the regulation of β-adrenergic system in lead-induced hypertension after lead withdrawn might also provide insight about the nature of this disease state

Protective Effect of Morocco Carob Honey Against Lead-Induced Anemia and Hepato-Renal Toxicity

OpenAIRE

Aicha Fassi Fihri; Noori S. Al-Waili; Redouan El-Haskoury; Meryem Bakour; Afaf Amarti; Mohammad J. Ansari; Badiaa Lyoussi

2016-01-01

Background/Aims: Natural honey has many biological activities including protective effect against toxic materials. The aim of this study was to evaluate the protective effect of carob honey against lead-induced hepato-renal toxicity and lead-induced anemia in rabbits. Methods: Twenty four male rabbits were allocated into four groups six rabbits each; group 1: control group, received distilled water (0.1 ml / kg.b.wt /daily); group 2: received oral lead acetate (2 g/kg.b.wt/daily); group 3: tr...

(18)F-choline PET/CT pitfalls in image interpretation: an update on 300 examined patients with prostate cancer.

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Calabria, Ferdinando; Chiaravalloti, Agostino; Schillaci, Orazio

2014-02-01

F-choline PET/CT is an important diagnostic tool in the management of patients with prostate cancer (PC). The aim of this study was to describe and discuss some abnormal sites of uptake that we observed, not due to PC recurrence. Three hundred patients were submitted to F-choline PET/CT for staging or restaging of PC. Whole-body PET/CT was acquired 40 minutes after the F-choline administration. We found abnormal uptake of the tracer, not related to PC, in 48/300 patients (16%). Most of these findings were due to inflammatory processes. Furthermore, some malignant conditions, such as a case of colon cancer, a case of bladder carcinoma, and a multiple myeloma, were diagnosed. Mild uptake was also detected in some benign diseases, such as thymoma, adrenal adenoma, and sarcoidosis. Six patients showed focal brain uptake in correspondence to a meningioma. It is necessary for nuclear physicians, during clinical practice, to consider the possibility of F-choline uptake in some benign or malignant conditions for the intrinsic pharmacologic property of the tracer. An accurate medical investigation, correlative imaging with CT and/or MRI with contrast agents, laboratory data, and above all, histologic examination are often necessary for correct diagnosis.

Maternal obesity caused by overnutrition exposure leads to reversal learning deficits and striatal disturbance in rats.

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Ting Wu

Full Text Available Maternal obesity caused by overnutrition during pregnancy increases susceptibility to metabolic risks in adulthood, such as obesity, insulin resistance, and type 2 diabetes; however, whether and how it affects the cognitive system associated with the brain remains elusive. Here, we report that pregnant obesity induced by exposure to excessive high fatty or highly palatable food specifically impaired reversal learning, a kind of adaptive behavior, while leaving serum metabolic metrics intact in the offspring of rats, suggesting a much earlier functional and structural defects possibly occurred in the central nervous system than in the metabolic system in the offspring born in unfavorable intrauterine nutritional environment. Mechanically, we found that above mentioned cognitive inflexibility might be associated with significant striatal disturbance including impaired dopamine homeostasis and disrupted leptin signaling in the adult offspring. These collective data add a novel perspective of understanding the adverse postnatal sequelae in central nervous system induced by developmental programming and the related molecular mechanism through which priming of risk for developmental disorders may occur during early life.

Metabolic pathways promoting intrahepatic fatty acid accumulation in methionine and choline deficiency: implications for the pathogenesis of steatohepatitis.

Science.gov (United States)

Macfarlane, David P; Zou, Xiantong; Andrew, Ruth; Morton, Nicholas M; Livingstone, Dawn E W; Aucott, Rebecca L; Nyirenda, Moffat J; Iredale, John P; Walker, Brian R

2011-02-01

The pathological mechanisms that distinguish simple steatosis from steatohepatitis (or NASH, with consequent risk of cirrhosis and hepatocellular cancer) remain incompletely defined. Whereas both a methionine- and choline-deficient diet (MCDD) and a choline-deficient diet (CDD) lead to hepatic triglyceride accumulation, MCDD alone is associated with hepatic insulin resistance and inflammation (steatohepatitis). We used metabolic tracer techniques, including stable isotope ([¹³C₄]palmitate) dilution and mass isotopomer distribution analysis (MIDA) of [¹³C₂]acetate, to define differences in intrahepatic fatty acid metabolism that could explain the contrasting effect of MCDD and CDD on NASH in C57Bl6 mice. Compared with control-supplemented (CS) diet, liver triglyceride pool sizes were similarly elevated in CDD and MCDD groups (24.37 ± 2.4, 45.94 ± 3.9, and 43.30 ± 3.5 μmol/liver for CS, CDD, and MCDD, respectively), but intrahepatic neutrophil infiltration and plasma alanine aminotransferase (31 ± 3, 48 ± 4, 231 ± 79 U/l, P triglyceride pool differed between groups. Unlike CDD, MCDD had a defect in hepatic triglyceride export that was confirmed using intravenous tyloxapol (142 ± 21, 122 ± 15, and 80 ± 7 mg·kg⁻¹·h⁻¹, P metabolism may promote the development of steatohepatitis. Similar mechanisms may predispose to hepatocyte damage in human NASH.

Sepsis-Induced Takotsubo Cardiomyopathy Leading to Torsades de Pointes

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Nirav Patel

2016-01-01

Full Text Available Background. Takotsubo cardiomyopathy (TCM is sudden and reversible myocardial dysfunction often attributable to physical or emotional triggers. Case Report. We describe a 51-year-old man presented to emergency department with sepsis from urinary tract infection (UTI. He was placed on cefepime for UTI and non-ST-elevation myocardial infarction protocol given elevated troponins with chest pain. Subsequently, patient was pulseless with torsades de pointes (TdP and then converted to sinus rhythm with cardioversion. An echocardiogram revealed low ejection fraction with hypokinesis of the apical wall. Over 48 hours, the patient was extubated and stable on 3 L/min nasal cannula. He underwent a cardiac catheterization to evaluate coronary artery disease (CAD and was found to have mild nonobstructive CAD with no further findings. Conclusion. TCM is a rare disorder presenting with symptoms similar to acute coronary syndrome. Though traditionally elicited by physical and emotional triggers leading to transient left ventricular dysfunction, our case suggests that it may also be triggered by a urinary tract infection and lead to severe QT prolongation and a malignant ventricular arrhythmia in TdP.

Intermittent Hypoxia-Induced Cardiovascular Remodeling Is Reversed by Normoxia in a Mouse Model of Sleep Apnea.

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Castro-Grattoni, Anabel L; Alvarez-Buvé, Roger; Torres, Marta; Farré, Ramon; Montserrat, Josep M; Dalmases, Mireia; Almendros, Isaac; Barbé, Ferran; Sánchez-de-la-Torre, Manuel

2016-06-01

Intermittent hypoxia (IH) is the principal injurious factor involved in the cardiovascular morbidity and mortality associated with OSA. The gold standard for treatment is CPAP, which eliminates IH and appears to reduce cardiovascular risk. There is no experimental evidence on the reversibility of cardiovascular remodeling after IH withdrawal. The objective of the present study is to assess the reversibility of early cardiovascular structural remodeling induced by IH after resumption of normoxic breathing in a novel recovery animal model mimicking OSA treatment. We investigated cardiovascular remodeling in C57BL/6 mice exposed to IH for 6 weeks vs the normoxia group and its spontaneous recovery after 6 subsequent weeks under normoxia. Aortic expansive remodeling was induced by IH, with intima-media thickening and without lumen perimeter changes. Elastic fiber network disorganization, fragmentation, and estrangement between the end points of disrupted fibers were increased by IH. Extracellular matrix turnover was altered, as visualized by collagen and mucoid interlaminar accumulation. Furthermore, left ventricular perivascular fibrosis was increased by IH, whereas cardiomyocytes size was unaffected. These cardiovascular remodeling events induced by IH were normalized after recovery in normoxia, mimicking CPAP treatment. The early structural cardiovascular remodeling induced by IH was normalized after IH removal, revealing a novel recovery model for studying the effects of OSA treatment. Our findings suggest the clinical relevance of early detection and effective treatment of OSA in patients to prevent the natural course of cardiovascular diseases. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Lead-induced DNA damage in Vicia faba root cells: Potential involvement of oxidative stress

OpenAIRE

Pourrut, Bertrand; Jean, Séverine; Silvestre, Jérôme; Pinelli, Eric

2011-01-01

Genotoxic effects of lead (0–20 µM) were investigated in whole-plant roots of Vicia faba L., grown hydroponically under controlled conditions. Lead-induced DNA damage in V. faba roots was evaluated by use of the comet assay, which allowed the detection of DNA strand-breakage and with the V. faba micronucleus test, which revealed chromosome aberrations. The results clearly indicate that lead induced DNA fragmentation in a dose-dependant manner with a maximum effect at 10 µM. In addition, at th...

Choline Modulation of the Aβ P1-40 Channel Reconstituted into a Model Lipid Membrane

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Daniela Meleleo

2010-01-01

Full Text Available Nicotinic acetylcholine receptors (AChRs, implicated in memory and learning, in subjects affected by Alzheimer's disease result altered. Stimulation of α7-nAChRs inhibits amyloid plaques and increases ACh release. β-amyloid peptide (AβP forms ion channels in the cell and model phospholipid membranes that are retained responsible in Alzheimer disease. We tested if choline, precursor of ACh, could affect the AβP1-40 channels in oxidized cholesterol (OxCh and in palmitoyl-oleoyl-phosphatidylcholine (POPC:Ch lipid bilayers. Choline concentrations of 5 × 10−11 M–1.5 × 10−8 M added to the cis- or trans-side of membrane quickly increased AβP1-40 ion channel frequency (events/min and ion conductance in OxCh membranes, but not in POPC:Ch membranes. Circular Dichroism (CD spectroscopy shows that after 24 and 48 hours of incubation with AβP1-40, choline stabilizes the random coil conformation of the peptide, making it less prone to fibrillate. These actions seem to be specific in that ACh is ineffective either in solution or on AβP1-40 channel incorporated into PLMs.

Comparison of the efficacy of two anticonvulsants, phenytoin and valproate to improve PCP and d-amphetamine induced deficits in a reversal learning task in the rat

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Nagi F Idris

2009-06-01

Full Text Available Recent studies in our laboratory have shown that PCP (phencyclidine and d-amphetamine induce a cognitive deficit in rats, in a paradigm of potential relevance for the pathology of schizophrenia. Atypical, but not classical antipsychotics and the anticonvulsant, lamotrigine have been shown to prevent a selective reversal learning deficit induced by PCP. In contrast, only haloperidol reversed the d-amphetamine-induced deficit. The present study aimed to explore the ability of two anticonvulsants with differing mechanism of action, valproate and phenytoin to attenuate the cognitive deficits induced by PCP and d-amphetamine in the reversal learning paradigm. PCP at 1.5mg/kg and d-amphetamine at 0.5mg/kg both produced a selective and significant reduction in performance of the reversal phase with no effect on the initial phase of the task in female-hooded Lister rats. Valproate (25-200mg/kg and phenytoin (25-50mg/kg had no effect on performance when administered alone. Valproate (100-200mg/kg, whose principle action is thought to be the enhancement of GABA transmission, was unable to prevent the cognitive deficit induced by either PCP or d-amphetamine. Conversely, phenytoin (50mg/kg, a use-dependent sodium channel inhibitor, significantly prevented the deficit induced by PCP, but not d-amphetamine. These results add to our earlier work with lamotrigine, and suggest that sodium channel blockade may be a mechanism by which some anticonvulsant drugs can prevent the PCP-induced deficit. These data have implications for the use of anticonvulsant drugs in the treatment of cognitive or psychotic disorders.

Biotinidase deficiency: a reversible metabolic encephalopathy. Neuroimaging and MR spectroscopic findings in a series of four patients

International Nuclear Information System (INIS)

Desai, Shrinivas; Ganesan, Karthik; Hegde, Anaita

2008-01-01

Biotinidase deficiency is a metabolic disorder characterized by inability to recycle biotin with resultant delayed myelination. Clinical findings include seizures, ataxia, alopecia and dermatitis with atypical findings of myoclonic jerks, neuropathy and spastic paraparesis. Neuroradiological findings include cerebral atrophy, encephalopathy and widened extracerebral CSF spaces. Many of the clinical and neuroradiological features are reversible except sensorineural hearing loss and optic atrophy. To understand and describe the neuroimaging and spectroscopic findings of biotinidase deficiency. We evaluated the spectrum of neuroimaging and spectroscopic findings in four patients with biotinidase deficiency with follow-up studies in three patients. The imaging findings were encephalopathy, low cerebral volume, ventriculomegaly and widened extracerebral CSF spaces. Uncommon findings were caudate involvement, parieto-occipital cortical abnormalities and one patient with restricted diffusion. Two patients had subdural effusions, which is uncommon in biotinidase deficiency. 1 H-MR spectroscopy revealed elevated lactate, reversal of the choline/creatine ratio and decreased NAA peaks. Follow-up studies revealed complete reversal of imaging findings in two patients. Biotinidase deficiency is a reversible metabolic encephalopathy. This study highlights the importance of early and prompt cliniconeuroradiological diagnosis of biotinidase deficiency as it has an extremely good clinical outcome if treatment is initiated from early infancy. (orig.)

Biotinidase deficiency: a reversible metabolic encephalopathy. Neuroimaging and MR spectroscopic findings in a series of four patients

Energy Technology Data Exchange (ETDEWEB)

Desai, Shrinivas [Jaslok Hospital and Research Centre, Department of CT and MRI, Mumbai (India); Ganesan, Karthik [Jaslok Hospital and Research Centre, Department of CT and MRI, Mumbai (India); University of California, San Diego, Department of Radiology, San Diego, CA (United States); Hegde, Anaita [Jaslok Hospital and Research Centre, Department of Paediatrics, Mumbai (India)

2008-08-15

Biotinidase deficiency is a metabolic disorder characterized by inability to recycle biotin with resultant delayed myelination. Clinical findings include seizures, ataxia, alopecia and dermatitis with atypical findings of myoclonic jerks, neuropathy and spastic paraparesis. Neuroradiological findings include cerebral atrophy, encephalopathy and widened extracerebral CSF spaces. Many of the clinical and neuroradiological features are reversible except sensorineural hearing loss and optic atrophy. To understand and describe the neuroimaging and spectroscopic findings of biotinidase deficiency. We evaluated the spectrum of neuroimaging and spectroscopic findings in four patients with biotinidase deficiency with follow-up studies in three patients. The imaging findings were encephalopathy, low cerebral volume, ventriculomegaly and widened extracerebral CSF spaces. Uncommon findings were caudate involvement, parieto-occipital cortical abnormalities and one patient with restricted diffusion. Two patients had subdural effusions, which is uncommon in biotinidase deficiency. {sup 1}H-MR spectroscopy revealed elevated lactate, reversal of the choline/creatine ratio and decreased NAA peaks. Follow-up studies revealed complete reversal of imaging findings in two patients. Biotinidase deficiency is a reversible metabolic encephalopathy. This study highlights the importance of early and prompt cliniconeuroradiological diagnosis of biotinidase deficiency as it has an extremely good clinical outcome if treatment is initiated from early infancy. (orig.)

75 FR 760 - Choline chloride; Exemption from the Requirement of a Tolerance

Science.gov (United States)

2010-01-06

... affected. The North American Industrial Classification System (NAICS) codes have been provided to assist... body functions including the maintenance of osmotic pressure, acid-base balance, muscular activity, and... nervous system and memory. Choline is necessary to promote proper development in the fetus and infant and...

The reverse remodeling response to sacubitril/valsartan therapy in heart failure with reduced ejection fraction.

Science.gov (United States)

Martens, Pieter; Beliën, Hanne; Dupont, Matthias; Vandervoort, Pieter; Mullens, Wilfried

2018-05-17

Major classes of medical therapy for heart failure with reduced ejection fraction (HFrEF) induce reverse remodeling. The revere remodeling response to sacubitril/valsartan remains unstudied. We performed a single-center, prospective assessor-blinded study to determine the reverse remodeling response of sacubitril/valsartan therapy in HFrEF patients with a class I indication (New York heart Association [NYHA]-class II-IV, Left ventricular ejection fraction [LVEF] sacubitril/valsartan were optimized to individual tolerance. Echocardiographic images were assessed offline by 2 investigators blinded to both the clinical data and timing of echocardiograms. One-hundred-twenty-five HFrEF patients (66 ± 10 years) were prospectively included. The amount of RAS-blocker before and after switch to sacubitril/valsartan was similar(P = .290), indicating individual optimal dosing of sacubitril/valsartan. Over a median(IQR) follow-up of 118(77-160) days after initiation of sacubitril/valsartan, LVEF improved (29.6 ± 6% vs 34.8 ± 6%; P sacubitril/valsartan leading to more reverse remodeling. Switching therapy in eligible HFrEF patients from a RAS-blocker to sacubitril/valsartan induces beneficial reverse remodeling of both metrics of systolic as diastolic function. © 2018 John Wiley & Sons Ltd.

Ultraviolet-induced reversion of cyc1 alleles in radiation-sensitive strains of yeast. III. rev 3 mutant strains

International Nuclear Information System (INIS)

Lawrence, C.W.; Crhistensen, R.B.

1979-01-01

The role of rev3 gene function in uv-induced mutagenesis in the yeast Saccharomyces cerevisiae has been examined by determining the reversion of 12 well-defined cyc1 mutations in diploid strains homozygous for the rev3-1 or rev3-3 allale. The 12 cyc1 alleles include one ochre, one amber, four initiation, two proline missense, and four frameshift mutations. We find that the rev3 mutations reduce the frequency of UV-induced reversion of all of the cyc1 alleles, though different classes of alleles respond to a different extent. These results imply that the rev3 gene function is required for the production of a wide variety of mutational events, though probably not all, and show that each of the three rev loci have different mutational phenotypes. Such diverse phenotypes are not predicted by the unitary model for bacterial mutagenes, suggesting that this is at best an incomplete description of eukaryotic mutagenesis

Protective effects of sodium selenite on lead nitrate-induced hepatotoxicity in diabetic and non-diabetic rats.

Science.gov (United States)

Kalender, Suna; Apaydin, Fatma Gökçe; Baş, Hatice; Kalender, Yusuf

2015-09-01

In the present study, the effect of sodium selenite on lead induced toxicity was studied in Wistar rats. Sodium selenite and lead nitrate were administered orally for 28 days to streptozotocin induced diabetic and non-diabetic rats. Eight groups of rats were used in the study: control, sodium selenite, lead nitrate, lead nitrate+sodium selenite, streptozotocin-induced diabetic-control, diabetic-sodium selenite, diabetic-lead nitrate, diabetic-lead nitrate+sodium selenite groups. Serum biochemical parameters, lipid peroxidation, antioxidant enzymes and histopathological changes in liver tissues were investigated in all groups. There were statistically significant changes in liver function tests, antioxidant enzyme activities and lipid peroxidation levels in lead nitrate and sodium selenite+lead nitrate treated groups, also in diabetic and non-diabetic groups. Furthermore, histopathological alterations were demonstrated in same groups. In the present study we found that sodium selenite treatment did not show completely protective effect on diabetes mellitus caused damages, but diabetic rats are more susceptible to lead toxicity than non-diabetic rats. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of Si on the reversibility of stress-induced martensite in Fe-Mn-Si shape memory alloys

Energy Technology Data Exchange (ETDEWEB)

Stanford, N. [Centre for Material and Fibre Innovation, Deakin University, Geelong, Victoria 3217 (Australia); Dunne, D.P., E-mail: druce_dunne@uow.edu.au [Faculty of Engineering, University of Wollongong, Wollongong, NSW 2522 (Australia)

2010-12-15

Fe-Mn-Si is a well-characterized ternary shape memory alloy. Research on this alloy has consistently shown that the addition of 5-6 wt.% Si is desirable to enhance the reversibility of stress-induced martensite vis-a-vis shape memory. This paper examines the effect of Si on the morphology and the crystallography of the martensite in the Fe-Mn-Si system. It is concluded that the addition of Si increases the c/a ratio of the martensite, reduces the transformation volume change and decreases the atomic spacing difference between the parallel close-packed directions in the austenite-martensite interface (habit) plane. It is proposed that, in addition to austenite strengthening, Si enhances reversibility by reducing the volume change and the interfacial atomic mismatch between the martensite and the austenite. Although shape memory is improved, transformation reversibility remains limited by the necessary misfit dislocations that accommodate the atomic spacing differences in the interface.

Effect of Si on the reversibility of stress-induced martensite in Fe-Mn-Si shape memory alloys

International Nuclear Information System (INIS)

Stanford, N.; Dunne, D.P.

2010-01-01

Fe-Mn-Si is a well-characterized ternary shape memory alloy. Research on this alloy has consistently shown that the addition of 5-6 wt.% Si is desirable to enhance the reversibility of stress-induced martensite vis-a-vis shape memory. This paper examines the effect of Si on the morphology and the crystallography of the martensite in the Fe-Mn-Si system. It is concluded that the addition of Si increases the c/a ratio of the martensite, reduces the transformation volume change and decreases the atomic spacing difference between the parallel close-packed directions in the austenite-martensite interface (habit) plane. It is proposed that, in addition to austenite strengthening, Si enhances reversibility by reducing the volume change and the interfacial atomic mismatch between the martensite and the austenite. Although shape memory is improved, transformation reversibility remains limited by the necessary misfit dislocations that accommodate the atomic spacing differences in the interface.

Mechanism of chlorphentermine-induced lymphocyte toxicity: initial investigations

International Nuclear Information System (INIS)

Sauers, L.J.; Wierda, D.; Reasor, M.J.

1986-01-01

Chlorphentermine (CP) inhibits the blastogenic response of mouse splenic and human peripheral blood lymphocytes to the T-cell mitogens, phytohemagglutinin (PHA) and concanavalin A (Con A). The purpose of these studies was to examine in vitro the mechanism mediating this immunosuppression. If mouse or human lymphocytes are pretreated with CP for 30 minutes, then stimulated with PHA, their blastogenic response is inhibited 80% and 45%, respectively. However, if CP is not added until 10 minutes or later following PHA stimulation, the inhibitory effect of the drug is essentially eliminated. The authors also determined that CP can potentiate Con A-induced agglutination of human lymphocytes. Enhanced agglutination can result from changes in the integrity of membrane phospholipids. Because changes in membrane phospholipid biochemistry characteristically occur within 10 minutes after mitogen-induced lymphocyte activation, the authors examined whether CP altered the incorporation of choline into cellular phospholipids. They found that CP decreases overall incorporation of 14 C-choline into cellular phospholipids of mouse lymphocytes by 45% during the first 4 hours of activation. These data suggest that the immunotoxicity associated with CP may be mediated by drug-induced changes at the membrane level that appear to occur early during lymphocyte activation

Prospective head-to-head comparison of {sup 11}C-choline-PET/MR and {sup 11}C-choline-PET/CT for restaging of biochemical recurrent prostate cancer

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Eiber, Matthias [Klinikum rechts der Isar, Department of Nuclear Medicine, Technische Universitaet Muenchen, Munich (Germany); David Geffen School of Medicine at UCLA, Department of Molecular and Medical Pharmacology, Los Angeles (United States); Rauscher, Isabel; Souvatzoglou, Michael; Schwaiger, Markus [Klinikum rechts der Isar, Department of Nuclear Medicine, Technische Universitaet Muenchen, Munich (Germany); Maurer, Tobias [Klinikum rechts der Isar, Department of Urology, Technische Universitaet Muenchen, Munich (Germany); Holzapfel, Konstantin [Klinikum rechts der Isar, Department of Radiology, Technische Universitaet Muenchen, Munich (Germany); Beer, Ambros J. [Klinikum rechts der Isar, Department of Nuclear Medicine, Technische Universitaet Muenchen, Munich (Germany); Ulm University, Department of Nuclear Medicine, Ulm (Germany)

2017-12-15

Whole-body integrated {sup 11}C-choline PET/MR might provide advantages compared to {sup 11}C-choline PET/CT for restaging of prostate cancer (PC) due to the high soft-tissue contrast and the use of multiparametric MRI, especially for detection of local recurrence and bone metastases. Ninety-four patients with recurrent PC underwent a single-injection/dual-imaging protocol with contrast-enhanced PET/CT followed by fully diagnostic PET/MR. Imaging datasets were read separately by two reader teams (team 1 and 2) assessing the presence of local recurrence, lymph node and bone metastases in predefined regions using a five-point scale. Detection rates were calculated. The diagnostic performance of PET/CT vs. PET/MR was compared using ROC analysis. Inter-observer and inter-modality variability, radiation exposure, and mean imaging time were evaluated. Clinical follow-up, imaging, and/or histopathology served as standard of reference (SOR). Seventy-five patients qualified for the final image analysis. A total of 188 regions were regarded as positive: local recurrence in 37 patients, 87 regions with lymph node metastases, and 64 regions with bone metastases. Mean detection rate between both readers teams for PET/MR was 84.7% compared to 77.3% for PET/CT (p > 0.05). Local recurrence was identified significantly more often in PET/MR compared to PET/CT by team 1. Lymph node and bone metastases were identified significantly more often in PET/CT compared to PET/MR by both teams. However, this difference was not present in the subgroup of patients with PSA values ≤2 ng/ml. Inter-modality and inter-observer agreement (K > 0.6) was moderate to substantial for nearly all categories. Mean reduction of radiation exposure for PET/MR compared to PET/CT was 79.7% (range, 72.6-86.2%). Mean imaging time for PET/CT was substantially lower (18.4 ± 0.7 min) compared to PET/MR (50.4 ± 7.9 min). {sup 11}C-choline PET/MR is a robust imaging modality for restaging biochemical recurrent PC

Lewis acidic (choline chloride.3ZnCl2) ionic liquid: A green and ...

Indian Academy of Sciences (India)

Choline chloride; zinc chloride; ionic liquid; one-pot; triarylmethane. 1. Introduction ... applications such as zinc electroplating11 and batter- ies.12 It has also been used as ... as indicated by Thin Layer Chromatography (TLC), the catalyst was ...

Noninvasive monitoring of radiation-induced treatment response using proton magnetic resonance spectroscopy and diffusion-weighted magnetic resonance imaging in a colorectal tumor model

International Nuclear Information System (INIS)

Seierstad, Therese; Roe, Kathrine; Olsen, Dag Rune

2007-01-01

Background and purpose: To examine whether in vivo proton magnetic resonance spectroscopy ( 1 H MRS) and diffusion-weighted magnetic resonance imaging (DW-MRI) can monitor radiation-induced changes in HT29 xenografts in mice. Materials and methods: HT29 xenografts in mice received a dose of 15 Gy. In vivo 1 H MRS and DW-MRI were acquired pretreatment and 1, 3, 6 and 10 days post-irradiation. After imaging, tumors were excised for histological analysis. The amounts of necrosis, fibrosis and viable cells in the cross sections were scored and compared to changes in apparent diffusion coefficient (ADC) and choline/water ratio. Results: Radiation-induced necrosis in the xenografts was observed as increased tumor ADC. In-growth of fibrosis three days post-irradiation restricting water mobility was accompanied by decreased tumor ADC. Choline/water ratio correlated with metabolic activity and tumor growth. Conclusions: ADC and choline/water ratio assessed by in vivo DW-MRI and 1 H MRS depicts radiation-induced changes in HT29 xenografts following irradiation

Cerebral palsy in adult patients: constraint-induced movement therapy is effective to reverse the nonuse of the affected upper limb

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Ana Cecília P. Oliveira

2016-01-01

Full Text Available ABSTRACT Objective To determine if the original protocol of Constraint-Induced Movement Therapy (CIMT, is adequate to reverse the nonuse of the affected upper limb (AUL in patients with Cerebral Palsy (CP in adulthood. Method The study included 10 patients diagnosed with CP hemiparesis had attended the adult protocol CIMT, from January/August 2009/2014. Results Average age 24.6 (SD 9.44; MAL average pretreatment How Often (HO = 0.72 and How Well (HW = 0.68 and post-treatment HO = 3.77 and HW = 3.60 (p ≤ 0.001 and pretreatment WMFT average = 21.03 and post-treatment average = 18.91 (p = 0.350. Conclusion The constraint-induced movement therapy is effective to reverse the nonuse learn of the AUL in adult patients with CP.

Folate, vitamin B12, alpha-tocopherol and selected liver components in periparturient dairy goats supplemented with choline and vitamin E

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V. Dell'Orto

2010-04-01

Full Text Available The influence of rumen-protected choline and vitamin E administration on status of folate, vitamin B12, and vitamin E and selected liver components was studied on 4 groups of 12 periparturient dairy goats: control, CTR; choline supplemented, RPC; vitamin E, VITE; choline and vitamin E, RPCE. Plasma folate did not differ between groups, except at parturition when RPC and RPCE goats had higher folate levels than CTR and VITE animals. Neither RPC nor vitamin E affected vitamin B12 plasma concentrations, while a time effect was observed after the third week of lactation, when B12 levels in each group started to increase. Alpha-tocopherol supplementation was associated with increased plasma a-tocopherol in the VITE and RPCE compared to the CRT and RPC groups, while RPC supplementation did not affect a-tocopherol levels in both RPC and RPCE groups compared to CTR and VITE ones. In control and RPC goats liver total lipid did not differ, while DNA contents and their ratio, were respectively higher and lower in RPC supplemented animals. Overall these results suggest that greater choline availability seems to be essential for optimising metabolic health and methyl group status, in dairy ruminants.

Vinclozolin exposure in utero induces postpubertal prostatitis and reduces sperm production via a reversible hormone-regulated mechanism.