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Sample records for valproic acid concentrations

  1. Hyperammonemia Associated with Valproic Acid Concentrations

    Directory of Open Access Journals (Sweden)

    Marta Vázquez

    2014-01-01

    Full Text Available Valproic acid, a branched short-chain fatty acid, has numerous action mechanisms which turn it into a broad spectrum anticonvulsant drug and make its use possible in some other pathologies such as bipolar disorder. It is extensively metabolized in liver, representing β-oxidation in the mitochondria one of its main metabolic route (40%. Carnitine is responsible for its entry into the mitochondria as any other fatty acid. Long-term high-dose VPA therapy or acute VPA overdose induces carnitine depletion, resulting in high levels of ammonia in blood. As a high correlation between salivary valproic acid levels and plasma ultrafiltrate levels was found in humans, saliva becomes a promising monitoring fluid in order to study valproic acid pharmacokinetics and its toxic effect. Extended-release (twice daily formulations of valproic acid or carnitine supplementation are the proposed two therapeutic strategies in order to reverse hyperammonemia.

  2. Valproic Acid

    Science.gov (United States)

    ... acid is in a class of medications called anticonvulsants. It works by increasing the amount of a ... older (about 1 in 500 people) who took anticonvulsants such as valproic acid to treat various conditions ...

  3. Use of hexadeuterated valproic acid and gas chromatography-mass spectrometry to determine the pharmacokinetics of valproic acid

    International Nuclear Information System (INIS)

    Acheampong, A.A.; Abbott, F.S.; Orr, J.M.; Ferguson, S.M.; Burton, R.W.

    1984-01-01

    Di-[( 3,3,3- 2 H3]propyl)acetic acid, a hexadeuterated analogue of valproic acid, was synthesized and its pharmacokinetic properties compared with valproic acid. Concentrations of valproic acid and [ 2 H]valproic acid in serum and saliva were determined by GC-MS using selected-ion monitoring. Saliva drug levels were measured with good precision down to 0.1 microgram/mL. Kinetic equivalence of valproic acid and [ 2 H]valproic acid was demonstrated in a single-dose study in a human volunteer. An isotope effect was observed for omega-oxidation, but the difference in metabolism was not sufficient to make [ 2 H]valproic acid biologically nonequivalent. The application of [ 2 H]valproic acid to determine the kinetics of valproic acid under steady-state concentrations was evaluated in the same volunteer. The kinetic data obtained with [ 2 H]valproic acid was consistent with previously reported values for valproic acid including kinetic differences observed between single-dose and steady-state experiments. Saliva levels of valproic acid were found to give a good correlation with total serum valproic acid under multiple-dose conditions. A concentration dependence was found for the ratio of saliva valproic acid to free valproic acid in serum, low ratios being observed at high serum concentrations of valproic acid

  4. Valproic Acid and Pregnancy

    Science.gov (United States)

    ... is possible. Studies have found that women with seizure disorders and women with bipolar disorder might have menstrual ... valproic acid to leave your body. Women with epilepsy or bipolar disorder who are planning a pregnancy ...

  5. Valproic Acid Induced Hyperammonaemic Encephalopathy

    International Nuclear Information System (INIS)

    Amanat, S.; Shahbaz, N.; Hassan, Y.

    2013-01-01

    Objective: To observe clinical and laboratory features of valproic acid-induced hyperammonaemic encephalopathy in patients taking valproic acid. Methods: Observational study was conducted at the Neurology Department, Dow University of Health Sciences, Civil Hospital, Karachi, from February 26, 2010 to March 20, 2011. Ten patients on valproic acid therapy of any age group with idiopathic or secondary epilepsy, who presented with encephalopathic symptoms, were registered and followed up during the study. Serum ammonia level, serum valproic acid level, liver function test, cerebrospinal fluid examination, electroencephalogram and brain imaging of all the patients were done. Other causes of encephalopathy were excluded after clinical and appropriate laboratory investigations. Microsoft Excel 2007 was used for statistical analysis. Results: Hyperammonaemia was found in all patients with encephalopathic symptoms. Rise in serum ammonia was independent of dose and serum level of valproic acid. Liver function was also found to be normal in 80% (n=8) of the patients. Valproic acid was withdrawn in all patients. Three (30%) patients improved only after the withdrawal of valproic acid. Six (60%) patients improved after L-Carnitine replacement, one (10%) after sodium benzoate. On followup, serum ammonia had reduced to normal in five (50%) patients and to more than half of the baseline level in two (20%) patients. Three (30%) patients were lost to followup after complete clinical improvement. Conclusion: Within therapeutic dose and serum levels, valproic acid can cause symptomatic hyperammonaemia resulting in encephalopathy. All patients taking valproic acid presenting with encephalopathic symptoms must be monitored for the condition. (author)

  6. Valproic Acid-induced Agranulocytosis

    Directory of Open Access Journals (Sweden)

    Hui-Chuan Hsu

    2009-06-01

    Full Text Available Valproic acid is considered to be the most well-tolerated antiepileptic drug. However, few cases of neutropenia or leukopenia caused by valproic acid have been reported. We present a patient who took valproic acid to treat a complication of brain surgery and in whom severe agranulocytosis occurred after 2.5 months. Valproic acid was stopped immediately, and granulocyte colony-stimulating factor was administered for 2 days. The patient's white blood cell count returned to normal within 2 weeks. The result of bone marrow aspiration was compatible with drug-induced agranulocytosis. This case illustrates that patients who take valproic acid may need regular checking of complete blood cell count.

  7. Soybean greatly reduces valproic acid plasma concentrations: A food–drug interaction study

    Science.gov (United States)

    Marahatta, Anu; Bhandary, Bidur; Jeong, Seul-Ki; Kim, Hyung-Ryong; Chae, Han-Jung

    2014-01-01

    The aim of this study was to investigate the effects of soy on the pharmacokinetics and pharmacodynamics of valproic acid (VPA). In a preclinical study, rats were pretreated with two different amounts of soy extract for five days (150 mg/kg and 500 mg/kg), which resulted in decreases of 57% and 65% in the Cmax of VPA, respectively. AUC of VPA decreased to 83% and 70% in the soy pretreatment groups. Interestingly, the excretion rate of VPA glucuronide (VPAG) was higher in the soy-fed groups. Levels of UDP-glucuronosyltransferase (UGT) UGT1A3, UGT1A6, UGT2B7 and UGT2B15 were elevated in the soy-treated group, and GABA concentrations were elevated in the brain after VPA administration. However, this was less pronounced in soy extract pretreated group than for the untreated group. This is the first study to report the effects of soy pretreatment on the pharmacokinetics and pharmacodynamics of VPA in rodents. PMID:24618639

  8. Soybean greatly reduces valproic acid plasma concentrations: a food-drug interaction study.

    Science.gov (United States)

    Marahatta, Anu; Bhandary, Bidur; Jeong, Seul-Ki; Kim, Hyung-Ryong; Chae, Han-Jung

    2014-03-12

    The aim of this study was to investigate the effects of soy on the pharmacokinetics and pharmacodynamics of valproic acid (VPA). In a preclinical study, rats were pretreated with two different amounts of soy extract for five days (150 mg/kg and 500 mg/kg), which resulted in decreases of 57% and 65% in the Cmax of VPA, respectively. AUC of VPA decreased to 83% and 70% in the soy pretreatment groups. Interestingly, the excretion rate of VPA glucuronide (VPAG) was higher in the soy-fed groups. Levels of UDP-glucuronosyltransferase (UGT) UGT1A3, UGT1A6, UGT2B7 and UGT2B15 were elevated in the soy-treated group, and GABA concentrations were elevated in the brain after VPA administration. However, this was less pronounced in soy extract pretreated group than for the untreated group. This is the first study to report the effects of soy pretreatment on the pharmacokinetics and pharmacodynamics of VPA in rodents.

  9. Association between the blood concentrations of ammonia and carnitine/amino acid of schizophrenic patients treated with valproic acid.

    Science.gov (United States)

    Ando, Masazumi; Amayasu, Hideaki; Itai, Takahiro; Yoshida, Hisahiro

    2017-01-01

    Administration of valproic acid (VPA) is complicated with approximately 0.9% of patients developing hyperammonemia, but the pathogenesis of this adverse effect remains to be clarified. The aim of the present study was to search for mechanisms associated with VPA-induced hyperammonemia in the light of changes in serum amino acids concentrations associated with the urea cycle of schizophrenic patients. Blood samples (10 mL) were obtained from 37 schizophrenic patients receiving VPA for the prevention of violent behaviors in the morning after overnight fast. Blood concentrations of ammonia, VPA, free carnitine, acyl-carnitine, and 40 amino acids including glutamate and citrulline were measured for each patient. Univariate and multivariate regression analyses were performed to identify amino acids or concomitantly administered drugs that were associated with variability in the blood concentrations of ammonia. The blood ammonia level was positively correlated with the serum glutamate concentration ( r  = 0.44, p  < 0.01) but negatively correlated with glutamine ( r  = -0.41, p  = 0.01), citrulline ( r  = -0.42, p  = 0.01), and glycine concentrations ( r  = -0.54, p  < 0.01). It was also revealed that the concomitant administration of the mood stabilizers ( p  = 0.04) risperidone ( p  = 0.03) and blonanserin ( p  < 0.01) was positively associated with the elevation of the blood ammonia level. We hypothisized that VPA would elevate the blood ammonia level of schizophrenic patients. The observed changes in serum amino acids are compatible with urea cycle dysfunction, possibly due to reduced carbamoyl-phosphate synthase 1 (CPS1) activity. We conclude that VPA should be prudently prescribed to schizophrenic patients, particularly those receiving mood stabilizers or certain antipsychotics.

  10. Removal of valproic acid by plasmapheresis in a patient treated for multiple sclerosis

    NARCIS (Netherlands)

    Bastiaans, D.E.T.; Uden, I.W.M. van; Ruiterkamp, R.A.; Jong, B.A. de

    2013-01-01

    We present a case of a patient with multiple sclerosis who was treated with plasmapheresis and valproic acid. We used therapeutic drug monitoring to determine whether plasma concentrations of valproic acid were kept within the therapeutic window and to determine the amount of valproic acid that was

  11. Severe Valproic Acid Intoxication Responding to Hemodialysis

    Directory of Open Access Journals (Sweden)

    Ali Ertuğ Arslanköylü

    2017-08-01

    Full Text Available Valproic acid is a commonly used antiepileptic drug which causes intoxication easily due to its narrow therapeutic window. Here, we present a child with valproic acid poisoning who responded to hemodialysis. A 14-year-old male patient with epilepsy and mental motor retardation was admitted to the pediatric intensive care unit due to valproic acid intoxication. Plasma valproic acid level was 710 µg/mL. The patient’s vital signs were stable and a decrease was observed in the valproic acid and ammonia levels with supportive treatment at the beginning. On the third day of the admission, hemodynamic and mental status of the patient deteriorated, plasma ammonia and lactate levels elevated, thus, we decided to perform hemodialysis. After hemodialysis, the patient’s hemodynamic status and mental function improved in conjunction with the reduction in valproic acid, ammonia and lactate levels. Thus he was transferred to the pediatric ward. Hemodialysis may be considered an effective treatment choice for severe valproic acid intoxication. Here, it was shown that hemodialysis may also be effective in patients with deteriorated general status under supportive treatment in the late phase of valproic acid intoxication.

  12. The Effect of Different Carbapenem Antibiotics (Ertapenem, Imipenem/Cilastatin, and Meropenem) on Serum Valproic Acid Concentrations.

    Science.gov (United States)

    Wu, Chien-Chih; Pai, Tsung-Yu; Hsiao, Fei-Yuan; Shen, Li-Jiuan; Wu, Fe-Lin Lin

    2016-10-01

    Carbapenem antibiotics (CBPMs) may significantly reduce the serum concentration of valproic acid (VPA), but the extent of this effect among various CBPMs is unknown. This study compared the extent and onset of the interactions among ertapenem, imipenem/cilastatin, and meropenem. A 5-year retrospective study was performed. Hospitalized patients over 18 years old who received VPA and a CBPM concurrently were enrolled via the pharmacy computer system. Patients who lacked VPA serum concentration measurements before or during CBPMs' use, had concurrent medication(s) that might interfere with VPA metabolism, or had a history of liver cirrhosis were excluded. Total VPA serum concentrations before and during CBPMs' use and after its discontinuation were recorded, and differences among various CBPMs were analyzed. Fifty-two patients were included in this analysis. Irrespective of the route of administration, VPA serum concentrations were subtherapeutic in 90% of the subjects during CBPMs' use. There was a significant decrease (P imipenem/cilastatin (N = 17), and meropenem (N = 26) groups, respectively. The effect of ertapenem and meropenem on VPA was significantly more expressed than that of imipenem/cilastatin (P imipenem/cilastatin. Because of the dramatic reduction of VPA serum concentration during CBPMs' use, concomitant use of VPA and CBPMs should be avoided.

  13. Thrombotic microangiopathy associated with Valproic acid toxicity.

    Science.gov (United States)

    Hebert, Sean A; Bohan, Timothy P; Erikson, Christian L; Swinford, Rita D

    2017-08-03

    Thrombotic microangiopathy (TMA) is a serious, sometimes life-threatening disorder marked by the presence of endothelial injury and microvascular thrombi. Drug-induced thrombotic microangiopathy (DI-TMA) is one specific TMA syndrome that occurs following drug exposure via drug-dependent antibodies or direct tissue toxicity. Common examples include calcineurin inhibitors Tacrolimus and Cyclosporine and antineoplastics Gemcitabine and Mitomycin. Valproic acid has not been implicated in DI-TMA. We present the first case of a patient meeting clinical criteria for DI-TMA following admission for valproic acid toxicity. An adolescent male with difficult to control epilepsy was admitted for impaired hepatic function while on valproic acid therapy. On the third hospital day, he developed severe metabolic lactic acidosis and multiorgan failure, prompting transfer to the pediatric intensive care unit. Progressive anemia and thrombocytopenia instigated an evaluation for thrombotic microangiopathy, where confirmed by concomitant hemolysis, elevated lactate dehydrogenase (LDH), low haptoglobin, and concurrent oliguric acute kidney injury. Thrombotic thrombocytopenic purpura was less likely with adequate ADAMTS13. Discontinuing valproic acid reversed the anemia, thrombocytopenia, and normalized the LDH and haptoglobin, supporting a drug-induced cause for the TMA. To the best of our knowledge, this is the first report of drug-induced TMA from valproic acid toxicity.

  14. Valproic Acid Suppositories for Management of Seizures for Geriatric Patients.

    Science.gov (United States)

    DiScala, Sandra L; Tran, Nhi N; Silverman, Michael A

    This case describes the use of valproic acid suppositories for secondary seizure prophylaxis in a geriatric veteran with a feeding and swallowing disorder. The effectiveness of valproic acid suppositories is outlined to reinforce the need for compounding pharmacies to have this formulation available to meet the needs of geriatric patients.

  15. Valproic acid monotherapy in pregnancy and major congenital malformations

    DEFF Research Database (Denmark)

    Jentink, Janneke; Loane, Maria A; Dolk, Helen

    2010-01-01

    The use of valproic acid in the first trimester of pregnancy is associated with an increased risk of spina bifida, but data on the risks of other congenital malformations are limited.......The use of valproic acid in the first trimester of pregnancy is associated with an increased risk of spina bifida, but data on the risks of other congenital malformations are limited....

  16. Compound list: valproic acid [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available valproic acid VPA 00005 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/valpr...oic_acid.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/valpr...oic_acid.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single/valpr...edbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/valproic_acid.Rat.in_vivo.Liver.Repeat.zip ftp:...//ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Kidney/Single/valproic_acid.Rat.in_vivo.Kidne

  17. The effect of valproic acid on rat ovarium and the protective role of ...

    African Journals Online (AJOL)

    ONOS

    2010-08-23

    Aug 23, 2010 ... specific ROS that mediates valproic acid-induced toxicity. In addition, valproic acid ... from murine pluripotent embryonic stem cells through an increase in ROS (Defoort ... vitamin E and folic acid. MATERIALS AND METHODS.

  18. Fatal Hyperammonemic Brain Injury from Valproic Acid Exposure

    Directory of Open Access Journals (Sweden)

    Danny Bega

    2012-12-01

    Full Text Available Background: Hyperammonemia is known to cause neuronal injury, and can result from valproic acid exposure. Prompt reduction of elevated ammonia levels may prevent permanent neurological injury. We report a case of fatal hyperammonemic brain injury in a woman exposed to valproic acid. Case: A 38-year-old woman with schizoaffective disorder and recent increase in valproic acid dosage presented with somnolence and confusion and rapidly progressed to obtundation. Brain MRI showed diffuse bilateral restricted diffusion in nearly the entire cerebral cortex. She had normal liver function tests but serum ammonia level was severely elevated at 288 µmol/l. Genetic testing showed no mutation in urea cycle enzymes. Despite successful elimination of ammonia with hemodialysis she developed fatal cerebral edema. Conclusion: Cerebral edema secondary to hyperammonemia is potentially reversible if recognized early. Ammonia excretion can be facilitated by initiation of hemodialysis and administration of scavenging agents (sodium phenylacetate and sodium benzoate. Severe hyperammonemia can result from valproic acid exposure even in the absence of hepatotoxicity or inborn errors of metabolism. It is important to check serum ammonia in any patient with encephalopathy who has had recent valproic acid exposure.

  19. The effect of a histone deacetylase inhibitor - valproic acid - on nucleoli in human leukaemic myeloblasts.

    Science.gov (United States)

    Smetana, K; Zápotocký, M

    2010-01-01

    The present study was undertaken to provide more information on nucleolar changes induced by a histone deacetylase inhibitor such as valproic acid in leukaemic myeloblasts at the single-cell level. For this study, RNA in nucleoli was visualized by a simple but sensitive cytochemical procedure in unfixed cytospins of short-term bone marrow cultures from patients suffering from acute myeloid leukaemia. Valproic acid in leukaemic myeloblasts markedly reduced the nucleolar size and also produced significant transformation of "active" to "resting" and "inactive" nucleoli that reflected the alteration of the nucleolar transcription in sensitive myeloblasts. On this occasion it should be added that valproic acid significantly increased the incidence of altered myeloblasts that changed to apoptotic cells or apoptotic bodies and cell ghosts. In contrast to the above-mentioned decreased nucleolar size, the nucleolar RNA concentration, expressed by computerassisted RNA image densitometry in valproic acidtreated myeloblasts, was not significantly changed. The results of the present study clearly indicated that the nucleolar size and transformation of "active" to "sleeping" or "inactive" nucleoli are convenient markers of the sensitivity and alteration of leukaemic myeloblasts produced by a histone deacetylase inhibitor, valproic acid, at the single-cell level.

  20. Case Report: Valproic Acid and Risperidone Treatment Leading to Development of Hyperammonemia and Mania

    Science.gov (United States)

    Carlson, Teri; Reynolds, Charles A.; Caplan, Rochelle

    2007-01-01

    This case report describes two children who developed hyperammonemia together with frank manic behavior during treatment with a combination of valproic acid and risperidone. One child had been maintained on valproic acid for years and risperidone was added. In the second case, valproic acid was introduced to a child who had been treated with…

  1. Valproic Acid Monotherapy in Pregnancy and Major Congenital Malformations.

    NARCIS (Netherlands)

    Jentink, J.; Loane, M.A.; Dolk, H.; Barisic, I.; Garne, E.; de Jong-van den Berg, L.T.W.; Morris, Joan K.

    2010-01-01

    Background: The use of valproic acid in the first trimester of pregnancy is associated with an increased risk of spina bifida, but data on the risks of other congenital malformations are limited. Methods: We first combined data from eight published cohort studies (1565 pregnancies in which the women

  2. Valproic Acid and Sleep Duration in Children with Epilepsy

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2009-09-01

    Full Text Available Sleep duration and behavior were assessed in 46 children (age range 1.7-17.4 years before and after tapering valproic acid (VPA administered for more than 6 months for epilepsy, in a study at University Children's Hospital, Zurich, Switzerland.

  3. Withdrawal of valproic acid treatment during pregnancy and seizure outcome

    DEFF Research Database (Denmark)

    Tomson, Torbjörn; Battino, Dina; Bonizzoni, Erminio

    2016-01-01

    Based on data from the EURAP observational International registry of antiepileptic drugs (AEDs) and pregnancy, we assessed changes in seizure control and subsequent AED changes in women who underwent attempts to withdraw valproic acid (VPA) during the first trimester of pregnancy. Applying Bayesi...

  4. Marked accumulation of valproic acid in embryonic neuroepithelium of the mouse during early organogenesis

    International Nuclear Information System (INIS)

    Dencker, L.; Nau, H.; D'Argy, R.

    1990-01-01

    Valproic acid, an antiepileptic drug, causes neural tube defects in mice and man. 14C-labeled valproic acid (sodium-salt) was administered to pregnant mice on days 8 and 9 of gestation (period of high sensitivity in regard to formation of neural tube defects in this species). Two dose levels of valproic acid (1 and 400 mg/kg) were used; in each case the total radioactivity administered was the same: 400 microCi/kg or 14.7 MBq/kg. Autoradiography combined with computerized densitometry revealed that in low-dose animals most of the radioactivity was confined to maternal liver and kidney, while at high doses more activity was observed in soft tissues and fluids, including amniotic fluid. In the embryo, the neuroepithelium showed the highest concentration, irrespective of dose and survival interval (30 min, 3 h, and 6 h). Upon administration of the high dose, up to five times more radioactivity (approximately 2,000 times more valproic acid) was recovered in embryonic tissues than after the low dose. It is concluded that high doses of VPA saturate the capacities of metabolism, excretion, and protein binding in the maternal organism, resulting in a higher proportion of the dose reaching the embryo, allowing more of the drug to be accumulated by the target organ, the neuroepithelium

  5. The efficiency of valproic acid in a child with trichotillomania

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    Sultan Kılıç

    2011-06-01

    Full Text Available Trichotillomania is a relatively rare impulse control disorder that causes patients to pull out own hair. Studies regarding the pharmacological treatment in children or adults are scarce, and there is a lack of consensus on drug treatment. The current trend is to use mood stabilizers for reducing repetitive behaviors.We present the case of 9-years-old child whose symptoms showed remarkable improvement after the administration of valproic acid. Our case is the second case in the literature that effectively treated with valproic acid. Additionally, this report indicates that this drug is potentially effective in reducing and also terminating complaints of trichotillomania. Further studies are needed to understand course of this disorder and considering the best treatment options. J Clin Exp Invest 2011;2(2:214-5

  6. Resistance to valproic acid as predictor of treatment resistance in genetic generalized epilepsies

    DEFF Research Database (Denmark)

    Gesche, Joanna; Khanevski, Marina; Solberg, Carl

    2017-01-01

    for refractory seizures. Resistance to valproic acid had a specificity of 100% to identify patients with drug resistance and correlated strongly with bad social outcome and seizure burden. Conversely, 21.2% of all patients with refractory seizures according to the ILAE definition later became seizure free...... (mainly with valproic acid). Our data suggest that "drug resistant GGE" must not be declared unless patients were adequately treated with valproic acid, and advocate resistance to valproic acid as a new clinical biomarker for drug-resistant GGE. A PowerPoint slide summarizing this article is available...

  7. Photocarcinogenesis of topical tazarotene and isotretinoin alone and in combination with valproic acid in hairless mice

    DEFF Research Database (Denmark)

    Lerche, Catharina Margrethe; Philipsen, Peter Alshede; Sehested, Maxwell

    2008-01-01

    Retinoids and the histone deacetylase inhibitor valproic acid have shown anticancer properties, but the photocarcinogenic or photoprotective effect is unclear. Therefore, we investigated whether a topical formulation of valproic acid is photocarcinogenic or photoprotective in hairless female C3.Cg/Tif...

  8. Valproic Acid in Women and Girls of Childbearing Age.

    Science.gov (United States)

    Gotlib, Dorothy; Ramaswamy, Rachel; Kurlander, Jacob E; DeRiggi, Alana; Riba, Michelle

    2017-09-01

    The aim of this paper is to evaluate recent literature on valproic acid (VPA) in women and girls of childbearing age and to emphasize new findings. Recent research confirms VPAs teratogenicity and risk of hormone disruption. VPA exposure in utero increases the risk for a variety of major congenital malformations (MCMs), reduced IQ and behavioral problems. In girls and women, VPA increases the risk of hormone abnormalities, obesity, and polycystic ovarian syndrome (PCOS). Despite guidelines recommending caution, VPA use continues to be prescribed to reproductive-aged women and girls. Despite significant and well-documented risk, adherence to guidelines in VPA use in reproductive-aged girls and women remains low.

  9. Extracorporeal treatment for valproic acid poisoning

    DEFF Research Database (Denmark)

    Ghannoum, Marc; Laliberté, Martin; Nolin, Thomas D

    2015-01-01

    . The workgroup concluded that VPA is moderately dialyzable (level of evidence = B) and made the following recommendations: ECTR is recommended in severe VPA poisoning (1D); recommendations for ECTR include a VPA concentration > 1300 mg/L (9000 μmol/L)(1D), the presence of cerebral edema (1D) or shock (1D......); suggestions for ECTR include a VPA concentration > 900 mg/L (6250 μmol/L)(2D), coma or respiratory depression requiring mechanical ventilation (2D), acute hyperammonemia (2D), or pH ≤ 7.10 (2D). Cessation of ECTR is indicated when clinical improvement is apparent (1D) or the serum VPA concentration is between...... 50 and 100 mg/L (350-700 μmol/L)(2D). Intermittent hemodialysis is the preferred ECTR in VPA poisoning (1D). If hemodialysis is not available, then intermittent hemoperfusion (1D) or continuous renal replacement therapy (2D) is an acceptable alternative. CONCLUSIONS: VPA is moderately dialyzable...

  10. Direct Determination of a Small-Molecule Drug, Valproic Acid, by an Electrically-Detected Microcantilever Biosensor for Personalized Diagnostics

    Directory of Open Access Journals (Sweden)

    Long-Sun Huang

    2015-01-01

    Full Text Available Direct, small-molecule determination of the antiepileptic drug, valproic acid, was investigated by a label-free, nanomechanical biosensor. Valproic acid has long been used as an antiepileptic medication, which is administered through therapeutic drug monitoring and has a narrow therapeutic dosage range of 50–100 μg·mL−1 in blood or serum. Unlike labeled and clinically-used measurement techniques, the label-free, electrical detection microcantilever biosensor can be miniaturized and simplified for use in portable or hand-held point-of-care platforms or personal diagnostic tools. A micromachined microcantilever sensor was packaged into the micro-channel of a fluidic system. The measurement of the antiepileptic drug, valproic acid, in phosphate-buffered saline and serum used a single free-standing, piezoresistive microcantilever biosensor in a thermally-controlled system. The measured surface stresses showed a profile over a concentration range of 50–500 μg·mL−1, which covered the clinically therapeutic range of 50–100 μg·mL−1. The estimated limit of detection (LOD was calculated to be 45 μg·mL−1, and the binding affinity between the drug and the antibody was measured at around 90 ± 21 μg·mL−1. Lastly, the results of the proposed device showed a similar profile in valproic acid drug detection with those of the clinically-used fluorescence polarization immunoassay.

  11. The use of valproic acid and multiple sclerosis

    DEFF Research Database (Denmark)

    Nielsen, Nete Munk; Svanström, Henrik; Stenager, Egon

    2014-01-01

    BACKGROUND: Animal studies have suggested that drugs inhibiting the enzyme histone deacetylase might have a beneficial effect on multiple sclerosis (MS). Valproic acid (VPA), an anti-epileptic drug, is the only widely used human drug with a histone deacetylase inhibitory effect. OBJECTIVE...... current VPA users nor recent users of VPA, who had ceased VPA treatment within the last year, were at a reduced risk of MS compared with non-users of VPA (HR = 1.30 (95% confidence interval, 0.44-3.80), n = 4, and HR = 1.22 (0.28-5.32), n = 2, respectively). Similarly, in an intention-to-treat analysis...

  12. Assessment of the role of in situ generated (E)-2,4-diene-valproic acid in the toxicity of valproic acid and (E)-2-ene-valproic acid in sandwich-cultured rat hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Surendradoss, Jayakumar; Chang, Thomas K.H.; Abbott, Frank S., E-mail: frank.abbott@ubc.ca

    2012-11-01

    Valproic acid (VPA) undergoes cytochrome P450-mediated desaturation to form 4-ene-VPA, which subsequently yields (E)-2,4-diene-VPA by β-oxidation. Another biotransformation pathway involves β-oxidation of VPA to form (E)-2-ene-VPA, which also generates (E)-2,4-diene-VPA by cytochrome P450-mediated desaturation. Although the synthetic form of (E)-2,4-diene-VPA is more hepatotoxic than VPA as shown in various experimental models, there is no conclusive evidence to implicate the in situ generated (E)-2,4-diene-VPA in VPA hepatotoxicity. The present study investigated the effects of modulating the in situ formation of (E)-2,4-diene-VPA on markers of oxidative stress (formation of 2′,7′-dichlorofluorescein; DCF), steatosis (accumulation of BODIPY 558/568 C{sub 12}), necrosis (release of lactate dehydrogenase; LDH), and on cellular total glutathione (GSH) levels in sandwich-cultured rat hepatocytes treated with VPA or (E)-2-ene-VPA. Treatment with either of these chemicals alone increased each of the toxicity endpoints. In VPA-treated hepatocytes, (E)-2,4-diene-VPA was detected only at trace levels, even after phenobarbital (PB) pretreatment and there was no effect on the toxicity of VPA. Furthermore, pretreatment with a cytochrome P450 enzyme inhibitor, 1-aminobenzotriazole (1-ABT), did not influence the extent of VPA toxicity in both PB-pretreated and vehicle-pretreated hepatocytes. However, in (E)-2-ene-VPA-treated hepatocytes, PB pretreatment greatly enhanced the levels of (E)-2,4-diene-VPA and this was accompanied by a further enhancement of the effects of (E)-2-ene-VPA on DCF formation, BODIPY accumulation, LDH release, and GSH depletion. Pretreatment with 1-ABT reduced the concentrations of (E)-2,4-diene-VPA and the extent of (E)-2-ene-VPA toxicity; however, this occurred in PB-pretreated hepatocytes, but not in control hepatocytes. In conclusion, in situ generated (E)-2,4-diene-VPA is not responsible for the hepatocyte toxicity of VPA, whereas it

  13. Effect of valproic acid on 65Zn distribution in the pregnant rat

    International Nuclear Information System (INIS)

    Keen, C.L.; Peters, J.M.; Hurley, L.S.

    1989-01-01

    The effect of valproic acid on the distribution of gavaged 65 Zn in maternal and embryonic tissue of Sprague-Dawley rats was examined 24 h after gavaging of the drug on d 13 of pregnancy. Valproic acid treatment resulted in a significantly higher retention of 65 Zn in maternal liver and lower amounts in uterus, placenta and embryos than in controls. Compared to controls, gel chromatography of maternal liver from valproic acid-treated dams showed higher 65 Zn counts associated with a protein peak of molecular weight of 6,500, the approximate molecular weight of the Zn-binding protein metallothionein. These results support the idea that the teratogenicity of valproic acid is in part due to an induction of embryonic Zn deficiency secondary to a drug-induced sequestering of Zn into maternal liver that results in a decrease in maternal plasma Zn and subsequent reduction in embryonic Zn uptake

  14. Valproic acid-induced hyperammonemic encephalopathy - a potentially fatal adverse drug reaction.

    Science.gov (United States)

    Sousa, Carla

    2013-12-01

    A patient with an early diagnosed epilepsy Valproic acid is one of the most widely used antiepileptic drugs. Hyperammonemic encephalopathy is a rare, but potentially fatal, adverse drug reaction to valproic acid. A patient with an early diagnosed epilepsy, treated with valproic acid, experienced an altered mental state after 10 days of treatment. Valproic acid serum levels were within limits, hepatic function tests were normal but ammonia levels were above the normal range. Valproic acid was stopped and the hyperammonemic encephalopathy was treated with lactulose 15 ml twice daily, metronidazole 250 mg four times daily and L-carnitine 1 g twice daily. Monitoring liver function and ammonia levels should be recommended in patients taking valproic acid. The constraints of the pharmaceutical market had to be taken into consideration and limited the pharmacological options for this patient's treatment. Idiosyncratic symptomatic hyperammonemic encephalopathy is completely reversible, but can induce coma and even death, if not timely detected. Clinical pharmacists can help detecting adverse drug reactions and provide evidence based information for the treatment.

  15. Study of Valproic Acid-Enhanced Hepatocyte Steatosis

    Science.gov (United States)

    Chang, Renin; Chou, Mei-Chia; Hung, Li-Ying; Wang, Mu-En; Hsu, Meng-Chieh; Chiu, Chih-Hsien

    2016-01-01

    Valproic acid (VPA) is one of the most widely used antiepilepsy drugs. However, several side effects, including weight gain and fatty liver, have been reported in patients following VPA treatment. In this study, we explored the molecular mechanisms of VPA-induced hepatic steatosis using FL83B cell line-based in vitro model. Using fluorescent lipid staining technique, we found that VPA enhanced oleic acid- (OLA-) induced lipid accumulation in a dose-dependent manner in hepatocytes; this may be due to upregulated lipid uptake, triacylglycerol (TAG) synthesis, and lipid droplet formation. Real-time PCR results showed that, following VPA treatment, the expression levels of genes encoding cluster of differentiation 36 (Cd36), low-density lipoprotein receptor-related protein 1 (Lrp1), diacylglycerol acyltransferase 2 (Dgat2), and perilipin 2 (Plin2) were increased, that of carnitine palmitoyltransferase I a (Cpt1a) was not affected, and those of acetyl-Co A carboxylase α (Acca) and fatty acid synthase (Fasn) were decreased. Furthermore, using immunofluorescence staining and flow cytometry analyses, we found that VPA also induced peroxisome proliferator-activated receptor γ (PPARγ) nuclear translocation and increased levels of cell-surface CD36. Based on these results, we propose that VPA may enhance OLA-induced hepatocyte steatosis through the upregulation of PPARγ- and CD36-dependent lipid uptake, TAG synthesis, and lipid droplet formation. PMID:27034954

  16. Study of Valproic Acid-Enhanced Hepatocyte Steatosis

    Directory of Open Access Journals (Sweden)

    Renin Chang

    2016-01-01

    Full Text Available Valproic acid (VPA is one of the most widely used antiepilepsy drugs. However, several side effects, including weight gain and fatty liver, have been reported in patients following VPA treatment. In this study, we explored the molecular mechanisms of VPA-induced hepatic steatosis using FL83B cell line-based in vitro model. Using fluorescent lipid staining technique, we found that VPA enhanced oleic acid- (OLA- induced lipid accumulation in a dose-dependent manner in hepatocytes; this may be due to upregulated lipid uptake, triacylglycerol (TAG synthesis, and lipid droplet formation. Real-time PCR results showed that, following VPA treatment, the expression levels of genes encoding cluster of differentiation 36 (Cd36, low-density lipoprotein receptor-related protein 1 (Lrp1, diacylglycerol acyltransferase 2 (Dgat2, and perilipin 2 (Plin2 were increased, that of carnitine palmitoyltransferase I a (Cpt1a was not affected, and those of acetyl-Co A carboxylase α (Acca and fatty acid synthase (Fasn were decreased. Furthermore, using immunofluorescence staining and flow cytometry analyses, we found that VPA also induced peroxisome proliferator-activated receptor γ (PPARγ nuclear translocation and increased levels of cell-surface CD36. Based on these results, we propose that VPA may enhance OLA-induced hepatocyte steatosis through the upregulation of PPARγ- and CD36-dependent lipid uptake, TAG synthesis, and lipid droplet formation.

  17. Comparison of trichostatin A and valproic acid treatment regimens in a mouse model of kidney fibrosis

    International Nuclear Information System (INIS)

    Van Beneden, Katrien; Geers, Caroline; Pauwels, Marina; Mannaerts, Inge; Wissing, Karl M.; Van den Branden, Christiane; Grunsven, Leo A. van

    2013-01-01

    Histone deacetylase (HDAC) inhibitors are promising new compounds for the therapy of fibrotic diseases. In this study we compared the effect of two HDAC inhibitors, trichostatin A and valproic acid, in an experimental model of kidney fibrosis. In mice, doxorubicin (adriamycin) can cause nephropathy characterized by chronic proteinuria, glomerular damage and interstitial inflammation and fibrosis, as seen in human focal segmental glomerulosclerosis. Two treatment regimens were applied, treatment was either started prior to the doxorubicin insult or delayed until a significant degree of proteinuria and fibrosis was present. Pre-treatment of trichostatin A significantly hampered glomerulosclerosis and tubulointerstitial fibrosis, as did the pre-treatment with valproic acid. In contrast, the development of proteinuria was only completely inhibited in the pre-treated valproic acid group, and not in the pre-treated trichostatin A animals. In the postponed treatment with valproic acid, a complete resolution of established doxorubicin-induced proteinuria was achieved within three days, whereas trichostatin A could not correct proteinuria in such a treatment regimen. However, both postponed regimens have comparable efficacy in maintaining the kidney fibrosis to the level reached at the start of the treatments. Moreover, not only the process of fibrosis, but also renal inflammation was attenuated by both HDAC inhibitors. Our data confirm a role for HDACs in renal fibrogenesis and point towards a therapeutic potential for HDAC inhibitors. The effect on renal disease progression and manifestation can however be different for individual HDAC inhibitors. - Highlights: • Valproic acid is a potent antiproteinuric drug, whereas trichostatin A is not. • Trichostatin A and valproic acid reduce kidney fibrosis in doxorubicin nephropathy. • Both valproic acid and trichostatin A attenuate renal inflammation

  18. Comparison of trichostatin A and valproic acid treatment regimens in a mouse model of kidney fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Van Beneden, Katrien, E-mail: kvbenede@vub.ac.be [Department of Human Anatomy, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium); Geers, Caroline [Department of Pathology, Universitair Ziekenhuis Brussel, Brussels (Belgium); Pauwels, Marina [Department of Human Anatomy, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium); Mannaerts, Inge [Department of Cell Biology, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium); Wissing, Karl M. [Department of Nephrology, Universitair Ziekenhuis Brussel, Brussels (Belgium); Van den Branden, Christiane [Department of Human Anatomy, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium); Grunsven, Leo A. van, E-mail: lvgrunsv@vub.ac.be [Department of Cell Biology, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium)

    2013-09-01

    Histone deacetylase (HDAC) inhibitors are promising new compounds for the therapy of fibrotic diseases. In this study we compared the effect of two HDAC inhibitors, trichostatin A and valproic acid, in an experimental model of kidney fibrosis. In mice, doxorubicin (adriamycin) can cause nephropathy characterized by chronic proteinuria, glomerular damage and interstitial inflammation and fibrosis, as seen in human focal segmental glomerulosclerosis. Two treatment regimens were applied, treatment was either started prior to the doxorubicin insult or delayed until a significant degree of proteinuria and fibrosis was present. Pre-treatment of trichostatin A significantly hampered glomerulosclerosis and tubulointerstitial fibrosis, as did the pre-treatment with valproic acid. In contrast, the development of proteinuria was only completely inhibited in the pre-treated valproic acid group, and not in the pre-treated trichostatin A animals. In the postponed treatment with valproic acid, a complete resolution of established doxorubicin-induced proteinuria was achieved within three days, whereas trichostatin A could not correct proteinuria in such a treatment regimen. However, both postponed regimens have comparable efficacy in maintaining the kidney fibrosis to the level reached at the start of the treatments. Moreover, not only the process of fibrosis, but also renal inflammation was attenuated by both HDAC inhibitors. Our data confirm a role for HDACs in renal fibrogenesis and point towards a therapeutic potential for HDAC inhibitors. The effect on renal disease progression and manifestation can however be different for individual HDAC inhibitors. - Highlights: • Valproic acid is a potent antiproteinuric drug, whereas trichostatin A is not. • Trichostatin A and valproic acid reduce kidney fibrosis in doxorubicin nephropathy. • Both valproic acid and trichostatin A attenuate renal inflammation.

  19. [Influence of valproic acid (depakine I.V.) on human placenta metabolism--experimental model].

    Science.gov (United States)

    Semczuk-Sikora, Anna; Rogowska, Wanda; Semczuk, Marian

    2003-08-01

    The pregnancy in women with epilepsy is associated with an increased incidence of congenital malformations in offspring. Currently, anti-epileptic drugs (AEDs) are concerned to be a major etiologic factor of abnormal fetal development but the pathomechanism of teratogenicity of AEDs is complex and not well understood. The purpose of this study was to evaluate an influence of one of the AED-valproic acid (VPA) on placental metabolism (glucose consumption and lactate production). Term human placental cotyledons were perfused in vitro using a recycling perfusion of maternal and fetal circulations. A total 18 placentas were perfused either with 75 micrograms/ml of VPA (therapeutic dose) or with 225 micrograms/ml of VPA (toxic dose). Eight placentas were perfused with a medium without VPA and served as controls. During 2.5 h of experiment, both maternal and fetal glucose consumption and lactate production were measured every 30 minutes. The introduction of different concentrations of VPA into the perfusion system did not effect placental glucose consumption and lactate production rates in both maternal and fetal compartments. The teratogenic effect of valproic acid is not associated with metabolic disturbances of glucose or lactate in the placental tissue.

  20. Computational characteristics of valproic acid binding to histone deacetylase

    International Nuclear Information System (INIS)

    Abou-Zeid, Laila A.; El-Mowafy, Abdalla M.; Eikel, D.; Nau, H.; El-Mazar, M.

    2007-01-01

    Recently, the anticpileptic drug valproic acid (VPA) has also demonstrated efficacy in the management of cancer and bipolar disorders. These actions are largely mediated by inhibition of the HDAC enzyme/induction of certain genes. Relative to other HDAC inhibitors such as trichostatin-A (TSA), VPA offers higher selectivity on cancer cells with virtually no detrimental effects on normal cells. The molecular underpinnings of these biological profiles for VPA remain undefined. We currently propose for an attempt to identify differences in the binding of VPA and TSA to HDAC. In this paper, conformational changes and energy calculations have derived. VPA had to accomplish conformational changes in its structure for best accommodation at the HDAC binding site. Energy computations showed that VPA has a lower binding affinitythan TSA (-53.80 vs. -66.30 Kcal/mol). These findings demonstrate that VPA binding to HDAC confers catalytic, conformational and computational characteristics that are distinct from those of TSA. These findings of VPA are consistent with a moderate inhibition of HDAC, a low toxicity on normal cells, and a higher selectivity on cancer cells than TSA. Accordingly, these newly identified binding properties of VPA can state a framework strategy for the rational design of VPA-related anticancer drugs with superior cytodifferentiating-and/or safety-profiles. (author)

  1. Neonatal episodic hypoglycemia: a finding of valproic acid withdrawal.

    Science.gov (United States)

    Çoban, Dilek; Kurtoğlu, Selim; Akın, Mustafa Ali; Akçakuş, Mustafa; Güneş, Tamer

    2010-01-01

    The treatment of epilepsy during pregnancy is a worldwide problem. Drugs need to be used to control seizures in the mothers. In utero, exposure to valproic acid (VPA) and phenytoin (PH) may cause congenital malformations and also withdrawal symptoms such as irritability, jitteriness and symptoms of hypoglycemia. We present here a newborn with episodic hypoglycemia due to in utero exposure to VPA and PH. The mother was diagnosed as having complex partial epilepsy and was treated with PH (200 mg/day) and VPA (600 mg/day). The offspring developed jitteriness on the second day of life. The infant was hypoglycemic (32 mg/dl). These findings were accepted as withdrawal symptoms, since serum levels of VPA and PH were 37.8 μg/ml (50-100 μg/ml) and 6.37 μg/dl (10-20 μg/ml), respectively. Measurement of blood glucose is important and should be carefully monitored in infants exposed to antiepileptics in utero.

  2. The valproic acid-induced rodent model of autism.

    Science.gov (United States)

    Nicolini, Chiara; Fahnestock, Margaret

    2018-01-01

    Autism is a lifelong neurodevelopmental disorder characterized by impairments in social communication and interaction and by repetitive patterns of behavior, interests and activities. While autism has a strong genetic component, environmental factors including toxins, pesticides, infection and drugs are known to confer autism susceptibility, likely by inducing epigenetic changes. In particular, exposure to valproic acid (VPA) during pregnancy has been demonstrated to increase the risk of autism in children. Furthermore, rodents prenatally exposed to this drug display behavioral phenotypes characteristics of the human condition. Indeed, in utero exposure of rodents to VPA represents a robust model of autism exhibiting face, construct and predictive validity. This model might better represent the many cases of idiopathic autism which are of environmental/epigenetic origins than do transgenic models carrying mutations in single autism-associated genes. The VPA model provides a valuable tool to investigate the neurobiology underlying autistic behavior and to screen for novel therapeutics. Here we review the VPA-induced rodent model of autism, highlighting its importance and reliability as an environmentally-induced animal model of autism. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Epigenetic modifications in valproic acid-induced teratogenesis

    International Nuclear Information System (INIS)

    Tung, Emily W.Y.; Winn, Louise M.

    2010-01-01

    Exposure to the anticonvulsant drug valproic acid (VPA) in utero is associated with a 1-2% increase in neural tube defects (NTDs), however the molecular mechanisms by which VPA induces teratogenesis are unknown. Previous studies demonstrated that VPA, a direct inhibitor of histone deacetylase, can induce histone hyperacetylation and other epigenetic changes such as histone methylation and DNA demethylation. The objective of this study was to determine if maternal exposure to VPA in mice has the ability to cause these epigenetic alterations in the embryo and thus contribute to its mechanism of teratogenesis. Pregnant CD-1 mice (GD 9.0) were administered a teratogenic dose of VPA (400 mg/kg, s.c.) and embryos extracted 1, 3, 6, and 24 h after injection. To assess embryonic histone acetylation and histone methylation, Western blotting was performed on whole embryo homogenates, as well as immunohistochemical staining on embryonic sections. To measure DNA methylation changes, the cytosine extension assay was performed. Results demonstrated that a significant increase in histone acetylation that peaked 3 h after VPA exposure was accompanied by an increase in histone methylation at histone H3 lysine 4 (H3K4) and a decrease in histone methylation at histone H3 lysine 9 (H3K9). Immunohistochemical staining revealed increased histone acetylation in the neuroepithelium, heart, and somites. A decrease in methylated histone H3K9 staining was observed in the neuroepithelium and somites, METHYLATED histone H3K4 staining was observed in the neuroepithelium. No significant differences in global or CpG island DNA methylation were observed in embryo homogenates. These results support the possibility that epigenetic modifications caused by VPA during early mouse organogenesis results in congenital malformations.

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

    Science.gov (United States)

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

    2013-01-01

    Metabolic encephalopathy is a rare but serious complication of valproic acid (VPA) therapy that usually presents with impaired consciousness or increased seizure frequency. Although it has been suggested that topiramate (TPM) increases the risk of VPA-induced encephalopathy, the additional risk in patients receiving TPM therapy has not been evaluated. We reviewed all adult patients who took VPA between January 2005 and February 2009 at the Seoul National University Hospital and identified patients with VPA-induced encephalopathy based on clinical and electroencephalography (EEG) data. Information on sex, age, serum ammonia level, serum VPA level, liver function test, and EEG was collected from patient registry and medical data. We enrolled 8,372 patients who received VPA therapy and 1,236 patients who received VPA/TPM combination therapy. We identified 11 patients with VPA-induced encephalopathy (0.13%), 7 of whom received a combination therapy of VPA and TPM. The odds ratio of VPA-induced encephalopathy with TPM over that without TPM was 10.16. There were no significant differences in sex distribution, number of antiepileptic agents, ammonia level, VPA serum level, underlying diseases, dosage of VPA, duration of VPA treatment, treatment of encephalopathy, and outcomes between the two groups. Our study showed that the prevalence of VPA-induced encephalopathy is approximately 0.1% among patients treated with VPA and that the risk of this condition, although still low, can increase by approximately 10 times in the presence of TPM therapy. Based on these results, we suggest that TPM should be carefully used in patients receiving VPA treatment. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

  5. The effects of valproic acid on renal corpuscle of pregnant rats and ...

    African Journals Online (AJOL)

    The effects of valproic acid on renal corpuscle of pregnant rats and protective role of folic acid and vitamin E. Ayfer Aktas, Yusuf Nergız, Yusuf Nergız, Murat Akkus, Murat Akkus, Yasemin Nasır, Yasemin Nasır ...

  6. Protective effects of valproic acid against airway hyperresponsiveness and airway remodeling in a mouse model of allergic airways disease.

    Science.gov (United States)

    Royce, Simon G; Dang, William; Ververis, Katherine; De Sampayo, Nishika; El-Osta, Assam; Tang, Mimi L K; Karagiannis, Tom C

    2011-12-01

    Airway remodeling and airway hyperresponsiveness are major aspects of asthma pathology that are not targeted optimally by existing anti-inflammatory drugs. Histone deacetylase inhibitors have a wide range of effects that may potentially abrogate aspects of remodeling. One such histone deacetylase inhibitor is valproic acid (2-propylvaleric acid). Valproic acid is used clinically as an anti-epileptic drug and is a potent inhibitor of class I histone deacetylases but also inhibits class II histone deacetylases. We used valproic acid as a molecular model of histone deacetylase inhibition in vivo in chronic allergic airways disease mice with airway remodeling and airway hyperresponsiveness. Wild-type Balb/c mice with allergic airways disease were treated with valproic acid or vehicle control. Airway inflammation was assessed by bronchoalveolar lavage fluid cell counts and examination of lung tissue sections. Remodeling was assessed by morphometric analysis of histochemically stained slides and lung function was assessed by invasive plethysmography measurement of airway resistance. Valproic acid treatment did not affect inflammation parameters; however, valproic acid treatment resulted in reduced epithelial thickness as compared to vehicle treated mice (p < 0.01), reduced subepithelial collagen deposition (p < 0.05) and attenuated airway hyperresponsiveness (p < 0.05 and p < 0.01 for the two highest doses of methacholine, respectively). These findings show that treatment with valproic acid can reduce structural airway remodeling changes and hyperresponsiveness, providing further evidence for the potential use of histone deacetylase inhibitors for the treatment of asthma.

  7. Enhanced long term microcircuit plasticity in the valproic acid animal model of autism

    NARCIS (Netherlands)

    Silva, G.; Le Bé, J.-V.; Riachi, I.; Rinaldi, T.; Markram, K.; Markram, H.

    2009-01-01

    A single intra-peritoneal injection of valproic acid (VPA) on embryonic day (ED) 11.5 to pregnant rats has been shown to produce severe autistic-like symptoms in the offspring. Previous studies showed that the microcircuitry is hyperreactive due to hyperconnectivity of glutamatergic synapses and

  8. Does folic acid use decrease the risk for spina bifida after in utero exposure to valproic acid?

    NARCIS (Netherlands)

    Jentink, J.; Bakker, M.K.; Nijenhuis, C.M.; Wilffert, B.; de Jong-van den Berg, L.T.W.

    Purpose Women with child wish are advised to take folic acid supplements to reduce the risk for spina bifida. However, there is less evidence for this protective effect in women using valproic acid (VPA). We investigated the effect of folic acid in women exposed to VPA in the first trimester of

  9. The Effect of Carnitine Supplementation on Hyperammonemia and Carnitine Deficiency Treated with Valproic Acid in a Psychiatric Setting

    OpenAIRE

    Nakamura, Masaru; Nagamine, Takahiko

    2015-01-01

    Objective: The aim of this study was to investigate the effect of levocarnitine (active isoform of carnitine, L-Carnitine) supplementation on serum ammonia and carnitine levels simultaneously, and their clinical outcomes in valproic acid-treated psychiatric subjects.

  10. Stevens - Johnson Syndrome Induced by Combination of Lamotrigine and Valproic Acid in a 9-Year-Old Boy

    LENUS (Irish Health Repository)

    Maduemem, K

    2017-06-01

    We describe the case history of a 9-year-old boy who developed Stevens-Johnson syndrome (SJS) following concomitant use of valproic acid and lamotrigine. He presented with rash and fever several weeks after introduction of lamotrigine, having been on valproic acid for seizure disorder. SJS happens to be one of the rare adverse reactions of antiepilepsy drugs (AED). Management is mainly supportive with care escalation when necessary because of the significant morbidity.

  11. Toxic epidermal necrolysis due to concomitant use of lamotrigine and valproic acid

    Directory of Open Access Journals (Sweden)

    Sukhjot Kaur

    2013-01-01

    Full Text Available Anti-epileptic drugs can be associated with a wide spectrum of cutaneous adverse reactions ranging from simple maculopapular rashes to more severe and life threatening reactions like Stevens-Johnson syndrome and toxic epidermal necrolysis. These rashes are well documented with older antiepileptic drugs like phenytoin, phenobarbitone and carbamazapine. Lamotrigine is a newer, unrelated antiepileptic drug that causes skin rashes in 3-10% of new users. Higher starting dose or rapid escalation, concurrent treatment with valproic acid, and a previous history of a rash with other antiepileptic drugs are well recognized risk factors for lamotrigine related serious rashes. We report two patients with toxic epidermal necrolysis, resulting from concomitant use of lamotrigine and valproic acid. It is emphasized that clinicians adhere to the recommended dosage guidelines and adopt a slow dose titration when initiating treatment with lamotrigine.

  12. Effects of amoxicillin/clavulanic acid on the pharmacokinetics of valproic acid

    Directory of Open Access Journals (Sweden)

    Lee SY

    2015-08-01

    Full Text Available Soo-Yun Lee,1 Wooseong Huh,2 Jin Ah Jung,3 Hye Min Yoo,2 Jae-Wook Ko,1,2 Jung-Ryul Kim2,4 1Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, 2Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Seoul, 3Department of Clinical Pharmacology, Inje University, Busan Paik Hospital, Busan, 4Department of Clinical Research and Evaluation, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea Abstract: Valproic acid (VPA is mainly metabolized via glucuronide, which is hydrolyzed by β-glucuronidase and undergoes enterohepatic circulation. Amoxicillin/clavulanic acid (AMC administration leads to decreased levels of β-glucuronidase-producing bacteria, suggesting that these antibiotics could interrupt enterohepatic circulation and thereby alter the pharmacokinetics of VPA. This study aimed to evaluate the effects of AMC on the pharmacokinetics of VPA. This was an open-label, two-treatment, one-sequence study in 16 healthy volunteers. Two treatments were evaluated; treatment VPA, in which a single dose of VPA 500 mg was administered, and treatment AMC + VPA, in which multiple doses of AMC 500/125 mg were administered three times daily for 7 days and then a single dose of VPA was administered. Blood samples were collected up to 48 hours. Pharmacokinetic parameters were calculated using noncompartmental methods. Fifteen subjects completed the study. Systemic exposures and peak concentrations of VPA were slightly lower with treatment AMC + VPA than with treatment VPA (AUClast, 851.0 h·mg/L vs 889.6 h·mg/L; Cmax, 52.1 mg/L vs 53.0 mg/L. There were no significant between-treatment effects on pharmacokinetics (95% confidence interval [CI] of AUClast and Cmax (95.7 [85.9–106.5] and 98.3 [91.6–105.6], respectively. Multiple doses of AMC had no significant effects on the pharmacokinetics of VPA; thus, no dose adjustment is necessary. Keywords: drug–drug interaction, pharmacokinetics

  13. Serum Leptin Levels in Epileptic Patients Treated with Topiramate and Valproic Acid

    Directory of Open Access Journals (Sweden)

    İrem Fatma Uludağ

    2011-03-01

    Full Text Available OBJECTIVE: Leptin is considered to be a signal factor that regulates body weight and energy expenditure, and there is a strong correlation between serum leptin concentrations, body mass index, and body fat mass in humans. Our aim in this study was to evaluate the role of leptin in valproic acid (VPA and topiramate (TPM related weight changes in epileptic patients. METHODS: Body mass index is calculated and serum leptin and insulin levels are measured in 56 patients with epilepsy (40 patients taking VPA and 16 patients taking VPA and TPM and in 40 healty control subjects. RESULTS: Obesity was seen in 21 patients (52.5% in VPA treated group, in 15 patients (37.5% in the control group and in only one male (6.3% in VPA and TPM treated group. Body mass index was lower in the group treated with VPA and TPM (p<0.001. Serum leptin concentrations were correlated with the body mass index (r=0.49, p<0.001 and were significantly higher in obese subjects (p<0.001 and in women (p<0.001. Serum leptin levels were significantly lower in patients treated with VPA and TPM (p<0.05. CONCLUSION: High levels of serum leptin in patients taking VPA and significantly low levels of serum leptin in patients taking VPA and TPM in our study are in agreement with the hypotheses that weight changes induced with VPA and TPM are related with the alterations in serum leptin levels

  14. Serum Leptin Levels in Epileptic Patients Treated with Topiramate and Valproic Acid

    Directory of Open Access Journals (Sweden)

    İrem Fatma Uludağ

    2011-03-01

    Full Text Available OBJECTIVE: Leptin is considered to be a signal factor that regulates body weight and energy expenditure, and there is a strong correlation between serum leptin concentrations, body mass index, and body fat mass in humans. Our aim in this study was to evaluate the role of leptin in valproic acid (VPA and topiramate (TPM related weight changes in epileptic patients. METHODS: Body mass index is calculated and serum leptin and insulin levels are measured in 56 patients with epilepsy (40 patients taking VPA and 16 patients taking VPA and TPM and in 40 healty control subjects. RESULTS: Obesity was seen in 21 patients (52.5% in VPA treated group, in 15 patients (37.5% in the control group and in only one male (6.3% in VPA and TPM treated group. Body mass index was lower in the group treated with VPA and TPM (p<0.001. Serum leptin concentrations were correlated with the body mass index (r=0.49, p<0.001 and were significantly higher in obese subjects (p<0.001 and in women (p<0.001. Serum leptin levels were significantly lower in patients treated with VPA and TPM (p<0.05. CONCLUSION: High levels of serum leptin in patients taking VPA and significantly low levels of serum leptin in patients taking VPA and TPM in our study are in agreement with the hypotheses that weight changes induced with VPA and TPM are related with the alterations in serum leptin levels.

  15. Enhanced long-term microcircuit plasticity in the valproic Acid animal model of autism

    DEFF Research Database (Denmark)

    Silva, Guilherme Testa; Le Bé, Jean-Vincent; Riachi, Imad

    2009-01-01

    A single intra-peritoneal injection of valproic acid (VPA) on embryonic day (ED) 11.5 to pregnant rats has been shown to produce severe autistic-like symptoms in the offspring. Previous studies showed that the microcircuitry is hyperreactive due to hyperconnectivity of glutamatergic synapses and ...... and hyperplastic due to over-expression of NMDA receptors. These changes were restricted to the dimensions of a minicolumn (...

  16. Enhanced long term microcircuit plasticity in the valproic acid animal model of autism

    OpenAIRE

    Guilherme T Silva; Guilherme T Silva; Jean-Vincent Le Bé; Imad Riachi; Tania Rinaldi; Kamila Markram; Henry Markram

    2009-01-01

    A single intra-peritoneal injection of valproic acid (VPA) on embryonic day (ED) 11.5 to pregnant rats has been shown to produce severe autistic-like symptoms in the offspring. Previous studies showed that the microcircuitry is hyperreactive due to hyperconnectivity of glutamatergic synapses and hyperplastic due to over-expression of NMDA receptors. These changes were restricted to the dimensions of a mini-column (<50μm). In the present study, we explored whether Long Term Microcircuit ...

  17. Enhanced Long-Term Microcircuit Plasticity in the Valproic Acid Animal Model of Autism

    OpenAIRE

    Silva, Guilherme Testa; Le Bé, Jean-Vincent; Riachi, Imad; Rinaldi, Tania; Markram, Kamila; Markram, Henry

    2009-01-01

    A single intra-peritoneal injection of valproic acid (VPA) on embryonic day (ED) 11.5 to pregnant rats has been shown to produce severe autistic-like symptoms in the offspring. Previous studies showed that the microcircuitry is hyperreactive due to hyperconnectivity of glutamatergic synapses and hyperplastic due to over-expression of NMDA receptors. These changes were restricted to the dimensions of a minicolumn (

  18. Derivatives of valproic acid are active against pentetrazol-induced seizures in immature rats

    Czech Academy of Sciences Publication Activity Database

    Mareš, Pavel; Kubová, Hana; Hen, N.; Yagen, B.; Bialer, M.

    2013-01-01

    Roč. 106, 1-2 (2013), s. 64-73 ISSN 0920-1211 R&D Projects: GA ČR(CZ) GAP304/10/1274; GA ČR(CZ) GBP304/12/G069 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : experimental seizures * anticonvulsant action * derivatives of valproic acid * immature rats Subject RIV: FH - Neurology Impact factor: 2.190, year: 2013

  19. Interaction between valproic acid and aspirin in epileptic children: serum protein binding and metabolic effects.

    Science.gov (United States)

    Orr, J M; Abbott, F S; Farrell, K; Ferguson, S; Sheppard, I; Godolphin, W

    1982-05-01

    In five of six epileptic children who were taking 18 to 49 mg/kg/day valproic acid (VPA), the steady-state serum free fractions of VPA rose from 12% to 43% when antipyretic doses of aspirin were also taken. Mean total VPA half-life (t1/2) rose from 10.4 +/- 2.7 to 12.9 +/- 1.8 hr and mean free VPA t1/2 rose from 6.7 +/- to 2.1 to 8.9 +2- 3.0 hr when salicylate was present in the serum. The in vitro albumin binding association constant (ka) for VPA was decreased by salicylate, but the in vivo ka value was not affected. The 12-hr (trough) concentrations of both free and total VPA were higher in the presence of serum salicylate in five of six patients. Renal excretion of unchanged VPA decreased in five of six patients, but the VPA carboxyl conjugate metabolite-excretion patterns were not consistently affected. Salicylate appeared to displace VPA from serum albumin in vivo, but the increased VPA t1/2 and changes in VPA elimination patterns suggest that serum salicylate also altered VPA metabolism.

  20. A rapid and simple procedure for monitoring valproic acid by gas chromatography

    Directory of Open Access Journals (Sweden)

    Mohamed Said Mostafa

    2018-02-01

    Full Text Available Valproic acid (VPA, a widely used antiepileptic drug, has a narrow therapeutic range of 50-100 μg/mL and shows large individual variability. It is very important to monitor the trough VPA concentration using a reliable method. The aim of this study was to develop and validate a rapid gas chromatographic (GC technique for VPA quantification in human plasma and to compare it with the traditional immunoassay method. VPA extraction from human serum was efficient by dichloromethane and hydrochloric acid using octanoic acid as an internal standard. GC analysis was performed using a gas-chromatograph equipped with a flame ionization detector (GC/FID. VPA detection and quantification were accomplished isothermally at 135°C on a Gs-BP 100% dimethylpolysiloxane capillary column (10 m×0.53 mm ID, 2.65 μm film thickness, Supelco, Bellefonte, PA. Injection port and detector temperature were 280°C. Retention times of VPA and internal standard were 1.83 min and 2.33 min, respectively. The calibration curve was linear over the concentration range of 5-320 μg/mL, with a lower limit of detection of 1.25 μg/mL. The internal and inter-day precision was less than 5.3% and 6.1%, respectively, and the accuracy was below 2.8%. VPA recovery was 94.6%. A quick and accurate method for VPA determination in human plasma was developed and validated. It resulted sufficiently selective and sensitive.

  1. Subchronic effects of valproic acid on gene expression profiles for lipid metabolism in mouse liver

    International Nuclear Information System (INIS)

    Lee, Min-Ho; Kim, Mingoo; Lee, Byung-Hoon; Kim, Ju-Han; Kang, Kyung-Sun; Kim, Hyung-Lae; Yoon, Byung-Il; Chung, Heekyoung; Kong, Gu; Lee, Mi-Ock

    2008-01-01

    Valproic acid (VPA) is used clinically to treat epilepsy, however it induces hepatotoxicity such as microvesicular steatosis. Acute hepatotoxicity of VPA has been well documented by biochemical studies and microarray analysis, but little is known about the chronic effects of VPA in the liver. In the present investigation, we profiled gene expression patterns in the mouse liver after subchronic treatment with VPA. VPA was administered orally at a dose of 100 mg/kg/day or 500 mg/kg/day to ICR mice, and the livers were obtained after 1, 2, or 4 weeks. The activities of serum liver enzymes did not change, whereas triglyceride concentration increased significantly. Microarray analysis revealed that 1325 genes of a set of 32,996 individual genes were VPA responsive when examined by two-way ANOVA (P 1.5). Consistent with our previous results obtained using an acute VPA exposure model (Lee et al., Toxicol Appl Pharmacol. 220:45-59, 2007), the most significantly over-represented biological terms for these genes included lipid, fatty acid, and steroid metabolism. Biological pathway analysis suggests that the genes responsible for increased biosynthesis of cholesterol and triglyceride, and for decreased fatty acid β-oxidation contribute to the abnormalities in lipid metabolism induced by subchronic VPA treatment. A comparison of the VPA-responsive genes in the acute and subchronic models extracted 15 commonly altered genes, such as Cyp4a14 and Adpn, which may have predictive power to distinguish the mode of action of hepatotoxicants. Our data provide a better understanding of the molecular mechanisms of VPA-induced hepatotoxicity and useful information to predict steatogenic hepatotoxicity

  2. Histone deacetylase inhibitor valproic acid promotes the induction of pluripotency in mouse fibroblasts by suppressing reprogramming-induced senescence stress

    Energy Technology Data Exchange (ETDEWEB)

    Zhai, Yingying; Chen, Xi; Yu, Dehai [Stem Cell and Cancer Center, First Affiliated Hospital, Jilin University, Changchun, Jilin 130061 (China); Stanford University Medical School, Palo Alto Veterans Institute for Research, Palo Alto, CA 94304 (United States); Li, Tao [Stanford University Medical School, Palo Alto Veterans Institute for Research, Palo Alto, CA 94304 (United States); Cui, Jiuwei; Wang, Guanjun [Stem Cell and Cancer Center, First Affiliated Hospital, Jilin University, Changchun, Jilin 130061 (China); Hu, Ji-Fan, E-mail: jifan@stanford.edu [Stem Cell and Cancer Center, First Affiliated Hospital, Jilin University, Changchun, Jilin 130061 (China); Stanford University Medical School, Palo Alto Veterans Institute for Research, Palo Alto, CA 94304 (United States); Li, Wei, E-mail: jdyylw@163.com [Stem Cell and Cancer Center, First Affiliated Hospital, Jilin University, Changchun, Jilin 130061 (China)

    2015-09-10

    Histone deacetylase inhibitor valproic acid (VPA) has been used to increase the reprogramming efficiency of induced pluripotent stem cell (iPSC) from somatic cells, yet the specific molecular mechanisms underlying this effect is unknown. Here, we demonstrate that reprogramming with lentiviruses carrying the iPSC-inducing factors (Oct4-Sox2-Klf4-cMyc, OSKM) caused senescence in mouse fibroblasts, establishing a stress barrier for cell reprogramming. Administration of VPA protected cells from reprogramming-induced senescent stress. Using an in vitro pre-mature senescence model, we found that VPA treatment increased cell proliferation and inhibited apoptosis through the suppression of the p16/p21 pathway. In addition, VPA also inhibited the G2/M phase blockage derived from the senescence stress. These findings highlight the role of VPA in breaking the cell senescence barrier required for the induction of pluripotency. - Highlights: • Histone deacetylase inhibitor valproic acid enhances iPSC induction. • Valproic acid suppresses reprogramming-induced senescence stress. • Valproic acid downregulates the p16/p21 pathway in reprogramming. • This study demonstrates a new mechanistic role of valproic acid in enhancing reprogramming.

  3. Frequency of different congenital anomalies in prenatally valproic acid treated chick embryos

    International Nuclear Information System (INIS)

    Akhtar, L.; Khan, M.Y.

    2016-01-01

    To determine the frequency of different congenital anomalies in surviving chick embryo on hatching after the prenatal administration of valproic acid by comparing with age-matched controls. Study Design: Experimental study. Place and Duration of Study: Anatomy Department, College of Physicians and Surgeons Pakistan (CPSP) Regional Centre, Islamabad, from February 2010 to February 2011. Material and Methods: Thirty fertilized chicken eggs were injected with valproic acid, incubated and then evaluated for different gross congenital anomalies, on hatching or day 22 of incubation whichever was earlier. Chicks of this group were labeled as experimental group-A. Similarly, another group of thirty fertilized chicken eggs labeled as control group-B, underwent sham treatment using normal saline. The weight and length of alive chicks, the total number of chicks with gross anomalies and the number of different types of gross anomalies in both groups were noted and statistically compared. Results: In control group-B, 28 chicks hatch out on 21 day of hatching with no visible gross deformities. Whereas in experimental group-A, 23 chicks were alive, out of which, 9 chicks were with delayed hatching on 22 days of hatching. The chicks with gross deformities were 8 (p=0.0008) which included: limb abnormalities (i.e. inverted feet) in 6 chicks (p=0.006), eye abnormality (i.e. closed palpebral fissure of both eyes) in 2 chick (p=0.2), 1 chick showed multiple deformities including gastroschisis, closed palpebral fissures and inverted foot (p=0.45). There were behavioral changes in 10 chicks (p=0.0001). There was statistically significant difference in their weights (p=0.03). Conclusion: Prenatal exposure of chick embryos to valproic acid increased the incidence of different gross deformities. (author)

  4. Diffuse alveolar hemorrhage due to valproic acid: Case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Francesco Inzirillo

    2015-01-01

    Full Text Available Valproic acid (VPA is one of the most frequently used antiepileptic drugs for the treatment of focal and generalized epilepsies, absence seizures, and Lennox-Gastaut syndrome (LGS. VPA has been demonstrated to have a negative effect on both the intrinsic and extrinsic coagulation systems and controversy exists about the clinical relevance of such hematological abnormalities. We describe a case of reversible lung hemorrage due to VPA. In English-language literature only two other similar cases (one of which fatal have been described so far.

  5. Cytoskeleton of hippocampal neurons as a target for valproic acid in an experimental model of depression.

    Science.gov (United States)

    Ferrero, Alejandro J; Cereseto, Marina; Sifonios, Laura L; Reinés, Analía; Peixoto, Estanislao; Rubio, Modesto C; Wikinski, Silvia

    2007-10-01

    Atrophy of pyramidal hippocampal neurons and of the entire hippocampus has been reported in experimental models of depression and in depressive patients respectively. We investigated the efficacy of valproic acid (VPA) for reversing a depressive-like behaviour and a cytoskeletal alteration in the hippocampus, the loss of the light neurofilament subunit (NF-L). Depressive-like behaviour was induced by inescapable stress. Animals were divided into four groups: two to assess the response to 21 days of treatment with 200 mg/kg (I.P.) of valproic acid, and two in which the treatment was interrupted and the effects of VPA were evaluated 90 days later. Depressive-like behaviour was evaluated by the quantification of escape movements in a swimming test. NF-L was quantified by immunohistochemistry in dentate gyrus and CA3 of hippocampus. VPA corrected the depressive-like behaviour and reversed the diminution of NF-L in the hippocampus. Ninety days after the end of the treatment, and in contrast to the results previously obtained with fluoxetine, no recurrence of the depressive-like behaviour was observed. Despite interruption of the treatment, a long-lasting effect of VPA was observed. A possible relationship between the effect on NF-L and the prevention of depressive-like behaviour recurrence could be suggested.

  6. Edaravone, a free radical scavenger, protects liver against valproic acid induced toxicity

    Directory of Open Access Journals (Sweden)

    Cakmak Neziha Hacihasanoglu

    2015-01-01

    Full Text Available Valproic acid (VPA, is a well established anticonvulsant drug that has been increasingly used in the treatment of many forms of generalized epilepsy. Edaravone (EDA; 3-methyl-1-phenyl-2-pyrazoline-5-one is a potent free radical scavenger. In this study, we aimed to investigate the effects of EDA on VPA-induced hepatic damage. Male Sprague Dawley rats were divided into four groups. Group I was control animals. Group II was control rats given valproic acid (500 mg kg-1 day for seven days. Group III was given only EDA (30 mg kg-1day for seven days. Group IV was given VPA+EDA (in same dose and time. EDA and VPA were given intraperitoneally. On the 8th day of experiment, blood samples and liver tissue were taken. Serum aspartate and alanine aminotransferase, alkaline phosphatase and bilirubin levels, liver myeloperoxidase, xanthine oxidase, adenosine deaminase, Na+/K+ATPase, sorbitol dehydrogenase, glutamate dehydrogenase, DT-diaphorase, arginase and thromboplastic activities, lipid peroxidation, protein carbonyl levels were increased whereas paraoxonase, biotinidase activities and glutathione levels were decreased in VPA group. Application of EDA with VPA protected against VPA-induced effects. These results demonstrated that administration of EDA is a potentially beneficial agent to reduce hepatic damage in VPA induced hepatotoxicity, probably by decreasing oxidative stress.

  7. Synergistically killing activity of aspirin and histone deacetylase inhibitor valproic acid (VPA) on hepatocellular cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xiaofei; Zhu, Yanshuang [Department of Infectious Diseases, Yiwu Central Hospita, 519 Nan men Street, Yiwu, Jinhua, Zhejing 322000 (China); He, Huabin [Department of Orthopedics, Yiwu Central Hospita, 519 Nan men Street, Yiwu, Jinhua, Zhejing 322000 (China); Lou, Lianqing; Ye, Weiwei; Chen, Yongxin [Department of Infectious Diseases, Yiwu Central Hospita, 519 Nan men Street, Yiwu, Jinhua, Zhejing 322000 (China); Wang, Jinghe, E-mail: Xiaofeili2000@163.com [Department of Infectious Diseases, Yiwu Central Hospita, 519 Nan men Street, Yiwu, Jinhua, Zhejing 322000 (China)

    2013-06-28

    Highlights: •Novel combination therapy using aspirin and valproic acid (VPA). •Combination of aspirin and VPA elicits synergistic cytotoxic effects. •Combination of aspirin and VPA significantly reduces the drug dosage required alone. •Combination of aspirin and VPA significantly inhibit tumor growth. •Lower dose of aspirin in combination therapy will minimize side effects of aspirin. -- Abstract: Aspirin and valproic acid (VPA) have been extensively studied for inducing various malignancies growth inhibition respectively, despite their severe side effects. Here, we developed a novel combination by aspirin and VPA on hepatocellular cancer cells (HCCs). The viability of HCC lines were analyzed by MTT assay, apoptotic analysis of HepG2 and SMMC-7721 cell was performed. Real time-PCR and Western blotting were performed to determine the expression of apoptosis related genes and proteins such as Survivin, Bcl-2/Bax, Cyclin D1 and p15. Moreover, orthotopic xenograft tumors were challenged in nude mice to establish murine model, and then therapeutic effect was analyzed after drug combination therapy. The viability of HCC lines’ significantly decreased after drug combination treatment, and cancer cell apoptosis in combination group increasingly induced compared with single drug use. Therapeutic effect was significantly enhanced by combination therapy in tumor volume and tumor weight decrease. From the data shown here, aspirin and VPA combination have a synergistic killing effect on hepatocellular cancers cells proliferation and apoptosis.

  8. Synergistically killing activity of aspirin and histone deacetylase inhibitor valproic acid (VPA) on hepatocellular cancer cells

    International Nuclear Information System (INIS)

    Li, Xiaofei; Zhu, Yanshuang; He, Huabin; Lou, Lianqing; Ye, Weiwei; Chen, Yongxin; Wang, Jinghe

    2013-01-01

    Highlights: •Novel combination therapy using aspirin and valproic acid (VPA). •Combination of aspirin and VPA elicits synergistic cytotoxic effects. •Combination of aspirin and VPA significantly reduces the drug dosage required alone. •Combination of aspirin and VPA significantly inhibit tumor growth. •Lower dose of aspirin in combination therapy will minimize side effects of aspirin. -- Abstract: Aspirin and valproic acid (VPA) have been extensively studied for inducing various malignancies growth inhibition respectively, despite their severe side effects. Here, we developed a novel combination by aspirin and VPA on hepatocellular cancer cells (HCCs). The viability of HCC lines were analyzed by MTT assay, apoptotic analysis of HepG2 and SMMC-7721 cell was performed. Real time-PCR and Western blotting were performed to determine the expression of apoptosis related genes and proteins such as Survivin, Bcl-2/Bax, Cyclin D1 and p15. Moreover, orthotopic xenograft tumors were challenged in nude mice to establish murine model, and then therapeutic effect was analyzed after drug combination therapy. The viability of HCC lines’ significantly decreased after drug combination treatment, and cancer cell apoptosis in combination group increasingly induced compared with single drug use. Therapeutic effect was significantly enhanced by combination therapy in tumor volume and tumor weight decrease. From the data shown here, aspirin and VPA combination have a synergistic killing effect on hepatocellular cancers cells proliferation and apoptosis

  9. Chir99021 and Valproic acid reduce the proliferative advantage of Apc mutant cells.

    Science.gov (United States)

    Langlands, Alistair J; Carroll, Thomas D; Chen, Yu; Näthke, Inke

    2018-02-15

    More than 90% of colorectal cancers carry mutations in Apc that drive tumourigenesis. A 'just-right' signalling model proposes that Apc mutations stimulate optimal, but not excessive Wnt signalling, resulting in a growth advantage of Apc mutant over wild-type cells. Reversal of this growth advantage constitutes a potential therapeutic approach. We utilised intestinal organoids to compare the growth of Apc mutant and wild-type cells. Organoids derived from Apc Min/+ mice recapitulate stages of intestinal polyposis in culture. They eventually form spherical cysts that reflect the competitive growth advantage of cells that have undergone loss of heterozygosity (LOH). We discovered that this emergence of cysts was inhibited by Chiron99021 and Valproic acid, which potentiates Wnt signalling. Chiron99021 and Valproic acid restrict the growth advantage of Apc mutant cells while stimulating that of wild-type cells, suggesting that excessive Wnt signalling reduces the relative fitness of Apc mutant cells. As a proof of concept, we demonstrated that Chiron99021-treated Apc mutant organoids were rendered susceptible to TSA-induced apoptosis, while wild-type cells were protected.

  10. Extracorporeal treatment for valproic acid poisoning: systematic review and recommendations from the EXTRIP workgroup.

    Science.gov (United States)

    Ghannoum, Marc; Laliberté, Martin; Nolin, Thomas D; MacTier, Robert; Lavergne, Valery; Hoffman, Robert S; Gosselin, Sophie

    2015-06-01

    The EXtracorporeal TReatments In Poisoning (EXTRIP) workgroup presents its systematic review and clinical recommendations on the use of extracorporeal treatment (ECTR) in valproic acid (VPA) poisoning. The lead authors reviewed all of the articles from a systematic literature search, extracted the data, summarized the key findings, and proposed structured voting statements following a predetermined format. A two-round modified Delphi method was chosen to reach a consensus on voting statements and the RAND/UCLA Appropriateness Method was used to quantify disagreement. Anonymous votes were compiled, returned, and discussed in person. A second vote was conducted to determine the final workgroup recommendations. The latest literature search conducted in November 2014 retrieved a total of 79 articles for final qualitative analysis, including one observational study, one uncontrolled cohort study with aggregate analysis, 70 case reports and case series, and 7 pharmacokinetic studies, yielding a very low quality of evidence for all recommendations. Clinical data were reported for 82 overdose patients while pharmaco/toxicokinetic grading was performed in 55 patients. The workgroup concluded that VPA is moderately dialyzable (level of evidence = B) and made the following recommendations: ECTR is recommended in severe VPA poisoning (1D); recommendations for ECTR include a VPA concentration > 1300 mg/L (9000 μmol/L)(1D), the presence of cerebral edema (1D) or shock (1D); suggestions for ECTR include a VPA concentration > 900 mg/L (6250 μmol/L)(2D), coma or respiratory depression requiring mechanical ventilation (2D), acute hyperammonemia (2D), or pH ≤ 7.10 (2D). Cessation of ECTR is indicated when clinical improvement is apparent (1D) or the serum VPA concentration is between 50 and 100 mg/L (350-700 μmol/L)(2D). Intermittent hemodialysis is the preferred ECTR in VPA poisoning (1D). If hemodialysis is not available, then intermittent hemoperfusion (1D) or continuous

  11. An Evaluation of Peripapillary Retinal Nerve Fiber Layer Thickness in Children With Epilepsy Receiving Treatment of Valproic Acid.

    Science.gov (United States)

    Dereci, Selim; Koca, Tuğba; Akçam, Mustafa; Türkyilmaz, Kemal

    2015-07-01

    We investigated the peripapillary retinal nerve fiber layer thickness with optical coherence tomography in epileptic children receiving valproic acid monotherapy. The study was conducted on children aged 8-16 years who were undergoing valproic acid monotherapy for epilepsy. The study group comprised a total of 40 children who met the inclusion criteria and 40 healthy age- and sex-matched children as a control group. Children with at least a 1-year history of epilepsy and taking 10-40 mg/kg/day treatment were included in the study. Peripapillary retinal nerve fiber layer thickness measurements were performed using Cirrus HD optical coherence tomography. All children and parents were informed about the study and informed consent was obtained from the parents of all the participants. The study group included 21 girls and 19 boys with a mean age of 10.6 ± 2.3 years. According to the results of optical coherence tomography measurements, the mean peripapillary retinal nerve fiber layer thickness was 91.6 ± 9.7 in the patient group and 95.5 ± 7.4 μm in the control group (P epilepsy who were receiving valproic acid monotherapy compared with healthy children. This situation can lead to undesirable results in terms of eye health. New studies are needed to investigate whether these findings are the result of epilepsy or can be attributed to valproic acid and whether there are adverse effects of valproic acid later in life. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. The Effect of Gallic Acid on Histopathologic Evaluation of Cerebellum in Valproic Acid-Induced Autism Animal Models

    Directory of Open Access Journals (Sweden)

    Parvin Samimi

    2016-06-01

    Full Text Available Autism spectrum disorder (ASD is counted as a worldwide public health problem. The possible causes of ASD are reactive oxygen species and free radicals. So, this study is aimed to evaluate the effects of Gallic acid, as an effective antioxidant, on histopathologic disorder of the cerebellum in valproic acid-induced autism animal models. 30 pregnant female rats were randomly divided into 5 groups, including: control, autism (or VAP and experimental 1, 2 and 3. Using a gavage needle, Gallic acid administered orally until about2 months of age. After the end of the treatment period, the rats were anesthetized with ether and their cerebellar tissues were removed for histopathologic studies. A significant decrease in the number of Purkinje and granular cells was observed in this study in VAP group compared to the control group (P≤0.05. A trend toward improvement was observed in the groups received 100 and 200 mg/kg of Gallic acid (P≤0.05. The results of this research revealed that Gallic acid reduces the side effects caused by valproic acid on cerebellar tissue of autistic rats. So, it should be considered for therapeutic goals.

  13. Should Pharmacies Be Included in Medication Reconciliation? A Report of Recurrent Valproic Acid Toxicity

    Directory of Open Access Journals (Sweden)

    B. Tate Cutshall

    2017-03-01

    Full Text Available Including outpatient pharmacies in the medication reconciliation process upon hospital discharge is not commonly performed. This case highlights the consequences of a patient refilling a discontinued prescription for valproic acid (VPA. We present a 32-year old male found unresponsive after ingesting delayed release divalproex sodium. Cerebral edema was visualized on magnetic resonance imaging. Hemodialysis and levo-carnitine treatment led to improved mental status, and VPA was discontinued. The same patient presented with VPA overdose eight months later after he continued to fill an outdated prescription. This case highlights consequences of VPA toxicity; it also demonstrates an opportunity to improve patient safety and high-value care by collaborating with outpatient pharmacies in the medication reconciliation process upon hospital discharge.

  14. A case of mania presenting with hypersexual behavior and gender dysphoria that resolved with valproic acid

    Directory of Open Access Journals (Sweden)

    Michelle R. Heare

    2016-11-01

    Full Text Available Hypersexuality and gender dysphoria have both been described in the literature as symptoms of mania. Hypersexuality is listed in the Diagnostic and Statistical Manual of Mental Disorders 5 as part of the diagnostic criteria for bipolar disorder. Gender dysphoria is less often described and its relation to mania remains unclear. This case report describes a young homosexual man presenting in a manic episode with co-morbid amphetamine abuse whose mania was marked by hypersexuality and the new onset desire to be a woman. Both of these symptoms resolved with the addition of valproic acid to antipsychotics. This case report presents the existing literature on hypersexuality and gender dysphoria in mania and describes a treatment option that has not been previously reported.

  15. Reduced Adult Hippocampal Neurogenesis and Cognitive Impairments following Prenatal Treatment of the Antiepileptic Drug Valproic Acid

    Directory of Open Access Journals (Sweden)

    Berry Juliandi

    2015-12-01

    Full Text Available Prenatal exposure to valproic acid (VPA, an established antiepileptic drug, has been reported to impair postnatal cognitive function in children born to VPA-treated epileptic mothers. However, how these defects arise and how they can be overcome remain unknown. Using mice, we found that comparable postnatal cognitive functional impairment is very likely correlated to the untimely enhancement of embryonic neurogenesis, which led to depletion of the neural precursor cell pool and consequently a decreased level of adult neurogenesis in the hippocampus. Moreover, hippocampal neurons in the offspring of VPA-treated mice showed abnormal morphology and activity. Surprisingly, these impairments could be ameliorated by voluntary running. Our study suggests that although prenatal exposure to antiepileptic drugs such as VPA may have detrimental effects that persist until adulthood, these effects may be offset by a simple physical activity such as running.

  16. Hyperconnectivity of local neocortical microcircuitry induced by prenatal exposure to valproic acid

    DEFF Research Database (Denmark)

    Rinaldi, Tania; Silberberg, Gilad; Markram, Henry

    2008-01-01

    Exposure to valproic acid (VPA) during embryogenesis can cause several teratogenic effects, including developmental delays and in particular autism in humans if exposure occurs during the third week of gestation. We examined the postnatal effects of embryonic exposure to VPA on microcircuit...... properties of juvenile rat neocortex using in vitro electrophysiology. We found that a single prenatal injection of VPA on embryonic day 11.5 causes a significant enhancement of the local recurrent connectivity formed by neocortical pyramidal neurons. The study of the biophysical properties...... of these connections revealed weaker excitatory synaptic responses. A marked decrease of the intrinsic excitability of pyramidal neurons was also observed. Furthermore, we demonstrate a diminished number of putative synaptic contacts in connection between layer 5 pyramidal neurons. Local hyperconnectivity may render...

  17. Syndrome of inappropriate antidiuretic hormone secretion (SIADH) or hyponatraemia associated with valproic Acid : four case reports from the Netherlands and a case/non-case analysis of vigibase

    NARCIS (Netherlands)

    Beers, Erna; van Puijenbroek, Eugène P; Bartelink, Imke H; van der Linden, Carolien M J; Jansen, Paul A F

    The Netherlands Pharmacovigilance Centre Lareb received four cases of severe symptomatic hyponatraemia or syndrome of inappropriate antidiuretic hormone secretion (SIADH) in association with valproic acid use, in which a causal relationship was suspected. This study describes these cases and gives

  18. Brain delivery of valproic acid via intranasal administration of nanostructured lipid carriers: in vivo pharmacodynamic studies using rat electroshock model

    Directory of Open Access Journals (Sweden)

    Sharareh Eskandari

    2011-02-01

    Full Text Available Sharareh Eskandari1, Jaleh Varshosaz1, Mohsen Minaiyan2, Majid Tabbakhian11Department of Pharmaceutics, 2Department of Pharmacology, School of Pharmacy and Isfahan Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, IranAbstract: The treatment of brain disorders is one of the greatest challenges in drug delivery because of a variety of main barriers in effective drug transport and maintaining therapeutic concentrations in the brain for a prolonged period. The objective of this study was delivery of valproic acid (VPA to the brain by intranasal route. For this purpose, nanostructured lipid carriers (NLCs were prepared by solvent diffusion method followed by ultrasonication and characterized for size, zeta potential, drug-loading percentage, and release. Six groups of rats each containing six animals received drug-loaded NLCs intraperitoneally (IP or intranasally. Brain responses were then examined by using maximal electroshock (MES. The hind limb tonic extension:flexion inhibition ratio was measured at 15-, 30-, 60-, 90-, and 120-minute intervals. The drug concentration was also measured in plasma and brain at the most protective point using gas chromatography method. The particle size of NLCs was 154 ± 16 nm with drug-loading percentage of 47% ± 0.8% and drug release of 75% ± 1.9% after 21 days. In vivo results showed that there was a significant difference between protective effects of NLCs of VPA and control group 15, 30, 60, and 90 minutes after treatment via intranasal route (P < 0.05. Similar protective effect was observed in rats treated with NLCs of VPA in intranasal route and positive control in IP route (P > 0.05. Results of drug determination in brain and plasma showed that brain:plasma concentration ratio was much higher after intranasal administration of NLCs of VPA than the positive control group (IP route. In conclusion, intranasal administration of NLCs of VPA provided a better protection

  19. Folic acid and pantothenic acid protection against valproic acid-induced neural tube defects in CD-1 mice

    Energy Technology Data Exchange (ETDEWEB)

    Dawson, Jennifer E [Department of Pharmacology and Toxicology and School of Environmental Studies, Queen' s University, Kingston, Ontario, K7L 3N6 (Canada); Raymond, Angela M [Department of Pharmacology and Toxicology and School of Environmental Studies, Queen' s University, Kingston, Ontario, K7L 3N6 (Canada); Winn, Louise M [Department of Pharmacology and Toxicology and School of Environmental Studies, Queen' s University, Kingston, Ontario, K7L 3N6 (Canada)

    2006-03-01

    In utero exposure to valproic acid (VPA) during pregnancy is associated with an increased risk of neural tube defects (NTDs). Although the mechanism by which VPA mediates these effects is unknown, VPA-initiated changes in embryonic protein levels have been implicated. The objectives of this study were to investigate the effect of in utero VPA exposure on embryonic protein levels of p53, NF-{kappa}B, Pim-1, c-Myb, Bax, and Bcl-2 in the CD-1 mouse. We also evaluated the protective effects of folic acid and pantothenic acid on VPA-induced NTDs and VPA-induced embryonic protein changes in this model. Pregnant CD-1 mice were administered a teratogenic dose of VPA prior to neural tube closure and embryonic protein levels were analyzed. In our study, VPA (400 mg/kg)-induced NTDs (24%) and VPA-exposed embryos with an NTD showed a 2-fold increase in p53, and 4-fold decreases in NF-{kappa}B, Pim-1, and c-Myb protein levels compared to their phenotypically normal littermates (P < 0.05). Additionally, VPA increased the ratio of embryonic Bax/Bcl-2 protein levels (P < 0.05). Pretreatment of pregnant dams with either folic acid or pantothenic acid prior to VPA significantly protected against VPA-induced NTDs (P < 0.05). Folic acid also reduced VPA-induced alterations in p53, NF-{kappa}B, Pim-1, c-Myb, and Bax/Bcl-2 protein levels, while pantothenic acid prevented VPA-induced alterations in NF-{kappa}B, Pim-1, and c-Myb. We hypothesize that folic acid and pantothenic acid protect CD-1 embryos from VPA-induced NTDs by independent, but not mutually exclusive mechanisms, both of which may be mediated by the prevention of VPA-induced alterations in proteins involved in neurulation.

  20. Radiochemically pure [1-14C]valproic acid--a mixture of labeled structural isomers

    International Nuclear Information System (INIS)

    Dickinson, R.G.; Wood, B.T.; Kluck, R.M.; Hooper, W.D.

    1986-01-01

    Ongoing studies of the disposition of valproic acid (VPA) and its glucuronide conjugate required the radiolabeled drug for greater sensitivity and tracing of oxidation metabolites. [1- 14 C]VPA hereinafter called LABEL (radiochemical purity greater than 98% as determined by paper and thin layer chromatography) was purchased from Amersham International, U.K. Quantitative analysis of VPA and VPA-glucuronide in bile and urine samples from rats given VPA and tracer LABEL by our standard gas chromatographic assay showed gross discrepancies with the results obtained by liquid scintillation counting of the same extracts. Examination of the purity of LABEL was therefore undertaken. Equilibration of LABEL between various organic-aqueous solvent pairs was identical to that of authentic VPA. However, gas chromatographic-mass spectrometric analysis of the trimethylsilyl derivative of LABEL revealed it to be a mixture of labeled 2-methylheptanoic acid (approximately 60%), 2-ethylhexanoic acid (approximately 30%), and 2-propylpentanoic acid (i.e., VPA, 5-10%). The origin of the isomers of VPA in LABEL was logically traced to the synthetic procedure--coupling of the Grignard reagent of (an isomeric mixture of 2-, 3-, and 4-) chloroheptane(s) with [ 14 C]carbon dioxide. This result highlights the inadequacy of the quality control procedures used and reinforces the necessity for caution in accepting the quoted purity of radiolabeled drugs

  1. Hyper-Connectivity and Hyper-Plasticity in the Medial Prefrontal Cortex in the Valproic Acid Animal Model of Autism

    OpenAIRE

    Rinaldi, Tania; Perrodin, Catherine; Markram, Henry

    2008-01-01

    The prefrontal cortex has been extensively implicated in autism to explain deficits in executive and other higher-order functions related to cognition, language, sociability and emotion. The possible changes at the level of the neuronal microcircuit are however not known. We studied microcircuit alterations in the prefrontal cortex in the valproic acid rat model of autism and found that the layer 5 pyramidal neurons are connected to significantly more neighbouring neurons than in controls. Th...

  2. Targeting anandamide metabolism rescues core and associated autistic-like symptoms in rats prenatally exposed to valproic acid

    OpenAIRE

    Servadio, M; Melancia, F; Manduca, A; di Masi, A; Schiavi, S; Cartocci, V; Pallottini, V; Campolongo, P; Ascenzi, P; Trezza, V

    2016-01-01

    Autism spectrum disorders (ASD) are characterized by altered sociability, compromised communication and stereotyped/repetitive behaviors, for which no specific treatments are currently available. Prenatal exposure to valproic acid (VPA) is a known, although still underestimated, environmental risk factor for ASD. Altered endocannabinoid activity has been observed in autistic patients, and endocannabinoids are known to modulate behavioral traits that are typically affected in ASD. On this basi...

  3. Edaravone ameliorates the adverse effects of valproic acid toxicity in small intestine.

    Science.gov (United States)

    Oktay, S; Alev, B; Tunali, S; Emekli-Alturfan, E; Tunali-Akbay, T; Koc-Ozturk, L; Yanardag, R; Yarat, A

    2015-06-01

    Valproic acid (VPA) is a drug used for the treatment of epilepsy, bipolar psychiatric disorders, and migraine. Previous studies have reported an increased generation of reactive oxygen species and oxidative stress in the toxic mechanism of VPA. Edaravone, a free radical scavenger for clinical use, can quench free radical reaction by trapping a variety of free radical species. In this study, effect of edaravone on some small intestine biochemical parameters in VPA-induced toxicity was investigated. Thirty seven Sprague Dawley female rats were randomly divided into four groups. The groups include control group, edaravone (30 mg(-1) kg(-1) day(-1)) given group, VPA (0.5 g(-1) kg(-1) day(-1)) given group, VPA + edaravone (in same dose) given group. Edaravone and VPA were given intraperitoneally for 7 days. Biochemical parameters such as malondialdehyde, as an index of lipid peroxidation(LPO), sialic acid (SA), glutathione levels and glutathione peroxidase, glutathione-S-transferase, superoxide dismutase, catalase, myeloperoxidase, alkaline phosphatase (ALP), and tissue factor (TF) activities were determined in small intestine samples by colorimetric methods. Decreased small intestine antioxidant enzyme activities, increased LPO and SA levels, and increased activities of ALP and TF were detected in the VPA group. Based on our results edaravone may be suggested to reverse the oxidative stress and inflammation due to VPA-induced small intestine toxicity. © The Author(s) 2014.

  4. Effects of royal jelly on genotoxicity and nephrotoxicity induced by valproic acid in albino mice

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    Sanaa R. Galaly

    2014-03-01

    Full Text Available Epilepsy is one of the most common neurological diseases affecting at least 50 million people worldwide. Valproic acid (VPA is a widely used antiepileptic medication for both generalized and partial seizures of epilepsy. The objective of the study was to investigate the anti-mutagenic and anti-histopathologic effects of royal jelly (RJ on VPA-induced genotoxicity and nephrotoxicity in male albino mice (Mus musculus. 80 Mice were used for 21 days; they were divided into eight groups, (G1 served as normal control group, G2 received VPA (100 mg/kg and (G3–G5 received RJ at doses 50, 100 and 200 mg/kg respectively. While (G6–G8 were administrated RJ simultaneously with VPA. In RJ treated mice at doses of 50 and 100 mg/kg, the kidney sections showed normal histological structure with non significant changes in chromosomal aberrations (CA and mitotic index (MI, while RJ at dose of 200 mg/kg showed mild inflammatory cells infiltration and hyperemic glomeruli but not highly significant changes in CA and MI. The cortex of VPA treated mice revealed congested glomeruli with inflammatory cells infiltration, and marked degeneration of almost structures of the glomeruli including some vacuoles in mesangial cells with dark mesangial substances on the ultrastructure level. Some proximal tubules showed degeneration of microvilli on the apical parts of some cells. Cells of the distal tubules attained obliterated lumen and vacuolated lining epithelium. The results also revealed that valproic acid induced a high frequency of CA in bone marrow cells of mice and MI was significantly decreased indicating bone marrow cytotoxicity. The treatment of mice with RJ at doses 50, 100 and 200 mg/kg for 21 days simultaneously with VPA resulted in abating the histological alterations in renal tissues with significant reduction in chromosomal aberrations, for doses of 50 and 100 mg/kg, and elevation in mitotic index (P < 0.05. RJ at doses 50 and 100 mg/kg appeared

  5. A simple and sensitive methodology for voltammetric determination of valproic acid in human blood plasma samples using 3-aminopropyletriethoxy silane coated magnetic nanoparticles modified pencil graphite electrode.

    Science.gov (United States)

    Zabardasti, Abedin; Afrouzi, Hossein; Talemi, Rasoul Pourtaghavi

    2017-07-01

    In this work, we have prepared a nano-material modified pencil graphite electrode for the sensing of valproic acid (VA) by immobilization 3-aminopropyletriethoxy silane coated magnetic nanoparticles (APTES-MNPs) on the pencil graphite surface (PGE). Electrochemical studies indicated that the APTES-MNPs efficiently increased the electron transfer kinetics between VA and the electrode and the free NH 2 groups of the APTES on the outer surface of magnetic nanoparticles can interact with carboxyl groups of VA. Based on this, we have proposed a sensitive, rapid and convenient electrochemical method for VA determination. Under the optimized conditions, the reduction peak current of VA is found to be proportional to its concentration in the range of 1.0 (±0.2) to 100.0 (±0.3) ppm with a detection limit of 0.4 (±0.1) ppm. The whole sensor fabrication process was characterized by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) methods with using [Fe(CN) 6 ] 3-/4- as an electrochemical redox indicator. The prepared modified electrode showed several advantages such as high sensitivity, selectivity, ease of preparation and good repeatability, reproducibility and stability. The proposed method was applied to determination of valproic acid in blood plasma samples and the obtained results were satisfactory accurate. Copyright © 2017. Published by Elsevier B.V.

  6. Dasatinib accelerates valproic acid-induced acute myeloid leukemia cell death by regulation of differentiation capacity.

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    Sook-Kyoung Heo

    Full Text Available Dasatinib is a compound developed for chronic myeloid leukemia as a multi-targeted kinase inhibitor against wild-type BCR-ABL and SRC family kinases. Valproic acid (VPA is an anti-epileptic drug that also acts as a class I histone deacetylase inhibitor. The aim of this research was to determine the anti-leukemic effects of dasatinib and VPA in combination and to identify their mechanism of action in acute myeloid leukemia (AML cells. Dasatinib was found to exert potent synergistic inhibitory effects on VPA-treated AML cells in association with G1 phase cell cycle arrest and apoptosis induction involving the cleavage of poly (ADP-ribose polymerase and caspase-3, -7 and -9. Dasatinib/VPA-induced cell death thus occurred via caspase-dependent apoptosis. Moreover, MEK/ERK and p38 MAPK inhibitors efficiently inhibited dasatinib/VPA-induced apoptosis. The combined effect of dasatinib and VPA on the differentiation capacity of AML cells was more powerful than the effect of each drug alone, being sufficiently strong to promote AML cell death through G1 cell cycle arrest and caspase-dependent apoptosis. MEK/ERK and p38 MAPK were found to control dasatinib/VPA-induced apoptosis as upstream regulators, and co-treatment with dasatinib and VPA to contribute to AML cell death through the regulation of differentiation capacity. Taken together, these results indicate that combined dasatinib and VPA treatment has a potential role in anti-leukemic therapy.

  7. Repeated prenatal exposure to valproic acid results in cerebellar hypoplasia and ataxia.

    Science.gov (United States)

    Main, Stacey L; Kulesza, Randy J

    2017-01-06

    Autism spectrum disorder (ASD) is a developmental brain disorder characterized by restricted and repetitive patterns of behavior, social and communication defects, and is commonly associated with difficulties with motor coordination. The etiology of ASD, while mostly idiopathic, has been linked to hereditary factors and teratogens, such as valproic acid (VPA). VPA is used clinically to treat epilepsy, mood disorders, and in the prevention of migraines. The use of VPA during pregnancy significantly increases the risk of ASD in the offspring. Neuropathological studies show decreased cerebellar function in patients with ASD, resulting in gait, balance and coordination impairments. Herein, we have exposed pregnant rats to a repeated oral dose of VPA on embryonic days 10 and 12 and performed a detailed investigation of the structure and function of the cerebellar vermis. We found that throughout all ten lobules of the cerebellar vermis, Purkinje cells were significantly smaller and expression of the calcium binding protein calbindin (CB) was significantly reduced. We also found that dendritic arbors of Purkinje cells were shorter and less complex. Additionally, animals exposed to a repeated dose of VPA performed significantly worse in a number of motor tasks, including beam walking and the rotarod. These results suggest that repeated embryonic exposure to VPA induces significant cerebellar dysfunction and is an effective animal model to study the cerebellar alterations in ASD. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. Ciliary body toxicities of systemic oxcarbazepine and valproic acid treatments: electron microscopic study.

    Science.gov (United States)

    Göktaş, Güleser; Aktaş, Zeynep; Erdoğan, Deniz; Seymen, Cemile Merve; Karaca, Emine Esra; Cansu, Ali; Serdaroğlu, Ayşe; Kaplanoğlu, Gülnur Take

    2015-01-01

    Ciliary body is responsible for humour aqueous production in posterior chamber. Valproic acid (VPA) has been widely used for the treatment of epilepsy and other neuropsychiatric diseases such as bipolar disease and major depression. Oxcarbazepine (OXC) is a new anti-epileptic agent that has been used recently for childhood epilepsies such as VPA. In this study, we aimed to investigate the effects of VPA and OXC treatments used as antiepileptic in ciliary body by electron microscopy. In our study, 40 Wistar rats (21 days old) were divided equally into four groups which were applied saline (group 1), VPA (group 2), OXC (group 3) and VPA + OXC (group 4). The as-prepared ocular tissues were characterized by transmission electron microscopy (TEM) technique in scanning and transmission electron microscopy (SEM-TEM) (Carl Zeiss EVO LS10). The results confirmed that VPA caused dense ciliary body degeneration. Additionally, ciliary body degeneration in group 4 was supposed to be due to VPA treatment. Ciliary body damage and secondary outcomes should be considered in patients with long-term VPA therapy.

  9. Antifibrogenic role of valproic acid in streptozotocin induced diabetic rat penis.

    Science.gov (United States)

    Kutlu, O; Karaguzel, E; Gurgen, S G; Okatan, A E; Kutlu, S; Bayraktar, C; Kazaz, I O; Eren, H

    2016-05-01

    We investigated the therapeutic effects of valproic acid (VPA) on erectile dysfunction and reducing penile fibrosis in streptozocin (STZ)-induced diabetic rats. Eighteen male rats were divided into three experimental groups (Control, STZ-DM, STZ-DM plus VPA) and diabetes was induced by transperitoneal single dose STZ. Eight weeks after, VPA and placebo treatments were given according to groups for 15 days. All rats were anesthetised for the measurement of in vivo erectile response to cavernous nerve stimulation. Afterward penes were evaluated histologically in terms of immune labelling scores of endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1). Slides were also evaluated in terms of collagen/smooth muscle ratio and penile apoptosis. After the treatment with VPA, erectile responses were found as improved when compared with STZ-DM rats but not statistically meaningful. eNOS and VEGF immune expressions diminished in penile corpora of STZ-DM rats and improved with VPA treatment. VPA led to decrease in TGF-β1 expression and collagen content of diabetic rats' penes. Penile apoptosis was not diminished with VPA. In conclusion, VPA treatment seems to be effective for reducing penile fibrosis in diabetic rats and more prolonged treatment period may enhance erectile functions. © 2015 Blackwell Verlag GmbH.

  10. Valproic acid improves the tolerance for the stress in learned helplessness rats.

    Science.gov (United States)

    Kobayashi, H; Iwata, M; Mitani, H; Yamada, T; Nakagome, K; Kaneko, K

    2012-04-01

    In this study, we investigated whether previously stressed rats with learned helplessness (LH) paradigm could recover from depressive-like behavior four weeks after the exposure, and also whether chronic treatment with valproic acid (VPA) could prevent behavioral despair due to the second stress on days 54 in these animals. Four weeks after induction of LH, we confirmed behavioral remission in the previously stressed rats. Two-way analysis of variance (ANOVA) performed with two factors, pretreatment (LH or Control) and drug (VPA or Saline), revealed a significant main effect of the drug on immobility time in forced swimming test. Post hoc test showed a shorter immobility time in the LH+VPA group than in the LH+Saline group. Immunohistochemical study of synapsin I showed a significant effect of drug by pretreatment interaction on immunoreactivity of synapsin I in the hippocampus: its expression levels in the regions were higher in the LH+VPA group than in the LH+Saline group. These results suggest that VPA could prevent the reappearance of stress-induced depressive-like behaviors in the rats recovering from prior stress, and that the drug-induced presynaptic changes in the expression of synapsin I in the hippocampus of LH animals might be related to improved tolerance toward the stress. Copyright © 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  11. Agmatine rescues autistic behaviors in the valproic acid-induced animal model of autism.

    Science.gov (United States)

    Kim, Ji-Woon; Seung, Hana; Kim, Ki Chan; Gonzales, Edson Luck T; Oh, Hyun Ah; Yang, Sung Min; Ko, Mee Jung; Han, Seol-Heui; Banerjee, Sourav; Shin, Chan Young

    2017-02-01

    Autism spectrum disorder (ASD) is an immensely challenging developmental disorder characterized primarily by two core behavioral symptoms of social communication deficits and restricted/repetitive behaviors. Investigating the etiological process and identifying an appropriate therapeutic target remain as formidable challenges to overcome ASD due to numerous risk factors and complex symptoms associated with the disorder. Among the various mechanisms that contribute to ASD, the maintenance of excitation and inhibition balance emerged as a key factor to regulate proper functioning of neuronal circuitry. Interestingly, our previous study involving the valproic acid animal model of autism (VPA animal model) has demonstrated excitatory-inhibitory imbalance (E/I imbalance) due to enhanced differentiation of glutamatergic neurons and reduced GABAergic neurons. Here, we investigated the potential of agmatine, an endogenous NMDA receptor antagonist, as a novel therapeutic candidate in ameliorating ASD symptoms by modulating E/I imbalance using the VPA animal model. We observed that a single treatment of agmatine rescued the impaired social behaviors as well as hyperactive and repetitive behaviors in the VPA animal model. We also observed that agmatine treatment rescued the overly activated ERK1/2 signaling in the prefrontal cortex and hippocampus of VPA animal models, possibly, by modulating over-excitability due to enhanced excitatory neural circuit. Taken together, our results have provided experimental evidence suggesting a possible therapeutic role of agmatine in ameliorating ASD-like symptoms in the VPA animal model of ASD. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. pH-Dependant Antifungal Activity of Valproic Acid against the Human Fungal Pathogen Candida albicans

    Directory of Open Access Journals (Sweden)

    Julien Chaillot

    2017-10-01

    Full Text Available Current antifungal drugs suffer from limitations including toxicity, the emergence of resistance and decreased efficacy at low pH that are typical of human vaginal surfaces. Here, we have shown that the antipsychotic drug valproic acid (VPA exhibited a strong antifungal activity against both sensitive and resistant Candida albicans in pH condition similar to that encountered in vagina. VPA exerted a strong anti-biofilm activity and attenuated damage of vaginal epithelial cells caused by C. albicans. We also showed that VPA synergizes with the allylamine antifungal, Terbinafine. We undertook a chemogenetic screen to delineate biological processes that underlies VPA-sensitivity in C. albicans and found that vacuole-related genes were required to tolerate VPA. Confocal fluorescence live-cell imaging revealed that VPA alters vacuole integrity and support a model where alteration of vacuoles contributes to the antifungal activity. Taken together, this study suggests that VPA could be used as an effective antifungal against vulvovaginal candidiasis.

  13. Enhanced long term microcircuit plasticity in the valproic acid animal model of autism

    Directory of Open Access Journals (Sweden)

    Guilherme T Silva

    2009-06-01

    Full Text Available A single intra-peritoneal injection of valproic acid (VPA on embryonic day (ED 11.5 to pregnant rats has been shown to produce severe autistic-like symptoms in the offspring. Previous studies showed that the microcircuitry is hyperreactive due to hyperconnectivity of glutamatergic synapses and hyperplastic due to over-expression of NMDA receptors. These changes were restricted to the dimensions of a mini-column (<50μm. In the present study, we explored whether Long Term Microcircuit Plasticity (LTMP was altered in this animal model. We performed multi-neuron patch-clamp recordings on clusters of layer V pyramidal cells in somatosensory cortex brain slices (PN 12-15, mapped the connectivity and characterized the synaptic properties for connected neurons. Pipettes were then withdrawn and the slice was perfused with 100μM sodium glutamate in artificial cerebrospinal fluid in the recording chamber for 12 h. When we re-patched the same cluster of neurons, we found enhanced LTMP only at inter-somatic distances beyond minicolumnar dimensions. These data suggest that hyperconnectivity is already near its peak within the dimensions of the minicolumn in the treated animals and that LTMP, which is normally restricted to within a minicolumn, spills over to drive hyperconnectivity across the dimensions of a minicolumn. This study provides further evidence to support the notion that the neocortex is highly plastic in response to new experiences in this animal model of autism.

  14. Enhanced long-term microcircuit plasticity in the valproic Acid animal model of autism.

    Science.gov (United States)

    Silva, Guilherme Testa; Le Bé, Jean-Vincent; Riachi, Imad; Rinaldi, Tania; Markram, Kamila; Markram, Henry

    2009-01-01

    A single intra-peritoneal injection of valproic acid (VPA) on embryonic day (ED) 11.5 to pregnant rats has been shown to produce severe autistic-like symptoms in the offspring. Previous studies showed that the microcircuitry is hyperreactive due to hyperconnectivity of glutamatergic synapses and hyperplastic due to over-expression of NMDA receptors. These changes were restricted to the dimensions of a minicolumn (brain slices (PN 12-15), mapped the connectivity and characterized the synaptic properties for connected neurons. Pipettes were then withdrawn and the slice was perfused with 100 μM sodium glutamate in artificial cerebrospinal fluid in the recording chamber for 12 h. When we re-patched the same cluster of neurons, we found enhanced LTMP only at inter-somatic distances beyond minicolumnar dimensions. These data suggest that hyperconnectivity is already near its peak within the dimensions of the minicolumn in the treated animals and that LTMP, which is normally restricted to within a minicolumn, spills over to drive hyperconnectivity across the dimensions of a minicolumn. This study provides further evidence to support the notion that the neocortex is highly plastic in response to new experiences in this animal model of autism.

  15. Valproic acid disrupts the oscillatory expression of core circadian rhythm transcription factors.

    Science.gov (United States)

    Griggs, Chanel A; Malm, Scott W; Jaime-Frias, Rosa; Smith, Catharine L

    2018-01-15

    Valproic acid (VPA) is a well-established therapeutic used in treatment of seizure and mood disorders as well as migraines and a known hepatotoxicant. About 50% of VPA users experience metabolic disruptions, including weight gain, hyperlipidemia, and hyperinsulinemia, among others. Several of these metabolic abnormalities are similar to the effects of circadian rhythm disruption. In the current study, we examine the effect of VPA exposure on the expression of core circadian transcription factors that drive the circadian clock via a transcription-translation feedback loop. In cells with an unsynchronized clock, VPA simultaneously upregulated the expression of genes encoding core circadian transcription factors that regulate the positive and negative limbs of the feedback loop. Using low dose glucocorticoid, we synchronized cultured fibroblast cells to a circadian oscillatory pattern. Whether VPA was added at the time of synchronization or 12h later at CT12, we found that VPA disrupted the oscillatory expression of multiple genes encoding essential transcription factors that regulate circadian rhythm. Therefore, we conclude that VPA has a potent effect on the circadian rhythm transcription-translation feedback loop that may be linked to negative VPA side effects in humans. Furthermore, our study suggests potential chronopharmacology implications of VPA usage. Copyright © 2017. Published by Elsevier Inc.

  16. Induction of superficial cortical layer neurons from mouse embryonic stem cells by valproic acid.

    Science.gov (United States)

    Juliandi, Berry; Abematsu, Masahiko; Sanosaka, Tsukasa; Tsujimura, Keita; Smith, Austin; Nakashima, Kinichi

    2012-01-01

    Within the developing mammalian cortex, neural progenitors first generate deep-layer neurons and subsequently more superficial-layer neurons, in an inside-out manner. It has been reported recently that mouse embryonic stem cells (mESCs) can, to some extent, recapitulate cortical development in vitro, with the sequential appearance of neurogenesis markers resembling that in the developing cortex. However, mESCs can only recapitulate early corticogenesis; superficial-layer neurons, which are normally produced in later developmental periods in vivo, are under-represented. This failure of mESCs to reproduce later corticogenesis in vitro implies the existence of crucial factor(s) that are absent or uninduced in existing culture systems. Here we show that mESCs can give rise to superficial-layer neurons efficiently when treated with valproic acid (VPA), a histone deacetylase inhibitor. VPA treatment increased the production of Cux1-positive superficial-layer neurons, and decreased that of Ctip2-positive deep-layer neurons. These results shed new light on the mechanisms of later corticogenesis. Copyright © 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  17. Differential Radiosensitizing Effect of Valproic Acid in Differentiation Versus Self-Renewal Promoting Culture Conditions

    International Nuclear Information System (INIS)

    Debeb, Bisrat G.; Xu Wei; Mok, Henry; Li Li; Robertson, Fredika; Ueno, Naoto T.; Reuben, Jim; Lucci, Anthony; Cristofanilli, Massimo; Woodward, Wendy A.

    2010-01-01

    Purpose: It has been shown that valproic acid (VA) enhances the proliferation and self-renewal of normal hematopoietic stem cells and that breast cancer stem/progenitor cells can be resistant to radiation. From these data, we hypothesized that VA would fail to radiosensitize breast cancer stem/progenitor cells grown to three-dimensional (3D) mammospheres. Methods and Materials: We used the MCF7 breast cancer cell line grown under stem cell-promoting culture conditions (3D mammosphere) and standard nonstem cell monolayer culture conditions (two-dimensional) to examine the effect of pretreatment with VA on radiation sensitivity in clonogenic survival assays and on the expression of embryonic stem cell transcription factors. Results: 3D-cultured MCF-7 cells expressed higher levels of Oct4, Nanog, and Sox2. The 3D passage enriched self-renewal and increased radioresistance in the 3D mammosphere formation assays. VA radiosensitized adherent cells but radioprotected 3D cells in single-fraction clonogenic assays. Moreover, fractionated radiation sensitized VA-treated adherent MCF7 cells but did not have a significant effect on VA-treated single cells grown to mammospheres. Conclusion: We have concluded that VA might preferentially radiosensitize differentiated cells compared with those expressing stem cell surrogates and that stem cell-promoting culture is a useful tool for in vitro evaluation of novel cancer therapeutic agents and radiosensitizers.

  18. Valproic acid induces cutaneous wound healing in vivo and enhances keratinocyte motility.

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    Soung-Hoon Lee

    Full Text Available BACKGROUND: Cutaneous wound healing is a complex process involving several signaling pathways such as the Wnt and extracellular signal-regulated kinase (ERK signaling pathways. Valproic acid (VPA is a commonly used antiepileptic drug that acts on these signaling pathways; however, the effect of VPA on cutaneous wound healing is unknown. METHODS AND FINDINGS: We created full-thickness wounds on the backs of C3H mice and then applied VPA. After 7 d, we observed marked healing and reduced wound size in VPA-treated mice. In the neo-epidermis of the wounds, β-catenin and markers for keratinocyte terminal differentiation were increased after VPA treatment. In addition, α-smooth muscle actin (α-SMA, collagen I and collagen III in the wounds were significantly increased. VPA induced proliferation and suppressed apoptosis of cells in the wounds, as determined by Ki67 and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL staining analyses, respectively. In vitro, VPA enhanced the motility of HaCaT keratinocytes by activating Wnt/β-catenin, ERK and phosphatidylinositol 3-kinase (PI3-kinase/Akt signaling pathways. CONCLUSIONS: VPA enhances cutaneous wound healing in a murine model and induces migration of HaCaT keratinocytes.

  19. Valproic acid decreases urothelial cancer cell proliferation and induces thrombospondin-1 expression

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    Byler Timothy K

    2012-08-01

    Full Text Available Abstract Background Prevention of bladder cancer recurrence is a central challenge in the management of this highly prevalent disease. The histone deacetylase inhibitor valproic acid (sodium valproate has anti-angiogenic properties and has been shown to decrease bladder cancer growth in model systems. We have previously shown reduced expression of thrombospondin-1 in a mouse model and in human bladder cancer relative to normal urothelium. We speculated that inhibition of angiogenesis by valproate might be mediated by this anti-angiogenic protein. Methods Bladder cancer cell lines UMUC3 and T24 were treated with valproate or another histone deacetylase inhibitor, vorinostat, in culture for a period of three days. Proliferation was assessed by alamar blue reduction. Gene expression was evaluated by reverse transcription of RNA and quantitative PCR. Results Proliferation assays showed treatment with valproate or vorinostat decreased proliferation in both cell lines. Histone deacetylase inhibition also increased relative expression of thrombospondin-1 up to 8 fold at 5 mM valproate. Conclusions Histone deacetylase inhibitors warrant further study for the prevention or treatment of bladder cancer.

  20. Valproic Acid, a Histone Deacetylase Inhibitor, in Combination with Paclitaxel for Anaplastic Thyroid Cancer: Results of a Multicenter Randomized Controlled Phase II/III Trial

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    Maria Graziella Catalano

    2016-01-01

    Full Text Available Anaplastic thyroid cancer (ATC has a median survival less than 5 months and, to date, no effective therapy exists. Taxanes have recently been stated as the main drug treatment for ATC, and the histone deacetylase inhibitor valproic acid efficiently potentiates the effects of paclitaxel in vitro. Based on these data, this trial assessed the efficacy and safety of the combination of paclitaxel and valproic acid for the treatment of ATC. This was a randomized, controlled phase II/III trial, performed on 25 ATC patients across 5 centers in northwest Italy. The experimental arm received the combination of paclitaxel (80 mg/m2/weekly and valproic acid (1,000 mg/day; the control arm received paclitaxel alone. Overall survival and disease progression, evaluated in terms of progression-free survival, were the primary outcomes. The secondary outcome was the pharmacokinetics of paclitaxel. The coadministration of valproic acid did not influence the pharmacokinetics of paclitaxel. Neither median survival nor median time to progression was statistically different in the two arms. Median survival of operated-on patients was significantly better than that of patients who were not operated on. The present trial demonstrates that the addition of valproic acid to paclitaxel has no effect on overall survival and disease progression of ATC patients. This trial is registered with EudraCT 2008-005221-11.

  1. Valproic acid prevents retinal degeneration in a murine model of normal tension glaucoma.

    Science.gov (United States)

    Kimura, Atsuko; Guo, Xiaoli; Noro, Takahiko; Harada, Chikako; Tanaka, Kohichi; Namekata, Kazuhiko; Harada, Takayuki

    2015-02-19

    Valproic acid (VPA) is widely used for treatment of epilepsy, mood disorders, migraines and neuropathic pain. It exerts its therapeutic benefits through modulation of multiple mechanisms including regulation of gamma-aminobutyric acid and glutamate neurotransmissions, activation of pro-survival protein kinases and inhibition of histone deacetylase. The evidence for neuroprotective properties associated with VPA is emerging. Herein, we investigated the therapeutic potential of VPA in a mouse model of normal tension glaucoma (NTG). Mice with glutamate/aspartate transporter gene deletion (GLAST KO mice) demonstrate progressive retinal ganglion cell (RGC) loss and optic nerve degeneration without elevated intraocular pressure, and exhibit glaucomatous pathology including glutamate neurotoxicity and oxidative stress in the retina. VPA (300mg/kg) or vehicle (PBS) was administered via intraperitoneal injection in GLAST KO mice daily for 2 weeks from the age of 3 weeks, which coincides with the onset of glaucomatous retinal degeneration. Following completion of the treatment period, the vehicle-treated GLAST KO mouse retina showed significant RGC death. Meanwhile, VPA treatment prevented RGC death and thinning of the inner retinal layer in GLAST KO mice. In addition, in vivo electrophysiological analyses demonstrated that visual impairment observed in vehicle-treated GLAST KO mice was ameliorated with VPA treatment, clearly establishing that VPA beneficially affects both histological and functional aspects of the glaucomatous retina. We found that VPA reduces oxidative stress induced in the GLAST KO retina and stimulates the cell survival signalling pathway associated with extracellular-signal-regulated kinases (ERK). This is the first study to report the neuroprotective effects of VPA in an animal model of NTG. Our findings raise intriguing possibilities that the widely prescribed drug VPA may be a novel candidate for treatment of glaucoma. Copyright © 2015 Elsevier

  2. Fluoxetine prevents the memory deficits and reduction in hippocampal cell proliferation caused by valproic acid.

    Science.gov (United States)

    Welbat, Jariya Umka; Sangrich, Preeyanuch; Sirichoat, Apiwat; Chaisawang, Pornthip; Chaijaroonkhanarak, Wunnee; Prachaney, Parichat; Pannangrong, Wanassanun; Wigmore, Peter

    2016-12-01

    Valproic acid (VPA), a commonly used antiepileptic drug, has been reported to cause cognitive impairments in patients. In a previous study, using a rodent model, we showed that VPA treatment impaired cognition which was associated with a reduction in the cell proliferation required for hippocampal neurogenesis. The antidepressant fluoxetine has been shown to increase hippocampal neurogenesis and to reverse the memory deficits found in a number of pathological conditions. In the present study we investigated the protective effects of fluoxetine treatment against the impairments in memory and hippocampal cell proliferation produced by VPA. Male Sprague Dawley rats received daily treatment with fluoxetine (10mg/kg) by oral gavage for 21days. Some rats were co-administered with VPA (300mg/kg, twice daily i.p. injections) for 14days from day 8 to day 21 of the fluoxetine treatment. Spatial memory was tested using the novel object location (NOL) test. The number of proliferating cells present in the sub granular zone of the dentate gyrus was quantified using Ki67 immunohistochemistry at the end of the experiment. Levels of the receptor Notch1, the neurotrophic factor BDNF and the neural differentiation marker DCX were determined by Western blotting. VPA-treated rats showed memory deficits, a decrease in the number of proliferating cells in the sub granular zone and decreases in the levels of Notch1 and BDNF but not DCX compared to control animals. These changes in behavior, cell proliferation and Notch1 and BDNF were prevented in animals which had received both VPA and fluoxetine. Rats receiving fluoxetine alone did not show a significant difference in the number of proliferating cells or behavior compared to controls. These results demonstrated that the spatial memory deficits and reduction of cell proliferation produced by VPA can be ameliorated by the simultaneous administration of the antidepressant fluoxetine. Crown Copyright © 2016. Published by Elsevier B

  3. Teratology study of derivatives of tetramethylcyclopropyl amide analogues of valproic acid in mice.

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    Okada, Akinobu; Onishi, Yuko; Aoki, Yoshinobu; Yagen, Boris; Sobol, Eyal; Bialer, Meir; Fujiwara, Michio

    2006-06-01

    Although valproic acid (VPA) is used extensively for treating various kinds of epilepsies, it is well known that it causes neural tube and skeletal defects in both humans and animals. The amide and urea derivatives of the tetramethylcylcopropyl VPA analogue, N-methoxy-2,2,3,3-tetramethylcyclopropanecarboxamide (N-methoxy-TMCD) and 2,2,3,3-tetramethylcyclopropanecarbonylurea (TMC-urea), were synthesized and shown to have a more potent anticonvulsant activity than VPA. The objective of this study was to investigate the teratogenic effects of these compounds in NMRI mice. Pregnant NMRI mice were given a single subcutaneous injection of either VPA, N-methoxy-TMCD, or TMC-urea at 1.8 and 3.6 mmol/kg on gestation day (GD) 8. Cesarean section was performed on GD 18. First, the live fetuses were examined to detect any external malformations, then their skeletons were double-stained for bone and cartilage and subsequently examined. Significant increases in fetal losses and neural tube defects were observed with administration of VPA at 3.6 mmol/kg when compared to the vehicle control. In contrast, upon cesarean section, there were no significant differences between either N-methoxy-TMCD or TMC-urea and the control groups for any parameter. Skeletal examination revealed that a number of the abnormalities were induced by VPA dose-dependently at high rates of incidence. These abnormalities were mainly at the axial skeletal level. However, lower frequencies of skeletal abnormality were observed with N-methoxy-TMCD and TMC-urea than with VPA. In addition to their more potent antiepileptic activity, these findings clearly indicate that N-methoxy-TMCD and TMC-urea are distinctly less teratogenic than VPA in NMRI mice.

  4. Valproic Acid Arrests Proliferation but Promotes Neuronal Differentiation of Adult Spinal NSPCs from SCI Rats.

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    Chu, Weihua; Yuan, Jichao; Huang, Lei; Xiang, Xin; Zhu, Haitao; Chen, Fei; Chen, Yanyan; Lin, Jiangkai; Feng, Hua

    2015-07-01

    Although the adult spinal cord contains a population of multipotent neural stem/precursor cells (NSPCs) exhibiting the potential to replace neurons, endogenous neurogenesis is very limited after spinal cord injury (SCI) because the activated NSPCs primarily differentiate into astrocytes rather than neurons. Valproic acid (VPA), a histone deacetylase inhibitor, exerts multiple pharmacological effects including fate regulation of stem cells. In this study, we cultured adult spinal NSPCs from chronic compressive SCI rats and treated with VPA. In spite of inhibiting the proliferation and arresting in the G0/G1 phase of NSPCs, VPA markedly promoted neuronal differentiation (β-tubulin III(+) cells) as well as decreased astrocytic differentiation (GFAP(+) cells). Cell cycle regulator p21(Cip/WAF1) and proneural genes Ngn2 and NeuroD1 were increased in the two processes respectively. In vivo, to minimize the possible inhibitory effects of VPA to the proliferation of NSPCs as well as avoid other neuroprotections of VPA in acute phase of SCI, we carried out a delayed intraperitoneal injection of VPA (150 mg/kg/12 h) to SCI rats from day 15 to day 22 after injury. Both of the newborn neuron marker doublecortin and the mature neuron marker neuron-specific nuclear protein were significantly enhanced after VPA treatment in the epicenter and adjacent segments of the injured spinal cord. Although the impaired corticospinal tracks had not significantly improved, Basso-Beattie-Bresnahan scores in VPA treatment group were better than control. Our study provide the first evidence that administration of VPA enhances the neurogenic potential of NSPCs after SCI and reveal the therapeutic value of delayed treatment of VPA to SCI.

  5. Development to term of cloned cattle derived from donor cells treated with valproic acid.

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    Juliano Rodrigues Sangalli

    Full Text Available Cloning of mammals by somatic cell nuclear transfer (SCNT is still plagued by low efficiency. The epigenetic modifications established during cellular differentiation are a major factor determining this low efficiency as they act as epigenetic barriers restricting reprogramming of somatic nuclei. In this regard, most factors that promote chromatin decondensation, including histone deacetylase inhibitors (HDACis, have been found to increase nuclear reprogramming efficiency, making their use common to improve SCNT rates. Herein we used valproic acid (VPA in SCNT to test whether the treatment of nuclear donor cells with this HDACi improves pre- and post-implantation development of cloned cattle. We found that the treatment of fibroblasts with VPA increased histone acetylation without affecting DNA methylation. Moreover, the treatment with VPA resulted in increased expression of IGF2R and PPARGC1A, but not of POU5F1. However, when treated cells were used as nuclear donors no difference of histone acetylation was found after oocyte reconstruction compared to the use of untreated cells. Moreover, shortly after artificial activation the histone acetylation levels were decreased in the embryos produced with VPA-treated cells. With respect to developmental rates, the use of treated cells as donors resulted in no difference during pre- and post-implantation development. In total, five clones developed to term; three produced with untreated cells and two with VPA-treated cells. Among the calves from treated group, one stillborn calf was delivered at day 270 of gestation whereas the other one was delivered at term but died shortly after birth. Among the calves from the control group, one died seven days after birth whereas the other two are still alive and healthy. Altogether, these results show that in spite of the alterations in fibroblasts resulting from the treatment with VPA, their use as donor cells in SCNT did not improve pre- and post

  6. Valproic Acid Use During Radiation Therapy for Glioblastoma Associated With Improved Survival

    Energy Technology Data Exchange (ETDEWEB)

    Barker, Christopher A., E-mail: barkerc@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Bishop, Andrew J.; Chang, Maria; Beal, Kathryn; Chan, Timothy A. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2013-07-01

    Purpose: Valproic acid (VA) is an antiepileptic drug (AED) and histone deacetylase (HDAC) inhibitor taken by patients with glioblastoma (GB) to manage seizures, and it can modulate the biologic effects of radiation therapy (RT). We investigated whether VA use during RT for GB was associated with overall survival (OS). Methods and Materials: Medical records of 544 adults with GB were retrospectively reviewed. Analyses were performed to determine the association of Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA) class, seizure history, and concurrent temozolomide (TMZ) and AED use during RT with OS. Results: Seizures before the end of RT were noted in 217 (40%) patients, and 403 (74%) were taking an AED during RT; 29 (7%) were taking VA. Median OS in patients taking VA was 16.9 months (vs 13.6 months taking another AED, P=.16). Among patients taking an AED during RT, OS was associated with VA (P=.047; hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.27-1.07), and RTOG RPA class (P<.0001; HR, 1.49; 95% CI, 1.37-1.61). Of the 5 most common AEDs, only VA was associated with OS. Median OS of patients receiving VA and TMZ during RT was 23.9 months (vs 15.2 months for patients taking another AED, P=.26). When the analysis was restricted to patients who received concurrent TMZ, VA use was marginally associated with OS (P=.057; HR, 0.54; 95% CI, −0.09 to 1.17), independently of RTOG RPA class and seizure history. Conclusions: VA use during RT for GB was associated with improved OS, independently of RTOG RPA, seizure history, and concurrent TMZ use. Further studies of treatment that combines HDAC inhibitors and RT are warranted.

  7. Valproic Acid Use During Radiation Therapy for Glioblastoma Associated With Improved Survival

    International Nuclear Information System (INIS)

    Barker, Christopher A.; Bishop, Andrew J.; Chang, Maria; Beal, Kathryn; Chan, Timothy A.

    2013-01-01

    Purpose: Valproic acid (VA) is an antiepileptic drug (AED) and histone deacetylase (HDAC) inhibitor taken by patients with glioblastoma (GB) to manage seizures, and it can modulate the biologic effects of radiation therapy (RT). We investigated whether VA use during RT for GB was associated with overall survival (OS). Methods and Materials: Medical records of 544 adults with GB were retrospectively reviewed. Analyses were performed to determine the association of Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA) class, seizure history, and concurrent temozolomide (TMZ) and AED use during RT with OS. Results: Seizures before the end of RT were noted in 217 (40%) patients, and 403 (74%) were taking an AED during RT; 29 (7%) were taking VA. Median OS in patients taking VA was 16.9 months (vs 13.6 months taking another AED, P=.16). Among patients taking an AED during RT, OS was associated with VA (P=.047; hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.27-1.07), and RTOG RPA class (P<.0001; HR, 1.49; 95% CI, 1.37-1.61). Of the 5 most common AEDs, only VA was associated with OS. Median OS of patients receiving VA and TMZ during RT was 23.9 months (vs 15.2 months for patients taking another AED, P=.26). When the analysis was restricted to patients who received concurrent TMZ, VA use was marginally associated with OS (P=.057; HR, 0.54; 95% CI, −0.09 to 1.17), independently of RTOG RPA class and seizure history. Conclusions: VA use during RT for GB was associated with improved OS, independently of RTOG RPA, seizure history, and concurrent TMZ use. Further studies of treatment that combines HDAC inhibitors and RT are warranted

  8. Abnormal emotional learning in a rat model of autism exposed to valproic acid in utero

    Directory of Open Access Journals (Sweden)

    Anwesha eBanerjee

    2014-11-01

    Full Text Available Autism Spectrum Disorders (ASD are complex neurodevelopmental disorders characterized by repetitive behavior and impaired social communication and interactions. Apart from these core symptoms, a significant number of ASD individuals display higher levels of anxiety and some ASD individuals exhibit impaired emotional learning. We therefore sought to further examine anxiety and emotional learning in an environmentally induced animal model of ASD that utilizes the administration of the known teratogen, valproic acid (VPA during gestation. Specifically we exposed dams to one of two different doses of VPA (500 and 600 mg/kg or vehicle on day 12.5 of gestation and examined the resultant progeny. Our data indicate that animals exposed to VPA in utero exhibit enhanced anxiety in the open field test and normal object recognition memory compared to control animals. Animals exposed to 500 mg/kg of VPA displayed normal acquisition of auditory fear conditioning, and exhibited reduced extinction of fear memory and normal litter survival rates as compared to control animals. We observed that animals exposed to 600 mg/kg of VPA exhibited a significant reduction in the acquisition of fear conditioning, a significant reduction in social interaction and a significant reduction in litter survival rates as compared to control animals. VPA (600 mg/kg exposed animals exhibited similar shock sensitivity and hearing as compared to control animals indicating the fear conditioning deficit observed in these animals was not likely due to sensory deficits, but rather due to deficits in learning or memory retrieval. In conclusion, considering that progeny from dams exposed to rather similar doses of VPA exhibit striking differences in emotional learning, the VPA model may serve as a useful tool to explore the molecular and cellular mechanisms that contribute to not only ASD, but also emotional learning.

  9. Environmental enrichment attenuates behavioral abnormalities in valproic acid-exposed autism model mice.

    Science.gov (United States)

    Yamaguchi, Hiroshi; Hara, Yuta; Ago, Yukio; Takano, Erika; Hasebe, Shigeru; Nakazawa, Takanobu; Hashimoto, Hitoshi; Matsuda, Toshio; Takuma, Kazuhiro

    2017-08-30

    We recently demonstrated that prenatal exposure to valproic acid (VPA) at embryonic day 12.5 causes autism spectrum disorder (ASD)-like phenotypes such as hypolocomotion, anxiety-like behavior, social deficits and cognitive impairment in mice and that it decreases dendritic spine density in the hippocampal CA1 region. Previous studies show that some abnormal behaviors are improved by environmental enrichment in ASD rodent models, but it is not known whether environmental enrichment improves cognitive impairment. In the present study, we examined the effects of early environmental enrichment on behavioral abnormalities and neuromorphological changes in prenatal VPA-treated mice. We also examined the role of dendritic spine formation and synaptic protein expression in the hippocampus. Mice were housed for 4 weeks from 4 weeks of age under either a standard or enriched environment. Enriched housing was found to increase hippocampal brain-derived neurotrophic factor mRNA levels in both control and VPA-exposed mice. Furthermore, in VPA-treated mice, the environmental enrichment improved anxiety-like behavior, social deficits and cognitive impairment, but not hypolocomotion. Prenatal VPA treatment caused loss of dendritic spines in the hippocampal CA1 region and decreases in mRNA levels of postsynaptic density protein-95 and SH3 and multiple ankyrin repeat domains 2 in the hippocampus. These hippocampal changes were improved by the enriched housing. These findings suggest that the environmental enrichment improved most ASD-like behaviors including cognitive impairment in the VPA-treated mice by enhancing dendritic spine function. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Valproic acid treatment response in vitro is determined by TP53 status in medulloblastoma.

    Science.gov (United States)

    Mascaro-Cordeiro, Bruna; Oliveira, Indhira Dias; Tesser-Gamba, Francine; Pavon, Lorena Favaro; Saba-Silva, Nasjla; Cavalheiro, Sergio; Dastoli, Patrícia; Toledo, Silvia Regina Caminada

    2018-05-22

    Histone deacetylate inhibitors (HDACi), as valproic acid (VA), have been reported to enhance efficacy and to prevent drug resistance in some tumors, including medulloblastoma (MB). In the present study, we investigated VA role, combined to cisplatin (CDDP) in cell viability and gene expression of MB cell lines. Dose-response curve determined IC 50 values for each treatment: (1) VA single, (2) CDDP single, and (3) VA and CDDP combined. Cytotoxicity and flow cytometry evaluated cell viability after exposure to treatments. Quantitative PCR evaluated gene expression levels of AKT, CTNNB1, GLI1, KDM6A, KDM6B, NOTCH2, PTCH1, and TERT, before and after treatment. Besides, we performed next-generation sequencing (NGS) for PTCH1, TERT, and TP53 genes. The most effective treatment to reduce viability was combined for D283MED and ONS-76; and CDDP single for DAOY cells (p AKT genes were overexpressed after treatments with VA. D283MED and ONS-76 cells presented variants in TERT and PTCH1, respectively and DAOY cell line presented a TP53 mutation. MB tumors belonging to SHH molecular subgroup, with TP53 MUT , would be the ones that present high risk in relation to VA use during the treatment, while TP53 WT MBs can benefit from VA therapy, both SHH and groups 3 and 4. Our study shows a new perspective about VA action in medulloblastoma cells, raising the possibility that VA may act in different patterns. According to the genetic background of MB cell, VA can stimulate cell cycle arrest and apoptosis or induce resistance to treatment via signaling pathways activation.

  11. Developmental disruption of amygdala transcriptome and socioemotional behavior in rats exposed to valproic acid prenatally.

    Science.gov (United States)

    Barrett, Catherine E; Hennessey, Thomas M; Gordon, Katelyn M; Ryan, Steve J; McNair, Morgan L; Ressler, Kerry J; Rainnie, Donald G

    2017-01-01

    The amygdala controls socioemotional behavior and has consistently been implicated in the etiology of autism spectrum disorder (ASD). Precocious amygdala development is commonly reported in ASD youth with the degree of overgrowth positively correlated to the severity of ASD symptoms. Prenatal exposure to VPA leads to an ASD phenotype in both humans and rats and has become a commonly used tool to model the complexity of ASD symptoms in the laboratory. Here, we examined abnormalities in gene expression in the amygdala and socioemotional behavior across development in the valproic acid (VPA) rat model of ASD. Rat dams received oral gavage of VPA (500 mg/kg) or saline daily between E11 and 13. Socioemotional behavior was tracked across development in both sexes. RNA sequencing and proteomics were performed on amygdala samples from male rats across development. Effects of VPA on time spent in social proximity and anxiety-like behavior were sex dependent, with social abnormalities presenting in males and heightened anxiety in females. Across time VPA stunted developmental and immune, but enhanced cellular death and disorder, pathways in the amygdala relative to saline controls. At postnatal day 10, gene pathways involved in nervous system and cellular development displayed predicted activations in prenatally exposed VPA amygdala samples. By juvenile age, however, transcriptomic and proteomic pathways displayed reductions in cellular growth and neural development. Alterations in immune pathways, calcium signaling, Rho GTPases, and protein kinase A signaling were also observed. As behavioral, developmental, and genomic alterations are similar to those reported in ASD, these results lend support to prenatal exposure to VPA as a useful tool for understanding how developmental insults to molecular pathways in the amygdala give rise to ASD-related syndromes.

  12. Valproic acid potentiates curcumin-mediated neuroprotection in Lipopolysaccharide induced rats

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    Amira eZaky

    2014-10-01

    Full Text Available The etiology of neuroinflammation is complex and comprises multifactorial, involving both genetic and environmental factors during which diverse genetic and epigenetic modulations are implicated. Curcumin (Cur, and valproic acid (VPA, histone deacetylase 1 inhibitor, have neuroprotective effects. The present study was designed with an aim to investigate the ability of co-treatment of both compounds (Cur or VPA (200mg/kg for four weeks to augment neuroprotection and enhance brain recovery from intra-peritoneal (IP injection of (250 µg/kg lipopolysaccharide (LPS-stimulated neuroinflammatory condition on rat brain cortex. Cortex activation and the effects of combined treatment and production of proinflammatory mediators, COX-2, APE1 and nitric oxide/iNOS were investigated. Neuroinflammation development was assessed by histological analyses and by investigating associated indices (BACE1, APP, PSEN-1 and PSEN-2. Furthermore we measured the expression profile of let-7 miRNAs members a, b, c, e and f in all groups, a highly abundant regulator of gene expression in the CNS. Protein and mRNA levels of neuroinflammation markers COX-2, BACE1, APP and iNOS were also attenuated by combined therapy. On the other hand, assessment of the indicated five let-7 members, showed distinct expression profile pattern in the different groups. Let-7 a, b and c disappeared in the induced group, an effect that was partially suppressed by co-addition of either Cur or VPA. These data suggest that the combined treatment induced significantly the expression of the five members when compared to rats treated with Cur or VPA only as well as to self-recovery group, which indicates a possible benefit from the synergistic effect of Cur-VPA combination as therapeutic agents for neuroinflammation and its associated disorders. The mechanism elucidated here highlights the particular drug-induced expression profile of let-7 family as new targets for future pharmacological development.

  13. Valproic Acid as a Potential Inhibitor of Plasmodium falciparum Histone Deacetylase 1 (PfHDAC1: An in Silico Approach

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    Mohamed A. Abdallah Elbadawi

    2015-02-01

    Full Text Available A new Plasmodium falciparum histone deacetylase1 (PfHDAC1 homology model was built based on the highest sequence identity available template human histone deacetylase 2 structure. The generated model was carefully evaluated for stereochemical accuracy, folding correctness and overall structure quality. All evaluations were acceptable and consistent. Docking a group of hydroxamic acid histone deacetylase inhibitors and valproic acid has shown binding poses that agree well with inhibitor-bound histone deacetylase-solved structural interactions. Docking affinity dG scores were in agreement with available experimental binding affinities. Further, enzyme-ligand complex stability and reliability were investigated by running 5-nanosecond molecular dynamics simulations. Thorough analysis of the simulation trajectories has shown that enzyme-ligand complexes were stable during the simulation period. Interestingly, the calculated theoretical binding energies of the docked hydroxamic acid inhibitors have shown that the model can discriminate between strong and weaker inhibitors and agrees well with the experimental affinities reported in the literature. The model and the docking methodology can be used in screening virtual libraries for PfHDAC1 inhibitors, since the docking scores have ranked ligands in accordance with experimental binding affinities. Valproic acid calculated theoretical binding energy suggests that it may inhibit PfHDAC1.

  14. Elevated NMDA receptor levels and enhanced postsynaptic long-term potentiation induced by prenatal exposure to valproic acid

    DEFF Research Database (Denmark)

    Rinaldi, Tania; Kulangara, Karina; Antoniello, Katia

    2007-01-01

    as the commonly linked kinase calcium/calmodulin-dependent protein kinase II. Synaptic plasticity experiments between pairs of pyramidal neurons revealed an augmented postsynaptic form of long-term potentiation. These results indicate that VPA significantly enhances NMDA receptor-mediated transmission and causes......Valproic acid (VPA) is a powerful teratogen causing birth defects in humans, including autism spectrum disorder (ASD), if exposure occurs during the first trimester of embryogenesis. Learning and memory alterations are common symptoms of ASD, but underlying molecular and synaptic alterations remain...

  15. The anti-epileptic drug valproic acid (VPA inhibits steroidogenesis in bovine theca and granulosa cells in vitro.

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    Claire Glister

    Full Text Available Valproic acid (VPA is used widely to treat epilepsy and bipolar disorder. Women undergoing VPA treatment reportedly have an increased incidence of polycystic ovarian syndrome (PCOS-like symptoms including hyperandrogenism and oligo- or amenorrhoea. To investigate potential direct effects of VPA on ovarian steroidogenesis we used primary bovine theca (TC and granulosa (GC cells maintained under conditions that preserve their 'follicular' phenotype. Effects of VPA (7.8-500 µg/ml on TC were tested with/without LH. Effects of VPA on GC were tested with/without FSH or IGF analogue. VPA reduced (P99% decrease; P<0.0001 with lesser effects on LHR, STAR, CYP11A1 and HSD3B1 mRNA (<90% decrease; P<0.05. VPA only reduced TC progesterone secretion induced by the highest (luteinizing LH dose tested; TC number was unaffected by VPA. At higher concentrations (125-500 µg/ml VPA inhibited basal, FSH- and IGF-stimulated estradiol secretion (P<0.0001 by GC without affecting progesterone secretion or cell number. VPA reversed FSH-induced upregulation of CYP19A1 and HSD17B1 mRNA abundance (P<0.001. The potent histone deacetylase (HDAC inhibitors trichostatin A and scriptaid also suppressed TC androstenedione secretion and granulosal cell oestrogen secretion suggesting that the action of VPA reflects its HDAC inhibitory properties. In conclusion, these findings refute the hypothesis that VPA has a direct stimulatory action on TC androgen output. On the contrary, VPA inhibits both LH-dependent androgen production and FSH/IGF-dependent estradiol production in this in vitro bovine model, likely by inhibition of HDAC.

  16. In vivo effects of naproxen, salicylic acid, and valproic acid on the pharmacokinetics of trichloroethylene and metabolites in rats.

    Science.gov (United States)

    Rouhou, Mouna Cheikh; Charest-Tardif, Ginette; Haddad, Sami

    2015-01-01

    It was recently demonstrated that some drugs modulate in vitro metabolism of trichloroethylene (TCE) in humans and rats. The objective was to assess in vivo interactions between TCE and three drugs: naproxen (NA), valproic acid (VA), and salicylic acid (SA). Animals were exposed to TCE by inhalation (50 ppm for 6 h) and administered a bolus dose of drug by gavage, equivalent to 10-fold greater than the recommended daily dose. Samples of blood, urine, and collected tissues were analyzed by headspace gas chromatography coupled to an electron capture detector for TCE and metabolites (trichloroethanol [TCOH] and trichloroacetate [TCA]) levels. Coexposure to NA and TCE significantly increased (up to 50%) total and free TCOH (TCOHtotal and TCOHfree, respectively) in blood. This modulation may be explained by an inhibition of glucuronidation. VA significantly elevated TCE levels in blood (up to 50%) with a marked effect on TCOHtotal excretion in urine but not in blood. In contrast, SA produced an increase in TCOHtotal levels in blood at 30, 60, and 90 min and urine after coexposure. Data confirm in vitro observations that NA, VA, and SA affect in vivo TCE kinetics. Future efforts need to be directed to evaluate whether populations chronically medicated with the considered drugs display greater health risks related to TCE exposure.

  17. All guns blazing: management and survival of massive valproic acid overdose – case report and literature review

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    Al Jawder S

    2018-01-01

    Full Text Available Shaikha Al Jawder,1 Eiman AlJishi,2 Shaikhah Al-Otaibi,2 Mohammed S Al-Shahrani3 1King Hamad University Hospital, Busaiteen, Bahrain; 2Emergency Medicine Department, 3Emergency and Critical Care Department, King Fahad Hospital of the University, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia Abstract: A 51-year-old woman, who intentionally ingested a massive dose of ~60 g of valproic acid which she was using as a mood stabilizer for bipolar affective disorder, presented within 30 minutes of ingestion to the emergency department. The patient was asymptomatic and was immediately started on decontamination therapy with activated charcoal (AC. Drug serum levels, liver functions, and ammonia levels were tested and followed up during treatment. Due to the massive ingestion and continuous rise in serum drug levels, the patient received regular multiple doses of AC, as well as l-carnitine for liver protection. The patient was started on extracorporeal therapy in the form of renal replacement therapy in the intensive care unit (ICU, followed by intermittent hemodialysis. Drug serum levels dropped significantly. Ammonia levels showed improvement with treatment. The patient was discharged from the ICU after 14 days of treatment. She was stable and in good condition with no residual hepatic or central nervous system (CNS manifestations. Keywords: valproic acid, multiple dose activated charcoal, l-carnitine, hemodialysis

  18. Increasing pro-survival factors within whole brain tissue of Sprague Dawley rats via intracerebral administration of modified valproic acid

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    Ryan C. Bates

    2015-08-01

    Full Text Available Neural tissue exposure to valproic acid (VPA increases several pro-survival phospho-proteins that can be used as biomarkers for indicating a beneficial drug response (pAktSer473, pGSK3βSer9, pErk1/2Thr202/Tyr204. Unfortunately, targeting VPA to neural tissue is a problem due to severe asymmetrical distribution, wherein the drug tends to remain in peripheral blood rather than localizing within the brain. Intracerebral delivery of an amide-linked VPA–PEG conjugate could address these issues by enhancing retention and promoting cerebro-global increases in pro-survival phospho-proteins. It is necessary to assay for the retained bioactivity of a PEGylated valproic acid molecule, along with locating an intracranial cannula placement that optimizes the increase of a known downstream biomarker for chronic VPA exposure. Here we show an acute injection of VPA–PEG conjugate within brain tissue increased virtually all of the assayed phospho-proteins, including well-known pro-survival factors. In contrast, an acute injection of VPA expectedly decreased signaling throughout the hour. Needle penetration into whole brain tissue is the intentional cause of trauma in this procedure. The trauma to brain tissue was observed to overcome known phospho-protein increases for unmodified VPA in the injected solution, while VPA–PEG conjugate appeared to induce significant increases in pro-survival phospho-proteins, despite the procedural trauma.

  19. Clinical Validation and Implications of Dried Blood Spot Sampling of Carbamazepine, Valproic Acid and Phenytoin in Patients with Epilepsy

    Science.gov (United States)

    Kong, Sing Teang; Lim, Shih-Hui; Lee, Wee Beng; Kumar, Pasikanthi Kishore; Wang, Hwee Yi Stella; Ng, Yan Lam Shannon; Wong, Pei Shieen; Ho, Paul C.

    2014-01-01

    To facilitate therapeutic monitoring of antiepileptic drugs (AEDs) by healthcare professionals for patients with epilepsy (PWE), we applied a GC-MS assay to measure three AEDs: carbamazepine (CBZ), phenytoin (PHT) and valproic acid (VPA) levels concurrently in one dried blood spot (DBS), and validated the DBS-measured levels to their plasma levels. 169 PWE on either mono- or polytherapy of CBZ, PHT or/and VPA were included. One DBS, containing ∼15 µL of blood, was acquired for the simultaneous measurement of the drug levels using GC-MS. Simple Deming regressions were performed to correlate the DBS levels with the plasma levels determined by the conventional immunoturbimetric assay in clinical practice. Statistical analyses of the results were done using MedCalc Version 12.6.1.0 and SPSS 21. DBS concentrations (Cdbs) were well-correlated to the plasma concentrations (Cplasma): r = 0.8381, 0.9305 and 0.8531 for CBZ, PHT and VPA respectively, The conversion formulas from Cdbs to plasma concentrations were [0.89×CdbsCBZ+1.00]µg/mL, [1.11×CdbsPHT−1.00]µg/mL and [0.92×CdbsVPA+12.48]µg/mL respectively. Inclusion of the red blood cells (RBC)/plasma partition ratio (K) and the individual hematocrit levels in the estimation of the theoretical Cplasma from Cdbs of PHT and VPA further improved the identity between the observed and the estimated theoretical Cplasma. Bland-Altman plots indicated that the theoretical and observed Cplasma of PHT and VPA agreed well, and >93.0% of concentrations was within 95% CI (±2SD); and similar agreement (1∶1) was also found between the observed Cdbs and Cplasma of CBZ. As the Cplasma of CBZ, PHT and VPA can be accurately estimated from their Cdbs, DBS can therefore be used for drug monitoring in PWE on any of these AEDs. PMID:25255292

  20. Phase II open label study of valproic acid in spinal muscular atrophy.

    Directory of Open Access Journals (Sweden)

    Kathryn J Swoboda

    Full Text Available Preliminary in vitro and in vivo studies with valproic acid (VPA in cell lines and patients with spinal muscular atrophy (SMA demonstrate increased expression of SMN, supporting the possibility of therapeutic benefit. We performed an open label trial of VPA in 42 subjects with SMA to assess safety and explore potential outcome measures to help guide design of future controlled clinical trials. Subjects included 2 SMA type I ages 2-3 years, 29 SMA type II ages 2-14 years and 11 type III ages 2-31 years, recruited from a natural history study. VPA was well-tolerated and without evident hepatotoxicity. Carnitine depletion was frequent and temporally associated with increased weakness in two subjects. Exploratory outcome measures included assessment of gross motor function via the modified Hammersmith Functional Motor Scale (MHFMS, electrophysiologic measures of innervation including maximum ulnar compound muscle action potential (CMAP amplitudes and motor unit number estimation (MUNE, body composition and bone density via dual-energy X-ray absorptiometry (DEXA, and quantitative blood SMN mRNA levels. Clear decline in motor function occurred in several subjects in association with weight gain; mean fat mass increased without a corresponding increase in lean mass. We observed an increased mean score on the MHFMS scale in 27 subjects with SMA type II (p

  1. Long-term valproic acid exposure increases the number of neocortical neurons in the developing rat brain. A possible new animal model of autism

    DEFF Research Database (Denmark)

    Sabers, Anne; Bertelsen, Freja C B; Scheel-Krüger, Jørgen

    2014-01-01

    The aim of this study was to test the hypothesis that long-term fetal valproic acid (VPA) exposure at doses relevant to the human clinic interferes with normal brain development. Pregnant rats were given intraperitoneal injections of VPA (20mg/kg or 100mg/kg) continuously during the last 9-12 day...

  2. New insights into the molecular and epigenetic effects of antitumor Pt(IV)-valproic acid conjugates in human ovarian cancer cells

    Czech Academy of Sciences Publication Activity Database

    Novohradský, Vojtěch; Zerzánková, Lenka; Štěpánková, Jana; Vrána, Oldřich; Raveendran, R.; Gibson, D.; Kašpárková, Jana; Brabec, Viktor

    2015-01-01

    Roč. 95, č. 3 (2015), s. 133-144 ISSN 0006-2952 R&D Projects: GA ČR(CZ) GA14-21053S; GA MŠk(CZ) LD14019 Institutional support: RVO:68081707 Keywords : HISTONE DEACETYLASE INHIBITORS * MALIGNANT PLEURAL MESOTHELIOMA * VALPROIC ACID Subject RIV: BO - Biophysics Impact factor: 5.091, year: 2015

  3. Modulation of Antioxidant Enzymatic Activities by Certain Antiepileptic Drugs (Valproic Acid, Oxcarbazepine, and Topiramate): Evidence in Humans and Experimental Models

    Science.gov (United States)

    Cárdenas-Rodríguez, Noemí; Coballase-Urrutia, Elvia; Rivera-Espinosa, Liliana; Romero-Toledo, Arantxa; Sampieri, Aristides III; Ortega-Cuellar, Daniel; Montesinos-Correa, Hortencia; Floriano-Sánchez, Esaú; Carmona-Aparicio, Liliana

    2013-01-01

    It is estimated that at least 100 million people worldwide will suffer from epilepsy at some point in their lives. This neurological disorder induces brain death due to the excessive liberation of glutamate, which activates the postsynaptic N-methyl-D-aspartic acid (NMDA) receptors, which in turn cause the reuptake of intracellular calcium (excitotoxicity). This excitotoxicity elicits a series of events leading to nitric oxide synthase (NOS) activation and the generation of reactive oxygen species (ROS). Several studies in experimental models and in humans have demonstrated that certain antiepileptic drugs (AEDs) exhibit antioxidant effects by modulating the activity of various enzymes associated with this type of stress. Considering the above-mentioned data, we aimed to compile evidence elucidating how AEDs such as valproic acid (VPA), oxcarbazepine (OXC), and topiramate (TPM) modulate oxidative stress. PMID:24454986

  4. Modulation of Antioxidant Enzymatic Activities by Certain Antiepileptic Drugs (Valproic Acid, Oxcarbazepine, and Topiramate: Evidence in Humans and Experimental Models

    Directory of Open Access Journals (Sweden)

    Noemí Cárdenas-Rodríguez

    2013-01-01

    Full Text Available It is estimated that at least 100 million people worldwide will suffer from epilepsy at some point in their lives. This neurological disorder induces brain death due to the excessive liberation of glutamate, which activates the postsynaptic N-methyl-D-aspartic acid (NMDA receptors, which in turn cause the reuptake of intracellular calcium (excitotoxicity. This excitotoxicity elicits a series of events leading to nitric oxide synthase (NOS activation and the generation of reactive oxygen species (ROS. Several studies in experimental models and in humans have demonstrated that certain antiepileptic drugs (AEDs exhibit antioxidant effects by modulating the activity of various enzymes associated with this type of stress. Considering the above-mentioned data, we aimed to compile evidence elucidating how AEDs such as valproic acid (VPA, oxcarbazepine (OXC, and topiramate (TPM modulate oxidative stress.

  5. Comparison of clinical, magnetic resonance and evoked potentials data in a case of valproic-acid-related hyperammonemic coma

    International Nuclear Information System (INIS)

    Hantson, Philippe; Grandin, Cecile; Duprez, Thierry; Nassogne, Marie-Cecile; Guerit, Jean-Michel

    2005-01-01

    Magnetic resonance (MR) multimodality evoked potentials (MEPs) and clinical findings were correlated in a 47-year-old epileptic man in whom parenteral valproic acid (VPA) therapy induced severe comatose hyperammonemic encephalopathy without biological signs of hepatotoxicity (or hepatocytic dysfunction). Although the plasma VPA level remained within a normal therapeutic range, the ammoniemia increased to a toxic peak level at 411 μmol/l 24 h after symptom onset, requiring VPA therapy discontinuation. Brain MR monitoring demonstrated early cytotoxic edema evolving into delayed vasogenic edema and final brain atrophy. Concomitantly to abnormalities within the brainstem on MR images, an increase in brainstem conduction at MEPs and clinical disturbance of brainstem reflexes were observed at the initial phase of the disease course. Later, the resolution of the MR and MEPs abnormalities paralleled the clinical recovery of the reflexes. (orig.)

  6. Role of SMAD4 in the mechanism of valproic acid's inhibitory effect on prostate cancer cell invasiveness.

    Science.gov (United States)

    Jiang, Wei; Zheng, Yi; Huang, Zhongxian; Wang, Muwen; Zhang, Yinan; Wang, Zheng; Jin, Xunbo; Xia, Qinghua

    2014-05-01

    To investigate the influence of the histone deacetylase inhibitor valproic acid (VPA) on SMAD4 expression and invasive ability of prostate cancer cell lines. DU145 and PC3 cell lines were treated with 0, 2, and 5 mMol/l of VPA; invasion of DU145 and PC3 cells were then examined by transwell assay. Immunohistochemistry and Western blot were used to examine SMAD4 protein expression in DU145 and PC3 cells. Compared with controls, VPA significantly suppressed invasiveness in both PC3 and DU145 cells in a dose-dependent way (P AKT protein (which was regarded as an effective indicator here), and meanwhile, SMAD4 expression was down-regulated after VPA treatment in a dose-dependent manner in both DU145 (P SMAD4 enhancers could form a basis for a novel prostate cancer treatment.

  7. Comparison of clinical, magnetic resonance and evoked potentials data in a case of valproic-acid-related hyperammonemic coma

    Energy Technology Data Exchange (ETDEWEB)

    Hantson, Philippe [Universite Catholique de Louvain, Department of Intensive Care, Cliniques Saint-Luc, Brussels (Belgium); Grandin, Cecile; Duprez, Thierry [Universite Catholique de Louvain, Department of Neuroradiology, Cliniques Saint-Luc, Brussels (Belgium); Nassogne, Marie-Cecile [Universite Catholique de Louvain, Department of Pediatric Neurology, Cliniques Saint-Luc, Brussels (Belgium); Guerit, Jean-Michel [Universite Catholique de Louvain, Laboratory of Neurophysiology, Cliniques Saint-Luc, Brussels (Belgium)

    2005-01-01

    Magnetic resonance (MR) multimodality evoked potentials (MEPs) and clinical findings were correlated in a 47-year-old epileptic man in whom parenteral valproic acid (VPA) therapy induced severe comatose hyperammonemic encephalopathy without biological signs of hepatotoxicity (or hepatocytic dysfunction). Although the plasma VPA level remained within a normal therapeutic range, the ammoniemia increased to a toxic peak level at 411 {mu}mol/l 24 h after symptom onset, requiring VPA therapy discontinuation. Brain MR monitoring demonstrated early cytotoxic edema evolving into delayed vasogenic edema and final brain atrophy. Concomitantly to abnormalities within the brainstem on MR images, an increase in brainstem conduction at MEPs and clinical disturbance of brainstem reflexes were observed at the initial phase of the disease course. Later, the resolution of the MR and MEPs abnormalities paralleled the clinical recovery of the reflexes. (orig.)

  8. The effects of peritoneal dialysis on the single dose and steady state pharmacokinetics of valproic acid in a uremic epileptic child.

    Science.gov (United States)

    Orr, J M; Farrell, K; Abbott, F S; Ferguson, S; Godolphin, W J

    1983-01-01

    The pharmacokinetics of valproic acid (VPA) have been studied during peritoneal dialysis in a uremic male epileptic child following a single 500 mg dose and after multiple doses over 5 months (700 mg daily) of valproic acid as the syrup. Serum level decline was biphasic in both instances with a terminal half-life of 27.2 after the single dose and 10.2 h at steady-state. Total serum clearance was 0.0236 l/h/kg after the single dose and increased to 0.0408 l/h/kg after 5 months. Free (intrinsic) serum clearances were 0.1489 and 0.1518 l/h/kg and serum free fractions were 0.224 and 0.272 respectively for the single dose and steady-state studies. Peritoneal dialysis for periods of 12 or 24 h removed an average of 4.5% of the VPA dose.

  9. Valproic acid induces hair regeneration in murine model and activates alkaline phosphatase activity in human dermal papilla cells.

    Directory of Open Access Journals (Sweden)

    Soung-Hoon Lee

    Full Text Available Alopecia is the common hair loss problem that can affect many people. However, current therapies for treatment of alopecia are limited by low efficacy and potentially undesirable side effects. We have identified a new function for valproic acid (VPA, a GSK3β inhibitor that activates the Wnt/β-catenin pathway, to promote hair re-growth in vitro and in vivo.Topical application of VPA to male C3H mice critically stimulated hair re-growth and induced terminally differentiated epidermal markers such as filaggrin and loricrin, and the dermal papilla marker alkaline phosphatase (ALP. VPA induced ALP in human dermal papilla cells by up-regulating the Wnt/β-catenin pathway, whereas minoxidil (MNX, a drug commonly used to treat alopecia, did not significantly affect the Wnt/β-catenin pathway. VPA analogs and other GSK3β inhibitors that activate the Wnt/β-catenin pathway such as 4-phenyl butyric acid, LiCl, and BeCl(2 also exhibited hair growth-promoting activities in vivo. Importantly, VPA, but not MNX, successfully stimulate hair growth in the wounds of C3H mice.Our findings indicate that small molecules that activate the Wnt/β-catenin pathway, such as VPA, can potentially be developed as drugs to stimulate hair re-growth.

  10. Altered attentional processing in male and female rats in a prenatal valproic acid exposure model of autism spectrum disorder.

    Science.gov (United States)

    Anshu, Kumari; Nair, Ajay Kumar; Kumaresan, U D; Kutty, Bindu M; Srinath, Shoba; Laxmi, T Rao

    2017-12-01

    Attention is foundational to efficient perception and optimal goal driven behavior. Intact attentional processing is crucial for the development of social and communication skills. Deficits in attention are therefore likely contributors to the core pathophysiology of autism spectrum disorder (ASD). Clinical evidence in ASD is suggestive of impairments in attention and its control, but the underlying mechanisms remain elusive. We examined sustained, spatially divided attention in a prenatal valproic acid (VPA) model of ASD using the 5-choice serial reaction time task (5-CSRTT). As compared to controls, male and female VPA rats had progressively lower accuracy and higher omissions with increasing attentional demands during 5-CSRTT training, and showed further performance decrements when subjected to parametric task manipulations. It is noteworthy that although VPA exposure induced attentional deficits in both sexes, there were task parameter specific sex differences. Importantly, we did not find evidence of impulsivity or motivational deficits in VPA rats but we did find reduced social preference, as well as sensorimotor deficits that suggest pre-attentional information processing impairments. Importantly, with fixed rules, graded difficulty levels, and more time, VPA rats could be successfully trained on the attentional task. To the best of our knowledge, this is the first study examining attentional functions in a VPA model. Our work underscores the need for studying both sexes in ASD animal models and validates the use of the VPA model in the quest for mechanistic understanding of aberrant attentional functions and for evaluating suitable therapeutic targets. Autism Res 2017, 10: 1929-1944. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. We studied rats prenatally exposed to valproic acid (VPA), an established rodent model of autism. Both male and female VPA rats had a range of attentional impairments with sex-specific characteristics

  11. In vitro interactions of amantadine hydrochloride, R-(-)-deprenyl hydrochloride and valproic acid sodium salt with antifungal agents against filamentous fungal species causing central nervous system infection.

    Science.gov (United States)

    Galgóczy, L; Tóth, Liliána; Virágh, M; Papp, T; Vágvölgyi, C S

    2012-12-01

    The mortality rates of fungal infections that affect the central nervous system are high in consequence of the absence of effective antifungal drugs with good penetration across the blood-brain barrier and the blood-cerebrospinal fluid barrier. In the present work in vitro antifungal activities of three good penetrating non-antifungal drugs (amantadine hydrochloride, R-(-)-deprenyl hydrochloride, valproic acid sodium salt) and their combinations with three antifungal agents (amphotericin B, itraconazole, terbinafine) were tested with broth microdilution method against eight fungal isolates belonging to Zygomycetes (Lichtheimia corymbifera, Rhizomucor miehei, Rhizopus microsporus var. rhizopodiformis, Saksenaeavasiformis) and Aspergillus genus (A. flavus, A. fumigatus, A. nidulans, A. terreus). These are known to be possible agents of central nervous fungal infections (CNFI). When used alone, the investigated nonantifungal drugs exerted slight antifungal effects. In their combinations with antifungal agents they acted antagonistically, additively and synergistically against zygomyceteous isolates. Primarily antagonistic interactions were revealed between the investigated drugs in case of Aspergilli, but additive and synergistic interactions were also observed. The additive and synergistic combinations allowed the usage of reduced concentrations of antifungal agents to inhibit the fungal growth in our study. These combinations would be a basis of an effective, less toxic therapy for treatment of CNFI.

  12. Whole-body pharmacokinetics of HDAC inhibitor drugs, butyric acid, valproic acid and 4-phenylbutyric acid measured with carbon-11 labeled analogs by PET

    International Nuclear Information System (INIS)

    Kim, Sung Won; Hooker, Jacob M.; Otto, Nicola; Win, Khaing; Muench, Lisa; Shea, Colleen; Carter, Pauline; King, Payton; Reid, Alicia E.; Volkow, Nora D.; Fowler, Joanna S.

    2013-01-01

    The fatty acids, n-butyric acid (BA), 4-phenylbutyric acid (PBA) and valproic acid (VPA, 2-propylpentanoic acid) have been used for many years in the treatment of a variety of CNS and peripheral organ diseases including cancer. New information that these drugs alter epigenetic processes through their inhibition of histone deacetylases (HDACs) has renewed interest in their biodistribution and pharmacokinetics and the relationship of these properties to their therapeutic and side effect profiles. In order to determine the pharmacokinetics and biodistribution of these drugs in primates, we synthesized their carbon-11 labeled analogues and performed dynamic positron emission tomography (PET) in six female baboons over 90 min. The carbon-11 labeled carboxylic acids were prepared by using 11 CO 2 and the appropriate Grignard reagents. [ 11 C]BA was metabolized rapidly (only 20% of the total carbon-11 in plasma was parent compound at 5 min post injection) whereas for VPA and PBA 98% and 85% of the radioactivity were the unmetabolized compound at 30 min after their administration respectively. The brain uptake of all three carboxylic acids was very low ( VPA > PBA), which is consistent with the need for very high doses for therapeutic efficacy. Most of the radioactivity was excreted through the kidneys and accumulated in the bladder. However, the organ biodistribution between the drugs differed. [ 11 C]BA showed relatively high uptake in spleen and pancreas whereas [ 11 C]PBA showed high uptake in liver and heart. Notably, [ 11 C]VPA showed exceptionally high heart uptake possibly due to its involvement in lipid metabolism. The unique biodistribution of each of these drugs may be of relevance in understanding their therapeutic and side effect profile including their teratogenic effects

  13. Long-term follow-up for efficacy and safety of treatment of retinitis pigmentosa with valproic acid.

    Science.gov (United States)

    Bhalla, Sheena; Joshi, Deval; Bhullar, Shaminder; Kasuga, Daniel; Park, Yeonhee; Kay, Christine N

    2013-07-01

    The purpose of this study was to determine the long-term efficacy and safety of valproic acid (VPA) treatment in patients with pigmentary retinal dystrophies. A retrospective chart review was conducted on 31 patients with a diagnosis of pigmentary retinal dystrophy prescribed VPA at a single centre. Visual field (VF), visual acuity (VA), length of treatment, liver enzymes and side effects were analysed. VF areas were defined using Goldmann VF (GVF) tracings recorded before, during and after VPA treatment using the V4e isopter for each eye. Using custom software, planimetric areas of VF were calculated. Five of the patients (10 eyes) had two Goldmann VF tracings, allowing comparison between baseline and follow-up VF. After 9.8 months of VPA, VF decreased by 0.145 cm(2) (26.478%) (p=0.432). For 22 of the patients (41 eyes), VA data was available, and logarithm of the minimum angle of resolution (logMAR) score changed by 0.056 log units (representing a decline in VA) after 14.9 months on VPA (p=0.002). Twelve patients (38.7%) reported negative side effects related to VPA use. VPA plays a complex role in patients with pigmentary retinal dystrophies and may be associated with VA and field decline as well as adverse side effects. Physicians should use caution with using VPA for pigmentary retinal dystrophies.

  14. Hyper-connectivity and hyper-plasticity in the medial prefrontal cortex in the valproic acid animal model of autism

    Directory of Open Access Journals (Sweden)

    Tania Rinaldi

    2008-10-01

    Full Text Available The prefrontal cortex has been extensively implicated in autism to explain deficits in executive and other higher-order functions related to cognition, language, sociability and emotion. The possible changes at the level of the neuronal microcircuit are however not known. We studied microcircuit alterations in the prefrontal cortex in the valproic acid rat model of autism and found that the layer 5 pyramidal neurons are connected to significantly more neighbouring neurons than in controls. These excitatory connections are more plastic displaying enhanced long-term potentiation of the strength of synapses. The microcircuit alterations found in the prefrontal cortex are therefore similar to the alterations previously found in the somatosensory cortex. Hyper-connectivity and hyper-plasticity in the prefrontal cortex implies hyper-functionality of one of the highest order processing regions in the brain, and stands in contrast to the hypo-functionality that is normally proposed in this region to explain some of the autistic symptoms. We propose that a number of deficits in autism such as sociability, attention, multi-tasking and repetitive behaviours, should be re-interpreted in the light of a hyper-functional prefrontal cortex.

  15. Synergistic apoptotic response between valproic acid and fludarabine in chronic lymphocytic leukaemia (CLL) cells involves the lysosomal protease cathepsin B

    International Nuclear Information System (INIS)

    Yoon, J-Y; Szwajcer, D; Ishdorj, G; Benjaminson, P; Xiao, W; Kumar, R; Johnston, J B; Gibson, S B

    2013-01-01

    Fludarabine, a nucleoside analogue, is commonly used in combination with other agents for the treatment of chronic lymphocytic leukaemia (CLL). In previous studies, valproic acid (VPA), an inhibitor of histone deacetylases, combined with fludarabine to synergistically increase apoptotic cell death in CLL cells. In the present study, we found that the combination of fludarabine and VPA decreases the level of the anti-apoptotic proteins Mcl-1 and XIAP in primary CLL cells. Treatment with fludarabine alone, or in combination with VPA, led to the loss of lysosome integrity, and chemical inhibition of the lysosomal protease cathepsin B, using CA074-Me, was sufficient to reduce apoptosis. VPA treatment increased cathepsin B levels and activities in primary CLL cells, thereby priming CLL cells for lysosome-mediated cell death. Six previously treated patients with relapsed CLL were treated with VPA, followed by VPA/fludarabine combination. The combined therapy resulted in reduced lymphocyte count in five out of six and reduced lymph node sizes in four out of six patients. In vivo VPA treatment increased histone-3 acetylation and cathepsin B expression levels. Thus, the synergistic apoptotic response with VPA and fludarabine in CLL is mediated by cathepsin B activation leading to a decrease in the anti-apoptotic proteins

  16. Synergistic combination of valproic acid and oncolytic parvovirus H-1PV as a potential therapy against cervical and pancreatic carcinomas.

    Science.gov (United States)

    Li, Junwei; Bonifati, Serena; Hristov, Georgi; Marttila, Tiina; Valmary-Degano, Séverine; Stanzel, Sven; Schnölzer, Martina; Mougin, Christiane; Aprahamian, Marc; Grekova, Svitlana P; Raykov, Zahari; Rommelaere, Jean; Marchini, Antonio

    2013-10-01

    The rat parvovirus H-1PV has oncolytic and tumour-suppressive properties potentially exploitable in cancer therapy. This possibility is being explored and results are encouraging, but it is necessary to improve the oncotoxicity of the virus. Here we show that this can be achieved by co-treating cancer cells with H-1PV and histone deacetylase inhibitors (HDACIs) such as valproic acid (VPA). We demonstrate that these agents act synergistically to kill a range of human cervical carcinoma and pancreatic carcinoma cell lines by inducing oxidative stress, DNA damage and apoptosis. Strikingly, in rat and mouse xenograft models, H-1PV/VPA co-treatment strongly inhibits tumour growth promoting complete tumour remission in all co-treated animals. At the molecular level, we found acetylation of the parvovirus nonstructural protein NS1 at residues K85 and K257 to modulate NS1-mediated transcription and cytotoxicity, both of which are enhanced by VPA treatment. These results warrant clinical evaluation of H-1PV/VPA co-treatment against cervical and pancreatic ductal carcinomas. © 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO.

  17. Behavioral alterations in autism model induced by valproic acid and translational analysis of circulating microRNA.

    Science.gov (United States)

    Hirsch, Mauro Mozael; Deckmann, Iohanna; Fontes-Dutra, Mellanie; Bauer-Negrini, Guilherme; Della-Flora Nunes, Gustavo; Nunes, Walquiria; Rabelo, Bruna; Riesgo, Rudimar; Margis, Rogerio; Bambini-Junior, Victorio; Gottfried, Carmem

    2018-05-01

    Autism spectrum disorder (ASD) is characterized by difficulties in social interaction, communication and language, and restricted repertoire of activities and interests. The etiology of ASD remains unknown and no clinical markers for diagnosis were identified. Environmental factors, including prenatal exposure to valproic acid (VPA), may contribute to increased risk of developing ASD. MicroRNA (miRNA) are small noncoding RNA that regulate gene expression and are frequently linked to biological processes affected in neurodevelopmental disorders. In this work, we analyzed the effects of resveratrol (an antioxidant and anti-inflammatory molecule) on behavioral alterations of the VPA model of autism, as well as the levels of circulating miRNA. We also evaluated the same set of miRNA in autistic patients. Rats of the VPA model of autism showed reduced total reciprocal social interaction, prevented by prenatal treatment with resveratrol (RSV). The levels of miR134-5p and miR138-5p increased in autistic patients. Interestingly, miR134-5p is also upregulated in animals of the VPA model, which is prevented by RSV. In conclusion, our findings revealed important preventive actions of RSV in the VPA model, ranging from behavior to molecular alterations. Further evaluation of preventive mechanisms of RSV can shed light in important biomarkers and etiological triggers of ASD. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. In Vivo Screening Using Transgenic Zebrafish Embryos Reveals New Effects of HDAC Inhibitors Trichostatin A and Valproic Acid on Organogenesis.

    Directory of Open Access Journals (Sweden)

    Ling Li

    Full Text Available The effects of endocrine disrupting chemicals (EDCs on reproduction are well known, whereas their developmental effects are much less characterized. However, exposure to endocrine disruptors during organogenesis may lead to deleterious and permanent problems later in life. Zebrafish (Danio rerio transgenic lines expressing the green fluorescent protein (GFP in specific organs and tissues are powerful tools to uncover developmental defects elicited by EDCs. Here, we used seven transgenic lines to visualize in vivo whether a series of EDCs and other pharmaceutical compounds can alter organogenesis in zebrafish. We used transgenic lines expressing GFP in pancreas, liver, blood vessels, inner ear, nervous system, pharyngeal tooth and pectoral fins. This screen revealed that four of the tested chemicals have detectable effects on different organs, which shows that the range of effects elicited by EDCs is wider than anticipated. The endocrine disruptor tetrabromobisphenol-A (TBBPA, as well as the three drugs diclofenac, trichostatin A (TSA and valproic acid (VPA induced abnormalities in the embryonic vascular system of zebrafish. Moreover, TSA and VPA induced specific alterations during the development of pancreas, an observation that was confirmed by in situ hybridization with specific markers. Developmental delays were also induced by TSA and VPA in the liver and in pharyngeal teeth, resulting in smaller organ size. Our results show that EDCs can induce a large range of developmental alterations during embryogenesis of zebrafish and establish GFP transgenic lines as powerful tools to screen for EDCs effects in vivo.

  19. Valproic Acid Promotes Survival of Facial Motor Neurons in Adult Rats After Facial Nerve Transection: a Pilot Study.

    Science.gov (United States)

    Zhang, Lili; Fan, Zhaomin; Han, Yuechen; Xu, Lei; Liu, Wenwen; Bai, Xiaohui; Zhou, Meijuan; Li, Jianfeng; Wang, Haibo

    2018-04-01

    Valproic acid (VPA), a medication primarily used to treat epilepsy and bipolar disorder, has been applied to the repair of central and peripheral nervous system injury. The present study investigated the effect of VPA on functional recovery, survival of facial motor neurons (FMNs), and expression of proteins in rats after facial nerve trunk transection by functional measurement, Nissl staining, TUNEL, immunofluorescence, and Western blot. Following facial nerve injury, all rats in group VPA showed a better functional recovery, which was significant at the given time, compared with group NS. The Nissl staining results demonstrated that the number of FMNs survival in group VPA was higher than that in group normal saline (NS). TUNEL staining showed that axonal injury of facial nerve could lead to neuronal apoptosis of FMNs. But treatment of VPA significantly reduced cell apoptosis by decreasing the expression of Bax protein and increased neuronal survival by upregulating the level of brain-derived neurotrophic factor (BDNF) and growth associated protein-43 (GAP-43) expression in injured FMNs compared with group NS. Overall, our findings suggest that VPA may advance functional recovery, reduce lesion-induced apoptosis, and promote neuron survival after facial nerve transection in rats. This study provides an experimental evidence for better understanding the mechanism of injury and repair of peripheral facial paralysis.

  20. Combined prenatal and postnatal butyl paraben exposure produces autism-like symptoms in offspring: comparison with valproic acid autistic model.

    Science.gov (United States)

    Ali, Elham H A; Elgoly, Amany H Mahmoud

    2013-10-01

    The aim of this work is to evaluate the impact of butyl paraben (BP) in brain of the pups developed for mothers administered BP from early pregnancy till weaning and its effect on studying the behavior, brain neurotransmitters and brain derived neurotrophic factor BDNF via comparing the results with valproic acid (VA) autistic-rat model preparing by a single oral injection dose of VA (800 mg/kg b.wt) at the 12.5 days of gestation. Butyl paraben was orally and subcutaneously administered (200 mg/kg b.wt) to pregnant rats from gestation day 1 to lactation day 21. The offspring male rats were subjected at the last 3 days of lactation to Morris water maze and three chamber sociability test then decapitated and the brain was excised and dissected to the cortex, hippocampus, cerebellum, midbrain and pons for the determination of norepinephrine, dopamine and serotonin (NE, DA and 5-HT) and cortex amino acids and whole brain BDNF. The results showed similar social and learning and memory behavioral deficits in VA rat model and the butyl paraben offspring in comparison with the controls. Also, some similar alterations were observed in monoamine content, amino acids and BDNF factor in the autistic-like model and butyl paraben offspring in comparison with the controls. The alterations were recorded notably in hippocampus and pons NE, midbrain DA, hippocampus and midbrain 5-HT, and frontal cortex GABA and asparagine. These data suggest that prenatal exposure to butyl paraben induced neuro-developmental disorders similar to some of the neurodevelopmental disorders observed in the VA model of autism. © 2013 Elsevier Inc. All rights reserved.

  1. Maternal DHA supplementation protects rat offspring against impairment of learning and memory following prenatal exposure to valproic acid.

    Science.gov (United States)

    Gao, Jingquan; Wu, Hongmei; Cao, Yonggang; Liang, Shuang; Sun, Caihong; Wang, Peng; Wang, Ji; Sun, Hongli; Wu, Lijie

    2016-09-01

    Docosahexaenoic acid (22:6n-3; DHA) is known to play a critical role in postnatal brain development. However, there have been no studies investigating the preventive effect of DHA on prenatal valproic acid (VPA)-induced behavioral and molecular alterations in offspring. The present study was to evaluate the neuroprotective effects in offspring using maternal feeding of DHA to rats exposed to VPA in pregnancy. In the present study, rats were exposed to VPA on day 12.5 of pregnancy; DHA was administered at the dosages of 100, 300 and 500 mg/kg/day for 3 weeks from day 1 to 21 of pregnancy. The results showed that maternal feeding of DHA to the prenatal exposed to VPA (1) prevented VPA-induced learning and memory impairment but did not change social-related behavior, (2) increased total DHA content in offspring plasma and hippocampus, (3) rescued VPA-induced neuronal loss and apoptosis of pyramidal cells in hippocampal CA1, (4) influenced the content of malondialdehyde and glutathione and the activities of superoxide dismutase and glutathione in the hippocampus, (5) altered levels of apoptosis-related proteins (Bcl-2, Bax and caspase-3) and inhibited the activity of caspase-3 in offspring hippocampus and (6) enhanced relative levels of p-CaMKII and p-CREB proteins in the hippocampus. These findings suggest that maternal feeding with DHA may prevent prenatal VPA-induced impairment of learning and memory, normalize several different molecules associated with oxidative stress and apoptosis in the hippocampus of offspring, and exert preventive effects on prenatal VPA-induced brain dysfunction. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Cytochrome P-450-catalyzed desaturation of valproic acid in vitro. Species differences, induction effects, and mechanistic studies

    International Nuclear Information System (INIS)

    Rettie, A.E.; Boberg, M.; Rettenmeier, A.W.; Baillie, T.A.

    1988-01-01

    The cytochrome P-450-mediated desaturation of valproic acid (VPA) to its hepatotoxic metabolite, 2-n-propyl-4-pentenoic acid (4-ene-VPA), was examined in liver microsomes from rats, mice, rabbits and humans. The highest substrate turnover was found with microsomes from rabbits (44.2 +/- 2.7 pmol of product/nmol P-450/15 min), while lower activities were observed in preparations from human, mouse, and rat liver, in that order. Pretreatment of animals with phenobarbital led to enhanced rates of formation of 4-ene-VPA in vitro and yielded induction ratios for desaturation ranging from 2.5 to 8.4, depending upon the species. Comparative studies in the rat showed that phenobarbital is a more potent inducer of olefin formation than either phenytoin or carbamazepine. The mechanism of the desaturation reaction was studied by inter- and intramolecular deuterium isotope effect experiments, which demonstrated that removal of a hydrogen atom from the subterminal C-4 position of VPA is rate limiting in the formation of both 4-ene- and 4-hydroxy-VPA. Hydroxylation at the neighboring C-5 position, on the other hand, was highly sensitive to deuterium substitution at that site, but not to deuteration at C-4. Based on these findings, it is proposed that 4-ene- and 4-hydroxy-VPA are products of a common P-450-dependent metabolic pathway, in which a carbon-centered free radical at C-4 serves as the key intermediate. 5-Hydroxy-VPA, in contrast, derives from an independent hydroxylation reaction

  3. Valproic acid reduces insulin-resistance, fat deposition and FOXO1-mediated gluconeogenesis in type-2 diabetic rat.

    Science.gov (United States)

    Khan, Sabbir; Kumar, Sandeep; Jena, Gopabandhu

    2016-06-01

    Recent evidences highlighted the role of histone deacetylases (HDACs) in insulin-resistance, gluconeogenesis and islet function. HDACs can modulate the expression of various genes, which directly or indirectly affect glucose metabolism. This study was aimed to evaluate the role of valproic acid (VPA) on fat deposition, insulin-resistance and gluconeogenesis in type-2 diabetic rat. Diabetes was developed in Sprague-Dawley rats by the combination of high-fat diet and low dose streptozotocin. VPA at the doses of 150 and 300 mg/kg/day and metformin (positive control) 150 mg/kg twice daily for 10 weeks were administered by oral gavage. Insulin-resistance, dyslipidemia and glycemia were evaluated by biochemical estimations, while fat accumulation and structural alteration were assessed by histopathology. Protein expression and insulin signaling were evaluated by western blot and immunohistochemistry. VPA treatment significantly reduced the plasma glucose, HbA1c, insulin-resistance, fat deposition in brown adipose tissue, white adipose tissue and liver, which are comparable to metformin treatment. Further, VPA inhibited the gluconeogenesis and glucagon expression as well as restored the histopathological alterations in pancreas and liver. Our findings provide new insights on the anti-diabetic role of VPA in type-2 diabetes mellitus by the modulation of insulin signaling and forkhead box protein O1 (FOXO1)-mediated gluconeogenesis. Since VPA is a well established clinical drug, the detailed molecular mechanisms of the present findings can be further investigated for possible clinical use. Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  4. Embryological exposure to valproic acid induces social interaction deficits in zebrafish (Danio rerio): A developmental behavior analysis.

    Science.gov (United States)

    Zimmermann, Fernanda Francine; Gaspary, Karina Vidarte; Leite, Carlos Eduardo; De Paula Cognato, Giana; Bonan, Carla Denise

    2015-01-01

    Changes in social behavior are associated with brain disorders, including mood disorders, stress, schizophrenia, Alzheimer's disease, and autism spectrum disorders (ASD). Autism is a complex neurodevelopmental disorder characterized by deficits in social interaction, impaired communication, anxiety, hyperactivity, and the presence of restricted interests. Zebrafish is one of the most social vertebrates used as a model in biomedical research, contributing to an understanding of the mechanisms that underlie social behavior. Valproic acid (VPA) is used as an anti-epileptic drug and mood stabilizer; however, prenatal VPA exposure in humans has been associated with an increased incidence of autism and it can also affect fetal brain development. Therefore, we conducted a behavioral screening at different periods of zebrafish development at 6, 30, 70, and 120dpf (days postfertilization) after VPA exposure in the early development stage to investigate social behavior, locomotion, aggression, and anxiety. VPA (48μM) exposure during the first 48hpf (hours postfertilization) did not promote changes on survival, morphology, and hatching rate at 24hpf, 48hpf, and 72hpf. The behavioral patterns suggest that VPA exposure induces changes in locomotor activity and anxiety at different developmental periods in zebrafish. Furthermore, a social interaction deficit is present at 70dpf and 120dpf. VPA exposure did not affect aggression in the adult stage at 70dpf and 120dpf. This is the first study that demonstrated zebrafish exposed to VPA during the first 48h of development exhibit deficits in social interaction, anxiety, and hyperactivity at different developmental periods. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Resveratrol Prevents Cellular and Behavioral Sensory Alterations in the Animal Model of Autism Induced by Valproic Acid

    Directory of Open Access Journals (Sweden)

    Mellanie Fontes-Dutra

    2018-05-01

    Full Text Available Autism spectrum disorder (ASD is characterized by impairments in both social communication and interaction and repetitive or stereotyped behaviors. Although its etiology remains unknown, genetic and environmental risk factors have been associated with this disorder, including the exposure to valproic acid (VPA during pregnancy. Resveratrol (RSV is an anti-inflammatory and antioxidant molecule known to prevent social impairments in the VPA animal model of autism. This study aimed to analyze the effects of prenatal exposure to VPA, as well as possible preventive effects of RSV, on sensory behavior, the localization of GABAergic parvalbumin (PV+ neurons in sensory brain regions and the expression of proteins of excitatory and inhibitory synapses. Pregnant rats were treated daily with RSV (3.6 mg/kg from E6.5 to E18.5 and injected with VPA (600 mg/kg in the E12.5. Male pups were analyzed in Nest Seeking (NS behavior and in whisker nuisance task (WNT. At P30, the tissues were removed and analyzed by immunofluorescence and western blotting. Our data showed for the first time an altered localization of PV+-neurons in primary sensory cortex and amygdala. We also showed a reduced level of gephyrin in the primary somatosensory area (PSSA of VPA animals. The treatment with RSV prevented all the aforementioned alterations triggered by VPA. Our data shed light on the relevance of sensory component in ASD and highlights the interplay between RSV and VPA animal model as an important tool to investigate the pathophysiology of ASD.

  6. Valproic acid attenuates skeletal muscle wasting by inhibiting C/EBPβ-regulated atrogin1 expression in cancer cachexia.

    Science.gov (United States)

    Sun, Rulin; Zhang, Santao; Hu, Wenjun; Lu, Xing; Lou, Ning; Yang, Zhende; Chen, Shaoyong; Zhang, Xiaoping; Yang, Hongmei

    2016-07-01

    Muscle wasting is the hallmark of cancer cachexia and is associated with poor quality of life and increased mortality. Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, has important biological effects in the treatment of muscular dystrophy. To verify whether VPA could ameliorate muscle wasting induced by cancer cachexia, we explored the role of VPA in two cancer cachectic mouse models [induced by colon-26 (C26) adenocarcinoma or Lewis lung carcinoma (LLC)] and atrophied C2C12 myotubes [induced by C26 cell conditioned medium (CCM) or LLC cell conditioned medium (LCM)]. Our data demonstrated that treatment with VPA increased the mass and cross-sectional area of skeletal muscles in tumor-bearing mice. Furthermore, treatment with VPA also increased the diameter of myotubes cultured in conditioned medium. The skeletal muscles in cachectic mice or atrophied myotubes treated with VPA exhibited reduced levels of CCAAT/enhancer binding protein beta (C/EBPβ), resulting in atrogin1 downregulation and the eventual alleviation of muscle wasting and myotube atrophy. Moreover, atrogin1 promoter activity in myotubes was stimulated by CCM via activating the C/EBPβ-responsive cis-element and subsequently inhibited by VPA. In contrast to the effect of VPA on the levels of C/EBPβ, the levels of inactivating forkhead box O3 (FoxO3a) were unaffected. In summary, VPA attenuated muscle wasting and myotube atrophy and reduced C/EBPβ binding to atrogin1 promoter locus in the myotubes. Our discoveries indicate that HDAC inhibition by VPA might be a promising new approach for the preservation of skeletal muscle in cancer cachexia. Copyright © 2016 the American Physiological Society.

  7. The effect of ketogenic diet in an animal model of autism induced by prenatal exposure to valproic acid.

    Science.gov (United States)

    Castro, Kamila; Baronio, Diego; Perry, Ingrid Schweigert; Riesgo, Rudimar Dos Santos; Gottfried, Carmem

    2017-07-01

    Autism spectrum disorder (ASD) is characterized by impairments in social interaction and communication, and by restricted repetitive behaviors and interests. Its etiology is still unknown, but different environmental factors during pregnancy, such as exposure to valproic acid (VPA), are associated with high incidence of ASD in children. In this context, prenatal exposure to VPA in rodents has been used as a reliable model of ASD. Ketogenic diet (KD) is an alternative therapeutic option for refractory epilepsy; however, the effects of this approach in ASD-like behavior need to be evaluated. We conducted a behavioral assessment of the effects of KD in the VPA model of autism. Pregnant animals received a single-intraperitoneal injection of 600 mg/kg VPA, and their offspring were separated into four groups: (1) control group with standard diet (C-SD), (2) control group with ketogenic diet (C-KD), (3) VPA group with standard diet (VPA-SD), and (4) VPA group with ketogenic diet (VPA-KD). When compared with the control group, VPA animals presented increased social impairment, repetitive behavior and higher nociceptive threshold. Interestingly, the VPA group fed with KD presented improvements in social behavior. These mice displayed higher scores in sociability index and social novelty index when compared with the SD-fed VPA mice. VPA mice chronically exposed to a KD presented behavioral improvements; however, the mechanism by which KD improves ASD-like features needs to be further investigated. In conclusion, the present study reinforces the potential use of KD as a treatment for the core deficits of ASD.

  8. Effect of histone deacetylase inhibitors trichostatin A and valproic acid on hair cell regeneration in zebrafish lateral line neuromasts

    Science.gov (United States)

    He, Yingzi; Cai, Chengfu; Tang, Dongmei; Sun, Shan; Li, Huawei

    2014-01-01

    In humans, auditory hair cells are not replaced when injured. Thus, cochlear hair cell loss causes progressive and permanent hearing loss. Conversely, non-mammalian vertebrates are capable of regenerating lost sensory hair cells. The zebrafish lateral line has numerous qualities that make it well-suited for studying hair cell development and regeneration. Histone deacetylase (HDAC) activity has been shown to have an important role in regenerative processes in vertebrates, but its function in hair cell regeneration in vivo is not fully understood. Here, we have examined the role of HDAC activity in hair cell regeneration in the zebrafish lateral line. We eliminated lateral line hair cells of 5-day post-fertilization larvae using neomycin and then treated the larvae with HDAC inhibitors. To assess hair cell regeneration, we used 5-bromo-2-deoxyuridine (BrdU) incorporation in zebrafish larvae to label mitotic cells after hair cell loss. We found that pharmacological inhibition of HDACs using trichostatin A (TSA) or valproic acid (VPA) increased histone acetylation in the regenerated neuromasts following neomycin-induced damage. We also showed that treatment with TSA or VPA decreased the number of supporting cells and regenerated hair cells in response to hair cell damage. Additionally, BrdU immunostaining and western blot analysis showed that TSA or VPA treatment caused a significant decrease in the percentage of S-phase cells and induced p21Cip1 and p27Kip1 expression, both of which are likely to explain the decrease in the amount of newly regenerated hair cells in treated embryos. Finally, we showed that HDAC inhibitors induced no observable cell death in neuromasts as measured by cleaved caspase-3 immunohistochemistry and western blot analysis. Taken together, our results demonstrate that HDAC activity has an important role in the regeneration of hair cells in the lateral line. PMID:25431550

  9. S-adenosyl methionine prevents ASD like behaviors triggered by early postnatal valproic acid exposure in very young mice.

    Science.gov (United States)

    Ornoy, Asher; Weinstein-Fudim, Liza; Tfilin, Matanel; Ergaz, Zivanit; Yanai, Joseph; Szyf, Moshe; Turgeman, Gadi

    2018-01-16

    A common animal model of ASD is the one induced by valproic acid (VPA), inducing epigenetic changes and oxidative stress. We studied the possible preventive effect of the methyl donor for epigenetic enzymatic reactions, S-adenosine methionine (SAM), on ASD like behavioral changes and on redox potential in the brain and liver in this model. ICR albino mice were injected on postnatal day 4 with one dose of 300 mg/kg of VPA, with normal saline (controls) or with VPA and SAM that was given orally for 3 days at the dose of 30 mg/kg body weight. From day 50, we carried out neurobehavioral tests and assessment of the antioxidant status of the prefrontal cerebral cortex, liver assessing SOD and CAT activity, lipid peroxidation and the expression of antioxidant genes. Mice injected with VPA exhibited neurobehavioral deficits typical of ASD that were more prominent in males. Changes in the activity of SOD and CAT increased lipid peroxidation and changes in the expression of antioxidant genes were observed in the prefrontal cortex of VPA treated mice, more prominent in females, while ASD like behavior was more prominent in males. There were no changes in the redox potential of the liver. The co-administration of VPA and SAM alleviated most ASD like neurobehavioral symptoms and normalized the redox potential in the prefrontal cortex. Early postnatal VPA administration induces ASD like behavior that is more severe in males, while the redox status changes are more severe in females; SAM corrects both. VPA-induced ASD seems to result from epigenetic changes, while the redox status changes may be secondary. Copyright © 2018. Published by Elsevier Inc.

  10. Valproic acid effects in the hippocampus and prefrontal cortex in an animal model of post-traumatic stress disorder.

    Science.gov (United States)

    Wilson, C Brad; McLaughlin, Leslie D; Ebenezer, Philip J; Nair, Anand R; Francis, Joseph

    2014-07-15

    Reactive oxygen species (ROS) and pro-inflammatory cytokines (PIC) are upregulated in post-traumatic stress disorder (PTSD). Histone deacetylase inhibitors (HDACi) modify genetic transcription and can diminish ROS and PIC escalation. They can also modulate levels of neurotransmitters such as catecholamines and serotonin (5-HT). Thus, this study sought to analyze the effects of the HDACi valproic acid (VA) on oxidative stress, inflammation, and neurotransmitter modulation via a predator exposure/psychosocial stress animal model of PTSD. PTSD-like effects were induced in male Sprague-Dawley rats (n=6/group×4 groups). The rats were secured in Plexiglas cylinders and placed in a cage with a cat for 1h on days 1, 11, and 40 of a 40-day stress regimen. PTSD rats were also subjected to psychosocial stress via daily cage cohort changes. At the conclusion of the stress regimen, the treatment group (PTSD+VA) and control group (Control+VA) rats were given VA in their drinking water for 30 days. The rats were then euthanized and their brains were dissected to remove the hippocampus and prefrontal cortex (PFC). Whole blood was collected to assess systemic oxidative stress. ROS and PIC mRNA and protein elevation in the PTSD group were normalized with VA. Anxiety decreased in this group via improved performance on the elevated plus-maze (EPM). No changes were attributed to VA in the control group, and no improvements were noted in the vehicle groups. Results indicate VA can attenuate oxidative stress and inflammation, enhance fear extinction, and correct neurotransmitter aberrancies in a rat model of PTSD. Copyright © 2014. Published by Elsevier B.V.

  11. Effect of histone deacetylase inhibitors trichostatin A and valproic acid on hair cell regeneration in zebrafish lateral line neuromasts

    Directory of Open Access Journals (Sweden)

    Yingzi eHe

    2014-11-01

    Full Text Available In humans, auditory hair cells are not replaced when injured. Thus, cochlear hair cell loss causes progressive and permanent hearing loss. Conversely, nonmammalian vertebrates are capable of regenerating lost sensory hair cells. The zebrafish lateral line has numerous qualities that make it well suited for studying hair cell development and regeneration. Histone deacetylase (HDAC activity has been shown to have an important role in regenerative processes in vertebrates, but its function in hair cell regeneration in vivo is not fully understood. Here, we have examined the role of HDAC activity in hair cell regeneration in the zebrafish lateral line. We eliminated lateral line hair cells of 5-day post-fertilization larvae using neomycin and then treated the larvae with HDAC inhibitors. To assess hair cell regeneration, we used 5-bromo-2-deoxyuridine (BrdU incorporation in zebrafish larvae to label mitotic cells after hair cell loss. We found that pharmacological inhibition of HDACs using trichostatin A (TSA or valproic acid (VPA increased histone acetylation in the regenerated neuromasts following neomycin-induced damage. We also showed that treatment with TSA or VPA decreased the number of supporting cells and regenerated hair cells in response to hair cell damage. Additionally, BrdU immunostaining and western blot analysis showed that TSA or VPA treatment caused a significant decrease in the percentage of S-phase cells and induced p21Cip1 and p27Kip1 expression, both of which are likely to explain the decrease in the amount of newly regenerated hair cells in treated embryos. Finally, we showed that HDAC inhibitors induced no observable cell death in neuromasts as measured by cleaved caspase-3 immunohistochemistry and western blot analysis. Taken together, our results demonstrate that HDAC activity has an important role in the regeneration of hair cells in the lateral line.

  12. Synergistic effects of fresh frozen plasma and valproic acid treatment in a combined model of traumatic brain injury and hemorrhagic shock

    DEFF Research Database (Denmark)

    Imam, Ayesha M; Jin, Guang; Duggan, Michael

    2013-01-01

    Traumatic brain injury (TBI) and hemorrhagic shock (HS) are major causes of trauma-related deaths and are especially lethal as a combined insult. Previously, we showed that early administration of fresh frozen plasma (FFP) decreased the size of the brain lesion and associated swelling in a swine...... model of combined TBI+HS. We have also shown separately that addition of valproic acid (VPA) to the resuscitation protocol attenuates inflammatory markers in the brain as well as the degree of TBI. The current study was performed to determine whether a combined FFP+VPA treatment strategy would exert...

  13. Determination of valproic acid in human plasma using dispersive liquid-liquid microextraction followed by gas chromatography-flame ionization detection

    Science.gov (United States)

    Fazeli-Bakhtiyari, Rana; Panahi-Azar, Vahid; Sorouraddin, Mohammad Hossein; Jouyban, Abolghasem

    2015-01-01

    Objective(s): Dispersive liquid-liquid microextraction coupled with gas chromatography (GC)-flame ionization detector was developed for the determination of valproic acid (VPA) in human plasma. Materials and Methods: Using a syringe, a mixture of suitable extraction solvent (40 µl chloroform) and disperser (1 ml acetone) was quickly added to 10 ml of diluted plasma sample containing VPA (pH, 1.0; concentration of NaCl, 4% (w/v)), resulting in a cloudy solution. After centrifugation (6000 rpm for 6 min), an aliquot (1 µl) of the sedimented organic phase was removed using a 1-µl GC microsyringe and injected into the GC system for analysis. One variable at a time optimization method was used to study various parameters affecting the extraction efficiency of target analyte. Then, the developed method was fully validated for its accuracy, precision, recovery, stability, and robustness. Results: Under the optimum extraction conditions, good linearity range was obtained for the calibration graph, with correlation coefficient higher than 0.998. Limit of detection and lower limit of quantitation were 3.2 and 6 μg/ml, respectively. The relative standard deviations of intra and inter-day analysis of examined compound were less than 11.5%. The relative recoveries were found in the range of 97 to 107.5%. Finally, the validated method was successfully applied to the analysis of VPA in patient sample. Conclusion: The presented method has acceptable levels of precision, accuracy and relative recovery and could be used for therapeutic drug monitoring of VPA in human plasma. PMID:26730332

  14. Evaluation of the efficacy of valproic acid and suberoylanilide hydroxamic acid (vorinostat in enhancing the effects of first-line tuberculosis drugs against intracellular Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Martin Rao

    2018-04-01

    Full Text Available Background: New tuberculosis (TB drug treatment regimens are urgently needed. This study evaluated the potential of the histone deacetylase inhibitors (HDIs valproic acid (VPA and suberoylanilide hydroxamic acid (SAHA to enhance the effects of first-line anti-TB drugs against intracellular Mycobacterium tuberculosis. Methods: M. tuberculosis H37Rv cultures were exposed to VPA or SAHA over 6 days, in the presence or absence of isoniazid (INH and rifampicin (RIF. The efficacy of VPA and SAHA against intracellular M. tuberculosis with and without INH or RIF was tested by treating infected macrophages. Bactericidal activity was assessed by counting mycobacterial colony-forming units (CFU. Results: VPA treatment exhibited superior bactericidal activity to SAHA (2-log CFU reduction, while both HDIs moderately improved the activity of RIF against extracellular M. tuberculosis. The bactericidal effect of VPA against intracellular M. tuberculosis was greater than that of SAHA (1-log CFU reduction and equalled that of INH (1.5-log CFU reduction. INH/RIF and VPA/SAHA combination treatment inhibited intracellular M. tuberculosis survival in a shorter time span than monotherapy (3 days vs. 6 days. Conclusions: VPA and SAHA have adjunctive potential to World Health Organization-recommended TB treatment regimens. Clinical evaluation of the two drugs with regard to reducing the treatment duration and improving treatment outcomes in TB is warranted. Keywords: Mycobacterium tuberculosis, Adjunct host-directed therapy, Tuberculosis, Histone deacetylase inhibitors, Repurposed drugs

  15. A Phase 2 Study of Concurrent Radiation Therapy, Temozolomide, and the Histone Deacetylase Inhibitor Valproic Acid for Patients With Glioblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Krauze, Andra V. [Radiation Oncology Branch, National Cancer Institute/National Institutes of Health, Bethesda, Maryland (United States); Myrehaug, Sten D. [Department of Radiation Oncology, Lakeridge Health Durham Regional Cancer Centre, Oshawa, Ontario (Canada); Chang, Michael G.; Holdford, Diane J. [Massey Cancer Center Virginia Commonwealth University, Richmond, Virginia (United States); Smith, Sharon; Shih, Joanna; Tofilon, Philip J. [Radiation Oncology Branch, National Cancer Institute/National Institutes of Health, Bethesda, Maryland (United States); Fine, Howard A. [New York University Langone Medical Center, New York, New York (United States); Camphausen, Kevin, E-mail: camphauk@mail.nih.gov [Radiation Oncology Branch, National Cancer Institute/National Institutes of Health, Bethesda, Maryland (United States)

    2015-08-01

    Purpose: Valproic acid (VPA) is an antiepileptic agent with histone deacetylase inhibitor (HDACi) activity shown to sensitize glioblastoma (GBM) cells to radiation in preclinical models. We evaluated the addition of VPA to standard radiation therapy (RT) plus temozolomide (TMZ) in patients with newly diagnosed GBM. Methods and Materials: Thirty-seven patients with newly diagnosed GBM were enrolled between July 2006 and April 2013. Patients received VPA, 25 mg/kg orally, divided into 2 daily doses concurrent with RT and TMZ. The first dose of VPA was given 1 week before the first day of RT at 10 to 15 mg/kg/day and subsequently increased up to 25 mg/kg/day over the week prior to radiation. VPA- and TMZ-related acute toxicities were evaluated using Common Toxicity Criteria version 3.0 (National Cancer Institute Cancer Therapy Evaluation Program) and Cancer Radiation Morbidity Scoring Scheme for toxicity and adverse event reporting (Radiation Therapy Oncology Group/European Organization for Research and Treatment). Results: A total of 81% of patients took VPA according to protocol. Median overall survival (OS) was 29.6 months (range: 21-63.8 months), and median progression-free survival (PFS) was 10.5 months (range: 6.8-51.2 months). OS at 6, 12, and 24 months was 97%, 86%, and 56%, respectively. PFS at 6, 12, and 24 months was 70%, 43%, and 38% respectively. The most common grade 3/4 toxicities of VPA in conjunction with RT/TMZ therapy were blood and bone marrow toxicity (32%), neurological toxicity (11%), and metabolic and laboratory toxicity (8%). Younger age and class V recursive partitioning analysis (RPA) results were significant for both OS and PFS. VPA levels were not correlated with grade 3 or 4 toxicity levels. Conclusions: Addition of VPA to concurrent RT/TMZ in patients with newly diagnosed GBM was well tolerated. Additionally, VPA may result in improved outcomes compared to historical data and merits further study.

  16. Valproic acid sensitizes metformin-resistant human renal cell carcinoma cells by upregulating H3 acetylation and EMT reversal.

    Science.gov (United States)

    Wei, Muyun; Mao, Shaowei; Lu, Guoliang; Li, Liang; Lan, Xiaopeng; Huang, Zhongxian; Chen, Yougen; Zhao, Miaoqing; Zhao, Yueran; Xia, Qinghua

    2018-04-17

    Metformin (Met) is a widely available diabetic drug and shows suppressed effects on renal cell carcinoma (RCC) metabolism and proliferation. Laboratory studies in RCC suggested that metformin has remarkable antitumor activities and seems to be a potential antitumor drug. But the facts that metformin may be not effective in reducing the risk of RCC in cancer clinical trials made it difficult to determine the benefits of metformin in RCC prevention and treatment. The mechanisms underlying the different conclusions between laboratory experiments and clinical analysis remains unclear. The goal of the present study was to determine whether long-term metformin use can induce resistance in RCC, whether metformin resistance could be used to explain the disaccord in laboratory and clinical studies, and whether the drug valproic acid (VPA), which inhibits histone deacetylase, exhibits synergistic cytotoxicity with metformin and can counteract the resistance of metformin in RCC. We performed CCK8, transwell, wound healing assay, flow cytometry and western blotting to detect the regulations of proliferation, migration, cell cycle and apoptosis in 786-O, ACHN and metformin resistance 786-O (786-M-R) cells treated with VPA, metformin or a combination of two drugs. We used TGF-β, SC79, LY294002, Rapamycin, protein kinase B (AKT) inhibitor to treat the 786-O or 786-M-R cells and detected the regulations in TGF-β /pSMAD3 and AMPK/AKT pathways. 786-M-R was refractory to metformin-induced antitumor effects on proliferation, migration, cell cycle and cell apoptosis. AMPK/AKT pathways and TGF-β/SMAD3 pathways showed low sensibilities in 786-M-R. The histone H3 acetylation diminished in the 786-M-R cells. However, the addition of VPA dramatically upregulated histone H3 acetylation, increased the sensibility of AKT and inhibited pSMAD3/SMAD4, letting the combination of VPA and metformin remarkably reappear the anti-tumour effects of metformin in 786-M-R cells. VPA not only exhibits

  17. Valproic acid exposure decreases Cbp/p300 protein expression and histone acetyltransferase activity in P19 cells

    Energy Technology Data Exchange (ETDEWEB)

    Lamparter, Christina L. [Department of Biomedical and Molecular Sciences, Graduate Program in Pharmacology and Toxicology, Queen' s University, Kingston, Ontario K7L 3N6 (Canada); Winn, Louise M., E-mail: winnl@queensu.ca [Department of Biomedical and Molecular Sciences, Graduate Program in Pharmacology and Toxicology, Queen' s University, Kingston, Ontario K7L 3N6 (Canada); School of Environmental Studies, Queen' s University, Kingston, Ontario K7L 3N6 (Canada)

    2016-09-01

    The teratogenicity of the antiepileptic drug valproic acid (VPA) is well established and its inhibition of histone deacetylases (HDAC) is proposed as an initiating factor. Recently, VPA-mediated HDAC inhibition was demonstrated to involve transcriptional downregulation of histone acetyltransferases (HATs), which was proposed to compensate for the increased acetylation resulting from HDAC inhibition. Cbp and p300 are HATs required for embryonic development and deficiencies in either are associated with congenital malformations and embryolethality. The objective of the present study was to characterize Cbp/p300 following VPA exposure in P19 cells. Consistent with previous studies, exposure to 5 mM VPA over 24 h induced a moderate decrease in Cbp/p300 mRNA, which preceded a strong decrease in total cellular protein mediated by ubiquitin-proteasome degradation. Nuclear Cbp/p300 protein was also decreased following VPA exposure, although to a lesser extent. Total cellular and nuclear p300 HAT activity was reduced proportionately to p300 protein levels, however while total cellular HAT activity also decreased, nuclear HAT activity was unaffected. Using the Cbp/p300 HAT inhibitor C646, we demonstrated that HAT inhibition similarly affected many of the same endpoints as VPA, including increased reactive oxygen species and caspase-3 cleavage, the latter of which could be attenuated by pre-treatment with the antioxidant catalase. C646 exposure also decreased NF-κB/p65 protein, which was not due to reduced mRNA and was not attenuated with catalase pre-treatment. This study provides support for an adaptive HAT response following VPA exposure and suggests that reduced Cbp/p300 HAT activity could contribute to VPA-mediated alterations. - Highlights: • VPA exposure in vitro downregulates Cbp/p300 mRNA and induces protein degradation. • Cbp/p300 histone acetyltransferase activity is similarly reduced with VPA exposure. • Inhibition of Cbp/p300 acetyltransferase activity

  18. Corrigendum to “Long-term valproic acid exposure increases the number of neocortical neurons in the developing rat brain" [Neurosci.Lett. 580 (2014) 12–16] A possible new animal model of autism

    DEFF Research Database (Denmark)

    Sabers, Anne; Bertelsen, Freja C B; Scheel-Krüger, Jørgen

    2015-01-01

    The aim of this study was to test the hypothesis that long-term fetal valproic acid (VPA) exposure at doses relevant to the human clinic interferes with normal brain development. Pregnant rats were given intraperitoneal injections of VPA (20 mg/kg or 100 mg/kg) continuously during the last 9–12 d...

  19. Determination of acute lethal and chronic lethal dose thresholds of valproic acid using 3D spheroids constructed from the immortal human hepatocyte cell line HepG2/C3A

    DEFF Research Database (Denmark)

    Fey, S. J.; Wrzesinski, K.

    2013-01-01

    describe here a culture system based on 3D spheroid culture of immortal hepatocytes which can determine the toxicity of valproic acid (or structurally or functionally related molecules) in vitro. The spheroids were used to follow changes in ATP production, glucose uptake and adenylate kinase following...

  20. Differential effects of valproic acid and enzyme-inducing anticonvulsants on nimodipine pharmacokinetics in epileptic patients

    Science.gov (United States)

    Tartara, A.; Galimberti, C.A.; Manni, R.; Parietti, L.; Zucca, C.; Baasch, H.; Caresia, L.; Mück, W.; Barzaghi, N.; Gatti, G.; Perucca, E.

    1991-01-01

    1 The single dose pharmacokinetics of orally administered nimodipine (60 mg) were investigated in normal subjects and in two groups of epileptic patients receiving chronic treatment with hepatic microsomal enzyme-inducing anticonvulsants (carbamazepine, phenobarbitone or phenytoin) and sodium valproate, respectively. 2 Compared with the values found in the control group, mean areas under the plasma nimodipine concentration curve were lowered by about seven-fold (P anticonvulsants and increased by about 50% (P < 0.05) in patients taking sodium valproate. 3 Nimodipine half-lives were shorter in enzyme-induced patients than in controls (3.9 ± 2.0 h vs 9.1 ± 3.4 h, means ± s.d., P < 0.01), but this difference could be artifactual since in the patients drug concentrations declined rapidly below the limit of assay, thus preventing identification of a possible slower terminal phase. In valproate-treated patients, half-lives (8.2 ± 1.8 h) were similar to those found in controls. PMID:1777370

  1. Gross hepatic changes in developing albino rats exposed to valproic acid

    International Nuclear Information System (INIS)

    Khan, M.; Khattak, S.T.; Elahi, M.

    2011-01-01

    Background: Valproid Acid (VPA) is a broad spectrum antiepileptic drug. Its use during pregnancy has been associated with congenital anomalies and hepatotoxicity. This study was designed to assess the effects of VPA on the gross structure of liver in developing albino rats exposed to the drug during various trimesters of pregnancy. Methods: In this experimental study 40 pregnant rats were divided into 4 equal groups A, B, C and D. Group A received VPA in a dose of 500 mg/Kg/day intraperitonealy (I/P) on days 3, 4 and 5 of gestation. Group B received the drug in a dose of 500 mg/Kg/day I/P on days 8, 9 and 10 of gestation. Group C received VPA in a dose of 500 mg/Kg/day I/P on days 16, 17 and 18 of gestation. Group D received no treatment and was kept as a control group. On day 21, the rats were euthanised by cervical dislocation. The liver of the foetuses were dissected out for the assessment of their gross structure. Results: Foetal liver of the experimental groups showed significant decrease in weight as well as relative tissue weight index (RTWI) as compared to the control group, although the gross appearance of the foetal liver was normal in all the groups. Conclusion: The use of VPA during various trimesters of pregnancy produces hepatotoxicity in the developing rats. So, the use of this drug during pregnancy should be carefully decided. (author)

  2. Metabolic syndrome and anticonvulsants: A comparative study of valproic acid and carbamazepine.

    Science.gov (United States)

    Rakitin, Aleksei; Kõks, Sulev; Haldre, Sulev

    2016-05-01

    The aim of this study was to compare the risk of metabolic syndrome (MS) and evaluate related factors for MS among people with epilepsy treated with valproate (VPA) or carbamazepine (CBZ). A total of 213 adult patients with epilepsy treated with VPA (n=118) or CBZ (n=95) monotherapy were included in the study. Participants were evaluated for the presence of MS, diagnosed according to the National Cholesterol Education Program Adult Treatment Panel III criteria. In the multiple logistic regression analysis, the risk of MS in CBZ- and VPA-treated patients was similar (odds ratio [OR]=0.99; 95% confidence interval [CI], 0.43-2.26; P=0.979). A lower proportion of CBZ-treated patients had abnormally low levels of high-density lipoprotein cholesterol (OR=0.10; 95% CI, 0.02-0.42; P=0.002), whereas a lower proportion of VPA-treated patients had abnormally high concentrations of fasting blood glucose (OR=0.30; 95% CI, 0.13-0.69; P=0.004). Females treated with VPA tended to have a higher risk of MS (OR=1.48; 95% CI, 0.50-4.41; P=0.485) compared to males (OR=0.74; 95% CI, 0.28-1.96; P=0.551), although this difference was not statistically significant. Although the overall risk of MS was similar in patients with epilepsy who were treated with VPA or CBZ, the distribution of MS components differed between treatment groups. Patients treated with CBZ or VPA less frequently had decreased high-density lipoprotein cholesterol levels or increased blood glucose concentrations, respectively. Females on VPA treatment could be at higher risk of MS than males. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  3. DNA Methylation Changes in Valproic Acid-Treated HeLa Cells as Assessed by Image Analysis, Immunofluorescence and Vibrational Microspectroscopy.

    Directory of Open Access Journals (Sweden)

    Giovana M B Veronezi

    Full Text Available Valproic acid (VPA, a well-known histone deacetylase inhibitor, has been reported to affect the DNA methylation status in addition to inducing histone hyperacetylation in several cell types. In HeLa cells, VPA promotes histone acetylation and chromatin remodeling. However, DNA demethylation was not checked in this cell model for standing effects longer than those provided by histone acetylation, which is a rapid and transient phenomenon. Demonstration of VPA-induced DNA demethylation in HeLa cells would contribute to understanding the effect of VPA on an aggressive tumor cell line. In the present work, DNA demethylation in VPA-treated HeLa cells was assessed by image analysis of chromatin texture, the abundance of 5-methylcytosine (5mC immunofluorescence signals and Fourier transform-infrared (FT-IR microspectroscopy centered on spectral regions related to the vibration of-CH3 groups. Image analysis indicated that increased chromatin unpacking promoted by a 4-h-treatment with 1.0 mM VPA persisted for 24 h in the absence of the drug, suggesting the occurrence of DNA demethylation that was confirmed by decreased 5mC immunofluorescence signals. FT-IR spectra of DNA samples from 1 mM or 20 mM VPA-treated cells subjected to a peak fitting analysis of the spectral window for-CH3 stretching vibrations showed decreased vibrations and energy of these groups as a function of the decreased abundance of 5mC induced by increased VPA concentrations. Only the 20 mM-VPA treatment caused an increase in the ratio of -CH3 bending vibrations evaluated at 1375 cm-1 in relation to in-plane vibrations of overall cytosines evaluated at 1492 cm-1. CH3 stretching vibrations showed to be more sensitive than-CH3 bending vibrations, as detected with FT-IR microspectroscopy, for studies aiming to associate vibrational spectroscopy and changes in DNA 5mC abundance.

  4. Data on social transmission of food preference in a model of autism induced by valproic acid and translational analysis of circulating microRNA

    Directory of Open Access Journals (Sweden)

    Mauro Mozael Hirsch

    2018-06-01

    Full Text Available This article contains data of Social Transmission of Food Preference in an animal model of autism and the evaluation of a set of microRNA analyzed in autistic patients and animal model of autism. The analyses of the absolute consumption of two flavored food by male rats prenatally exposed to valproic acid (VPA and treated with resveratrol (RSV, showed that VPA animals show a trend to eat less of the flavored food presented by a demonstrator rat. We also identified 13 microRNA with similar levels among rodents’ experimental groups, as well as 11 microRNA with no alterations between autistic and control subjects. Further evaluation of mechanisms of VPA and RSV actions on behavioral and molecular alterations can shed light in important biomarkers and etiological triggers of autistic spectrum disorders. Keywords: Autism, Social transmission of food preference, microRNA, Resveratrol, Translational research, Preclinical models, Valproate

  5. Randomized Phase II trial of paclitaxel plus valproic acid vs paclitaxel alone as second-line therapy for patients with advanced gastric cancer

    Directory of Open Access Journals (Sweden)

    Fushida S

    2015-04-01

    Full Text Available Sachio Fushida,1 Masahide Kaji,2 Katsunobu Oyama,1 Yasuo Hirono,3 Hideaki Nezuka,4 Toshiya Takeda,5 Tomoya Tsukada,1 Daisuke Fujimoto,3 Shigekazu Ohyama,6 Takashi Fujimura,7 Tetsuo Ohta1 On behalf of the Digestive Disease Support Organization (DDSO 1Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, 2Department of Surgery, Toyama Prefectural Central Hospital, Toyama, 3First Department of Surgery, Fukui University Hospital, Fukui, 4Department of Surgery, Yatsuo General Hospital, Toyama, 5Department of Surgery, Ishikawa Matto Central Hospital, Hakusan, 6Department of Surgery, Kanazawa Medical Center, Kanazawa, 7Toyama City Hospital, Toyama, Japan Abstract: The standard regimen of second-line chemotherapy for patients with unresectable gastric cancer has not been established. However, weekly paclitaxel (wPTX has become the preferable second-line chemotherapy in Japan. Histone deacetylase (HDAC inhibitors have been shown to have antiproliferative activity through cell-cycle arrest, differentiation, and apoptosis in gastric cancer cells. One HDAC inhibitor, valproic acid (VPA, also inhibits tumor growth by inducing apoptosis, and enhances the efficacy of paclitaxel in a mouse xenograft model of gastric cancer. wPTX plus VPA as a second-line chemotherapy is expected to improve survival in gastric cancer patients. A multicenter randomized Phase II study was conducted to compare the effects of wPTX plus VPA and wPTX alone. A total of 66 patients participated in this study. The primary end point of the study was overall survival, and secondary end points were progression-free survival, response rate, and assessment of peripheral neuropathy. Keywords: valproic acid, paclitaxel, second-line therapy, advanced gastric cancer 

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

    Science.gov (United States)

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

    2016-06-01

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

  7. Different effects of valproic acid on photoreceptor loss in Rd1 and Rd10 retinal degeneration mice.

    Science.gov (United States)

    Mitton, Kenneth P; Guzman, Alvaro E; Deshpande, Mrinalini; Byrd, David; DeLooff, Camryn; Mkoyan, Kristina; Zlojutro, Paul; Wallace, Adrianne; Metcalf, Brandon; Laux, Kirsten; Sotzen, Jason; Tran, Trung

    2014-01-01

    The histone-deacetylase inhibitor activity of valproic acid (VPA) was discovered after VPA's adoption as an anticonvulsant. This generated speculation for VPA's potential to increase the expression of neuroprotective genes. Clinical trials for retinitis pigmentosa (RP) are currently active, testing VPA's potential to reduce photoreceptor loss; however, we lack information regarding the effects of VPA on available mammalian models of retinal degeneration, nor do we know if retinal gene expression is perturbed by VPA in a predictable way. Thus, we examined the effects of systemic VPA on neurotrophic factor and Nrl-related gene expression in the mouse retina and compared VPA's effects on the rate of photoreceptor loss in two strains of mice, Pde6b(rd1/rd1) and Pde6b(rd10/rd10) . The expression of Bdnf, Gdnf, Cntf, and Fgf2 was measured by quantitative PCR after single and multiple doses of VPA (intraperitoneal) in wild-type and Pde6b(rd1/rd1) mice. Pde6b(rd1/rd1) mice were treated with daily doses of VPA during the period of rapid photoreceptor loss. Pde6b(rd10/rd10) mice were also treated with systemic VPA to compare in a partial loss-of-function model. Retinal morphology was assessed by virtual microscopy or spectral-domain optical coherence tomography (SD-OCT). Full-field and focal electroretinography (ERG) analysis were employed with Pde6b(rd10/rd10) mice to measure retinal function. In wild-type postnatal mice, a single VPA dose increased the expression of Bdnf and Gdnf in the neural retina after 18 h, while the expression of Cntf was reduced by 70%. Daily dosing of wild-type mice from postnatal day P17 to P28 resulted in smaller increases in Bdnf and Gdnf expression, normal Cntf expression, and reduced Fgf2 expression (25%). Nrl gene expression was decreased by 50%, while Crx gene expression was not affected. Rod-specific expression of Mef2c and Nr2e3 was decreased substantially by VPA treatment, while Rhodopsin and Pde6b gene expression was normal at P28. Daily

  8. Specific cellular signal-transduction responses to in vivo combination therapy with ATRA, valproic acid and theophylline in acute myeloid leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Skavland, J; Jørgensen, K M [Hematology Section, Institute of Medicine, University of Bergen, Bergen (Norway); Hadziavdic, K [Department of Informatics, University of Bergen, Bergen (Norway); Hovland, R [Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen (Norway); Jonassen, I [Department of Informatics, University of Bergen, Bergen (Norway); Computational Biology Unit, Bergen Centre for Computational Science, University of Bergen, Bergen (Norway); Bruserud, Ø; Gjertsen, B T, E-mail: bjorn.gjertsen@med.uib.no [Hematology Section, Institute of Medicine, University of Bergen, Bergen (Norway); Hematology Section, Department of Medicine, Haukeland University Hospital, Bergen (Norway)

    2011-02-01

    Acute myeloid leukemia (AML) frequently comprises mutations in genes that cause perturbation in intracellular signaling pathways, thereby altering normal responses to growth factors and cytokines. Such oncogenic cellular signal transduction may be therapeutic if targeted directly or through epigenetic regulation. We treated 24 selected elderly AML patients with all-trans retinoic acid for 2 days before adding theophylline and the histone deacetylase inhibitor valproic acid (ClinicalTrials.gov NCT00175812; EudraCT no. 2004-001663-22), and sampled 11 patients for peripheral blood at day 0, 2 and 7 for single-cell analysis of basal level and signal-transduction responses to relevant myeloid growth factors (granulocyte-colony-stimulating factor, granulocyte/macrophage-colony-stimulating factor, interleukin-3, Flt3L, stem cell factor, erythropoietin, CXCL-12) on 10 signaling molecules (CREB, STAT1/3/5, p38, Erk1/2, Akt, c-Cbl, ZAP70/Syk and rpS6). Pretreatment analysis by unsupervised clustering and principal component analysis divided the patients into three distinguishable signaling clusters (non-potentiated, potentiated basal and potentiated signaling). Signal-transduction pathways were modulated during therapy and patients moved between the clusters. Patients with multiple leukemic clones demonstrated distinct stimulation responses and therapy-induced modulation. Individual signaling profiles together with clinical and hematological information may be used to early identify AML patients in whom epigenetic and signal-transduction targeted therapy is beneficial.

  9. The interplay between ventro striatal BDNF levels and the effects of valproic acid on the acquisition of ethanol-induced conditioned place preference in mice.

    Science.gov (United States)

    Dos Santos, Manuel Alves; Escudeiro, Sarah Sousa; Vasconcelos, Germana Silva; Matos, Natália Castelo Branco; de Souza, Marcos Romário Matos; Patrocínio, Manoel Cláudio Azevedo; Dantas, Leonardo Pimentel; Macêdo, Danielle; Vasconcelos, Silvânia Maria Mendes

    2017-11-01

    Alcohol addiction is a chronic, relapsing and progressive brain disease with serious consequences for health. Compulsive use of alcohol is associated with the capacity to change brain structures involved with the reward pathway, such as ventral striatum. Recent evidence suggests a role of chromatin remodeling in the pathophysiology of alcohol dependence and addictive-like behaviors. In addition, neuroadaptive changes mediated by the brain-derived neurotrophic factor (BDNF) seems to be an interesting pharmacological target for alcoholism treatment. In the present study, we evaluated the effects of the deacetylase inhibitor valproic acid (VPA) (300mg/kg) on the conditioned rewarding effects of ethanol using conditioned place preference (CPP) (15% v/v; 2g/kg). Ethanol rewarding effect was investigated using a biased protocol of CPP. BDNF levels were measured in the ventral striatum. Ethanol administration induced CPP. VPA pretreatment did not reduce ethanol-CPP acquisition. VPA pretreatment increased BDNF levels when compared to ethanol induced-CPP. VPA pretreatment increased BDNF levels even in saline conditioned mice. Taken together, our results indicate a modulatory effect of VPA on the BDNF levels in the ventral striatum. Overall, this study brings initial insights into the involvement of neurotrophic mechanisms in the ventral striatum in ethanol-induced addictive-like behavior. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Valproic acid reduces hair loss and improves survival in patients receiving temozolomide-based radiation therapy for high-grade glioma.

    Science.gov (United States)

    Watanabe, Shinichi; Kuwabara, Yui; Suehiro, Satoshi; Yamashita, Daisuke; Tanaka, Mamoru; Tanaka, Akihiro; Ohue, Shiro; Araki, Hiroaki

    2017-03-01

    Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, is also used to manage seizures in glioblastoma patients. HDAC inhibitors can protect normal cells and tissues from the deleterious effects of radiotherapy, and VPA is reported to improve the survival of glioblastoma patients receiving chemoradiation therapy. VPA also promotes hair growth, and thus has the potential to reduce the radiotherapy side effect of hair loss while improving the survival of patients with glioblastoma. The purpose of this study was to determine whether VPA use during radiotherapy for high-grade glioma is associated with decreased side effects of radiotherapy and an improvement in overall survival (OS) and progression-free survival (PFS). Medical records of 112 patients with high-grade glioma were retrospectively reviewed. We grouped patients by VPA use or non-use during radiotherapy, and evaluated hair loss, OS, and PFS. The radiation dose and fractionation at the onset of hair loss were 4 Gy and two fractions higher, respectively, in the VPA group compared with the VPA non-use group (P hair loss and improvement in survival. Hair loss prevention benefits patients suffering from the deleterious effects of radiation.

  11. Resting-state fMRI revealed different brain activities responding to valproic acid and levetiracetam in benign epilepsy with central-temporal spikes

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Qirui; Zhang, Zhiqiang; Xu, Qiang; Wu, Han; Li, Zhipeng; Lu, Guangming [Nanjing University School of Medicine, Department of Medical Imaging, Jinling Hospital, Nanjing (China); Yang, Fang; Li, Qian [Nanjing University School of Medicine, Department of Neurology, Jinling Hospital, Nanjing (China); Hu, Zheng [Nanjing Children' s Hospital, Department of Neurology, Nanjing (China); Dante, Mantini [Faculty of Kinesiology and Rehabilitation Sciences, KU Leuven (Belgium); Li, Kai [Suzhou University, Laboratory of Molecular Medicine, Suzhou (China)

    2017-05-15

    Our aim was to investigate regional difference in brain activities in response to antiepileptic drug (AED) medications in benign epilepsy with central-temporal spikes (BECTS) using resting-state functional magnetic resonance imaging (fMRI). Fifty-seven patients with BECTS underwent resting-state fMRI scans after receiving either valproic acid (VPA) (n = 15), levetiracetam (LEV) (n = 21), or no medication (n = 21). fMRI regional homogeneity (ReHo) parameter among the three groups of patients were compared and were correlated with total doses of AED in the two medicated groups. Compared with patients on no-medication, patients receiving either VPA or LEV showed decreased ReHo in the central-temporal region, frontal cortex, and thalamus. In particular, the VPA group showed greater ReHo decrease in the thalamus and milder in cortices and caudate heads compared with the LEV group. In addition, the VPA group demonstrated a negative correlation between ReHo values in the central-temporal region and medication dose. Both VPA and LEV inhibit resting-state neural activity in the central-temporal region, which is the main epileptogenic focus of BECTS. VPA reduced brain activity in the cortical epileptogenic regions and thalamus evenly, whereas LEV reduced brain activity predominantly in the cortices. Interestingly, VPA showed a cumulative effect on inhibiting brain activity in the epileptogenic regions in BECTS. (orig.)

  12. Encapsulation of valproic acid and sodic phenytoin in ordered mesoporous SiO 2 solids for the treatment of temporal lobe epilepsy

    Science.gov (United States)

    López, T.; Basaldella, E. I.; Ojeda, M. L.; Manjarrez, J.; Alexander-Katz, R.

    2006-10-01

    Temporal lobe epilepsy is one of the most frequent types of human neurological diseases, and a variety of surgical procedures have been developed for the treatment of intractable cases. An alternative is the use of drug-containing reservoirs based on nanostructured materials of controlled pore sizes in order to deliver the drug without causing secondary effects. Ordered SiO 2 nanostructures were developed as drug reservoirs. The latter were prepared by the sol-gel process using tetraethyl orthosilicate TEOS as precursor to form the "sol" and P123 surfactant as the organic structure-directing agent. In addition to the nontoxic nature of amorphous silica, uniform and tunable pore sizes between 2.5 and 30 nm can be obtained in this way. The aim of this study is to investigate the potential of these materials for the storage and release of drugs in the brain. For that, we loaded valproic acid (VH) and sodic phenytoin (PH) molecules into an ordered mesoporous SiO 2 by impregnation and characterized the drug impregnated SiO 2 by standard physical and spectroscopic techniques to identify the parameters necessary to improve the capacity and quality of the reservoirs. Finally, a study of neurohistopathology of the effects of these reservoirs on brain tissue is presented.

  13. Oxytocin attenuates deficits in social interaction but not recognition memory in a prenatal valproic acid-induced mouse model of autism.

    Science.gov (United States)

    Hara, Yuta; Ago, Yukio; Higuchi, Momoko; Hasebe, Shigeru; Nakazawa, Takanobu; Hashimoto, Hitoshi; Matsuda, Toshio; Takuma, Kazuhiro

    2017-11-01

    Recent studies have reported that oxytocin ameliorates behavioral abnormalities in both animal models and individuals with autism spectrum disorders (ASD). However, the mechanisms underlying the ameliorating effects of oxytocin remain unclear. In this study, we examined the effects of intranasal oxytocin on impairments in social interaction and recognition memory in an ASD mouse model in which animals are prenatally exposed to valproic acid (VPA). We found that a single intranasal administration of oxytocin restored social interaction deficits for up to 2h in mice prenatally exposed to VPA, but there was no effect on recognition memory impairments. Additionally, administration of oxytocin across 2weeks improved prenatal VPA-induced social interaction deficits for at least 24h. In contrast, there were no effects on the time spent sniffing in control mice. Immunohistochemical analysis revealed that intranasal administration of oxytocin increased c-Fos expression in the paraventricular nuclei (PVN), prefrontal cortex, and somatosensory cortex, but not the hippocampal CA1 and CA3 regions of VPA-exposed mice, suggesting the former regions may underlie the effects of oxytocin. These findings suggest that oxytocin attenuates social interaction deficits through the activation of higher cortical areas and the PVN in an ASD mouse model. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Morphological abnormalities of embryonic cranial nerves after in utero exposure to valproic acid: implications for the pathogenesis of autism with multiple developmental anomalies.

    Science.gov (United States)

    Tashiro, Yasura; Oyabu, Akiko; Imura, Yoshio; Uchida, Atsuko; Narita, Naoko; Narita, Masaaki

    2011-06-01

    Autism is often associated with multiple developmental anomalies including asymmetric facial palsy. In order to establish the etiology of autism with facial palsy, research into developmental abnormalities of the peripheral facial nerves is necessary. In the present study, to investigate the development of peripheral cranial nerves for use in an animal model of autism, rat embryos were treated with valproic acid (VPA) in utero and their cranial nerves were visualized by immunostaining. Treatment with VPA after embryonic day 9 had a significant effect on the peripheral fibers of several cranial nerves. Following VPA treatment, immunoreactivity within the trigeminal, facial, glossopharyngeal and vagus nerves was significantly reduced. Additionally, abnormal axonal pathways were observed in the peripheral facial nerves. Thus, the morphology of several cranial nerves, including the facial nerve, can be affected by prenatal VPA exposure as early as E13. Our findings indicate that disruption of early facial nerve development is involved in the etiology of asymmetric facial palsy, and may suggest a link to the etiology of autism. Copyright © 2011 ISDN. Published by Elsevier Ltd. All rights reserved.

  15. Cell type-specific anti-cancer properties of valproic acid: independent effects on HDAC activity and Erk1/2 phosphorylation

    DEFF Research Database (Denmark)

    Gotfryd, Kamil; Skladchikova, Galina; Lepekhin, Eugene E

    2010-01-01

    lines (BT4C, BT4Cn, U87MG, N2a, PC12-E2, CSML0, CSML100, HeLa, L929, Swiss 3T3). Results: VPA induced significant histone deacetylase (HDAC) inhibition in most of the cell lines, but the degree of inhibition was highly cell type-specific. Moreover, cell growth, motility and the degree of Erk1......ABSTRACT: BACKGROUND: The anti-epileptic drug valproic acid (VPA) has attracted attention as an anti-cancer agent. Methods: The present study investigated effects of VPA exposure on histone deacetylase (HDAC) inhibition, cell growth, cell speed, and the degree of Erk1/2 phosphorylation in 10 cell....../2 phosphorylation were inhibited, activated, or unaffected by VPA in a cell type-specific manner. Importantly, no relationship was found between the effects of VPA on HDAC inhibition and changes in the degree of Erk1/2 phosphorylation, cell growth, or motility. In contrast, VPA-induced modulation of the MAPK...

  16. Resting-state fMRI revealed different brain activities responding to valproic acid and levetiracetam in benign epilepsy with central-temporal spikes

    International Nuclear Information System (INIS)

    Zhang, Qirui; Zhang, Zhiqiang; Xu, Qiang; Wu, Han; Li, Zhipeng; Lu, Guangming; Yang, Fang; Li, Qian; Hu, Zheng; Dante, Mantini; Li, Kai

    2017-01-01

    Our aim was to investigate regional difference in brain activities in response to antiepileptic drug (AED) medications in benign epilepsy with central-temporal spikes (BECTS) using resting-state functional magnetic resonance imaging (fMRI). Fifty-seven patients with BECTS underwent resting-state fMRI scans after receiving either valproic acid (VPA) (n = 15), levetiracetam (LEV) (n = 21), or no medication (n = 21). fMRI regional homogeneity (ReHo) parameter among the three groups of patients were compared and were correlated with total doses of AED in the two medicated groups. Compared with patients on no-medication, patients receiving either VPA or LEV showed decreased ReHo in the central-temporal region, frontal cortex, and thalamus. In particular, the VPA group showed greater ReHo decrease in the thalamus and milder in cortices and caudate heads compared with the LEV group. In addition, the VPA group demonstrated a negative correlation between ReHo values in the central-temporal region and medication dose. Both VPA and LEV inhibit resting-state neural activity in the central-temporal region, which is the main epileptogenic focus of BECTS. VPA reduced brain activity in the cortical epileptogenic regions and thalamus evenly, whereas LEV reduced brain activity predominantly in the cortices. Interestingly, VPA showed a cumulative effect on inhibiting brain activity in the epileptogenic regions in BECTS. (orig.)

  17. Glutathione depletion by valproic acid in sandwich-cultured rat hepatocytes: Role of biotransformation and temporal relationship with onset of toxicity

    International Nuclear Information System (INIS)

    Kiang, Tony K.L.; Teng Xiaowei; Surendradoss, Jayakumar; Karagiozov, Stoyan; Abbott, Frank S.; Chang, Thomas K.H.

    2011-01-01

    The present study was conducted in sandwich-cultured rat hepatocytes to investigate the chemical basis of glutathione (GSH) depletion by valproic acid (VPA) and evaluate the role of GSH depletion in VPA toxicity. Among the synthetic metabolites of VPA investigated, 4-ene-VPA and (E)-2,4-diene-VPA decreased cellular levels of total GSH, but only (E)-2,4-diene-VPA was more effective and more potent than the parent drug. The in situ generated, cytochrome P450-dependent 4-ene-VPA did not contribute to GSH depletion by VPA, as suggested by the experiment with a cytochrome P450 inhibitor, 1-aminobenzotriazole, to decrease the formation of this metabolite. In support of a role for metabolites, alpha-F-VPA and octanoic acid, which do not undergo biotransformation to form a 2,4-diene metabolite, CoA ester, or glucuronide, did not deplete GSH. A time course experiment showed that GSH depletion did not occur prior to the increase in 2',7'-dichlorofluorescein (a marker of oxidative stress), the decrease in [2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium] (WST-1) product formation (a marker of cell viability), or the increase in lactate dehydrogenase (LDH) release (a marker of necrosis) in VPA-treated hepatocytes. In conclusion, the cytochrome P450-mediated 4-ene-VPA pathway does not play a role in the in situ depletion of GSH by VPA, and GSH depletion is not an initiating event in VPA toxicity in sandwich-cultured rat hepatocytes.

  18. Male-specific alteration in excitatory post-synaptic development and social interaction in pre-natal valproic acid exposure model of autism spectrum disorder.

    Science.gov (United States)

    Kim, Ki Chan; Kim, Pitna; Go, Hyo Sang; Choi, Chang Soon; Park, Jin Hee; Kim, Hee Jin; Jeon, Se Jin; Dela Pena, Ike Campomayor; Han, Seol-Heui; Cheong, Jae Hoon; Ryu, Jong Hoon; Shin, Chan Young

    2013-03-01

    Autism spectrum disorder (ASD) is a pervasive developmental disorder characterized by three main behavioral symptoms including social deficits, impaired communication, and stereotyped and repetitive behaviors. ASD prevalence shows gender bias to male. Prenatal exposure to valproic acid (VPA), a drug used in epilepsy and bipolar disorder, induces autistic symptoms in both human and rodents. As we reported previously, prenatally VPA-exposed animals at E12 showed impairment in social behavior without any overt reproductive toxicity. Social interactions were not significantly different between male and female rats in control condition. However, VPA-exposed male offspring showed significantly impaired social interaction while female offspring showed only marginal deficits in social interaction. Similar male inclination was observed in hyperactivity behavior induced by VPA. In addition to the ASD-like behavioral phenotype, prenatally VPA-exposed rat offspring shows crooked tail phenotype, which was not different between male and female groups. Both male and female rat showed reduced GABAergic neuronal marker GAD and increased glutamatergic neuronal marker vGluT1 expression. Interestingly, despite of the similar increased expression of vGluT1, post-synaptic marker proteins such as PSD-95 and α-CAMKII expression was significantly elevated only in male offspring. Electron microscopy showed increased number of post-synapse in male but not in female at 4 weeks of age. These results might suggest that the altered glutamatergic neuronal differentiation leads to deranged post-synaptic maturation only in male offspring prenatally exposed to VPA. Consistent with the increased post-synaptic compartment, VPA-exposed male rats showed higher sensitivity to electric shock than VPA-exposed female rats. These results suggest that prenatally VPA-exposed rats show the male preponderance of ASD-like behaviors including defective social interaction similar to human autistic patients, which

  19. SMA CARNIVAL TRIAL PART II: a prospective, single-armed trial of L-carnitine and valproic acid in ambulatory children with spinal muscular atrophy.

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    John T Kissel

    Full Text Available BACKGROUND: Multiple lines of evidence have suggested that valproic acid (VPA might benefit patients with spinal muscular atrophy (SMA. The SMA CARNIVAL TRIAL was a two part prospective trial to evaluate oral VPA and L-carnitine in SMA children. Part 1 targeted non-ambulatory children ages 2-8 in a 12 month cross over design. We report here Part 2, a twelve month prospective, open-label trial of VPA and L-carnitine in ambulatory SMA children. METHODS: This study involved 33 genetically proven type 3 SMA subjects ages 3-17 years. Subjects underwent two baseline assessments over 4-6 weeks and then were placed on VPA and L-carnitine for 12 months. Assessments were performed at baseline, 3, 6 and 12 months. Primary outcomes included safety, adverse events and the change at 6 and 12 months in motor function assessed using the Modified Hammersmith Functional Motor Scale Extend (MHFMS-Extend, timed motor tests and fine motor modules. Secondary outcomes included changes in ulnar compound muscle action potential amplitudes (CMAP, handheld dynamometry, pulmonary function, and Pediatric Quality of Life Inventory scores. RESULTS: Twenty-eight subjects completed the study. VPA and carnitine were generally well tolerated. Although adverse events occurred in 85% of subjects, they were usually mild and transient. Weight gain of 20% above body weight occurred in 17% of subjects. There was no significant change in any primary outcome at six or 12 months. Some pulmonary function measures showed improvement at one year as expected with normal growth. CMAP significantly improved suggesting a modest biologic effect not clinically meaningful. CONCLUSIONS: This study, coupled with the CARNIVAL Part 1 study, indicate that VPA is not effective in improving strength or function in SMA children. The outcomes used in this study are feasible and reliable, and can be employed in future trials in SMA. TRIAL REGSITRATION: Clinicaltrials.gov NCT00227266.

  20. Evaluation of muscle strength and motor abilities in children with type II and III spinal muscle atrophy treated with valproic acid

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    Zanoteli Edmar

    2011-03-01

    Full Text Available Abstract Background Spinal muscular atrophy (SMA is an autosomal recessive disorder that affects the motoneurons of the spinal anterior horn, resulting in hypotonia and muscle weakness. The disease is caused by deletion or mutation in the telomeric copy of SMN gene (SMN1 and clinical severity is in part determined by the copy number of the centromeric copy of the SMN gene (SMN2. The SMN2 mRNA lacks exon 7, resulting in a production of lower amounts of the full-length SMN protein. Knowledge of the molecular mechanism of diseases has led to the discovery of drugs capable of increasing SMN protein level through activation of SMN2 gene. One of these drugs is the valproic acid (VPA, a histone deacetylase inhibitor. Methods Twenty-two patients with type II and III SMA, aged between 2 and 18 years, were treated with VPA and were evaluated five times during a one-year period using the Manual Muscle Test (Medical Research Council scale-MRC, the Hammersmith Functional Motor Scale (HFMS, and the Barthel Index. Results After 12 months of therapy, the patients did not gain muscle strength. The group of children with SMA type II presented a significant gain in HFMS scores during the treatment. This improvement was not observed in the group of type III patients. The analysis of the HFMS scores during the treatment period in the groups of patients younger and older than 6 years of age did not show any significant result. There was an improvement of the daily activities at the end of the VPA treatment period. Conclusion Treatment of SMA patients with VPA may be a potential alternative to alleviate the progression of the disease. Trial Registration ClinicalTrials.gov: NCT01033331

  1. Improvement by methylphenidate and atomoxetine of social interaction deficits and recognition memory impairment in a mouse model of valproic acid-induced autism.

    Science.gov (United States)

    Hara, Yuta; Ago, Yukio; Taruta, Atsuki; Katashiba, Keisuke; Hasebe, Shigeru; Takano, Erika; Onaka, Yusuke; Hashimoto, Hitoshi; Matsuda, Toshio; Takuma, Kazuhiro

    2016-09-01

    Rodents exposed prenatally to valproic acid (VPA) show autism-related behavioral abnormalities. We recently found that prenatal VPA exposure causes a reduction of dopaminergic activity in the prefrontal cortex of male, but not female, mice. This suggests that reduced prefrontal dopaminergic activity is associated with behavioral abnormalities in VPA-treated mice. In the present study, we examined whether the attention deficit/hyperactivity disorder drugs methylphenidate and atomoxetine (which increase dopamine release in the prefrontal cortex, but not striatum, in mice) could alleviate the behavioral abnormalities and changes in dendritic spine morphology induced by prenatal VPA exposure. We found that methylphenidate and atomoxetine increased prefrontal dopamine and noradrenaline release in VPA-treated mice. Acute treatment with methylphenidate or atomoxetine did not alleviate the social interaction deficits or recognition memory impairment in VPA-treated mice, while chronic treatment for 2 weeks did. Methylphenidate or atomoxetine for 2 weeks also improved the prenatal VPA-induced decrease in dendritic spine density in the prefrontal cortex. The effects of these drugs on behaviors and dendritic spine morphology were antagonized by concomitant treatment with the dopamine-D1 receptor antagonist SCH39166 or the dopamine-D2 receptor antagonist raclopride, but not by the α2 -adrenoceptor antagonist idazoxan. These findings suggest that chronic treatment with methylphenidate or atomoxetine improves abnormal behaviors and diminishes the reduction in spine density in VPA-treated mice via a prefrontal dopaminergic system-dependent mechanism. Autism Res 2016, 9: 926-939. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

  2. Modulation of sphingosine 1-phosphate (S1P) attenuates spatial learning and memory impairments in the valproic acid rat model of autism.

    Science.gov (United States)

    Wu, Hongmei; Zhang, Quanzhi; Gao, Jingquan; Sun, Caihong; Wang, Jia; Xia, Wei; Cao, Yonggang; Hao, Yanqiu; Wu, Lijie

    2018-03-01

    Autism spectrum disorders (ASD) are a set of pervasive neurodevelopmental disorders that manifest in early childhood, and it is growing up to be a major cause of disability in children. However, the etiology and treatment of ASD are not well understood. In our previous study, we found that serum levels of sphingosine 1-phosphate (S1P) were increased significantly in children with autism, indicating that S1P levels may be involved in ASD. The objective of this study was to identify a link between increased levels of S1P and neurobehavioral changes in autism. We utilized a valproic acid (VPA) -induced rat model of autism to evaluate the levels of S1P and the expression of sphingosine kinase (SphK), a key enzyme for S1P production, in serum and hippocampal tissue. Furthermore, we assessed cognitive functional changes and histopathological and neurochemical alterations in VPA-exposed rats after SphK blockade to explore the possible link between increased levels of S1P and neurobehavioral changes in autism. We found that SphK2 and S1P are upregulated in hippocampal tissue from VPA-exposed rats, while pharmacological inhibition of SphK reduced S1P levels, attenuated spatial learning and memory impairments, increased the expression of phosphorylated CaMKII and CREB and autophagy-related proteins, inhibited cytochrome c release, decreased the expression of apoptosis related proteins, and protected against neuronal loss in the hippocampus. We have demonstrated that an increased level of SphK2/S1P is involved in the spatial learning and memory impairments of autism, and this signaling pathway represents a novel therapeutic target and direction for future studies.

  3. Preconditioning mesenchymal stem cells with the mood stabilizers lithium and valproic acid enhances therapeutic efficacy in a mouse model of Huntington's disease.

    Science.gov (United States)

    Linares, Gabriel R; Chiu, Chi-Tso; Scheuing, Lisa; Leng, Yan; Liao, Hsiao-Mei; Maric, Dragan; Chuang, De-Maw

    2016-07-01

    Huntington's disease (HD) is a fatal neurodegenerative disorder caused by CAG repeat expansions in the huntingtin gene. Although, stem cell-based therapy has emerged as a potential treatment for neurodegenerative diseases, limitations remain, including optimizing delivery to the brain and donor cell loss after transplantation. One strategy to boost cell survival and efficacy is to precondition cells before transplantation. Because the neuroprotective actions of the mood stabilizers lithium and valproic acid (VPA) induce multiple pro-survival signaling pathways, we hypothesized that preconditioning bone marrow-derived mesenchymal stem cells (MSCs) with lithium and VPA prior to intranasal delivery to the brain would enhance their therapeutic efficacy, and thereby facilitate functional recovery in N171-82Q HD transgenic mice. MSCs were treated in the presence or absence of combined lithium and VPA, and were then delivered by brain-targeted single intranasal administration to eight-week old HD mice. Histological analysis confirmed the presence of MSCs in the brain. Open-field test revealed that ambulatory distance and mean velocity were significantly improved in HD mice that received preconditioned MSCs, compared to HD vehicle-control and HD mice transplanted with non-preconditioned MSCs. Greater benefits on motor function were observed in HD mice given preconditioned MSCs, while HD mice treated with non-preconditioned MSCs showed no functional benefits. Moreover, preconditioned MSCs reduced striatal neuronal loss and huntingtin aggregates in HD mice. Gene expression profiling of preconditioned MSCs revealed a robust increase in expression of genes involved in trophic effects, antioxidant, anti-apoptosis, cytokine/chemokine receptor, migration, mitochondrial energy metabolism, and stress response signaling pathways. Consistent with this finding, preconditioned MSCs demonstrated increased survival after transplantation into the brain compared to non-preconditioned cells

  4. Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development.

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    Eric J Hill

    Full Text Available Mood stabilising drugs such as lithium (LiCl and valproic acid (VPA are the first line agents for treating conditions such as Bipolar disorder and Epilepsy. However, these drugs have potential developmental effects that are not fully understood. This study explores the use of a simple human neurosphere-based in vitro model to characterise the pharmacological and toxicological effects of LiCl and VPA using gene expression changes linked to phenotypic alterations in cells. Treatment with VPA and LiCl resulted in the differential expression of 331 and 164 genes respectively. In the subset of VPA targeted genes, 114 were downregulated whilst 217 genes were upregulated. In the subset of LiCl targeted genes, 73 were downregulated and 91 were upregulated. Gene ontology (GO term enrichment analysis was used to highlight the most relevant GO terms associated with a given gene list following toxin exposure. In addition, in order to phenotypically anchor the gene expression data, changes in the heterogeneity of cell subtype populations and cell cycle phase were monitored using flow cytometry. Whilst LiCl exposure did not significantly alter the proportion of cells expressing markers for stem cells/undifferentiated cells (Oct4, SSEA4, neurons (Neurofilament M, astrocytes (GFAP or cell cycle phase, the drug caused a 1.4-fold increase in total cell number. In contrast, exposure to VPA resulted in significant upregulation of Oct4, SSEA, Neurofilament M and GFAP with significant decreases in both G2/M phase cells and cell number. This neurosphere model might provide the basis of a human-based cellular approach for the regulatory exploration of developmental impact of potential toxic chemicals.

  5. Effects of valproic acid and pioglitazone on cell cycle progression and proliferation of T-cell acute lymphoblastic leukemia Jurkat cells

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    Marie Saghaeian Jazi

    2016-07-01

    Full Text Available Objective(s: T-cell acute lymphoblastic leukemia (T-ALL is an aggressive hematologic malignant tumor. Administration of chemical compounds influencing apoptosis and T cell development has been discussed as promising novel therapeutic strategies. Valproic acid (VPA as a recently emerged anti-neoplastic histone deacetylase (HDAC inhibitor and pioglitazone (PGZ as a high-affinity peroxisome proliferator-activated receptor-gamma (PPARγ agonist have been shown to induce apoptosis and cell cycle arrest in different studies. Here, we aimed to investigate the underlying molecular mechanisms involved in anti-proliferative effects of these compounds on human Jurkat cells. Materials and Methods: Treated cells were evaluated for cell cycle progression and apoptosis using flowcytometry and MTT viability assay. Real-time RT-PCR was carried out to measure the alterations in key genes associated with cell death and cell cycle arrest. Results: Our findings illustrated that both VPA and PGZ can inhibit Jurkat E6.1 cells in vitro after   24 hr; however, PGZ 400 μM presents the most anti-proliferative effect. Interestingly, treated cells have been arrested in G2/M with deregulated cell division cycle 25A (Cdc25A phosphatase and cyclin-dependent kinase inhibitor 1B (CDKN1B or p27 expression. Expression of cyclin D1 gene was inhibited when DNA synthesis entry was declined. Cell cycle deregulation in PGZ and VPA-exposed cells generated an increase in the proportion of aneuploid cell population, which has not reported before. Conclusion: These findings define that anti-proliferative effects of PGZ and VPA on Jurkat cell line are mediated by cell cycle deregulation. Thus, we suggest PGZ and VPA may relieve potential therapeutic application against apoptosis-resistant malignancies.

  6. SMA CARNI-VAL trial part I: double-blind, randomized, placebo-controlled trial of L-carnitine and valproic acid in spinal muscular atrophy.

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    Kathryn J Swoboda

    2010-08-01

    Full Text Available Valproic acid (VPA has demonstrated potential as a therapeutic candidate for spinal muscular atrophy (SMA in vitro and in vivo.Two cohorts of subjects were enrolled in the SMA CARNIVAL TRIAL, a non-ambulatory group of "sitters" (cohort 1 and an ambulatory group of "walkers" (cohort 2. Here, we present results for cohort 1: a multicenter phase II randomized double-blind intention-to-treat protocol in non-ambulatory SMA subjects 2-8 years of age. Sixty-one subjects were randomized 1:1 to placebo or treatment for the first six months; all received active treatment the subsequent six months. The primary outcome was change in the modified Hammersmith Functional Motor Scale (MHFMS score following six months of treatment. Secondary outcomes included safety and adverse event data, and change in MHFMS score for twelve versus six months of active treatment, body composition, quantitative SMN mRNA levels, maximum ulnar CMAP amplitudes, myometry and PFT measures.At 6 months, there was no difference in change from the baseline MHFMS score between treatment and placebo groups (difference = 0.643, 95% CI = -1.22-2.51. Adverse events occurred in >80% of subjects and were more common in the treatment group. Excessive weight gain was the most frequent drug-related adverse event, and increased fat mass was negatively related to change in MHFMS values (p = 0.0409. Post-hoc analysis found that children ages two to three years that received 12 months treatment, when adjusted for baseline weight, had significantly improved MHFMS scores (p = 0.03 compared to those who received placebo the first six months. A linear regression analysis limited to the influence of age demonstrates young age as a significant factor in improved MHFMS scores (p = 0.007.This study demonstrated no benefit from six months treatment with VPA and L-carnitine in a young non-ambulatory cohort of subjects with SMA. Weight gain, age and treatment duration were significant confounding variables that

  7. Systemic administration of valproic acid and zonisamide promotes the survival and differentiation of induced pluripotent stem cell–derived dopaminergic neurons

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    Tatsuya eYoshikawa

    2013-02-01

    Full Text Available Cell replacement therapy using embryonic stem cells (ESCs and induced pluripotent stem cells (iPSCs is a promising strategy for the treatment of neurologic diseases such as Parkinson’s disease (PD. However, a limiting factor for effective cell transplantation is the low survival rate of grafted cells, especially neurons. In this study, we modified the host environment and investigated whether the simultaneous administration of soluble factors can improve the survival and differentiation of murine iPSC-derived dopaminergic (DA neurons in host brains. With the goal of applying this technology in clinical settings in the near future, we selected drugs that were already approved for clinical use. The drugs included two commonly used anticonvulsants, valproic acid (VPA and zonisamide (ZNS, and estradiol (E2, also known as biologically active estrogen. Following neural induction of murine iPSCs, we collected neural progenitor cells by sorting PSA-NCAM+ cells, then treated the PSA-NCAM+ cells with drugs for four days. An immunofluorescence study revealed that 0.01 mM and 0.1 mM of VPA and 10 nM of E2 increased the percentage of tyrosine hydroxylase+ (TH: a DA neuron marker cells in vitro. Furthermore, 0.1 mM of VPA increased the percentage of TH+ cells that simultaneously express the midbrain markers FOXA2 and NURR1. Next, in order to determine the effects of the drugs in vivo, the iPSC-derived NPCs were transplanted into the striata of intact SD rats. The animals received intraperitoneal injections of one of the drugs for four weeks, then were subjected to an immunofluorescence study. VPA administration (150 mg/kg/daily increased the number of NeuN+ postmitotic neurons and TH+ DA neurons in the grafts. Furthermore, VPA (150 mg/kg/daily and ZNS (30 mg/kg/daily increased the number of TH+FOXA2+ midbrain DA neurons. These results suggest that the systemic administration of VPA and ZNS may improve the efficiency of cell replacement therapy using i

  8. Effects of valproic acid and dexamethasone administration on early bio-markers and gene expression profile in acute kidney ischemia-reperfusion injury in the rat.

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    Ryan W Speir

    Full Text Available Renal ischemia-reperfusion (IR causes acute kidney injury (AKI with high mortality and morbidity. The objective of this investigation was to ameliorate kidney IR injury and identify novel biomarkers for kidney injury and repair. Under general anesthesia, left renal ischemia was induced in Wister rats by occluding renal artery for 45 minutes, followed by reperfusion and right nephrectomy. Thirty minutes prior to ischemia, rats (n = 8/group received Valproic Acid (150 mg/kg; VPA, Dexamethasone (3 mg/kg; Dex or Vehicle (saline intraperitoneally. Animals were sacrificed at 3, 24 or 120 h post-IR. Plasma creatinine (mg/dL at 24 h was reduced (P<0.05 in VPA (2.7±1.8 and Dex (2.3±1.2 compared to Vehicle (3.8±0.5 group. At 3 h, urine albumin (mg/mL was higher in Vehicle (1.47±0.10, VPA (0.84±0.62 and Dex (1.04±0.73 compared to naïve (uninjured/untreated control (0.14±0.26 group. At 24 h post-IR urine lipocalin-2 (μg/mL was higher (P<0.05 in VPA, Dex and Vehicle groups (9.61-11.36 compared to naïve group (0.67±0.29; also, kidney injury molecule-1 (KIM-1; ng/mL was higher (P<0.05 in VPA, Dex and Vehicle groups (13.7-18.7 compared to naïve group (1.7±1.9. Histopathology demonstrated reduced (P<0.05 ischemic injury in the renal cortex in VPA (Grade 1.6±1.5 compared to Vehicle (Grade 2.9±1.1. Inflammatory cytokines IL1β and IL6 were downregulated and anti-apoptotic molecule BCL2 was upregulated in VPA group. Furthermore, kidney DNA microarray demonstrated reduced injury, stress, and apoptosis related gene expression in the VPA administered rats. VPA appears to ameliorate kidney IR injury via reduced inflammatory cytokine, apoptosis/stress related gene expression, and improved regeneration. KIM-1, lipocalin-2 and albumin appear to be promising early urine biomarkers for the diagnosis of AKI.

  9. Anti-inflammatory and Anti-apoptotic Effect of Valproic Acid and Doxycycline Independent from MMP Inhibition in Early Radiation Damage

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    Ferda Hoşgörler

    2016-10-01

    Full Text Available Background: Matrix metalloproteinase (MMP inhibitors decrease inflammation in normal tissues and suppress cancer progress in normal tissues. Valproic acid (VA and doxycycline (DX are MMP inhibitors that have radio-protective effects. Their ability to inhibit MMPs in irradiated tissue is unknown and the role of MMPs in radio-protective effects has not been tested to date. Aims: The purpose of this study was to examine whether administration of VA and DX to rats before irradiation affects tissue inflammation and apoptosis in the early phase of radiation, and whether the effect of these drugs is mediated by MMP inhibition. Study Design: Animal experimentation. Methods: Twenty-six Wistar rats were randomized into four groups: control (CTRL, radiation (RT, VA plus radiation (VA+RT, and DX plus radiation (DX+RT.Three study groups were exposed to a single dose of abdominal 10 Gy gamma radiation; the CTRL group received no radiation. Single doses of VA 300 mg/kg and DX 100 mg/kg were administered to each rat before radiation and all rats were sacrificed 8 hours after irradiation, at which point small intestine tissue samples were taken for analyses. Levels of inflammatory cytokines (TNF-α, IL-1β, and IL-6 and matrix metalloproteinases (MMP-2 and MMP 9 were measured by ELISA, MMP activities were measured by gelatin and casein zymography and apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Results: VA decreased the levels of TNF-α and IL-1β proteins insignificantly and decreased apoptosis significantly in the irradiated tissue, but did not inhibit MMPs. In contrast, VA protected the basal MMP activities, which decreased in response to irradiation. No effect of DX was observed on the levels of inflammatory cytokines or activities of MMPs in the early phases of radiation apoptosis. Conclusion: Our findings indicated that VA protects against inflammation and apoptosis, and DX exhibits anti-apoptotic effects in

  10. Corrigendum to “Long-term valproic acid exposure increases the number of neocortical neurons in the developing rat brain" [Neurosci.Lett. 580 (2014) 12–16] A possible new animal model of autism

    DEFF Research Database (Denmark)

    Sabers, Anne; Bertelsen, Freja C B; Scheel-Krüger, Jørgen

    2015-01-01

    The aim of this study was to test the hypothesis that long-term fetal valproic acid (VPA) exposure at doses relevant to the human clinic interferes with normal brain development. Pregnant rats were given intraperitoneal injections of VPA (20 mg/kg or 100 mg/kg) continuously during the last 9......–12 days of pregnancy and during the lactation period until sacrifice on the 23rd postnatal day. Total number of neocortical neurons was estimated using the optical fraction at or and frontal cortical thicknesses were sampled in VPA exposed pups compared with an unexposed control group. We found that pups....... Pups exposed to 100 mg/kg, but not to 20 mg/kg VPA displayed a significant (p brain development by disturbing neocortical organization...

  11. MCB-2 concentration meter for boric acid

    International Nuclear Information System (INIS)

    Lisecki, W.

    1978-01-01

    The principles are explained of the thermal neutron absorption method for monitoring boric acid concentration in the WWER type reactor coolant. The design principles and the characteristics of four variants are described of the MSB-2 type boric acid concentration monitor developed by IBJ. (B.S.)

  12. Insuficiência aguda hepática associada ao ácido valpróico na infância: relato de três casos Acute hepatic failure with valproic acid in children: report of three cases

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    Sérgio A. Antoniuk

    1996-12-01

    Full Text Available Relatamos três casos da insuficiência aguda hepática associada ao uso de ácido valpróico (AVP em crianças epilépticas. A idade variou de 2 anos e 8 meses a 5 anos e 1 mês. Todos os pacientes apresentavam epilepsia de difícil controle e dois deles tinham desenvolvimento psicomotor severamente comprometido. O AVP foi usado em associação com outros antiepilépticos (carbamazepina em dois, fenobarbital em um. Todos os pacientes apresentaram sinais clínicos de insuficiência hepática.Vômitos, edema e icterícia foram os sinais iniciais. Febre ocorreu em dois pacientes. Os exames laboratoriais mostraram transaminases pouco aumentadas (inferiores a 194 U/l e níveis de bilirrubina entre 5,5 e 19,8 mg%. Um dos pacientes usava a droga há 12 meses e os dois outros, há menos de 6 meses. Dois pacientes apresentaram resolução do quadro hepático após a retirada da droga e um faleceu. Com este relato, salientamos a toxicidade do AVP em crianças epilépticas mesmo acima de dois anos de idade, principalmente em uso de politerapia, com comprometimento neurológico, e que o quadro pode ser reversível com a retirada da droga.We report the cases of three epileptic children who developed hepatotoxicity induced by valproic acid. Two patients had developmental delay. Including the one who died, all patients were receiving polytherapy (carbamazepine in two and phenobarbital in one. The patients age ranged from 2 years and 8 months to 5 years and 1 month. The onset of hepatic complications occurred within 6 months of valproate therapy in two patients and 12 months in one. All patients developed the classical clinical signs of hepatotoxicity. Vomiting, edema and jaundice were the initial symptoms. Fever occurred in two patients. The serum levels of glutamic oxaloacetic transaminase were mildly elevated with a maximum of 194 IU. The bilirubin levels ranged from 5.5 to 19.8 mg%. Two patients recovered clinically and showed normalization of the

  13. Differences in immunolocalization of Kim-1, RPA-1, and RPA-2 in kidneys of gentamicin-, cisplatin-, and valproic acid-treated rats: potential role of iNOS and nitrotyrosine.

    Science.gov (United States)

    Zhang, Jun; Goering, Peter L; Espandiari, Parvaneh; Shaw, Martin; Bonventre, Joseph V; Vaidya, Vishal S; Brown, Ronald P; Keenan, Joe; Kilty, Cormac G; Sadrieh, Nakissa; Hanig, Joseph P

    2009-08-01

    The present study compared the immunolocalization of Kim-1, renal papillary antigen (RPA)-1, and RPA-2 with that of inducible nitric oxide synthase (iNOS) and nitrotyrosine in kidneys of gentamicin sulfate (Gen)- and cisplatin (Cis)-treated rats. The specificity of acute kidney injury (AKI) biomarkers, iNOS, and nitrotyrosine was evaluated by dosing rats with valproic acid (VPA). Sprague-Dawley (SD) rats were injected subcutaneously (sc) with 100 mg/kg/day of Gen for six or fourteen days; a single intraperitoneal (ip) dose of 1, 3, or 6 mg/kg of Cis; or 650 mg/kg/day of VPA (ip) for four days. In Gen-treated rats, Kim-1 was expressed in the epithelial cells, mainly in the S1/S2 segments but less so in the S3 segment, and RPA-1 was increased in the epithelial cells of collecting ducts (CD) in the cortex. Spatial expression of iNOS or nitrotyrosine with Kim-1 or RPA-1 was detected. In Cis-treated rats, Kim-1 was expressed only in the S3 segment cells, and RPA-1 and RPA-2 were increased in the epithelial cells of medullary CD or medullary loop of Henle (LH), respectively. Spatial expression of iNOS or nitrotyrosine with RPA-1 or RPA-2 was also identified. These findings suggest that peroxynitrite formation may be involved in the pathogenesis of Gen and Cis nephrotoxicity and that Kim-1, RPA-1, and RPA-2 have the potential to serve as site-specific biomarkers for Gen or Cis AKI.

  14. Radiolysis of concentrated nitric acid solutions

    International Nuclear Information System (INIS)

    Nagaishi, R.; Jiang, P.Y.; Katsumura, Y.; Domae, M.; Ishigure, K.

    1995-01-01

    A study on electron pulse- and 60 Co γ-radiolysis of concentrated nitric acid and nitrate solutions has been carried out to elucidate the radiation induced reactions taking place in the solutions. Dissociation into NO 2 - and O( 3 P) was proposed as a direct action of the radiation on nitrate and gave the G-values were dependent on the chemical forms of nitrate: g s2 (-NO 3 - )=1.6 and g s2 (-HNO 3 )=2.2 (molecules/100eV). Based on the experimental yields of HNO 2 and reduced Ce IV , the primary yields of radiolysis products of water, g w , were evaluated to clarify the effects of nitrate on spur reactions of water in various nitrate solutions. (author)

  15. The pharmacokinetics of oxcarbazepine and its active metabolite 10-hydroxy-carbazepine in healthy subjects and in epileptic patients treated with phenobarbitone or valproic acid.

    Science.gov (United States)

    Tartara, A; Galimberti, C A; Manni, R; Morini, R; Limido, G; Gatti, G; Bartoli, A; Strada, G; Perucca, E

    1993-01-01

    The kinetics of oxcarbazepine (OXC) and its active metabolite 10-hydroxy-carbazepine (10-OH-CZ) after a single oral OXC dose (600 mg) were compared in healthy control subjects and in epileptic patients treated with phenobarbitone or sodium valproate (n = 8 in each group). In all groups, serum 10-OH-CZ concentrations were much higher than those of the parent drug. In patients on valproate, the kinetics of OXC and 10-OH-CZ did not differ significantly from those observed in controls. In patients on phenobarbitone, AUC values of both OXC and 10-OH-CZ were lower than in controls (2.9 +/- 0.4 vs 5.1 +/- 0.7 microg ml(-1) h and 89 +/- 7 vs 119 +/- 10 microg ml(-1) h respectively, means +/- s.e. mean, P effect is unlikely to be of great clinical significance. PMID:12959317

  16. Comparison of the efficacy of carbamazepine, haloperidol and valproic acid in the treatment of children with Sydenham´s chorea: clinical follow-up of 18 patients Comparación de la eficacia de carbamazepina, haloperidol y acido valproico en el tratamiento de niños con corea de Sydenham: seguimiento clínico de 18 pacientes

    Directory of Open Access Journals (Sweden)

    Joaquín Peña

    2002-06-01

    Full Text Available In order to compare and contrast the efficacy of haloperidol, carbamazepine, and valproic acid in the treatment of Sydenham´s chorea a prospective study including 18 cases of this disorder was undertaken. Age of patients ranged from 7 to 15 years. Ten children were female and 8 were male. All but one had generalized, either symmetric or asymmetric chorea. The patients were divided in three equal groups, and were given a standardized dose of each of the drugs built-up over a week. Following therapy, the six children receiving valproic acid showed remarkable improvement, without side effects. Five patients receiving carbamazepine showed improvement without side effects. Only three of the patients that received haloperidol improved. In the 4 cases that did not show clinical improvement after one week of treatment, therapy with valproic acid led to disappearance of the symptoms in a lapse that ranged from 4 to 7 days. Recurrence related to discontinuation of treatment was observed in two patients. In view of the present results we recommend valproic acid as the first choice drug to treat Sydenham chorea.A fin de comparar y contrastar la eficacia de haloperidol, carbamazepina y ácido valproico en el tratamiento de la corea de Sydenham, se realizó un estudio prospectivo que incluyó 18 casos de esta patología. La edad de los pacientes varió de 7 a 15 años. Diez de los niños eran varones y el resto hembras. A excepción de uno de ellos, todos tenían corea generalizada, simétrica ó asimétrica. Los pacientes fueron divididos en tres grupos iguales, a cada uno de los cuales se le administró una dosis estandarizada de los medicamentos mencionados durante una semana. Luego del tratamiento, los seis pacientes que recibieron ácido valproico mostraron mejoría notable sin efectos colaterales. Cinco de los seis pacientes que recibieron carbamazepina exhibieron mejoría sin efectos colaterales. Solo tres de los pacientes que recibieron haloperidol

  17. Serum bile acid concentrations in dairy cattle with hepatic lipidosis.

    Science.gov (United States)

    Garry, F B; Fettman, M J; Curtis, C R; Smith, J A

    1994-01-01

    This study was designed to evaluate serum bile acid measurements as indicatory, of liver function and/or hepatic fat infiltration in dairy cattle. Serum bile acid concentrations were measured in healthy dairy cattle at different stages of lactation after fasting or feeding. Bile acid concentrations were compared with liver fat content and sulfobromophthalein (BSP) half-life (T 1/2). Serum bile acid concentrations were higher in cows in early lactation and with higher daily milk production. Compared with prefasting values, bile acid concentrations were decreased at 8, 14, and 24 hours of fasting. Blood samples from fed cows at 1- to 2-hour intervals had wide and inconsistent variations in bile acid concentration. Because serum bile acids correlated well with BSP T 1/2, it is suggested that both measurements evaluate a similar aspect of liver function. Neither bile acids nor BSP T 1/2 correlated with differences in liver fat content among cows. Because of large variability in serum bile acid concentrations in fed cows and the lack of correlation of measured values with liver fat content, bile acid determinations do not appear useful for showing changes in hepatic function in fed cows with subclinical hepatic lipidosis nor serve as a screening test for this condition.

  18. High Concentrations of Tranexamic Acid Inhibit Ionotropic Glutamate Receptors.

    Science.gov (United States)

    Lecker, Irene; Wang, Dian-Shi; Kaneshwaran, Kirusanthy; Mazer, C David; Orser, Beverley A

    2017-07-01

    The antifibrinolytic drug tranexamic acid is structurally similar to the amino acid glycine and may cause seizures and myoclonus by acting as a competitive antagonist of glycine receptors. Glycine is an obligatory co-agonist of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors. Thus, it is plausible that tranexamic acid inhibits NMDA receptors by acting as a competitive antagonist at the glycine binding site. The aim of this study was to determine whether tranexamic acid inhibits NMDA receptors, as well as α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and kainate subtypes of ionotropic glutamate receptors. Tranexamic acid modulation of NMDA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, and kainate receptors was studied using whole cell voltage-clamp recordings of current from cultured mouse hippocampal neurons. Tranexamic acid rapidly and reversibly inhibited NMDA receptors (half maximal inhibitory concentration = 241 ± 45 mM, mean ± SD; 95% CI, 200 to 281; n = 5) and shifted the glycine concentration-response curve for NMDA-evoked current to the right. Tranexamic acid also inhibited α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (half maximal inhibitory concentration = 231 ± 91 mM; 95% CI, 148 to 314; n = 5 to 6) and kainate receptors (half maximal inhibitory concentration = 90 ± 24 mM; 95% CI, 68 to 112; n = 5). Tranexamic acid inhibits NMDA receptors likely by reducing the binding of the co-agonist glycine and also inhibits α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and kainate receptors. Receptor blockade occurs at high millimolar concentrations of tranexamic acid, similar to the concentrations that occur after topical application to peripheral tissues. Glutamate receptors in tissues including bone, heart, and nerves play various physiologic roles, and tranexamic acid inhibition of these receptors may contribute to adverse drug effects.

  19. ORGANIC ACIDS CONCENTRATION IN WINE STOCKS AFTER Saccharomyces cerevisiae FERMENTATION

    Directory of Open Access Journals (Sweden)

    V. N. Bayraktar

    2013-04-01

    Full Text Available The biochemical constituents in wine stocks that influence the flavor and quality of wine are investigated in the paper. The tested parameters consist of volume fraction of ethanol, residual sugar, phenolic compounds, tartaric, malic, citric, lactic, acetic acids, titratable acidity and volatile acids. The wine stocks that were received from white and red grape varieties Tairov`s selection were tested. There was a correlation between titratable acidity and volatile acids in the wine stocks from white and red grape varieties. High correlation was also found between lactic and acetic acids, between volatile acids, acetic acid and sugar. It was determined that wine stocks with a high concentration of ethanol originated from those yeast strains of Saccharomyces cerevisiae, in a fermented grape must of high speed of enzyme activity. The taste of wine stocks correlated with the ratio of tartaric to malic acid. Analysis showed significant differences between the varieties of white and red wine stocks in concentrations of organic acids, phenolic compounds, residual sugar, and volume fraction of ethanol. Positive correlation was indicated for both studied groups for volatile acids and acetic acid, tartaric, malic, lactic acids and total sugar. Prospective yeast cultures with high productivity of alcohol (ethanol were selected for winemaking biotechnology.

  20. Ion exchange separation of low boric acid concentrations from water

    International Nuclear Information System (INIS)

    Kysela, J.; Brabec, J.; Peterka, F.

    1975-01-01

    Boric acid poisoning of the moderator of the TR-O experimental heavy water reactor was studied. The possibility is discussed of removing boric acid from heavy water by means of a strong basic anion exchanger, below the residual concentration of 0.01 mg B/l. Measurements of the usable capacities of the strong basic anion exchanger Zerollit FF showed that the penetration of boric acid during the sorption period does not exceed the value of 0.015 mg B/l. The dependence was found of capacity on the boric acid concentration in the solution. Analytical methods used to determine B in water are also described. (author)

  1. Effects of acid concentration on intramolecular charge transfer ...

    Indian Academy of Sciences (India)

    rate. Time-dependent density functional theory calculations have been performed to understand the observed spectroscopic results. Keywords. Intramolecular charge transfer; absorption and fluorescence; time resolved fluorescence measurements; acid concentration dependence; time-dependent density functional theory.

  2. Relations between fatty acid synthesis, pyruvate concentration and cell concentration of suspensions of isolated rat hepatocytes

    NARCIS (Netherlands)

    Beynen, A.C.; Geelen, M.J.H.

    1984-01-01

    1. 1. The cell concentration of suspensions of isolated rat hepatocytes affects both the rate of pyruvate accumulation in the incubation medium and the rate of fatty acid synthesis. 2. 2. At low cell concentrations pyruvate accumulation is directly related to the cell concentration but levels off

  3. Control of exogenous factors affecting plasma homovanillic acid concentration.

    Science.gov (United States)

    Davidson, M; Giordani, A B; Mohs, R C; Mykytyn, V V; Platt, S; Aryan, Z S; Davis, K L

    1987-04-01

    Measurements of plasma homovanillic acid (pHVA) concentrations appear to be a valid research strategy in psychiatric disorders in which a central dopamine (DA) abnormality has been implicated. This study provides guidance about the control of some of the exogenous factors affecting pHVA concentrations. Fasting for 14 hours eliminates the dietary effects on pHVA in healthy human subjects. Changing position, walking for 30 minutes, or smoking two cigarettes has no effect on pHVA concentrations.

  4. Reactivity of the cadmium ion in concentrated phosphoric acid solutions.

    Science.gov (United States)

    De Gyves, J; Gonzales, J; Louis, C; Bessiere, J

    1989-07-01

    The solvation transfer coefficients which characterize the changes of ion reactivity with phosphoric acid concentration have been calculated for cadmium from the constants of the successive chloride complexes, and for silver and diethyldithiophosphate from potentiometric measurements. They evidence the strong desolvation of the cadmium species in concentrated phosphoric acid media, causing a remarkable increase of its reactivity. They allow the results of liquid-liquid extraction, precipitation and flotation reactions to be correctly interpreted and their changes to be foreseen when the reagents are modified.

  5. Procedure for reducing hydrogen ion concentration in acidic anion eluate

    International Nuclear Information System (INIS)

    Parobek, P.; Baloun, S.; Plevac, S.

    1992-01-01

    A procedure is suggested for reducing the concentration of hydrogen ions in the acidic anionic eluate formed during the separation of uranium. The procedure involves anex elution, precipitation, filtration, precipitate rinsing, and anex rinsing. The procedure is included in the uranium elution process and requires at least one ion exchanger column and at least one tank in the continuous or discontinuous mode. Sparing the neutralizing agent by reducing the hydrogen ion concentration in the acidic anionic eluate is a major asset of this procedure. (Z.S.). 1 fig

  6. Pretreatment on Corn Stover with Low Concentration of Formic Acid

    DEFF Research Database (Denmark)

    Xu, Jian; Thomsen, Mette Hedegaard; Thomsen, Anne Belinda

    2009-01-01

    the cellulose easily degraded into sugars and further fermented to ethanol. In this work, hydrothermal pretreatment on corn stover at 195 degrees for 15 min with and without lower concentration of formic acid was compared in terms of sugar recoveries and ethanol fermentation. For pretreatment with formic acid...... pretreatment without formic acid. Toxicity tests of liquor parts showed that there were no inhibitions found for both pretreatment conditions. After simultaneous saccharification and fermentation (SSF) of the pretreated corn stover with Baker's yeast, the highest ethanol yield of 76.5% of the theoretical...

  7. DECIDER: prospective randomized multicenter phase II trial of low-dose decitabine (DAC) administered alone or in combination with the histone deacetylase inhibitor valproic acid (VPA) and all-trans retinoic acid (ATRA) in patients >60 years with acute myeloid leukemia who are ineligible for induction chemotherapy

    International Nuclear Information System (INIS)

    Grishina, Olga; Schmoor, Claudia; Döhner, Konstanze; Hackanson, Björn; Lubrich, Beate; May, Annette M.; Cieslik, Caroline; Müller, Michael J.; Lübbert, Michael

    2015-01-01

    Acute myeloid leukemia (AML) is predominantly a disease of older patients with a poor long-term survival. Approval of decitabine (DAC) in the European Union (EU) in 2012 for the treatment of patients with AML ≥65 years marks the potential for hypomethylating agents in elderly AML. Nevertheless the situation is dissatisfactory and the quest for novel treatment approaches, including combination epigenetic therapy is actively ongoing. The given randomized trial should be helpful in investigating the question whether combinations of DAC with the histone deacetylase (HDAC) inhibitor valproic acid (VPA) and/or all-trans retinoic acid (ATRA), which in vitro show a very promising synergism, are superior to the DAC monotherapy. The accompanying translational research project will contribute to find surrogate molecular end points for drug efficacy and better tailor epigenetic therapy. An additional aim of the study is to investigate the prognostic value of geriatric assessments for elderly AML patients treated non-intensively. DECIDER is a prospective, randomized, observer blind, parallel group, multicenter, Phase II study with a 2x2 factorial design. The primary endpoint is objective best overall response (complete remission (CR) and partial remission (PR)). The target population is AML patients aged 60 years or older and unfit for standard induction chemotherapy. Patients are randomized to one of the four treatment groups: DAC alone or in combination with VPA or ATRA or with both add-on drugs. One interim safety analysis was planned and carried out with the objective to stop early one or more of the treatment arms in case of an unacceptable death rate. This analysis showed that in all treatment arms the critical stopping rule was not reached. No important safety issues were observed. The Data Monitoring Committee (DMC) recommended continuing the study as planned. The first patient was included in December 2011. A total of 189 out of 200 planned patients were randomized

  8. Acid curing and baking of bastnasite ore and concentrate

    International Nuclear Information System (INIS)

    Topkaya, Y.; Akkurt, S.

    1998-01-01

    Full text: In this study, the hydrometallurgical evaluation of a rare earth ore as well as a concentrate obtained from this was done at laboratory. For the mentioned study, a bastnasite type rare earth ore located in Beylikahir in Turkey was used. The total rare earth oxide (REO) content of the deposit was estimated to be 1 million tons with an average concentration of 3.42%REO. The rare earths were contained in bastnasite mineral. The other constituents of the ore were calcium fluoride (52.5%), barite (25.4%), calcite (2.8%) and minor amounts of thorium, iron, manganese, etc. The bastnasite mineral occurred either as cement material between fluoride and barite particles or as intimately associated with these minerals. The rare earth elements were enriched considerably in sub-sieve sizes. After extensive research about the physical concentration of this ore, two different metallurgical routes were followed for the extraction of REE from the ore itself or the preconcentrate obtained by attrition scrubbing and desliming by cyclones. In order to increase the grade of the concentrate, upgrading of the preconcentrate by multigravity was also tried. The two metallurgical routes tested were: Sulphuric acid curing and water leaching; Sulphuric acid baking and subsequent water leaching. The results of the leaching experiments were found to be quite promising. Leach recoveries up to 90% were easily obtainable. In the case of acid baking, hydrofluoric acid recover as a by-product was also possible

  9. Measurement of plasma homovanillic acid concentrations in schizophrenic patients.

    Science.gov (United States)

    Kaminski, R; Powchick, P; Warne, P A; Goldstein, M; McQueeney, R T; Davidson, M

    1990-01-01

    1. Several lines of evidence suggest that abnormalities of central dopaminergic transmission may be involved in the expression of some schizophrenic symptoms. However, elucidation of the role of dopamine (DA) in schizophrenia has eluded investigative efforts partially because no accurate and easily repeatable measure of brain DA activity exists. 2. The development of a technique to measure homovanillic acid in plasma has offered the possibility of performing serial measurements of this major DA metabolite. 3. Assuming that plasma homovanillic acid (PHVA) concentrations is an index of brain DA activity, measurement of PHVA can play a role in elucidating the DA abnormality in schizophrenia. 4. Results to date suggest that plasma homovanillic acid concentrations are lower in chronic schizophrenic patients compared to normal controls, and that PHVA values correlate with schizophrenic symptom severity. 5. In addition, PHVA levels were shown to initially rise and subsequently decline during chronic neuroleptic administration in treatment responsive but not in treatment refractory schizophrenic patients.

  10. Fully Automated Concentration Control of the Acidic Texturisation Process

    OpenAIRE

    Dannenberg, T.; Zimmer, M.; Rentsch, J.

    2012-01-01

    To enable a concentration control in the acidic texturing process we have closed the feedback loop from analytical data to the dosing mechanism of the used process tool. In order to analyze the process bath we used near-infrared spectroscopy in an online setup as well as ion chromatography as an inline method in a second approach. Using the developed dosing algorithm allows a concentration optimization of HF and HNO3 in dependence of the Si concentrations. This allows a further optimization o...

  11. Effect of Hydrochloric Acid Concentration on the Conversion of Sugarcane Bagasse to Levulinic Acid

    Science.gov (United States)

    Anggorowati, Heni; Jamilatun, Siti; Cahyono, Rochim B.; Budiman, Arief

    2018-01-01

    Levulinic acid is a new green platform chemical used to the synthesis of a variety of materials for numerous applications such as fuel additives, polymers and resins. It can be produced using renewable resources such as biomass like sugarcane bagasse which are cheap and widely available as waste in Indonesia. In this study, sugarcane bagasse was hydrolyzed using hydrochloric acid with a solid liquid ratio 1:10. The effects of hydrochloric acid concentration at temperature of 180 °C and reaction time of 30 min were studied. The presence of levulinic acid in product of hydrolysis was measured with gas chromatography (GC). It was found that the highest concentration of levulinic acid was obtained at 1 M hydrochloric acid in 25.56 yield%.

  12. The nitric acid decomposition of calcined danburite concentrate of Ak-Arkhar Deposit

    International Nuclear Information System (INIS)

    Kurbonov, A.S.; Mamatov, E.D.; Suleymani, M.; Borudzherdi, A.; Mirsaidov, U.M.

    2011-01-01

    Present article is devoted to nitric acid decomposition of calcined danburite concentrate of Ak-Arkhar Deposit of Tajikistan. The obtaining of boric acid from pre backed danburite concentrate by decomposition of nitric acid was studied. The chemical composition of danburite concentrate was determined. The laboratory study of danburite leaching by nitric acid was conducted. The influence of temperature, process duration, nitric acid concentration on nitric acid decomposition of calcined danburite concentrate of Ak-Arkhar Deposit was studied as well. The optimal conditions of nitric acid decomposition of calcined danburite concentrate of Ak-Arkhar Deposit, including temperature, process duration, nitric acid concentration and particle size were proposed.

  13. Hydrochloric acid leach of Agnew Lake uranium concentrate

    International Nuclear Information System (INIS)

    Haque, K.E.; Ipekoglue, B.

    1981-10-01

    Hydrochloric acid leaching was conducted on the radioactive mineral concentrate separated from the Agenw Lake uranium ore. Leach tests conducted at the optimum conditions (75 0 C; 36 hours; 66.0 Kg HCl/tonne; solid:liquid -1:1) resulted in the extraction of 87% uranium and 84% radium. The radionuclide level of the residue was U-0.016%, Th-0.24% and Ra-65 pCi/g solids. However to obtain a residue almost free of radium (i.e., Ra level at the detection limit: 4-6 pCi/g solids), the first stage leach residue was further treated with hydrochloric acid. The radium level in the best second stage leach residue was also above the target level. Therefore, multistage (3 or 4) hydrochloric acid and/or neutral chloride leaching is recommended to obtain tailings almost free of radionuclide

  14. Highly Concentrated Acetic Acid Poisoning: 400 Cases Reviewed

    Directory of Open Access Journals (Sweden)

    Konstantin Brusin

    2012-12-01

    Full Text Available Background: Caustic substance ingestion is known for causing a wide array of gastrointestinal and systemic complications. In Russia, ingestion of acetic acid is a major problem which annually affects 11.2 per 100,000 individuals. The objective of this study was to report and analyze main complications and outcomes of patients with 70% concentrated acetic acid poisoning. Methods: This was a retrospective study of patients with acetic acid ingestion who were treated at Sverdlovsk Regional Poisoning Treatment Center during 2006 to 2012. GI mucosal injury of each patient was assessed with endoscopy according to Zargar’s scale. Data analysis was performed to analyze the predictors of stricture formation and mortality. Results: A total of 400 patients with median age of 47 yr were included. GI injury grade I was found in 66 cases (16.5%, IIa in 117 (29.3%, IIb in 120 (30%, IIIa in 27 (16.7% and IIIb in 70 (17.5%. 11% of patients developed strictures and overall mortality rate was 21%. Main complications were hemolysis (55%, renal injury (35%, pneumonia (27% and bleeding during the first 3 days (27%. Predictors of mortality were age 60 to 79 years, grade IIIa and IIIb of GI injury, pneumonia, stages “I”, “F” and “L” of kidney damage according to the RIFLE scale and administration of prednisolone. Predictors of stricture formation were ingestion of over 100 mL of acetic acid and grade IIb and IIIa of GI injury. Conclusion: Highly concentrated acetic acid is still frequently ingested in Russia with a high mortality rate. Patients with higher grades of GI injury, pneumonia, renal injury and higher amount of acid ingested should be more carefully monitored as they are more susceptible to develop fatal consequences.          

  15. Airborne Precursors Predict Maternal Serum Perfluoroalkyl Acid Concentrations.

    Science.gov (United States)

    Makey, Colleen M; Webster, Thomas F; Martin, Jonathan W; Shoeib, Mahiba; Harner, Tom; Dix-Cooper, Linda; Webster, Glenys M

    2017-07-05

    Human exposure to persistent perfluoroalkyl acids (PFAAs), including perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorooctanesulfonate (PFOS), can occur directly from contaminated food, water, air, and dust. However, precursors to PFAAs (PreFAAs), such as dipolyfluoroalkyl phosphates (diPAPs), fluorotelomer alcohols (FTOHs), perfluorooctyl sulfonamides (FOSAs), and sulfonamidoethanols (FOSEs), which can be biotransformed to PFAAs, may also be a source of exposure. PFAAs were analyzed in 50 maternal sera samples collected in 2007-2008 from participants in Vancouver, Canada, while PFAAs and PreFAAs were measured in matching samples of residential bedroom air collected by passive sampler and in sieved vacuum dust (<150 μm). Concentrations of PreFAAs were higher than for PFAAs in air and dust. Positive associations were discovered between airborne 10:2 FTOH and serum PFOA and PFNA and between airborne MeFOSE and serum PFOS. On average, serum PFOS concentrations were 2.3 ng/mL (95%CI: 0.40, 4.3) higher in participants with airborne MeFOSE concentrations in the highest tertile relative to the lowest tertile. Among all PFAAs, only PFNA in air and vacuum dust predicted serum PFNA. Results suggest that airborne PFAA precursors were a source of PFOA, PFNA, and PFOS exposure in this population.

  16. Association between Serum Unmetabolized Folic Acid Concentrations and Folic Acid from Fortified Foods.

    Science.gov (United States)

    Palchetti, Cecília Zanin; Paniz, Clóvis; de Carli, Eduardo; Marchioni, Dirce M; Colli, Célia; Steluti, Josiane; Pfeiffer, Christine M; Fazili, Zia; Guerra-Shinohara, Elvira Maria

    2017-01-01

    To investigate the association between serum unmetabolized folic acid (UMFA) concentrations and folic acid from fortified foods and nutrients known as dietary methyl-group donors (folate, methionine, choline, betaine and vitamins B2, B6 and B12) in participants exposed to mandatory fortification of wheat and maize flours with folic acid. Cross-sectional study carried out with 144 healthy Brazilian participants, both sexes, supplement nonusers. Serum folate, UMFA, vitamin B12 and total plasma homocysteine (tHcy) were biochemically measured. Dietary intake was assessed by 2 non-consecutive 24-hour dietary recalls (24-HRs) and deattenuated energy-adjusted nutrient data were used for statistical analysis. Ninety eight (68.1%) participants were women. Median (interquartile range) age was 35.5 (28.0-52.0) years. Elevated serum folate concentrations (>45 nmol/L) were found in 17 (11.8%), while folate deficiency ( 1 nmol/L (90th percentile). UMFA concentrations were positively correlated with folic acid intake and negatively correlated to choline, methionine and vitamin B6 intakes. Participants in the lowest quartile of UMFA concentrations had lower dietary intake of total folate (DFEs) and folic acid, and higher dietary intake of methionine, choline and vitamin B6 than participants in the highest quartile of UMFA. Folic acid intake (OR [95% CI] = 1.02 [1.01-1.04)] and being a male (OR [95% CI] = 0.40 [0.19-0.87) were associated with increased and reduced odds for UMFA concentrations > 0.55 nmol/L (median values), respectively. UMFA concentrations were directly influenced by folic acid intake from fortified foods in a healthy convenience sample of adult Brazilians exposed to mandatory flour fortification with folic acid.

  17. Use of extractive distillation to produce concentrated nitric acid

    International Nuclear Information System (INIS)

    Campbell, P.C.; Griffin, T.P.; Irwin, C.F.

    1981-04-01

    Concentrated nitric acid (> 95 wt %) is needed for the treatment of off-gases from a fuels-reprocessing plant. The production of concentrated nitric acid by means of extractive distillation in the two-pot apparatus was studied to determine the steady-state behavior of the system. Four parameters, EDP volume (V/sub EDP/) and temperature (T/sub EDP/), acid feed rate, and solvent recycle, were independently varied. The major response factors were percent recovery (CPRR) and product purity (CCP). Stage efficiencies also provided information about the system response. Correlations developed for the response parameters are: CPRR = 0.02(V/sub EDP/ - 800 cc) + 53.5; CCP = -0.87 (T/sub EDP/ - 140 0 C) + 81; eta/sub V,EDP/ = 9.1(F/sub feed/ - 11.5 cc/min) - 0.047(V/sub EDP/ - 800 cc) - 2.8(F/sub Mg(NO 3 ) 2 / - 50 cc/min) + 390; and eta/sub L,EDP/ = 1.9(T/sub EDP/ - 140 0 C) + 79. A computer simulation of the process capable of predicting steady-state conditions was developed, but it requires further work

  18. Dietary Sodium Modifies Serum Uric Acid Concentrations in Humans.

    Science.gov (United States)

    Todd, Alwyn S; Walker, Robert J; MacGinley, Robert J; Kelly, Jaimon; Merriman, Tony R; Major, Tanya J; Johnson, Richard J

    2017-11-06

    Subjects with hypertension are frequently obese or insulin resistant, both conditions in which hyperuricemia is common. Obese and insulin-resistant subjects are also known to have blood pressure that is more sensitive to changes in dietary sodium intake. Whether hyperuricemia is a resulting consequence, moderating or contributing factor to the development of hypertension has not been fully evaluated and very few studies have reported interactions between sodium intake and serum uric acid. We performed further analysis of our randomized controlled clinical trials (Australian New Zealand Clinical Trials Registry #12609000161224 and #12609000292279) designed to assess the effects of modifying sodium intake on concentrations of serum markers, including uric acid. Uric acid and other variables (including blood pressure, renin, and aldosterone) were measured at baseline and 4 weeks following the commencement of low (60 mmol/day), moderate (150 mmol/day), and high (200-250 mmol/day) dietary sodium intake. The median aldosterone-to-renin ratio was 1.90 [pg/ml]/[pg/ml] (range 0.10-11.04). Serum uric acid fell significantly in both the moderate and high interventions compared to the low sodium intervention. This pattern of response occurred when all subjects were analyzed, and when normotensive or hypertensive subjects were analyzed alone. Although previously reported in hypertensive subjects, these data provide evidence in normotensive subjects of an interaction between dietary sodium intake and serum uric acid. As this interaction is present in the absence of hypertension, it is possible it could play a role in hypertension development, and will need to be considered in future trials of dietary sodium intake. The trials were registered with the Australian and New Zealand Clinical Trials Registry as ACTRN12609000161224 and ACTRN1260. © American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  19. Fasting plasma chenodeoxycholic acid and cholic acid concentrations are inversely correlated with insulin sensitivity in adults

    Directory of Open Access Journals (Sweden)

    Laville Martine

    2011-07-01

    Full Text Available Abstract Background Accumulating data suggest a novel role for bile acids (BAs in modulating metabolic homeostasis. BA treatment has been shown to improve glucose tolerance and to increase energy expenditure in mice. Here, we investigated the relationship between fasting plasma BAs concentrations and metabolic parameters in humans. Findings Fasting plasma glucose, insulin and lipid profile were measured in 14 healthy volunteers, 20 patients with type 2 diabetes (T2D, and 22 non-diabetic abdominally obese subjects. Insulin sensitivity was also assessed by the determination of the glucose infusion rate (GIR during a hyperinsulinemic-euglycemic clamp in a subgroup of patients (9 healthy and 16 T2D subjects. Energy expenditure was measured by indirect calorimetry. Plasma cholic acid (CA, chenodeoxycholic acid (CDCA and deoxycholic acid (DCA concentrations were analyzed by gas chromatograph-mass spectrometry. In univariable analysis, a positive association was found between HOMA-IR and plasma CDCA (β = 0.09, p = 0.001, CA (β = 0.03, p = 0.09 and DCA concentrations (β = 0.07, p Conclusions Both plasma CDCA, CA and DCA concentrations were negatively associated with insulin sensitivity in a wide range of subjects.

  20. Inhibition of fatty acid mobilization by arterial free fatty acid concentration

    DEFF Research Database (Denmark)

    Madsen, J; Bülow, J; Nielsen, N E

    1986-01-01

    Subcutaneous, inguinal adipose tissue from dogs was perfused with blood in which the free fatty acid (FFA) concentration was varied corresponding to FFA/albumin molar ratios between 1 and 6. Otherwise the composition of the perfusate was kept constant. In order to stimulate lipolysis, isoprenaline...

  1. Polyaspartic Acid Concentration Controls the Rate of Calcium Phosphate Nanorod Formation in High Concentration Systems

    Energy Technology Data Exchange (ETDEWEB)

    Krogstad, Daniel V. [Biosystems and; Wang, Dongbo [Biosystems and; Lin-Gibson, Sheng [Biosystems and

    2017-08-31

    Polyelectrolytes are known to greatly affect calcium phosphate (CaP) mineralization. The reaction kinetics as well as the CaP phase, morphology and aggregation state depend on the relative concentrations of the polyelectrolyte and the inorganic ions in a complex, nonlinear manner. This study examines the structural evolution and kinetics of polyaspartic acid (pAsp) directed CaP mineralization at high concentrations of polyelectrolytes, calcium, and total phosphate (19–30 mg/mL pAsp, 50–100 mM Ca2+, Ca/P = 2). Using a novel combination of characterization techniques including cryogenic transmission electron microscopy (cryo-TEM), spectrophotometry, X-ray total scattering pair distribution function analysis, and attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), it was determined that the CaP mineralization occurred over four transition steps. The steps include the formation of aggregates of pAsp stabilized CaP spherical nanoparticles (sNP), crystallization of sNP, oriented attachment of the sNP into nanorods, and further crystallization of the nanorods. The intermediate aggregate sizes and the reaction kinetics were found to be highly polymer concentration dependent while the sizes of the particles were not concentration dependent. This study demonstrates the complex role of pAsp in controlling the mechanism as well as the kinetics of CaP mineralization.

  2. 21 CFR 146.148 - Reduced acid frozen concentrated orange juice.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Reduced acid frozen concentrated orange juice. 146... Canned Fruit Juices and Beverages § 146.148 Reduced acid frozen concentrated orange juice. (a) Reduced acid frozen concentrated orange juice is the food that complies with the requirements for composition...

  3. Amino Acid Composition of an Organic Brown Rice Protein Concentrate and Isolate Compared to Soy and Whey Concentrates and Isolates

    Directory of Open Access Journals (Sweden)

    Douglas S. Kalman

    2014-06-01

    Full Text Available A protein concentrate (Oryzatein-80™ and a protein isolate (Oryzatein-90™ from organic whole-grain brown rice were analyzed for their amino acid composition. Two samples from different batches of Oryzatein-90™ and one sample of Oryzatein-80™ were provided by Axiom Foods (Los Angeles, CA, USA. Preparation and analysis was carried out by Covance Laboratories (Madison, WI, USA. After hydrolysis in 6-N hydrochloric acid for 24 h at approximately 110 °C and further chemical stabilization, samples were analyzed by HPLC after pre-injection derivitization. Total amino acid content of both the isolate and the concentrate was approximately 78% by weight with 36% essential amino acids and 18% branched-chain amino acids. These results are similar to the profiles of raw and cooked brown rice except in the case of glutamic acid which was 3% lower in the isolate and concentrate. The amino acid content and profile of the Oryzatein-90™ isolate was similar to published values for soy protein isolate but the total, essential, and branched-chain amino acid content of whey protein isolate was 20%, 39% and 33% greater, respectively, than that of Oryzatein-90™. These results provide a valuable addition to the nutrient database of protein isolates and concentrates from cereal grains.

  4. Amino Acid Composition of an Organic Brown Rice Protein Concentrate and Isolate Compared to Soy and Whey Concentrates and Isolates.

    Science.gov (United States)

    Kalman, Douglas S

    2014-06-30

    A protein concentrate (Oryzatein-80™) and a protein isolate (Oryzatein-90™) from organic whole-grain brown rice were analyzed for their amino acid composition. Two samples from different batches of Oryzatein-90™ and one sample of Oryzatein-80™ were provided by Axiom Foods (Los Angeles, CA, USA). Preparation and analysis was carried out by Covance Laboratories (Madison, WI, USA). After hydrolysis in 6-N hydrochloric acid for 24 h at approximately 110 °C and further chemical stabilization, samples were analyzed by HPLC after pre-injection derivitization. Total amino acid content of both the isolate and the concentrate was approximately 78% by weight with 36% essential amino acids and 18% branched-chain amino acids. These results are similar to the profiles of raw and cooked brown rice except in the case of glutamic acid which was 3% lower in the isolate and concentrate. The amino acid content and profile of the Oryzatein-90™ isolate was similar to published values for soy protein isolate but the total, essential, and branched-chain amino acid content of whey protein isolate was 20%, 39% and 33% greater, respectively, than that of Oryzatein-90™. These results provide a valuable addition to the nutrient database of protein isolates and concentrates from cereal grains.

  5. Cadmium Alters the Concentration of Fatty Acids in THP-1 Macrophages.

    Science.gov (United States)

    Olszowski, Tomasz; Gutowska, Izabela; Baranowska-Bosiacka, Irena; Łukomska, Agnieszka; Drozd, Arleta; Chlubek, Dariusz

    2018-03-01

    Fatty acid composition of human immune cells influences their function. The aim of this study was to evaluate the effects of known toxicant and immunomodulator, cadmium, at low concentrations on levels of selected fatty acids (FAs) in THP-1 macrophages. The differentiation of THP-1 monocytes into macrophages was achieved by administration of phorbol myristate acetate. Macrophages were incubated with various cadmium chloride (CdCl 2 ) solutions for 48 h at final concentrations of 5 nM, 20 nM, 200 nM, and 2 μM CdCl 2 . Fatty acids were extracted from samples according to the Folch method. The fatty acid levels were determined using gas chromatography. The following fatty acids were analyzed: long-chain saturated fatty acids (SFAs) palmitic acid and stearic acid, very long-chain saturated fatty acid (VLSFA) arachidic acid, monounsaturated fatty acids (MUFAs) palmitoleic acid, oleic acid and vaccenic acid, and n-6 polyunsaturated fatty acids (PUFAs) linoleic acid and arachidonic acid. Treatment of macrophages with very low concentrations of cadmium (5-200 nM) resulted in significant reduction in the levels of arachidic, palmitoleic, oleic, vaccenic, and linoleic acids and significant increase in arachidonic acid levels (following exposure to 5 nM Cd), without significant reduction of palmitic and stearic acid levels. Treatment of macrophages with the highest tested cadmium concentration (2 μM) produced significant reduction in the levels of all examined FAs: SFAs, VLSFA, MUFAs, and PUFAs. In conclusion, cadmium at tested concentrations caused significant alterations in THP-1 macrophage fatty acid levels, disrupting their composition, which might dysregulate fatty acid/lipid metabolism thus affecting macrophage behavior and inflammatory state.

  6. Process for recovering a uranium containing concentrate and purified phosphoric acid from a wet process phosphoric acid containing uranium

    International Nuclear Information System (INIS)

    Weterings, C.A.M.; Janssen, J.A.

    1985-01-01

    A process is claimed for recovering from a wet process phosphoric acid which contains uranium, a uranium containing concentrate and a purified phosphoric acid. The wet process phosphoric acid is treated with a precipitant in the presence of a reducing agent and an aliphatic ketone

  7. Process for recovering a uranium containing concentrate and purified phosphoric acid from a wet process phosphoric acid containing uranium

    Energy Technology Data Exchange (ETDEWEB)

    Weterings, C.A.M.; Janssen, J.A.

    1985-04-30

    A process is claimed for recovering from a wet process phosphoric acid which contains uranium, a uranium containing concentrate and a purified phosphoric acid. The wet process phosphoric acid is treated with a precipitant in the presence of a reducing agent and an aliphatic ketone.

  8. Influence of bleaching on flavor of 34% whey protein concentrate and residual benzoic acid concentration in dried whey products

    Science.gov (United States)

    Previous studies have shown that bleaching negatively affects the flavor of 70% whey protein concentrate (WPC70), but bleaching effects on lower-protein products have not been established. Benzoyl peroxide (BP), a whey bleaching agent, degrades to benzoic acid (BA) and may elevate BA concentrations...

  9. Influence of Bleaching on Flavor of 34% Whey Protein Concentrate and Residual Benzoic Acid Concentration in Dried Whey Proteins

    Science.gov (United States)

    Previous studies have shown that bleaching negatively affects the flavor of 70% whey protein concentrate (WPC70), but bleaching effects on lower-protein products have not been established. Benzoyl peroxide (BP), a whey bleaching agent, degrades to benzoic acid (BA) and may elevate BA concentrations...

  10. Analysis of hyaluronic acid concentration in rat vocal folds during estral and gravidic puerperal cycles

    OpenAIRE

    de Sá Pedroso, José Eduardo; Camponês do Brasil, Osíris; Maciel Martins, João Roberto; Nader, Helena Bociane; Simões, Manuel de Jesus

    2009-01-01

    Hormone plays an important role in the larynx. Among other substances, vocal folds contain hyaluronic acid, which tissue concentration may vary according to hormone action. AIM: the objective of this study is to analyze hyaluronic acid concentration in the vocal folds during estral and gravidic-puerperal cycles. MATERIALS AND METHODS: Experimental study. 40 adult rats were divided into two groups. In the first group we used 20 rats to establish the concentration of hyaluronic acid during the ...

  11. Elevational Variation in Soil Amino Acid and Inorganic Nitrogen Concentrations in Taibai Mountain, China.

    Directory of Open Access Journals (Sweden)

    Xiaochuang Cao

    Full Text Available Amino acids are important sources of soil organic nitrogen (N, which is essential for plant nutrition, but detailed information about which amino acids predominant and whether amino acid composition varies with elevation is lacking. In this study, we hypothesized that the concentrations of amino acids in soil would increase and their composition would vary along the elevational gradient of Taibai Mountain, as plant-derived organic matter accumulated and N mineralization and microbial immobilization of amino acids slowed with reduced soil temperature. Results showed that the concentrations of soil extractable total N, extractable organic N and amino acids significantly increased with elevation due to the accumulation of soil organic matter and the greater N content. Soil extractable organic N concentration was significantly greater than that of the extractable inorganic N (NO3--N + NH4+-N. On average, soil adsorbed amino acid concentration was approximately 5-fold greater than that of the free amino acids, which indicates that adsorbed amino acids extracted with the strong salt solution likely represent a potential source for the replenishment of free amino acids. We found no appreciable evidence to suggest that amino acids with simple molecular structure were dominant at low elevations, whereas amino acids with high molecular weight and complex aromatic structure dominated the high elevations. Across the elevational gradient, the amino acid pool was dominated by alanine, aspartic acid, glycine, glutamic acid, histidine, serine and threonine. These seven amino acids accounted for approximately 68.9% of the total hydrolyzable amino acid pool. The proportions of isoleucine, tyrosine and methionine varied with elevation, while soil major amino acid composition (including alanine, arginine, aspartic acid, glycine, histidine, leucine, phenylalanine, serine, threonine and valine did not vary appreciably with elevation (p>0.10. The compositional

  12. Determination of conjugated linoleic acid (CLA) concentrations in milk chocolate.

    Science.gov (United States)

    Hurst, W J; Tarka, S M; Dobson, G; Reid, C M

    2001-03-01

    The fatty acids from a series of milk-chocolate-based confectionery samples were analyzed as methyl esters by GC to determine the presence and amount of conjugated linoleic acid (CLA). A single peak corresponding to the 9-cis,11-trans isomer and ranging from less than 0.1% to nearly 0.2% of the total fatty acids, corresponding to up to 0.3 mg per g of chocolate, was observed. One of the chocolate extracts and a milk extract were subjected to silver ion HPLC and GC-MS in order to confirm the identity of the major isomer and tentatively identity minor isomers.

  13. Determination of concentration and molar absorptivity of hypochlorous acid and hypobromous acid species by hydrogen peroxide titration

    Science.gov (United States)

    Uehara, H.; Arakaki, T.

    2017-12-01

    Hypochlorous acid and hypobromous acid (abbreviated as "HypoX acids") are the main ingredients of bleaching and bactericides. The HypoX acids change their chemical forms depending on environmental factors such as pH and various chemical reactions. For example, it has been reported that hypobromite ion in water changes to carcinogenic bromate by photochemical reaction with ultraviolet light. In this study, concentrations of HypoX acids were determined by UV-VIS absorbance measurement utilizing the fact that HypoX acids react with hydrogen peroxide and do not co-exist in the solution. The method for determining the concentration by titration with hydrogen peroxide can be carried out simpler and more efficiently than the DPD method or the current titration method generally used for chlorine concentration measurement. Molar absorptivity between 250 - 500 nm of HypoX acids, including their conjugate base species, was determined by solving theoretical acid-base formula including molar fraction of each chemical species at various pHs. Molar absorptivity of OCl- and OBr- between 250 - 500 nm was determined based on the concentrations obtained from titration with hydrogen peroxide and absorbance at pH > 10, where OCl- and OBr- dominate. Furthermore, the HypoX acids solutions were irradiated with a solar simulator, and the photolysis rate constants were obtained. Based on those values, the half-lives were calculated and the behavior of HypoX acids in the environment was elucidated.

  14. Serum uric acid concentration in patients with type-2 diabetes mellitus during diet or glibenclamide therapy

    International Nuclear Information System (INIS)

    Mahmood, I.H.

    2007-01-01

    To investigate serum uric acid concentration in patients with type 2 diabetes mellitus. This is a case control study conducted in Al-Wafa Diabetic Center in Mosul over a period of one year starting from January 1, 2005 to January 1, 2006. Serum glucose concentration and uric acid concentration were measured in both control and patient's groups (group 1 patients on diet therapy, group 2 patients on glibenclamide therapy and group 3 involve naturopathic patients). Serum glucose concentration was high in the diabetic groups as compared with the control group (P 0.2) except in group-3 (P<0.05). A negative correlation was reported between hyperglycemia and uric acid concentration of the different groups. Serum uric acid concentration is slightly reduced in type 2 diabetic patients particularly in the complicated patients with peripheral neuropathy and this may be due to the oxidative stress that decreases the antioxidant capacity of the body involving uric acid. (author)

  15. High serum uric acid concentration predicts poor survival in patients with breast cancer.

    Science.gov (United States)

    Yue, Cai-Feng; Feng, Pin-Ning; Yao, Zhen-Rong; Yu, Xue-Gao; Lin, Wen-Bin; Qian, Yuan-Min; Guo, Yun-Miao; Li, Lai-Sheng; Liu, Min

    2017-10-01

    Uric acid is a product of purine metabolism. Recently, uric acid has gained much attraction in cancer. In this study, we aim to investigate the clinicopathological and prognostic significance of serum uric acid concentration in breast cancer patients. A total of 443 female patients with histopathologically diagnosed breast cancer were included. After a mean follow-up time of 56months, survival was analysed using the Kaplan-Meier method. To further evaluate the prognostic significance of uric acid concentrations, univariate and multivariate Cox regression analyses were applied. Of the clinicopathological parameters, uric acid concentration was associated with age, body mass index, ER status and PR status. Univariate analysis identified that patients with increased uric acid concentration had a significantly inferior overall survival (HR 2.13, 95% CI 1.15-3.94, p=0.016). In multivariate analysis, we found that high uric acid concentration is an independent prognostic factor predicting death, but insufficient to predict local relapse or distant metastasis. Kaplan-Meier analysis indicated that high uric acid concentration is related to the poor overall survival (p=0.013). High uric acid concentration predicts poor survival in patients with breast cancer, and might serve as a potential marker for appropriate management of breast cancer patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Valproic acid modulates platelet and coagulation function ex vivo

    DEFF Research Database (Denmark)

    Bambakidis, Ted; Dekker, Simone E; Halaweish, Ihab

    2017-01-01

    of coagulopathy, it remains unknown whether this is a direct effect of the drug, or the establishment of an overall prosurvival phenotype. We thus conducted an ex-vivo experiment to determine if VPA has an effect on coagulation and platelet function. Ten swine were subjected to traumatic brain injury (TBI...

  17. Novel Polymeric Prodrugs of Valproic Acid as Anti- Epilepsy Drugs ...

    African Journals Online (AJOL)

    Epilepsy Drugs: Synthesis, Characterization and In-vitro ... The release of VPA from polymeric prodrugs was studied using cellophane ... pharmacokinetics and accessibility in market [8]. ..... between the drug and polymer chain can affect.

  18. Novel Polymeric Prodrugs of Valproic Acid as Anti- Epilepsy Drugs ...

    African Journals Online (AJOL)

    The release of VPA from polymeric prodrugs was studied using cellophane membrane dialysis bags containing aqueous buffer solutions (pH 1, 7 and 10) at 37 oC. The quantity of released drug was detected by ultraviolet (UV) spectroscopy. Results: 1H-NMR and elemental analyses data for calculating mole composition of ...

  19. Avelumab With Valproic Acid in Virus-associated Cancer

    Science.gov (United States)

    2018-06-11

    Cancer That is Associated With a Chronic Viral Infection; p16 Positive SCCHN; Squamous Cell Carcinoma of the Cervix; p16 Positive Squamous Cell Carcinoma of the Vagina or Vulva; p16 Positive Squamous Cell Carcinoma of the Penis; p16 Positive Squamous Cell Carcinoma of the Anus or Anal Canal; EBER Positive NPC; EBER Positive Hodgkins and Non-hodgkins Lymphona

  20. Using Conductivity Measurements to Determine the Identities and Concentrations of Unknown Acids: An Inquiry Laboratory Experiment

    Science.gov (United States)

    Smith, K. Christopher; Garza, Ariana

    2015-01-01

    This paper describes a student designed experiment using titrations involving conductivity measurements to identify unknown acids as being either HCl or H[subscript 2]SO[subscript 4], and to determine the concentrations of the acids, thereby improving the utility of standard acid-base titrations. Using an inquiry context, students gain experience…

  1. Plasma Concentration of Ascorbic Acid and Some Hematological ...

    African Journals Online (AJOL)

    hanumantp

    Annals of Medical and Health Sciences Research | Jan-Jun 2012 | Vol 2 | Issue 1 |. Address for ... acid, which is a vital antioxidant, and blood cell production or morphology may be affected. Objective: To .... Morley A. A platelet cycle in normal individuals. Austr Ann ... practices and the role of mothers and community health.

  2. Relationship between abscisic acid (ABA) concentration and some ...

    African Journals Online (AJOL)

    This work investigated the effects of endogenous abscisic acid (ABA) and physiologic parameters related to yield in two wheat cultivars (Triticum aestivum L.), Marvdasht and Zagros (sensitive and tolerant to terminal season drought, respectively) grown in pots under well watered and water-stressed starting from anthesis ...

  3. Plasma Concentration of Ascorbic Acid and Some Hematological ...

    African Journals Online (AJOL)

    Background: Tobacco snuffing, like cigarette smoking, is known to be a common habit among the adults of Igbo communities in Nigeria. In view of the various pharmacological actions of nicotine and other additive constituents of tobacco snuff, there is growing concern that ascorbic acid, which is a vital antioxidant, and blood ...

  4. Metabolic syndrome, alcohol consumption and genetic factors are associated with serum uric acid concentration.

    Directory of Open Access Journals (Sweden)

    Blanka Stibůrková

    Full Text Available Uric acid is the end product of purine metabolism in humans, and increased serum uric acid concentrations lead to gout. The objective of the current study was to identify factors that are independently associated with serum uric acid concentrations in a cohort of Czech control individuals.The cohort consisted of 589 healthy subjects aged 18-65 years. We studied the associations between the serum uric acid concentration and the following: (i demographic, anthropometric and other variables previously reported to be associated with serum uric acid concentrations; (ii the presence of metabolic syndrome and the levels of metabolic syndrome components; and (iii selected genetic variants of the MTHFR (c.665C>T, c.1286A>C, SLC2A9 (c.844G>A, c.881G>A and ABCG2 genes (c.421C>A. A backward model selection procedure was used to build two multiple linear regression models; in the second model, the number of metabolic syndrome criteria that were met replaced the metabolic syndrome-related variables.The models had coefficients of determination of 0.59 and 0.53. The serum uric acid concentration strongly correlated with conventional determinants including male sex, and with metabolic syndrome-related variables. In the simplified second model, the serum uric acid concentration positively correlated with the number of metabolic syndrome criteria that were met, and this model retained the explanatory power of the first model. Moderate wine drinking did not increase serum uric acid concentrations, and the urate transporter ABCG2, unlike MTHFR, was a genetic determinant of serum uric acid concentrations.Metabolic syndrome, moderate wine drinking and the c.421C>A variant in the ABCG gene are independently associated with the serum uric acid concentration. Our model indicates that uric acid should be clinically monitored in persons with metabolic syndrome.

  5. Evaluation of ultrasonic technique to characterize the concentration of boric acid in liquid medium

    International Nuclear Information System (INIS)

    Kohara, Richard Yuzo Ramida

    2015-01-01

    This dissertation is to analyze the viability of using ultrasonic technique to characterize the concentration of boric acid in liquid medium non-invasively, therefore, ultrasonic tests were performed relating different boric acid concentrations with the travel time of the ultrasonic wave, also were evaluated factors able to mask the characterization of these concentrations by ultrasonic technique. The results showed that the ultrasonic technique allows the characterization of boric acid concentrations in liquid medium in very simple terms by the ultrasonic wave travel time, requiring further studies in complex conditions. (author)

  6. Preparative concentration of nucleic acids fragments by capillary isotachophoretic analyzer

    Czech Academy of Sciences Publication Activity Database

    Datinská, Vladimíra; Voráčová, Ivona; Berka, J.; Foret, František

    2018-01-01

    Roč. 1548 (2018), s. 100-103 ISSN 0021-9673 R&D Projects: GA MŠk(CZ) LQ1601; GA ČR(CZ) GBP206/12/G014; GA MŠk(CZ) 8F17003 Institutional support: RVO:68081715 Keywords : DNA * isotachophoresis * nucleic acids * sample preparation Subject RIV: CB - Analytical Chemistry, Separation OBOR OECD: Analytical chemistry Impact factor: 3.981, year: 2016

  7. Preparative concentration of nucleic acids fragments by capillary isotachophoretic analyzer

    Czech Academy of Sciences Publication Activity Database

    Datinská, Vladimíra; Voráčová, Ivona; Berka, J.; Foret, František

    2018-01-01

    Roč. 1548, MAY (2018), s. 100-103 ISSN 0021-9673 R&D Projects: GA MŠk(CZ) LQ1601; GA ČR(CZ) GBP206/12/G014; GA MŠk(CZ) 8F17003 Institutional support: RVO:68081715 Keywords : DNA * isotachophoresis * nucleic acids * sample preparation Subject RIV: CB - Analytical Chemistry, Separation OBOR OECD: Analytical chemistry Impact factor: 3.981, year: 2016

  8. High plasma uric acid concentration: causes and consequences

    Directory of Open Access Journals (Sweden)

    de Oliveira Erick

    2012-04-01

    Full Text Available Abstract High plasma uric acid (UA is a precipitating factor for gout and renal calculi as well as a strong risk factor for Metabolic Syndrome and cardiovascular disease. The main causes for higher plasma UA are either lower excretion, higher synthesis or both. Higher waist circumference and the BMI are associated with higher insulin resistance and leptin production, and both reduce uric acid excretion. The synthesis of fatty acids (tryglicerides in the liver is associated with the de novo synthesis of purine, accelerating UA production. The role played by diet on hyperuricemia has not yet been fully clarified, but high intake of fructose-rich industrialized food and high alcohol intake (particularly beer seem to influence uricemia. It is not known whether UA would be a causal factor or an antioxidant protective response. Most authors do not consider the UA as a risk factor, but presenting antioxidant function. UA contributes to > 50% of the antioxidant capacity of the blood. There is still no consensus if UA is a protective or a risk factor, however, it seems that acute elevation is a protective factor, whereas chronic elevation a risk for disease.

  9. Method for the recovery of uranium from a concentrate using pure phosphoric acid

    International Nuclear Information System (INIS)

    1980-01-01

    Procedure for the recovery of an uranium bearing concentrate and pure phosphoric acid from a wet process phosphoric acid from the treatment fluid with a precipitation means in conjunction with an organic diluent, the thus formed precipitate to separate and from the remaining mixture of phosphoric acid and diluent the phosphoric acid to extract, characterised in that one applies an inorganic fluorine compound. (G.C.)

  10. 3.6. The kinetics of sulfuric acid decomposition of calcined concentrate of borosilicate ore

    International Nuclear Information System (INIS)

    Mirsaidov, U.M.; Kurbonov, A.S.; Mamatov, E.D.

    2015-01-01

    Present article is devoted to kinetics of sulfuric acid decomposition of calcined concentrate of borosilicate ore. The experimental data of kinetics of extraction of boron oxide from danburite at sulfuric acid decomposition were obtained at 20-90 deg C temperature range and process duration 15-90 minutes. The flowsheet of obtaining of boric acid from borosilicate ores of Ak-Arkhar Deposit by sulfuric acid method was proposed.

  11. Process for the winning of a concentrate containing uranium and purified phosphoric acid, as well as the concentrate containing uranium and purified phosphoric acid obtained by this process

    International Nuclear Information System (INIS)

    1980-01-01

    The uranium containing concentrate and purified phosphoric acid are obtained by treating wet phosphoric acid with an inorganic fluorine compound (ammonium fluoride) and an aliphatic ketone (acetone) in the presence of a reducing agent (finely divided iron). The ketone is added first and the formed uranium precipitate is separated from the solution. If the fluorine compound is added first, the yield is lowered by a factor of 2. (Th.P.)

  12. Rheology of dilute acid hydrolyzed corn stover at high solids concentration.

    Science.gov (United States)

    Ehrhardt, M R; Monz, T O; Root, T W; Connelly, R K; Scott, C T; Klingenberg, D J

    2010-02-01

    The rheological properties of acid hydrolyzed corn stover at high solids concentration (20-35 wt.%) were investigated using torque rheometry. These materials are yield stress fluids whose rheological properties can be well represented by the Bingham model. Yield stresses increase with increasing solids concentration and decrease with increasing hydrolysis reaction temperature, acid concentration, and rheometer temperature. Plastic viscosities increase with increasing solids concentration and tend to decrease with increasing reaction temperature and acid concentration. The solids concentration dependence of the yield stress is consistent with that reported for other fibrous systems. The changes in yield stress with reaction conditions are consistent with observed changes in particle size. This study illustrates that torque rheometry can be used effectively to measure rheological properties of concentrated biomass.

  13. Study of the interaction metallic cation - ligand in concentrated phosphorus acid media; Etude de l'interaction cation metallique - ligand en milieu acide phosphorique concentre

    Energy Technology Data Exchange (ETDEWEB)

    Sefiani, N.; Azzi, M.; Hlaibi, M. [Faculte des Sciences Ain Chock, Laboratoire d' Electrochimie et Chimie de l' Environnement (LECE), Casablanca (Morocco); Kossair, A. [Centre de Recherche des Phosphates Mineraux (CERPHOS), Casablanca (Morocco)

    2005-07-01

    The phosphoric acid is more and more used with a high purity. The recovery of recycling element (uranium, vanadium, rare earth...) and the elimination of toxic element (cadmium, molybdenum, lead...) contained in the phosphoric acid are generally realized by extraction or precipitation. It is then very important to understand these impurities behavior in the phosphoric media in order to control their elimination. In this work, the authors considered the presence of some metallic cations (V, Al, fe, U) and fluorides ions as impurity in concentrated phosphoric acid media. (A.L.B.)

  14. Effect of Nitric Acid Concentrations on Synthesis and Stability of Maghemite Nanoparticles Suspension

    Directory of Open Access Journals (Sweden)

    Irwan Nurdin

    2014-01-01

    Full Text Available Maghemite (γ-Fe2O3 nanoparticles have been synthesized using a chemical coprecipitation method at different nitric acid concentrations as an oxidizing agent. Characterization of all samples performed by several techniques including X-ray diffraction (XRD, transmission electron microscopy (TEM, alternating gradient magnetometry (AGM, thermogravimetric analysis (TGA, dynamic light scattering (DLS, and zeta potential. The XRD patterns confirmed that the particles were maghemite. The crystallite size of all samples decreases with the increasing concentration of nitric acid. TEM observation showed that the particles have spherical morphology with narrow particle size distribution. The particles showed superparamagnetic behavior with decreased magnetization values at the increasing concentration of nitric acid. TGA measurement showed that the stability temperature decreases with the increasing concentration of nitric acid. DLS measurement showed that the hydrodynamic particle sizes decrease with the increasing concentration of nitric acid. Zeta potential values show a decrease with the increasing concentration of nitric acid. The increasing concentration of nitric acid in synthesis of maghemite nanoparticles produced smaller size particles, lower magnetization, better thermal stability, and more stable maghemite nanoparticles suspension.

  15. Effect of succinic acid concentration in poly(glycerol citrate/succinate) properties

    International Nuclear Information System (INIS)

    Brioude, Michel M.; Guimaraes, Danilo H.; Fiuza, Raigenis P.; Jose, Nadia M.

    2011-01-01

    In this work were prepared and characterized polymer based on glycerol, citric and succinic acid, in three different ratios to evaluate the effect of succinic acid concentration in materials properties. The polymers were obtained by polycondensation reaction between polyol and poly acids, and were characterized by X-ray diffraction (XRD), infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), scanning differential calorimetry (DSC), scanning electron microscopy (SEM). The materials are amorphous polyesters and its thermal and morphological properties change depending on the succinic acid concentration. (author)

  16. 4.3. Decomposition of danburite concentrate of Ak-Arkar Deposit by nitric acid

    International Nuclear Information System (INIS)

    Mirsaidov, U.M.; Kurbonov, A.S.; Mamatov, E.D.

    2015-01-01

    Present article is devoted to decomposition of danburite concentrate of Ak-Arkar Deposit by nitric acid. The influence of temperature on reaction process was studied. The dependence of extraction rate of oxides (B 2 O 3 , Al 2 O 3 , Fe 2 O 3 and Ca O) at nitric acid processing on temperature ranges from 25 to 95 deg C was defined. The dependence of extraction rate of oxides (B 2 O 3 , Al 2 O 3 , Fe 2 O 3 and Ca O) at nitric acid processing on process duration (5-60 minutes) was defined as well. The optimal conditions of decomposition of danburite concentrate by nitric acid were proposed.

  17. Effects on grape amino acid concentration through foliar application of three different elicitors.

    Science.gov (United States)

    Gutiérrez-Gamboa, G; Portu, J; Santamaría, P; López, R; Garde-Cerdán, T

    2017-09-01

    Elicitors play an important role in the defense against pathogens as an alternative to chemical pesticides by increasing secondary metabolites. Their effect on grape amino acid has been little investigated. Thus, the aim of this research was to study the influence of methyl jasmonate (MeJ), chitosan (CHT), and a yeast extract (YE) on grape amino acid composition, through foliar applications to grapevines. The must amino acid concentration was analyzed by HPLC. The results showed that CHT and YE treatments decreased the must concentration of several amino acids, affecting total amino acid content (from 2364 to 1961, and 1818mg/L, respectively). However, MeJ treatment had a slight effect on grape amino acid content, increasing the concentration of Met (from 8.95 to 12.13mg/L) and Phe (from 7.96 to 9.29mg/L). It seems to be that, the resistance induction through CHT and YE treatments results in physiological costs to grapevines associated with a decrease on grape amino acid concentration. Consequently, MeJ applications, as a viticultural practice, could be a better tool than CHT and YE treatments, because did not affect grape amino acid concentration. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Recovery of uranium in the production of concentrated phosphoric acid by a hemihydrate process

    International Nuclear Information System (INIS)

    Nakajima, S.; Miyamoto, M.

    1983-01-01

    Nissan Chemical Industries as manufacturers of phosphoric acid have studied the recovery of uranium, based on a concentrated phosphoric acid production process. The process consists of two stages, a hemihydrate stage with a formation of hemihydrate and a filtration section, followed by a dihydrate stage with hydration and a filtration section. In the hemihydrate stage, phosphate is treated with a mixture of phosphoric acid and sulphuric acid to produce phosphoric acid and hydrous calcium sulphate; the product is recovered in the filtration section and its concentration is 40-50% P 2 O 3 . In the dihydrate stage, the hemihydrate is transformed by re-dissolution and hydration, producing hydrous calcium sulphate, i.e. gypsum. This process therefore comprises two parts, each with different acid concentrations. As the extraction of uranium is easier in the case of a low concentration of phosphoric acid, the process consists of the recovery of uranium starting from the filtrate of the hydration section. The tests have shown that the yield of recovery of uranium was of the order of 80% disregarding the handling losses and no disadvantageous effect has been found in the combination of the process of uranium extraction with the process of concentrated phosphoric acid production. Compared with the classical process where uranium is recovered from acid with 30% P 2 O 5 , the process of producing high-concentration phosphoric acid such as the Nissan process, in which the uranium recovery is effected from acid with 15% P 2 O 5 from the hydration section, presents many advantages [fr

  19. Relationship between the concentrations of plasma phospholipid stearic acid and plasma lipoprotein lipids in healthy men.

    Science.gov (United States)

    Li, D

    2001-01-01

    This study investigated the correlation between the plasma phospholipid (PL) saturated fatty acid (SFA) concentration (as a surrogate marker of SFA intake) and plasma lipid and lipoprotein lipid concentrations in 139 healthy Australian men aged 20-55 years old with widely varying intakes of saturated fat (vegans, n=18; ovolacto vegetarians, n=43; moderate meat eaters, n=60; high meat eaters, n=18). Both the ovolacto vegetarian and vegan groups demonstrated significant decreases in plasma total cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C) and triacylglycerol concentrations compared with both the high-meat-eater and moderate-meat-eater groups. Total SFA and individual SFA [palmitic acid (16:0), stearic acid (18:0) and arachidic acid (20:0)] in the plasma PL were significantly lower in both the ovolacto vegetarian and vegan groups than in both the high- and moderate-meat-eater groups, while myristic acid (14:0) was significantly lower in the vegans than in the high-meat-eaters. Bivariate analysis of the results showed that the plasma PL stearic acid concentration was strongly positively correlated with plasma TC (P<0.0001), LDL-C (P<0.0001) and triacylglycerol (P<0.0001), with r(2) values of 0.655, 0.518 and 0.43 respectively. In multiple linear regression, after controlling for potential confounding factors (such as exercise, dietary group, age, body mass index, plasma PL myristic acid, palmitic acid and arachidic acid, and dietary total fat, saturated fat, cholesterol, carbohydrate and fibre intake), the plasma PL stearic acid concentration was still strongly positively correlated with plasma TC (P<0.0001) and LDL-C (P=0.006) concentrations. Based on the present data, it would seem appropriate for the population to reduce their dietary total SFA intake rather than to replace other SFA with stearic acid.

  20. Circadian changes in endogenous concentrations of indole-3-acetic acid, melatonin, serotonin, abscisic acid and jasmonic acid in Characeae (Chara australis Brown).

    Science.gov (United States)

    Beilby, Mary J; Turi, Christina E; Baker, Teesha C; Tymm, Fiona Jm; Murch, Susan J

    2015-01-01

    Giant-celled Characeae (Chara australis Brown), grown for 4 months on 12/12 hr day/night cycle and summer/autumn temperatures, exhibited distinct concentration maxima in auxin (indole-3-acetic acid; IAA), melatonin and serotonin about 4 hr after subjective daybreak. These concentration peaks persisted after 3 day pretreatment in continuous darkness: confirming a circadian rhythm, rather than a response to "light on." The plants pretreated for 3 d in continuous light exhibited several large IAA concentration maxima throughout the 24 hr. The melatonin and serotonin concentrations decreased and were less synchronized with IAA. Chara plants grown on 9/15 hr day/night cycle for 4 months and winter/spring temperatures contained much smaller concentrations of IAA, melatonin and serotonin. The IAA concentration maxima were observed in subjective dark phase. Serotonin concentration peaks were weakly correlated with those of IAA. Melatonin concentration was low and mostly independent of circadian cycle. The "dark" IAA concentration peaks persisted in plants treated for 3 d in the dark. The plants pretreated for 3 d in the light again developed more IAA concentration peaks. In this case the concentration maxima in melatonin and serotonin became more synchronous with those in IAA. The abscisic acid (ABA) and jasmonic acid (JA) concentrations were also measured in plants on winter regime. The ABA concentration did not exhibit circadian pattern, while JA concentration peaks were out of phase with those of IAA. The data are discussed in terms of crosstalk between metabolic pathways.

  1. Concentration and fractionation of hydrophobic organic acid constituents from natural waters by liquid chromatography

    Science.gov (United States)

    Thurman, E.M.; Malcolm, R.L.

    1979-01-01

    A scheme is presented which used adsorption chromatography with pH gradient elution and size-exclusion chromatography to concentrate and separate hydrophobic organic acids from water. A review of chromatographic processes involved in the flow scheme is also presented. Organic analytes which appear in each aqueous fraction are quantified by dissolved organic carbon analysis. Hydrophobic organic acids in a water sample are concentrated on a porous acrylic resin. These acids usually constitute approximately 30-50 percent of the dissolved organic carbon in an unpolluted water sample and are eluted with an aqueous eluent (dilute base). The concentrate is then passed through a column of polyacryloylmorpholine gel, which separates the acids into high- and low-molecular-weight fractions. The high- and low-molecular-weight eluates are reconcentrated by adsorption chromatography, then are eluted with a pH gradient into strong acids (predominately carboxylic acids) and weak acids (predominately phenolic compounds). For standard compounds and samples of unpolluted waters, the scheme fractionates humic substances into strong and weak acid fractions that are separated from the low molecular weight acids. A new method utilizing conductivity is also presented to estimate the acidic components in the methanol fraction.

  2. Chronic sucrose intake decreases concentrations of n6 fatty acids, but not docosahexaenoic acid in the rat brain phospholipids.

    Science.gov (United States)

    Mašek, Tomislav; Starčević, Kristina

    2017-07-13

    We investigated the influence of high sucrose intake, administered in drinking water, on the lipid profile of the brain and on the expression of SREBP1c and Δ-desaturase genes. Adult male rats received 30% sucrose solution for 20 weeks (Sucrose group), or plain water (Control group). After the 20th week of sucrose treatment, the Sucrose group showed permanent hyperglycemia. Sucrose treatment also increased the amount of total lipids and fatty acids in the brain. The brain fatty acid profile of total lipids as well as phosphatidylethanolamine, phosphatidylcholine and cardiolipin of the Sucrose group was extensively changed. The most interesting change was a significant decrease in n6 fatty acids, including the important arachidonic acid, whereas the content of oleic and docosahexaenoic acid remained unchanged. RT-qPCR revealed an increase in Δ-5-desaturase and SREBP1c gene expression. In conclusion, high sucrose intake via drinking water extensively changes rat brain fatty acid profile by decreasing n6 fatty acids, including arachidonic acid. In contrast, the content of docosahexaenoic acid remains constant in the brain total lipids as well as in phospholipids. Changes in the brain fatty acid profile reflect changes in the lipid metabolism of the rat lipogenic tissues and concentrations in the circulation. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Hormesis in Cholestatic Liver Disease; Preconditioning with Low Bile Acid Concentrations Protects against Bile Acid-Induced Toxicity.

    Directory of Open Access Journals (Sweden)

    Esther M Verhaag

    Full Text Available Cholestasis is characterized by accumulation of bile acids and inflammation, causing hepatocellular damage. Still, liver damage markers are highest in acute cholestasis and drop when this condition becomes chronic, indicating that hepatocytes adapt towards the hostile environment. This may be explained by a hormetic response in hepatocytes that limits cell death during cholestasis.To investigate the mechanisms that underlie the hormetic response that protect hepatocytes against experimental cholestatic conditions.HepG2.rNtcp cells were preconditioned (24 h with sub-apoptotic concentrations (0.1-50 μM of various bile acids, the superoxide donor menadione, TNF-α or the Farsenoid X Receptor agonist GW4064, followed by a challenge with the apoptosis-inducing bile acid glycochenodeoxycholic acid (GCDCA; 200 μM for 4 h, menadione (50 μM, 6 h or cytokine mixture (CM; 6 h. Levels of apoptotic and necrotic cell death, mRNA expression of the bile salt export pump (ABCB11 and bile acid sensors, as well as intracellular GCDCA levels were analyzed.Preconditioning with the pro-apoptotic bile acids GCDCA, taurocholic acid, or the protective bile acids (tauroursodeoxycholic acid reduced GCDCA-induced caspase-3/7 activity in HepG2.rNtcp cells. Bile acid preconditioning did not induce significant levels of necrosis in GCDCA-challenged HepG2.rNtcp cells. In contrast, preconditioning with cholic acid, menadione or TNF-α potentiated GCDCA-induced apoptosis. GCDCA preconditioning specifically reduced GCDCA-induced cell death and not CM- or menadione-induced apoptosis. The hormetic effect of GCDCA preconditioning was concentration- and time-dependent. GCDCA-, CDCA- and GW4064- preconditioning enhanced ABCB11 mRNA levels, but in contrast to the bile acids, GW4064 did not significantly reduce GCDCA-induced caspase-3/7 activity. The GCDCA challenge strongly increased intracellular levels of this bile acid, which was not lowered by GCDCA

  4. Using Simple Quadratic Equations to Estimate Equilibrium Concentrations of an Acid

    Science.gov (United States)

    Brilleslyper, Michael A.

    2004-01-01

    Application of quadratic equations to standard problem in chemistry like finding equilibrium concentrations of ions in an acid solution is explained. This clearly shows that pure mathematical analysis has meaningful applications in other areas as well.

  5. Forced swimming and imipramine modify plasma and brain amino acid concentrations in mice.

    Science.gov (United States)

    Murakami, Tatsuro; Yamane, Haruka; Tomonaga, Shozo; Furuse, Mitsuhiro

    2009-01-05

    The relationships between monoamine metabolism and forced swimming or antidepressants have been well studied, however information is lacking regarding amino acid metabolism under these conditions. Therefore, the aim of the present study was to investigate the effects of forced swimming and imipramine on amino acid concentrations in plasma, the cerebral cortex and the hypothalamus in mice. Forced swimming caused cerebral cortex concentrations of L-glutamine, L-alanine, and taurine to be increased, while imipramine treatment caused decreased concentrations of L-glutamate, L-alanine, L-tyrosine, L-methionine, and L-ornithine. In the hypothalamus, forced swimming decreased the concentration of L-serine while imipramine treatment caused increased concentration of beta-alanine. Forced swimming caused increased plasma concentration of taurine, while concentrations of L-serine, L-asparagine, L-glutamine and beta-alanine were decreased. Imipramine treatment caused increased plasma concentration of all amino acid, except for L-aspartate and taurine. In conclusion, forced swimming and imipramine treatment modify central and peripheral amino acid metabolism. These results may aid in the identification of amino acids that have antidepressant-like effects, or may help to refine the dosages of antidepressant drugs.

  6. Acid pressure leaching of a concentrate containing uranium, thorium and rare earth elements

    International Nuclear Information System (INIS)

    Lan Xinghua; Peng Ruqing.

    1987-01-01

    The acid pressure leaching of a concentrate containing rinkolite for recovering uranium, thorium and rare earth elements is described. The laboratory and the pilot plant test results are given. Under the optimum leaching conditions, the recovery of uranium, thorium and rare earth elements are 82.9%, 86.0% and 88.3% respectively. These results show that the acid pressure leaching process is a effective process for treating the concentrate

  7. The development of precisely analytical method for the concentrated boric acid solution in the NPP systems

    Energy Technology Data Exchange (ETDEWEB)

    Sung, G. B.; Jung, K. H.; Kang, D. W. [KEPRI, Taejon (Korea, Republic of); Park, C. S. [KEPCO, Taejon (Korea, Republic of)

    1999-05-01

    Boric acid is used for reactivity control in nuclear reactors, which frequently results in leftover boric acid. This extra boric acid is stored in boric acid storage tank after the concentration process by boric acid evaporator. Apart from this excess, highly concentrated boric acid is stored in safety-related boric acid storage tank. Accordingly, proper maintenance of these boric acid is one of the greatest safety concerns. The solubility of boric acid decreases with decreasing temperature resulting in its precipitation. Consequently, the temperature of boric acid storage tanks is maintained at high temperature. The following analysis should be also performed at the similar temperature to prevent the formation of boric acid precipitation, which is difficult to achieve affecting the accuracy of analytical results. This paper presents a new sampling and measuring technique that makes up for the difficulties mentioned above and shows several advantages including improved reliability and short analysis time. This method is based on gravimetry and dilution method and is expected to be widely used in field application.

  8. The impact of water concentration on the catalytic oxidation of ethanol on platinum electrode in concentrated phosphoric acid

    Energy Technology Data Exchange (ETDEWEB)

    Camargo, A.P.M.; Previdello, B.A.F.; Varela, H.; Gonzalez, E.R. [Instituto de Quimica de Sao Carlos, Universidade de Sao Paulo, C.P. 780, CEP 13560-970 Sao Carlos, SP (Brazil)

    2010-01-15

    The electro-oxidation of ethanol on platinum in phosphoric acid opens the door to promote the oxidation reaction at higher temperatures. However, the effect of the presence of water is not well understood. In this work, the electro-oxidation of ethanol on platinum was studied in concentrated phosphoric acid containing different concentrations of water at room temperature. The results show that effect of bulk water on the rate electro-oxidation is highest at 0.60 V and decreases for increasing potentials. This was suggested as due to the increasing formation of oxygenated species on the electrode surface with potential, which in turn is more efficient than the increase of water content in the electrolyte. Altogether, these results were interpreted as an evidence of a Langmuir-Hinshelwood step involving oxygenated species as one of the adsorbed partners. (author)

  9. Nitrogen balance, plasma free amino acid concentrations and urinary orotic acid excretion during long-term fasting in cats.

    Science.gov (United States)

    Biourge, V; Groff, J M; Fisher, C; Bee, D; Morris, J G; Rogers, Q R

    1994-07-01

    The purpose of this study was to ascertain the changes in nitrogen balance, plasma free amino acid concentrations, urinary orotic acid excretion and body weight during long-term fasting in adult obese cats. Results from eight cats that fasted rather than eat an unpalatable diet are reported. After 5 to 6 wk of weight loss, six of the eight cats developed signs of hepatic lipidosis, and the livers of all cats were severely infiltrated with lipids. Cats lost (mean +/- SE) 33.2 +/- 1.4% of their pre-fasting body weight. Mean nitrogen balance (+/- SE) was -547 +/- 54 mg.d-1.kg-2/3 for the first week, and then the net nitrogen losses decreased to a plateau (-303 +/- 52 mg.d-1.kg-2/3) after 4 wk. Fasting was associated with a decrease in plasma concentration of essential amino acids. When plasma amino acid concentrations were considered individually, concentrations of alanine, methionine, taurine, citrulline, arginine and tryptophan decreased the most (> or = 50%), whereas concentrations of glutamine, glutamate and ornithine significantly increased. Orotic acid was not detected in the urine during the fast. After 1 wk of fasting, obese cats had reduced nitrogen excretion, but not to the same extent as has been shown in obese humans or obese rats. It is suggested that the availability of several amino acids may become limiting for liver protein synthesis during fasting and that these deficiencies may contribute to the development of hepatic lipidosis. Orotic acid was not linked to hepatic lipidosis caused by fasting in cats.

  10. Continuous tests of Phosphoric Acid - dihydrate process - from phosphatic concentrate of Itataia-CE ore

    International Nuclear Information System (INIS)

    Santos Benedetto, J. dos.

    1984-01-01

    A consolidation of principal studies and continuous tests done with phosphatic concentrated of Itataia ore intending phosphoric acid production by humid-route dihydrate way process is presented. The production of phosphoric acid is applied in uranium extraction process by solvents. (author) [pt

  11. Peripartum cardiomyopathy is associated with increased uric acid concentrations: A population based study.

    Science.gov (United States)

    Sagy, Iftach; Salman, Amjad Abu; Kezerle, Louise; Erez, Offer; Yoel, Idan; Barski, Leonid

    Peri-partum cardiomyopathy (PPCM) is a clinical heart failure that usually develops during the final stage of pregnancy or the first months following delivery. High maternal serum uric acid concentrations have been previous associated with heart failure and preeclampsia. 1) To explored the clinical characteristics of PPCM patients; and 2) to determine the association between maternal serum uric acid concentrations and PPCM. This is a retrospective population based case control study. Cases and controls were matched 1:4 (for gestational age, medical history of cardiac conditions and creatinine); conditional logistic regression was used to identify clinical parameters that were associated with PPCM. The prevalence of peripartum cardiomyopathy at our institution was 1-3832 deliveries (42/160,964). In a matched multivariate analysis high maternal serum uric acid concentrations were associated with PPCM (O.R 1.336, 95% C.I 1.003-1.778). Uric acid concentrations were higher within the Non-Jewish patients and mothers of male infant with PPCM in compare to those without PPCM (p value 0.003 and 0.01 respectively). PPCM patients had increased maternal serum uric acid concentrations. This observation aligns with previous report regarding the increased uric acid concentration in women with preeclampsia and congestive heart failure, suggestive of a common underlying mechanism that mediates the myocardial damage. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Analysis of hyaluronic acid concentration in rat vocal folds during estral and gravidic puerperal cycles.

    Science.gov (United States)

    Pedroso, José Eduardo de Sá; Brasil, Osíris Camponês do; Martins, João Roberto Maciel; Nader, Helena Bociane; Simões, Manuel de Jesus

    2009-01-01

    Hormone plays an important role in the larynx. Among other substances, vocal folds contain hyaluronic acid, which tissue concentration may vary according to hormone action. the objective of this study is to analyze hyaluronic acid concentration in the vocal folds during estral and gravidic-puerperal cycles. Experimental study. 40 adult rats were divided into two groups. In the first group we used 20 rats to establish the concentration of hyaluronic acid during the estral cycle and in the second group, 20 animals were submitted to the same procedure but during the gravidic-puerperal cycle. Variations in hyaluronic acid concentration was not observed during the estral cycle. In the gravidic puerperal cycle group, an increase in hyaluronic acid concentration was observed in the puerperal subgroup. Comparing the two groups of estral and gravidic-puerperal cycles, no difference was observed. In comparing all subgroups of estral and gravidic-puerperal cycles, an increase in hyaluronic acid concentration was noticed only in the puerperal phase.

  13. Effect of citric acid concentration and hydrolysis time on physicochemical properties of sweet potato starches.

    Science.gov (United States)

    Surendra Babu, Ayenampudi; Parimalavalli, Ramanathan; Rudra, Shalini Gaur

    2015-09-01

    Physicochemical properties of citric acid treated sweet potato starches were investigated in the present study. Sweet potato starch was hydrolyzed using citric acid with different concentrations (1 and 5%) and time periods (1 and 11 h) at 45 °C and was denoted as citric acid treated starch (CTS1 to CTS4) based on their experimental conditions. The recovery yield of acid treated starches was above 85%. The CTS4 sample displayed the highest amylose (around 31%) and water holding capacity its melting temperature was 47.66 °C. The digestibility rate was slightly increased for 78.58% for the CTS3 and CTS4. The gel strength of acid modified starches ranged from 0.27 kg to 1.11 kg. RVA results of acid thinned starches confirmed a low viscosity profile. CTS3 starch illustrated lower enthalpy compared to all other modified starches. All starch samples exhibited a shear-thinning behavior. SEM analysis revealed that the extent of visible degradation was increased at higher hydrolysis time and acid concentration. The CTS3 satisfied the criteria required for starch to act as a fat mimetic. Overall results conveyed that the citric acid treatment of sweet potato starch with 5% acid concentration and 11h period was an ideal condition for the preparation of a fat replacer. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Effects of Low Phytanic Acid-Concentrated DHA on Activated Microglial Cells: Comparison with a Standard Phytanic Acid-Concentrated DHA.

    Science.gov (United States)

    Ruiz-Roso, María Belén; Olivares-Álvaro, Elena; Quintela, José Carlos; Ballesteros, Sandra; Espinosa-Parrilla, Juan F; Ruiz-Roso, Baltasar; Lahera, Vicente; de Las Heras, Natalia; Martín-Fernández, Beatriz

    2018-05-30

    Docosahexaenoic acid (DHA, 22:6 n-3) is an essential omega-3 (ω-3) long chain polyunsaturated fatty acid of neuronal membranes involved in normal growth, development, and function. DHA has been proposed to reduce deleterious effects in neurodegenerative processes. Even though, some inconsistencies in findings from clinical and pre-clinical studies with DHA could be attributed to the presence of phytanic acid (PhA) in standard DHA treatments. Thus, the aim of our study was to analyze and compare the effects of a low PhA-concentrated DHA with a standard PhA-concentrated DHA under different neurotoxic conditions in BV-2 activated microglial cells. To this end, mouse microglial BV-2 cells were stimulated with either lipopolysaccharide (LPS) or hydrogen peroxide (H 2 O 2 ) and co-incubated with DHA 50 ppm of PhA (DHA (PhA:50)) or DHA 500 ppm of PhA (DHA (PhA:500)). Cell viability, superoxide anion (O 2 - ) production, Interleukin 6 (L-6), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), glutathione peroxidase (GtPx), glutathione reductase (GtRd), Caspase-3, and the brain-derived neurotrophic factor (BDNF) protein expression were explored. Low PhA-concentrated DHA protected against LPS or H 2 O 2 -induced cell viability reduction in BV-2 activated cells and O 2 - production reduction compared to DHA (PhA:500). Low PhA-concentrated DHA also decreased COX-2, IL-6, iNOS, GtPx, GtRd, and SOD-1 protein expression when compared to DHA (PhA:500). Furthermore, low PhA-concentrated DHA increased BDNF protein expression in comparison to DHA (PhA:500). The study provides data supporting the beneficial effect of low PhA-concentrated DHA in neurotoxic injury when compared to a standard PhA-concentrated DHA in activated microglia.

  15. Influence of phytic acid concentration on performance of phytic acid conversion coatings on the AZ91D magnesium alloy

    International Nuclear Information System (INIS)

    Cui Xiufang; Li Ying; Li Qingfen; Jin Guo; Ding Minghui; Wang Fuhui

    2008-01-01

    In this study, the phytic acid conversion coating, a new environmentally friendly chemical protective coating for magnesium alloys, was prepared. The influences of phytic acid concentration on the formation process, microstructure, chemical state and corrosion resistance of the conversion coatings on AZ91D magnesium alloy were investigated by means of weight gain measurement, field-emission scanning electron microscopy (FESEM), Fourier transform infrared (FTIR) spectroscopy, potentiodynamic polarization method and electrochemical impedance spectroscopy (EIS), respectively. And the depth profile of all elements in the optimal conversion coatings was analyzed by auger electron spectroscopy (AES). The results show that the growth, microstructure, chemical state and corrosion resistance of the conversion coatings are all obviously affected by the phytic acid concentration. The concentration of 5 g l -1 corresponds to the maximum weight gain. The main elements of the coating are Mg, Al, O, P, and C, which are distributed gradually in depth. The functional groups of conversion coatings formed in higher concentration phytic acid solution are closer to the constituent of phytic acid than those formed in lower concentration phytic acid solution. The coatings formed in 1-5 g l -1 are integrated and uniform. However, those formed in 20-50 g l -1 have some micro-cracks on the α phase. The coating formed in 5 g l -1 has the best corrosion resistance, whose open circuit current density decreases about six orders than that of the untreated sample, although the coatings deposited in 1-20 g l -1 can all improve the corrosion resistance of AZ91D

  16. Relationships between fruit nutrients and concentrations of flavonoids and chlorogenic acid in 'Elstar' apple skin

    NARCIS (Netherlands)

    Awad, M.A.; Jager, de A.

    2002-01-01

    The relationships between fruit N, P, K, Mg and Ca concentrations during the season and flavonoid and chlorogenic acid concentrations in skin of `Elstar¿ apples at maturity have been studied during three seasons in a nutrition experiment (with the mutant `Elshof¿), and in a separate experiment with

  17. Influence of zirconium ion concentration in model extraction systems TBP - diluents - Zr+4 - nitric acid

    International Nuclear Information System (INIS)

    Rogoz, F.; Tlalka, M.

    1987-07-01

    In systems containing TBP, MBP, DBP and 1-butanol stable emulsions and precipitates are formed which separation is difficult in certain domain of concentration in zirconium ions. MPB and DBP increase stability of primary emulsion in kerosen and carbon tetrachloride but for different concentrations of nitric acid. Addition of 1-butanol decreases slightly the stability of primary emulsion [fr

  18. Serum uric acid concentrations are directly associated with the presence of benign multiple sclerosis.

    Science.gov (United States)

    Simental-Mendía, Esteban; Simental-Mendía, Luis E; Guerrero-Romero, Fernando

    2017-09-01

    It has been reported that patients with multiple sclerosis (MS) exhibit lower serum uric acid levels; however, the association between uric acid concentrations and benign MS (BMS) has not been assessed. Hence, the objective of the present study was to determine whether the serum concentrations of uric acid are associated with the presence of BMS. Men and non-pregnant women over 16 years of age with diagnosis of MS were enrolled in a cross-sectional study. Expanded Disability Status Scale score acid were exclusion criteria. According to subtype of disease, the eligible patients were allocated into groups with BMS and other varieties of MS. A logistic regression analysis was conducted in order to evaluate the association between serum concentrations of uric acid and BMS. A total of 106 patients were included, 39 in the group with BMS and 67 in the group with other varieties of MS. The logistic regression analysis adjusted by age, sex, and disease duration showed that increased concentrations of uric acid, indeed within the physiological levels, are significantly associated with the presence of BMS (OR = 2.60; 95% CI: 1.55-4.38, p uric acid, indeed within the physiological range, are likely linked to the presence of BMS.

  19. Alterations in serum amino acid concentrations in dogs with protein-losing enteropathy.

    Science.gov (United States)

    Kathrani, Aarti; Allenspach, Karin; Fascetti, Andrea J; Larsen, Jennifer A; Hall, Edward J

    2018-03-31

    Certain amino acids are decreased in humans with inflammatory bowel disease (IBD) and supplementation with the same amino acids has shown beneficial effects in animal models of IBD. Currently, the amino acid status of dogs with protein-losing enteropathy (PLE) is unknown. To determine if serum amino acid concentrations are abnormal in dogs with PLE and correlated with clinical and laboratory variables and outcome. Thirty client-owned dogs diagnosed with PLE and 12 apparently healthy dogs seen at Bristol Veterinary School. Retrospective study using stored residual serum from fasted dogs with PLE, collected at the time of diagnostic investigation and from apparently healthy dogs. Serum was analyzed for 30 amino acids using an automated high-performance liquid chromatography amino acid analyzer. Serum tryptophan concentrations were significantly decreased in dogs with PLE (median, 22 nmol/mL; range, 1-80 nmol/mL) compared with apparently healthy control dogs (median, 77.5 nmol/mL; range, 42-135 nmol/mL, P PLE and apparently healthy. Serum tryptophan concentrations were also significantly correlated with serum albumin concentrations in dogs with PLE (P = .001, R 2 = 0.506). Decreased serum tryptophan concentration might play a role in the pathogenesis of canine PLE or be a consequence of the disease. © 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  20. A procedure for reducing the concentration of hydrogen ions in acid anionic eluate and equipment therefore

    International Nuclear Information System (INIS)

    Parobek, P.; Baloun, S.; Plevac, S.

    1989-01-01

    The method is described of reducing the concentration of hydrogen ions in acid anionic eluate produced in the separation of uranium or other metals, in which anion exchanger elution, precipitation, filtration and precipitate and anion exchanger washing are used. The technological line for such elution comprises at least one ion exchange column and at least one container. They together form the first and the second stages of preparation of the acid anion elution solution, the sorption-elution separation of hydrogen ions on an cation exchanger being inserted between them. The preparation of the solution is divide into two stages. In the first stage, the acid and part of the solution for the preparation of the acid anion elution solution are supplied. The resulting enriched acid elution solution is fe onto the cation exchanger where the hydrogen ion concentration i reduced. It is then carried into the second stage where it is mixed with the remaining part of the solution. (B.S.)

  1. Effects of squat exercise and branched-chain amino acid supplementation on plasma free amino acid concentrations in young women.

    Science.gov (United States)

    Shimomura, Yoshiharu; Kobayashi, Hisamine; Mawatari, Kazunori; Akita, Keiichi; Inaguma, Asami; Watanabe, Satoko; Bajotto, Gustavo; Sato, Juichi

    2009-06-01

    The present study was conducted to examine alterations in plasma free amino acid concentrations induced by squat exercise and branched-chain amino acid (BCAA) supplementation in young, untrained female subjects. In the morning on the exercise session day, participants ingested drinks containing either BCAA (isoleucine:leucine:valine=1:2.3:1.2) or dextrin (placebo) at 0.1 g/kg body weight 15 min before a squat exercise session, which consisted of 7 sets of 20 squats, with 3 min intervals between sets. In the placebo trial, plasma BCAA concentrations were decreased subsequent to exercise, whereas they were significantly increased in the BCAA trial until 2 h after exercise. Marked changes in other free amino acids in response to squat exercise and BCAA supplementation were observed. In particular, plasma concentrations of methionine and aromatic amino acids were temporarily decreased in the BCAA trial, being significantly lower than those in the placebo trial. These results suggest that BCAA intake before exercise affects methionine and aromatic amino acid metabolism.

  2. Concentration of eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA of Asian catfish oil by urea complexation: optimization of reaction conditions

    Directory of Open Access Journals (Sweden)

    Pornpisanu Thammapat

    2016-04-01

    Full Text Available Optimization of the concentrating conditions of eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA extracted from Asian catfish oil was studied to obtain a maximum concentration. The crude fish oil was extracted from the belly flap and adipose tissue of Asian catfish, and the extracted oil was used as fresh crude oil. The EPA and DHA were concentrated by the urea complexation method. A hexagonal rotatable design was applied to examine the effects of crystallization temperature and urea-to-fatty acid ratio on the total content of EPA and DHA (Y1 and the liquid recovery yield (Y2 . The second order polynomial regression models for Y1 and Y2 were employed to generate the response surfaces. Under the optimum conditions of -20 °C and a urea-to-fatty acid ratio of 4 (w/w, the total concentration of EPA and DHA could be increased by up to 88%, while a liquid recovery yield of 26% was obtained.

  3. Uric acid concentrations are associated with insulin resistance and birthweight in normotensive pregnant women.

    Science.gov (United States)

    Laughon, S Katherine; Catov, Janet; Roberts, James M

    2009-12-01

    We sought to investigate whether uric acid concentrations are increased in pregnant women with insulin resistance and to correlate both with fetal growth. Uric acid, glucose, and insulin were measured in plasma at 20.4 (+/-2.0) weeks' gestation in 263 women. The association between uric acid and insulin resistance, as estimated using the homeostasis model assessment (HOMA), was analyzed and related to birthweights. In 212 (80.6%) women who remained normotensive throughout pregnancy, HOMA increased 1.23 U per 1-mg/dL increase in uric acid (95% confidence interval, 1.07-1.42; P=.003). Infants born to normotensive women in the upper quartile of uric acid and lowest HOMA quartile weighed 435.6 g less than infants of women with highest uric acid and HOMA quartiles (Pinsulin resistance in midpregnancy. Hyperuricemia was associated with lower birthweight in normotensive women, and this effect was attenuated by insulin resistance.

  4. Corrosion by concentrated sulfuric acid in carbon steel pipes and tanks: state of the art

    Energy Technology Data Exchange (ETDEWEB)

    Panossian, Zehbour; Almeida, Neusvaldo Lira de; Sousa, Raquel Maria Ferreira de [Instituto de Pesquisas Tecnologicas (IPT), Sao Paulo, SP (Brazil); Pimenta, Gutemberg de Souza [PETROBRAS S.A., Rio de Janeiro, RJ (Brazil). Centro de Pesquisas e Desenvolvimento (CENPES); Marques, Leandro Bordalo Schmidt [PETROBRAS Engenharia, Rio de Janeiro, RJ (Brazil)

    2009-07-01

    PETROBRAS, allied to the policy of reduction of emission of pollutants, has been adjusting the processes of the new refineries to obtain products with lower sulfur content. Thus, the sulfur dioxide, extracted from the process gases of a new refinery to be built in the Northeast, will be used to produce sulfuric acid with concentration between (94-96) %. This acid will be stored in carbon steel tanks and transported through a buried 8-km carbon steel pipe from the refinery to a pier, where it will be loaded onto ships and sent to the consumer markets. Therefore, the corrosion resistance of carbon steel by concentrated acid will become a great concern for the mentioned storage and transportation. When the carbon steel comes into contact with concentrated sulfuric acid, there is an immediate acid attack with the formation of hydrogen gas and ferrous ions which, in turn, forms a protective layer of FeSO{sub 4} on the metallic surface. The durability of the tanks and pipes made of carbon steel will depend on the preservation of this protective layer. This work presents a review of the carbon steel corrosion in concentrated sulfuric acid and discusses the preventive methods against this corrosion, including anodic protection. (author)

  5. Wolframite Conversion in Treating a Mixed Wolframite-Scheelite Concentrate by Sulfuric Acid

    Science.gov (United States)

    Shen, Leiting; Li, Xiaobin; Zhou, Qiusheng; Peng, Zhihong; Liu, Guihua; Qi, Tiangui; Taskinen, Pekka

    2018-02-01

    Complete wolframite conversion in sulfuric acid is significant for expanding the applicability of the sulfuric acid method for producing ammonium paratungstate. In this paper, the conversion of wolframite in treating a mixed wolframite-scheelite concentrate by sulfuric acid was studied systematically. The results show that the conversion of wolframite in sulfuric acid is more difficult than that of scheelite, requiring rigorous reaction conditions. A solid H2WO4 layer forms on the surfaces of the wolframite particles and becomes denser with increasing H2SO4 concentration, thus hindering the conversion. Furthermore, the difficulty in wolframite conversion can be mainly attributed to the accumulation of Fe2+ (and/or Mn2+) in the H2SO4 solution, which can be solved by reducing Fe2+ (and/or Mn2+) concentration through oxidization and/or a two-stage process. Additionally, the solid converted product of the mixed wolframite-scheelite concentrate has an excellent leachability of tungsten in an aqueous ammonium carbonate solution at ambient temperature, with approximately 99% WO3 recovery. This work presents a route for manufacturing ammonium paratungstate by treating the mixed concentrate in sulfuric acid followed by leaching in ammonium carbonate solution.

  6. Changes of amino acid concentrations in the rat vestibular nuclei after inferior cerebellar peduncle transection.

    Science.gov (United States)

    Sun, Yizhe; Godfrey, Donald A; Godfrey, Timothy G; Rubin, Allan M

    2007-02-15

    Although there is a close relationship between the vestibular nuclear complex (VNC) and the cerebellum, little is known about the contribution of cerebellar inputs to amino acid neurotransmission in the VNC. Microdissection of freeze-dried brain sections and high-performance liquid chromatography (HPLC) were combined to measure changes of amino acid concentrations within the VNC of rats following transection of the cerebellovestibular connections in the inferior cerebellar peduncle. Distributions of 12 amino acids within the VNC at 2, 4, 7, and 30 days after surgery were compared with those for control and sham-lesioned rats. Concentrations of gamma-aminobutyric acid (GABA) decreased by 2 days after unilateral peduncle transection in nearly all VNC regions on the lesioned side and to lesser extents on the unlesioned side and showed partial recovery up to 30 days postsurgery. Asymmetries between the two sides of the VNC were maintained through 30 days. Glutamate concentrations were reduced bilaterally in virtually all regions of the VNC by 2 days and showed complete recovery in most VNC regions by 30 days. Glutamine concentrations increased, starting 2 days after surgery, especially on the lesioned side, so that there was asymmetry generally opposite that of glutamate. Concentrations of taurine, aspartate, and glycine also underwent partially reversible changes after peduncle transection. The results suggest that GABA and glutamate are prominent neurotransmitters in bilateral projections from the cerebellum to the VNC and that amino acid metabolism in the VNC is strongly influenced by its cerebellar connections.

  7. The concentration of free amino acids in blood serum of dairy cows with primary ketosis.

    Science.gov (United States)

    Marczuk, J; Brodzki, P; Brodzki, A; Kurek, Ł

    2018-03-01

    Ketosis is a common condition found in the initial stages of lactation in high-yielding dairy cows. The major cause of ketosis is a negative energy balance. During the energy deficiency, proteolysis processes develop parallel to lipolysis. During proteolysis, muscle tissue can be used as a source of amino acid. To date, the participation of amino acids in gluconeogenesis (glucogenic amino acids) and ketogenesis (ketogenic amino acids) has not been determined in detail. This paper presents the study on determination of the parameters of protein and free amino acid metabolism in blood serum of dairy cows with primary ketosis compared to healthy cows. This study contributes to better understanding of the role of amino acids in pathogenesis of ketosis. A total of 30 cows, divided into two groups: experimental (15 cows with ketosis) and control (15 healthy cows), were included in the study. The concentrations of glucose, β-hydroxybutyrate, total protein, albumin, urea, and free amino acids were determined in peripheral blood. Statistically significantly higher concentrations of glutamine, glutamic acid, isoleucine (p≤0.001), and tyrosine (p≤0.05) were found in cows with primary ketosis compared to healthy cows. Significant decrease in the concentrations of asparagine, histidine, methionine, and serine (p≤0.001), alanine, leucine, lysine and proline (p≤0.05) was observed. Significant increase of total ketogenic and glucogenic amino acids (p≤0.05), and an increased ratio of total ketogenic and glucogenic amino acids to total amino acids (p≤0.001) were noted in cows with ketosis. In our study, the changes, in particular observed in amino acid concentration in cows with primary ketosis, indicate its intensive use in both ketogenesis and gluconeogenesis processes. Therefore, a detailed understanding of the role that amino acids play in gluconeogenesis and ketogenesis will improve ketosis diagnostics and monitoring the course of a ketosis episode. Perhaps, the

  8. Device for regulating light water nuclear reactors by changing the boric acid concentration in the cooling water circuit

    International Nuclear Information System (INIS)

    Brown, W.W.; Van der Schoot, M.R.

    1980-01-01

    Small changes in boric acid concentration can be carried out quickly by a combination of an ion exchanger with temperature-dependent capacity and an evaporator. No boric acid need be extracted from the circuit or added to it. However, if large changes of concentration are required, boric acid has to be added. The evaporator is then used to separate distilled water and concentrated boric acid when the cooling water is diluted. (DG) [de

  9. Efficiency of deactivation of skin contaminated with 241Am in concentrated acid

    International Nuclear Information System (INIS)

    Il'in, L.A.; Ivannikov, A.T.; Popov, B.A.; Altukhova, G.A.; Parfenova, I.M.

    1980-01-01

    Data are given on the decontamination, by means of water, soap, and Pentacin, of a burnt skin surface contaminated by 241 Am in 0.05, 1, or 8 n HNO 3 . The effectiveness of such decontamination depended on the concentration of the acid, the time when treatment started, and the washing agent used. The most effective agent proved to be a 3% soap solution which, if applied early enough (within 5 min), removed as much as 98% of the radionuclide. Soap treatment diminished considerably the severity of the chemical burn and the penetration of 241 Am into the derma and its skin absorption. The effect from the decontamination was less marked when it was done at a later time and when the acid was more concentrated. Preliminary recommendations on decontamination of skin exposed to radionuclides in concentrated acids are given [ru

  10. Threshold changes in rat brain docosahexaenoic acid incorporation and concentration following graded reductions in dietary alpha-linolenic acid

    Science.gov (United States)

    Taha, Ameer Y.; Chang, Lisa; Chen, Mei

    2016-01-01

    Background This study tested the dietary level of alpha-linolenic acid (α-LNA, 18:3n-3) sufficient to maintain brain 14C-Docosahexaenoic acid (DHA, 22:6n-3) metabolism and concentration following graded α-LNA reduction. Methods 18–21 day male Fischer-344 (CDF) rats were randomized to the AIN-93G diet containing as a % of total fatty acids, 4.6% (“n-3 adequate”), 3.6%, 2.7%, 0.9% or 0.2% (“n-3 deficient”) α-LNA for 15 weeks. Rats were intravenously infused with 14C-DHA to steady state for 5 minutes, serial blood samples collected to obtain plasma and brains excised following microwave fixation. Labeled and unlabeled DHA concentrations were measured in plasma and brain to calculate the incorporation coefficient, k*, and incorporation rate, Jin. Results Compared to 4.6% α-LNA controls, k* was significantly increased in ethanolamine glycerophospholipids in the 0.2% α-LNA group. Circulating unesterified DHA and brain incorporation rates (Jin) were significantly reduced at 0.2% α-LNA. Brain total lipid and phospholipid DHA concentrations were reduced at or below 0.9% α-LNA. Conclusion Threshold changes for brain DHA metabolism and concentration were maintained at or below 0.9% dietary α-LNA, suggesting the presence of homeostatic mechanisms to maintain brain DHA metabolism when dietary α-LNA intake is low. PMID:26869088

  11. Concentration and distribution of dissolved amino acids in a shallow hydrothermal system, Vulcano Island (Italy)

    Energy Technology Data Exchange (ETDEWEB)

    Svensson, E.; Skoog, A. [University of Connecticut, Groton, CT (United States). Dept. of Marine Sciences; Amend, J.P. [Washington University, St. Louis, MO (United States). Dept. of Earth and Planetary Sciences

    2004-09-01

    Hydrothermal systems are known to harbour a large number of microorganisms, but the organic chemical composition of the solution that comprises their potential substrate is largely unknown. Concentrations and distributions of dissolved free amino acids (DFAA) and dissolved combined amino acids (DCAA) were determined in fluids from the moderate-temperature (42-89{sup o}C), shallow hydrothermal system on the volcanically active island of Vulcano, Italy. The seven samples represent three different geological settings on the island; shallow ({approx} 1 m) submarine vents, geothermal wells, and seeps in heated beach sediments, in addition to ambient local seawater from the bay, Baia di Levante. All hydrothermal sites, with one exception, had TDAA concentrations that were 3-114 times higher than local seawater in Baia di Levante. There were large similarities in amino acid concentration and composition among samples from the same geological setting. The highest amino acid concentrations were found at sites with acidic and reducing conditions, which also had the largest freshwater component. An unusually high fraction of the TDAA pool was represented by DFAA (33-87%), possibly due to in situ acid hydrolysis of DCAA to DFAA. Both DFAA and DCAA concentrations were correlated to DOC, indicating similar source and sink functions for these pools. The yield of TDAA (TDAA-carbon as fraction of organic carbon) ranged from 2% to 25%, which is high compared with non-hydrothermal settings, and indicates high biological lability. The mole fraction of {beta}-alanine plus {gamma}-aminobutyric acid (% BALA + GABA) was 2-2.7% of TDAA, also indicating high biological lability. Owing to the high over-all amino acid concentrations, the high fraction of DFAAs, and the high biological lability of the organic matter, organic matter in general and amino acids specifically could represent significant carbon and energy sources for archaea and bacteria in this hydrothermal system. The clear

  12. Mass transfer during sulfuric acid concentration by evaporation into the air flow

    Directory of Open Access Journals (Sweden)

    V. K. Lukashov

    2016-12-01

    Full Text Available This article shows the results of the study of mass transfer under periodic concentration of sulfuric acid by evaporation inthe gas flow, neutral with respect to the components of acid.Used mathematical model for mass transferbases on the proposed simplified physical representations.This model has allowed to construct an algorithm for calculation the coefficient of mass transfer from the liquid phase into the gas flow. The algorithm uses the experimental data of change the amount of acid and concentration of the water taken from the laboratory tests. Time-based Nusselt diffusion criterion represent the results of the study at different modes of the evaporation process.It has been found that the character of the influence of temperature and initial acid concentration on Nusselt diffusion criterion depends on the variation range of the mass fraction of water in the acid.It is shown that these dependences are well approximated by an exponential function from the dimensionless parameters of the process. This allows usingthem for calculation the mass transfer coefficient into the gas phase in a batch process of concentrating in the range of investigated modes.

  13. Perfluoroalkyl Acid Concentrations in Blood Samples Subjected to Transportation and Processing Delay.

    Science.gov (United States)

    Bach, Cathrine Carlsen; Henriksen, Tine Brink; Bossi, Rossana; Bech, Bodil Hammer; Fuglsang, Jens; Olsen, Jørn; Nohr, Ellen Aagaard

    2015-01-01

    In studies of perfluoroalkyl acids, the validity and comparability of measured concentrations may be affected by differences in the handling of biospecimens. We aimed to investigate whether measured plasma levels of perfluoroalkyl acids differed between blood samples subjected to delay and transportation prior to processing and samples with immediate processing and freezing. Pregnant women recruited at Aarhus University Hospital, Denmark, (n = 88) provided paired blood samples. For each pair of samples, one was immediately processed and plasma was frozen, and the other was delayed and transported as whole blood before processing and freezing of plasma (similar to the Danish National Birth Cohort). We measured 12 perfluoroalkyl acids and present results for compounds with more than 50% of samples above the lower limit of quantification. For samples taken in the winter, relative differences between the paired samples ranged between -77 and +38% for individual perfluoroalkyl acids. In most cases concentrations were lower in the delayed and transported samples, e.g. the relative difference was -29% (95% confidence interval -30; -27) for perfluorooctane sulfonate. For perfluorooctanoate there was no difference between the two setups [corresponding estimate 1% (0, 3)]. Differences were negligible in the summer for all compounds. Transport of blood samples and processing delay, similar to conditions applied in some large, population-based studies, may affect measured perfluoroalkyl acid concentrations, mainly when outdoor temperatures are low. Attention to processing conditions is needed in studies of perfluoroalkyl acid exposure in humans.

  14. Hybrid ATDL-gamma distribution model for predicting area source acid gas concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Jakeman, A J; Taylor, J A

    1985-01-01

    An air quality model is developed to predict the distribution of concentrations of acid gas in an urban airshed. The model is hybrid in character, combining reliable features of a deterministic ATDL-based model with statistical distributional approaches. The gamma distribution was identified from a range of distributional models as the best model. The paper shows that the assumptions of a previous hybrid model may be relaxed and presents a methodology for characterizing the uncertainty associated with model predictions. Results are demonstrated for the 98-percentile predictions of 24-h average data over annual periods at six monitoring sites. This percentile relates to the World Health Organization goal for acid gas concentrations.

  15. Investigations on uranyl nitrate solubility in nitric acid in different concentrations at temperatures of 50C

    International Nuclear Information System (INIS)

    Deigele, E.

    1983-01-01

    The solubility of uranyl nitrate was studied in nitric acid solutions of different concentrations at a temperature of 5 0 C. This temperature was chosen with a view to using water as coolant and to facilitate the handling of the strong acid solutions. Accurate curves were established by a multitude of accurate measurements in the high concentration range. Further solubility curves can be derived from this basic curve. Some of the precipitates in the interesting regions of the solubility curve were analyzed. (orig./EF) [de

  16. Serum free amino acid concentration in hepatic lipidosis of dairy cows in the periparturient period.

    Science.gov (United States)

    Shibano, Ken-ichi; Kawamura, Seiichi

    2006-04-01

    Blood samples were taken from eight multiparous cows at a dairy farm on eight occasions between the prepartum period and peak lactation to study the serum concentrations of amino acids and biochemical constituents. The cows were classified as having either severe hepatic lipidosis (HL) or non-hepatic lipidosis (non-HL) according to their clinical condition after calving and changes in serum biochemical parameters. The serum concentrations of beta-hydroxybutyric acid were higher in the HL group than in the non-HL group (ANOVA: phepatic lipidosis.

  17. Effects of debrisoquin and haloperidol on plasma homovanillic acid concentration in schizophrenic patients.

    Science.gov (United States)

    Davidson, M; Losonczy, M F; Mohs, R C; Lesser, J C; Powchik, P; Freed, L B; Davis, B M; Mykytyn, V V; Davis, K L

    1987-12-01

    Plasma levels of the dopamine metabolite homovanillic acid (pHVA) may potentially reflect upon central dopamine activity. This study examines the effects of debrisoquin, haloperidol, and the two drugs combined on pHVA concentrations of schizophrenic patients. Debrisoquin is a drug that suppresses the peripheral formation of homovanillic acid without affecting the central formation. Acute haloperidol administration consistently increased pHVA concentrations in patients pretreated or not pretreated with debrisoquin, suggesting that this increment reflects haloperidol's central and not peripheral effects.

  18. Study of the interaction metallic cation - ligand in concentrated phosphorus acid media

    International Nuclear Information System (INIS)

    Sefiani, N.; Azzi, M.; Hlaibi, M.; Kossair, A.

    2005-01-01

    The phosphoric acid is more and more used with a high purity. The recovery of recycling element (uranium, vanadium, rare earth...) and the elimination of toxic element (cadmium, molybdenum, lead...) contained in the phosphoric acid are generally realized by extraction or precipitation. It is then very important to understand these impurities behavior in the phosphoric media in order to control their elimination. In this work, the authors considered the presence of some metallic cations (V, Al, fe, U) and fluorides ions as impurity in concentrated phosphoric acid media. (A.L.B.)

  19. 59Ni and 63Ni separation from boric acid concentrates produced at NPP

    International Nuclear Information System (INIS)

    Fisera, O.

    2010-01-01

    Procedure for direct separation of radionickel from boric acid concentrate was developed. Quantitative separation from 100 mL of real concentrate on the column filled with 3 mL of PAN-DMG composite material was achieved. PAN-DMG material (dimethylglyoxime in porous beads of polyacrylonitrile) was compared with Ni Resin and DMG-PAN material exhibited higher sorption capacity for nickel than Ni Resin. (author)

  20. D-amino acid oxidase activator gene (DAOA) variation affects cerebrospinal fluid homovanillic acid concentrations in healthy Caucasians

    DEFF Research Database (Denmark)

    Andreou, Dimitrios; Saetre, Peter; Werge, Thomas

    2012-01-01

    The D-amino acid oxidase activator (DAOA) protein regulates the function of D-amino oxidase (DAO), an enzyme that catalyzes the oxidative deamination of D-3,4-dihydroxyphenylalanine (D-DOPA) and D-serine. D-DOPA is converted to L-3,4-DOPA, a precursor of dopamine, whereas D-serine participates...... in glutamatergic transmission. We hypothesized that DAOA polymorphisms are associated with dopamine, serotonin and noradrenaline turnover in the human brain. Four single-nucleotide polymorphisms, previously reported to be associated with schizophrenia, were genotyped. Cerebrospinal fluid (CSF) samples were drawn...... by lumbar puncture, and the concentrations of the major dopamine metabolite homovanillic acid (HVA), the major serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) and the major noradrenaline metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) were measured. Two of the investigated polymorphisms, rs...

  1. Diel changes in metal concentrations in a geogenically acidic river: Rio Agrio, Argentina

    Science.gov (United States)

    Parker, Stephen R.; Gammons, Christopher H.; Pedrozo, Fernando L.; Wood, Scott A.

    2008-12-01

    Rio Agrio in Patagonia, Argentina is a geogenically acidic stream that derives its low-pH waters from condensation of acidic gases near its headwaters on the flanks of the active Copahue Volcano. This study reports the results of three diel (24-h) water samplings in three different pH regimes (3.2, 4.4 and 6.3) along the river. Changes in the concentration and speciation of Fe dominated the diel chemical changes at all three sites, although the timing and intensity of these cycles were different in each reach. At the two acidic sampling sites, total dissolved Fe and dissolved Fe(III) concentrations decreased during the day and increased at night, whereas dissolved Fe(II) showed the reverse pattern. These cycles are explained by Fe(III) photoreduction, as well as enhanced rates of precipitation of hydrous ferric oxide (HFO) during the warm afternoon hours. A strong correlation was observed between Fe(III) and As at the furthest upstream (pH 3.2) site, most likely due to co-precipitation of As with HFO. At the downstream (pH 6.3) location, Fe(II) concentrations increased at night, as did concentrations of rare earth elements and dissolved Al. Photoreduction does not appear to be an important process at pH 6.3, although it may be indirectly responsible for the observed diel cycle of Fe(II) due to advection of photochemically produced Fe(II) from acidic upstream waters. The results of this study of a naturally-acidic river are very similar to diel trends recently obtained from mining-impacted streams receiving acid rock drainage. The results are also used to explore the link between geochemistry and microbiology in acidic eco-systems. For example, Fe(III) photoreduction produces chemical potential energy (in the form of metastable Fe 2+) that helps support the bacterial community in this unique extreme environment.

  2. Salicylic acid induces apoptosis in colon carcinoma cells grown in-vitro: Influence of oxygen and salicylic acid concentration

    Energy Technology Data Exchange (ETDEWEB)

    Zitta, Karina; Meybohm, Patrick; Bein, Berthold; Huang, Ying; Heinrich, Christin; Scholz, Jens; Steinfath, Markus; Albrecht, Martin, E-mail: Albrecht@anaesthesie.uni-kiel.de

    2012-04-15

    In solid tumors the hypoxic environment can promote tumor progression and resistance to therapy. Recently, acetylsalicylic acid a major component of analgesic drugs and its metabolite salicylic acid (SA) have been shown to reduce the risk of colon cancer, but the mechanisms of action remain still unclear. Here we elucidate the effects of physiologically relevant concentrations of SA on colon carcinoma cells (CaCo-2) grown under normoxic and hypoxic conditions. Western blotting, caspase-3/7 apoptosis assays, MTS cell-proliferation assays, LDH cytotoxicity assays and hydrogen peroxide measurements were performed to investigate the effects of 1 and 10 {mu}M SA on CaCo-2 cells grown under normoxic conditions and cells exposed to hypoxia. Under normoxic conditions, SA did not influence cell proliferation or LDH release of CaCo-2 cells. However, caspase-3/7 activity was significantly increased. Under hypoxia, cell proliferation was reduced and LDH release and caspase-3/7 activities were increased. None of these parameters was altered by the addition of SA under hypoxic conditions. Hypoxia increased hydrogen peroxide concentrations 300-fold and SA significantly augmented the release of hydrogen peroxide under normoxic, but not under hypoxic conditions. Phosphorylation of the pro-survival kinases akt and erk1/2 was not changed by SA under hypoxic conditions, whereas under normoxia SA reduced phosphorylation of erk1/2 after 2 hours. We conclude that in colon carcinoma cells effects of SA on apoptosis and cellular signaling are dependent on the availability of oxygen. -- Highlights: Black-Right-Pointing-Pointer Effects of salicylic acid on colon carcinoma cells grown under normoxic and hypoxic conditions Black-Right-Pointing-Pointer Salicylic acid increases caspase-3/7 activity and hydrogen peroxide release under normoxia Black-Right-Pointing-Pointer Salicylic acid decreases pro-survival erk-1/2 phosphorylation under normoxia Black-Right-Pointing-Pointer Salicylic acid does

  3. Salicylic acid induces apoptosis in colon carcinoma cells grown in-vitro: Influence of oxygen and salicylic acid concentration

    International Nuclear Information System (INIS)

    Zitta, Karina; Meybohm, Patrick; Bein, Berthold; Huang, Ying; Heinrich, Christin; Scholz, Jens; Steinfath, Markus; Albrecht, Martin

    2012-01-01

    In solid tumors the hypoxic environment can promote tumor progression and resistance to therapy. Recently, acetylsalicylic acid a major component of analgesic drugs and its metabolite salicylic acid (SA) have been shown to reduce the risk of colon cancer, but the mechanisms of action remain still unclear. Here we elucidate the effects of physiologically relevant concentrations of SA on colon carcinoma cells (CaCo-2) grown under normoxic and hypoxic conditions. Western blotting, caspase-3/7 apoptosis assays, MTS cell-proliferation assays, LDH cytotoxicity assays and hydrogen peroxide measurements were performed to investigate the effects of 1 and 10 μM SA on CaCo-2 cells grown under normoxic conditions and cells exposed to hypoxia. Under normoxic conditions, SA did not influence cell proliferation or LDH release of CaCo-2 cells. However, caspase-3/7 activity was significantly increased. Under hypoxia, cell proliferation was reduced and LDH release and caspase-3/7 activities were increased. None of these parameters was altered by the addition of SA under hypoxic conditions. Hypoxia increased hydrogen peroxide concentrations 300-fold and SA significantly augmented the release of hydrogen peroxide under normoxic, but not under hypoxic conditions. Phosphorylation of the pro-survival kinases akt and erk1/2 was not changed by SA under hypoxic conditions, whereas under normoxia SA reduced phosphorylation of erk1/2 after 2 hours. We conclude that in colon carcinoma cells effects of SA on apoptosis and cellular signaling are dependent on the availability of oxygen. -- Highlights: ► Effects of salicylic acid on colon carcinoma cells grown under normoxic and hypoxic conditions ► Salicylic acid increases caspase-3/7 activity and hydrogen peroxide release under normoxia ► Salicylic acid decreases pro-survival erk-1/2 phosphorylation under normoxia ► Salicylic acid does not influence any of the investigated parameters under hypoxia

  4. Effects of Fungicide Treatment on Free Amino Acid Concentration and Acrylamide-Forming Potential in Wheat.

    Science.gov (United States)

    Curtis, Tanya Y; Powers, Stephen J; Halford, Nigel G

    2016-12-28

    Acrylamide forms from free asparagine and reducing sugars during frying, baking, roasting, or high-temperature processing, and cereal products are major contributors to dietary acrylamide intake. Free asparagine concentration is the determining factor for acrylamide-forming potential in cereals, and this study investigated the effect of fungicide application on free asparagine accumulation in wheat grain. Free amino acid concentrations were measured in flour from 47 varieties of wheat grown in a field trial in 2011-2012. The wheat had been supplied with nitrogen and sulfur and treated with growth regulators and fungicides. Acrylamide formation was measured after the flour had been heated at 180 °C for 20 min. Flour was also analyzed from 24 (of the 47) varieties grown in adjacent plots that were treated in identical fashion except that no fungicide was applied, resulting in visible infection by Septoria tritici, yellow rust, and brown rust. Free asparagine concentration in the fungicide-treated wheat ranged from 1.596 to 3.987 mmol kg -1 , with a significant (p fungicide treatment, the increases in acrylamide ranging from 2.7 to 370%. Free aspartic acid concentration also increased, whereas free glutamic acid concentration increased in some varieties but decreased in others, and free proline concentration decreased. The study showed disease control by fungicide application to be an important crop management measure for mitigating the problem of acrylamide formation in wheat products.

  5. Growing and laying performance of Japanese quail fed diet supplemented with different concentrations of acetic acid

    Directory of Open Access Journals (Sweden)

    Youssef A. Attia

    2013-04-01

    Full Text Available In order to evaluate the effect of acetic acid on growing and laying performance of Japanese Quail (JQ, 180 15-day-old JQ were divided into 4 groups. During the growing (15-42 days of age and laying (43-84 days of age periods, the groups fed the same basal diets supplemented with 0, 1.5, 3 and 6% of acetic acid. Each diet was fed to five replicates of 9 JQ (3 males:6 females during the growing period. During the laying period, 128 birds were housed in 32 cages (4 birds per cage, 1 male and 3 females, 8 replicates per treatment. Birds were housed in wire cages (46L×43W×20H cm in an open room. Acetic acid supplementation at 3% in the diets significantly increased the growth and laying rate and the Haugh unit score. The liver percentage significantly decreased with acetic acid at 6%. Acetic acid at 3% significantly increased hemoglobin concentrations at 6 weeks of age and increased weight of day old chicks hatched. Acetic acid affected the immune system as manifested by an excess of cellular reactions in the intestine as well as lymphoid hyperplasia in the spleen tissue. Degenerative changes in the covering epithelium of the intestinal villi were noted at the 6% concentration of acetic acid. Hepatocyte vacuolation and fatty changes were also observed at this concentration of treatment. In conclusion, 3% acetic acid may be used as a feed supplement for JQ during the growing and laying period to improve the productive performance.

  6. Urea, Uric Acid, Prolactin and fT4 Concentrations in Aqueous Humor of Keratoconus Patients.

    Science.gov (United States)

    Stachon, Tanja; Stachon, Axel; Hartmann, Ulrike; Seitz, Berthold; Langenbucher, Achim; Szentmáry, Nóra

    2017-06-01

    Keratoconus is a noninflammatory disease of the cornea associated with progressive thinning and conical shape. Metabolic alterations in the urea cycle, with changes in collagen fibril stability, oxidative stress, thyroid hormones and prolactin with regulatory effect on biosynthesis and biomechanical stability of corneal stroma, may all play a role in keratoconus etiology. Our purpose was to determine urea, uric acid, prolactin and free thyroxin (fT4) concentrations in human aqueous humor (hAH) of keratoconus and cataract patients. hAH was collected from 100 keratoconus (penetrating keratoplasty) (41.9 ± 14.9 years, 69 males) and 100 cataract patients (cataract surgery) (71.2 ± 12.4 years, 58 males). Urea, uric acid, prolactin and fT4 concentrations were measured by Siemens clinical chemistry or immunoassay system. For statistical analysis, a generalized linear model (GLM) was used. Urea concentration was 11.88 ± 3.03 mg/dl in keratoconus and 16.44 ± 6.40 mg/dl in cataract patients, uric acid 2.04 ± 0.59 mg/dl in keratoconus and 2.18 ± 0.73 mg/dl in cataract groups. Prolactin concentration was 3.18 ± 0.34 ng/ml in keratoconus and 3.33 ± 0.32 ng/ml in cataract patients, fT4 20.57 ± 4.76 pmol/l in KC and 19.06 ± 3.86 pmol/l in cataract group. Urea concentration was effected through gender (p = 0.039), age (p = 0.001) and diagnosis (p = 0.025). Uric acid concentration was not effected through any of the analyzed parameters (p > 0.056). Prolactin and fT4 concentration were effected only through diagnosis (p = 0.009 and p = 0.006). Urea and prolactin concentrations are decreased, fT4 concentration is increased in aqueous humor of keratoconus patients, and uric acid concentration remains unchanged. Urea concentration in aqueous humor is also increased in older and male patients. Therefore, metabolic disorder and hormonal balance may both have an impact on keratoconus development. Further studies are necessary to assess the specific impact.

  7. Role of lauric acid-potassium hydroxide concentration on bacterial contamination of spray washed broiler carcasses

    Science.gov (United States)

    A series of experiments were conducted to examine reductions in bacterial contamination of broiler carcasses washed in a spray cabinet with various concentrations of lauric acid (LA)-potassium hydroxide (KOH) solutions. Fifty eviscerated carcasses and 5 ceca were obtained from the processing line of...

  8. Removing ferric ions from concentrated acid leaching solution of an uranium ore by jarosite

    International Nuclear Information System (INIS)

    Song Huanbi; Hu Yezang

    1997-01-01

    The author expounds the fundamental rules of removing ferric ions by jarosite and presents results of removing ferric ions from concentrated acid curing-trickle leaching solution of an uranium ore. It turns out that the method can be applied to uranium hydrometallurgical process effectively

  9. Dry Matter Production and Leaf Elemental Concentrations of Rambutan Grown on an Acid Ultisol

    Science.gov (United States)

    Little is known about the adaptability of rambutan (Nephelium lappaceum) to highly acidic soils rich in aluminum (Al). A 2-yr field study was conducted to determine the effects of various levels of soil Al on dry matter production, plant growth, and nutrient concentration in the leaves of four cult...

  10. The influence of nitrate concentrations and acidity on the electrocatalytic reduction of nitrate on platinum

    NARCIS (Netherlands)

    Groot, de M.T.; Koper, M.T.M.

    2004-01-01

    A study was performed to determine the influence of nitrate concentration and acidity on the reaction rate and selectivity of the electrocatalytic nitrate reduction on platinum. There are two different nitrate reduction mechanisms on platinum: a direct mechanism (0.4–0.1 V vs. SHE) and an indirect

  11. Changes in sodium and uric acid concentrations in plasma during the menstrual cycle.

    Science.gov (United States)

    Mira, M; Stewart, P M; Gebski, V; Llewellyn-Jones, D; Abraham, S F

    1984-03-01

    Hormonal changes during the menstrual cycle are well documented, but many other biochemical variables have not been studied. We find that in the luteal phase of the menstrual cycle the concentrations of sodium and uric acid are significantly lower. The changes may be of significance for the determination of the normal reference interval.

  12. Effects of pH, titratable acidity and calcium concentration of non ...

    African Journals Online (AJOL)

    It has also been reported that experimental addition of calcium in beverages can reduce the progression of erosion. This study was carried out to investigate effects the of pH, titratable acidity and calcium concentration of non alcoholic carbonated beverages on enamel erosion of extracted human premolar teeth. Method: ...

  13. Effects of plant proteins on postprandial, free plasma amino acid concentrations in rainbow trout (Oncorhynchus mykiss)

    DEFF Research Database (Denmark)

    Larsen, Bodil Katrine; Dalsgaard, Anne Johanne Tang; Pedersen, Per Bovbjerg

    2012-01-01

    proteins from wheat, peas, field beans, sunflower and soybean. Blood samples were obtained from the caudal vein of 7 fish in each dietary treatment group prior to feeding, as well as: 2, 4, 6, 8, 12, 24, 48 and 72 h after feeding (sampling 7 new fish at each time point), and plasma amino acid......Postprandial patterns in plasma free amino acid concentrations were investigated in juvenile rainbow trout (Oncorhynchus mykiss) fed either a fish meal based diet (FM) or a diet (VEG) where 59% of fish meal protein (corresponding to 46% of total dietary protein) was replaced by a matrix of plant...... the two dietary treatment groups correlated largely with the amino acid content of the two diets except for methionine, lysine and arginine, where the differences were more extreme than what would be expected from differences in dietary concentrations. The apparent protein digestibility coefficient...

  14. Postprandial Plasma Concentrations of Individual Bile Acids and FGF-19 in Patients With Type 2 Diabetes

    DEFF Research Database (Denmark)

    Sonne, David P; van Nierop, F Samuel; Kulik, Willem

    2016-01-01

    and FGF-19 concentrations. RESULTS: Postprandial total bile acid concentrations increased with increasing meal fat content (P vs controls (oral glucose tolerance test, low and medium fat meals, P fat meal, P = .30). Differences......, Hellerup, Denmark. PARTICIPANTS: Fifteen patients with T2D and 15 healthy matched controls with normal glucose tolerance. INTERVENTIONS: A 75-g oral glucose tolerance test and three isocaloric and isovolemic liquid meals with low, medium, and high fat content, respectively. MAIN OUTCOME MEASURES: Bile acid......CONTEXT: Bile acids regulate lipid and carbohydrate metabolism by interaction with membrane or intracellular proteins including the nuclear farnesoid X receptor (FXR). Postprandial activation of ileal FXR leads to secretion of fibroblast growth factor 19 (FGF-19), a gut hormone that may...

  15. Dynamic changes in amino acid concentration profiles in patients with sepsis.

    Directory of Open Access Journals (Sweden)

    Longxiang Su

    Full Text Available The goal of this work was to explore the dynamic concentration profiles of 42 amino acids and the significance of these profiles in relation to sepsis, with the aim of providing guidance for clinical therapies.Thirty-five critically ill patients with sepsis were included. These patients were further divided into sepsis (12 cases and severe sepsis (23 cases groups or survivor (20 cases and non-survivor (15 cases groups. Serum samples from the patients were collected on days 1, 3, 5, 7, 10, and 14 following intensive care unit (ICU admission, and the serum concentrations of 42 amino acids were measured.The metabolic spectrum of the amino acids changed dramatically in patients with sepsis. As the disease progressed further or with poor prognosis, the levels of the different amino acids gradually increased, decreased, or fluctuated over time. The concentrations of sulfur-containing amino acids (SAAs, especially taurine, decreased significantly as the severity of sepsis worsened or with poor prognosis of the patient. The serum concentrations of SAAs, especially taurine, exhibited weak negative correlations with the Sequential Organ Failure Assessment (SOFA (r=-0.319 and Acute Physiology and Chronic Health Evaluation (APACHE II (r=-0.325 scores. The areas under the receiver operating characteristic curves of cystine, taurine, and SAA levels and the SOFA and APACHE II scores, which denoted disease prognosis, were 0.623, 0.674, 0.678, 0.86, and 0.857, respectively.Critically ill patients with disorders of amino acid metabolism, especially of SAAs such as cystine and taurine, may provide an indicator of the need for the nutritional support of sepsis in the clinic.ClinicalTrial.gov identifier NCT01818830.

  16. Influence of temperature, hydrogen and boric acid concentration on IGSCC susceptibility of unsensitized 316 stainless steel

    Energy Technology Data Exchange (ETDEWEB)

    Arioka, Koji [Inst. of Nuclear Safety System Inc., Mihama, Fukui (Japan)

    2002-09-01

    IGSCC susceptibility of unsensitized 316SS under PWR primary water was studied as a function of solution temperature, dissolved hydrogen, and boric acid concentration by SSRT test using specimens with cold deformed hump. IGSCC growth rate was dependent on temperature and the obtained activation energy was 21.6K cal/mol. Regarding the influence of dissolved hydrogen, there was a simple monotonic increase in crack growth rate with the increasing hydrogen concentration within the PWR primary water chemistry specifications. Also, there was a remarkable difference in IGSCC susceptibility with regard to the effect to boric acid concentration. Within the tested concentration, the IGSCC susceptibility under high concentrated boric acid solution (2300ppm B) was inhibited in comparison with that under 500ppm B. These temperature and dissolved hydrogen dependencies of IGSCC susceptibility were similar to the literature on published data on irradiated 316SS. Although further study is required to clarify the mechanism, however the similarity of the dependencies suggests that the rate-limited IGSCC process of un-irradiated 316SS is related to that of IASCC. (author)

  17. Passive Sampler for Measurements of Atmospheric Nitric Acid Vapor (HNO3 Concentrations

    Directory of Open Access Journals (Sweden)

    Andrzej Bytnerowicz

    2001-01-01

    Full Text Available Nitric acid (HNO3 vapor is an important nitrogenous air pollutant responsible for increasing saturation of forests with nitrogen and direct injury to plants. The USDA Forest Service and University of California researchers have developed a simple and inexpensive passive sampler for monitoring air concentrations of HNO3. Nitric acid is selectively absorbed on 47-mm Nylasorb nylon filters with no interference from particulate NO3-. Concentrations determined with the passive samplers closely corresponded with those measured with the co-located honeycomb annular denuder systems. The PVC protective caps of standardized dimensions protect nylon filters from rain and wind and allow for reliable measurements of ambient HNO3 concentrations. The described samplers have been successfully used in Sequoia National Park, the San Bernardino Mountains, and on Mammoth Mountain in California.

  18. Plasma ascorbic acid concentrations in prevalent patients with end-stage renal disease on hemodialysis.

    Science.gov (United States)

    Sirover, William D; Liu, Yuguan; Logan, Amanda; Hunter, Krystal; Benz, Robert L; Prasad, Deepali; Avila, Jose; Venkatchalam, Thaliga; Weisberg, Lawrence S; Handelman, Garry J

    2015-05-01

    To determine the prevalence of vitamin C (ascorbic acid [AA]) deficiency in patients with end-stage renal disease, the effect of supplemental AA on plasma AA concentrations, and the extrinsic and intrinsic factors that affect plasma AA concentrations in this patient population. In study 1, we compared the effect of hemodialysis (HD) on plasma AA concentrations between patients with low and high pre-HD AA concentrations. In study 2, we analyzed kinetic and nonkinetic factors for their association with increased plasma AA concentrations in patients on maintenance HD. Study 1 was performed in a single outpatient HD clinic in Cherry Hill, New Jersey. Study 2 was performed in 4 outpatient HD clinics in Southern New Jersey. In study 1, we collected plasma samples from 8 adult patients on maintenance HD at various time points around their HD treatment and assayed them for AA concentration. In study 2, we enrolled 203 adult patients and measured pre-HD plasma AA concentrations. We ascertained supplemental AA use and assessed dietary AA intake. In study 1, plasma AA concentrations were compared during the intradialytic and interdialytic period. In study 2, pre-HD plasma AA concentrations were correlated with supplement use and demographic factors. Study 1 showed that over the course of a single HD treatment, the plasma AA concentration decreased by a mean (±standard deviation) of 60% (±6.6). In study 2, the median pre-HD plasma AA concentration was 15.7 μM (interquartile range, 8.7-66.8) in patients who did not take a supplement and 50.6 μM (interquartile range, 25.1-88.8) in patients who did take a supplement (P HD plasma AA concentration ≥30 μM. HD depletes plasma AA concentrations, and AA supplementation allows patients to achieve higher plasma AA concentrations. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  19. Negative symptoms in nondeficit syndrome respond to neuroleptic treatment with changes in plasma homovanillic acid concentrations.

    Science.gov (United States)

    Suzuki, E; Kanba, S; Koshikawa, H; Nibuya, M; Yagi, G; Asai, M

    1996-05-01

    Deficit syndrome (DS) in schizophrenia is characterized by serious, chronic, and primary negative symptoms. We investigated differences in response to neuroleptic treatment between 8 DS patients and 6 nondeficit syndrome (NDS) patients who had the selective dopamine-D2 receptor blocker bromperidol added to their neuroleptic regimens. First, 9 mg/d was administered for 4 weeks, followed by 18 mg/d for another 4 weeks. Plasma homovanillic acid (pHVA) and plasma bromperidol concentrations were measured, and psychiatric symptoms were scored. In the NDS patients, both positive and negative symptoms improved. However, only the positive symptom scores changed in the DS patients. On day 4, pHVA concentrations of the NDS patients alone were significantly elevated. Plasma bromperidol concentrations did not differ between the groups. These results suggest that bromperidol exerts different effects on negative symptoms and pHVA concentrations between NDS and DS patients, effects that are unrelated to plasma bromperidol concentrations.

  20. Comparison of gene expression and fatty acid profiles in concentrate and forage finished beef.

    Science.gov (United States)

    Buchanan, J W; Garmyn, A J; Hilton, G G; VanOverbeke, D L; Duan, Q; Beitz, D C; Mateescu, R G

    2013-01-01

    Fatty acid profiles and intramuscular expression of genes involved in fatty acid metabolism were characterized in concentrate- (CO) and forage- (FO) based finishing systems. Intramuscular samples from the adductor were taken at slaughter from 99 heifers finished on a CO diet and 58 heifers finished on a FO diet. Strip loins were obtained at fabrication to evaluate fatty acid profiles of LM muscle for all 157 heifers by using gas chromatography fatty acid methyl ester analysis. Composition was analyzed for differences by using the General Linear Model (GLM) procedure in SAS. Differences in fatty acid profile included a greater atherogenic index, greater percentage total MUFA, decreased omega-3 to omega-6 ratio, decreased percentage total PUFA, and decreased percentage omega-3 fatty acids in CO- compared with FO-finished heifers (P0.05). Upregulation was observed for PPARγ, fatty acid synthase (FASN), and fatty acid binding protein 4 (FABP4) in FO-finished compared with CO-finished heifers in both atherogenic index categories (P<0.05). Upregulation of diglyceride acyl transferase 2 (DGAT2) was observed in FO-finished heifers with a HAI (P<0.05). Expression of steroyl Co-A desaturase (SCD) was upregulated in CO-finished heifers with a LAI, and downregulated in FO-finished heifers with a HAI (P<0.05). Expression of adiponectin (ADIPOQ) was significantly downregulated in CO-finished heifers with a HAI compared with all other categories (P<0.05). The genes identified in this study which exhibit differential regulation in response to diet or in animals with extreme fatty acid profiles may provide genetic markers for selecting desirable fatty acid profiles in future selection programs.

  1. Efficient fermentation of xylose to ethanol at high formic acid concentrations by metabolically engineered Saccharomyces cerevisiae

    Energy Technology Data Exchange (ETDEWEB)

    Hasunuma, Tomohisa; Yoshimura, Kazuya; Matsuda, Fumio [Kobe Univ., Hyogo (Japan). Organization of Advanced Science and Technology; Sung, Kyung-mo; Sanda, Tomoya; Kondo, Akihiko [Kobe Univ., Hyogo (Japan). Dept. of Chemical Science and Engineering

    2011-05-15

    Recombinant yeast strains highly tolerant to formic acid during xylose fermentation were constructed. Microarray analysis of xylose-fermenting Saccharomyces cerevisiae strain overexpressing endogenous xylulokinase in addition to xylose reductase and xylitol dehydrogenase from Pichia stipitis revealed that upregulation of formate dehydrogenase genes (FDH1 and FDH2) was one of the most prominent transcriptional events against excess formic acid. The quantification of formic acid in medium indicated that the innate activity of FDH was too weak to detoxify formic acid. To reinforce the capability for formic acid breakdown, the FDH1 gene was additionally overexpressed in the xylose-metabolizing recombinant yeast. This modification allowed the yeast to rapidly decompose excess formic acid. The yield and final ethanol concentration in the presence of 20 mM formic acid is as essentially same as that of control. The fermentation profile also indicated that the production of xylitol and glycerol, major by-products in xylose fermentation, was not affected by the upregulation of FDH activity. (orig.)

  2. Postprandial changes in plasma acylcarnitine concentrations as markers of fatty acid flux in overweight and obesity.

    Science.gov (United States)

    Ramos-Roman, Maria A; Sweetman, Lawrence; Valdez, Maressa J; Parks, Elizabeth J

    2012-02-01

    This study determined whether reductions in postprandial plasma nonesterified fatty acid (FFA) flux would lead to reductions in plasma acylcarnitine (AC) concentrations. Plasma AC was measured by liquid chromatography with tandem mass spectrometry in the fasting state and over 6 hours after a high-fat (50% energy) meal was fed to 16 overweight and obese subjects with a wide range of insulin sensitivities. Body composition was measured by dual-energy x-ray absorptiometry; insulin sensitivity by insulin-modified, frequently sampled intravenous glucose tolerance test; substrate oxidation by indirect calorimetry; blood metabolite and hormone concentrations biochemically; and fatty acid flux by using stable isotope tracers. Lean body mass and fasting fat oxidation correlated positively (r > 0.522, P 0.515, P Conditions that impact fatty acid flux contribute to the control of postprandial plasma AC concentrations. These data underscore the need for a better understanding of postprandial fatty acid oxidation and dietary fat delivery in the setting of adipose insulin resistance to determine how postprandial lipemia contributes to chronic disease risk. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Capillary electrophoresis method with UV-detection for analysis of free amino acids concentrations in food.

    Science.gov (United States)

    Omar, Mei Musa Ali; Elbashir, Abdalla Ahmed; Schmitz, Oliver J

    2017-01-01

    Simple and inexpensive capillary electrophoresis with UV-detection method (CE-UV) was optimized and validated for determination of six amino acids namely (alanine, asparagine, glutamine, proline, serine and valine) for Sudanese food. Amino acids in the samples were derivatized with 4-chloro-7-nitro-2,1,3-benzoxadiazole (NBD-Cl) prior to CE-UV analysis. Labeling reaction conditions (100mM borate buffer at pH 8.5, labeling reaction time 60min, temperature 70°C and NBD-Cl concentration 40mM) were systematically investigated. The optimal conditions for the separation were 100mM borate buffer at pH 9.7 and detected at 475nm. The method was validated in terms of linearity, limit of detection (LOD), limit of quantification (LOQ), precision (repeatability) (RSD%) and accuracy (recovery). Good linearity was achieved for all amino acids (r(2)>0.9981) in the concentration range of 2.5-40mg/L. The LODs in the range of 0.32-0.56mg/L were obtained. Recoveries of amino acids ranging from 85% to 108%, (n=3) were obtained. The validated method was successfully applied for the determination of amino acids for Sudanese food samples. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Effect of dimethylamine on the gas phase sulfuric acid concentration measured by Chemical Ionization Mass Spectrometry

    CERN Document Server

    Rondo, L.; Kürten, A.; Adamov, A.; Bianchi, F.; Breitenlechner, M.; Duplissy, J.; Franchin, A.; Dommen, J.; Donahue, N. M.; Dunne, E. M.; Flagan, R. C.; Hakala, J.; Hansel, A.; Keskinen, H.; Kim, J.; Jokinen, T.; Lehtipalo, K.; Leiminger, M.; Praplan, A.; Riccobono, F.; Rissanen, M. P.; Sarnela, N.; Schobesberger, S.; Simon, M.; Sipilä, M.; Smith, J. N.; Tomé, A.; Tröstl, J.; Tsagkogeorgas, G.; Vaattovaara, P.; Winkler, P. M.; Williamson, C.; Wimmer, D.; Baltensperger, U.; Kirkby, J.; Kulmala, M.; Petäjä, T.; Worsnop, D. R.; Curtius, J.

    2016-01-01

    Sulfuric acid is widely recognized as a very important substance driving atmospheric aerosolnucleation. Based on quantum chemical calculations it has been suggested that the quantitative detectionof gas phase sulfuric acid (H2SO4) by use of Chemical Ionization Mass Spectrometry (CIMS) could be biased inthe presence of gas phase amines such as dimethylamine (DMA). An experiment (CLOUD7 campaign) was setup at the CLOUD (Cosmics Leaving OUtdoor Droplets) chamber to investigate the quantitative detection ofH2SO4in the presence of dimethylamine by CIMS at atmospherically relevant concentrations. For the first time inthe CLOUD experiment, the monomer sulfuric acid concentration was measured by a CIMS and by two CI-APi-TOF(Chemical Ionization-Atmospheric Pressure interface-Time Of Flight) mass spectrometers. In addition, neutralsulfuric acid clusters were measured with the CI-APi-TOFs. The CLOUD7 measurements show that in the presenceof dimethylamine (<5 to 70 pptv) the sulfuric acid monomer measured by the CIMS...

  5. Serum Sialic Acid Concentration and Content in ApoB-Containing Lipoproteins in Liver Diseases.

    Science.gov (United States)

    Gudowska, Monika; Gruszewska, Ewa; Cylwik, Bogdan; Panasiuk, Anatol; Filisiak, Robert; Szmitkowski, Maciej; Chrostek, Lech

    2016-01-01

    The great significance for the metabolism of lipoproteins is the composition of carbohydrate chain of apolipoproteins, where sialic acid (SA) is located. In VILDL and LDL sialic acid is attached to apolipoprotein B. The sialylation of serum proteins including apolipoprotein B can be affected in the course of liver diseases. Therefore, the aim of this study was to assess the effect of liver diseases on the concentration and content of SA in ApoB-containing lipoproteins. The tested group consisted of 165 patients (118 males, 47 females) with liver diseases: alcoholic cirrhosis, non-alcoholic cirrhosis, chronic hepatitis, toxic hepatitis, chronic viral hepatitis, and liver cancer. ApoB-containing lipoproteins were isolated by a turbidimetric procedure and SA concentration was measured according to an enzymatic method. There was a significant increase in the serum concentration of SA in ApoB-containing lipoproteins in viral hepatitis. Although the serum concentration of ApoB was not significantly different between specific liver diseases, the serum levels of SA in ApoB-containing lipoproteins appeared to be different. There is an association between SA concentration and triglycerides in alcoholic cirrhosis and viral hepatitis. Also, in viral hepatitis SA concentration correlated negatively with HDL-cholesterol. The content of SA in ApoB-containing lipoproteins in alcoholic cirrhosis and viral hepatitis was significantly higher than that in the control group, but did not differ between diseases. This study may explain the variations in serum lipids and lipoproteins in liver diseases. It seems that the reason for these abnormalities is the changes in the concentration of sialic acid in ApoB-containing lipoproteins.

  6. Concentration-Discharge Behavior of Contaminants in a Stream Impacted by Acid Mine Drainage

    Science.gov (United States)

    Shaw, M. E.; Klein, M.; Herndon, E.

    2017-12-01

    Acid mine drainage (AMD) has severely degraded streams throughout the Appalachian coal region of the United States. AMD occurs when pyrite contained in coal is exposed to water and air during mining activities and oxidized to release high concentrations of sulfate, metals, and acidity into water bodies. Little is known about the concentration-discharge (CQ) relationships of solutes in AMD-impacted streams due to the complicated nature of acid mine drainage systems. For example, streams may receive inputs from multiple sources that include runoff, constructed treatment systems, and abandoned mines that bypass these systems to continue to contaminate the streams. It is important to understand the CQ relationships of contaminants in AMD-impacted streams in order to elucidate contaminant sources and to predict effects on aquatic ecosystems. Here, we study the CQ behaviors of acid and metals in a contaminated watershed in northeastern Ohio where limestone channels have been installed to remediate water draining from a mine pool into the stream. Stream chemistry was measured in samples collected once per day or once per hour during storm events, and stream flow was measured continuously at the watershed outlet. Increases in stream velocity during storm events resulted in an increase in pH (from 3 to 6) that subsequently decreased back to 3 as flow decreased. Additionally, Fe and Mn concentrations in the stream were high during baseflow (7 and 15 mg/L, respectively) and decreased with increasing discharge during storm events. These results indicate that the treatment system is only effective at neutralizing stream acidity and removing metals when water flow through the limestone channel is continuous. We infer that the acidic and metal-rich baseflow derives from upwelling of contaminated groundwater or subsurface flow from a mine pool. Ongoing studies aim to isolate the source of this baseflow contamination and evaluate the geochemical transformations that occur as it

  7. The Role of Concentration and Solvent Character in the Molecular Organization of Humic Acids

    Directory of Open Access Journals (Sweden)

    Martina Klučáková

    2016-10-01

    Full Text Available The molecular organization of humic acids in different aqueous solutions was studied over a wide concentration range (0.01–10 g·dm−3. Solutions of humic acids were prepared in three different media: NaOH, NaCl, and NaOH neutralized by HCl after dissolution of the humic sample. Potentiometry, conductometry, densitometry, and high resolution ultrasound spectrometry were used in order to investigate conformational changes in the humic systems. The molecular organization of humic acids in the studied systems could be divided into three concentration ranges. The rearrangements were observed at concentrations of ~0.02 g·dm−3 and ~1 g·dm−3. The first “switch-over point” was connected with changes in the hydration shells of humic particles resulting in changes in their elasticity. The compressibility of water in the hydration shells is less than the compressibility of bulk water. The transfer of hydration water into bulk water increased the total compressibility of the solution, reducing the ultrasonic velocity. The aggregation of humic particles and the formation of rigid structures in systems with concentrations higher than 1 g·dm−3 was detected.

  8. Rice Hull Ash and Silicic Acid as Adsorbents for Concentration of Bacteriocins†

    OpenAIRE

    Janes, M. E.; Nannapaneni, R.; Proctor, A.; Johnson, M. G.

    1998-01-01

    A model procedure has been developed for the rapid extraction of five bacteriocins (nisin, pediocin RS2, leucocin BC2, lactocin GI3, and enterocin CS1) from concentrated freeze-dried crude culture supernatants by adsorption onto acid or alkaline rice hull ash (RHA) or silicic acid (SA). Bacteriocins were adsorbed onto RHA or SA by a pH-dependent method and desorbed by decreasing the pH to 2.5 or 3.0 and heating at 90°C for 5 min. The maximum adsorption and optimal pH range for different bacte...

  9. Development of ion-exchange properties of bamboo charcoal modified with concentrated nitric acid

    Science.gov (United States)

    Khandaker, S.; Kuba, T.; Toyohara, Y.; Kamida, S.; Uchikawa, Y.

    2017-08-01

    The surface chemistry and the structural properties of activated carbon can be altered by the acidic modification. The objective of this study is to investigate the changes occurring in bamboo charcoal (BC) during activation with concentrated nitric acid. Low temperature (500°C) carbonized BC has been prepared and oxidized with 70% concentrated boiling nitric acid (BC-AC). The porous properties of the BC are analyzed with nitrogen adsorption isotherm at 77 K. The surface structure is observed by Field emission scanning electronic microscope (FESEM) and the surface functional groups are examined by Fourier transform infrared (FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS) and the pH of the point of zero charge (pHPZC). The results reveal that severe oxidation with HNO3 considerably decreases the surface area of BC with enhanced pore widening and FESEM observation demonstrates the erosive effect of oxidation. The FTIR analysis detects that some absorption bands are assigned for carboxyl, aldehyde and ketone groups on BC-AC. The XPS analysis also clearly shows that the ratio of oxygen and acidic functional groups has been enriched significantly on the BC-AC. The low pHPZC value of BC-AC confirms that the surface is highly acidic for the fixation of acidic functional groups on surface. In general, the existence of the abundant amount of acidic functional groups on adsorbents enhances the sorption of heavy metals ions in aqueous solution. Therefore, it is strongly expected that the modified BC, activated under the proposed conditions would be a promising ion exchanger in aqueous solution and can be applied for the adsorption of different heavy metal ions and radioactive materials from effluent.

  10. Demographic, reproductive, and dietary determinants of perfluorooctane sulfonic (PFOS) and perfluorooctanoic acid (PFOA) concentrations in human colostrum

    NARCIS (Netherlands)

    Jusko, T.A.; Oktapodas, M.; Palkovičová Murinová, L.; Babjaková, J.; Verner, M.A.; DeWitt, J.C.; Babinská, K.; Thevenet-Morrison, K.; Čonka, K.; Drobná, B.; Thurston, S.W.; Lawrence, B.P.; Dozier, A.M.; Jarvinen-Seppo, K.M.; Patayová, H.; Trnovec, T.; Legler, J.; Hertz-Picciotto, I.; Lamoree, M.H.

    2016-01-01

    To determine demographic, reproductive, and maternal dietary factors that predict perfluoroalkyl substance (PFAS) concentrations in breast milk, we measured perfluorooctane sulfonic (PFOS) and perfluorooctanoic acid (PFOA) concentrations, using liquid chromatography-mass spectrometry, in 184

  11. Lipoic acid effects on glutamate and taurine concentrations in rat hippocampus after pilocarpine-induced seizures

    Directory of Open Access Journals (Sweden)

    P S Santos

    2011-01-01

    Full Text Available Pilocarpine-induced seizures can be mediated by increases in oxidative stress and by cerebral amino acid changes. The present research suggests that antioxidant compounds may afford some level of neuroprotection against the neurotoxicity of seizures in cellular level. The objective of the present study was to evaluate the lipoic acid (LA effects in glutamate and taurine contents in rat hippocampus after pilocarpine-induced seizures. Wistar rats were treated intraperitoneally (i.p. with 0.9% saline (Control, pilocarpine (400 mg/kg, Pilocarpine, LA (10 mg/kg, LA, and the association of LA (10 mg/kg plus pilocarpine (400 mg/kg, that was injected 30 min before of administration of LA (LA plus pilocarpine. Animals were observed during 24 h. The amino acid concentrations were measured using high-performance liquid chromatograph (HPLC. In pilocarpine group, it was observed a significant increase in glutamate content (37% and a decrease in taurine level (18% in rat hippocampus, when compared to control group. Antioxidant pretreatment significantly reduced the glutamate level (28% and augmented taurine content (32% in rat hippocampus, when compared to pilocarpine group. Our findings strongly support amino acid changes in hippocampus during seizures induced by pilocarpine, and suggest that glutamate-induced brain damage plays a crucial role in pathogenic consequences of seizures, and imply that strong protective effect could be achieved using lipoic acid through the release or decrease in metabolization rate of taurine amino acid during seizures.

  12. Rhodamine B conjugates of triterpenoic acids are cytotoxic mitocans even at nanomolar concentrations.

    Science.gov (United States)

    Sommerwerk, Sven; Heller, Lucie; Kerzig, Christoph; Kramell, Annemarie E; Csuk, René

    2017-02-15

    Triterpenoic acids 1-6 exhibited very low or no cytotoxicity at all, but their corresponding 2,3-di-O-acetyl-piperazinyl amides 13-18 showed low EC 50 values for several human tumor cell lines. Their cytotoxicity, however, was also high for the non-malignant mouse fibroblasts NIH 3T3. A significant improvement was achieved by preparing the rhodamine B derivatives 19-24. While rhodamine B is not cytotoxic (up to a concentration of 30μM - cut-off of the assay), the triterpenoid piperazine-spacered rhodamine B derivatives were cytotoxic in nano-molar concentration. Compound 24 (a diacetylated maslinic acid derivative) was most toxic for several human tumor cell lines but less toxic for mouse fibroblasts NIH 3T3. Staining and double-staining experiments revealed 24 to act as a mitocan. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  13. Effect of polysulfone concentration on the performance of membrane-assisted lead acid battery

    Directory of Open Access Journals (Sweden)

    Ahmad Fauzi Ismail

    2002-11-01

    Full Text Available The application of lead acid battery in tropical countries normally faces the problem of water decomposition. This phenomenon is due to the factor of charge-discharge reaction in the battery and heat accumulation caused by hot tropical climate and heat generated from engine compartment. The objective of this study is to analyze the effect of polysulfone concentration on the performance of membrane-assisted lead-acid battery. Gas separation membranes, prepared through wet-dry phase inversion method and using various polysulfone concentrated formulations, were applied on the battery vent holes, for the purpose of preventing electrolyte from evaporating to the atmosphere. The best membrane, which retains the most electrolyte, will be chosen to be applied on the soon-to-be-developed “membrane-assisted maintenance- free battery”. This maintenance-free battery will need no topping up of deionized water every time the electrolyte level goes low.

  14. Determination of oil and fatty acids concentration in seeds of coastal halophytic Sueada aegyptica plant

    Directory of Open Access Journals (Sweden)

    Tahereh Assadi

    2013-04-01

    Full Text Available Background: Suaeda aegyptica (S. aegyptica species belong to the Chenepodiaceae family, the second largest family in the world of plants kingdom. It is indigenous to arid and semi-arid regions of the world and salty coastal zones Persian Gulf of Iran. It is an annual succulent halophyte plant which is characterized by producing oily seeds, high growth rate and large number of biomass. The aim of this study was analysis and determination of oil and fatty acids concentration in the S. aegyptica seed. Material and Methods: The seeds of S. aegyptica were collected form coastal zones of Persian Gulf in Bushehr province, washed and dried. The fatty acids content of the dried seeds were extracted in n-hexane solvent by soxhellet apparatus. The residue of n-hexane in oily phase was evaporated by rotary evaporator and remaining oil was collected for fatty acids analysis. In the presence of potassium hydroxide and BF3 by refluxing for 30 minutes, the methyl ester derivative of fatty acids were produced. Then the resulted derivatives were analyzed by gas chromatography (GC-FID. Results: The seeds of S. aegyptica contains eight fatty acids as: Pelargonic (C9, Capric (C10, Undecylic (C11, Tridecylic (C13, Myristic (C14, Palmitic (C16, Stearic (C18, Linoleic (18:2 and Linolenic (18:3. Average oil content in seeds 014/0 ± 87 / percent. Conclusion: The ratio of unsaturated fatty acids was higher than the saturated ones. Linoleic and Palmitic acids are major unsaturated and saturated fatty acids of S. aegyptica seed respectively.

  15. Uranium recovery from the concentrated phosphoric acid prepared by the hemi-hydrate process

    Energy Technology Data Exchange (ETDEWEB)

    Fouad, E A; Mahdy, M A; Bakr, M Y [Nuclear materials authority, Cairo, (Egypt); Zatout, A A [Faculty of engineering, Alex. university, Alex, (Egypt)

    1995-10-01

    It has been proved that the uranium dissolution from El-sebaiya phosphate ore was possible by using 10 Kg of K Cl O{sub 4}/ ton rock during the preparation of high strength phosphoric acid using the hemi hydrate process. In the present work, effective extraction of uranium (about 90%) from the high strength phosphoric acid using a new synergistic solvent mixture of 0.75 M D 2 EHPA/0.1 M TOHPO had been a success. Stripping of uranium from the organic phase was possible by 10 M phosphoric acid while the direct precipitation of uranium concentrate from the later was feasible by using N H{sub 4} F in presence of acetone. 8 figs.

  16. Uranium recovery from the concentrated phosphoric acid prepared by the hemi-hydrate process

    International Nuclear Information System (INIS)

    Fouad, E.A.; Mahdy, M.A.; Bakr, M.Y.; Zatout, A.A.

    1995-01-01

    It has been proved that the uranium dissolution from El-sebaiya phosphate ore was possible by using 10 Kg of K Cl O 4 / ton rock during the preparation of high strength phosphoric acid using the hemi hydrate process. In the present work, effective extraction of uranium (about 90%) from the high strength phosphoric acid using a new synergistic solvent mixture of 0.75 M D 2 EHPA/0.1 M TOHPO had been a success. Stripping of uranium from the organic phase was possible by 10 M phosphoric acid while the direct precipitation of uranium concentrate from the later was feasible by using N H 4 F in presence of acetone. 8 figs

  17. Biohydrogen Production from Pineapple Waste: Effect of Substrate Concentration and Acid Pretreatment

    Science.gov (United States)

    Cahyari, K.; Putri, A. M.; Oktaviani, E. D.; Hidayat, M. A.; Norajsha, J. D.

    2018-05-01

    Biohydrogen is the ultimate choice of energy carrier in future due to its superior qualities such as fewer greenhouse gases emission, high energy density (142 kJ/gram), and high energy conversion using a fuel cell. Production of biohydrogen from organic waste e.g. pineapple waste offers a simultaneous solution for renewable energy production and waste management. It is estimated that pineapple cultivation in Indonesia generated more than 1 million ton/year comprising of rotten pineapple fruit, leaves, and stems. Majority of this waste is dumped into landfill area without any treatments which lead to many environmental problems. This research was meant to investigate the utilization of pineapple waste i.e. peel and the core of pineapple fruit and leaves to produce biohydrogen through mesophilic dark fermentation (30°C, 1 atm, pH 5.0). Effect of dilute acid treatment and substrate concentration was particularly investigated in these experiments. Peel and core of pineapple waste were subjected to fermentation at 3 various substrate concentration i.e. 8.8, 17.6 and 26.4-gram VS/liter. Meanwhile, pineapple leaves were pretreated using dilute acid (H2SO4) at 0.2, 0.3 and 0.4 N and followed by dark fermentation. Results show that the highest yield of biohydrogen was obtained at a substrate concentration of 26.4-gram VS/liter both for peel and core of the waste. Pretreatment using dilute acid (H2SO4) 0.3 N might improve fermentation process with a higher yield at 0.8 ml/gram VS. Hydrogen percentage in biogas produced during fermentation process was in the range between 5 – 32% of volume ratio. In summary, it is possible to utilize pineapple waste for production of biohydrogen at an optimum substrate concentration of 26.4-gram VS/liter and acid pretreatment (H2SO4) of 0.3 N.

  18. Negative symptoms in nondeficit syndrome respond to neuroleptic treatment with changes in plasma homovanillic acid concentrations.

    OpenAIRE

    Suzuki, E; Kanba, S; Koshikawa, H; Nibuya, M; Yagi, G; Asai, M

    1996-01-01

    Deficit syndrome (DS) in schizophrenia is characterized by serious, chronic, and primary negative symptoms. We investigated differences in response to neuroleptic treatment between 8 DS patients and 6 nondeficit syndrome (NDS) patients who had the selective dopamine-D2 receptor blocker bromperidol added to their neuroleptic regimens. First, 9 mg/d was administered for 4 weeks, followed by 18 mg/d for another 4 weeks. Plasma homovanillic acid (pHVA) and plasma bromperidol concentrations were m...

  19. Influence of nitric acid concentration on the characteristics of active carbons obtained from a mineral coal

    Energy Technology Data Exchange (ETDEWEB)

    Khelifi, A.; Temdrara, L.; Addoun, A. [Laboratoire d' Etude Physicochimique des Materiaux et Application a l' Environnement, Faculte de Chimie, USTHB, BP. 32 El Alia, Bab Ezzouar 16111, Algiers (Algeria); Almazan-Almazan, M.C.; Perez-Mendoza, M.; Domingo-Garcia, M.; Lopez-Garzon, F.J [Departamento de Quimica Inorganica, Facultad de Ciencias, 18071 Granada (Spain); Lopez-Domingo, F.J. [Departamento de CCIA, ETS de Ingenieria Informatica y Telecomunicacion, Granada, 18071 (Spain)

    2010-10-15

    This paper deals with the effect of the concentration of nitric acid solutions on the properties of activated carbons obtained by the oxidation of a parent activated carbon. For this purpose a mineral coal from Algeria has been used as raw material to prepare the parent active carbon AC. This was further treated with nitric acid solutions. The analysis of the samples includes the chemical and textural characterization. The former was carried out by selective titrations and FTIR spectroscopy. The latter, by nitrogen and carbon dioxide adsorption at 77 and 273 K, respectively, and by adsorption of organic probes (benzene, dichloromethane, cyclohexane and 2,2-dimethyl butane) at 303 K. The nitrogen adsorption isotherms have been analysed by using the BET equation, {alpha}{sub s}-method and molecular simulation. The Dubinin-Radushkevich approach has been applied to the carbon dioxide and vapours adsorption data. The results show that the treatment with 2 N nitric acid solution is very appropriate because it introduces a large amount of oxygen containing groups with a small change of the textural characteristics of the parent AC. More concentrated nitric acid solutions change in large extent the textural properties although they also introduce large amount of chemical groups. (author)

  20. Trends in Pinus ponderosa foliar pigment concentration due to chronic exposure of ozone and acid rain

    International Nuclear Information System (INIS)

    Neuman, L.; Houpis, J.; Anderson, P.

    1991-01-01

    To determine the effects of ozone and acid rain on mature Ponderosa pine trees, Lawrence Livermore National Lab. has collaborated with University of California Berkeley, University of California Davis, California State University Chico, and the US Forest Service at the latter's Chico Tree Improvement Center. Foliar tissue from mature grafted scions of Pinus ponderosa were exposed to two times ambient ozone for ten months and to acid rain (3.0 pH) weekly for 10 weeks using branch exposure chambers. Pigment extracts were analyzed spectrophotometrically for concentrations of chlorophylls a and b, and carotenoid pigments, at 662 nm, 644 nm, and 470 nm, respectively. Pigment concentrations were expressed on a surface area basis. Preliminary results revealed that chlorophyll a showed a downward trend due to the ozone treatment. Acid rain caused no effects on these three pigments, however, chlorophyll b showed an upward trend due to the interaction of ozone and acid rain. The carotenoid pigments showed no changes due to the treatments either singly, or in combination

  1. Cesium sorption from concentrated acidic tank wastes using ammonium molybdophosphate-polyacrylonitrile composite sorbents

    International Nuclear Information System (INIS)

    Todd, T.A.; Mann, N.R.; Tranter, T.J.; Sebesta, F.; John, J.; Motl, A.

    2002-01-01

    Ammonium molybdophosphate-polyacrylonitrile (AMP-PAN) composite sorbents have been evaluated for the removal of cesium from Idaho National Engineering and Environmental Laboratory (INEEL) concentrated acidic tank waste. Batch contacts were performed to qualitatively evaluate the effects of increased nitric acid, sodium and potassium. An equilibrium isotherm was generated with simulated concentrated tank waste solutions and fit to the Langmuir equation. Additional batch contact experiments were performed to determine if mercury, plutonium and americium would sorb onto AMP-PAN. Dynamic sorption was evaluated in column tests employing 1.5 cm 3 columns operating at 5, 10 and 20 bed volumes of flow per hour. Results indicate, as expected, that dynamic cesium sorption capacity is reduced as the flowrate is increased. Calculated dynamic capacities for cesium were 22.5, 19.8 and 19.6 mg Cs/g sorbent, for 5, 10 and 20 bed volume per hour flows, respectively. The thermal stability of loaded AMP-PAN was evaluated by performing thermogravimetric analysis (TGA) on samples of AMP, PAN (polymer), and AMP-PAN. Results indicate that AMP-PAN is stable to 400 deg C, with less than a 10% loss of weight, which is at least partially due to loss of water of hydration. The evaluation of AMP-PAN indicates that it will effectively remove cesium from concentrated acidic tank waste solutions. (author)

  2. D-tagatose, a stereoisomer of D-fructose, increases blood uric acid concentration.

    Science.gov (United States)

    Buemann, B; Toubro, S; Holst, J J; Rehfeld, J F; Bibby, B M; Astrup, A

    2000-08-01

    D-Fructose has been found to increase uric acid production by accelerating the degradation of purine nucleotides, probably due to hepatocellular depletion of inorganic phosphate (Pi) by an accumulation of ketohexose-1-phosphate. The hyperuricemic effect of D-tagatose, a stereoisomer of D-fructose, may be greater than that of D-fructose, as the subsequent degradation of D-tagatose-1-phosphate is slower than the degradation of D-fructose-1-phosphate. We tested the effect of 30 g oral D-tagatose versus D-fructose on plasma uric acid and other metabolic parameters in 8 male subjects by a double-blind crossover design. Both the peak concentration and 4-hour area under the curve (AUC) of serum uric acid were significantly higher after D-tagatose compared with either 30 g D-fructose or plain water. The decline in serum Pi concentration was greater at 50 minutes after D-tagatose versus D-fructose. The thermogenic and lactacidemic responses to D-tagatose were blunted compared with D-fructose. D-Tagatose attenuated the glycemic and insulinemic responses to a meal that was consumed 255 minutes after its administration. Moreover, both fructose and D-tagatose increased plasma concentrations of cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1). The metabolic effects of D-tagatose occurred despite its putative poor absorption.

  3. Rapid measurement of plasma free fatty acid concentration and isotopic enrichment using LC/MS

    Science.gov (United States)

    Persson, Xuan-Mai T.; Błachnio-Zabielska, Agnieszka Urszula; Jensen, Michael D.

    2010-01-01

    Measurements of plasma free fatty acids (FFA) concentration and isotopic enrichment are commonly used to evaluate FFA metabolism. Until now, gas chromatography-combustion-isotope ratio mass spectrometry (GC/C/IRMS) was the best method to measure isotopic enrichment in the methyl derivatives of 13C-labeled fatty acids. Although IRMS is excellent for analyzing enrichment, it requires time-consuming derivatization steps and is not optimal for measuring FFA concentrations. We developed a new, rapid, and reliable method for simultaneous quantification of 13C-labeled fatty acids in plasma using high-performance liquid chromatography-mass spectrometry (HPLC/MS). This method involves a very quick Dole extraction procedure and direct injection of the samples on the HPLC system. After chromatographic separation, the samples are directed to the mass spectrometer for electrospray ionization (ESI) and analysis in the negative mode using single ion monitoring. By employing equipment with two columns connected parallel to a mass spectrometer, we can double the throughput to the mass spectrometer, reducing the analysis time per sample to 5 min. Palmitate flux measured using this approach agreed well with the GC/C/IRMS method. This HPLC/MS method provides accurate and precise measures of FFA concentration and enrichment. PMID:20526002

  4. Effect of Drying Temperature on Rosmarinic Acid and Sinensetin Concentration in Orthosiphon stamineus Herbal Leaves

    Science.gov (United States)

    Abdullah, Sriyana; Razak Shaari, Abdul; Hajar Rukunudin, Ibni; Syarhabil Ahmad, Muhammad

    2018-03-01

    The objective of this work was to investigate the effects of drying temperature on the concentration of O rthosiphon stamineus biomarker compounds which were rosmarinic acid (RA) and sinensetin (SEN). The thin layer drying approach was used to dry O. stamineus leaves at various temperatures of 30, 40 and 50°C using a laboratory scale hot air dryer. The dried leaves were then extracted using 60% aqueous methanol prior to quantification. The RA and SEN concentrations in the dried leaves extracts were quantified by the high performance liquid chromatography. The concentration of RA for the dried leaves at 30 and 40°C were higher as compared to that of the fresh leaves. This may due to the response of the plant cells to abiotic stress. The concentration of RA also showed a significant reduction when the temperature was increased to 50°C. In contrast, the SEN concentration in O. stamineus dried leaf extract was lower than that of the fresh samples. The concentrations of SEN depicted insignificant effects by drying at 30 and 50°C, and the highest value was obtained in the samples dried at 40°C. Results showed that the drying process was found to affect the concentration of both compounds; therefore suitable drying conditions should be adopted to enhance the medicinal values of the plant species.

  5. Inflammatory markers in dependence on the plasma concentration of 37 fatty acids after the coronary stent implantation.

    Science.gov (United States)

    Handl, Jiří; Meloun, Milan; Mužáková, Vladimíra

    2018-02-05

    Using the regression model building the relationships between the concentration of 37 fatty acids of blood plasma phospholipids of 41 patients with coronary artery disease after coronary stent implantation, the inflammatory response and oxidative stress markers were estimated. The dynamics of the inflammatory response and the oxidative stress was indicated by measuring plasma concentrations of highly sensitive C-reactive protein, interleukin-6, serum amyloid A and malondialdehyde before, 24h after stent implantation. The multiple linear regression analysis was preceded by an exploratory data analysis, principal component analysis, factor analysis and cluster analysis, which proved a hidden internal relation of 37 fatty acids. The concentration of cerotic acid (C26:0) has been positively associated with an increase of malondialdehyde concentration after stent implantation, while the concentrations of tetracosatetraenoic (C24:4 N6) and nonadecanoic (C19:0) acids were associated with decrease of lipoperoxidation. The increase of interleukin-6 during the 24h after implantation was associated with higher levels of pentadecanoic acid (C15:0) and lower levels of α-linolenic acid (C18:3 N3). Regression models found several significant fatty acids at which the strength of the parameter β for each fatty acid on selected markers of C-reactive protein, malondialdehyde, interleukin-6 and serum amyloid A was estimated. Parameter β testifies to the power of the positive or negative relationship of the fatty acid concentration on the concentration of selected markers. The influencing effect of the cerotic acid (C26:0) concentration in plasma phospholipids exhibiting parameter β=140.4 is, for example, 3.5 times higher than this effect of n-3 tetracosapentaenoic acid (C24:5 N3) with β=40.0. Composition of fatty acids in plasma phospholipids shows spectrum of fatty acids available for intercellular communication in systemic inflammatory response of organism and should affect

  6. Mineral Element Concentrations in Vegetables Cultivated in Acidic Compared to Alkaline Areas of South Sweden

    Directory of Open Access Journals (Sweden)

    Ingegerd Rosborg

    2009-01-01

    Full Text Available A study in 1997, on mineral levels in acidic compared to alkaline well waters, and in women’s hair, revealed higher concentrations of a number of mineral elements like Ca, Mo and Se in alkaline waters and hair. Thus, median Ca levels were six times higher in well water and five times higher in hair from the alkaline area compared to the acidic area. This finding raised the probability of similar differences in vegetables from these areas. Thus, in the year 2006, 60 women who had participated in the study in 1997 were asked to cultivate parsley, lettuce, carrot and chive. During the spring of 2006, the women from the water and hair study of 1997, 30 of them from the acidic area and 30 women from the alkaline district cultivated vegetables: carrot (Daucus carota L, parsley (Petroselinum crispum, chive (Allium schoenoprasum and lettuce (Eruca sativa. The vegetables were harvested, and rinsed in tap water from the kitchens of the participating women in August. The concentrations of about 35 elements and ions were determined by ICP OES and ICP-MS predominantly. In addition, soil samples from the different cultivators were also analyzed for a number of elements. Lettuce and parsley showed the highest concentrations of mineral elements per gram dry weight. Only Mo concentrations were significantly higher in all the different vegetables from the alkaline district compared to vegetables from the acidic areas. On the other hand, the concentrations of Ba, Br, Mn, Rb and Zn were higher in all the different vegetables from the acidic area. In the soil, only pH and exchangeable Ca from the alkaline area were higher than from the acidic area, while exchangeable Fe, Mn and Na concentrations were higher in soils from the acidic area. Soil elements like Al, Fe, Li, Ni, Pb, Si, Ti, V, Zn and Zr were found in higher concentrations in lettuce and parsley, which were attributed to soil particles being splashed on the plants by the rain and absorbed by the leaves

  7. Study of Gamma-Hydroxybutyric Acid (GHB Concentrations in Postmortem Blood and Urine

    Directory of Open Access Journals (Sweden)

    Huda M Hassan

    2015-12-01

    Full Text Available Gamma-hydroxybutyric acid (GHB is present in blood and urine of the general population as an endogenous compound. The published concentrations in postmortem blood ranged from 0-168 mg/L in cases with no previous history of GHB use. Interpretation of GHB results should be carefully considered due to the wide distribution of endogenous concentrations. The objectives of this study are to evaluate and verify the accuracy of a proposed published (50 mg/L cut-off in 120 blood and 64 urine samples in postmortem cases selected randomly, and to identify GHB-related fatalities. GHB was determined by gas chromatography– mass spectrometry (GC–MS after extraction of the blood and urine in the presence of the internal standard GHB-D6.  The GHB concentration in majority of the blood samples (95% was ≤ 50 mg/L, while in 81% it ranged from 10-50 mg/L. In 95% of the urine samples, the GHB concentration ranged from 10-20 mg/L while 82% of the samples had a concentration of 500 mg/L. The proposed published GHB concentration of 50 mg/L may be used as a cut-off to distinguish between natural endogenous concentrations and exogenous use, but this is not sufficient by itself. The detected GHB concentrations, both in vivo and in postmortem samples, require careful interpretation, not only due to its endogenous nature, but also due to the possibility of postmortem production and also due to its rapid metabolism and excretion.In order to distinguish the endogenous GHB concentration from those reflecting abusive GHB levels, defining a specific cut-off value in biological samples is very crucial. Other matrices, such as vitreous humour, femoral blood and hair must also be considered when interpreting postmortem GHB concentrations.

  8. Safflower oil consumption does not increase plasma conjugated linoleic acid concentrations in humans.

    Science.gov (United States)

    Herbel, B K; McGuire, M K; McGuire, M A; Shultz, T D

    1998-02-01

    Conjugated linoleic acid (CLA) is a mixture of positional and geometric isomers of linoleic acid (LA) with conjugated double bonds. CLA has anticarcinogenic properties and has been identified in human tissues, dairy products, meats, and certain vegetable oils. A variety of animal products are good sources of CLA, but plant oils contain much less. However, plant oils are a rich source of LA, which may be isomerized to CLA by intestinal microorganisms in humans. To investigate the effect of triacylglycerol-esterified LA consumption on plasma concentrations of esterified CLA in total lipids, a dietary intervention (6 wk) was conducted with six men and six women. During the intervention period a salad dressing containing 21 g safflower oil providing 16 g LA/d was added to the subjects' daily diets. Three-day diet records and fasting blood were obtained initially and during dietary and postdietary intervention periods. Although LA intake increased significantly during the dietary intervention, plasma CLA concentrations were not affected. Plasma total cholesterol and LDL-cholesterol concentrations were significantly lower after addition of safflower oil to the diet. In summary, consumption of triacylglycerol-esterified LA in safflower oil did not increase plasma concentrations of esterified CLA in total lipids.

  9. The determination of vitamin C, organic acids, phenolic compounds concentration of Red and Golden delicious apple grown in Lorestan province

    Directory of Open Access Journals (Sweden)

    ebrahim Falahi

    2013-08-01

    Results: Ascorbic acid concentrations in Red and Golden delicious apples were 9.49 and 9.09 mg and 9.29 mg in total per 100 grams. Malic acid concentrations in Red and Golden delicious apples were 0.26 and 0.27 and citric acid concentrations in Red and Golden delicious apples were 0.28 mg per 100 grams in both cultivars. Acidity of Red delicious was 4 and Golden delicious was about 3.7. The acidity of Red delicious was higher than the Golden one. α-farensene was the most phenolic compound in both cultivars. Conclusion: Finally, apple cultivars grown in Lorestan have 3 times more ascorbic acid than the amount which mentioned in Iranian Food Consumption Table. There were no significant relation about malic and citric acid in both cultivars.

  10. Investigation into sorption of uranium fron its high-concentrated nitric acid solutions on resin AMP

    International Nuclear Information System (INIS)

    Savel'eva, V.I.; Sudarikov, B.N.; Kireeva, G.N.; Ryzhkova, V.N.; Kandaryuk, V.V.

    1976-01-01

    Sorption of uranium has been studied on strongly basic anion-exchange resin from nitric acid solutions with concentration in metal 10-150 g/l in presence of sodium, calcium, and aluminium nitrates. Sorption of uranium from solutions has been performed by the static method with the aid of contacting the initial solution with airdry resin for 4 hours, resin to solution ratio being 1:12.5. It has been established that sorption of uranium increases with a rise in concentration of salting out agents in the following order: Al(NO 3 ) 3 > Ca(NO 3 ) 2 > Na(NO 3 ). It has been shown spectrophotometricatly that in solutions of nitrates and HNO 3 with a concentration 3 exceeds 6 mol/l

  11. Heterogeneous photocatalytic degradation of p-toluenesulfonic acid using concentrated solar radiation in slurry photoreactor

    International Nuclear Information System (INIS)

    Kamble, Sanjay P.; Sawant, Sudhir B.; Pangarkar, Vishwas G.

    2007-01-01

    In this work, the photocatalytic degradation (PCD) of p-toluenesulfonic acid (p-TSA) in batch reactor using concentrated solar radiation was investigated. The effect of the various operating parameters such as initial concentration of substrate, catalyst loading, solution pH and types of ions on photocatalytic degradation has been studied in a batch reactor to derive the optimum conditions. The rate of photocatalytic degradation was found to be maximum at the self pH (pH 3.34) of p-TSA. It was also observed that in the presence of anions and cations, the rate of PCD decreases drastically. The kinetics of photocatalytic degradation of p-TSA was studied. The PCD of p-TSA was also carried at these optimized conditions in a bench scale slurry bubble column reactor using concentrated solar radiation

  12. Reduced gamma-aminobutyric acid concentration is associated with physical disability in progressive multiple sclerosis

    Science.gov (United States)

    Solanky, Bhavana S.; Muhlert, Nils; Tur, Carmen; Edden, Richard A. E.; Wheeler-Kingshott, Claudia A. M.; Miller, David H.; Thompson, Alan J.; Ciccarelli, Olga

    2015-01-01

    Neurodegeneration is thought to be the major cause of ongoing, irreversible disability in progressive stages of multiple sclerosis. Gamma-aminobutyric acid is the principle inhibitory neurotransmitter in the brain. The aims of this study were to investigate if gamma-aminobutyric acid levels (i) are abnormal in patients with secondary progressive multiple sclerosis compared with healthy controls; and (ii) correlate with physical and cognitive performance in this patient population. Thirty patients with secondary progressive multiple sclerosis and 17 healthy control subjects underwent single-voxel MEGA-PRESS (MEscher-GArwood Point RESolved Spectroscopy) magnetic resonance spectroscopy at 3 T, to quantify gamma-aminobutyric acid levels in the prefrontal cortex, right hippocampus and left sensorimotor cortex. All subjects were assessed clinically and underwent a cognitive assessment. Multiple linear regression models were used to compare differences in gamma-aminobutyric acid concentrations between patients and controls adjusting for age, gender and tissue fractions within each spectroscopic voxel. Regression was used to examine the relationships between the cognitive function and physical disability scores specific for these regions with gamma-aminobuytric acid levels, adjusting for age, gender, and total N-acetyl-aspartate and glutamine-glutamate complex levels. When compared with controls, patients performed significantly worse on all motor and sensory tests, and were cognitively impaired in processing speed and verbal memory. Patients had significantly lower gamma-aminobutyric acid levels in the hippocampus (adjusted difference = −0.403 mM, 95% confidence intervals −0.792, −0.014, P = 0.043) and sensorimotor cortex (adjusted difference = −0.385 mM, 95% confidence intervals −0.667, −0.104, P = 0.009) compared with controls. In patients, reduced motor function in the right upper and lower limb was associated with lower gamma-aminobutyric acid

  13. The association between concentration of Uric Acid and metabolic syndrome among adolescents

    Directory of Open Access Journals (Sweden)

    Homeira Rashidi

    2015-11-01

    Full Text Available Background: Metabolic syndromes are known as a set of risk factors for the development of cardio-vascular disease and diabetes in the individual. The association between concentration of uric acid and metabolic syndrome in adolescents has yet to be established thoroughly. The aim of this study was to investigate the relationship between uric acid and metabolic syndrome in a sample of adolescents. Methods: This cross-sectional study was conducted from September 23, 2009 to September 22, 2010 in Jundishapur University of Medical Sciences, Ahvaz, Iran. In this study, 240 individuals aged 10-19 years were randomly selected among participants of the Ahvaz MetS study (120 subjects normal and 120 subjects MetS. The serum levels of UA were measured by a colorimetric method. In the normal group, anyone with abdominal obesity, high systolic or diastolic blood pressure, High-density lipoprotein (HDL≤40 mg/dl, TG≤110 mg/dl, fasting blood sugar (FBS≤100 mg/dl or diabetes was excluded from the study. History of Anticonvulsive drugs or steroids use was the criteria for exclusion for both groups. Results: Of the 240 subjects aged a mean of 14.95±2.64 years, mean of uric acid in metabolic syndrome group was 4.8±1.4 mg/dl and in the control group was 4.18±1.01 mg/d (P=0.001. Participants were divided into three groups based on uric acid levels: ≤4.9 mg/dl, 4.9-5.7 mg/dl and >5.7 mg/dl. The risk of metabolic syndrome was significantly higher in third group of uric acid than the second and first group (odds ratio [OR], 3.7; 95% confidence interval [CI], 1.70 - 8.04 and (OR, 5.9; 95% CI, 2.42-14.35, P<0.001. In addition, uric acid level was inversely associated with hyperglycemia. The ORs of hypertriglyceridemia for the second and third group of uric acid were 4.36 (95% CI, 2.01- 9.47 5.75 (95% CI, 2.43-13.61 respectively, compared with lowest group of UA. Conclusion: The results showed that hyperuricemia was significantly linked with increased risk for

  14. Fatty Acid and Cholesterol Concentrations in Usually Consumed Fish in Brazil

    Directory of Open Access Journals (Sweden)

    Carlos Scherr

    2015-02-01

    Full Text Available Background: Several studies have demonstrated clinical benefits of fish consumption for the cardiovascular system. These effects are attributed to the increased amounts of polyunsaturated fatty acids in these foods. However, the concentrations of fatty acids may vary according to region. Objective: The goal of this study was to determine the amount of,cholesterol and fatty acids in 10 Brazilian fishes and in a non-native farmed salmon usually consumed in Brazil. Methods: The concentrations of cholesterol and fatty acids, especially omega-3, were determined in grilled fishes. Each fish sample was divided in 3 sub-samples (chops and each one was extracted from the fish to minimize possible differences in muscle and fat contents. Results: The largest cholesterol amount was found in white grouper (107.6 mg/100 g of fish and the smallest in badejo (70 mg/100 g. Omega-3 amount varied from 0.01 g/100 g in badejo to 0.900 g/100 g in weakfish. Saturated fat varied from 0.687 g/100 g in seabass to 4.530 g/100 g in filhote. The salmon had the greatest concentration of polyunsaturated fats (3.29 g/100 g and the highest content of monounsaturated was found in pescadinha (5.98 g/100 g. Whiting and boyfriend had the best omega-6/omega 3 ratios respectively 2.22 and 1.19, however these species showed very little amounts of omega-3. Conclusion: All studied Brazilian fishes and imported salmon have low amounts of saturated fat and most of them also have low amounts of omega-3.

  15. Concentrations of retinol and tocopherols in the milk of cows supplemented with conjugated linoleic acid.

    Science.gov (United States)

    Gessner, D K; Most, E; Schlegel, G; Kupczyk, K; Schwarz, F J; Eder, K

    2015-12-01

    This study was performed to investigate the hypothesis that supplementation of conjugated linoleic acid (CLA) changes the concentrations of retinol and tocopherols in the milk of cows. To investigate this hypothesis, Holstein cows received daily from 3 weeks ante-partum to 14 weeks post-partum either 172 g of a CLA-free rumen-protected control fat (control group, n = 20) or the same amount of a rumen-protected CLA fat, supplying 4.3 g of cis-9, trans-11 CLA and 3.8 g of trans-10, cis-12 CLA per d (CLA group, n = 20). Milk samples (collected at weeks 1, 3, 5, 8 and 11 of lactation) were analysed for retinol, α- and γ-tocopherol concentrations. Milk of cows supplemented with CLA had higher concentrations of retinol (+34%), α-tocopherol (+44%) and γ-tocopherol (+21%) than milk of control cows (p tocopherol and γ-tocopherol, respectively, p tocopherols, concentrations of thiobarbituric acid-reactive substances, determined in milk of week 5, were lower in cows of the CLA group than in control cows, indicative of a lower susceptibility of milk lipids to peroxidation. Plasma concentrations of retinol and α-tocopherol, determined at 1 and 5 weeks post-partum, were not different between the two groups of cows. In conclusion, this study shows that supplementing dairy cows with a moderate amount of CLA causes an increase of the concentrations of vitamins A and E in the milk and results in an increased output of those vitamins via milk. These effects might be beneficial with respect to the nutritional value of dairy products and the susceptibility of milk fat to oxidative deterioration. Journal of Animal Physiology and Animal Nutrition © 2015 Blackwell Verlag GmbH.

  16. Associations of fatty acids in cerebrospinal fluid with peripheral glucose concentrations and energy metabolism.

    Directory of Open Access Journals (Sweden)

    Reiner Jumpertz

    Full Text Available Rodent experiments have emphasized a role of central fatty acid (FA species, such as oleic acid, in regulating peripheral glucose and energy metabolism. Thus, we hypothesized that central FAs are related to peripheral glucose regulation and energy expenditure in humans. To test this we measured FA species profiles in cerebrospinal fluid (CSF and plasma of 32 individuals who stayed in our clinical inpatient unit for 6 days. Body composition was measured by dual energy X-ray absorptiometry and glucose regulation by an oral glucose test (OGTT followed by measurements of 24 hour (24EE and sleep energy expenditure (SLEEP as well as respiratory quotient (RQ in a respiratory chamber. CSF was obtained via lumbar punctures; FA concentrations were measured by liquid chromatography/mass spectrometry. As expected, FA concentrations were higher in plasma compared to CSF. Individuals with high concentrations of CSF very-long-chain saturated FAs had lower rates of SLEEP. In the plasma moderate associations of these FAs with higher 24EE were observed. Moreover, CSF monounsaturated long-chain FA (palmitoleic and oleic acid concentrations were associated with lower RQs and lower glucose area under the curve during the OGTT. Thus, FAs in the CSF strongly correlated with peripheral metabolic traits. These physiological parameters were most specific to long-chain monounsaturated (C16:1, C18:1 and very-long-chain saturated (C24:0, C26:0 FAs.Together with previous animal experiments these initial cross-sectional human data indicate that central FA species are linked to peripheral glucose and energy homeostasis.

  17. Effects of total gastrectomy on plasma silicon and amino acid concentrations in men.

    Science.gov (United States)

    Tatara, Marcin R; Krupski, Witold; Szpetnar, Maria; Dąbrowski, Andrzej; Bury, Paweł; Szabelska, Anna; Charuta, Anna; Boguszewska-Czubara, Anna; Maciejewski, Ryszard; Wallner, Grzegorz

    2015-12-01

    The aim of the study was to determine one-year effects of total gastrectomy on plasma silicon and free amino acid concentrations in patients and evaluate changes of volumetric bone mineral density (vBMD) in lumbar spine. Eight patients were enrolled to the control (CTR) group. Six patients subjected to total gastrectomy (GX group) were included to the experimental group. vBMD in trabecular and cortical bone was measured in lumbar vertebrae at baseline (before surgery) and one year later using quantitative computed tomography. Plasma concentrations of silicon and free amino acids were determined at baseline and one year later using photometric method and ion-exchange chromatography. Body weights within CTR and GX groups were not different after one-year follow-up when compared to the baseline values (P > 0.05). An average annual decrease of vBMD in the trabecular bone in the gastrectomized patients reached 15.0% in lumbar spine and was significantly different in comparison to the percentage changes observed in CTR group (P = 0.02). One-year percentage change of vBMD in the cortical bone in L1 and L2 has shown significantly decreased values by 10.5 and 9.1% in the GX group when compared to the percentage change observed in the controls (P silicon was significantly lowered by 26.7% one year after the total gastrectomy when compared to the baseline value (P = 0.009). Total gastrectomy in patients has induced severe osteoporotic changes in lumbar spine within one-year period. The observed osteoporotic changes were associated with decreased plasma concentration of silicon indicating importance of exocrine and endocrine functions of stomach for silicon homeostasis maintenance. Gastrectomy-induced bone loss was not related to decreased amino acid concentration in plasma obtained from overnight fasted patients. © 2015 by the Society for Experimental Biology and Medicine.

  18. Effect of acid concentration and pulp properties on hydrolysis reactions of mercerized sisal.

    Science.gov (United States)

    Lacerda, Talita M; Zambon, Márcia D; Frollini, Elisabete

    2013-03-01

    The influence of sulfuric acid concentration (H2SO4 5-25%, 100°C), crystallinity and fibers size on the hydrolysis reaction of sisal pulps were investigated, with the goal of evaluating both the liquor composition, as an important step in the production of bioethanol, and the residual non-hydrolyzed pulp, to determine its potential application as materials. Aliquots were withdrawn from the reaction media, and the liquor composition was analyzed by HPLC. The residual non-hydrolyzed pulps were characterized by SEM, their average molar mass and crystallinity index, and their size distribution was determined using a fiber analyzer. Sulfuric acid 25% led to the highest glucose content (approximately 10gL(-1)), and this acid concentration was chosen to evaluate the influence of both the fiber size and crystallinity of the starting pulp on hydrolysis. The results showed that fibers with higher length and lower crystallinity favored glucose production in approximately 12%, with respect to the highly crystalline shorter fibers. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Thermodynamic and kinetic modelling of the reduction of concentrated nitric acid

    International Nuclear Information System (INIS)

    Sicsic, David

    2011-01-01

    This research thesis aimed at determining and quantifying the different stages of the reduction mechanism in the case of concentrated nitric acid. After having reported the results of a bibliographical study on the chemical and electrochemical behaviour of concentrated nitric media (generalities, chemical equilibriums, NOx reactivity, electrochemical reduction of nitric acid), the author reports the development and discusses the results of a thermodynamic simulation of a nitric environment at 25 C. This allowed the main species to be identified in the liquid and gaseous phases of nitric acid solutions. The author reports an experimental electrochemical investigation coupled with analytic techniques (infrared and UV-visible spectroscopy) and shows that the reduction process depends on the cathodic overvoltage, and identifies three potential areas. A kinetic modelling of the stationary state and of the impedance is then developed in order to better determine, discuss and quantify the reduction process. The application of this kinetic model to the preliminary results of an electrochemical study performed on 304 L steel is then discussed [fr

  20. Variation of ascorbic acid concentration in fruits of cultivated and wild apples.

    Science.gov (United States)

    Fang, Ting; Zhen, Qiaoling; Liao, Liao; Owiti, Albert; Zhao, Li; Korban, Schuyler S; Han, Yuepeng

    2017-06-15

    Ascorbic acid (AsA) content in mature fruits of 457 apple accessions were measured, and a great variation in AsA concentration was detected. Wild fruits showed significantly higher level of AsA than cultivated fruits. Fruit AsA content was positively correlated with malic acid content, but negatively correlated with fruit weight and soluble solid content. Thus, the difference in AsA content between the wild and cultivated fruits could be attributed to an indirect consequence of human selection for larger fruit size, less acidity, and increased sweetness during apple domestication. Additionally, AsA concentration was extremely high in fruit at the juvenile stage, but dramatically decreased at the expanding and mature stages. The expression levels of three genes controlling AsA accumulation, MdGGP1, MdDHAR3-3, and MdNAT7-2, were significantly negatively correlated with AsA contents in fruits, suggesting a feedback regulation mechanism in AsA-related gene expression. Our results could be helpful for future apple breeding. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Low serum uric acid concentration augments insulin effects on the prevalence of metabolic syndrome.

    Science.gov (United States)

    Porchia, Leonardo M; Gonzalez-Mejia, M Elba; Torres-Rasgado, Enrique; Ruiz-Vivanco, Guadalupe; Pérez-Fuentes, Ricardo

    2018-05-01

    Insulin and uric acid were shown affect the prevalence of Metabolic Syndrome (MetS), but no studies examine their interaction. Therefore, we conducted this study to determine their biological interaction in subjects from central Mexico. 433 subjects were enrolled for a cross-sectional study. MetS was defined according to the Harmonizing Definition. Hyperuricemia was defined as ≥7.0 mg/dL in males and ≥5.8 mg/dL in females. Hyperinsulinemia was defined as ≥11.0 μU/mL. Pearson correlation coefficient (r) was calculated to determine the association between uric acid or insulin and MetS. Logistic regression was used to determine the risk (odds ratio) of developing MetS. Biological interactions were determined by the PROCESS Macro and Anderson's method. Insulin and uric acid levels were elevated in MetS positive group (p uric acid and insulin was associated with the number of MetS components (PROCESS Model 1, interaction coefficient = -0.009, 95%CI: -0.017 to -0.001, p = .036). Johnson-Neyman analysis suggests the interaction is lost when uric acid concentration increased >7.0 mg/dL. When the cohort was separated by hyperinsulinemia and hyperuricemia, there was a significant risk of developing MetS for subjects with hyperuricemia (odds ratio = 2.3; 95%CI: 1.1-4.8, p uric acid and insulin augments the prevalence of MetS; however, no biological interaction was determined for hyperuricemia and hyperinsulinemia. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  2. Effect of subinhibitory concentrations of chlorogenic acid on reducing the virulence factor production by Staphylococcus aureus.

    Science.gov (United States)

    Li, Guanghui; Qiao, Mingyu; Guo, Yan; Wang, Xin; Xu, Yunfeng; Xia, Xiaodong

    2014-09-01

    Chlorogenic acid (CA) has been reported to inhibit several pathogens, but the influence of subinhibitory concentrations of CA on virulence expression of pathogens has not been fully elucidated. The aim of this study was to explore the effect of CA on the virulence factor production of Staphylococcus aureus. The minimum inhibitory concentration (MIC) of CA against S. aureus was determined using a broth microdilution method. Hemolysin assays, coagulase titer assays, adherence to solid-phase fibrinogen assays, Western blot, and real-time reverse transcriptase-polymerase chain reaction were performed to evaluate the effect of subinhibitory concentrations of CA on the virulence factors of S. aureus. MIC of CA against S. aureus ATCC29213 was found to be 2.56 mg/mL. At subinhibitory concentrations, CA significantly inhibited the hemolysis and dose-dependently decreased coagulase titer. Reduced binding to fibrinogen and decreased production of SEA were observed with treatment of CA at concentrations ranging from 1/16MIC to 1/2MIC. CA markedly inhibited the expression of hla, sea, and agr genes in S. aureus. These data demonstrate that the virulence expression of S. aureus could be reduced by CA and suggest that CA could be potentially developed as a supplemental strategy to control S. aureus infection and to prevent staphylococcal food poisoning.

  3. Analysis of Factors Influencing Soil Salinity, Acidity, and Arsenic Concentration in a Polder in Southwest Bangladesh

    Science.gov (United States)

    Ayers, J. C.; Patton, B.; Fry, D. C.; Goodbred, S. L., Jr.

    2017-12-01

    Soil samples were collected on Polder 32 in the coastal zone of SW Bangladesh in wet (October) and dry (May) seasons from 2013-2017 and analyzed to characterize the problems of soil salinization and arsenic contamination and identify their causes. Soils are entisols formed from recently deposited, predominantly silt-sized sediments with low carbon concentrations typical of the local mangrove forests. Soluble (DI extract) arsenic concentrations were below the Government of Bangladesh limit of 50 ppb for drinking water. Soil acidity and extract arsenic concentrations exhibit spatial variation but no consistent trends. In October soil extract As is higher and S and pH are lower than in May. These observations suggest that wet season rainwater oxidizes pyrite, reducing soil S and releasing H+, causing pH to decrease. Released iron is oxidized to form Hydrous Ferric Oxyhydroxides (HFOs), which sorb As and increase extractable As in wet season soils. Changes in pH are small due to pH buffering by soil carbonates. Soil and rice paddy water salinities are consistently higher in May than October, reaching levels in May that reduce rice yields. Rice grown in paddies should be unaffected by salt concentrations in the wet season, while arsenic concentrations in soil may be high enough to cause unsafe As levels in produced rice.

  4. Effective depolymerization of concentrated acid hydrolysis lignin using a carbon-supported ruthenium catalyst in ethanol/formic acid media.

    Science.gov (United States)

    Kristianto, Ivan; Limarta, Susan Olivia; Lee, Hyunjoo; Ha, Jeong-Myeong; Suh, Dong Jin; Jae, Jungho

    2017-06-01

    Lignin isolated by two-step concentrated acid hydrolysis of empty fruit bunch (EFB) was effectively depolymerized into a high-quality bio-oil using formic acid (FA) as an in-situ hydrogen source and Ru/C as a catalyst in supercritical ethanol. A bio-oil yield of 66.3wt% with an average molecular weight of 822g/mol and an aromatic monomer content of 6.1wt% was achieved at 350°C and a FA-to-lignin mass ratio of 3 after a reaction time of 60min. The combination of Ru/C and FA also resulted in a significant reduction in the oxygen content of the bio-oil by ∼60% and a corresponding increase in the higher heating value (HHV) to 32.7MJ/kg due to the enhanced hydrodeoxygenation activity. An examination of the FA decomposition characteristics revealed that Ru/C provides a greater increase in the rate of hydrogen production from FA, explaining the efficient depolymerization of lignin in a combined system. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Perfluoroalkyl Acid Concentrations in Blood Samples Subjected to Transportation and Processing Delay

    DEFF Research Database (Denmark)

    Bach, Cathrine Carlsen; Henriksen, Tine Brink; Bossi, Rossana

    2015-01-01

    and transportation prior to processing and samples with immediate processing and freezing. METHODS: Pregnant women recruited at Aarhus University Hospital, Denmark, (n = 88) provided paired blood samples. For each pair of samples, one was immediately processed and plasma was frozen, and the other was delayed...... and transported as whole blood before processing and freezing of plasma (similar to the Danish National Birth Cohort). We measured 12 perfluoroalkyl acids and present results for compounds with more than 50% of samples above the lower limit of quantification. RESULTS: For samples taken in the winter, relative...... differences between the paired samples ranged between -77 and +38% for individual perfluoroalkyl acids. In most cases concentrations were lower in the delayed and transported samples, e.g. the relative difference was -29% (95% confidence interval -30; -27) for perfluorooctane sulfonate. For perfluorooctanoate...

  6. Suitable Concentrations of Uric Acid Can Reduce Cell Death in Models of OGD and Cerebral Ischemia-Reperfusion Injury.

    Science.gov (United States)

    Zhang, Bin; Yang, Ning; Lin, Shao-Peng; Zhang, Feng

    2017-07-01

    Cerebral infarction (CI) is a common clinical cerebrovascular disease, and to explore the pathophysiological mechanisms and seek effective treatment means are the hotspot and difficult point in medical research nowadays. Numerous studies have confirmed that uric acid plays an important role in CI, but the mechanism has not yet been clarified. When treating HT22 and BV-2 cells with different concentrations of uric acid, uric acid below 450 μM does not have significant effect on cell viability, but uric acid more than 500 μM can significantly inhibit cell viability. After establishing models of OGD (oxygen-glucose deprivation) with HT22 and BV-2 cells, uric acid at a low concentration (50 μM) cannot improve cell viability and apoptosis, and Reactive oxygen species (ROS) levels during OGD/reoxygenation; a suitable concentration (300 μM) of uric acid can significantly improve cell viability and apoptosis, and reduce ROS production during OGD/reoxygenation; but a high concentration (1000 μM) of uric acid can further reduce cell viability and enhance ROS production. After establishing middle cerebral artery occlusion of male rats with suture method, damage and increase of ROS production in brain tissue could be seen, and after adding suitable concentration of uric acid, the degree of brain damage and ROS production was reduced. Therefore, different concentrations of uric acid should have different effect, and suitable concentrations of uric acid have neuroprotective effect, and this finding may provide guidance for study on the clinical curative effect of uric acid.

  7. Phytic acid concentration influences iron bioavailability from biofortified beans in Rwandese women with low iron status.

    Science.gov (United States)

    Petry, Nicolai; Egli, Ines; Gahutu, Jean B; Tugirimana, Pierrot L; Boy, Erick; Hurrell, Richard

    2014-11-01

    The common bean is a staple crop in many African and Latin American countries and is the focus of biofortification initiatives. Bean iron concentration has been doubled by selective plant breeding, but the additional iron is reported to be of low bioavailability, most likely due to high phytic acid (PA) concentrations. The present study evaluated the impact of PA on iron bioavailability from iron-biofortified beans. Iron absorption, based on erythrocyte incorporation of stable iron isotopes, was measured in 22 Rwandese women who consumed multiple, composite bean meals with potatoes or rice in a crossover design. Iron absorption from meals containing biofortified beans (8.8 mg Fe, 1320 mg PA/100 g) and control beans (5.4 mg Fe, 980 mg PA/100 g) was measured with beans containing either their native PA concentration or with beans that were ∼50% dephytinized or >95% dephytinized. The iron concentration of the cooked composite meals with biofortified beans was 54% higher than in the same meals with control beans. With native PA concentrations, fractional iron absorption from the control bean meals was 9.2%, 30% higher than that from the biofortified bean meals (P bean meals (406 μg) was 19% higher (P bean meals. With ∼50% and >95% dephytinization, the quantity of iron absorbed from the biofortified bean meals increased to 599 and 746 μg, respectively, which was 37% (P bean meals. PA strongly decreases iron bioavailability from iron-biofortified beans, and a high PA concentration is an important impediment to the optimal effectiveness of bean iron biofortification. Plant breeders should focus on lowering the PA concentration of high-iron beans. This trial was registered at clinicaltrials.gov as NCT01521273. © 2014 American Society for Nutrition.

  8. Treatment with clozapine and its effect on plasma homovanillic acid and norepinephrine concentrations in schizophrenia.

    Science.gov (United States)

    Davidson, M; Kahn, R S; Stern, R G; Hirschowitz, J; Apter, S; Knott, P; Davis, K L

    1993-02-01

    Measurement of plasma concentrations of the dopamine metabolite, homovanillic acid (pHVA), is an indirect tool to assess changes in dopamine turnover. Levels of pHVA have been reported to decrease during treatment with conventional antidopaminergic, neuroleptics, with the decrement correlating with symptomatic improvement in schizophrenic symptoms. Clozapine, an atypical neuroleptic, is the only drug proved to be effective in treatment-refractory patients. However, the mechanism mediating this unique efficacy has not been fully elucidated. This study examined the effect of clozapine on pHVA concentrations in schizophrenic patients. Since clozapine potently binds to alpha 2-adrenergic receptors, plasma norepinephrine (pNE) concentrations were also measured. Twenty-eight treatment-refractory schizophrenic patients (24 men, 4 women) were treated with clozapine (up to 600 mg/day) for 5 weeks, after a minimum 1-week drug-free period. Symptomatology and pHVA and pNE concentrations were measured at the last drug-free day and weekly for 5 weeks. Fourteen patients responded to clozapine treatment, while an equal number did not. Mean pHVA concentrations did not significantly change during treatment with clozapine. Although clozapine tended to lower pHVA concentrations in treatment responders, the effect was small and not significant. Clozapine treatment significantly raised pNE concentrations, but this did not differentiate responders from nonresponders to clozapine. These findings suggest that clozapine's effect on DA turnover is small and that clozapine may be effective in treatment-refractory schizophrenia by mechanisms other than, or in addition to, dopamine receptor blockade. However, since about one-third of NE is metabolized into HVA, the clozapine-induced increase in pNE may have overshadowed a possible lowering effect of clozapine on pHVA.

  9. Procedure for recovery from an uranium containing concentrate and phosphoric acid, as well as an uranium containing concentrate and phosphoric acid obtained by this procedure

    International Nuclear Information System (INIS)

    1980-01-01

    The phosphate ore is dissolved in sulphuric acid and the formed calcium sulphate is separated from the solution. The uranium is then precipitated by adding ammonium fluoride solution to the remaining phosphoric acid solution. When the phosphate ore is dissolved in sulphuric acid, fluorine gas is liberated and this is then used to produce the ammonium fluoride solution. (Th.P.)

  10. Intraileal casein infusion increases plasma concentrations of amino acids in humans: A randomized cross over trial.

    Science.gov (United States)

    Ripken, Dina; van Avesaat, Mark; Troost, Freddy J; Masclee, Ad A; Witkamp, Renger F; Hendriks, Henk F

    2017-02-01

    Activation of the ileal brake by casein induces satiety signals and reduces energy intake. However, adverse effects of intraileal casein administration have not been studied before. These adverse effects may include impaired amino acid digestion, absorption and immune activation. To investigate the effects of intraileal infusion of native casein on plasma amino acid appearance, immune activation and gastrointestinal (GI) symptoms. A randomized single-blind cross over study was performed in 13 healthy subjects (6 male; mean age 26 ± 2.9 years; mean body mass index 22.8 ± 0.4 kg/m -2 ), who were intubated with a naso-ileal feeding catheter. Thirty minutes after intake of a standardized breakfast, participants received an ileal infusion, containing either control (C) consisting of saline, a low-dose (17.2 kcal) casein (LP) or a high-dose (51.7 kcal) of casein (HP) over a period of 90 min. Blood samples were collected for analysis of amino acids (AAs), C-reactive protein (CRP), pro-inflammatory cytokines and oxylipins at regular intervals. Furthermore, GI symptom questionnaires were collected before, during and after ileal infusion. None of the subjects reported any GI symptoms before, during or after ileal infusion of C, LP and HP. Plasma concentrations of all AAs analyzed were significantly increased after infusion of HP as compared to C (p casein, respectively. Ileal casein infusion did not affect plasma concentrations of CRP, IL-6, IL-8, IL-1β and TNF-α. Infusion of HP resulted in a decreased concentration of 11,12-dihydroxyeicosatrienoic acid whereas none of the other oxylipins analyzed were affected. A single intraileal infusion of native casein results in a concentration and time dependent increase of AAs in plasma, suggesting an effective digestion and absorption of AAs present in casein. Also, ileal infusion did not result in immune activation nor in GI symptoms. CLINICALTRIALS.GOV: NCT01509469. Copyright © 2016 The Authors. Published by Elsevier

  11. Hydrogen evolution activity and electrochemical stability of selected transition metal carbides in concentrated phosphoric acid

    DEFF Research Database (Denmark)

    Tomás García, Antonio Luis; Jensen, Jens Oluf; Bjerrum, Niels J.

    2014-01-01

    phosphoric acid were investigated in a temperature range from 80 to 170°C. A significant dependence of the activities on temperature was observed for all five carbide samples. Through the entire temperature range Group 6 metal carbides showed higher activity than that of the Group 5 metal carbides......Alternative catalysts based on carbides of Group 5 (niobium and tantalum) and 6 (chromium, molybdenum and tungsten) metals were prepared as films on the metallic substrates. The electrochemical activities of these carbide electrodes towards the hydrogen evolution reaction (HER) in concentrated...

  12. Estimation of very low concentrations of Ruthenium by spectrophotometric method using barbituric acid as complexing agent

    International Nuclear Information System (INIS)

    Ramakrishna Reddy, S.; Srinivasan, R.; Mallika, C.; Kamachi Mudali, U.; Natarajan, R.

    2012-01-01

    Spectrophotometric method employing numerous chromogenic reagents like thiourea, 1,10-phenanthroline, thiocyanate and tropolone is reported in the literature for the estimation of very low concentrations of Ru. A sensitive spectrophotometric method has been developed for the determination of ruthenium in the concentration range 1.5 to 6.5 ppm in the present work. This method is based on the reaction of ruthenium with barbituric acid to produce ruthenium(ll)tris-violurate, (Ru(H 2 Va) 3 ) -1 complex which gives a stable deep-red coloured solution. The maximum absorption of the complex is at 491 nm due to the inverted t 2g → Π(L-L ligand) electron - transfer transition. The molar absorptivity of the coloured species is 9,851 dm 3 mol -1 cm -1

  13. Lack of effect of laboratory-provoked anxiety on plasma homovanillic acid concentration in normal subjects.

    Science.gov (United States)

    Zemishlany, Z; Davidson, M

    1996-08-15

    The present study was undertaken to investigate if acute anxiety can affect plasma concentrations of homovanillic acid (pHVA). Since elevated pHVA levels have been associated with severity of schizophrenic symptoms, the results of this study will help determine if the pHVA elevations are directly related to psychosis or if anxiety is also a contributory factor. Anxiety was provoked in 10 young normal subjects by a combined paradigm of mental arithmetic task and threat of electrical shock. A significant increase in self-ratings of anxiety, blood pressure, and plasma levels of norepinephrine, 3-methoxy-4-hydroxyphenylethyleneglycol and growth hormone indicated that the paradigm used was effective in provoking anxiety; however, anxiety did not affect pHVA concentrations. The results may support the notion that increased pHVA levels in severely ill schizophrenic patients are related to the schizophrenic pathophysiology rather than to anxiety.

  14. Increments in plasma homovanillic acid concentrations after neuroleptic discontinuation are associated with worsening of schizophrenic symptoms.

    Science.gov (United States)

    Khan, R S; Amin, F; Powchik, P; Knott, P; Goldstein, M; Apter, S; Kerman, B; Jaff, S; Davidson, M

    1990-01-01

    1. Thirty-two male schizophrenic patients participated in this study. 2. Plasma concentrations of the dopamine metabolite, homovanillic acid (pHVA) were assessed once on neuroleptic medication and twice a week for a maximum of six weeks after its discontinuation. 3. Psychiatric symptomatology was assessed once on neuroleptic medication and once a week for a maximum of six weeks after its discontinuation, using the brief psychiatric rating scale (BPRS). 4. pHVA and total BPRS score increased significantly after discontinuation of neuroleptic as compared to baseline. 5. The magnitude of pHVA and BPRS increments after discontinuation of neuroleptic correlated significantly. 6. Results of this study suggest that worsening of schizophrenic symptoms after discontinuation of neuroleptic treatment is associated with increased pHVA concentrations.

  15. Use of milk fatty acids to estimate plasma nonesterified fatty acid concentrations as an indicator of animal energy balance.

    Science.gov (United States)

    Dórea, J R R; French, E A; Armentano, L E

    2017-08-01

    Negative energy balance is an important part of the lactation cycle, and measuring the current energy balance of a cow is useful in both applied and research settings. The objectives of this study were (1) to determine if milk fatty acid (FA) proportions were consistently related to plasma nonesterified fatty acids (NEFA); (2) to determine if an individual cow with a measured milk FA profile is above or below a NEFA concentration, (3) to test the universality of the models developed within the University of Wisconsin and US Dairy Forage Research Center cows. Blood samples were collected on the same day as milk sampling from 105 Holstein cows from 3 studies. Plasma NEFA was quantified and a threshold of 600 µEq/L was applied to classify animals above this concentration as having high NEFA (NEFA high ). Thirty milk FA proportions and 4 milk FA ratios were screened to evaluate their capacity to classify cows with NEFA high according to determined milk FA threshold. In addition, 6 linear regression models were created using individual milk FA proportions and ratios. To evaluate the universality of the linear relationship between milk FA and plasma NEFA found in the internal data set, 90 treatment means from 21 papers published in the literature were compiled to test the model predictions. From the 30 screened milk FA, the odd short-chain fatty acids (C7:0, C9:0, C11:0, and C13:0) had sensitivity slightly greater than the other short-chain fatty acids (83.3, 94.8, 80.0, and 85.9%, respectively). The sensitivities for milk FA C6:0, C8:0, C10:0, and C12:0 were 78.8, 85.3, 80.1, and 83.9%, respectively. The threshold values to detect NEFA high cows for the last group of milk FA were ≤2.0, ≤0.94, ≤1.4, and ≤1.8 g/100 g of FA, respectively. The milk FA C14:0 and C15:0 had sensitivities of 88.7 and 85.0% and a threshold of ≤6.8 and ≤0.53 g/100 g of FA, respectively. The linear regressions using the milk FA ratios C18:1 to C15:0 and C17:0 to C15:0 presented lower

  16. Estimate of serum immunoglobulin G concentration using refractometry with or without caprylic acid fractionation.

    Science.gov (United States)

    Morrill, K M; Polo, J; Lago, A; Campbell, J; Quigley, J; Tyler, H

    2013-07-01

    Objectives of this study were to develop a rapid calf-side test to determine serum IgG concentrations using caprylic acid (CA) fractionation, followed by refractometry of the IgG-rich supernatant and compare the accuracy of this method with results obtained using refractometry using raw serum. Serum samples (n=200) were obtained from 1-d-old calves, frozen (-20°C), and shipped to the laboratory. Samples were allowed to thaw for 1h at room temperature. Fractionation with CA was conducted by adding 1mL of serum to a tube containing 45, 60, or 75µL of CA and 0.5, 1.0, or 1.5mL of 0.06 M acetic acid. The tube contents were mixed well, allowed to react for 1 min, and then centrifuged at 3,300 × g for 0, 10, or 20 min at 25°C. The %Brix and refractive index of the fractionated supernatant were determined using a digital refractometer. Nonfractionated serum was analyzed for %Brix (BRn), refractive index (nDn), and IgG concentration by radial immunodiffusion. The mean serum IgG concentration was 19.0 mg/mL [standard deviation (SD)=9.7], with a range of 3.5 to 47.0 mg/mL. The mean serum BRn was 8.6 (SD=0.91), with a range of 6.8 to 11.0. The mean serum nDn was 1.34566 (SD=0.00140), with a range of 1.34300 to 1.34930. Serum nDn was positively correlated with IgG concentration (correlation coefficient=0.86; n=185). Fractionated samples treated with 1mL 0.6 M acetic acid and 60µL of CA and not centrifuged before analysis resulted in a strong relationship between the refractive index of the fractionated supernatant and IgG (correlation coefficient=0.80; n=45). Regression was used to determine cut points indicative of 10, 12, and 14 mg of IgG/mL to determine the sensitivity and specificity of refractometry to identify failure of passive transfer (serum IgG refractometry of nonfractionated calf serum provides a strong estimate of IgG concentration and 7.8% Brix may be used as the cut point to identify failure of passive transfer in 1-d-old calves. Copyright © 2013 American

  17. Changes in relative and absolute concentrations of plasma phospholipid fatty acids observed in a randomized trial of Omega-3 fatty acids supplementation in Uganda.

    Science.gov (United States)

    Song, Xiaoling; Diep, Pho; Schenk, Jeannette M; Casper, Corey; Orem, Jackson; Makhoul, Zeina; Lampe, Johanna W; Neuhouser, Marian L

    2016-11-01

    Expressing circulating phospholipid fatty acids (PLFAs) in relative concentrations has some limitations: the total of all fatty acids are summed to 100%; therefore, the values of individual fatty acid are not independent. In this study we examined if both relative and absolute metrics could effectively measure changes in circulating PLFA concentrations in an intervention trial. 66 HIV and HHV8 infected patients in Uganda were randomized to take 3g/d of either long-chain omega-3 fatty acids (1856mg EPA and 1232mg DHA) or high-oleic safflower oil in a 12-week double-blind trial. Plasma samples were collected at baseline and end of trial. Relative weight percentage and absolute concentrations of 41 plasma PLFAs were measured using gas chromatography. Total cholesterol was also measured. Intervention-effect changes in concentrations were calculated as differences between end of 12-week trial and baseline. Pearson correlations of relative and absolute concentration changes in individual PLFAs were high (>0.6) for 37 of the 41 PLFAs analyzed. In the intervention arm, 17 PLFAs changed significantly in relative concentration and 16 in absolute concentration, 15 of which were identical. Absolute concentration of total PLFAs decreased 95.1mg/L (95% CI: 26.0, 164.2; P=0.0085), but total cholesterol did not change significantly in the intervention arm. No significant change was observed in any of the measurements in the placebo arm. Both relative weight percentage and absolute concentrations could effectively measure changes in plasma PLFA concentrations. EPA and DHA supplementation changes the concentrations of multiple plasma PLFAs besides EPA and DHA.Both relative weight percentage and absolute concentrations could effectively measure changes in plasma phospholipid fatty acid (PLFA) concentrations. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. The association of plasma gamma-aminobutyric acid concentration with postoperative delirium in critically ill patients.

    Science.gov (United States)

    Yoshitaka, Shiho; Egi, Moritoki; Kanazawa, Tomoyuki; Toda, Yuichiro; Morita, Kiyoshi

    2014-12-01

    Delirium is a common complication in postoperative, critically ill patients. The mechanism of postoperative delirium is not well understood but many studies have shown significant associations between benzodiazepine use, alcohol withdrawal and cirrhosis, and an increased risk of delirium. We aimed to investigate a possible link with alterations of gamma-aminobutyric acid (GABA) activity. A prospective observational investigation of 40 patients > 20 years old who had undergone elective surgery with general anaesthesia and were expected to need postoperative intensive care for more than 48 hours. We assessed postoperative delirium using the confusion assessment method in the intensive care unit at 1 hour after the operation and on postoperative Day (POD) 1 and POD 2. We collected blood samples for measurement of plasma GABA concentrations before the operation and on POD 1 and 2. Postoperative delirium and perioperative plasma GABA concentrations in patients with and without delirium. Postoperative delirium occurred in 13 of the patients. Patients with delirium had significantly higher Acute Physiology and Chronic Health Evaluation II scores than patients without delirium. The mean plasma GABA concentration on POD 2 was significantly lower in patients with delirium than in those without delirium. After adjustment of relevant variables, plasma GABA concentration on POD 2 was independently associated with postoperative delirium. Plasma GABA level on POD 2 has a significant independent association with postoperative delirium.

  19. Separation and concentration of lead, uranium and copper using polystyrene resins functionalised with azobenzylphosphonic acid ligands

    International Nuclear Information System (INIS)

    Ueda, Kazumasa; Sato, Yuko; Yoshimura, Osamu; Yamamoto, Yoshikazu

    1988-01-01

    Two polystyrene resins functionalised with azobenzylphosphonic acid ligands were synthesised and applications for the concentration, separation and determination of micro- or milligram concentrations of metal ions were studied. Physical and chemical properties such as specific mass, water content and ion-exchange capacity were measured and the characteristics of the resins were examined. The resins were especially useful for the concentration of Pbsup(II), Usup(VI) and Cusup(II) by batch and column operations, and effective separations of Pbsup(II) from Group VIII and IIB ions could be achieved by selecting the eluents. Trace amounts of Pbsup(II), Usup(VI), Cusup(II), Mnsup(II), Znsup(II) and Fesup(III) were quantitatively retained on the resin columns at neutral pH and easily recovered by elution with 2M HCl and 2M HNO 3 . The resins were successfully applied to the concentration of trace amounts of metals in river and sea waters prior to spectroscopic determinations. (author)

  20. The serum uric acid concentration is not causally linked to diabetic nephropathy in type 1 diabetes.

    Science.gov (United States)

    Ahola, Aila J; Sandholm, Niina; Forsblom, Carol; Harjutsalo, Valma; Dahlström, Emma; Groop, Per-Henrik

    2017-05-01

    Previous studies have shown a relationship between uric acid concentration and progression of renal disease. Here we studied causality between the serum uric acid concentration and progression of diabetic nephropathy in 3895 individuals with type 1 diabetes in the FinnDiane Study. The renal status was assessed with the urinary albumin excretion rate and estimated glomerular filtration rate (eGFR) at baseline and at the end of the follow-up. Based on previous genomewide association studies on serum uric acid concentration, 23 single nucleotide polymorphisms (SNPs) with good imputation quality were selected for the SNP score. This score was used to assess the causality between serum uric acid and renal complications using a Mendelian randomization approach. At baseline, the serum uric acid concentration was higher with worsening renal status. In multivariable Cox regression analyses, baseline serum uric acid concentration was not independently associated with progression of diabetic nephropathy over a mean follow-up of 7 years. However, over the same period, baseline serum uric acid was independently associated with the decline in eGFR. In the cross-sectional logistic regression analyses, the SNP score was associated with the serum uric acid concentration. Nevertheless, the Mendelian randomization showed no causality between uric acid and diabetic nephropathy, eGFR categories, or eGFR as a continuous variable. Thus, our results suggest that the serum uric acid concentration is not causally related to diabetic nephropathy but is a downstream marker of kidney damage. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  1. Detailed dimethylacetal and fatty acid composition of rumen content from lambs fed lucerne or concentrate supplemented with soybean oil.

    Science.gov (United States)

    Alves, Susana P; Santos-Silva, José; Cabrita, Ana R J; Fonseca, António J M; Bessa, Rui J B

    2013-01-01

    Lipid metabolism in the rumen is responsible for the complex fatty acid profile of rumen outflow compared with the dietary fatty acid composition, contributing to the lipid profile of ruminant products. A method for the detailed dimethylacetal and fatty acid analysis of rumen contents was developed and applied to rumen content collected from lambs fed lucerne or concentrate based diets supplemented with soybean oil. The methodological approach developed consisted on a basic/acid direct transesterification followed by thin-layer chromatography to isolate fatty acid methyl esters from dimethylacetal, oxo- fatty acid and fatty acid dimethylesters. The dimethylacetal composition was quite similar to the fatty acid composition, presenting even-, odd- and branched-chain structures. Total and individual odd- and branched-chain dimethylacetals were mostly affected by basal diet. The presence of 18:1 dimethylacetals indicates that biohydrogenation intermediates might be incorporated in structural microbial lipids. Moreover, medium-chain fatty acid dimethylesters were identified for the first time in the rumen content despite their concentration being relatively low. The fatty acids containing 18 carbon-chain lengths comprise the majority of the fatty acids present in the rumen content, most of them being biohydrogenation intermediates of 18:2n-6 and 18:3n-3. Additionally, three oxo- fatty acids were identified in rumen samples, and 16-O-18:0 might be produced during biohydrogenation of the 18:3n-3.

  2. Using Spectrophotometric Titrations To Characterize Humic Acid Reactivity at Environmental Concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Janot, N.; Benedetti, M. F. [Univ Paris Diderot, Lab Geochim Eaux, UMR CNRS 7154, IPGP, F-75025 Paris 13 (France); Janot, N.; Reiller, P. E. [CE Saclay, CEA DEN DANS DPC SECR, Lab Speciat Radionucleides and Mol, F-91191 Gif Sur Yvette (France); Korshin, G. V. [Univ Washington, Dept Civil and Environm Engn, Seattle, WA 98195 (United States)

    2010-07-01

    Potentiometric titration is a common method to characterize dissolved organic matter (DOM) reactivity. Because of the sensitivity of pH electrodes, it is necessary to work with very high DOM ({>=}1 g/L) concentrations that are unrealistic compared to those found in natural waters (0. 1 to 100 mg/L). To obtain proton binding data for concentrations closer to environmental values, spectroscopic titration methodology is a viable alternative to traditional potentiometric titrations. Spectrophotometric titrations and UV visible spectra of a diluted solution of purified Aldrich humic acid (5 mg(DOC)/L) are used to estimate changes in proton binding moieties as function of pH and ionic strength after calculation of differential absorbance spectra variations. After electrostatic correction of spectrophotometric data, there is a linear operational correlation between spectrophotometric and potentiometric data which can be used as a transfer function between the two properties. Spectrophotometric titrations are then used to determine the changes of humic acid protonation after adsorption onto alpha-alumina. (authors)

  3. Influence of lactose hydrolysis and solids concentration on alcohol production by yeast in acid whey ultrafiltrate

    Energy Technology Data Exchange (ETDEWEB)

    O' leary, V S; Sutton, C; Bencivengo, M; Sullivan, B; Holsinger, V H

    1977-11-01

    Alcohol yields of 6.5 percent were obtained with Saccharomyces cerevisiae in lactase-hydrolyzed acid whey permeate containing 30 to 35 percent total solids. Maximum alcohol yields obtained with Kluyveromyces fragilis were 4.5 percent in lactase-hydrolyzed acid whey permeate at a solids concentration of 20 percent and 3.7 percent in normal permeate at a solids concentration of 10 percent. Saccharomyces cerevisiae efficiently converted the glucose present in lactase-hydrolyzed whey permeates containing 5 to 30 percent total solids (2 to 13 percent glucose) to alcohol. However, the galactose, which comprised about half the available carbohydrate in lactase-hydrolyzed whey, was not utilized by S. cerevisiae, so that even though alcohol yields were higher when this organism was used, the process was wasteful in that a substantial proportion of the substrate was not fermented. For the process to become commercially feasible, an efficient means of rapidly converting both the galactose and glucose to alcohol must be found.

  4. Using Spectrophotometric Titrations To Characterize Humic Acid Reactivity at Environmental Concentrations

    International Nuclear Information System (INIS)

    Janot, N.; Benedetti, M. F.; Janot, N.; Reiller, P. E.; Korshin, G. V.

    2010-01-01

    Potentiometric titration is a common method to characterize dissolved organic matter (DOM) reactivity. Because of the sensitivity of pH electrodes, it is necessary to work with very high DOM (≥1 g/L) concentrations that are unrealistic compared to those found in natural waters (0. 1 to 100 mg/L). To obtain proton binding data for concentrations closer to environmental values, spectroscopic titration methodology is a viable alternative to traditional potentiometric titrations. Spectrophotometric titrations and UV visible spectra of a diluted solution of purified Aldrich humic acid (5 mg(DOC)/L) are used to estimate changes in proton binding moieties as function of pH and ionic strength after calculation of differential absorbance spectra variations. After electrostatic correction of spectrophotometric data, there is a linear operational correlation between spectrophotometric and potentiometric data which can be used as a transfer function between the two properties. Spectrophotometric titrations are then used to determine the changes of humic acid protonation after adsorption onto alpha-alumina. (authors)

  5. Supra-physiological folic acid concentrations induce aberrant DNA methylation in normal human cells in vitro.

    Science.gov (United States)

    Charles, Michelle A; Johnson, Ian T; Belshaw, Nigel J

    2012-07-01

    The micronutrients folate and selenium may modulate DNA methylation patterns by affecting intracellular levels of the methyl donor S-adenosylmethionine (SAM) and/or the product of methylation reactions S-adenosylhomocysteine (SAH). WI-38 fibroblasts and FHC colon epithelial cells were cultured in the presence of two forms of folate or four forms of selenium at physiologically-relevant doses, and their effects on LINE-1 methylation, gene-specific CpG island (CGI) methylation and intracellular SAM:SAH were determined. At physiologically-relevant doses the forms of folate or selenium had no effect on LINE-1 or CGI methylation, nor on intracellular SAM:SAH. However the commercial cell culture media used for the selenium studies, containing supra-physiological concentrations of folic acid, induced LINE-1 hypomethylation, CGI hypermethylation and decreased intracellular SAM:SAH in both cell lines. We conclude that the exposure of normal human cells to supra-physiological folic acid concentrations present in commercial cell culture media perturbs the intracellular SAM:SAH ratio and induces aberrant DNA methylation.

  6. Silicon Decreases Dimethylarsinic Acid Concentration in Rice Grain and Mitigates Straighthead Disorder.

    Science.gov (United States)

    Limmer, Matthew Alan; Wise, Patrick; Dykes, Gretchen E; Seyfferth, Angelia L

    2018-04-17

    While root Si transporters play a role in the uptake of arsenite and organic As species dimethylarsinic acid (DMA) and monomethylarsonic acid (MMA) in rice ( Oryza sativa L.), the impact of Si addition on the accumulation of DMA and MMA in reproductive tissues has not been directly evaluated, particularly in isolation from inorganic As species. Furthermore, DMA and MMA are suspected causal agents of straighthead disorder. We performed a hydroponic study to disentangle the impact of Si on accumulation of DMA and MMA in rice grain. At 5 μM, MMA was toxic to rice, regardless of Si addition, although Si significantly decreased root MMA concentrations. Plants dosed with 5 μM DMA grew well vegetatively but exhibited straighthead disorder at the lowest Si dose, and this DMA-induced yield loss reversed with increasing solution Si. Increasing Si also significantly decreased DMA concentrations in roots, straw, husk, and grain, particularly in mature plants. Si restricted grain DMA through competition for root uptake and downregulation of root Si transporters particularly at later stages of growth when Si uptake was greatest. Our finding that DMA causes straighthead disorder under low Si availability but not under high Si availability suggests Si as a straighthead management strategy.

  7. Influence of deficit irrigation strategies on fatty acid and tocopherol concentration of almond (Prunus dulcis).

    Science.gov (United States)

    Zhu, Ying; Taylor, Cathy; Sommer, Karl; Wilkinson, Kerry; Wirthensohn, Michelle

    2015-04-15

    The effects of deficit irrigation on almond fatty acid and tocopherol levels were studied in a field trial. Mature almond trees were subjected to three levels of deficit irrigation (85%, 70% and 55% of potential crop evapotranspiration (ETo), as well as control (100% ETo) and over-irrigation (120% ETo) treatments. Two deficit irrigation strategies were employed: regulated deficit irrigation (RDI) and sustained deficit irrigation (SDI). Moderate deficit irrigation (85% RDI and 85% SDI) had no detrimental impact on almond kernel lipid content, but severe and extreme deficiencies (70% and 55%) influenced lipid content. Unsaturated fatty acid (USFA) and saturated fatty acid (SFA) contents fluctuated under these treatments, the oleic/linoleic ratio increased under moderate water deficiency, but decreased under severe and extreme water deficiency. Almond tocopherols concentration was relatively stable under deficit irrigation. The variation between years indicated climate has an effect on almond fruit development. In conclusion it is feasible to irrigate almond trees using less water than the normal requirement, without significant loss of kernel quality. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Water-lactose behavior as a function of concentration and presence of lactic acid in lactose model systems.

    Science.gov (United States)

    Wijayasinghe, Rangani; Vasiljevic, Todor; Chandrapala, Jayani

    2015-12-01

    The presence of high amounts of lactic acid in acid whey restricts its ability to be further processed because lactose appears to remain in its amorphous form. A systematic study is lacking in this regard especially during the concentration step. Hence, the main aim of the study was to establish the structure and behavior of water molecules surrounding lactose in the presence of 1% (wt/wt) lactic acid at a concentration up to 50% (wt/wt). Furthermore, the crystallization nature of freeze-dried lactose with or without lactic acid was established using differential scanning calorimetry and Fourier transform infrared spectroscopy. Two mechanisms were proposed to describe the behavior of water molecules around lactose molecules during the concentration of pure lactose and lactose solutions with lactic acid. Pure lactose solution exhibited a water evaporation enthalpy of ~679 J·g(-1), whereas lactose+ lactic acid solution resulted in ~965 J·g(-1) at a 50% (wt/wt) concentration. This indicates a greater energy requirement for water removal around lactose in the presence of lactic acid. Higher crystallization temperatures were observed with the presence of lactic acid, indicating a delay in crystallization. Furthermore, less crystalline lactose (~12%) was obtained in the presence of lactic acid, indicating high amorphous nature compared with pure lactose where ~50% crystallinity was obtained. The Fourier transform infrared spectra revealed that the strong hydration layer consisting lactic acid and H3O(+) ions surrounded lactose molecules via strong H bonds, which restricted water mobility, induced a change in structure of lactose, or both, creating unfavorable conditions for lactose crystallization. Thus, partial or complete removal of lactic acid from acid whey may be the first step toward improving the ability of acid whey to be processed. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  9. Higher concentrations of branched-chain amino acids in breast milk of obese mothers.

    Science.gov (United States)

    De Luca, Arnaud; Hankard, Régis; Alexandre-Gouabau, Marie-Cécile; Ferchaud-Roucher, Véronique; Darmaun, Dominique; Boquien, Clair-Yves

    2016-01-01

    Nutrition during fetal life and early childhood is thought to play a crucial role in the risk for developing metabolic syndrome and cardiovascular diseases in the future adult and branched-chain amino acids (BCAA) intake may play a role in the development of obesity. The aim of this study was to compare the breast milk amino acid profiles of obese and normal weight (control) breast-feeding mothers. Fifty obese and 50 control breast-feeding mothers were enrolled. Age and parity were similar in both groups. Breast milk samples were collected at the end of the first month of lactation. Free amino acid (FAA) concentrations in breast milk were determined by ultra-performance liquid chromatography tandem mass spectrometry. Comparisons between groups were performed using a two-tailed paired t test. We analyzed 45 breast milk samples from each group. Body mass index was 34.3 ± 3.9 kg/m(2) in the obese group and 21.6 ± 1.4 kg/m(2) in the control group (P milk of obese mothers (95.5 ± 38.2 μM versus 79.8 ± 30.9 μM; P = 0.037), as was tyrosine concentration (13.8 ± 7.1 μM versus 10.6 ± 5.2 μM; P = 0.016). The mature breast milk of obese mothers contained 20% more BCAA and 30% more tyrosine than breast milk of control mothers. Whether altered breast milk FAA profile affects metabolic risk in the breast-fed child remains to be explored. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Kinetics modelling of the concentrated nitric acid reduction on 304L stainless steel

    International Nuclear Information System (INIS)

    Benoit, Marie

    2016-01-01

    In France, the spent nuclear fuel reprocessing involves the use of nitric acid at various concentrations and temperatures. The corrosiveness of these nitric mixtures leads to the use of corrosion resistant materials such as austenitic stainless steels (SS), which naturally forms a protective oxide layer under those conditions. The goal of this work is to study the influence of the passive layer on the mechanism and kinetics of concentrated nitric acid reduction reaction (NRR). We firstly focused on a single step in the reduction reaction (Fe(III)/Fe(II) couple in acidic solution) on passivated zirconium with different oxide layer thicknesses. The electrochemical impedance spectroscopy can lead to estimate the semiconducting properties of the film: the space charge capacitance (from the Mott-Schottky equation) allowed to estimate the number of charge carriers in the oxide. We experimentally compare the NRR on gold (on which no passive layer is formed) and SS, respectively. The chemical composition (chromium enrichment) and thickness of the SS passive layer are characterized by electrochemical impedance spectroscopy (EIS) and X-ray photoelectron spectroscopy (XPS), and the mechanism and kinetics of NRR are studied by chrono-amperometry and EIS. On gold electrode, two mechanisms occur successively as a function of cathodic overpotential. at lower over potentials (0.85≤E/SHE≤1.15 V) we propose that NRR follows the Vetter's mechanism, whereas at higher over potentials (0.65≤E/ESH≤ 0.85 V), Schmid's mechanism may occur. On SS, the presence of the passive layer slows down the NRR by a factor 10"4. Moreover, depending on the experimental conditions (4 M to 8 M, 40 C to 100 C) Schmid's mechanism may occur or not in the potential range investigated. Finally, based on the EIS results, we propose a quantitative modelling of the NRR mechanism on stainless steel electrodes. (author) [fr

  11. Study of vanadium(IV) species and corresponding electrochemical performance in concentrated sulfuric acid media

    International Nuclear Information System (INIS)

    Wu Xuewen; Wang Jinjin; Liu Suqin; Wu Xiongwei; Li Sha

    2011-01-01

    Highlights: → Two new UV/Vis absorbance peaks are found in V(IV) sulfuric acid solutions. → We give the structural information on the new corresponding V(IV) species. → Reaction route is given with increasing sulfuric acid and V(IV) concentrations. → We find V(IV) species corresponding to the reversible electrochemical reaction. → A mixed-valence intermediate is invoked in the reversible reaction. - Abstract: The vanadium(IV) ion is found to form the [VO(SO 4 )(H 2 O) 4 ].H 2 O complex, as well as the dimer, [VO(H 2 O) 3 ] 2 (μ-SO 4 ) 2 , in concentrated H 2 SO 4 media. Their formation mechanisms were investigated by UV-Visible spectroscopy (UV-Vis), Raman spectroscopy, X-ray diffraction (XRD), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). UV-Vis spectroscopy study showed that [VO(SO 4 )(H 2 O) 4 ].H 2 O concentration in H 2 SO 4 solution was proportional to concentrations of VO 2+ and SO 4 2- . The increased deviation from the near centrosymmetry of the octahedral complexes is due to the replacement of an equatorial water oxygen in [VO(H 2 O) 5 ]SO 4 by a sulfate oxygen in [VO(SO 4 )(H 2 O) 4 ].H 2 O. The dimer shows symmetrical structure, which correlates very well with non-activity in UV-Vis spectroscopic analysis. Structural information on both vanadium(IV) species can be confirmed by Raman and XRD measurements of crystals from the supersaturated solution of VOSO 4 in 1 M, 6 M and 12 M sulfuric acid. A solution of vanadium(IV) (0.05 M) in 12 M H 2 SO 4 , in which the vanadium(IV) species is [VO(H 2 O) 3 ] 2 (μ-SO 4 ) 2 , exhibits a reversible redox behavior near 1.14 V (vs. SCE) on the carbon paper electrode.

  12. Distribution and seasonal variation of concentrations of particulate carbohydrates and uronic acids in the northern Indian Ocean

    Digital Repository Service at National Institute of Oceanography (India)

    Khodse, V.B.; Fernandes, L.; Gopalakrishna, V.V.; Bhosle, N.B.; Fernandes, V.; Matondkar, S.G.P.; Bhushan, R.

    particulate carbohydrate (TPCHO), total particulate uronic acid (TPURA) and total particulate neutral carbohydrate (TPNCHO) concentrations and composition. Strong spatial, temporal and depth related variations were evident in the distribution...

  13. Bioavailability of zinc to rats from defatted soy flour, acid-precipitated soy concentrate and neutralized soy concentrate as determined by intrinsic and extrinsic labeling techniques

    International Nuclear Information System (INIS)

    Ketelsen, S.M.; Stuart, M.A.; Weaver, C.M.; Forbes, R.M.; Erdman, J.W. Jr.

    1984-01-01

    The bioavailability of 65Zn from intrinsically and extrinsically labeled soy flour, acid-precipitated soy concentrate and neutralized soy concentrate was evaluated in rats. Weanling rats were fed marginally zinc-deficient diets, providing 8 ppm zinc from one of these three soy products, for 7 days. The rats then received a radioactively labeled test meal, identical in composition to the previous diet except that the soy product was either intrinsically or extrinsically labeled with 65Zn. After the test meal the rats were again fed diets the same as those consumed prior to the test meal. Whole-body retention of 65Zn at 24 hours and 12 days as well as 65Zn retained in tibias of rats given meals containing neutralized concentrate-based meals was significantly lower than for rats given meals containing the soy flour or acid-precipitated concentrate. In addition, retention of 65Zn from the extrinsically labeled acid-precipitated concentrate-based meal was significantly higher than from the same product intrinsically labeled. These findings confirm the results of previous feeding studies from which it was suggested that neutralization of soy protein concentrates reduces zinc bioavailability to the rat. In addition, the results are taken to suggest that experimental conditions may influence the validity of the extrinsic labeling technique for zinc

  14. Concentration of gadolinium-diethylene triamine pentaacetic acid in human kidney

    International Nuclear Information System (INIS)

    Takeda, Masayuki; Katayama, Yasushi; Tsutsui, Toshiki; Komeyama, Takeshi; Mizusawa, Takaki; Tanikawa, Toshiki; Sato, Shotaro

    1993-01-01

    Although gadolinium diethylene triamine pentaacetic acid (Gd-DTPA) has been used as a contrast material in magnetic resonance imaging, it is known that contrast enhancement effect disappears if the concentration of Gd-DTPA increases beyond some levels. In this study, to evaluate the proper pulse sequences for dynamic magnetic resonance imaging (MRI) in the human kidney, the concentration of Gd-DTPA was quantitatively measured by inductively coupled plasma (ICP) emission spectrometry in human biological samples after administration of Gd-DTPA, and the signal intensity of MRI is the solution of several concentrations of Gd-DTPA was measured. In using a low magnetic field apparatus, signal intensity linearly correlated with the concentration of Gd-DTPA between 0 and 2.0 μmol/g under saturation recovery sequences (flip angle was 60deg or 90deg). Using a high magnetic field apparatus, signal intensity linearly correlated with the concentration of Gd-DTPA between 0 and 2.0 or 3.0 μmol/g under spin echo or gradient-echo sequences. Gd-DTPA concentration of the renal cortex ranged from 0.132 to 0.152 μmol/g tissue at 5 min after intravenous injection of Gd-DTPA 0.05 mmol/kg body weight in 7 patients with adrenal tumor or renal cell cancer, and 1 patient with both urinary bladder cancer and prostatic cancer. Seven of them showed normal renal function and the other had renal insufficiency (GFR 25 ml/min/1.48 m 2 ). Gd-DTPA concentrations of renal medulla and renal cell cancer tissue were 0.123 and 0.108 μmol/g tissue, respectively, at 5 min after intravenous injection of Gd-DTPA 0.05 mmol/kg body weight. These results suggest that the signal intensity of renal cortex, renal medulla, and renal cell cancer tissue may linearly correlate with Gd-DTPA concentration of tissues at 5 min after intravenous injection of Gd-DTPA 0.5 mmol/kg body weight. (author)

  15. [Analyze nanofiltration separation rule of chlorogenic acid from low concentration ethanol by Donnan effect and solution-diffusion effect].

    Science.gov (United States)

    Li, Cun-Yu; Liu, Li-Cheng; Jin, Li-Yang; Li, Hong-Yang; Peng, Guo-Ping

    2017-07-01

    To separate chlorogenic acid from low concentration ethanol and explore the influence of Donnan effect and solution-diffusion effect on the nanofiltration separation rule. The experiment showed that solution pH and ethanol volume percent had influences on the separation of chlorogenic acid. Within the pH values from 3 to 7 for chlorogenic acid in 30% ethanol, the rejection rate of chlorogenic acid was changed by 70.27%. Through the response surface method for quadratic regression model, an interaction had been found in molecule weight cut-off, pH and ethanol volume percent. In fixed nanofiltration apparatus, the existence states of chlorogenic acid determinedits separation rules. With the increase of ethanol concentration, the free form chlorogenic acid was easily adsorbed, dissolved on membrane surface and then caused high transmittance due to the solution-diffusion effect. However, at the same time, due to the double effects of Donnan effect and solution-diffusion effect, the ionic state of chlorogenic acid was hard to be adsorbed in membrane surface and thus caused high rejection rate. The combination of Box-Behnken design and response surface analysis can well optimize the concentrate process by nanofiltration, and the results showed that nanofiltration had several big advantages over the traditional vacuum concentrate technology, meanwhile, and solved the problems of low efficiency and serious component lossesin the Chinese medicines separation process for low concentration organic solvent-water solution. Copyright© by the Chinese Pharmaceutical Association.

  16. Consumption of high doses of chlorogenic acid, present in coffee, or black tea increases plasma total homocysteine concentrations in humans

    NARCIS (Netherlands)

    Olthof, M.R.; Hollman, P.C.; Zock, P.L.; Katan, M.B.

    2001-01-01

    In population studies, high intakes of coffee are associated with raised concentrations of plasma homocysteine, a predictor of risk of cardiovascular disease. Chlorogenic acid is a major polyphenol in coffee; coffee drinkers consume up to 1 g chlorogenic acid/d. OBJECTIVE: We studied whether

  17. Serum uric acid concentrations and SLC2A9 genetic variation in Hispanic children: The Viva La Familia Study

    Science.gov (United States)

    Elevated concentrations of serum uric acid are associated with increased risk of gout and renal and cardiovascular diseases. Genetic studies in adults have consistently identified associations of solute carrier family 2, member 9 (SLC2A9), polymorphisms with variation in serum uric acid. However, it...

  18. Association of three genetic loci with uric acid concentration and risk of gout: a genome-wide association study

    NARCIS (Netherlands)

    A. Dehghan (Abbas); A. Köttgen (Anna); Q. Yang (Qiong Fang); S.J. Hwang; W.H.L. Kao (Wen); F. Rivadeneira Ramirez (Fernando); E.A. Boerwinkle (Eric); D. Levy (Daniel); A. Hofman (Albert); B.C. Astor (Brad); E.J. Benjamin (Emelia); P. Tikka-Kleemola (Päivi); J.C.M. Witteman (Jacqueline); J. Coresh (Josef); C.S. Fox (Caroline)

    2008-01-01

    textabstractBackground: Hyperuricaemia, a highly heritable trait, is a key risk factor for gout. We aimed to identify novel genes associated with serum uric acid concentration and gout. Methods: Genome-wide association studies were done for serum uric acid in 7699 participants in the Framingham

  19. Multistage dilute acid leaching of a medium grade iron ore to super-concentrate

    Directory of Open Access Journals (Sweden)

    Adeleke A.A.

    2014-01-01

    Full Text Available The phosphorous laden Koton Karfe iron ore is a medium grade iron ore deposit in Nigeria that can be upgraded as a super-concentrate for use at the Aladja Steel Midrex plant. The 75 μm size sample fraction of the ore was preconcentrated with shaking table and leached in the oven at atmospheric pressure with dilute hydrochloric acid in single and multistage leaching sequences of H2O-HCl-H2O and HCl-H2O-H2O. The as-received, as-tabled and asleached samples were then subjected to X-ray fluorescence and microscopic analyses. The results obtained showed that the H2O-HCl-H2O route produced a higher grade concentrate that assayed 68.54% Fe indicating about 58% upgrade in iron content; while the phosphorus and sulphur contents were reduced by about 77 and 99.6% respectively. In addition, the silicon, manganese, and titanium contents were drastically reduced, while potassium was completely eliminated. The upgrade of iron content in the ore to 68.54% and the drastic reduction in phosphorous and sulphur contents has thus rendered the Koton Karfe iron ore suitable for use as a super concentrate for the Aladja steel plant direct reduction iron making process.

  20. Synthesis and concentration of 2-monoacylglycerols rich in polyunsaturated fatty acids.

    Science.gov (United States)

    Zhang, Yu; Wang, Xiaosan; Xie, Dan; Zou, Shuo; Jin, Qingzhe; Wang, Xingguo

    2018-06-01

    Polyunsaturated fatty acids (PUFA) in 2-monoacylglycerols form exhibit various biological activities and have potential applications in food and pharmaceuticals. Preparation of 2-monoacylglycerols was conducted by enzymatic enthanolysis. The effects of lipase type, substrate weight ratio, reaction time and lipase load on the 2-monoacylglycerols content in the crude product were investigated. Lipozyme 435 behaved as 1,3-specific and high-catalytic-activity lipase in this reaction. Under the optimal conditions (ethanol:oil = 3:1 (w/w), 8% Lipozyme 435, 3 h), 27% 2-monoacylglycerols were obtained. After solvent extraction of 2-monoacylglycerols, the abilities of low temperature crystallization and molecular distillation to concentrate 2-PUFA-monoacylglycerols were compared. Low temperature crystallization concentrated 81.13% and 74.29% PUFA by acetonitrile and hexane, respectively, with over 90% in 2-monoacylglycerol forms. Conversely, molecular distillation yielded a PUFA concentration of 72% but decreased the 2-monoacylglycerols content to 69.81%. Thus, the method including enzymatic ethanolysis and low temperature crystallization is suitable for preparation of 2-monoacylglycerols rich in PUFA. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Passivity and passivity breakdown of 304L stainless steel in hot and concentrated nitric acid

    International Nuclear Information System (INIS)

    Gillard-Tcharkhtchi, Elsa

    2014-01-01

    The objective of this study is to characterize the oxidation behavior of 304L stainless steel (SS) in representative conditions of spent nuclear fuel reprocessing, i.e. in hot and concentrated nitric acid. In these conditions the SS electrochemical potential is in the passive domain and its corrosion rate is low. However when the media becomes more aggressive, the potential may be shifted towards the trans-passive domain characterized with a high corrosion rate. Passivity and passivity breakdown in the trans-passive domain are of a major interest for the industry. So as to characterize these phenomenons, this work was undertaken with the following representative conditions: a 304L SS from an industrial sheet was studied, the media was hot and concentrated HNO 3 , long term tests were performed. First, the surface of an immersed 304L SS was characterized with several complementary techniques from the micro to the nanometer scale. Then oxidation kinetics was studied in the passive and in the trans-passive domain. The oxidation behavior was studied thanks to weight loss determination and surface analysis. Finally, oxidation evolution as a function of the potential was studied from the passive to the trans-passive domain. In particular, this allowed us to obtain the anodic curve of 304L SS in hot and concentrated and to define precisely the 304L SS limits of in such conditions. (author) [fr

  2. Radionuclide concentrations in raw and purified phosphoric acids from Brazil and their processing wastes: implications for radiation exposures.

    Science.gov (United States)

    da Conceição, Fabiano Tomazini; Antunes, Maria Lúcia Pereira; Durrant, Steven F

    2012-02-01

    Radionuclides from the U and Th natural series are present in alkaline rocks, which are used as feedstock in Brazil for the production of raw phosphoric acid, which can be considered as a NORM (naturally occurring radioactive material). As a result of the purification of raw phosphoric acid to food-grade phosphoric acid, two by-products are generated, i.e., solid and liquid wastes. Taking this into account, the main aim of this study was to evaluate the fluxes of natural radionuclide in the production of food-grade phosphoric acids in Brazil, to determine the radiological impact caused by ingestion of food-grade phosphoric acid, and to evaluate the solid waste environmental hazards caused by its application in crop soils. Radiological characterization of raw phosphoric acid, food-grade phosphoric acid, solid waste, and liquid waste was performed by alpha and gamma spectrometry. The (238)U, (234)U, (226)Ra, and (232)Th activity concentrations varied depending on the source of raw phosphoric acid. Decreasing radionuclides activity concentrations in raw phosphoric acids used by the producer of the purified phosphoric acid were observed as follows: Tapira (raw phosphoric acid D) > Catalão (raw phosphoric acids B and C) > Cajati (raw phosphoric acid A). The industrial purification process produces a reduction in radionuclide activity concentrations in food-grade phosphoric acid in relation to raw phosphoric acid produced in plant D and single raw phosphoric acid used in recent years. The most common use of food-grade phosphoric acid is in cola soft drinks, with an average consumption in Brazil of 72 l per person per year. Each liter of cola soft drink contains 0.5 ml of food-grade phosphoric acid, which gives an annual average intake of 36 ml of food-grade phosphoric acid per person. Under these conditions, radionuclide intake through consumption of food-grade phosphoric acid per year per person via cola soft drinks is not hazardous to human health in Brazil

  3. Selective oxidation of glycerol to formic acid in highly concentrated aqueous solutions with molecular oxygen using V-substituted phosphomolybdic acids

    KAUST Repository

    Zhang, Jizhe

    2014-01-01

    Formic acid is an important commodity chemical as well as a promising medium for hydrogen storage and hydrogen production. In this paper, we report that formic acid can be produced through selective oxidation of glycerol, a low-cost by-product of biodiesel, by using vanadium-substituted phosphomolybdic acids as catalysts and molecular oxygen as the oxidant. Significantly, this catalytic system allows for high-concentration conversions and thus leads to exceptional efficiency. Specifically, 3.64 g of formic acid was produced from 10 g of glycerol/water (50/50 in weight) solution. © 2014 the Partner Organisations.

  4. Plasma capric acid concentrations in healthy subjects determined by high-performance liquid chromatography.

    Science.gov (United States)

    Shrestha, Rojeet; Hui, Shu-Ping; Imai, Hiromitsu; Hashimoto, Satoru; Uemura, Naoto; Takeda, Seiji; Fuda, Hirotoshi; Suzuki, Akira; Yamaguchi, Satoshi; Hirano, Ken-Ichi; Chiba, Hitoshi

    2015-09-01

    Capric acid (FA10:0, decanoic acid) is a medium-chain fatty acid abundant in tropical oils such as coconut oil, whereas small amounts are present in milk of goat, cow, and human. Orally ingested FA10:0 is transported to the liver and quickly burnt within it. Only few reports are available for FA10:0 concentrations in human plasma. Fasting (n = 5, male/female = 3/2, age 31 ± 9.3 years old) and non-fasting (n = 106, male/female = 44/62, age 21.9 ± 3.2 years old) blood samples were collected from apparently healthy Japanese volunteers. The total FA10:0 in the plasma were measured by high-performance liquid chromatography after derivatization with 2-nitrophenylhydrazine followed by UV detection. Inter and intra-assay coefficient of variation of FA10:0 assay at three different concentrations ranged in 1.7-3.9 and 1.3-5.4%, respectively, with an analytical recovery of 95.2-104.0%. FA10:0 concentration was below detection limit (0.1 µmol/L) in each fasting human plasma. FA10:0 was not detected in 50 (47.2%) of 106 non-fasting blood samples, while 29 (27.4%) plasma samples contained FA10:0 less than or equal to 0.5 µmol/L (0.4 ± 0.1), and 27 (25.5%) contained it at more than 0.5 µmol/L (0.9 ± 0.3). A half of the non-fasting plasma samples contained detectable FA10:0. This simple, precise, and accurate high-performance liquid chromatography method might be useful for monitoring plasma FA10:0 during medium-chain triglycerides therapy. © The Author(s) 2015.

  5. Serum uric acid concentration and metabolic syndrome among elderly Koreans: The Korean Urban Rural Elderly (KURE) study.

    Science.gov (United States)

    Choi, Hansol; Kim, Hyeon Chang; Song, Bo Mi; Park, Ji Hye; Lee, Ju-Mi; Yoon, Da-Lim; Yoon, Young Mi; Rhee, Yumie; Youm, Yousik; Kim, Chang Oh

    2016-01-01

    Epidemiologic studies have demonstrated that elevated serum uric acid concentration is an independent risk factor for metabolic syndrome. However, few studies have focused on elderly populations. Thus, we investigated the association of serum uric acid concentration with metabolic syndrome in community-dwelling elderly Koreans. This cross-sectional analysis included 2940 participants (986 men and 1954 women) aged 65 years or older who participated in a baseline health assessment for the Korean Urban Rural Elderly cohort study from 2012 to 2014. Serum uric acid concentration was analyzed using both continuous and dichotomous variables. Hyperuricemia was defined as a uric acid concentration ≥7.0 mg/dL in men and ≥6.0 mg/dL in women. Metabolic syndrome was defined according to the 2009 harmonizing definition. Multiple logistic regression models were used to investigate independent association between serum uric acid and metabolic syndrome, after adjusting for age, body mass index, LDL cholesterol, glycated hemoglobin, blood urea nitrogen, estimated glomerular filtration rate health behaviors, and medications. Prevalence of metabolic syndrome and its components increased significantly according to uric acid concentration in both sexes. The adjusted odds ratios for having metabolic syndrome per 1.0mg/dL higher uric acid concentration were 1.16 (95% CI: 1.03-1.31) in men and 1.27 (95% CI: 1.13-1.42) in women. Hyperuricemia was also associated with metabolic syndrome, with adjusted odds ratios of 1.71 (95% CI: 1.11-2.63) in men and 1.55 (95% CI: 1.05-2.29) in women. Elevated serum uric acid concentration was independently associated with an increased prevalence of metabolic syndrome in community-dwelling elderly Koreans. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Selection of suitable mineral acid and its concentration for biphasic dilute acid hydrolysis of the sodium dithionite delignified Prosopis juliflora to hydrolyze maximum holocellulose.

    Science.gov (United States)

    Naseeruddin, Shaik; Desai, Suseelendra; Venkateswar Rao, L

    2016-02-01

    Two grams of delignified substrate at 10% (w/v) level was subjected to biphasic dilute acid hydrolysis using phosphoric acid, hydrochloric acid and sulfuric acid separately at 110 °C for 10 min in phase-I and 121 °C for 15 min in phase-II. Combinations of acid concentrations in two phases were varied for maximum holocellulose hydrolysis with release of fewer inhibitors, to select the suitable acid and its concentration. Among three acids, sulfuric acid in combination of 1 & 2% (v/v) hydrolyzed maximum holocellulose of 25.44±0.44% releasing 0.51±0.02 g/L of phenolics and 0.12±0.002 g/L of furans, respectively. Further, hydrolysis of delignified substrate using selected acid by varying reaction time and temperature hydrolyzed 55.58±1.78% of holocellulose releasing 2.11±0.07 g/L and 1.37±0.03 g/L of phenolics and furans, respectively at conditions of 110 °C for 45 min in phase-I & 121 °C for 60 min in phase-II. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Influence of photoperiod and temperature on frost hardiness and free amino acid concentrations in black spruce seedlings

    Energy Technology Data Exchange (ETDEWEB)

    1993-01-01

    Because photoperiod and temperature both influence amino acid metabolism in plants, seasonal reductions in day length and temperature may be responsible for the changes in amino acid concentrations that occur in conifers with the onset of winter. Since such fluctuations in conifers occur in association with the development of frost hardiness, it has been suggested that the accumulation of specific free amino acids may be related to the development of frost hardiness. This study was designed to determine the effects of photoperiod and temperature on proline, arginine, and tryptophan concentrations in the shoots of black spruce seedlings in relation to the development of hardiness to -20C.

  8. Acid leaching of scheelite concentrates; Lixiviacion acida de concentrado de scheelita

    Energy Technology Data Exchange (ETDEWEB)

    Navarro, P.; Vargas, C.; Alguacil, F. J.

    2005-07-01

    The acid leaching in hydrochloric media of a tungsten concentrate (scheelite, CaWO{sub 4}) was studied. Of the above-mentioned, an insoluble solid (H{sub 2}WO{sub 4}) was obtained which were treated with an alkaline solution of sodium hydroxide, achieving the complete solubilization of the tungsten as wolframate ion (WO''2{sub 4}). The transformed fraction of tungsten increases with the temperature, as well as with a finer grain. A maximum dissolution of 88.5% (400 g/l HCL, 363 K and 20 {mu}m of particle size) was achieved for a 3 h process, of the dissolution process was interpreted by the recessive core model with formation of a layer of solid product for the whole range of variation of the parameters in study. the activation energy value was found to be 28.0kJ/mol. (Author) 6 refs.

  9. HIV, prospective memory, and cerebrospinal fluid concentrations of quinolinic acid and phosphorylated Tau.

    Science.gov (United States)

    Anderson, Albert M; Croteau, David; Ellis, Ronald J; Rosario, Debra; Potter, Michael; Guillemin, Gilles J; Brew, Bruce J; Woods, Steven Paul; Letendre, Scott L

    2018-06-15

    There is mounting evidence that prospective memory (PM) is impaired during HIV infection despite treatment. In this prospective study, 66 adults (43 HIV+ and 23 HIV negative) underwent PM assessment and cerebrospinal fluid (CSF) examination. HIV+ participants had significantly lower PM but significantly higher CSF concentrations of CXCL10 and quinolinic acid (QUIN). Higher CSF phosphorylated Tau (pTau) was associated with worse PM. In a secondary analysis excluding outliers, higher QUIN correlated with higher pTau. CSF QUIN is thus elevated during HIV infection despite antiretroviral therapy and could indirectly contribute to impaired PM by influencing the formation of pTau. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Effect of Phosphoric Acid Concentration on the Optical Properties of Partially Phosphorylated PVA Complexes

    Directory of Open Access Journals (Sweden)

    Asmalina Mohamed Saat

    2014-01-01

    Full Text Available Partially phosphorylated polyvinyl alcohol (PPVA films were prepared at five mole ratios of phosphoric acid (PA using solution casting technique. The optical properties of the PPVA films were examined using UV-visible (UV and photoluminescence (PL spectroscopy. The UV absorption spectra reveal that the absorption peaks are blue-shifted with an increase in PA concentration added to the pure PVA. The PL spectra show the presence of peaks which are characteristic of isotactic (389–398, 460–462 nm, syndiotactic (418–420 nm, and atactic (440–446 nm configurations of the PPVA. The results also show the peak of O–P–O bonding at a wavelength range of 481–489 nm.

  11. Study on the concentration of unsaturated fatty acid methyl esters by urea complexation

    International Nuclear Information System (INIS)

    Jiang, B.; Liu, Y.

    2014-01-01

    This study was done to obtain concentrated unsaturated fatty acid methyl esters (FAME) by urea complexation from soybean derived FAME. Effects of urea-to-FAME ratio, 95% ethanol-to-FAME ratio, crystallization temperature and time on the purification of unsaturated FAME were investigated through single factor experiments. Optimum conditions to obtain maximum FAME yield of NUCF with the purity of unsaturated FAME greater than 98% were established using Box-Behnken design (BBD) method and response surface methodology (RSM). Under optimal conditions, the FAME yield was 58.08%, and the purity of unsaturated FAME was 98% at a urea-to-FAME ratio of 1.23, 95% ethanol-to-FAME ratio of 7 and crystallization temperature of 0 degree C. Verification results revealed that the predicted values were reasonably close to experimentally observed values of 56.93% and 98.01%. (author)

  12. Increased concentration of vasopressin in plasma of essential fatty acid-deficient rats

    DEFF Research Database (Denmark)

    Hansen, Harald S.; Jensen, B.; Warberg, J.

    1985-01-01

    The effect of essential fatty acid deficiency (EFA-D) on the plasma concentration of arginine-vasopressin (AVP) and the urinary AVP excretion was investigated. Weanling rats were fed a fat-free diet (FF-rats). Control rats received the same diet in which 6% by wt. of sucrose was replaced by arachis...... oil. After 4-6 weeks of feeding, urine and plasma were analysed for AVP, osmolality, sodium and potassium. When compared to control rats FF-rats had decreased urine volume (6.0 ± 1.6 ml/24 hr versus 11.7 ± 3.2 ml/24 hr), increased urine osmolality (2409 ± 691 mOsm/kg versus 1260 ± 434 m...

  13. Complex formation of trivalent americium with salicylic acid at very low concentrations

    International Nuclear Information System (INIS)

    Melanie Mueller; Margret Acker; Steffen Taut; Gert Bernhard; Forschungszentrum Dresden-Rossendorf, Dresden

    2010-01-01

    For the first time, the complexation of americium(III) with salicylic acid was studied at trace metal concentrations using a 2.0 m Long Path Flow Cell for UV-vis spectroscopy. The detection limit of Am(III) in aqueous solution at pH 3.0 was found to be 5 x 10 -9 M. Two Am(III)-salicylate complexes were formed at pH 5.0 in 0.1 M NaClO 4 , indicated by a clear red shift of the absorption maximum. The absorption spectra obtained from spectrophotometric titration were analyzed by means of factor analysis and complex stabilities were calculated to be log β 110 = 2.56 ± 0.08 and log β 120 = 3.93 ± 0.19. (author)

  14. Digestibility by lambs offered alfalfa hay treated with a propionic acid hay preservative and baled at different concentrations of moisture

    Science.gov (United States)

    Eighteen crossbred wether lambs (76.1 ± 8.18 lb initial BW) were used for a 2 period digestion study to evaluate the effect of hay preservative concentration (0, 0.56, or 0.98% buffered propionic acid) and hay moisture concentration at baling (19.6, 23.8, or 27.4% moisture) on digestibility of alfal...

  15. Effect of N deposition on tree amino acid concentrations in two Sphagnum species

    Energy Technology Data Exchange (ETDEWEB)

    Karsisto, M; Kitunen, V [Finnish Forest Research Inst., Vantaa (Finland). Vantaa Research Centre; Jauhiainen, J [Joensuu Univ. (Finland). Dept. of Biology; Vasander, H [Helsinki Univ. (Finland). Dept. of Forest Ecology

    1997-12-31

    Nitrogen saturation of ecosystems occurs when the availability of nitrogen is not a growth limiting factor. This situation can be reached through fertilisation or by nitrogen deposition. Prolonged nitrogen saturation may overload the ecosystem and cause changes in the vigour and eventually in the composition of plant communities. But before this stage is reached, certain changes in nitrogen metabolism occur. These changes can be used as an early warning of nitrogen overload to ecosystems. A change in the amino acid pool of plants has been used as an indication of various kind of stress, including, temperature, nutrient imbalance, shading, drought or excess water. It has been postulated that such stresses have an effect on protein synthesis but not on the nitrogen uptake of plants. The result is an increase in the concentration of NH{sub 4}{sup +} ions in plant cells, which may have toxic effects to the plant and the processes that assimilate the free NH{sub 4}{sup +} ions. One of such process is the synthesis of amino acids, especially those containing a significant proportion of nitrogen, e.g. arginine, glutamine and asparagine. This study about the quantification of amino acids in two species of Sphagnum mosses is part of a larger study, the aim of which is to clarify how a number of Sphagnum species will cope with climatic change and nitrogen deposition. Sphagna are the most important members of the peat forming communities in the boreal zone. Sphagnum communities are formed by species specialised to grow in conditions of low nutrient availability, mainly provided via deposition. The present structure and composition of mire communities may be endangered due to elevated levels of nitrogen deposition that have persisted over the last few decades. (20 refs.)

  16. Effect of N deposition on tree amino acid concentrations in two Sphagnum species

    Energy Technology Data Exchange (ETDEWEB)

    Karsisto, M.; Kitunen, V. [Finnish Forest Research Inst., Vantaa (Finland). Vantaa Research Centre; Jauhiainen, J. [Joensuu Univ. (Finland). Dept. of Biology; Vasander, H. [Helsinki Univ. (Finland). Dept. of Forest Ecology

    1996-12-31

    Nitrogen saturation of ecosystems occurs when the availability of nitrogen is not a growth limiting factor. This situation can be reached through fertilisation or by nitrogen deposition. Prolonged nitrogen saturation may overload the ecosystem and cause changes in the vigour and eventually in the composition of plant communities. But before this stage is reached, certain changes in nitrogen metabolism occur. These changes can be used as an early warning of nitrogen overload to ecosystems. A change in the amino acid pool of plants has been used as an indication of various kind of stress, including, temperature, nutrient imbalance, shading, drought or excess water. It has been postulated that such stresses have an effect on protein synthesis but not on the nitrogen uptake of plants. The result is an increase in the concentration of NH{sub 4}{sup +} ions in plant cells, which may have toxic effects to the plant and the processes that assimilate the free NH{sub 4}{sup +} ions. One of such process is the synthesis of amino acids, especially those containing a significant proportion of nitrogen, e.g. arginine, glutamine and asparagine. This study about the quantification of amino acids in two species of Sphagnum mosses is part of a larger study, the aim of which is to clarify how a number of Sphagnum species will cope with climatic change and nitrogen deposition. Sphagna are the most important members of the peat forming communities in the boreal zone. Sphagnum communities are formed by species specialised to grow in conditions of low nutrient availability, mainly provided via deposition. The present structure and composition of mire communities may be endangered due to elevated levels of nitrogen deposition that have persisted over the last few decades. (20 refs.)

  17. Application of Lime Additive on Cementation of Concentrated Low Activities Liquid Radwaste Containing Boric Acid

    International Nuclear Information System (INIS)

    Bahdir-Johan

    2000-01-01

    The effect of lime additive on the waste form containing boric acid and the activity 1 μCi/ml have been studied. The studying parameter was the optimum lime additive in concentrate. The sample was made by cement slurry containing boric acid. The cement slurry composition are water/cement ratio (W/C) was 0.35, sand/cement ratio (S/C) was 0.75 and boric (B) was 15000 ppm. On this condition into cement slurry was added the lime additive (K/C) 0.05 -0.8 by weigh. The quality test included density, compressive strength and leaching rate. The density was determination by weighing and measuring sample volume, compressive strength determination using Paul Weber apparatus and leaching rate tested using aquadest. The result of this research are the lime/cement ratio (K/C) 0.30; the density (ρ) 2.449 ± 0.008 g.cm -3 , the compressive strength (Γ) 44.005 ± 0.012 N.mm -2 and the leaching rate (Rn) 7.20x10 -4 -0.90x10 -4 g.cm -2 day -1 . According to this research the quality of the waste form has been complied the IAEA quality standard. (author)

  18. Catalyst evaluation for oxygen reduction reaction in concentrated phosphoric acid at elevated temperatures

    Science.gov (United States)

    Hu, Yang; Jiang, Yiliang; Jensen, Jens Oluf; Cleemann, Lars N.; Li, Qingfeng

    2018-01-01

    Phosphoric acid is the common electrolyte for high-temperature polymer electrolyte fuel cells (HT-PEMFCs) that have advantages such as enhanced CO tolerance and simplified heat and water management. The currently used rotating disk electrode technique is limited to tests in dilute solutions at low temperatures and hence is not suitable for catalyst evaluation for HT-PEMFCs. In this study, we have designed and constructed a half-cell setup to measure the intrinsic activities of catalysts towards the oxygen reduction reaction (ORR) in conditions close to HT-PEMFC cathodes. By optimization of the hydrophobic characteristics of electrodes and the catalyst layer thickness, ORR activities of typical Pt/C catalysts are successfully measured in concentrated phosphoric acid at temperatures above 100 °C. In terms of mass-specific activities, the catalyst exhibits about two times higher activity in the half-cell electrode than that observed in fuel cells, indicating the feasibility of the technique as well as the potential for further improvement of fuel cell electrode performance.

  19. Influence of Concentration and Agitation of Sodium Hypochlorite and Peracetic Acid Solutions on Tissue Dissolution.

    Science.gov (United States)

    Tanomaru-Filho, Mário; Silveira, Bruna Ramos Franco; Martelo, Roberta Bosso; Guerreiro-Tanomaru, Juliane Maria

    2015-11-01

    To evaluated the tissue dissolution of sodium hypochlorite (NaOCl) and peracetic acid (PA) solutions at different concentrations, with or without ultrasonic agitation. The following solutions were analyzed: 2.5% NaOCl, 0.5, 1 and 2% PA, 1% PA associated with 6.5% hydrogen peroxide (HP) and saline. Fragments of bovine pulp tissue with 25 ± 2g mg were immersed into test tubes containing 4 mL of the solutions for 10 minutes. In the groups with agitation, pulp tissues were submitted to 2 cycles of 1 minute of ultrasonic agitation. The specimens were weighed after the removal from the solutions. The percentage of mass loss was calculated according to the difference of mass before and after exposure to solutions. Data were submitted to ANOVA and Tukey tests (p Peracetic acid solution has pulp tissue dissolution. However, this ability is lower than 2.5% NaOCl solution. The sodium hypochlorite solution shows higher ability to dissolve tissue than PA.

  20. Adsorptive removal of fermentation inhibitors from concentrated acid hydrolyzates of lignocellulosic biomass.

    Science.gov (United States)

    Sainio, Tuomo; Turku, Irina; Heinonen, Jari

    2011-05-01

    Adsorptive purification of concentrated acid hydrolyzate of lignocellulose was investigated. Cation exchange resin (CS16GC), neutral polymer adsorbent (XAD-16), and granulated activated carbon (GAC) were studied to remove furfural, HMF, and acetic acid from a synthetic hydrolyzate containing 20 wt.% H(2)SO(4). Adsorption isotherms were determined experimentally. Loading and regeneration were investigated in a laboratory scale column. GAC has the highest adsorption capacity, but regeneration with water was not feasible. XAD-16 and CS16GC had lower adsorption capacities but also shorter cycle times due to easier regeneration. Productivity increased when regenerating with 50 wt.% EtOH(aq) solution. To compare adsorbents, process performance was quantified by productivity and fraction of inhibitors removed. GAC yields highest performance when high purity is required and ethanol can be used in regeneration. For lower purities, XAD-16 and GAC yield approximately equal performance. When using ethanol must be avoided, CS16GC offers highest productivity. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Highly improved synthesis of gold nanobipyramids by tuning the concentration of hydrochloric acid

    Energy Technology Data Exchange (ETDEWEB)

    Qi, Ying; Zhu, Jian; Li, Jianjun; Zhao, Junwu, E-mail: nanoptzhao@163.com [Xi’an Jiaotong University, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology (China)

    2016-07-15

    Fabrication of gold nanobipyramids (Au BPs) has attracted great attention because they exhibit more advantageous plasmonic properties. In this study, Au BPs were synthesized by the well-known seeded growth in the presence of hydrochloric acid (HCl). The effects of the ingredients, including HCl, silver nitrate (AgNO{sub 3}), l-Ascorbic acid (AA), and seeds on the structure and yield of the Au BPs were systemically investigated. The results showed that the abundant HCl could improve the yield of Au BPs and decrease the longitudinal surface plasmon resonance wavelength. Under the circumstance of higher concentration of AA and AgNO{sub 3}, more byproducts were resulted. In addition, the effect of HCl under different ratios of seed solution to AA has also been studied. The results showed that the yield was less sensitive to HCl when the amount of seed solution was small. If substantial AA was added to the system, then abundant HCl should be introduced correspondingly to improve the yield of Au BPs.

  2. A simple procedure for preparing chitin oligomers through acetone precipitation after hydrolysis in concentrated hydrochloric acid.

    Science.gov (United States)

    Kazami, Nao; Sakaguchi, Masayoshi; Mizutani, Daisuke; Masuda, Tatsuhiko; Wakita, Satoshi; Oyama, Fumitaka; Kawakita, Masao; Sugahara, Yasusato

    2015-11-05

    Chitin oligomers are of interest because of their numerous biologically relevant properties. To prepare chitin oligomers containing 4-6 GlcNAc units [(GlcNAc)4-6], α- and β-chitin were hydrolyzed with concentrated hydrochloric acid at 40 °C. The reactant was mixed with acetone to recover the acetone-insoluble material, and (GlcNAc)4-6 was efficiently recovered after subsequent water extraction. Composition analysis using gel permeation chromatography and MALDI-TOF mass spectrometry indicated that (GlcNAc)4-6 could be isolated from the acetone-insoluble material with recoveries of approximately 17% and 21% from the starting α-chitin and β-chitin, respectively. The acetone precipitation method is highly useful for recovering chitin oligomers from the acid hydrolysate of chitin. The changes in the molecular size and higher-order structure of chitin during the course of hydrolysis were also analyzed, and a model that explains the process of oligomer accumulation is proposed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Measuring the concentration of carboxylic acid groups in torrefied spruce wood.

    Science.gov (United States)

    Khazraie Shoulaifar, Tooran; Demartini, Nikolai; Ivaska, Ari; Fardim, Pedro; Hupa, Mikko

    2012-11-01

    Torrefaction is moderate thermal treatment (∼200-300°C) to improve the energy density, handling and storage properties of biomass fuels. In biomass, carboxylic sites are partially responsible for its hygroscopic. These sites are degraded to varying extents during torrefaction. In this paper, we apply methylene blue sorption and potentiometric titration to measure the concentration of carboxylic acid groups in spruce wood torrefied for 30min at temperatures between 180 and 300°C. The results from both methods were applicable and the values agreed well. A decrease in the equilibrium moisture content at different humidity was also measured for the torrefied wood samples, which is in good agreement with the decrease in carboxylic acid sites. Thus both methods offer a means of directly measuring the decomposition of carboxylic groups in biomass during torrefaction as a valuable parameter in evaluating the extent of torrefaction which provides new information to the chemical changes occurring during torrefaction. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Low Dose Gamma Irradiation Does Not Affect the Quality or Total Ascorbic Acid Concentration of "Sweetheart" Passionfruit (Passiflora edulis).

    Science.gov (United States)

    Golding, John B; Blades, Barbara L; Satyan, Shashirekha; Spohr, Lorraine J; Harris, Anne; Jessup, Andrew J; Archer, John R; Davies, Justin B; Banos, Connie

    2015-08-26

    Passionfruit ( Passiflora edulis , Sims, cultivar "Sweetheart") were subject to gamma irradiation at levels suitable for phytosanitary purposes (0, 150, 400 and 1000 Gy) then stored at 8 °C and assessed for fruit quality and total ascorbic acid concentration after one and fourteen days. Irradiation at any dose (≤1000 Gy) did not affect passionfruit quality (overall fruit quality, colour, firmness, fruit shrivel, stem condition, weight loss, total soluble solids level (TSS), titratable acidity (TA) level, TSS/TA ratio, juice pH and rot development), nor the total ascorbic acid concentration. The length of time in storage affected some fruit quality parameters and total ascorbic acid concentration, with longer storage periods resulting in lower quality fruit and lower total ascorbic acid concentration, irrespective of irradiation. There was no interaction between irradiation treatment and storage time, indicating that irradiation did not influence the effect of storage on passionfruit quality. The results showed that the application of 150, 400 and 1000 Gy gamma irradiation to "Sweetheart" purple passionfruit did not produce any deleterious effects on fruit quality or total ascorbic acid concentration during cold storage, thus supporting the use of low dose irradiation as a phytosanitary treatment against quarantine pests in purple passionfruit.

  5. [Quantitative determination of the main metabolites of acetylsalicylic acid/2nd communication: the concentrations of salicylic acid and its metabolites in patients with renal insufficiency (author's transl)].

    Science.gov (United States)

    Daneels, R; Loew, D; Pütter, J

    1975-07-01

    Quantitative Determination of the Main Metabolites of Acetylsalicylic Acid / 2nd Communication: The concentrations of salicylic acid and its metabolies in patients with renal insufficiency 9 patients suffering from renal insufficiencies of varing degrees and treated regularly by hemodialysis were given 1.5 g Colfarit (microcapsulated acetyl salicylic acid) as a single dose. The concentrations of salicylic acid (SA), salicyluric acid (SU), further salicylic acid conjugates (SAC) and salicyluric acid conjugates (SUC) were determined in the blood plasma. Likewise urea and creatinine were determined. SA concentration decreased continually and, at the end of the trial (72 h after application), had vanished almost completely from the plasma of most patients. SU increased at first and decreased afterwards. With the exception of the dailysis time SAC and SUC increased during the trial. After 3 days the SUC level was more than 50% of total salicylate (SSS) in most patients. SSS (the sum of SA + SU + SAC + SUC) did not change very much before dialysis, but showed a rather high decrease during the first hours of dialysis. tafter dialysis the SSS levels rose again, apparently as a consequence of a redistribution and of the synthesis of conjugates with decreased tissue affinity. It could be shown that SSS in the blood plasma does not parallel SSS in the whole body. The interindividual variation of SA metabolism as well as the variation of the biological blank values was rather high. The results are discussed with regard to salicylate pharmacokinetics in renal insufficiency and to normal salicylate metabolism.

  6. Concentration and entry rate of amino acids in buffalo calves fed on two planes of crude protein

    International Nuclear Information System (INIS)

    Verma, D.N.; Singh, U.B.; Varma, A.; Ranjhan, S.K.

    1974-01-01

    Amino acid entry rates into the body pool have been estimated in buffalo calves using a single injection isotope dilution technique. The animals received 2 levels of crude protein, 13 percent lower and 19 percent higher than NRC recommendation. The concentrations of free amino acid in plasma were 5.49 and 7.17 mg/100 ml in animals fed on low and high crude protein diet, respectively. There was significant differences in the plasma amino acid concentration and entry rates between the groups. Amino acid entry rates were 79.17 and 117.78 mg per min in groups fed on low and high plane of crude protein respectively, showing that availability of amino acid is better in animals given ratio high in crude protein contents. (author)

  7. Optical measurement for the concentrations of the pickling acid with near infrared spectroscopy in steel making industry

    Science.gov (United States)

    Kang, Gumin; Lee, Kwangchil; Park, Haesung; Lee, Jinho; Jung, Youngjean; Kim, Kyoungsik

    2010-08-01

    In the manufacturing process of stainless steel, it is essential to pickle the oxide layer of steel surface for high corrosion resistance and fine surface quality. Pickling liquor of stainless steel is commonly composed of mixed hydrofluoric and nitric acid. Real time monitoring of concentrations of each acid is crucial to optimize pickling process. It also reduces cost of production and decreases the generation of waste acid. We used non-contact near infrared spectroscopy technique and rapid analysis method, for the quantification of each acid in an on-line manner. Multivariate calibration such as partial least square regression method is employed for the better prediction results.

  8. Determination of Optimum Duration and Concentration of Stevia (Stevia rebaudiana Bert.) Seed Priming with Boric Acid (H3BO3)

    OpenAIRE

    SHAHVERDI, Mehdi Aghighi; OMIDI, Heshmat; TABATABAEI, Seyed Jalal

    2017-01-01

    In order to determine optimal duration and concentration of Stevia seed priming with boric acid for improving germination, an experimental factorial completely randomized design with three replications was conducted in the laboratory of Seed Science and Technology, Shahed University of Tehran in 2015. The first factor was different concentrations of boric acid (0, 0.5, 1.0, 1.5 and 2.0 percent) and the second factor was priming duration (0, 8, 16, 24 and 32 hours). Effects of concentration an...

  9. Concentration of phenolic acids and flavonoids in aronia melanocarpa (choke berry) juice by osmotic membrane distillation

    DEFF Research Database (Denmark)

    Fjerbæk Søtoft, Lene; Christensen, Knud Villy; Horn, Vibeke G

    2009-01-01

    melanocarpa is among the red fruits with the highest content of antioxidants [2] and has gained must interest due to the content of phenolic acids, procyanidins and polyphenolic compounds as anthocyanins [3]. In this study, osmotic membrane distillation (OMD) has been tested for the concentration of not only...... sugars, but in particular potentially bioactive components such as phenolic acids and flavonoids. OMD is carried out on 37 kg aronia juice at 30°C and the juice is concentrated from 12 wt% to 74 wt% dry matter. The juice is filtered to remove kernels, peel residues etc before concentration by OMD...

  10. Effect of silage type and energy concentration on conjugated linoleic acid (CLA) in milk fat from dairy cows

    DEFF Research Database (Denmark)

    Nielsen, T.S.; Sejrsen, K.; Andersen, H.R

    2004-01-01

    40 lactating cows were fed either clovergrass or maize silage and a low or high dietary energy concentration in a 2x2 factorial design. The maize silage diets rich in starch and linoleic acid resulted in a higher content of c9t11 and t10c12 CLA in milk fat than the grass silage diets. A high energy...... concentration plus maize silage led to a pronounced shift in the biohydrogenation pathway of linoleic acid, the highest t10c12 CLA content and lowest milk fat percentage. Energy concentration had no effect on milk fat CLA content or milk fat percentage in grass silage fed cows....

  11. Volatile fatty acids production in the rumen of young heifers given diets containing a large proportion of concentrate

    International Nuclear Information System (INIS)

    Oshio, Shuichi; Tahata, Ichiro; Kobayashi, Haruo; Ami, Tsuyako

    1977-01-01

    The rate of production of volatile fatty acids (VFA) in the rumen of animals on high concentrate feeding was studied with eighteen young heifers fitted with a permanent rumen fistula, using a single injection method of 14 C-acetate and polyethylene glycol (PEG) in order to get some basic informations of rumen fermentation on concentrate diets. The results obtained were as follows; 1) The pH value, total VFA concentration, and proportion of each acid on all-concentrate diets showed distinguished differences in comparison with those of the animals fed a large proportion of hay, but varied widely between days and heifers. 2) VFA proportions were significantly correlated with pH. At the pH value of about 5.2, acetic acid was minimum, and propionic acid and valeric acid were maximum in molar proportion. 3) It was suggested that, in the case of all-concentrate feeding for a long period, the VFA production in the rumen was depressed to 33.5-41% of digestible energy. In the animals fed hay and concentrate, the percentage was about 50%. (auth.)

  12. Serum urea and uric acid concentration in pregnant women in sub ...

    African Journals Online (AJOL)

    pregnant blackAfrican women. Uric acid levels for the pregnant women were significantly raised, and the relationship between uric acid elevation and gestational proteinuric hypertensionwas discussed. In conclusion, we recommend that uric acid ...

  13. Humic acid transport in saturated porous media: influence of flow velocity and influent concentration.

    Science.gov (United States)

    Wei, Xiaorong; Shao, Mingan; Du, Lina; Horton, Robert

    2014-12-01

    Understanding the transport of humic acids (HAs) in porous media can provide important and practical evidence needed for accurate prediction of organic/inorganic contaminant transport in different environmental media and interfaces. A series of column transport experiments was conducted to evaluate the transport of HA in different porous media at different flow velocities and influent HA concentrations. Low flow velocity and influent concentration were found to favor the adsorption and deposition of HA onto sand grains packed into columns and to give higher equilibrium distribution coefficients and deposition rate coefficients, which resulted in an increased fraction of HA being retained in columns. Consequently, retardation factors were increased and the transport of HA through the columns was delayed. These results suggest that the transport of HA in porous media is primarily controlled by the attachment of HA to the solid matrix. Accordingly, this attachment should be considered in studies of HA behavior in porous media. Copyright © 2014. Published by Elsevier B.V.

  14. Estimate of colostral immunoglobulin G concentration using refractometry without or with caprylic acid fractionation.

    Science.gov (United States)

    Morrill, K M; Conrad, E; Polo, J; Lago, A; Campbell, J; Quigley, J; Tyler, H

    2012-07-01

    Our objectives were to evaluate the use of refractometry as a means of estimating immunoglobulin G (IgG) concentration of bovine maternal colostrum (MC) and determine if fractionation of MC using caprylic acid (CA) improved estimates of IgG. Samples (n=85) of MC were collected from a single dairy in California and used to determine the method of CA fraction that produced the best prediction of IgG based on CA fractionation followed by refractometry. Subsequently, samples of MC (n=827) were collected from 67 farms in 12 states to compare refractometry with or without CA fractionation as methods to estimate IgG concentration. Samples were collected from the feeding pool and consisted of fresh (n=196), previously frozen (n=479), or refrigerated (n=152) MC. Samples were further classified by the number freeze-thaw cycles before analysis. Fractionation with CA was conducted by adding 1 mL of MC to a tube containing 75 μL of CA and 1 mL of 0.06 M acetic acid. The tube was shaken and allowed to react for 1 min. Refractive index of the IgG-rich supernatant (nDf) was determined using a digital refractometer. Whole, nonfractionated MC was analyzed for IgG by radial immunodiffusion (RID) and refractive index (nDw). The relationship between nDf and IgG (r=0.53; n=805) was weak, whereas that between nDw and IgG was stronger (r=0.73; n=823). Fresh samples analyzed by refractometry that subsequently went through 1 freeze-thaw cycle before RID analysis resulted in the strongest relationship between IgG and nDf or nDw (r=0.93 and 0.90, respectively). The MC samples collected fresh on the farm but frozen 2 or more times before analysis by refractometry or RID had low correlations between IgG and nDf and nDw (r=0.09 and 0.01). Samples refrigerated or frozen on the farm before analysis had weaker relationships between RID and nDf or nDw (r=0.38 to 0.80), regardless of the number of freeze-thaw cycles. Breed and lactation number did not affect the accuracy of either test. These

  15. Effect of compost and humic acid in mobility and concentration of cadmium and chromium in soil and plant

    Directory of Open Access Journals (Sweden)

    A. Chaab

    2016-12-01

    Full Text Available The effect of compost and humic acid in mobility and concentration of cadmium and chromium in contaminated soil were investigated. Experiment was carried out with three levels of soil cadmium and chromium and two organic matters (compost and humic acid. The study was performed in a randomized complete block design with 3 replicates. Results indicated that application of organic substances enhanced movement of cadmium and chromium in soil column. Humic acid is more effective than compost on the mobility of cadmium and chromium in soil. Mobility of cadmium and chromium in the lower depths of soil column were increased. Cadmium and chromium concentration in shoots and roots enhanced due to increasing those concentration in soil and application of organic substances. Increase in cadmium in shoots can be attributed to the high mobility of this element in maize plant. Maize root chromium concentration was greater than shoot chromium concentration. Humic acid was more effective than compost as cadmium and chromium concentration in root and shoot was concerned. Low mobility of chromium in plant and accumulation of chromium in roots can be reasons of decreasing of chromium concentration in shoot of plant and its bioaccumulation.

  16. Osteonecrosis of the jaw: effect of bisphosphonate type, local concentration, and acidic milieu on the pathomechanism.

    Science.gov (United States)

    Otto, Sven; Pautke, Christoph; Opelz, Christine; Westphal, Ines; Drosse, Inga; Schwager, Joanna; Bauss, Frieder; Ehrenfeld, Michael; Schieker, Matthias

    2010-11-01

    Osteonecrosis of the jaw has been reported in patients receiving high doses of intravenous nitrogen-containing bisphosphonates (N-BPs) because of malignant disease. The exact pathomechanisms have been elusive and questions of paramount importance remain unanswered. Recent studies have indicated toxic effects of bisphosphonates on different cell types, apart from osteoclast inhibition. Multipotent stem cells play an important role in the processes of wound healing and bone regeneration, which seem to be especially impaired in the jaws of patients receiving high doses of N-BPs. Therefore, the aim of the present study was to investigate the effects of different bisphosphonate derivatives and dose levels combined with varying pH levels on the mesenchymal stem cells in vitro. The effect of 2 N-BPs (zoledronate and ibandronate) and 1 non-N-BP (clodronate) on immortalized mesenchymal stem cells was tested at different concentrations, reflecting 1, 3, and 6 months and 1, 3, 5, and 10 years of exposure to standard oncology doses of the 2 N-BPs and equimolar concentrations of clodronate at different pH values (7.4, 7.0, 6.7, and 6.3). Cell viability and activity were analyzed using a WST assay. Cell motility was investigated using scratch wound assays and visualized using time-lapse microscopy. Both types of bisphosphonates revealed remarkable differences. Zoledronate and ibandronate showed a dose- and pH-dependent cellular toxicity. Increasing concentrations of both N-BPs and an acidic milieu led to a significant decrease in cell viability and activity (P key role in the pathogenesis of osteonecrosis of the jaw in patients receiving high doses of N-BPs for malignant diseases. Also the potency of N-BPs might be different, suggesting a greater risk of osteonecrosis of the jaw with zoledronate. Copyright © 2010 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  17. ESR study of /sup 99/Tc(II) complex formed by reduction of ammonium pertechnetate with ascorbic acid in concentrated hydrochloric acid

    Energy Technology Data Exchange (ETDEWEB)

    Kudo, T; Tsuchihashi, N; Ogata, T

    1987-07-30

    Paramagnetic /sup 99/Tc complex formed by the reduction of ammonium pertechnetate by ascorbic acid with excess sodium nitrite in concentrated hydrochloric acid was investigated by ESR technique. This complex had total electron spin S=1/2 and the obtained ESR parameters are 2.032, 2.043; and 264, 108 gauss, respectively. It was concluded that the formed species was low spin /sup 99/Tc(II) complex. (author) 13 refs.

  18. In Vivo Dentate Nucleus Gamma-aminobutyric Acid Concentration in Essential Tremor vs. Controls.

    Science.gov (United States)

    Louis, Elan D; Hernandez, Nora; Dyke, Jonathan P; Ma, Ruoyun E; Dydak, Ulrike

    2018-04-01

    Despite its high prevalence, essential tremor (ET) is among the most poorly understood neurological diseases. The presence and extent of Purkinje cell (PC) loss in ET is the subject of controversy. PCs are a major storehouse of central nervous system gamma-aminobutyric acid (GABA), releasing GABA at the level of the dentate nucleus. It is therefore conceivable that cerebellar dentate nucleus GABA concentration could be an in vivo marker of PC number. We used in vivo 1 H magnetic resonance spectroscopy (MRS) to quantify GABA concentrations in two cerebellar volumes of interest, left and right, which included the dentate nucleus, comparing 45 ET cases to 35 age-matched controls. 1 H MRS was performed using a 3.0-T Siemens Tim Trio scanner. The MEGA-PRESS J-editing sequence was used for GABA detection in two cerebellar volumes of interest (left and right) that included the dentate nucleus. The two groups did not differ with respect to our primary outcome of GABA concentration (given in institutional units). For the right dentate nucleus, [GABA] in ET cases = 2.01 ± 0.45 and [GABA] in controls = 1.86 ± 0.53, p = 0.17. For the left dentate nucleus, [GABA] in ET cases = 1.68 ± 0.49 and [GABA] controls = 1.80 ± 0.53, p = 0.33. The controls had similar dentate nucleus [GABA] in the right vs. left dentate nucleus (p = 0.52); however, in ET cases, the value on the right was considerably higher than that on the left (p = 0.001). We did not detect a reduction in dentate nucleus GABA concentration in ET cases vs. One interpretation of the finding is that it does not support the existence of PC loss in ET; however, an alternative interpretation is the observed pattern could be due to the effects of terminal sprouting in ET (i.e., collateral sprouting from surviving PCs making up for the loss of GABA-ergic terminals from PC degeneration). Further research is needed.

  19. Surface Patterning of Benzene Carboxylic Acids on Graphite: Influence of structure, solvent, and concentration on molecular self-assembly

    Science.gov (United States)

    Florio, Gina; Stiso, Kimberly; Campanelli, Joseph; Dessources, Kimberly; Folkes, Trudi

    2012-02-01

    Scanning tunneling microscopy (STM) was used to investigate the molecular self-assembly of four different benzene carboxylic acid derivatives at the liquid/graphite interface: pyromellitic acid (1,2,4,5-benzenetetracarboxylic acid), trimellitic acid (1,2,4-benzenetricarboxylic acid), trimesic acid (1,3,5-benzenetricarboxylic acid), and 1,3,5-benzenetriacetic acid. A range of two dimensional networks are observed that depend sensitively on the number of carboxylic acids present, the nature of the solvent, and the solution concentration. We will describe our recent efforts to determine (a) the preferential two-dimensional structure(s) for each benzene carboxylic acid at the liquid/graphite interface, (b) the thermodynamic and kinetic factors influencing self-assembly (or lack thereof), (c) the role solvent plays in the assembly, (e) the effect of in situ versus ex situ dilution on surface packing density, and (f) the temporal evolution of the self-assembled monolayer. Results of computational analysis of analog molecules and model monolayer films will also be presented to aid assignment of network structures and to provide a qualitative picture of surface adsorption and network formation.

  20. Effects of total replacement of soybean meal and corn on ruminal fermentation, volatile fatty acids, protozoa concentration, and gas production

    Directory of Open Access Journals (Sweden)

    A. Bahri

    2018-03-01

    Full Text Available The main purpose of this study is to evaluate the effect of total replacement of soybean meal and corn with triticale and faba bean or field pea on rumen fermentation, protozoa counts, and gas production of lactating ewes. A total of 30 Sicilo-Sarde ewes were randomly allocated into three groups and were fed 1.8 kg drymatter of oat hay plus 500 g of one of three concentrates: the first concentrate (CS was mainly composed of soybean meal, corn, and barley; the second (TFB was formed by triticale and faba bean; and the third (TFP was composed of triticale and field pea. The type of concentrate did not affect ruminal pH or ammonia nitrogen concentration (P  >  0.05. The individual concentrations of volatile fatty acids showed a significant interaction between the type of concentrate and sampling time (P  <  0.05, except for Butyric and Isobutyric acids. Within a post-feeding time, the pattern of evolution of total volatile fatty, acetic, and propionic acids differed significantly at 2 h post feeding (P  <  0.05, while butyric and valeric acid changed at 0 and 4 h post feeding. The type of concentrate affected the total number of ciliate protozoa and the Isotricha species (P  <  0.05, whereas Entodinium, Ophryoscolex, and Polyplastron were similar among concentrates (P  >  0.05. The cumulative gas production from the in vitro fermentation, the time of incubation, and their interaction was affected by concentrate (P  <  0.001. The substitution of soybean meal and corn in the concentrate with faba bean or field peas and triticale might maintain rumen parameters of dairy ewes.

  1. Evidence for the complex relationship between free amino acid and sugar concentrations and acrylamide-forming potential in potato

    Science.gov (United States)

    Muttucumaru, N; Powers, SJ; Elmore, JS; Briddon, A; Mottram, DS; Halford, NG

    2014-01-01

    Free amino acids and reducing sugars participate in the Maillard reaction during high-temperature cooking and processing. This results not only in the formation of colour, aroma and flavour compounds, but also undesirable contaminants, including acrylamide, which forms when the amino acid that participates in the reaction is asparagine. In this study, tubers of 13 varieties of potato (Solanum tuberosum), which had been produced in a field trial in 2010 and sampled immediately after harvest or after storage for 6 months, were analysed to show the relationship between the concentrations of free asparagine, other free amino acids, sugars and acrylamide-forming potential. The varieties comprised five that are normally used for crisping, seven that are used for French fry production and one that is used for boiling. Acrylamide formation was measured in heated flour, and correlated with glucose and fructose concentration. In French fry varieties, which contain higher concentrations of sugars, acrylamide formation also correlated with free asparagine concentration, demonstrating the complex relationship between precursor concentration and acrylamide-forming potential in potato. Storage of the potatoes for 6 months at 9°C had a significant, variety-dependent impact on sugar and amino acid concentrations and acrylamide-forming potential. PMID:25540460

  2. Separation of Rhenium from Lead-Rich Molybdenite Concentrate via Hydrochloric Acid Leaching Followed by Oxidative Roasting

    Directory of Open Access Journals (Sweden)

    Guanghui Li

    2016-11-01

    Full Text Available Lead-rich molybdenite is a typical rhenium-bearing molybdenum resource in China, which has not been efficiently utilized due to its high contents of lead and gangue minerals. In this study, hydrochloric acid was used for preliminarily removing lead and calcite from a lead-rich molybdenite concentrate. Oxidative roasting-ammonia leaching was then carried out for separation of rhenium and extraction of molybdenum. The hydrochloric acid leaching experiments revealed that 93.6% Pb and 97.4% Ca were removed when the leaching was performed at 95 °C for 10 min with HCl concentration of 8 wt. % and liquid-solid ratio of 5 (mL/g. The results of direct oxidative roasting indicated that 89.3% rhenium was volatilized from the raw concentrate after roasting at 600 °C for 120 min in air. In contrast, the rhenium volatilization was enhanced distinctly to 98.0% after the acid-leached concentrate (leaching residue was roasted at 550 °C for 100 min. By the subsequent ammonia leaching, 91.5% molybdenum was leached out from the calcine produced from oxidative roasting of the acid-leached concentrate, while only 79.3% Mo was leached from the calcine produced by roasting molybdenite concentrate without pretreatment.

  3. [Concentration of glutathione (GSH), ascorbic acid (vitamin C) and substances reacting with thiobarbituric acid (TBA-rs) in single human brain metastases].

    Science.gov (United States)

    Dudek, Henryk; Farbiszewski, Ryszard; Rydzewska, Maria; Michno, Tadeusz; Kozłowski, Andrzej

    2005-01-01

    The aim of the study was to estimate the concentration of glutathione (GSH), ascorbic acid (vitamin C) and thiobarbituric acid (TBA-rs) in single human brain metastases and histologically unchanged nerve tissue. The research was conducted on fragments of neoplasmatic tissue collected from 45 patients undergoing surgery in the Department of Neurosurgery, Medical University of Białystok in years 1996-2002. Concentration of GSH was evaluated using the GSH-400 method, vitamin C using the method of Kyaw and TBA-rs using the method of Salaris and Babs. It has been found that there is a decrease of concentration of GSH and vitamin C and a considerable increase (p TBA-rs in investigated single brain human metastasis in correlation to the concentration of the mentioned above substances in unchanged nerve tissue.

  4. Simultaneous determination of nitric acid and uranium concentrations in aqueous solution from measurements of electrical conductivity, density, and temperature

    International Nuclear Information System (INIS)

    Spencer, B.B.

    1991-01-01

    Nuclear fuel reprocessing plants handle aqueous solutions of nitric acid and uranium in large quantities. Automatic control of process operations requires reliable measurements of these solutes concentration, but this is difficult to directly measure. Physical properties such as solution density and electrical conductivity vary with solute concentration and temperature. Conductivity, density and temperature can be measured accurately with relatively simple and inexpensive devices. These properties can be used to determine solute concentrations will good correlations. This paper provides the appropriate correlations for solutions containing 2 to 6 Molar (M) nitric acid and 0 to 300 g/L uranium metal at temperatures from 25--90 degrees C. The equations are most accurate below 5 M nitric acid, due to a broad maximum in the conductivity curve at 6 M. 12 refs., 9 figs., 6 tabs

  5. Comparison of Plasma Amino Acid Concentrations in End-stage Renal Disease Patients on Hemodialysis and Peritoneal Dialysis.

    OpenAIRE

    Kim, Dong Hee; Yang, Dong Ho; Hong, Sae Yong

    1998-01-01

    Objectives Recent reports have suggested that patients treated by CAPD have a relatively increased risk of death compared to patients undergoing HD, although the cause of this discrepancy is poorly understood. Protein malnutrition is an important risk factor in ESRD. Also, amino acid concentrations, for which the physiological function differs from that of protein, may be an independent risk factor in ESRD. There is no doubt concerning the prevalence of low amino acid levels in both HD and CA...

  6. Hormesis in Cholestatic Liver Disease; Preconditioning with Low Bile Acid Concentrations Protects against Bile Acid-Induced Toxicity

    NARCIS (Netherlands)

    Verhaag, Esther M.; Buist-Homan, Manon; Koehorst, Martijn; Groen, Albert K.; Moshage, Han; Faber, Klaas Nico

    2016-01-01

    Cholestasis is characterized by accumulation of bile acids and inflammation, causing hepatocellular damage. Still, liver damage markers are highest in acute cholestasis and drop when this condition becomes chronic, indicating that hepatocytes adapt towards the hostile environment. This may be

  7. Hormesis in Cholestatic Liver Disease; Preconditioning with Low Bile Acid Concentrations Protects against Bile Acid-Induced Toxicity

    NARCIS (Netherlands)

    Verhaag, Esther M.; Buist-Homan, Manon; Koehorst, Martijn; Groen, Albert K.; Moshage, Han; Faber, Klaas Nico

    2016-01-01

    Introduction Cholestasis is characterized by accumulation of bile acids and inflammation, causing hepatocellular damage. Still, liver damage markers are highest in acute cholestasis and drop when this condition becomes chronic, indicating that hepatocytes adapt towards the hostile environment. This

  8. Mid-gestational serum uric acid concentration effect on neonate birth weight and insulin resistance in pregnant women.

    Science.gov (United States)

    Nasri, Khadijeh; Razavi, Maryamsadat; Rezvanfar, Mohammad Reza; Mashhadi, Esmat; Chehrei, Ali; Mohammadbeigi, Abolfazl

    2015-01-01

    To investigate the relationship between mid-gestational serum uric acid and birth weight in diabetic pregnant women with or without insulin resistance. In a prospective cohort study, fasting uric acid, blood glucose, and serum insulin were measured in 247 pregnant women between 20-22 weeks of gestational period. Insulin resistance was estimated using the homeostasis model assessment-insulin resistance (HOMA-IR). Stratification analysis and independent t-test was used to assess the association between uric acid and birth weights regarding to insulin resistance. The means of the mid-gestational serum uric acid concentrations were not significantly different in women with and without insulin resistance. But stratification analysis showed that there was a significant difference between uric acid concentration and macrosomic birth in diabetic women without insulin resistance. Higher mid - gestation serum uric acid concentration, even if it does not exceed the normal range, is accompanied by lower birth weight only in non-insulin resistance women. Insulin resistance could have a negative confounding effect on hyperuriemia and birth weight.

  9. Structural evidence for solvent-stabilisation by aspartic acid as a mechanism for halophilic protein stability in high salt concentrations.

    Science.gov (United States)

    Lenton, Samuel; Walsh, Danielle L; Rhys, Natasha H; Soper, Alan K; Dougan, Lorna

    2016-07-21

    Halophilic organisms have adapted to survive in high salt environments, where mesophilic organisms would perish. One of the biggest challenges faced by halophilic proteins is the ability to maintain both the structure and function at molar concentrations of salt. A distinct adaptation of halophilic proteins, compared to mesophilic homologues, is the abundance of aspartic acid on the protein surface. Mutagenesis and crystallographic studies of halophilic proteins suggest an important role for solvent interactions with the surface aspartic acid residues. This interaction, between the regions of the acidic protein surface and the solvent, is thought to maintain a hydration layer around the protein at molar salt concentrations thereby allowing halophilic proteins to retain their functional state. Here we present neutron diffraction data of the monomeric zwitterionic form of aspartic acid solutions at physiological pH in 0.25 M and 2.5 M concentration of potassium chloride, to mimic mesophilic and halophilic-like environmental conditions. We have used isotopic substitution in combination with empirical potential structure refinement to extract atomic-scale information from the data. Our study provides structural insights that support the hypothesis that carboxyl groups on acidic residues bind water more tightly under high salt conditions, in support of the residue-ion interaction model of halophilic protein stabilisation. Furthermore our data show that in the presence of high salt the self-association between the zwitterionic form of aspartic acid molecules is reduced, suggesting a possible mechanism through which protein aggregation is prevented.

  10. EFFECT OF NITROGEN SOURCE AND INITIAL SUGAR CONCENTRATION ON LACTIC ACID FERMENTATION OF PINEAPPLE WASTE USING L.DELBRUECKII

    Directory of Open Access Journals (Sweden)

    Abdullah Moch Busairi

    2012-02-01

    Full Text Available The liquid pineapple waste contains mainly sucrose, glucose, fructose and other nutrients. It therefore can potentially be used as carbon source for lactic acid fermentation. The lactic acid is utilised in food technology as pH regulator, microbial preservative, buffering agent and in the chemical industry. Recently, lactic acid has been considered to be an important raw material for production of biodegradable lactate polymer. The experiments were carried out in batch fermentation at anaerobic condition with stirring speed: 50 rpm, temperature: 40 oC, pH: 6.0, and inoculum size: 5%. Effect of nitrogen source and initial sugar concentration were studied. The effect of nitrogen source on lactic acid production shows that the yeast extract is highest yield , followed by urea , corn steep liquor, malt sprout and ammonium sulphates with the yield of 78.52; 26.68; 19.14; 14.10 and 5.6 %, respectively. The highest yield of initial sugar concentration on lactic acid production obtained was 78.52 % (54.97 g/l at 70 g/l, if the concentration of sugar was increased to 110 g/l , the lactic acid production or yield decrease to51.53 g/l or 54.24%.

  11. Gladiolus development in response to bulb treatment with different concentrations of humic acids

    Directory of Open Access Journals (Sweden)

    Marihus Altoé Baldotto

    2013-02-01

    Full Text Available Gladiolus is an ornamental species produced for cut flowers and propagated by corms. The early flowering and increase in the number of flower buds, besides the production of commercial corms are constant challenges to be addressed in the crop improvement. Commercial production of ornamentals is technologically accelerated by means of growth regulators. Among them, the auxins stand out for their key role in the adventitious rooting and cell elongation. Alternatively, the humic substances present in the organic matter also have biostimulating effect, which is very similar to the auxinic effect. Therefore, this work aimed to study the growth and development of gladiolus in response to application of different concentrations of humic acids (HA isolated from vermicompost. Corms were soaked for 24 hours in solutions containing 0, 10, 20, 30 and 40 mmol L-1 of C from HA. The corms were planted in 10-dm³ plastic bags filled with substrate and kept in a greenhouse. Growth of shoots and roots was evaluated. The results showed that the use of HA accelerates growth, and anticipates and increases flowering of Gladiolus.

  12. Effect of Digestion and Storage of Human Milk on Free Fatty Acid Concentration and Cytotoxicity

    Science.gov (United States)

    Penn, Alexander H.; Altshuler, Angelina E.; Small, James W.; Taylor, Sharon F.; Dobkins, Karen R.; Schmid-Schönbein, Geert W.

    2014-01-01

    Objectives Fat is digested in the intestine into free fatty acids (FFAs), which are detergents and therefore toxic to cells at micromolar concentration. The mucosal barrier protects cells in the adult intestine, but this barrier may not be fully developed in premature infants. Lipase-digested infant formula, but not fresh human milk, has elevated FFAs and is cytotoxic to intestinal cells, and therefore could contribute to intestinal injury in necrotizing enterocolitis (NEC). But even infants exclusively fed breast milk may develop NEC. Our objective was to determine if stored milk and milk from donor milk banks (DM) could also become cytotoxic, especially after digestion. Methods We exposed cultured rat intestinal epithelial cells or human neutrophils to DM and milk collected fresh and stored at 4 or −20 °C for up to 12 weeks and then treated for 2 hours (37°C) with 0.1 or 1 mg/ml pancreatic lipase and/or trypsin and chymotrypsin. Results DM and milk stored 3 days (at 4 or −20 °C) and then digested were cytotoxic. Storage at −20 °C for 8 and 12 weeks resulted in an additional increase in cytotoxicity. Protease digestion decreased, but did not eliminate cell death. Conclusions Current storage practices may allow milk to become cytotoxic and contribute to intestinal damage in NEC. PMID:24840512

  13. Urinary concentration of 3-phenoxybenzoic acid in elementary students in South Korea

    Directory of Open Access Journals (Sweden)

    Hye Mi Jo

    2015-10-01

    Full Text Available Objectives Pyrethroid pesticides are among the most commonly using insecticides in South Korean households and have been the subject of considerable interest among public health professionals for their potential health effects. The objective of this study is to examine the level of urinary 3-phenoxybenzoic acid (3-PBA among elementary students in South Korea. Methods We conducted a cross-sectional study to evaluate pyrethroid pesticide exposure levels by measuring the urinary metabolites of 3-PBA using a gas chromatography-mass spectrometry method in March 2011. Study participants were 70 Asan-area and Incheon-area elementary students. Results All respondents had values above the detection limit, and the geometric means of 3-PBA in all children were 1.85 μg/L and 1.46 μg/g creatinine. Children with the top 10% urinary levels of 3-PBA were more likely to be girls, under nine years of age, living in a rural area, and living in a residential type apartment. Conclusions South Korean children have a higher concentration of urinary 3-PBA compared with those of other countries. Further research identifying exposure pathways and intervention efforts to reduce environmental pesticide use are needed in South Korea.

  14. Concentration determination of nucleic acids and proteins using the micro-volume BioSpec-nano-spectrophotometer.

    Science.gov (United States)

    Sukumaran, Suja

    2011-02-17

    Nucleic acid quantitation procedures have advanced significantly in the last three decades. More and more, molecular biologists require consistent small-volume analysis of nucleic acid samples for their experiments. The BioSpec-nano provides a potential solution to the problems of inaccurate, non-reproducible results, inherent in current DNA quantitation methods, via specialized optics and a sensitive PDA detector. The BioSpec-nano also has automated functionality such that mounting, measurement, and cleaning are done by the instrument, thereby eliminating tedious, repetitive, and inconsistent placement of the fiber optic element and manual cleaning. In this study, data is presented on the quantification of DNA and protein, as well as on measurement reproducibility and accuracy. Automated sample contact and rapid scanning allows measurement in three seconds, resulting in excellent throughput. Data analysis is carried out using the built-in features of the software. The formula used for calculating DNA concentration is: Sample Concentration = DF · (OD260-OD320)· NACF (1) Where DF = sample dilution factor and NACF = nucleic acid concentration factor. The Nucleic Acid concentration factor is set in accordance with the analyte selected. Protein concentration results can be expressed as μg/mL or as moles/L by entering e280 and molecular weight values respectively. When residue values for Tyr, Trp and Cysteine (S-S bond) are entered in the e280Calc tab, the extinction coefficient values are calculated as e280 = 5500 x (Trp residues) + 1490 x (Tyr residues) + 125 x (cysteine S-S bond). The e280 value is used by the software for concentration calculation. In addition to concentration determination of nucleic acids and protein, the BioSpec-nano can be used as an ultra micro-volume spectrophotometer for many other analytes or as a standard spectrophotometer using 5 mm pathlength cells.

  15. Concentration Determination of Nucleic Acids and Proteins Using the Micro-volume Bio-spec Nano Spectrophotometer

    Science.gov (United States)

    Sukumaran, Suja

    2011-01-01

    Nucleic Acid quantitation procedures have advanced significantly in the last three decades. More and more, molecular biologists require consistent small-volume analysis of nucleic acid samples for their experiments. The BioSpec-nano provides a potential solution to the problems of inaccurate, non-reproducible results, inherent in current DNA quantitation methods, via specialized optics and a sensitive PDA detector. The BioSpec-nano also has automated functionality such that mounting, measurement, and cleaning are done by the instrument, thereby eliminating tedious, repetitive, and inconsistent placement of the fiber optic element and manual cleaning. In this study, data is presented on the quantification of DNA and protein, as well as on measurement reproducibility and accuracy. Automated sample contact and rapid scanning allows measurement in three seconds, resulting in excellent throughput. Data analysis is carried out using the built-in features of the software. The formula used for calculating DNA concentration is: Sample Concentration = DF · (OD260-OD320)· NACF (1) Where DF = sample dilution factor and NACF = nucleic acid concentration factor. The Nucleic Acid concentration factor is set in accordance with the analyte selected1. Protein concentration results can be expressed as μg/ mL or as moles/L by entering e280 and molecular weight values respectively. When residue values for Tyr, Trp and Cysteine (S-S bond) are entered in the e280Calc tab, the extinction coefficient values are calculated as e280 = 5500 x (Trp residues) + 1490 x (Tyr residues) + 125 x (cysteine S-S bond). The e280 value is used by the software for concentration calculation. In addition to concentration determination of nucleic acids and protein, the BioSpec-nano can be used as an ultra micro-volume spectrophotometer for many other analytes or as a standard spectrophotometer using 5 mm pathlength cells. PMID:21372788

  16. Determination of free acid in highly concentrated organic and aqueous solutions of plutonium (IV) and uranium (VI) nitrate

    International Nuclear Information System (INIS)

    Wagner, J.F.; Lacour, J.L.

    1989-01-01

    Free acidity is an important parameter in the nuclear reprocessing control. The accuracy on the determination of free acidity is not really required in the nuclear reprocessing control itself but is necessary for certain types of analysis such as spectrophotometry (Pu (VI), Am (III),...), density determinations. A new titripotentiometric method for free acidity determination in concentrated U(VI) and Pu(IV) solutions is presented. This method is based on the complexing properties of dipicolinic acid (pyridine 2.6 dicarboxylic acid) and medium effect with H 2 O/DMSO mixture. This method can be used either in organic or aqueous phases with ratio /H + I/ metal ≥ 5.10 -2 and a relative standard deviation of 1%

  17. Short Communication: Elevated Concentrations of Oleic Acid and Long-Chain Fatty Acids in Milk Fat of Multiparous Subclinical Ketotic Cows

    NARCIS (Netherlands)

    Haelst, van Y.N.T.; Beeckman, A.; Knegsel, van A.T.M.; Fievez, V.

    2008-01-01

    The objective of this study was to determine whether concentrations of specific fatty acids in milk fat are a candidate for the early detection of subclinical ketosis. The case study included multiparous cows fed a lipogenic diet or a mixed glucogenic:lipogenic diet during the first 9 wk of

  18. The effect of different concentrations of citric acid on motility patterns of bovine epididymal sperms in Hams F10 milieu

    Directory of Open Access Journals (Sweden)

    K Abdy

    2008-11-01

    Full Text Available The aim of this study was to investigate the effect of three concentration of citric acid on motility patterns of bovine epididymal sperms. For this purpose, 50 pairs of bovine testicles were collected immediately after slaughter form urmia abattoir and transferred to the laboratory alongside 5oc ice pack. Epididymal tail sperms were collected with a few incisions in vascular areas and transferred to hams f10 milieu with 10% fetal calf serum and counted after 15 minutes of incubation at 37oc in Co2 incubator. Concentrations of 50 million sperms per ml were proposal and in the normal sperm pH rang of 6.7-7.4, 0.1, 0.2 and 0.3 normal concentration of citric acid were added to sperm continuity micro tubes (normal concentration of acid equals 7 mg/ml of bovine serum and at 15, 30, 45, 60, 90, 120, 180, 240 and 360 minutes the motility patterns of epididymal sperms were evaluated using the computer assisted sperms analyzing (CASA method. Data were analyzed with one-way ANOVA using the SPSS 15 software. The results indicated significant differences in various indices of sperm motility patterns (Curvilinear   Velocity, Straight-line Velocity, Average Path Velocity, Mean Angel Degree, Amplitude of Lateral Head Displacement, Beat-Cross Frequency, Linearity, Wobble particularly at 0.3 normal concentration of citric acid compared with the control.

  19. Increases in plasma motilin follow each episode of gallbladder emptying during the interdigestive period, and changes in serum bile acid concentration correlate to plasma motilin

    DEFF Research Database (Denmark)

    Qvist, N; Oster-Jørgensen, E; Pedersen, S A

    1995-01-01

    concentration of bile acids also showed a cyclic variation in relation to gallbladder motility. During periods of gallbladder emptying serum bile acid concentration had a median value of 1.78 mumol/l, as compared with a median value of 1.17 mumol/l during periods of gallbladder filling. This difference did......, and in cases of two or more emptying periods during the MMC cycle the concentration decreased in between. The shape of the serum bile acid profile is dependent on the intestinal transport and absorption of bile acids, and the significance of the cyclic variation in serum concentration of bile acids in relation...

  20. Increased dietary long-chain polyunsaturated fatty acids alter serum fatty acid concentrations and lower risk of urine stone formation in cats.

    Directory of Open Access Journals (Sweden)

    Jean A Hall

    Full Text Available The lifespan of cats with non-obstructive kidney stones is shortened compared with healthy cats indicating a need to reduce stone formation and minimize chronic kidney disease. The purpose of this study was to investigate the effects of increasing dietary polyunsaturated fatty acids (PUFA on urine characteristics. Domestic-short-hair cats (n = 12; mean age 5.6 years were randomized into two groups and fed one of two dry-cat foods in a cross-over study design. For one week before study initiation, all cats consumed control food that contained 0.07% arachidonic acid (AA, but no eicosapentaenoic acid (EPA or docosahexaenoic acid (DHA. Group 1 continued eating control food for 56 days. Group 2 was fed test food for 56 days, which was control food plus fish oil and high-AA oil. Test food contained 0.17% AA, 0.09% EPA and 0.18% DHA. After 56 days, cats were fed the opposite food for another 56 days. At baseline and after each feeding period, serum was analyzed for fatty acid concentrations, and urine for specific gravity, calcium concentration, relative-super-saturation for struvite crystals, and a calcium-oxalate-titrimetric test was performed. After consuming test food, cats had increased (all P<0.001 serum concentrations of EPA (173%, DHA (61%, and AA (35%; decreased urine specific gravity (P = 0.02; decreased urine calcium concentration (P = 0.06; decreased relative-super-saturation for struvite crystals (P = 0.03; and increased resistance to oxalate crystal formation (P = 0.06 compared with cats consuming control food. Oxalate crystal formation was correlated with serum calcium concentration (r = 0.41; P<0.01. These data show benefits for reducing urine stone formation in cats by increasing dietary PUFA.

  1. Raman spectroscopic study of the aging and nitration of actinide processing anion-exchange resins in concentrated nitric acid

    International Nuclear Information System (INIS)

    Buscher, C. T.; Donohoe, R. J.; Mecklenburg, S. L.; Berg, J. M.; Tait, C. D.; Huchton, K. M.; Morris, D. E.

    1999-01-01

    Degradation of two types of anion exchange resins, Dowex 11 and Reillex HPQ, from the action of concentrated nitric acid (4 to 12 M) and radiolysis [from depleted uranium as UO 2 2+ nitrate species and 239 Pu as Pu(IV) nitrate species] was followed as a function of time with Raman vibrational spectroscopy. Elevated temperatures (∼50 degree sign C) were used in the absence of actinide metal loading to simulate longer exposures of the resin to a HNO 3 process stream and waste storage conditions. In the absence of actinide loading, only minor changes in the Dowex resin at acid concentrations ≤10 M were observed, while at 12 M acid concentration, the emergence of a Raman peak at 1345 cm-1 indicates the addition of nitro functional groups to the resin. Similar studies with the Reillex resin show it to be more resistant to nitric acid attack at all acid concentrations. Incorporation of weakly radioactive depleted uranium as the UO 2 2+ nitrate species to the ion-exchange sites of Dowex 11 under differing nitric acid concentrations (6 to 12 M) at room temperature showed no Raman evidence of resin degradation or nitration, even after several hundred days of contact. In contrast, Raman spectra for Dowex 11 in the presence of 239 Pu as Pu(IV) nitrate species reveal numerous changes indicating resin alterations, including a new mode at 1345 cm-1 consistent with a Pu(IV)-nitrate catalyzed addition of nitro groups to the resin backbone. (c) 2000 Society for Applied Spectroscopy

  2. Effects of dietary sulfur concentration and forage-to-concentrate ratio on ruminal fermentation, sulfur metabolism, and short-chain fatty acid absorption in beef heifers.

    Science.gov (United States)

    Amat, S; McKinnon, J J; Penner, G B; Hendrick, S

    2014-02-01

    This study evaluated the effects of dietary S concentration and forage-to-concentrate ratio (F:C) on ruminal fermentation, S metabolism, and short-chain fatty acid (SCFA) absorption in beef heifers. Sixteen ruminally cannulated heifers (initial BW 628 ± 48 kg) were used in a randomized complete block design with a 2 × 2 factorial treatment arrangement. The main factors included F:C (4% forage vs. 51% forage, DM basis) and the S concentration, which was modified using differing sources of wheat dried distillers grains with solubles (DDGS) to achieve low- and high-S diets (LS = 0.30% vs. HS = 0.67% S on a DM basis). Elemental S was also added to increase the S content for the HS diets. Serum sulfate concentration from blood, sulfide (S(2-)), and SCFA concentrations from ruminal fluid, hydrogen sulfide (H2S) concentration from the ruminal gas cap, and urinary sulfate concentration were determined. Continuous rumen pH and SCFA (acetate, butyrate, and propionate) absorption were measured. There were no interactions between S concentration and F:C. The F:C did not affect DMI (P = 0.26) or ruminal S metabolite concentrations (P ≥ 0.19), but ruminal pH was lower (P ruminal pH (P ruminal H2S (P Ruminal H2S was positively correlated with serum sulfate (r = 0.89; P Ruminal acetate concentration was not affected (P = 0.26) by dietary S concentration. Heifers fed the HS diet had lower (P = 0.01) ruminal propionate concentration and tended to have lower (P = 0.06) butyrate concentration than heifers fed the LS diet. Ruminal acetate was greater (P = 0.01) and butyrate was less (P < 0.01) with the high F:C diet than the low F:C diet. Both HS (P = 0.06) and low F:C (P = 0.07) diets tended to reduce urine output. Feeding HS diets reduced SCFA absorption (P < 0.05). In summary, S metabolism in beef heifers was not influenced by the F:C, but HS reduced DMI, inhibited SCFA absorption, and increased urinary S excretion.

  3. Short-term folic acid supplementation induces variable and paradoxical changes in plasma homocyst(e)ine concentrations.

    Science.gov (United States)

    Malinow, M R; Duell, P B; Williams, M A; Kruger, W D; Evans, A A; Anderson, P H; Block, P C; Hess, D L; Upson, B M; Graf, E E; Irvin-Jones, A; Wang, L

    2001-01-01

    Folic acid is presently the mainstay of treatment for most subjects with elevated plasma homocyst(e)ine concentrations [Plasma or serum homocyst(e)ine, or total homocysteine, refers to the sum of the sulfhydryl amino acid homocysteine and the homocysteinyl moieties of the disulfides homocystine and homocystein-cysteine, whether free or bound to plasma proteins.] Changes in homocyst(e)ine in response to folic acid supplementation are characterized by considerable interindividual variation. The purpose of this study was to identify factors that contribute to heterogeneity in short-term responses to folic acid supplementation. The effects of folic acid supplementation (1 or 2 mg per day) for 3 wk on plasma homocyst(e)ine concentrations were assessed in 304 men and women. Overall, folic acid supplementation increased mean plasma folate 31.5 +/- 98.0 nmol/L and decreased mean plasma homocyst(e)ine concentrations 1.2 +/- 2.4 micromol/L. There was evidence of substantial interindividual variation in the homocyst(e)ine response from -18.5 to +7.1 micromol/L, including an increase in homocyst(e)ine in 20% of subjects (mean increase 1.5 +/- 1.4 micromol/L). Basal homocyst(e)ine, age, male gender, cigarette smoking, use of multivitamins, methylene tetrahydrofolate reductase, and cystathionine beta-synthase polymorphisms accounted for 47.6% of the interindividual variability in the change in homocyst(e)ine after folic acid supplementation, but about 50% of variability in response to folic acid was not explained by the variables we studied.

  4. Body condition score, nonesterified fatty acids and beta-hydroxybutyrate concentrations in goats with subclinical ketosis

    Directory of Open Access Journals (Sweden)

    V. Marutsova

    2017-12-01

    Full Text Available Abstract. Studies were conducted to establish the influence of the values of β-hydroxybutyric acid (ВНВА and non-esterified fatty acids (NEFA in the blood on the assessment of body condition score (BCS of goats with subclinical ketosis (SCK. A total of 113 dairy goats with yearly milk yield of 680 L, in their 2nd to 3rd lactation and average body weight 50-60 кg were included in the study. The goats were divided in three groups: І group (n=27 – pregnant (from pre-partum days 15 to 0; ІІ group (n=28 – recently kidded (from postpartum days 0 to 15 and ІІІ group (n=58 – lactating (from postpartum days 30 to 45. It was established that the quantity of BHBA in goats from control groups I, II and III were between 0.17±0.11 mmol/l and 0.56±0.11 mmol/l. In goats from the three groups with SCK signs, blood BHBA was statistically significantly elevated vs control goats – from 0.88±0.11 mmol/l to 1.2±0.42 mmol/l (р<0.001. Blood ВНВА <0.8 mmol/l in goats are indicative a good transition from pregnancy to lactation, whereas an amount between 0.8 mmol/l and 1.6 mmol /l are indicative of the SCK. Blood BHBA concentrations indicative for clinical ketosis were not established in goats from the three groups (ВНВА <1.6 mmol/l. The body condition scores (BCS of goats from the control groups was within the reference range – 2.45±0.3 – 2.85±0.2, whereas in goats with SCK – declines of varying degrees of reliability. In goats from the three groups with SCK signs, blood NEFA was statistically significantly elevated vs control groups.

  5. Fasting and postprandial serum bile acid concentrations in 10 healthy female red-eared terrapins (Trachemys scripta elegans).

    Science.gov (United States)

    Knotkova, Z; Dorrestein, G M; Jekl, V; Janouskova, J; Knotek, Z

    2008-10-25

    The fasting and postprandial serum concentrations of bile acids and other blood constituents were measured in a group of 10 clinically healthy, female, six-year-old captive red-eared terrapins (Trachemys scripta elegans). The terrapins were housed in a temperate room and maintained in four aquaria in which the water temperature ranged from 24 to 27 degrees C and the temperature above the basking site ranged from 27 to 30 degrees C. The serum concentrations of bile acids were measured four times in a period of five months, and at the second sampling the fasting and two postprandial (after 24 and 48 hours) serum concentrations of total protein, albumin, glucose, uric acid, cholesterol, triglycerides, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and bile acids were determined. Coelioscopy revealed vitellogenic and previtellogenic follicles on the ovaries of all the terrapins, and eggs with calcified shells were detected in two of them. The livers were mostly pink to deep yellow in colour, with sharp edges, a smooth serosal surface, distinct large superficial vessels, and multifocal melanin deposits. Liver biopsies revealed fine, more or less oil red O-positive lipid droplets in all the hepatocytes, but in none of the cases was it considered to be pathological lipidosis. The mean (sd) bile acid concentrations ranged from 7.35 (4.52) to 10.04 (7.40) micromol/l. The fasting and postprandial concentrations were 3.1 (2.3), 4.5 (5.4) (24 hours) and 2.2 (1.5) (48 hours) micromol/l. High concentrations between 27.6 and 66.6 micromol/l were associated with lipaemia. There were no significant differences between the biochemical profiles of the fasting and postprandial serum samples.

  6. Serum alpha-tocopherol and ascorbic acid concentrations in Type 1 and Type 2 diabetic patients with and without angiopathy.

    Science.gov (United States)

    Skrha, Jan; Prázný, Martin; Hilgertová, Jirina; Weiserová, Hana

    2003-03-01

    Alpha-tocopherol and ascorbic acid form a part of scavenger system influencing the level of oxidative stress in diabetes mellitus. The aim of this study was to evaluate serum concentrations of alpha-tocopherol and ascorbic acid in Type 1 and Type 2 diabetes mellitus and to compare them with the presence of vascular complications as well as with oxidative stress and endothelial dysfunction. A total of 38 Type 1 and 62 Type 2 diabetic patients were subdivided into those with and without angiopathy. Serum alpha-tocopherol and ascorbic acid concentrations were estimated in all patients and in 38 healthy persons. Their results were compared with diabetes control, with oxidative stress measured by plasma malondialdehyde and with endothelial dysfunction estimated by serum N-acetyl-beta-glucosaminidase activity. In addition, the differences in biochemical variables were compared between patients with and without angiopathy. Serum alpha-tocopherol related to the sum of cholesterol and triglyceride concentrations (AT/CHT ratio) was significantly lower in diabetic patients with macroangiopathy than in those without vascular changes (pascorbic acid levels were significantly lower only in Type 2 diabetic patients with macroangiopathy as compared with healthy controls as well as with patients without vascular disease (pcholesterol or triglyceride concentrations in both Type 1 and Type 2 diabetic patients. The presence of oxidative stress together with endothelial dysfunction measured by N-acetyl-beta-glucosaminidase activity was accompanied by lower AT/CHT ratio (pascorbic acid concentration in serum. Their low concentrations may participate at the increased level of oxidative stress in these individuals.

  7. Myocardial scintigraphy with 16 /sup 123/I hexadecene 9 oique acid: influence of plasma concentrations of fatty acids and glucose

    Energy Technology Data Exchange (ETDEWEB)

    Comet, M.; Pilichowski, P.; Wolf, J.E.; Busquet, G.; Dubois, F.; Mathieu, J.P.; Pernin, C.; Riche, F. (C.H.R.U. de Grenoble (France)); Vidal, M. (U.S.M.G., 38 - Grenoble (France))

    1983-01-01

    After I.V. injection of /sup 123/I hexadecene-9 oic acid to dogs, the decreasing part of the myocardial activity curve is fitted with an exponential which period is calculated. Then the procedure is repeated after I.V. injection of heparin alone (6 dogs), of heparin during an intralipid perfusion (6 dogs) and lastly during a perfusion of a solution of glucose, insulin and potassium (7 dogs). In the two last protocols only, the period of the curve is significantly increased. The increase of the period means perhaps an increase of the intracellular accumulation of fatty acids. Patients must be in the same nutritional state to allow comparison between periods and a measure of the plasma level of NEFA is necessary before each injection of the labelled fatty acid.

  8. Myocardial scintigraphy with 16 123I hexadecene 9 oique acid: influence of plasma concentrations of fatty acids and glucose

    International Nuclear Information System (INIS)

    Comet, M.; Pilichowski, P.; Wolf, J.E.; Busquet, G.; Dubois, F.; Mathieu, J.P.; Pernin, C.; Riche, F.; Vidal, M.

    1983-01-01

    After I.V. injection of 123 I hexadecene-9 oic acid to dogs, the decreasing part of the myocardial activity curve is fitted with an exponential which period is calculated. Then the procedure is repeated after I.V. injection of heparin alone (6 dogs), of heparin during an intralipid perfusion (6 dogs) and lastly during a perfusion of a solution of glucose, insulin and potassium (7 dogs). In the two last protocols only, the period of the curve is significantly increased. The increase of the period means perhaps an increase of the intracellular accumulation of fatty acids. Patients must be in the same nutritional state to allow comparison between periods and a measure of the plasma level of NEFA is necessary before each injection of the labelled fatty acid [fr

  9. Fatty acid concentration and proximate composition of acid silage from Nile tilapia (Oreochromis niloticus) waste, farmed in Indaiatuba – SP

    OpenAIRE

    Sales, Ronaldo de Oliveira; Universidade Federal do Ceará; Park, Kil Jin; Universidade Estadual de Campinas; de Morais, Selene Maia; Universidade Estadual de Ceará

    2013-01-01

    This study was conducted to determine the composition and fatty acid profile of the Nile tilapia waste silage with the aim of investigating its nutritional potential. Four lots (5 kg each) of Nile tilapia waste was ground with 3% (w/w) formic acid, stored at 27°C room temperature for 90 days in polyethylene boxes with holes, through which gases went out and then the levels of moisture, protein, ash and total lipids were analyzed obtaining: 77.25, 16.31, 3.17 and 3.26% respectively. 22 types o...

  10. Influence of concentration, time and method of application of citric acid and sodium citrate in root conditioning

    Science.gov (United States)

    CAVASSIM, Rodrigo; LEITE, Fábio Renato Manzolli; ZANDIM, Daniela Leal; DANTAS, Andrea Abi Rached; RACHED, Ricardo Samih Georges Abi; SAMPAIO, José Eduardo Cezar

    2012-01-01

    Objective The aim of this study was to establish the parameters of concentration, time and mode of application of citric acid and sodium citrate in relation to root conditioning. Material and Methods A total of 495 samples were obtained and equally distributed among 11 groups (5 for testing different concentrations of citric acid, 5 for testing different concentrations of sodium citrate and 1 control group). After laboratorial processing, the samples were analyzed under scanning electron microscopy. A previously calibrated and blind examiner evaluated micrographs of the samples. Non-parametric statistical analysis was performed to analyze the data obtained. Results Brushing 25% citric acid for 3 min, promoted greater exposure of collagen fibers in comparison with the brushing of 1% citric acid for 1 minute and its topical application at 1% for 3 min. Sodium citrate exposed collagen fibers in a few number of samples. Conclusion Despite the lack of statistical significance, better results for collagen exposure were obtained with brushing application of 25% citric acid for 3 min than with other application parameter. Sodium citrate produced a few number of samples with collagen exposure, so it is not indicated for root conditioning. PMID:22858707

  11. Isolation of bacterial cellulose nanocrystalline from pineapple peel waste: Optimization of acid concentration in the hydrolysis method

    Science.gov (United States)

    Anwar, Budiman; Rosyid, Nurul Huda; Effendi, Devi Bentia; Nandiyanto, Asep Bayu Dani; Mudzakir, Ahmad; Hidayat, Topik

    2016-02-01

    Isolation of needle-shaped bacterial cellulose nanocrystalline with a diameter of 16-64 nm, a fiber length of 258-806 nm, and a degree of crystallinity of 64% from pineapple peel waste using an acid hydrolysis process was investigated. Experimental showed that selective concentration of acid played important roles in isolating the bacterial cellulose nanocrystalline from the cellulose source. To achieve the successful isolation of bacterial cellulose nanocrystalline, various acid concentrations were tested. To confirm the effect of acid concentration on the successful isolation process, the reaction conditions were fixed at a temperature of 50°C, a hydrolysis time of 30 minutes, and a bacterial cellulose-to-acid ratio of 1:50. Pineapple peel waste was used as a model for a cellulose source because to the best of our knowledge, there is no report on the use of this raw material for producing bacterial cellulose nanocrystalline. In fact, this material can be used as an alternative for ecofriendly and cost-free cellulose sources. Therefore, understanding in how to isolate bacterial cellulose nanocrystalline from pineapple peel waste has the potential for large-scale production of inexpensive cellulose nanocrystalline.

  12. Influence of concentration, time and method of application of citric acid and sodium citrate in root conditioning

    Directory of Open Access Journals (Sweden)

    Rodrigo Cavassim

    2012-06-01

    Full Text Available OBJECTIVES: The aim of this study was to establish the parameters of concentration, time and mode of application of citric acid and sodium citrate in relation to root conditioning. MATERIAL AND METHODS: A total of 495 samples were obtained and equally distributed among 11 groups (5 for testing different concentrations of citric acid, 5 for testing different concentrations of sodium citrate and 1 control group. After laboratorial processing, the samples were analyzed under scanning electron microscopy. A previously calibrated and blind examiner evaluated micrographs of the samples. Non-parametric statistical analysis was performed to analyze the data obtained. RESULTS: Brushing 25% citric acid for 3 min, promoted greater exposure of collagen fibers in comparison with the brushing of 1% citric acid for 1 minute and its topical application at 1% for 3 min. Sodium citrate exposed collagen fibers in a few number of samples. CONCLUSION: Despite the lack of statistical significance, better results for collagen exposure were obtained with brushing application of 25% citric acid for 3 min than with other application parameter. Sodium citrate produced a few number of samples with collagen exposure, so it is not indicated for root conditioning.

  13. Effect of Phosphoric Acid Concentration on the Characteristics of Sugarcane Bagasse Activated Carbon

    Science.gov (United States)

    Adib, M. R. M.; Suraya, W. M. S. W.; Rafidah, H.; Amirza, A. R. M.; Attahirah, M. H. M. N.; Hani, M. S. N. Q.; Adnan, M. S.

    2016-07-01

    Impregnation method is one of the crucial steps involved in producing activated carbon using chemical activation process. Chemicals employed in this step is effective at decomposing the structure of material and forming micropores that helps in adsorption of contaminants. This paper explains thorough procedures that have been involved in producing sugarcane bagasse activated carbon (SBAC) by using 5%, 10%, 20%, 30% phosphoric acid (H3PO4) during the impregnation step. Concentration of H3PO4 used in the process of producing SBAC was optimized through several tests including bulk density, ash content, iodine adsorption and pore size diameter and the charactesristic of optimum SBAC produced has been compared with commercial activated carbon (CAC). Batch study has been carried out by using the SBAC produced from optimum condition to investigate the performance of SBAC in removal of turbidity and chemical oxygen demand (COD) from textile wastewater. From characteristic study, SBAC with 30% H3PO4 has shown the optimum value of bulk density, ash content, iodine adsorption and pore size diameter of 0.3023 g cm-3, 4.35%, 974.96 mg/g and 0.21-0.41 µm, respectively. These values are comparable to the characteristics of CAC. Experimental result from the batch study has been concluded that the SBAC has a promising potential in removing turbidity and COD of 75.5% and 66.3%, respectively which was a slightly lower than CAC which were able to remove 82.8% of turbidity and 70% of COD. As a conclusion, the SBAC is comparable with CAC in terms of their characteristics and the capability of removing contaminants from textile wastewater. Therefore, it has a commercial value to be used as an alternative of low-cost material in producing CAC.

  14. Fogging low concentrated organic acid in a fattening pig unit – Effect on animal health and microclimate

    Directory of Open Access Journals (Sweden)

    Heiko Stein

    2016-09-01

    Although fogging of tartaric acid is limited to a concentration of 0.1% due to its irritating effect on the respiratory mucosa, reduction of microbial load can be achieved, but it would be enhanced by using more powerful fogging systems.

  15. Ascorbic acid concentrations in aqueous humor after systemic vitamin C supplementation in patients with cataract: pilot study.

    Science.gov (United States)

    Hah, Young-Sool; Chung, Hye Jin; Sontakke, Sneha B; Chung, In-Young; Ju, Sunmi; Seo, Seong-Wook; Yoo, Ji-Myong; Kim, Seong-Jae

    2017-07-11

    To measure ascorbic acid concentration in aqueous humor of patients with cataract after oral or intravenous vitamin C supplementation. Forty-two eyes of 42 patients with senile cataract who underwent uncomplicated cataract surgery were enrolled. Patients (n = 14 each) were administered oral vitamin C (2 g), intravenous vitamin C (20 g) or no treatment (control group) on the day before surgery. Samples of aqueous humor (0.1 cm 3 ) were obtained by anterior chamber aspiration at the beginning of surgery and stored at -80 °C. Ascorbic acid concentration in aqueous humor was measured by high-pressure liquid chromatography. The mean age at surgery was 62.5 years, with no difference among the three groups. The mean ± standard deviation concentrations of ascorbic acid in aqueous humor in the control and oral and intravenous vitamin C groups were 1347 ± 331 μmol/L, 1859 ± 408 μmol/L and 2387 ± 445 μmol/L, respectively. Ascorbic acid concentration was significantly lower in the control than in the oral (P humor is increased by systemic vitamin C supplementation, with intravenous administration being more effective than oral administration.

  16. Excluded volume effects caused by high concentration addition of acid generators in chemically amplified resists used for extreme ultraviolet lithography

    Science.gov (United States)

    Kozawa, Takahiro; Watanabe, Kyoko; Matsuoka, Kyoko; Yamamoto, Hiroki; Komuro, Yoshitaka; Kawana, Daisuke; Yamazaki, Akiyoshi

    2017-08-01

    The resolution of lithography used for the high-volume production of semiconductor devices has been improved to meet the market demands for highly integrated circuits. With the reduction in feature size, the molecular size becomes non-negligible in the resist material design. In this study, the excluded volume effects caused by adding high-concentration acid generators were investigated for triphenylsulfonium nonaflate. The resist film density was measured by X-ray diffractometry. The dependences of absorption coefficient and protected unit concentration on acid generator weight ratio were calculated from the measured film density. Using these values, the effects on the decomposition yield of acid generators, the protected unit fluctuation, and the line edge roughness (LER) were evaluated by simulation on the basis of sensitization and reaction mechanisms of chemically amplified extreme ultraviolet resists. The positive effects of the increase in acid generator weight ratio on LER were predominant below the acid generator weight ratio of 0.3, while the negative effects became equivalent to the positive effects above the acid generator weight ratio of 0.3 owing to the excluded volume effects.

  17. Effect of pulp preconditioning on acidification, proteolysis, sugars and free fatty acids concentration during fermentation of cocoa (Theobroma cacao) beans.

    Science.gov (United States)

    Afoakwa, Emmanuel Ohene; Quao, Jennifer; Budu, Agnes Simpson; Takrama, Jemmy; Saalia, Firibu Kwesi

    2011-11-01

    Changes in acidification, proteolysis, sugars and free fatty acids (FFAs) concentrations of Ghanaian cocoa beans as affected by pulp preconditioning (pod storage or PS) and fermentation were investigated. Non-volatile acidity, pH, proteolysis, sugars (total, reducing and non-reducing) and FFAs concentrations were analysed using standard methods. Increasing PS consistently decreased the non-volatile acidity with concomitant increase in pH during fermentation of the beans. Fermentation decreased the pH of the unstored beans from 6.7 to 4.9 within the first 4 days and then increased slightly again to 5.3 by the sixth day. Protein, total sugars and non-reducing sugars decreased significantly (p cocoa beans was largely affected by fermentation than by PS.

  18. Effect of Na2CO3 degumming concentration on LiBr-formic acid-silk fibroin solution properties

    Directory of Open Access Journals (Sweden)

    Liu Zhi

    2016-01-01

    Full Text Available Salt-acid system has been proved to be of high efficiency for silk fibroin dissolution. Using salt-acid system to dissolve silk, native silk fibrils can be preserved in the regenerated solution. Increasing experiments indicate that acquirement of silk fibrils in solution is strongly associated with the degumming process. In this study, the effect of sodium carbonate degumming concentration on solution properties based on lithium bromide-formic acid dissolution system was systematically investigated. Results showed that the morphology transformation of silk fibroin in solution from nanospheres to nanofibrils is determined by sodium carbonate concentration during the degumming process. Solutions containing different silk fibroin structure exhibited different rheological behaviors and different electrospinnability, leading to different electrospun nanofibre properties. The results have guiding significance for preparation and application of silk fibroin solutions.

  19. Inhibition of Erwinia chrysanthemi growth to different concentrations of folic acid: possible use of folic acid as bacteriostatic agent and fortifying of Solanum tuberosum potato

    Directory of Open Access Journals (Sweden)

    Andrea Marcelo Correa

    2017-05-01

    Full Text Available Introduction:The enterobacteria of the Erwinia spp genus produce disease in potatoes, which is a tuber of mass consumption. The regulation of DNA methylation can regulate the proliferation of Erwinia in such a way that the concentrations of folic acid may have an effect on the microorganism pathogenic ability. On the other hand, the folic acid prevents the appearance of neural tube defects in humans. Objective: To evaluate folic acid as a bacteriostatic agent of Erwinia and, at the same time, as part of the fortification of mass consumption food such as the potatoes. Materials and methods: The biochemical characterization of the Erwinia chrysanthemi was carried out and its growth compared to different concentrations of folic acid was studied. Results: When increasing the concentrations of the vitamin from 0.3 µg/L up to 6.8 µg/L, the bacterial growth of Erwinia chrysanthemi is inhibited. The vitamin inhibits the growth in cultivation of Erwinia chrysanthemi and acts as a bacteriostatic agent. This aspect is of great importance given that, theoretically, if potatoes were fortified with micro-nutrient, this would act against the infectious agent and, at the same time, contribute to the adequate intake of the vitamin in the general population.

  20. Associations between maternal long-chain polyunsaturated fatty acid concentrations and child cognition at 7 years of age: the MEFAB birth cohort

    NARCIS (Netherlands)

    Brouwer-Brolsma, Elske; Van de Rest, Ondine; Godschalk, Roger; Zeegers, Marij; De Groot, Renate

    2017-01-01

    Concentrations of the fish fatty acids EPA and DHA are low among Dutch women of reproductive age. As the human brain incorporates high concentrations of these fatty acids in utero, particularly during third trimester of gestation, these low EPA and DHA concentrations may have adverse consequences