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Sample records for n-acetylcysteine amide decreases

  1. N-acetylcysteine amid reduces pancreatic damage in a rat model of acute necrotizing pancreatitis.

    Science.gov (United States)

    Turkyilmaz, Serdar; Usta, Arif; Cekic, Arif Burak; Alhan, Etem; Kural, Birgül Vanizor; Ercin, Cengiz

    2016-06-15

    Inflammatory explosion and oxidative stress are important mechanisms of injury in acute necrotizing pancreatitis (ANP). This study investigated the effects of N-acetylcysteine amid (NACA), a novel cell-permeant antioxidant with anti-inflammatory activity, on experimental ANP in rats. Fifty-two adult male Sprague-Dawley rats were used, and ANP was induced by cerulein. The animals were divided into four groups which were sham + saline, sham + NACA, ANP + saline, and ANP + NACA. NACA (2.2 mg/kg, i.p) was administered for 6 h, after the induction of ANP. The extent of acinar cell injury, mortality, systemic cardiorespiratory variables, functional capillary density, renal/hepatic functions, and changes in some enzyme markers for pancreas and lung tissues were investigated. Induction of ANP increased mortality from 0% in the sham group to 43.75% in the ANP + saline group (P pancreatic necrosis, serum amylase, alanine aminotransferase (ALT), interleukin-6, LDH in bronchoalveolar lavage fluid, serum urea, tissue myeloperoxidase in pancreas and lung tissues and malondialdehyde. There was less pronounced increase in these parameters in NACA treated group. Compared with ANP group, ANP + NACA group had lower levels of pancreatic necrosis (0.5 ± 0.2 versus 1.45 ± 0.2, P pancreatitis indicates its potential usefulness in the management of ANP. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Potentiation of lead-induced cell death in PC12 cells by glutamate: Protection by N-acetylcysteine amide (NACA), a novel thiol antioxidant

    International Nuclear Information System (INIS)

    Penugonda, Suman; Mare, Suneetha; Lutz, P.; Banks, William A.; Ercal, Nuran

    2006-01-01

    Oxidative stress has been implicated as an important factor in many neurological diseases. Oxidative toxicity in a number of these conditions is induced by excessive glutamate release and subsequent glutamatergic neuronal stimulation. This, in turn, causes increased generation of reactive oxygen species (ROS), oxidative stress, excitotoxicity, and neuronal damage. Recent studies indicate that the glutamatergic neurotransmitter system is involved in lead-induced neurotoxicity. Therefore, this study aimed to (1) investigate the potential effects of glutamate on lead-induced PC12 cell death and (2) elucidate whether the novel thiol antioxidant N-acetylcysteine amide (NACA) had any protective abilities against such cytotoxicity. Our results suggest that glutamate (1 mM) potentiates lead-induced cytotoxicity by increased generation of ROS, decreased proliferation (MTS), decreased glutathione (GSH) levels, and depletion of cellular adenosine-triphosphate (ATP). Consistent with its ability to decrease ATP levels and induce cell death, lead also increased caspase-3 activity, an effect potentiated by glutamate. Exposure to glutamate and lead elevated the cellular malondialdehyde (MDA) levels and phospholipase-A 2 (PLA 2 ) activity and diminished the glutamine synthetase (GS) activity. NACA protected PC12 cells from the cytotoxic effects of glutamate plus lead, as evaluated by MTS assay. NACA reduced the decrease in the cellular ATP levels and restored the intracellular GSH levels. The increased levels of ROS and MDA in glutamate-lead treated cells were significantly decreased by NACA. In conclusion, our data showed that glutamate potentiated the effects of lead-induced PC12 cell death by a mechanism involving mitochondrial dysfunction (ATP depletion) and oxidative stress. NACA had a protective role against the combined toxic effects of glutamate and lead by inhibiting lipid peroxidation and scavenging ROS, thus preserving intracellular GSH

  3. Systematic Review of Human and Animal Studies Examining the Efficacy and Safety of N-Acetylcysteine (NAC and N-Acetylcysteine Amide (NACA in Traumatic Brain Injury: Impact on Neurofunctional Outcome and Biomarkers of Oxidative Stress and Inflammation

    Directory of Open Access Journals (Sweden)

    Junaid Bhatti

    2018-01-01

    Full Text Available BackgroundNo new therapies for traumatic brain injury (TBI have been officially translated into current practice. At the tissue and cellular level, both inflammatory and oxidative processes may be exacerbated post-injury and contribute to further brain damage. N-acetylcysteine (NAC has the potential to downregulate both processes. This review focuses on the potential neuroprotective utility of NAC and N-acetylcysteine amide (NACA post-TBI.MethodsMedline, Embase, Cochrane Library, and ClinicalTrials.gov were searched up to July 2017. Studies that examined clinical and laboratory effects of NAC and NACA post-TBI in human and animal studies were included. Risk of bias was assessed in human and animal studies according to the design of each study (randomized or not. The primary outcome assessed was the effect of NAC/NACA treatment on functional outcome, while secondary outcomes included the impact on biomarkers of inflammation and oxidation. Due to the clinical and methodological heterogeneity observed across studies, no meta-analyses were conducted.ResultsOur analyses revealed only three human trials, including two randomized controlled trials (RCTs and 20 animal studies conducted using standardized animal models of brain injury. The two RCTs reported improvement in the functional outcome post-NAC/NACA administration. Overall, the evidence from animal studies is more robust and demonstrated substantial improvement of cognition and psychomotor performance following NAC/NACA use. Animal studies also reported significantly more cortical sparing, reduced apoptosis, and lower levels of biomarkers of inflammation and oxidative stress. No safety concerns were reported in any of the studies included in this analysis.ConclusionEvidence from the animal literature demonstrates a robust association for the prophylactic application of NAC and NACA post-TBI with improved neurofunctional outcomes and downregulation of inflammatory and oxidative stress markers at

  4. Novel sila-amide derivatives of N-acetylcysteine protects platelets from oxidative stress-induced apoptosis.

    Science.gov (United States)

    Paul, Manoj; Thushara, Ram M; Jagadish, Swamy; Zakai, Uzma I; West, Robert; Kemparaju, Kempaiah; Girish, Kesturu S

    2017-02-01

    Oxidative stress-induced platelet apoptosis is one among the many causes for the development and progression of many disorders like cardiovascular diseases, arthritis, Alzheimer's disease and many chronic inflammatory responses. Many studies have demonstrated the less optimal effect of N-acetyl cysteine (NAC) in oxidative stress-induced cellular damage. This could be due to its less lipophilicity which makes it difficult to enter the cellular membrane. Therefore in the present study, lipophilic sila-amide derivatives (6a and 6b) synthesized through the reaction of NAC with 3-Aminopropyltrimethylsilane and aminomethyltrimethylsilane were used to determine their protective property against oxidative stress-induced platelet apoptosis. At a concentration of 10 µM, compound 6a and 6b were able to significantly inhibit Rotenone/H 2 O 2 induced platelet apoptotic markers like reactive oxygen species, intracellular calcium level, mitochondrial membrane potential, cytochrome c release from mitochondrial to the cytosol, caspase-9 and -3 activity and phosphatidylserine externalization. Therefore, the compounds can be extrapolated as therapeutic agents to protect platelets from oxidative stress-induced platelet apoptosis and its associated complications.

  5. N-acetylcysteine plus deferoxamine for patients with prolonged hypotension does not decrease acute kidney injury incidence: a double blind, randomized, placebo-controlled trial.

    Science.gov (United States)

    Fraga, Cassiana Mazon; Tomasi, Cristiane Damiani; Damasio, Danusa de Castro; Vuolo, Francieli; Ritter, Cristiane; Dal-Pizzol, Felipe

    2016-10-17

    The aim was to test the primary hypothesis that in patients suffering from shock, treatment with N-acetylcysteine (NAC) plus deferoxamine (DFX) decreases the incidence of acute kidney injury (AKI). A double-blind, randomized, placebo-controlled trial was conducted in a general intensive care unit in an academic hospital. Patients were included if they had new-onset hypotension, defined as mean arterial blood pressure hypotension did not decrease the incidence of AKI. Clinicaltrials.gov NCT00870883 (Registered 25 March 2009.).

  6. N-acetylcysteine for treatment of autism, a case report

    Directory of Open Access Journals (Sweden)

    Ahmad Ghanizadeh

    2012-01-01

    Full Text Available There are a limited number of Food and Drug Administration (FDA-approved medications for the treatment of autism. Meanwhile, oxidative stress and neuroinflammation are supposed to play a causative role in autism. N-acetylcysteine may provide cystine, a precursor for glutathione (GSH, which is an important antioxidant factor in the brain. We here report a child with autism, whose symptoms were markedly decreased after taking oral N-acetylcysteine 800 mg/day, in three divided doses. His social interaction was significantly increased. The score of social impairment on a visual analog scale decreased from 10 to 6 in the two-month trial. The aggressive behaviors decreased from 10 to 3. This case suggests that N-acetylcysteine may decrease some symptoms of autism.

  7. Effects of Prussian blue and N-acetylcysteine on thallium toxicity in mice.

    Science.gov (United States)

    Meggs, W J; Cahill-Morasco, R; Shih, R D; Goldfrank, L R; Hoffman, R S

    1997-01-01

    Thallium poisoning is now rare but still occurs as a result of homicide attempts. Prussian blue's efficacy in the treatment of experimental thallium poisoning has been demonstrated in animal models, and its use in humans is supported by anecdotal data. Since thallium binds sulfhydryl groups, the use of N-acetylcysteine is also considered as a potential antidote. To compare the efficacy of Prussian blue and N-acetylcysteine in a murine model of thallium poisoning. Female Swiss albino mice with free access to food and water were used. Two study doses of thallium, given as a subcutaneous injection of thallium acetate dissolved in sterile water, were chosen: 70 mg/kg (LD90) and 85 mg/kg (> LD100). A randomized, placebo controlled study was conducted with survival at 120 h chosen as the outcome measure. Four treatment groups were studied: control, Prussian blue, N-acetylcysteine, and the combination of Prussian blue and N-acetylcysteine. Prussian blue was dissolved in water and given by oral gavage at a dose of 50 mg/kg. N-acetylcysteine was diluted in normal saline and given as intraperitoneal injections of 200 mg/kg. Sterile water by gavage and normal saline by peritoneal injection were given as control treatments whenever an active agent was not given. Survival was recorded over a 120 h study period and compared at 120 h by a Fisher's exact test. At 120 h following subcutaneous injection of thallium 70 mg/kg, only 10% of the control animals survived. Treatment with N-acetylcysteine or Prussian blue increased survival to 35% (p = 0.13) and 50% (p = 0.014), respectively. The addition of N-acetylcysteine to Prussian blue offered no benefit over Prussian blue therapy alone. Prussian blue was found to decrease mortality from thallium poisoning at a dose equal to the LD90 in this model, but not a dose greater than the LD100. No role for N-acetylcysteine in the treatment of thallium poisoning was demonstrated by this study.

  8. Effect of intravenous N-acetylcysteine infusion on haemostatic parameters in healthy subjects

    DEFF Research Database (Denmark)

    Knudsen, TT; Thorsen, S; Jensen, SA

    2005-01-01

    volunteers. METHODS: Haemostatic parameters in 10 healthy subjects were analysed before and following intravenous infusion of therapeutic doses of N-acetylcysteine, as well as in vitro. RESULTS: N-acetylcysteine induced significant decreases in plasma levels of vitamin K dependent haemostatic proteins...... in vivo, being maximal at one hour following the start of infusion, with maximal decreases from 1.00 to 0.73 (0.67-0.79) (mean (95% confidence interval)), 0.66 (0.58-0.73), 0.81 (0.73-0.90), 0.64 (0.57-0.70), 0.74 (0.65-0.82), and 0.61 (0.54-0.67) for factor II, VII, IX, and X activities, protein C...... activity, and free protein S reactivity, respectively. These data suggest that N-acetylcysteine induces protein modifications affecting activity. Five subjects developed an adverse reaction to infusion of N-acetylcysteine and these were associated with a rapid increase in levels of factor VIII and its...

  9. N-acetylcysteine alleviates the meconium-induced acute lung injury.

    Science.gov (United States)

    Mokra, D; Drgova, A; Petras, M; Mokry, J; Antosova, M; Calkovska, A

    2015-01-01

    Meconium aspiration in newborns causes lung inflammation and injury, which may lead to meconium aspiration syndrome (MAS). In this study, the effect of the antioxidant N-acetylcysteine on respiratory and inflammatory parameters were studied in a model of MAS. Oxygen-ventilated rabbits were intratracheally given 4 mL/kg of meconium (25 mg/mL) or saline. Thirty minutes later, meconium-instilled animals were administered N-acetylcysteine (10 mg/kg; i.v.), or were left without treatment. The animals were oxygen-ventilated for additional 5 h. Ventilatory pressures, oxygenation, right-to-left pulmonary shunts, and leukocyte count were measured. At the end of experiment, trachea and lung were excised. The left lung was saline-lavaged and a total and differential count of cells in bronchoalveolar lavage fluid (BAL) was determined. Right lung tissue strips were used for detection of lung edema (expressed as wet/dry weight ratio) and peroxidation (expressed by thiobarbituric acid-reactive substances, TBARS). In lung and tracheal strips, airway reactivity to acetylcholine was measured. In addition, TBARS and total antioxidant status were determined in the plasma. Meconium instillation induced polymorphonuclear-derived inflammation and oxidative stress. N-acetylcysteine improved oxygenation, reduced lung edema, decreased polymorphonuclears in BAL fluid, and diminished peroxidation and meconium-induced airway hyperreactivity compared with untreated animals. In conclusion, N-acetylcysteine effectively improved lung functions in an animal model of MAS.

  10. Damage induced by paracetamol compared with N-acetylcysteine

    Directory of Open Access Journals (Sweden)

    Abdullah Kisaoglu

    2014-09-01

    Conclusion: Thiamine pyrophosphate and N-acetylcysteine had a similar positive effect on oxidative damage caused by paracetamol hepatotoxicity. These findings show that TPP may be beneficial in paracetamol hepatotoxicity.

  11. The effect of N-acetylcysteine or bupropion on methamphetamine self-administration and methamphetamine-triggered reinstatement of female rats.

    Science.gov (United States)

    Charntikov, Sergios; Pittenger, Steven T; Pudiak, Cindy M; Bevins, Rick A

    2018-03-28

    N-acetylcysteine and bupropion are two promising candidate medications for treatment of substance use disorder. The effects of N-acetylcysteine or bupropion on methamphetamine self-administration of female rats are not well understood. To fill this gap, this study assessed the effects of N-acetylcysteine (0, 30, 60, or 120 mg/kg) and bupropion (0, 10, 30, and 60 mg/kg) on methamphetamine self-administration of female rats across the natural estrous cycle. Following a completed dose-response curve, responding for methamphetamine self-administration was extinguished and the effects of N-acetylcysteine or bupropion on methamphetamine-triggered reinstatement was evaluated in separate experiments. N-acetylcysteine did not decrease responding maintained by methamphetamine or methamphetamine-triggered reinstatement. Bupropion significantly decreased methamphetamine self-administration and methamphetamine-triggered reinstatement in female rats with highest dose (60 mg/kg) also significantly decreasing general chamber activity. In a companion experiment, testing the effect of bupropion on responding maintained by sucrose, we confirmed non-specificity of bupropion's effects as bupropion also decreased responding for sucrose. Considered together, our findings suggest that while N-acetylcysteine has considerable promise for treatment of cocaine dependence it may not generalize to other stimulants like methamphetamine. Furthermore, although bupropion has been shown to effectively decrease methamphetamine self-administration, and presently methamphetamine-triggered reinstatement, its locomotor and reward suppressing effects warrant further investigation including both sexes. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. N-acetylcysteine modulates the cytotoxic effects of Paclitaxel.

    Science.gov (United States)

    Lyle, Patricia Anne; Mitsopoulos, Panagiotis; Suntres, Zacharias E

    2011-01-01

    Paclitaxel is a microtubule-stabilizing drug known to cause mitotic G2/M arrest and apoptosis. It also increases the generation of reactive oxygen species (ROS) known to be involved in both apoptotic and necrotic cell death. Antioxidants, such as N-acetylcysteine (NAC), prevent the deleterious effects of ROS and modulate the regulation of apoptotic-linked cellular proteins. A549 human adenocarcinoma alveolar epithelial cells were treated with 5.0 mM NAC, 1.0 μM paclitaxel, or co-incubated with both NAC and paclitaxel for a 24-hour incubation period. The effects of NAC in paclitaxel-induced cytotoxicity were evaluated by measuring cell viability, production of ROS, and apoptosis. Challenge of cells with paclitaxel resulted in time/concentration-dependent decreases in cell viability and increases in intracellular levels of ROS, and apoptosis, all effects being abrogated by co-treatment with NAC. NAC reduced the paclitaxel-induced increase in activated caspase-10 levels, but potentiated that for caspase-3. NAC alters the cytotoxicity of paclitaxel in vitro by decreasing the levels of ROS, preventing apoptosis, and modulating apoptotic cellular proteins. Copyright © 2011 S. Karger AG, Basel.

  13. Trichotillomania: a good response to treatment with N-acetylcysteine.

    Science.gov (United States)

    Barroso, Livia Ariane Lopes; Sternberg, Flavia; Souza, Maria Natalia Inacio de Fraia E; Nunes, Gisele Jacobino de Barros

    2017-01-01

    Trichotillomania is considered a behavioral disorder and is characterized by the recurring habit of pulling one's hair, resulting in secondary alopecia. It affects 1% of the adult population, and 2 to 4.4% of psychiatric patients meet the diagnostic criteria. It can occur at any age and is more prevalent in adolescents and females. Its occurrence in childhood is not uncommon and tends to have a more favorable clinical course. The scalp, eyebrows and eyelashes are the most commonly affected sites. Glutamate modulating agents, such as N-acetylcysteine, have been shown to be a promising treatment. N-acetylcysteine acts by reducing oxidative stress and normalizing glutaminergic transmission. In this paper, we report a case of trichotillomania with an excellent response to N-acetylcysteine.

  14. Trichotillomania: a good response to treatment with N-acetylcysteine*

    Science.gov (United States)

    Barroso, Livia Ariane Lopes; Sternberg, Flavia; Souza, Maria Natalia Inacio de Fraia e; Nunes, Gisele Jacobino de Barros

    2017-01-01

    Trichotillomania is considered a behavioral disorder and is characterized by the recurring habit of pulling one's hair, resulting in secondary alopecia. It affects 1% of the adult population, and 2 to 4.4% of psychiatric patients meet the diagnostic criteria. It can occur at any age and is more prevalent in adolescents and females. Its occurrence in childhood is not uncommon and tends to have a more favorable clinical course. The scalp, eyebrows and eyelashes are the most commonly affected sites. Glutamate modulating agents, such as N-acetylcysteine, have been shown to be a promising treatment. N-acetylcysteine acts by reducing oxidative stress and normalizing glutaminergic transmission. In this paper, we report a case of trichotillomania with an excellent response to N-acetylcysteine. PMID:28954106

  15. N-Acetylcysteine in the prevention of ototoxicity

    DEFF Research Database (Denmark)

    Tepel, Martin

    2007-01-01

    Prevention of ototoxicity after the administration of aminoglycoside antibiotics has been notably difficult, in particular in patients with chronic kidney disease. Feldman et al. report that oral administration of 600 mg N-acetylcysteine twice daily significantly ameliorates gentamicin-induced ot......-induced ototoxicity in hemodialysis patients. That approach may help to prevent aminoglycoside-induced hearing loss in these high-risk patients in daily practice.......Prevention of ototoxicity after the administration of aminoglycoside antibiotics has been notably difficult, in particular in patients with chronic kidney disease. Feldman et al. report that oral administration of 600 mg N-acetylcysteine twice daily significantly ameliorates gentamicin...

  16. Recommendations for the paracetamol treatment nomogram and side effects of N-acetylcysteine

    NARCIS (Netherlands)

    Koppen, A.; van Riel, A.; de Vries, I.; Meulenbelt, J.

    2014-01-01

    Treatment of paracetamol intoxication consists of administration of N-acetylcysteine, preferably shortly after paracetamol ingestion. In most countries, the decision to treat patients with N-acetylcysteine depends on the paracetamol plasma concentration. In the literature, different arguments are

  17. Systematic review of N-acetylcysteine in cystic fibrosis

    NARCIS (Netherlands)

    Duijvestijn, YCM; Brand, PLP

    A systematic review was carried out to evaluate whether the use of N-acetylcysteine to improve lung function in patients with cystic fibrosis is supported by published evidence. Medline and the Cochrane Library were searched and the reference lists of all retrieved papers and of relevant chapters of

  18. Bivirkninger ved N-acetylcystein-behandling af paracetamolforgiftede patienter

    DEFF Research Database (Denmark)

    Schmidt, L E; Dalhoff, K P

    1999-01-01

    Treatment of paracetamol intoxication with N-acetylcysteine (NAC) is standard in Denmark. NAC is considered safe with relatively few side effects. It is recommended that all patients be treated irrespective of paracetamol dose or time from intoxication to treatment start. Consequently a higher nu...

  19. N-acetylcysteine reduces oxidative stress in sickle cell patients

    NARCIS (Netherlands)

    Nur, Erfan; Brandjes, Dees P.; Teerlink, Tom; Otten, Hans-Martin; Oude Elferink, Ronald P. J.; Muskiet, Frits; Evers, Ludo M.; ten Cate, Hugo; Biemond, Bart J.; Duits, Ashley J.; Schnog, John-John B.

    2012-01-01

    Oxidative stress is of importance in the pathophysiology of sickle cell disease (SCD). In this open label randomized pilot study the effects of oral N-acetylcysteine (NAC) on phosphatidylserine (PS) expression as marker of cellular oxidative damage (primary end point), and markers of hemolysis,

  20. N-acetylcysteine reduces oxidative stress in sickle cell patients

    NARCIS (Netherlands)

    Nur, Erfan; Brandjes, Dees P.; Teerlink, Tom; Otten, Hans-Martin; Elferink, Ronald P. J. Oude; Muskiet, Frits; Evers, Ludo M.; ten Cate, Hugo; Biemond, Bart J.; Duits, Ashley J.; Schnog, John-John B.

    Oxidative stress is of importance in the pathophysiology of sickle cell disease (SCD). In this open label randomized pilot study the effects of oral N-acetylcysteine (NAC) on phosphatidylserine (PS) expression as marker of cellular oxidative damage (primary end point), and markers of hemolysis,

  1. Pharmacodynamic Effect of N-Acetylcysteine as Adjunctive Therapy ...

    African Journals Online (AJOL)

    Purpose: To evaluate the pharmacodynamic effect of N-acetylcysteine (NAC) in mild systemic lupus erythematosus (SLE) patients in order to implement NAC as adjunctive therapy in SLE population. Methods: Forty mild SLE patients were randomly allocated to receive 1800 mg of NAC with SLE standard therapy or receive ...

  2. N-acetylcysteine enhances nitroglycerin-induced headache and cranial arterial responses

    DEFF Research Database (Denmark)

    Iversen, Helle Klingenberg

    1992-01-01

    with N-acetylcysteine (100 mg/kg) or placebo. Arterial diameters were measured with high frequency ultrasound, and pain was scored by use of a previously evaluated 10-point scale. Plasma levels of free (n = 2) and total (n = 11) N-acetylcysteine were determined. N-Acetylcysteine potentiated the headache...

  3. Effect of intravenous N-acetylcysteine infusion on haemostatic parameters in healthy subjects

    DEFF Research Database (Denmark)

    Knudsen, T T; Thorsen, S; Jensen, S A

    2005-01-01

    BACKGROUND AND AIMS: N-acetylcysteine is used to treat paracetamol overdose but depresses the activity of plasma coagulation factors II, VII, and X, which are often used to assess liver injury. The aim of this study was to investigate the effect of N-acetylcysteine on haemostasis in normal...

  4. N-Acetylcysteine in the Treatment of Excoriation Disorder

    DEFF Research Database (Denmark)

    Grant, Jon E.; Chamberlain, Samuel R.; Redden, Sarah A.

    2016-01-01

    Importance Excoriation (skin-picking) disorder (SPD) is a disabling, underrecognized condition in which individuals repeatedly pick at their skin, leading to noticeable tissue damage. To date, there has been no clearly effective pharmacologic or psychological treatment for SPD. Objective To deter......Importance Excoriation (skin-picking) disorder (SPD) is a disabling, underrecognized condition in which individuals repeatedly pick at their skin, leading to noticeable tissue damage. To date, there has been no clearly effective pharmacologic or psychological treatment for SPD. Objective...... To determine whether N-acetylcysteine, an amino acid that appears to restore extracellular glutamate concentration in the nucleus accumbens, will be more effective than placebo in reducing compulsive picking behavior. Design, Setting, and Participants A randomized, double-blind trial was conducted...

  5. N-acetylcysteine effectively diminished meconium-induced oxidative stress in adult rabbits.

    Science.gov (United States)

    Mokra, D; Drgova, A; Mokry, J; Antosova, M; Durdik, P; Calkovska, A

    2015-02-01

    Since inflammation and oxidative stress are fundamental in the pathophysiology of neonatal meconium aspiration syndrome (MAS), various anti-inflammatory drugs have been used in experimental and clinical studies on MAS. This pilot study evaluated therapeutic potential of N-acetylcysteine in modulation of meconium-induced inflammation and oxidative lung injury. Oxygen-ventilated adult rabbits were intratracheally given 4 ml/kg of meconium (25 mg/ml) or saline (Sal, n = 6). Thirty minutes later, meconium-instilled animals were treated with intravenous N-acetylcysteine (10 mg/kg, Mec + NAC, n=6) or were non-treated (Mec, n = 6). All animals were oxygen-ventilated for additional 5 hours. Total and differential blood leukocyte counts were determined at baseline, and at 1, 3 and 5 h of the treatment. After sacrificing animals, left lung was saline-lavaged and total and differential cell counts in the bronchoalveolar lavage fluid were determined. Right lung was used for biochemical analyses and for estimation of wet-dry weight ratio. In lung tissue homogenate, thiobarbituric acid-reactive substances (TBARS), dityrosine, lysine-lipid peroxidation (LPO) products, and total antioxidant status (TAS) were detected. In isolated lung mitochondria, TBARS, dityrosine, lysine-LPO products, thiol group content, conjugated dienes, and activity of cytochrome c oxidase were estimated. To evaluate systemic effects of meconium instillation and NAC treatment, TBARS and TAS were determined also in plasma. To evaluate participation of eosinophils in the meconium-induced inflammation, eosinophil cationic protein (ECP) was detected in plasma and lung homogenate. Meconium instillation increased oxidation markers and ECP in the lung and decreased TAS (all Pmeconium-induced inflammation and oxidative lung injury.

  6. Effectiveness of liposomal-N-acetylcysteine against LPS-induced lung injuries in rodents.

    Science.gov (United States)

    Mitsopoulos, Panagiotis; Omri, Abdelwahab; Alipour, Misagh; Vermeulen, Natasha; Smith, Milton G; Suntres, Zacharias E

    2008-11-03

    Acute lung injury (ALI) and its most severe form, the acute respiratory distress syndrome (ARDS) are frequent complications in critically ill patients and are responsible for significant morbidity and mortality. So far, experimental evidence supports the role of oxidants and oxidative injury in the pathogenesis of ALI/ARDS. In this study, the antioxidant effects of conventional N-acetylcysteine (NAC) and liposomally entrapped N-acetylcysteine (L-NAC) were evaluated in experimental animals challenged with lipopolysaccharide (LPS). Rats were pretreated with empty liposomes, NAC, or L-NAC (25mg/kg body weight, iv); 4h later were challenged with LPS (E. coli, LPS 0111:B4) and sacrificed 20h later. Challenge of saline (SAL)-pretreated animals with LPS resulted in lung injury as evidenced by increases in wet lung weight (edema), increases in lipid peroxidation (marker of oxidative stress), decreases of lung angiotensin-converting enzyme (ACE) (injury marker for pulmonary endothelial cells) and increases in the pro-inflammatory eicosanoids, thromboxane B(2) and leukotriene B(4). The LPS challenge also increased pulmonary myeloperoxidase activity and chloramine concentrations indicative of neutrophil infiltration and activation of the inflammatory response. Pretreatment of animals with L-NAC resulted in significant increases in the levels of non-protein thiols and NAC levels in lung homogenates (p<0.05) and bronchoalveolar lavage fluids (p<0.001), respectively. L-NAC was significantly (p<0.05) more effective than NAC or empty liposomes in attenuating the LPS-induced lung injuries as indicated by the aforementioned injury markers. Our results suggested that the delivery of NAC as a liposomal formulation improved its prophylactic effectiveness against LPS-induced lung injuries.

  7. Administration of N-acetylcysteine causes beneficial posttranslational modifications of transthyretin in hemodialysis patients

    DEFF Research Database (Denmark)

    Scholze, Alexandra

    2013-01-01

    INTRODUCTION AND AIMS: The thiol antioxidant N-acetylcysteine (NAC) may mediate interactions with protein-associated cysteine residues, however, information on protein level in vivo are missing. Therefore, in the present study we aimed to analyze N-acetylcysteine-induced modifications of the prot......INTRODUCTION AND AIMS: The thiol antioxidant N-acetylcysteine (NAC) may mediate interactions with protein-associated cysteine residues, however, information on protein level in vivo are missing. Therefore, in the present study we aimed to analyze N-acetylcysteine-induced modifications...... by formation of mixed disulfides. METHODS: Plasma levels of TTR were determined by a non-commercial enzyme-linked immunosorbent assay (ELISA) using polyclonal rabbit anti-human TTR antibodies. Spectra of immunoprecipitated TTR were obtained using an AutoflexSpeed matrix assisted laser desorption ionization...

  8. N-ACETYLCYSTEINE IN SEVERE FALCIPARUM MALARIA IN THAILAND

    Science.gov (United States)

    Treeprasertsuk, Sombat; Krudsood, Srivicha; Tosukhowong, Thanawat; Maek-A-Nantawat, Wirach; Vannaphan, Suparp; Saengnetswang, Tosaporn; Looareesuwan, Sornchai; Kuhn, Walter F; Brittenham, Gary; Carroll, James

    2011-01-01

    One hundred and eight patients with severe falciparum malaria underwent a placebo controlled trial with the antioxidant, N-acetylcysteine (NAC), as an adjunctive therapy along with standard intravenous artesunate therapy. Three NAC dosage regimens were used: an intravenous loading dose of 140 mg/kg followed by 70 mg/kg every four hours intravenously for up to 18 doses (Group 1); a single intravenous loading dose followed by oral NAC in the same amount as for Group 1 (Group 2); a regimen identical to Group 1 except that oral NAC was administered after the first 24 hours (Group 3). Fifty-four patients received placebo plus artesunate. Two critically ill patients died in Group 1. No patient sustained an adverse reaction to the NAC other than vomiting, and the deaths were attributed to severe disease with multiple organ involvement. The excellent results with NAC, the lack of adverse effects, and the rationale for NAC benefit supports the need for a large, double blind trial of NAC as an adjunctive therapy for severe malaria. PMID:12971512

  9. Attenuation of phosphamidon-induced oxidative stress and immune dysfunction in rats treated with N-acetylcysteine

    Directory of Open Access Journals (Sweden)

    S.G. Suke

    2008-09-01

    Full Text Available The effect of N-acetylcysteine, a thiolic antioxidant, on attenuation of phosphamidon-induced oxidative stress and immune dysfunction was evaluated in adult male Wistar rats weighing 200-250 g. Rats were divided into four groups, 8 animals/group, and treated with phosphamidon, N-acetylcysteine or the combination of both for 28 days. Oral administration of phosphamidon (1.74 mg/kg, an organophosphate insecticide, increased serum malondialdehyde (3.83 ± 0.18 vs 2.91 ± 0.24 nmol/mL; P < 0.05 and decreased erythrocyte superoxide dismutase (567.8 ± 24.36 vs 749.16 ± 102.61 U/gHb; P < 0.05, catalase activity (1.86 ± 0.18 vs 2.43 ± 0.08 U/gHb; P < 0.05 and whole blood glutathione levels (1.25 ± 0.21 vs 2.28 ± 0.08 mg/gHb; P < 0.05 showing phosphamidon-induced oxidative stress. Phosphamidon exposure markedly suppressed humoral immune response as assessed by antibody titer to ovalbumin (4.71 ± 0.51 vs 8.00 ± 0.12 -log2; P < 0.05, and cell-mediated immune response as assessed by leukocyte migration inhibition (25.24 ± 1.04 vs 70.8 ± 1.09%; P < 0.05 and macrophage migration inhibition (20.38 ± 0.99 vs 67.16 ± 5.30%; P < 0.05 response. Phosphamidon exposure decreased IFN-у levels (40.7 ± 3.21 vs 55.84 ± 3.02 pg/mL; P < 0.05 suggesting a profound effect of phosphamidon on cell-mediated immune response. A phosphamidon-induced increase in TNF-α level (64.19 ± 6.0 vs 23.16 ± 4.0 pg/mL; P < 0.05 suggests a contributory role of immunocytes in oxidative stress. Co-administration of N-acetylcysteine (3.5 mmol/kg, orally with phosphamidon attenuated the adverse effects of phosphamidon. These findings suggest that oral N-acetylcysteine treatment exerts protective effect and attenuates free radical injury and immune dysfunction caused by subchronic phosphamidon exposure.

  10. N-acetylcysteine improves established monocrotaline-induced pulmonary hypertension in rats

    Science.gov (United States)

    2014-01-01

    Background The outcome of patients suffering from pulmonary arterial hypertension (PAH) are predominantly determined by the response of the right ventricle to the increase afterload secondary to high vascular pulmonary resistance. However, little is known about the effects of the current available or experimental PAH treatments on the heart. Recently, inflammation has been implicated in the pathophysiology of PAH. N-acetylcysteine (NAC), a well-known safe anti-oxidant drug, has immuno-modulatory and cardioprotective properties. We therefore hypothesized that NAC could reduce the severity of pulmonary hypertension (PH) in rats exposed to monocrotaline (MCT), lowering inflammation and preserving pulmonary vascular system and right heart function. Methods Saline-treated control, MCT-exposed, MCT-exposed and NAC treated rats (day 14–28) were evaluated at day 28 following MCT for hemodynamic parameters (right ventricular systolic pressure, mean pulmonary arterial pressure and cardiac output), right ventricular hypertrophy, pulmonary vascular morphometry, lung inflammatory cells immunohistochemistry (monocyte/macrophages and dendritic cells), IL-6 expression, cardiomyocyte hypertrophy and cardiac fibrosis. Results The treatment with NAC significantly decreased pulmonary vascular remodeling, lung inflammation, and improved total pulmonary resistance (from 0.71 ± 0.05 for MCT group to 0.50 ± 0.06 for MCT + NAC group, p pulmonary vascular and right heart function in experimental PH. PMID:24929652

  11. N-acetylcysteine supplementation reduces oxidative stress for cytosine arabinoside in rat model.

    Science.gov (United States)

    Balci, Yasemin Isik; Acer, Semra; Yagci, Ramazan; Kucukatay, Vural; Sarbay, Hakan; Bozkurt, Kerem; Polat, Aziz

    2017-02-01

    Cytosine arabinoside (ARA-C) is a pyrimidine analog that may cause keratoconjunctivitis when used in high doses. The underlying mechanism may be the increased amounts of reactive oxygen radicals that may damage the DNA synthesis of corneal and conjunctival epithelial cells. Topical corticosteroids are one of the prophylactic treatments for keratoconjunctivitis induced by ARA-C. Forty Wistar-type albino rats were included in this study the rats were divided into four groups. The first group (Group 1) received only ARA-C, the second group (Group 2) received ARA-C and N-acetylcysteine (NAC), the third group (Group 3) received only NAC and the fourth group (Group 4) was the control group. The total oxidant status (TOS), the total antioxidant capacity and the oxidative stress index (OSI) measurements of the cornea and the conjunctiva were evaluated in these four groups. The mean TOS and OSI value was the highest in Group 1 and the lowest in Group 3. The differences in TOS and OSI values were statistically significant between Group 1 and Group 2. There are decreases in TOS and OSI values in rats which received ARA-C with NAC administration. NAC may have a protective effect on ARA-C-induced keratoconjunctivitis.

  12. N-Acetylcysteine Prevents Retrograde Motor Neuron Death after Neonatal Peripheral Nerve Injury.

    Science.gov (United States)

    Catapano, Joseph; Zhang, Jennifer; Scholl, David; Chiang, Cameron; Gordon, Tessa; Borschel, Gregory H

    2017-05-01

    Neuronal death may be an overlooked and unaddressed component of disability following neonatal nerve injuries, such as obstetric brachial plexus injury. N-acetylcysteine and acetyl-L-carnitine improve survival of neurons after adult nerve injury, but it is unknown whether they improve survival after neonatal injury, when neurons are most susceptible to retrograde neuronal death. The authors' objective was to examine whether N-acetylcysteine or acetyl-L-carnitine treatment improves survival of neonatal motor or sensory neurons in a rat model of neonatal nerve injury. Rat pups received either a sciatic nerve crush or transection injury at postnatal day 3 and were then randomized to receive either intraperitoneal vehicle (5% dextrose), N-acetylcysteine (750 mg/kg), or acetyl-L-carnitine (300 mg/kg) once or twice daily. Four weeks after injury, surviving neurons were retrograde-labeled with 4% Fluoro-Gold. The lumbar spinal cord and L4/L5 dorsal root ganglia were then harvested and sectioned to count surviving motor and sensory neurons. Transection and crush injuries resulted in significant motor and sensory neuron loss, with transection injury resulting in significantly less neuron survival. High-dose N-acetylcysteine (750 mg/kg twice daily) significantly increased motor neuron survival after neonatal sciatic nerve crush and transection injury. Neither N-acetylcysteine nor acetyl-L-carnitine treatment improved sensory neuron survival. Proximal neonatal nerve injuries, such as obstetric brachial plexus injury, produce significant retrograde neuronal death after injury. High-dose N-acetylcysteine significantly increases motor neuron survival, which may improve functional outcomes after obstetrical brachial plexus injury.

  13. Formation of the thioester, N-acetyl, S-lactoylcysteine, by reaction of N-acetylcysteine with pyruvaldehyde in aqueous solution. [in prebiotic evolution

    Science.gov (United States)

    Weber, A. L.

    1982-01-01

    N-acetylcysteine reacts efficiently with pyruvaldehyde (methylglyoxal) in aqueous solution (pH 7.0) in the presence of a weak base, like imidazole or phosphate, to give the thioester, N-acetyl, S-lactoylcysteine. Reactions of 100 mM N-acetylcysteine with 14 mM, 24 mM and 41 mM pyruvaldehyde yield, respectively, 86%, 76% and 59% N-acetyl, S-lactoylcysteine based on pyruvaldehyde. The decrease in the percent yield at higher pyruvaldehyde concentrations suggests that during its formation the thioester is not only consumed by hydrolysis, but also by reaction with some substance in the pyruvaldehyde preparation. Indeed, purified N-acetyl, S-lactoylcysteine disappears much more rapidly in the presence of pyruvaldehyde than in its absence. Presumably, N-acetyl, S-lactoylcysteine synthesis occurs by rearrangement of the hemithioacetal of N-acetylcysteine and pyruvaldehyde. The significance of this pathway of thioester formation to molecular evolution is discussed.

  14. Altered peripheral vasodilator profile of nitroglycerin during long-term infusion of N-acetylcysteine

    DEFF Research Database (Denmark)

    Boesgaard, S; Iversen, Helle Klingenberg; Wroblewski, H

    1994-01-01

    OBJECTIVES: The aim of this study was to compare the short- and long-term effects of intravenous nitroglycerin plus placebo and nitroglycerin plus N-acetylcysteine on peripheral arteries, veins and microcirculation in humans. BACKGROUND: The thiol donor N-acetylcysteine may potentiate the hemodyn......) or placebo for 23 h in a double-blind, randomized, crossover study. Venous volume, the diameter of the radial and temporal arteries, calf blood flow and subcutaneous blood flow were measured at baseline and repeated after 1 and 23 h of infusion. RESULTS: Prolonged coadministration of N...

  15. [ROLE OF NEUTRAL SPHINGOMYELINASE IN AGE-DEPENDENT MUSCLE INSULIN RESISTANCE DEVELOPMENT AND ITS IMPROVEMENT WITH N-ACETYLCYSTEINE].

    Science.gov (United States)

    Babenko, N A; Timofiĭchuk, O A; Belyĭ, A N

    2015-01-01

    In the present study, we evaluated the role of ceramide in age-dependent and etoposide-induced insulin resistance. A significant increase in the level of ceramide and decrease of gluthatione (GSH) content and tissue sensitivity to insulin has been observed in 24-month-old rats as compared with 3-month-old animals. Etoposide imitates ageing-like changes in muscle tissue of young rats. N-acetylcysteine as well as specific neutral sphingomyelinase (nSMase) inhibitor--GW4869, decreases ceramide content and increases GSH level, and enhances the insulin-induced [3H-D-glucose uptake in the "aged" tissue. These data indicate that nSMase play important role in the age- and drug-induced ceramide-dependent insuline resistance.

  16. Effect of taurine and N-acetylcysteine on methionine restriction-mediated adiposity resistance.

    Science.gov (United States)

    Elshorbagy, Amany K; Valdivia-Garcia, Maria; Mattocks, Dwight A L; Plummer, Jason D; Orentreich, David S; Orentreich, Norman; Refsum, Helga; Perrone, Carmen E

    2013-04-01

    Methionine-restricted (MR) rats, which are lean and insulin sensitive, have low serum total cysteine (tCys) and taurine and decreased hepatic expression and activity indices of stearoyl-coenzyme A desaturase-1 (SCD1). These effects are partly or completely reversed by cysteine supplementation. We investigated whether reversal of MR phenotypes can be achieved by other sulfur compounds, namely taurine or N-acetylcysteine (NAC). MR and control-fed (CF) rats were supplemented with taurine (0.5%) or NAC (0.5%) for 12weeks. Adiposity, serum sulfur amino acids (SAA), Scd1 gene expression in liver and white adipose tissue, and SCD1 activity indices (calculated from serum fatty acid profile) were monitored. Taurine supplementation of MR rats did not restore weight gain or hepatic Scd1 expression or indices to CF levels, but further decreased adiposity. Taurine supplementation of CF rats did not affect adiposity, but lowered triglyceridemia. NAC supplementation in MR rats raised tCys and partly or completely reversed MR effects on weight, fat %, Scd1 expression in liver and white adipose tissue, and estimated SCD1 activity. In CF rats, NAC decreased body fat % and lowered SCD1-18 activity index (Ptaurine as a mediator of increased adiposity produced by cysteine in MR, and show that NAC, similar to L-cysteine, blocks anti-obesity effects of MR. Our data show that dietary SAA can influence adiposity in part through mechanisms that converge on SCD1 function. This may have implications for understanding and preventing human obesity. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Acute ethanol administration reduces the antidote effect of N-acetylcysteine after acetaminophen overdose in mice

    DEFF Research Database (Denmark)

    Dalhoff, K; Hansen, P B; Ott, P

    1991-01-01

    given ethanol or saline alone only 7% and 3%, respectively, survived 96 h. 4. The data suggest that the protective effect of N-acetylcysteine on acetaminophen-induced toxicity in fed mice is reduced by concomitant administration of ethanol. This may explain the clinical observation that ingestion...

  18. Cardiovascular effects of N-acetylcysteine in meconium-induced acute lung injury.

    Science.gov (United States)

    Mokra, D; Tonhajzerova, I; Pistekova, H; Visnovcova, Z; Drgova, A; Mokry, J; Calkovska, A

    2015-01-01

    Anti-inflammatory drugs are increasingly used for treatment of neonatal meconium aspiration syndrome (MAS), but their adverse effects are poorly known. Therefore, the aim of this study was to evaluate the effects of the antioxidant N-acetylcysteine on cardiovascular parameters in an animal model of MAS. Oxygen-ventilated rabbits were intratracheally instilled 4 mL/kg of meconium suspension (25 mg/mL) or saline. Thirty minutes later, meconium-instilled animals were given N-acetylcysteine (10 mg/kg, i.v.) or the same volume of saline. Changes in cardiovascular parameters (blood pressure, heart rate, and heart rate variability) were recorded over a 5-min course of solution administration, over 5 min after its end, and then hourly for 5 h. Oxidation markers (thiobarbituric acid-reactive substances (TBARS) and total antioxidant status) and aldosterone, as a non-specific marker of cardiovascular injury, were determined in plasma. Meconium instillation did not evoke any significant cardiovascular changes, but induced oxidative stress and elevated plasma aldosterone. N-acetylcysteine significantly reduced the mentioned markers of injury. However, its administration was associated with short-term increases in blood pressure and in several parameters of heart rate variability. Considering these effects of N-acetylcysteine, its intravenous administration in newborns with MAS should be carefully monitored.

  19. The Effect of N-acetylcysteine on postoperative pain after laparoscopic cholecystectomy: a randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Shahram Seyfi

    2017-05-01

    Full Text Available Background: Postoperative pain is one of the most common complications following laparoscopic cholecystectomy. Because the majority of the analgesic drugs including opioids and nonsteroidal anti-inflammatory drugs have many side effects, using drugs with lesser side effects is beneficial. The aim of this study was to evaluate the effect of N-acetylcysteine on the pain after laparoscopic cholecystectomy. Methods: In a randomized clinical trial, in two university-affiliated teaching hospitals in Babol City (Shahid Beheshti and Shahid Yahyanezhad Hospitals, Iran, from August 2015 to March 2015, a total number of 38 patients with age of 20-50 years, who were candidates for laparoscopic cholecystectomy with American Society of Anesthesiologists Class-I were chosen and randomly assigned into two groups. The night before operation, 1200 mg oral N-acetylcysteine is given to intervention group. Also, they received 600 mg IV N-acetylcysteine in the morning before operation. In the control group, two vitamin C effervescent tablets as placebo were given at night before operation and 3 ml sterile water as placebo was injected in the morning of operation. Amount of pethidine consumption and the changes in hemodynamic in two groups was recorded and analyzed at 24 hours after operation. Results: The average of patients age was not significant different between two groups (P=0.23. Average of pain score in placebo group was 3.5 and in N-acetylcysteine group was 2.7 that it was not significant difference between two groups (P=0.06. Average of pethidine consumption in placebo group was 52 mg and in N-acetylcysteine group was 29 mg in 24 hours, that the difference was statistically significant between two groups (P=0.01 Conclusion: As the results of the study, it can be concluded that the anti-inflammatory effects N- acetylcysteine can inhibit the function of lipoproteins and prostaglandins, reduced glutathione peroxidase and dismutase has been restored and can be

  20. The Role of N-Acetylcysteine in the Prevention of Contrast-Induced Nephrotoxicity

    International Nuclear Information System (INIS)

    Sandhu, Caron; Belli, Anna-Maria; Oliveira, David B.

    2006-01-01

    Purpose. To determine the role of prophylactic N-acetylcysteine in the prevention of contrast-induced nephrotoxicity. Methods. One hundred and sixteen patients undergoing noncoronary angiography, with or without pre-existing renal impairment, were randomly assigned to receive prophylactic oral N-acetylcysteine or no treatment. Serum creatinine (sCr) was measured prior to angiography and 48 hr after the procedure. Urine samples were collected before and after the examination for measurement of malondialdehyde (MDA) concentration. Contrast-induced nephrotoxicity (CIN) was defined as a rise in serum creatinine of 0.5 mg/dl (44 mmol/l) at 48 hr. Results. Complete data were available on 106 patients, 53 of whom had received N-acetylcysteine. There were no significant differences between the two groups in baseline characteristics, type of angiogram, or volume and concentration of contrast used. Three patients (2.8%), all of whom had received N-acetylcysteine, developed CIN. In the N-acetylcysteine group, the mean serum creatinine in patients with renal impairment was 151.0 ± 44.2 μmol/l prior to the procedure and 155.6 ± 48.6 μmol/l (p = 0.49) after the procedure. Respective values for those without renal impairment were 79.6 ± 15.1 μmol/l and 81.2 ± 20.0 μmol/l (p = 0.65). In the group that had not received N-acetylcysteine, the mean serum creatinine levels before and after the procedure were 150.0 ± 58.1 and 141.4 ± 48.0 μmol/l (p = 0.17) in patients with renal impairment and 79.7 ± 14.2 and 81.4 ± 15.4 μmol/l (p = 0.34) in those without renal impairment. In both groups, no significant change in urinary MDA concentration was observed. Conclusion. There is no benefit to the prophylactic administration of N-acetylcysteine in patients undergoing peripheral angiography using current contrast media

  1. Vitamin B5 and N-Acetylcysteine in Nonalcoholic Steatohepatitis: A Preclinical Study in a Dietary Mouse Model.

    Science.gov (United States)

    Machado, Mariana Verdelho; Kruger, Leandi; Jewell, Mark L; Michelotti, Gregory Alexander; Pereira, Thiago de Almeida; Xie, Guanhua; Moylan, Cynthia A; Diehl, Anna Mae

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the number one cause of chronic liver disease and second indication for liver transplantation in the Western world. Effective therapy is still not available. Previously we showed a critical role for caspase-2 in the pathogenesis of nonalcoholic steatohepatitis (NASH), the potentially progressive form of NAFLD. An imbalance between free coenzyme A (CoA) and acyl-CoA ratio is known to induce caspase-2 activation. We aimed to evaluate CoA metabolism and the effects of supplementation with CoA precursors, pantothenate and cysteine, in mouse models of NASH. CoA metabolism was evaluated in methionine-choline deficient (MCD) and Western diet mouse models of NASH. MCD diet-fed mice were treated with pantothenate and N-acetylcysteine or placebo to determine effects on NASH. Liver free CoA content was reduced, pantothenate kinase (PANK), the rate-limiting enzyme in the CoA biosynthesis pathway, was down-regulated, and CoA degrading enzymes were increased in mice with NASH. Decreased hepatic free CoA content was associated with increased caspase-2 activity and correlated with worse liver cell apoptosis, inflammation, and fibrosis. Treatment with pantothenate and N-acetylcysteine did not inhibit caspase-2 activation, improve NASH, normalize PANK expression, or restore free CoA levels in MCD diet-fed mice. In mice with NASH, hepatic CoA metabolism is impaired, leading to decreased free CoA content, activation of caspase-2, and increased liver cell apoptosis. Dietary supplementation with CoA precursors did not restore CoA levels or improve NASH, suggesting that alternative approaches are necessary to normalize free CoA during NASH.

  2. Effects of Zinc and N-Acetylcysteine in Damage Caused by Lead Exposure in Young Rats.

    Science.gov (United States)

    Pedroso, Taíse F; Oliveira, Cláudia S; Fonseca, Mariana M; Oliveira, Vitor A; Pereira, Maria Ester

    2017-12-01

    This study investigated the toxicity of rats exposed to lead acetate (AcPb) during the second phase of brain development (8-12 days postnatal) in hematological and cerebral parameters. Moreover, the preventive effect of zinc chloride (ZnCl 2 ) and N-acetylcysteine (NAC) was investigated. Pups were injected subcutaneously with saline (0.9% NaCl solution), ZnCl 2 (27 mg/kg/day), NAC (5 mg/kg/day) or ZnCl 2 plus NAC for 5 days (3rd-7th postnatal days), and with saline (0.9% NaCl solution) or AcPb (7 mg/kg/day) in the five subsequent days (8th-12th postnatal days). Animals were sacrificed 21 days after the last AcPb exposure. Pups exposed to AcPb presented inhibition of blood porphobilinogen-synthase (PBG-synthase) activity without changes in hemoglobin content. ZnCl 2 pre-exposure partially prevented PBG-synthase inhibition. Regarding neurotoxicity biomarkers, animals exposed to AcPb presented a decrease in cerebrum acetylcholinesterase (AChE) activity and an increase in Pb accumulation in blood and cerebrum. These changes were prevented by pre-treatment with ZnCl 2 , NAC, and ZnCl 2 plus NAC. AcPb exposure caused no alteration in behavioral tasks. In short, results show that AcPb inhibited the activity of two important enzymatic biomarkers up to 21 days after the end of the exposure. Moreover, ZnCl 2 and NAC prevented the alterations induced by AcPb.

  3. Antioxidant treatment with N-acetylcysteine during adult respiratory distress syndrome

    DEFF Research Database (Denmark)

    Jepsen, S; Herlevsen, P; Knudsen, P

    1992-01-01

    OBJECTIVE: To examine whether the antioxidant N-acetylcysteine could ameliorate the course of the adult respiratory distress syndrome (ARDS) in man. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Medical and surgical ICU in a regional hospital. PATIENTS: Sixty-six ICU patients...... with ARDS. INTERVENTIONS: Patients with ARDS (PaO2/FiO2 ratio less than 250 torr) were treated with either the antioxidant N-acetylcysteine 150 mg/kg as a loading dose and then 20 mg/kg/hr, or with placebo for 6 days. MEASUREMENTS AND MAIN RESULTS: No improvement could be demonstrated in the PaO2/FiO2 ratio...

  4. The effect of N-acetylcysteine and melatonin in adult SHR with established hypertension

    Czech Academy of Sciences Publication Activity Database

    Pecháňová, O.; Zicha, Josef; Paulis, L.; Kojšová, S.; Jendeková, L.; Dobešová, Zdenka; Sládková, M.; Šimko, F.; Kuneš, Jaroslav

    2006-01-01

    Roč. 48, č. 4 (2006), s. 776-777 ISSN 0194-911X. [Annual Meeting of the European Council for Cardiovascular Research (ECCR) /11./. 29.09.2006-01.10.2006, La Colle sur Loup] Grant - others:VEGA(SK) 2/6148/26; VEGA(SK) 1/3429/06; VEGA(SK) 1/3442/06 Keywords : N-acetylcysteine * melatonin * SHR * hypertension Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  5. A randomised, double blind trial of N-Acetylcysteine for hearing protection during stapes surgery.

    Directory of Open Access Journals (Sweden)

    Dan Bagger-Sjöbäck

    Full Text Available Otosclerosis is a disorder that impairs middle ear function, leading to conductive hearing loss. Surgical treatment results in large improvement of hearing at low sound frequencies, but high-frequency hearing often suffers. A likely reason for this is that inner ear sensory cells are damaged by surgical trauma and loud sounds generated during the operation. Animal studies have shown that antioxidants such as N-Acetylcysteine can protect the inner ear from noise, surgical trauma, and some ototoxic substances, but it is not known if this works in humans. This trial was performed to determine whether antioxidants improve surgical results at high frequencies.We performed a randomized, double-blind and placebo-controlled parallel group clinical trial at three Swedish university clinics. Using block-stratified randomization, 156 adult patients undergoing stapedotomy were assigned to intravenous N-Acetylcysteine (150 mg/kg body weight or matching placebo (1:1 ratio, starting one hour before surgery. The primary outcome was the hearing threshold at 6 and 8 kHz; secondary outcomes included the severity of tinnitus and vertigo.One year after surgery, high-frequency hearing had improved 2.7 ± 3.8 dB in the placebo group (67 patients analysed and 2.4 ± 3.7 dB in the treated group (72 patients; means ± 95% confidence interval, p = 0.54; linear mixed model. Surgery improved tinnitus, but there was no significant intergroup difference. Post-operative balance disturbance was common but improved during the first year, without significant difference between groups. Four patients receiving N-Acetylcysteine experienced mild side effects such as nausea and vomiting.N-Acetylcysteine has no effect on hearing thresholds, tinnitus, or balance disturbance after stapedotomy.ClinicalTrials.gov NCT00525551.

  6. Antioxidant treatment with N-acetylcysteine during adult respiratory distress syndrome

    DEFF Research Database (Denmark)

    Jepsen, S; Herlevsen, P; Knudsen, P

    1992-01-01

    OBJECTIVE: To examine whether the antioxidant N-acetylcysteine could ameliorate the course of the adult respiratory distress syndrome (ARDS) in man. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Medical and surgical ICU in a regional hospital. PATIENTS: Sixty-six ICU patients...... with ARDS. INTERVENTIONS: Patients with ARDS (PaO2/FiO2 ratio less than 250 torr) were treated with either the antioxidant N-acetylcysteine 150 mg/kg as a loading dose and then 20 mg/kg/hr, or with placebo for 6 days. MEASUREMENTS AND MAIN RESULTS: No improvement could be demonstrated in the PaO2/FiO2 ratio...... in the study group as compared with the control group on any day. Pulmonary compliance was higher in the N-acetylcysteine group than in the placebo group on all days, but this difference did not reach the chosen 5% level of significance. No difference between the two groups could be demonstrated on chest...

  7. N-Acetylcysteine's Role in Sepsis and Potential Benefit in Patients With Microcirculatory Derangements.

    Science.gov (United States)

    Chertoff, Jason

    2018-02-01

    To review the data surrounding the utility of N-acetylcysteine (NAC) in sepsis and identify areas needed for additional research. A review of articles describing the mechanisms of action and clinical use of NAC in sepsis. Despite many advances in critical care medicine, still as many as 50% of patients with septic shock die. Treatments thus far have focused on resuscitation and restoration of macrocirculatory targets in the early phases of sepsis, with less focus on microcirculatory dysfunction. N-acetylcysteine, due to its anti-inflammatory and antioxidative properties, has been readily investigated in sepsis and has yielded largely incongruous and disappointing results. In addition to its known anti-inflammatory and antioxidative roles, one underappreciated property of NAC is its ability to vasodilate the microcirculation and improve locoregional blood flow. Some investigators have sought to capitalize on this mechanism with promising results, as evidenced by microcirculatory vasodilation, improvements in regional blood flow and oxygen delivery, and reductions in lactic acidosis, organ failure, and mortality. In addition to its antioxidant and anti-inflammatory properties, N-acetylcysteine possesses vasodilatory properties that could benefit the microcirculation in sepsis. It is imperative that we investigate these properties to uncover NAC's full potential for benefit in sepsis.

  8. N-acetylcysteine, a glutamate modulator, in the treatment of trichotillomania: a double-blind, placebo-controlled study.

    Science.gov (United States)

    Grant, Jon E; Odlaug, Brian L; Kim, Suck Won

    2009-07-01

    Trichotillomania is characterized by repetitive hair pulling that causes noticeable hair loss. Data on the pharmacologic treatment of trichotillomania are limited to conflicting studies of serotonergic medications. N-acetylcysteine, an amino acid, seems to restore the extracellular glutamate concentration in the nucleus accumbens and, therefore, offers promise in the reduction of compulsive behavior. To determine the efficacy and tolerability of N-acetylcysteine in adults with trichotillomania. Twelve-week, double-blind, placebo-controlled trial. Ambulatory care center. Fifty individuals with trichotillomania (45 women and 5 men; mean [SD] age, 34.3 [12.1] years). N-acetylcysteine (dosing range, 1200-2400 mg/d) or placebo was administered for 12 weeks. Patients were assessed using the Massachusetts General Hospital Hair Pulling Scale, the Clinical Global Impression scale, the Psychiatric Institute Trichotillomania Scale, and measures of depression, anxiety, and psychosocial functioning. Outcomes were examined using analysis of variance modeling analyses and linear regression in an intention-to-treat population. Patients assigned to receive N-acetylcysteine had significantly greater reductions in hair-pulling symptoms as measured using the Massachusetts General Hospital Hair Pulling Scale (P Trichotillomania Scale (P = .001). Fifty-six percent of patients "much or very much improved" with N-acetylcysteine use compared with 16% taking placebo (P = .003). Significant improvement was initially noted after 9 weeks of treatment. This study, the first to our knowledge that examines the efficacy of a glutamatergic agent in the treatment of trichotillomania, found that N-acetylcysteine demonstrated statistically significant reductions in trichotillomania symptoms. No adverse events occurred in the N-acetylcysteine group, and N-acetylcysteine was well tolerated. Pharmacologic modulation of the glutamate system may prove to be useful in the control of a range of compulsive

  9. N-Acetylcysteine reduces cocaine-cue attentional bias and differentially alters cocaine self-administration based on dosing order.

    Science.gov (United States)

    Levi Bolin, B; Alcorn, Joseph L; Lile, Joshua A; Rush, Craig R; Rayapati, Abner O; Hays, Lon R; Stoops, William W

    2017-09-01

    Disrupted glutamate homeostasis is thought to contribute to cocaine-use disorder, in particular, by enhancing the incentive salience of cocaine stimuli. n-Acetylcysteine might be useful in cocaine-use disorder by normalizing glutamate function. In prior studies, n-acetylcysteine blocked the reinstatement of cocaine seeking in laboratory animals and reduced the salience of cocaine stimuli and delayed relapse in humans. The present study determined the ability of maintenance on n-acetylcysteine (0 or 2400mg/day, counterbalanced) to reduce the incentive salience of cocaine stimuli, as measured by an attentional bias task, and attenuate intranasal cocaine self-administration (0, 30, and 60mg). Fourteen individuals (N=14) who met criteria for cocaine abuse or dependence completed this within-subjects, double-blind, crossover-design study. Cocaine-cue attentional bias was greatest following administration of 0mg cocaine during placebo maintenance, and was attenuated by n-acetylcysteine. Cocaine maintained responding during placebo and n-acetylcysteine maintenance, but the reinforcing effects of cocaine were significantly attenuated across both maintenance conditions in participants maintained on n-acetylcysteine first compared to participants maintained on placebo first. These results collectively suggest that a reduction in the incentive salience of cocaine-related stimuli during n-acetylcysteine maintenance may be accompanied by reductions in cocaine self-administration. These results are in agreement with, and link, prior preclinical and clinical trial results suggesting that n-acetylcysteine might be useful for preventing cocaine relapse by attenuating the incentive salience of cocaine cues. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. N-acetylcysteine protects rats with chronic renal failure from gadolinium-chelate nephrotoxicity.

    Directory of Open Access Journals (Sweden)

    Leonardo Victor Barbosa Pereira

    Full Text Available The aim of this study was to evaluate the effect of Gd-chelate on renal function, iron parameters and oxidative stress in rats with CRF and a possible protective effect of the antioxidant N-Acetylcysteine (NAC. Male Wistar rats were submitted to 5/6 nephrectomy (Nx to induced CRF. An ionic-cyclic Gd (Gadoterate Meglumine was administrated (1.5 mM/KgBW, intravenously 21 days after Nx. Clearance studies were performed in 4 groups of anesthetized animals 48 hours following Gd- chelate administration: 1--Nx (n = 7; 2--Nx+NAC (n = 6; 3--Nx+Gd (n = 7; 4--Nx+NAC+Gd (4.8 g/L in drinking water, initiated 2 days before Gd-chelate administration and maintained during 4 days (n = 6. This group was compared with a control. We measured glomerular filtration rate, GFR (inulin clearance, ml/min/kg BW, proteinuria (mg/24 hs, serum iron (µg/dL; serum ferritin (ng/mL; transferrin saturation (%, TIBC (µg/dL and TBARS (nmles/ml. Normal rats treated with the same dose of Gd-chelate presented similar GFR and proteinuria when compared with normal controls, indicating that at this dose Gd-chelate is not nephrotoxic to normal rats. Gd-chelate administration to Nx-rats results in a decrease of GFR and increased proteinuria associated with a decrease in TIBC, elevation of ferritin serum levels, transferrin oversaturation and plasmatic TBARS compared with Nx-rats. The prophylactic treatment with NAC reversed the decrease in GFR and the increase in proteinuria and all alterations in iron parameters and TBARS induced by Gd-chelate. NAC administration to Nx rat did not modify the inulin clearance and iron kinetics, indicating that the ameliorating effect of NAC was specific to Gd-chelate. These results suggest that NAC can prevent Gd-chelate nephrotoxicity in patients with chronic renal failure.

  11. Effect of N-Acetylcysteine in Protecting from Simultaneous Noise and Carbon Monoxide Induced Hair Cell Loss

    Directory of Open Access Journals (Sweden)

    Akram Pourbakht

    2011-06-01

    Full Text Available Background and Aim: N-acetylcysteine, a glutathione precursor and reactive oxygen species scavenger, is reported to be effective in reducing noise-induced hearing loss. Many workers in industry are exposed simultaneously to noise and chemical pollutants such as carbon monoxide. We investigated effectiveness of N-acetylcysteine in protecting the cochlea from simultaneous noise and carbon monoxide damages.Methods: Twelve rabbits were exposed simeltaneously to 100 dB sound pressure level of broad band noise and carbon monoxide 8 hours a day for 5 days. One hour before exposure, experimental group received 325 mg/kg of N-acetylcysteine while normal saline was administered for the control group. The protective effect of N-acetylcysteine was evaluated 3 weeks after exposure by histological assessment of the hair cells.Results: Simultaneous exposure to noise and carbon monoxide resulted in a considerable damage to the outer hair cells; however, the inner hair cells and the pillar cells remained intact. Use of N-acetylcysteine in the experimental group significantly reduced the extent of outer hair cell loss.Conclusion: N-acetylcysteine attenuates simultaneous noise and carbon monoxide induced hair cell damage in rabbits.

  12. N-acetylcysteine improves established monocrotaline-induced pulmonary hypertension in rats.

    Science.gov (United States)

    Chaumais, Marie-Camille; Ranchoux, Benoît; Montani, David; Dorfmüller, Peter; Tu, Ly; Lecerf, Florence; Raymond, Nicolas; Guignabert, Christophe; Price, Laura; Simonneau, Gérald; Cohen-Kaminsky, Sylvia; Humbert, Marc; Perros, Frédéric

    2014-06-14

    The outcome of patients suffering from pulmonary arterial hypertension (PAH) are predominantly determined by the response of the right ventricle to the increase afterload secondary to high vascular pulmonary resistance. However, little is known about the effects of the current available or experimental PAH treatments on the heart. Recently, inflammation has been implicated in the pathophysiology of PAH. N-acetylcysteine (NAC), a well-known safe anti-oxidant drug, has immuno-modulatory and cardioprotective properties. We therefore hypothesized that NAC could reduce the severity of pulmonary hypertension (PH) in rats exposed to monocrotaline (MCT), lowering inflammation and preserving pulmonary vascular system and right heart function. Saline-treated control, MCT-exposed, MCT-exposed and NAC treated rats (day 14-28) were evaluated at day 28 following MCT for hemodynamic parameters (right ventricular systolic pressure, mean pulmonary arterial pressure and cardiac output), right ventricular hypertrophy, pulmonary vascular morphometry, lung inflammatory cells immunohistochemistry (monocyte/macrophages and dendritic cells), IL-6 expression, cardiomyocyte hypertrophy and cardiac fibrosis. The treatment with NAC significantly decreased pulmonary vascular remodeling, lung inflammation, and improved total pulmonary resistance (from 0.71 ± 0.05 for MCT group to 0.50 ± 0.06 for MCT + NAC group, p < 0.05). Right ventricular function was also improved with NAC treatment associated with a significant decrease in cardiomyocyte hypertrophy (625 ± 69 vs. 439 ± 21 μm2 for MCT and MCT + NAC group respectively, p < 0.001) and heart fibrosis (14.1 ± 0.8 vs. 8.8 ± 0.1% for MCT and MCT + NAC group respectively, p < 0.001). Through its immuno-modulatory and cardioprotective properties, NAC has beneficial effect on pulmonary vascular and right heart function in experimental PH.

  13. The effects of N-acetylcysteine on hepatic function during isoflurane anaesthesia for laparoscopic surgery patients

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    Serbülent Gökhan Beyaz

    2011-01-01

    Full Text Available Introduction: Although most general anaesthesia procedures are performed without any complications, volatile agents may have adverse effects on various living systems. This study aims to compare the antioxidant effects of isoflurane and N-acetylcysteine (NAC on liver function. Methods: Forty-one patients in the ASA I-II risk groups, who were scheduled to undergo gynaecologic laparoscopy, were randomly divided into two groups: The placebo (group P, n=21 and the NAC group (group N, n=20. In both groups, anaesthesia was maintained with 1-2% isoflurane in 50% Oxygen-50% N 2 O at 6 l/min, also administered by inhalation. Venous blood samples were obtained before anaesthesia induction, and then in the postoperative 1 st hour and at the 24 th hour. The samples were centrifuged and serum levels of glutathione S-transferase (GST, malondialdehyde (MDA, aspartate amino transferase (AST, alanine amino transferase (ALT, lactate dehydrogenase (LDH, gamma glutamyltranspeptidase (GGT, prothrombin time (PT, activated partial thromboplastin time (aPTT and international normalised ratio were determined. Results: GST levels were significantly higher in group N than in group P in the postoperative 1 st hour. Postoperative values of GST in the two groups were higher when compared to preoperative values (P<0.05. When postoperative levels were compared with preoperative levels, the postoperative MDA levels of group N were significantly higher (P<0.05. Levels of AST, ALT, GGT and LDH in both groups revealed significant decreases at the postoperative 1 st hour and postoperative 24 th hour compared to preoperative values (P<0.05, P<0.001. PT values were significantly higher in both groups in the postoperative 1 st hour and 24 th hour (P<0.05, P<0.001, although there were no differences in aPTT levels. Conclusion: Our results showed that liver functions were well preserved with administration of NAC during anaesthesia with isoflurane. Isoflurane with NAC has lesser

  14. N-Acetylcysteine protects against trichloroethene-mediated autoimmunity by attenuating oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Gangduo; Wang, Jianling; Ma, Huaxian; Ansari, G.A.S.; Khan, M. Firoze, E-mail: mfkhan@utmb.edu

    2013-11-15

    Exposure to trichloroethene (TCE), a ubiquitous environmental contaminant, is known to induce autoimmunity both in humans and animal models. However, mechanisms underlying TCE-mediated autoimmunity remain largely unknown. Previous studies from our laboratory in MRL +/+ mice suggest that oxidative stress may contribute to TCE-induced autoimmune response. The current study was undertaken to further assess the role of oxidative stress in TCE-induced autoimmunity by supplementing with an antioxidant N-acetylcysteine (NAC). Groups of female MRL +/+ mice were given TCE, NAC or TCE + NAC for 6 weeks (TCE, 10 mmol/kg, i.p., every 4th day; NAC, 250 mg/kg/day through drinking water). TCE exposure led to significant increases in serum levels of anti-nuclear, anti-dsDNA and anti-Sm antibodies. TCE exposure also led to significant induction of anti-malondiadelhyde (MDA)- and anti-hydroxynonenal (HNE)-protein adduct antibodies which were associated with increased ANA in the sera along with increased MDA-/HNE-protein adducts in the livers and kidneys, and increases in protein oxidation (carbonylation) in the sera, livers and kidneys, suggesting an overall increase in oxidative stress. Moreover, TCE exposure also resulted in increased release of IL-17 from splenocytes and increases in IL-17 mRNA expression. Remarkably, NAC supplementation attenuated not only the TCE-induced oxidative stress, IL-17 release and mRNA expression, but also the markers of autoimmunity, as evident from decreased levels of ANA, anti-dsDNA and anti-Sm antibodies in the sera. These results provide further support to a role of oxidative stress in TCE-induced autoimmune response. Attenuation of TCE-induced autoimmunity in mice by NAC provides an approach for preventive and/or therapeutic strategies. - Highlights: • TCE led to increased autoantibodies, supporting its potential to induce autoimmunity. • TCE exposure led to increases in lipid perioxidation and protein carbonyls. • TCE exposure resulted in

  15. N-acetylcysteine and captopril protect DNA and cells against radiolysis by fast neutrons

    Energy Technology Data Exchange (ETDEWEB)

    Spotheim-Maurizot, M. (CNRS, 45 - Orleans (France). Centre de Biophysique Moleculaire); Garnier, F. (CNRS, 45 - Orleans (France). Centre de Biophysique Moleculaire); Kieda, C. (CNRS, 45 - Orleans (France). Centre de Biophysique Moleculaire); Sabattier, R. (Centre Hospitalier Regional d' Orleans, 45 (France). Service de Radiotherapie); Charlier, M. (CNRS, 45 - Orleans (France). Centre de Biophysique Moleculaire)

    1993-10-01

    N-Acetylcysteine and captopril, respectively mucolytic and antihypertensive drugs, contain free sulfhydryl groups. Since in general thiols have well-established radioprotective abilities, we sought putative radioprotective effects of these drugs against therapeutic fast neutrons. We show that pBR322 plasmid DNA is indeed protected against radiolytic strand breakage by both drugs. The oxygen independent protection is consistent with a hydroxyl radical scavenging mechanism. A clonogenicity assay reveals an increase of the survival of SCL-1 cultured keratinocytes irradiated in the presence of the drugs compared with cells irradiated without drugs. Our results suggest possible interferences between treatment with drugs bearing-SH groups and radiotherapy. (orig.)

  16. Effect of chronic N-acetylcysteine treatment on the development of spontaneous hypertension

    Czech Academy of Sciences Publication Activity Database

    Pecháňová, Olga; Zicha, Josef; Kojšová, S.; Dobešová, Zdenka; Jendeková, L.; Kuneš, Jaroslav

    2006-01-01

    Roč. 110, č. 2 (2006), s. 235-242 ISSN 0143-5221 R&D Projects: GA ČR(CZ) GA305/03/0769; GA MZd(CZ) NR7786 Grant - others:VEGA(SK) 2/3185/24; VEGA(SK) 2/6148/26; VEGA(SK) 1/1171/24; SAV(SK) APVT-51-017902 Institutional research plan: CEZ:AV0Z50110509 Keywords : N-acetylcysteine * NF-kB * nitric oxide synthase Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 3.263, year: 2006

  17. No net splanchnic release of glutathione in man during N-acetylcysteine infusion

    DEFF Research Database (Denmark)

    Poulsen, H E; Vilstrup, H; Almdal, T

    1993-01-01

    Glutathione and amino acid concentrations were measured in arterial and hepatic vein plasma in four healthy volunteers and two patients with cirrhosis. There was no significant splanchnic efflux of glutathione (95% confidence limits, -0.501 to 0.405 mumol/min). After infusion of N-acetylcysteine ......Glutathione and amino acid concentrations were measured in arterial and hepatic vein plasma in four healthy volunteers and two patients with cirrhosis. There was no significant splanchnic efflux of glutathione (95% confidence limits, -0.501 to 0.405 mumol/min). After infusion of N...

  18. Pre-clinical evaluation of N-acetylcysteine reveals side effects in the mdx mouse model of Duchenne muscular dystrophy.

    Science.gov (United States)

    Pinniger, Gavin J; Terrill, Jessica R; Assan, Evanna B; Grounds, Miranda D; Arthur, Peter G

    2017-12-01

    Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disease associated with increased inflammation and oxidative stress. The antioxidant N-acetylcysteine (NAC) has been proposed as a therapeutic intervention for DMD boys, but potential adverse effects of NAC have not been widely investigated. We used young (6 weeks old) growing mdx mice to investigate the capacity of NAC supplementation (2% in drinking water for 6 weeks) to improve dystrophic muscle function and to explore broader systemic effects of NAC treatment. NAC treatment improved normalised measures of muscle function, and decreased inflammation and oxidative stress, but significantly reduced body weight gain, muscle weight and liver weight. Unexpected significant adverse effects of NAC on body and muscle weights indicate that interpretation of muscle function based on normalised force measures should be made with caution and careful consideration is needed when proposing the use of NAC as a therapeutic treatment for young DMD boys. Duchenne muscular dystrophy (DMD) is a fatal X-linked muscle wasting disease characterised by severe muscle weakness, necrosis, inflammation and oxidative stress. The antioxidant N-acetylcysteine (NAC) has been proposed as a potential therapeutic intervention for DMD boys. We investigated the capacity of NAC to improve dystrophic muscle function in the mdx mouse model of DMD. Young (6 weeks old) mdx and non-dystrophic C57 mice receiving 2% NAC in drinking water for 6 weeks were compared with untreated mice. Grip strength and body weight were measured weekly, before the 12 week old mice were anaesthetised and extensor digitorum longus (EDL) muscles were excised for functional analysis and tissues were sampled for biochemical analyses. Compared to untreated mice, the mean (SD) normalised grip strength was significantly greater in NAC-treated mdx [3.13 (0.58) vs 4.87 (0.78) g body weight (bw) -1 ; P effects of NAC emphasise the need for caution when interpreting

  19. Prevention of biofilm formation by dairy products and N-acetylcysteine on voice prostheses in an artificial throat.

    Science.gov (United States)

    Schwandt, Leonora Q; Van Weissenbruch, Ranny; Stokroos, Ietse; Van der Mei, Henny C; Busscher, Henk J; Albers, Frans W J

    2004-08-01

    To evaluate the preventive effect of buttermilk, Yakult Light fermented milk drink and N-acetylcysteine on biofilm formation on voice prostheses in vitro. Groningen button and Provox 2 voice prostheses were inoculated with a mixture of bacteria and yeasts isolated from previously explanted Groningen button voice prostheses. After 5 h, separate throats were flushed with buttermilk, Yakult Light fermented milk drink, N-acetylcysteine or phosphate-buffered saline, which served as a control. After 7 days, the microflora on each voice prosthesis was determined. On Groningen button voice prostheses, buttermilk, Yakult Light fermented milk drink and N-acetylcysteine all reduced the amount of both bacteria and yeasts. On Provox 2 voice prostheses, buttermilk, Yakult Light fermented milk drink and N-acetylcysteine reduced the amount of bacteria but, conversely, increased the amount of yeasts. These in vitro experiments demonstrate that biofilm formation on voice prostheses is reduced in an artificial throat by the use of buttermilk, Yakult Light fermented milk drink and N-acetylcysteine. However, the structural differences between the type of voice prostheses may influence the ultimate effects.

  20. Effects of N-acetylcysteine and L-arginine in the antioxidant system of C2C12 cells.

    Science.gov (United States)

    Da Silva, E P; Lambertucci, R H

    2015-06-01

    The aim of this study was to evaluate the effects of N-acetylcysteine or L-arginine in the antioxidant system of skeletal muscle cells in culture. We used C2C12 cells which were supplemented or not with N-acetylcysteine or L-arginine at different time points. Antioxidant enzymes' activities and protein expression were evaluated. Additionally, superoxide production by cytochrome c reduction method was carried out. It was observed that the supplementation with either N-acetylcysteine or L-arginine was capable to acutely reduce superoxide production (after 30 and 60 minutes). Surprisingly, N-acetylcysteine supplementation also induced an increased production of superoxide during the period of 24 hours. Moreover, both supplements were capable to improve the activity and protein expression of some antioxidants enzymes. In conclusion, we have found new evidences showing that N-acetylcysteine or L-arginine supplementation can provide some benefits to the antioxidant system of skeletal muscle cells in culture. Further studies have to be carried out to evaluate if such benefits could also occur in an in vivo model, with possible benefits for athletes' health and performance.

  1. Probenecid, an organic anion transporter 1 and 3 inhibitor, increases plasma and brain exposure of N-acetylcysteine.

    Science.gov (United States)

    Hagos, Fanuel T; Daood, Monica J; Ocque, Jacob A; Nolin, Thomas D; Bayir, Hulya; Poloyac, Samuel M; Kochanek, Patrick M; Clark, Robert S B; Empey, Philip E

    2017-04-01

    1. N-acetylcysteine (NAC) is being investigated as an antioxidant for several conditions including traumatic brain injury, but the mechanism by which it crosses membrane barriers is unknown. We have attempted to understand how the transporter inhibitor, probenecid, affects NAC pharmacokinetics and to evaluate the interaction of NAC with transporters. 2. Juvenile Sprague-Dawley rats were administered NAC alone or in combination with probenecid intraperitoneally. Plasma and brain samples were collected serially and NAC concentrations were measured. Transporter studies were conducted with human embryonic kidney-293 cells that overexpress organic anion transporter (OAT)1 or OAT3 and with human multi-drug resistance-associated protein (MRP)1 or MRP4 membrane vesicles. 3. NAC area under the curve was increased in plasma (1.65-fold) and brain (2.41-fold) by probenecid. The apparent plasma clearance was decreased by 65%. Time- and concentration-dependent NAC uptake that was inhibitable by probenecid was observed with OAT1 and OAT3. No uptake of NAC was observed with MRP1 or MRP4. 4. Our results indicate for the first time that NAC is substrate for OAT1 and OAT3 and that probenecid increases NAC plasma and brain exposure in vivo. These data provide insight regarding how NAC crosses biological barriers and suggest a promising therapeutic strategy to increase NAC exposure.

  2. N-Acetylcysteine protects inner ear hair cells and spiral ganglion neurons from manganese exposure by regulating ROS levels.

    Science.gov (United States)

    Wang, Weilong; Li, Dan; Ding, Xuerui; Zhao, Qianqian; Chen, Jiawei; Tian, Keyong; Qiu, Yang; Lu, Lianjun

    2017-09-05

    Manganese (Mn) is an indispensable cofactor for many enzymes and a basic factor for many reproductive and metabolic pathways. However, exposure to high concentrations of Mn can result in deleterious effects on the central nervous system and peripheral nerves, including nerves associated with the auditory system. Based on our studies of cochlear organotypic cultures, Mn exposure induces a significant loss of hair cells (HCs), auditory nerve fibers (ANFs) and spiral ganglion neurons (SGNs) in a concentration-dependent manner. Additionally, N-acetylcysteine (NAC), a glutathione (GSH) provider and a direct scavenger of reactive oxygen species (ROS), clearly decreases Mn-induced ROS accumulation, caspase-3 activation and TUNEL staining, which indicate increased cell survival. Based on these results, Mn exposure exerts ototoxic and neurotoxic effects on the auditory system. Furthermore, 20mM NAC may prevent 1mM Mn-induced hair cell loss and axonal degeneration, indicating that NAC could be a promising drug for clinical applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. A Promise in the Treatment of Endometriosis: An Observational Cohort Study on Ovarian Endometrioma Reduction by N-Acetylcysteine

    Directory of Open Access Journals (Sweden)

    Maria Grazia Porpora

    2013-01-01

    Full Text Available Urged by the unmet medical needs in endometriosis treatment, often with undesirable side effects, and encouraged by N-acetylcysteine (NAC efficacy in an animal model of endometriosis and by the virtual absence of toxicity of this natural compound, we performed an observational cohort study on ovarian endometriosis. NAC treatment or no treatment was offered to 92 consecutive Italian women referred to our university hospital with ultrasound confirmed diagnosis of ovarian endometriosis and scheduled to undergo laparoscopy 3 months later. According to patients acceptance or refusal, NAC-treated and untreated groups finally comprised 73 and 72 endometriomas, respectively. After 3 months, within NAC-treated patients cyst mean diameter was slightly reduced (-1.5 mm versus a significant increase (+6.6 mm in untreated patients (P=0.001. Particularly, during NAC treatment, more cysts reduced and fewer cysts increased their size. Our results are better than those reported after hormonal treatments. Twenty-four NAC-treated patients—versus 1 within controls—cancelled scheduled laparoscopy due to cysts decrease/disappearance and/or relevant pain reduction (21 cases or pregnancy (1 case. Eight pregnancies occurred in NAC-treated patients and 6 in untreated patients. We can conclude that NAC actually represents a simple effective treatment for endometriosis, without side effects, and a suitable approach for women desiring a pregnancy.

  4. Inhibitory Effect on Cerebral Inflammatory Response following Traumatic Brain Injury in Rats: A Potential Neuroprotective Mechanism of N-Acetylcysteine

    Directory of Open Access Journals (Sweden)

    Gang Chen

    2008-01-01

    Full Text Available Although N-acetylcysteine (NAC has been shown to be neuroprotective for traumatic brain injury (TBI, the mechanisms for this beneficial effect are still poorly understood. Cerebral inflammation plays an important role in the pathogenesis of secondary brain injury after TBI. However, it has not been investigated whether NAC modulates TBI-induced cerebral inflammatory response. In this work, we investigated the effect of NAC administration on cortical expressions of nuclear factor kappa B (NF-κB and inflammatory proteins such as interleukin-1β (IL-1β, tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6, and intercellular adhesion molecule-1 (ICAM-1 after TBI. As a result, we found that NF-κB, proinflammatory cytokines, and ICAM-1 were increased in all injured animals. In animals given NAC post-TBI, NF-κB, IL-1β, TNF-α, and ICAM-1 were decreased in comparison to vehicle-treated animals. Measures of IL-6 showed no change after NAC treatment. NAC administration reduced brain edema, BBB permeability, and apoptotic index in the injured brain. The results suggest that post-TBI NAC administration may attenuate inflammatory response in the injured rat brain, and this may be one mechanism by which NAC ameliorates secondary brain damage following TBI.

  5. The Coadministration of N-Acetylcysteine Ameliorates the Effects of Arsenic Trioxide on the Male Mouse Genital System

    Directory of Open Access Journals (Sweden)

    Raquel Frenedoso da Silva

    2016-01-01

    Full Text Available Arsenic trioxide (As2O3 has shown effectiveness in treatment of leukemia but is also associated with reproductive toxicity. Since remediation with N-acetylcysteine (NAC may mitigate the adverse effects caused by exposure, we assessed the effects of As2O3 and its potential reversibility after exposure cessation or coadministration of NAC. Animals received 0.3 or 3.0 mg/Kg/day of As2O3 subcutaneously and 40 mM of NAC in tap water. As2O3 treatment impaired spermatogenesis and sperm motility and decreased seminal vesicle weight and testosterone serum levels; after suspension of treatment, these parameters remained altered. When NAC was administered, animals showed improvement in sperm parameters and seminal vesicle weight. In vitro epididymal contractility was increased in As2O3-treated animals. We concluded that As2O3 is toxic to the male mouse genital system by compromising sperm quality and quantity; these effects persisted even after suspension of the treatment. However, the coadministration of NAC ameliorates the harmful effects of the drug on the male genital system.

  6. N-acetylcysteine prevents cadmium-induced apoptosis in human breast cancer MDA-MB468 cell line.

    Science.gov (United States)

    Panjehpour, M; Alaie, S H

    2014-05-11

    Cadmium is a heavy metal posing severe risks and destructive effects on human health. Although cadmium was classified as a human carcinogen, it has been also shown to be a cytotoxic agent that induces cell death either by necrosis or apoptosis. In this study, we investigated the protective role of N-acetylcysteine, a free radical scavenger, on cadmium induced apoptosis in MDA-MB468 cells. The breast cancer cells were exposed to increasing concentrations of CdCl2 in the presence and absence of NAC and the cell viability was assessed using MTT assay. The microscopic studies of apoptosis were carried out with fluorescent staining. To investigate the induction of apoptosis, cellular DNA was isolated using DNA kit extraction and analyzed electrophoretically. The results showed significant decrease in cellular viability upon 48 hours exposure to CdCl2 in a dose-dependent manner (p cadmium cytotoxicity effects and protected cells from apoptotic death. DNA Hoechst staining showed the apoptotic bodies. The electrophoresis of extracted DNA identified a fragmentation pattern consistent with apoptosis mechanism. The results suggest that cytotoxic effects and induction of apoptosis caused by CdCl2 are mediated, by oxidative stress.

  7. 7-N-Acetylcysteine-pyrrole conjugate-A potent DNA reactive metabolite of pyrrolizidine alkaloids.

    Science.gov (United States)

    He, Xiaobo; Ma, Liang; Xia, Qingsu; Fu, Peter P

    2016-10-01

    Plants containing pyrrolizidine alkaloids (PAs) are widespread throughout the world and are the most common poisonous plants affecting livestock, wildlife, and humans. PAs require metabolic activation to form reactive dehydropyrrolizidine alkaloids (dehydro-PAs) that are capable of alkylating cellular DNA and proteins, form (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-DNA and DHP-protein adducts, and lead to cytotoxicity, genotoxicity, and tumorigenicity. In this study, we determined that the metabolism of riddelliine and monocrotaline by human and rat liver microsomes in the presence of N-acetylcysteine both produced 7-N-acetylcysteine-DHP (7-NAC-DHP) and DHP. Reactions of 7-NAC-DHP with 2'-deoxyguanosine (dG), 2'-deoxyadenosine (dA), and calf thymus DNA in aqueous solution followed by enzymatic hydrolysis yielded DHP-dG and/or DHP-dA adducts. These results indicate that 7-NAC-DHP is a reactive metabolite that can lead to DNA adduct formation. Copyright © 2016. Published by Elsevier B.V.

  8. 7-N-Acetylcysteine-pyrrole conjugate—A potent DNA reactive metabolite of pyrrolizidine alkaloids

    Directory of Open Access Journals (Sweden)

    Xiaobo He

    2016-10-01

    Full Text Available Plants containing pyrrolizidine alkaloids (PAs are widespread throughout the world and are the most common poisonous plants affecting livestock, wildlife, and humans. PAs require metabolic activation to form reactive dehydropyrrolizidine alkaloids (dehydro-PAs that are capable of alkylating cellular DNA and proteins, form (±-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP-DNA and DHP-protein adducts, and lead to cytotoxicity, genotoxicity, and tumorigenicity. In this study, we determined that the metabolism of riddelliine and monocrotaline by human and rat liver microsomes in the presence of N-acetylcysteine both produced 7-N-acetylcysteine-DHP (7-NAC-DHP and DHP. Reactions of 7-NAC-DHP with 2′-deoxyguanosine (dG, 2′-deoxyadenosine (dA, and calf thymus DNA in aqueous solution followed by enzymatic hydrolysis yielded DHP-dG and/or DHP-dA adducts. These results indicate that 7-NAC-DHP is a reactive metabolite that can lead to DNA adduct formation.

  9. Protective Effects of Liposomal N-Acetylcysteine against Paraquat-Induced Cytotoxicity and Gene Expression

    Directory of Open Access Journals (Sweden)

    Panagiotis Mitsopoulos

    2011-01-01

    Full Text Available Paraquat (PQ is a herbicide that preferentially accumulates in the lung and exerts its cytotoxicity via the generation of reactive oxygen species (ROS. There is no specific treatment for paraquat poisoning. Attempts have been made to increase the antioxidant status in the lung using antioxidants (e.g., superoxide dismutase, vitamin E, N-acetylcysteine but the outcome from such treatments is limited. Encapsulation of antioxidants in liposomes improves their therapeutic potential against oxidant-induced lung damage because liposomes facilitate intracellular delivery and prolong the retention of entrapped agents inside the cell. In the present study, we compared the effectiveness of conventional N-acetylcysteine (NAC and liposomal-NAC (L-NAC against PQ-induced cytotoxicity and examined the mechanism(s by which these antioxidant formulations conferred cytoprotection. The effects of NAC or L-NAC against PQ-induced cytotoxicity in A549 cells were assessed by measuring cellular PQ uptake, intracellular glutathione content, ROS levels, mitochondrial membrane potential, cellular gene expression, inflammatory cytokine release and cell viability. Pretreatment of cells with L-NAC was significantly more effective than pretreatment with the conventional drug in reducing PQ-induced cytotoxicity, as indicated by the biomarkers used in this study. Our results suggested that the delivery of NAC as a liposomal formulation improves its effectiveness in counteracting PQ-induced cytotoxicity.

  10. Protective Effects of Liposomal N-Acetylcysteine against Paraquat-Induced Cytotoxicity and Gene Expression.

    Science.gov (United States)

    Mitsopoulos, Panagiotis; Suntres, Zacharias E

    2011-01-01

    Paraquat (PQ) is a herbicide that preferentially accumulates in the lung and exerts its cytotoxicity via the generation of reactive oxygen species (ROS). There is no specific treatment for paraquat poisoning. Attempts have been made to increase the antioxidant status in the lung using antioxidants (e.g., superoxide dismutase, vitamin E, N-acetylcysteine) but the outcome from such treatments is limited. Encapsulation of antioxidants in liposomes improves their therapeutic potential against oxidant-induced lung damage because liposomes facilitate intracellular delivery and prolong the retention of entrapped agents inside the cell. In the present study, we compared the effectiveness of conventional N-acetylcysteine (NAC) and liposomal-NAC (L-NAC) against PQ-induced cytotoxicity and examined the mechanism(s) by which these antioxidant formulations conferred cytoprotection. The effects of NAC or L-NAC against PQ-induced cytotoxicity in A549 cells were assessed by measuring cellular PQ uptake, intracellular glutathione content, ROS levels, mitochondrial membrane potential, cellular gene expression, inflammatory cytokine release and cell viability. Pretreatment of cells with L-NAC was significantly more effective than pretreatment with the conventional drug in reducing PQ-induced cytotoxicity, as indicated by the biomarkers used in this study. Our results suggested that the delivery of NAC as a liposomal formulation improves its effectiveness in counteracting PQ-induced cytotoxicity.

  11. Protective Effects of N-acetylcysteine and a Prostaglandin E1 Analog, Alprostadil, Against Hepatic Ischemia: Reperfusion Injury in Rats.

    Science.gov (United States)

    Hsieh, Cheng-Chu; Hsieh, Shu-Chen; Chiu, Jen-Hwey; Wu, Ying-Ling

    2014-01-01

    Ischemia-reperfusion (I/R) injury has a complex pathophysiology resulting from a number of contributing factors. Therefore, it is difficult to achieve effective treatment or protection by individually targeting the mediators or mechanisms. Our aim was to analyze the individual and combined effects of N-acetylcysteine (NAC) and the prostaglandin E1 (PGE1) analog alprostadil on hepatic I/R injury in rats. Thirty male Sprague-Dawley rats were randomly divided into five groups (six rats per group) as follows: Control group, I/R group, I/R + NAC group, I/R + alprostadil group, and I/R + NAC + alprostadil group. The rats received injections of NAC (150 mg/kg) and/or alprostadil (0.05 μg/kg) over a period of 30 min prior to ischemia. These rats were then subjected to 60 min of hepatic ischemia followed by a 60-min reperfusion period. Hepatic superoxide dismutase (SOD), catalase, and glutathione levels were significantly decreased as a result of I/R injury, but they were increased in groups treated with NAC. Hepatic malondialdehyde (MDA), myeloperoxidase (MPO), and nitric oxide (NO) activities were significantly increased after I/R injury, but they were decreased in the groups with NAC treatment. Alprostadil decreased NO production, but had no effect on MDA and MPO. Histological results showed that both NAC and alprostadil were effective in improving liver tissue morphology during I/R injury. Although NAC and alprostadil did not have a synergistic effect, our findings suggest that treatment with either NAC or alprostadil has benefits for ameliorating hepatic I/R injury.

  12. Protective Effects of N-acetylcysteine and a Prostaglandin E1 Analog, Alprostadil, Against Hepatic Ischemia: Reperfusion Injury in Rats

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    Cheng-Chu Hsieh

    2014-01-01

    Full Text Available Ischemia–reperfusion (I/R injury has a complex pathophysiology resulting from a number of contributing factors. Therefore, it is difficult to achieve effective treatment or protection by individually targeting the mediators or mechanisms. Our aim was to analyze the individual and combined effects of N-acetylcysteine (NAC and the prostaglandin E1 (PGE1 analog alprostadil on hepatic I/R injury in rats. Thirty male Sprague-Dawley rats were randomly divided into five groups (six rats per group as follows: Control group, I/R group, I/R+NAC group, I/R+alprostadil group, and I/R+NAC+alprostadil group. The rats received injections of NAC (150 mg/kg and/or alprostadil (0.05 μg/kg over a period of 30 min prior to ischemia. These rats were then subjected to 60 min of hepatic ischemia followed by a 60-min reperfusion period. Hepatic superoxide dismutase (SOD, catalase, and glutathione levels were significantly decreased as a result of I/R injury, but they were increased in groups treated with NAC. Hepatic malondialdehyde (MDA, myeloperoxidase (MPO, and nitric oxide (NO activities were significantly increased after I/R injury, but they were decreased in the groups with NAC treatment. Alprostadil decreased NO production, but had no effect on MDA and MPO. Histological results showed that both NAC and alprostadil were effective in improving liver tissue morphology during I/R injury. Although NAC and alprostadil did not have a synergistic effect, our findings suggest that treatment with either NAC or alprostadil has benefits for ameliorating hepatic I/R injury.

  13. Arterial morphology responds differently to Captopril then N-acetylcysteine in a monocrotaline rat model of pulmonary hypertension

    Science.gov (United States)

    Molthen, Robert; Wu, Qingping; Baumgardt, Shelley; Kohlhepp, Laura; Shingrani, Rahul; Krenz, Gary

    2010-03-01

    Pulmonary hypertension (PH) is an incurable condition inevitably resulting in death because of increased right heart workload and eventual failure. PH causes pulmonary vascular remodeling, including muscularization of the arteries, and a reduction in the typically large vascular compliance of the pulmonary circulation. We used a rat model of monocrotaline (MCT) induced PH to evaluated and compared Captopril (an angiotensin converting enzyme inhibitor with antioxidant capacity) and N-acetylcysteine (NAC, a mucolytic with a large antioxidant capacity) as possible treatments. Twenty-eight days after MCT injection, the rats were sacrificed and heart, blood, and lungs were studied to measure indices such as right ventricular hypertrophy (RVH), hematocrit, pulmonary vascular resistance (PVR), vessel morphology and biomechanics. We implemented microfocal X-ray computed tomography to image the pulmonary arterial tree at intravascular pressures of 30, 21, 12, and 6 mmHg and then used automated vessel detection and measurement algorithms to perform morphological analysis and estimate the distensibility of the arterial tree. The vessel detection and measurement algorithms quickly and effectively mapped and measured the vascular trees at each intravascular pressure. Monocrotaline treatment, and the ensuing PH, resulted in a significantly decreased arterial distensibility, increased PVR, and tended to decrease the length of the main pulmonary trunk. In rats with PH induced by monocrotaline, Captopril treatment significantly increased arterial distensibility and decrease PVR. NAC treatment did not result in an improvement, it did not significantly increase distensibility and resulted in further increase in PVR. Interestingly, NAC tended to increase peripheral vascular density. The results suggest that arterial distensibility may be more important than distal collateral pathways in maintaining PVR at normally low values.

  14. Antihypertensive mechanisms of chronic captopril (CPT) or N-Acetylcysteine (NAC) treatment in L-NAME hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Dobešová, Zdenka; Zicha, Josef; Pecháňová, Olga; Kuneš, Jaroslav

    2005-01-01

    Roč. 46, č. 4 (2005), s. 912-913 ISSN 0194-911X. [Annual Meeting of the European Council for Cardiovascular Research (ECCR) /10./. 14.10.2005-16.10.2005, La Colle sur Loup] R&D Projects: GA MZd(CZ) NR7786 Keywords : antihypertensive mechanism * captopril * N-Acetylcysteine * L-NAME hypertension Subject RIV: ED - Physiology

  15. Risk factors in the development of adverse reactions to N-acetylcysteine in patients with paracetamol poisoning

    DEFF Research Database (Denmark)

    Schmidt, L E; Dalhoff, K

    2001-01-01

    AIMS: To identify risk factors in the development of side-effects to N-acetylcysteine (NAC) in patients with paracetamol poisoning. METHODS: A retrospective study was carried out based upon the hospital charts of 529 consecutive patients admitted with paracetamol poisoning, all treated with NAC, ...

  16. Prevention of biofilm formation by dairy products and N-acetylcysteine on voice prostheses in an artificial throat

    NARCIS (Netherlands)

    Schwandt, LQ; Van Weissenbruch, R; Stokroos, [No Value; Van der Mei, HC; Busscher, HJ; Albers, FWJ

    Objective - To evaluate the preventive effect of buttermilk, Yakult Light fermented milk drink and N-acetylcysteine on biofilm formation on voice prostheses in vitro. Material and Methods - Groningen button and Provox(R) 2 voice prostheses were inoculated with a mixture of bacteria and yeasts

  17. Sepsis in the central nervous system and antioxidant strategies with N-acetylcysteine, vitamins and statins.

    Science.gov (United States)

    Steckert, Amanda Valnier; de Castro, Adalberto Alves; Quevedo, Joao; Dal-Pizzol, Felipe

    2014-02-01

    Sepsis is the complex syndrome characterized by an imbalance between proinflammatory and antiinflammatory response to infection. The brain may be affected during the sepsis, and acute and long-term brain dysfunctions have been observed in both animal models and septic patients. Oxidative stress and antioxidant systems may prove the basis underling brain dysfunction in sepsis. The antioxidant therapy may be theoretically achieved by the following strategies: restoring endogenous antioxidants and nutrients and supplementation with exogenous trace elements, vitamins, and nutrients with antioxidant proprieties; or administering drugs that reduce oxidative stress, such as N-acetylcysteine (NAC), vitamins and statins. In the review, we described below the involvement of oxidative stress and antioxidants defenses and potential utility of these strategies and present data regarding their use in sepsis.

  18. N-acetylcysteine manipulation fails to elicit an increase in glutathione in a teleost model

    DEFF Research Database (Denmark)

    Birnie-Gauvin, Kim; Larsen, Martin Hage; Aarestrup, Kim

    2018-01-01

    be synthesized from administered N-acetylcysteine (NAC). NAC has therefore often been used in a wide range of taxa to manipulate levels of GSH. Our objective was to validate this approach in a wild temperate teleost fish model, the brown trout (Salmo trutta). We used intracoelomic injections of NAC in saline...... and vegetable shortening, at two different concentrations (100 and 400 mg/kg), with the appropriate controls and shams, under controlled laboratory settings. We found that NAC failed to elicit an increase in GSH over three time periods and concluded that NAC is not an effective method to enhance GSH levels...... in teleost fish using the concentrations and vehicles tested here. We emphasize the importance of validation studies across all new species/taxa when possible and suggest that more investigation is required with regard toNAC manipulation in fish if this approach is to be used...

  19. Add-on treatment with N-acetylcysteine for bipolar depression

    DEFF Research Database (Denmark)

    Ellegaard, Pernille Kempel; Licht, Rasmus Wentzer; Poulsen, Henrik Enghusen

    2018-01-01

    BACKGROUND: Oxidative stress and inflammation may be involved in the development and progression of mood disorders, including bipolar disorder. Currently, there is a scarcity of useful treatment options for bipolar depressive episodes, especially compared with the efficacy of treatment for acute...... depressive episode. Participants will undertake a 20-week, adjunctive, randomized, double-blinded, parallel group placebo-controlled trial comparing 3 grams of adjunctive NAC daily with placebo. The primary outcome is the mean change over time from baseline to end of study on the Montgomery-Asberg Depression...... mania. N-Acetylcysteine (NAC) has been explored for psychiatric disorders for some time given its antioxidant and anti-inflammatory properties. The current trial aims at testing the clinical effects of adjunctive NAC treatment (compared to placebo) for bipolar depression. We will also explore...

  20. S-nitroso-N-acetylcysteine attenuates liver fibrosis in experimental nonalcoholic steatohepatitis

    Directory of Open Access Journals (Sweden)

    Mazo DF

    2013-06-01

    Full Text Available Daniel FC Mazo,1 Marcelo G de Oliveira,2 Isabel VA Pereira,1 Bruno Cogliati,3 José T Stefano,1 Gabriela FP de Souza,2 Fabíola Rabelo,1 Fabiana R Lima,4 Venâncio A Ferreira Alves,4 Flair J Carrilho,1 Claudia PMS de Oliveira1 1University of São Paulo School of Medicine, Department of Gastroenterology, Clinical Division, Hepatology Branch (LIM-07, Sao Paulo, Brazil; 2Institute of Chemistry, University of Campinas, Campinas, Sao Paulo, Brazil; 3University of Sao Paulo School of Veterinary Medicine and Animal Science, Department of Pathology, Sao Paulo, Brazil; 4University of São Paulo School of Medicine, Department of Pathology (LIM14, São Paulo, Brazil Abstract: S-Nitroso-N-acetylcysteine (SNAC is a water soluble primary S-nitrosothiol capable of transferring and releasing nitric oxide and inducing several biochemical activities, including modulation of hepatic stellate cell activation. In this study, we evaluated the antifibrotic activity of SNAC in an animal model of nonalcoholic steatohepatitis (NASH induced in Sprague-Dawley rats fed with a choline-deficient, high trans fat diet and exposed to diethylnitrosamine for 8 weeks. The rats were divided into three groups: SNAC, which received oral SNAC solution daily; NASH, which received the vehicle; and control, which received standard diet and vehicle. Genes related to fibrosis (matrix metalloproteinases [MMP]-13, -9, and -2, transforming growth factor ß-1 [TGFß-1], collagen-1a, and tissue inhibitors of metalloproteinase [TIMP-1 and -2] and oxidative stress (heat-shock proteins [HSP]-60 and -90 were evaluated. SNAC led to a 34.4% reduction in the collagen occupied area associated with upregulation of MMP-13 and -9 and downregulation of HSP-60, TIMP-2, TGFß-1, and collagen-1α. These results indicate that oral SNAC administration may represent a potential antifibrotic treatment for NASH. Keywords: nitric oxide, S-nitroso-N-acetylcysteine, fibrogenesis, NASH, diethylnitrosamine

  1. Synergistic protective effect of N-acetylcysteine and taurine against cisplatin-induced nephrotoxicity in rats

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    Abdel-Wahab WM

    2017-03-01

    Full Text Available Wessam M Abdel-Wahab,1,2 Farouzia I Moussa,2 Najwa A Saad3 1Department of Biology, College of Medicine, University of Dammam, Dammam, Saudi Arabia; 2Department of Zoology, Faculty of Science, University of Alexandria, Alexandria, Egypt; 3Department of Zoology, Faculty of Science, University of Benghazi, Benghazi, Libya Abstract: Cisplatin (cis-diaminedichloroplatinum II; CDDP is an effective anticancer drug, but it has limitations because of its nephrotoxicity. This study investigates the protective effect of N-acetylcysteine (NAC and taurine (TAU, both individually and in combination, against CDDP nephrotoxicity in rats. For this purpose, 48 male rats were assigned into eight groups (n=6 as follows: 1 control group, 2 NAC group, 3 TAU group, 4 NAC–TAU group, 5 CDDP group, 6 CDDP–NAC group, 7 CDDP–TAU group, and 8 CDDP–NAC–TAU group. Cisplatin was administered as a single intraperitoneal injection at a concentration of 6 mg/kg. Three days after CDDP administration, NAC (50 mg/kg and/or TAU (50 mg/kg were administered three times weekly for four consecutive weeks. Kidney function markers in serum, urinary glucose and protein, as well as oxidant and antioxidant parameters in renal tissue were assessed. Administration of CDDP significantly elevated urinary glucose and protein, as well as serum creatinine, urea, and uric acid. Moreover, CDDP enhanced lipid peroxidation and suppressed the major enzymatic antioxidants in the kidney tissue. Treatment with NAC or TAU protected against the alterations in the serum, urine, and renal tissue when used individually along with CDDP. Furthermore, a combined therapy of both was more effective in ameliorating CDDP-induced nephrotoxicity, which points out to their synergistic effect. Keywords: cisplatin, nephrotoxicity, oxidative stress, N-acetylcysteine, taurine

  2. OralN-acetylcysteine and exercise tolerance in mild chronic obstructive pulmonary disease.

    Science.gov (United States)

    Hirai, Daniel M; Jones, Joshua H; Zelt, Joel T; da Silva, Marianne L; Bentley, Robert F; Edgett, Brittany A; Gurd, Brendon J; Tschakovsky, Michael E; O'Donnell, Denis E; Neder, J Alberto

    2017-05-01

    Heightened oxidative stress is implicated in the progressive impairment of skeletal muscle vascular and mitochondrial function in chronic obstructive pulmonary disease (COPD). Whether accumulation of reactive oxygen species contributes to exercise intolerance in the early stages of COPD is unknown. The purpose of the present study was to determine the effects of oral antioxidant treatment with N -acetylcysteine (NAC) on respiratory, cardiovascular, and locomotor muscle function and exercise tolerance in patients with mild COPD. Thirteen patients [forced expiratory volume in 1 s (FEV 1 )-to-forced vital capacity ratio exercise tests were performed with noninvasive measurements of central hemodynamics (stroke volume, heart rate, and cardiac output via impedance cardiography), arterial blood pressure, pulmonary ventilation and gas exchange, quadriceps muscle oxygenation (near-infrared spectroscopy), and estimated capillary blood flow. Nine patients completed the study with no major adverse clinical effects. Although NAC elevated plasma glutathione by ~27% compared with placebo ( P exercise tolerance (placebo: 325 ± 47 s, NAC: 336 ± 51 s), central hemodynamics, arterial blood pressure, pulmonary ventilation or gas exchange, locomotor muscle oxygenation, or capillary blood flow from rest to exercise between conditions ( P > 0.05 for all). In conclusion, modulation of plasma redox status with oral NAC treatment was not translated into beneficial effects on central or peripheral components of the oxygen transport pathway, thereby failing to improve exercise tolerance in nonhypoxemic patients with mild COPD. NEW & NOTEWORTHY Acute antioxidant treatment with N -acetylcysteine (NAC) elevated plasma glutathione but did not modulate central or peripheral components of the O 2 transport pathway, thereby failing to improve exercise tolerance in patients with mild chronic obstructive pulmonary disease (COPD). Copyright © 2017 the American Physiological Society.

  3. Ceftriaxone- and N-acetylcysteine-induced brain tolerance to ischemia: Influence on glutamate levels in focal cerebral ischemia.

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    Weronika Krzyżanowska

    Full Text Available One of the major players in the pathophysiology of cerebral ischemia is disrupted homeostasis of glutamatergic neurotransmission, resulting in elevated extracellular glutamate (Glu concentrations and excitotoxicity-related cell death. In the brain, Glu concentrations are regulated by Glu transporters, including Glu transporter-1 (GLT-1 and cystine/Glu antiporter (system xc-. Modulation of these transporters by administration of ceftriaxone (CEF, 200 mg/kg, i.p. or N-acetylcysteine (NAC, 150 mg/kg, i.p. for 5 days before focal cerebral ischemia may induce brain tolerance to ischemia by significantly limiting stroke-related damage and normalizing Glu concentrations. In the present study, focal cerebral ischemia was induced by 90-minute middle cerebral artery occlusion (MCAO. We compared the effects of CEF and NAC pretreatment on Glu concentrations in extracellular fluid and cellular-specific expression of GLT-1 and xCT with the effects of two reference preconditioning methods, namely, ischemic preconditioning and chemical preconditioning in rats. Both CEF and NAC significantly reduced Glu levels in the frontal cortex and hippocampus during focal cerebral ischemia, and this decrease was comparable with the Glu level achieved with the reference preconditioning strategies. The results of immunofluorescence staining of GLT-1 and xCT on astrocytes, neurons and microglia accounted for the observed changes in extracellular Glu levels to a certain extent. Briefly, after MCAO, the expression of GLT-1 on astrocytes decreased, but pretreatment with CEF seemed to prevent this downregulation. In addition, every intervention used in this study seemed to reduce xCT expression on astrocytes and neurons. The results of this study indicate that modulation of Glu transporter expression may restore Glu homeostasis. Moreover, our results suggest that CEF and NAC may induce brain tolerance to ischemia by influencing GLT-1 and system xc- expression levels. These

  4. N-acetylcysteine does not prevent contrast nephropathy in patients with renal impairment undergoing emergency CT: a randomized study.

    Science.gov (United States)

    Poletti, Pierre-Alexandre; Platon, Alexandra; De Seigneux, Sophie; Dupuis-Lozeron, Elise; Sarasin, François; Becker, Christoph D; Perneger, Thomas; Saudan, Patrick; Martin, Pierre-Yves

    2013-06-03

    Patients admitted to the emergency room with renal impairment and undergoing a contrast computed tomography (CT) are at high risk of developing contrast nephropathy as emergency precludes sufficient hydration prior to contrast use. The value of an ultra-high dose of intravenous N-acetylcysteine in this setting is unknown. From 2008 to 2010, we randomized 120 consecutive patients admitted to the emergency room with an estimated clearance lower than 60 ml/min/1.73 m2 by MDRD (mean GFR 42 ml/min/1.73 m2) to either placebo or 6000 mg N-acetylcysteine iv one hour before contrast CT in addition to iv saline. Serum cystatin C and creatinine were measured one hour prior to and at day 2, 4 and 10 after contrast injection. Nephrotoxicity was defined either as 25% or 44 μmol/l increase in serum creatinine or cystatin C levels compared to baseline values. Contrast nephrotoxicity occurred in 22% of patients who received placebo (13/58) and 27% of patients who received N-acetylcysteine (14/52, p = 0.66). Ultra-high dose intravenous N-acetylcysteine did not alter creatinine or cystatin C levels. No secondary effects were noted within the 2 groups during follow-up. An ultra-high dose of intravenous N-acetylcysteine is ineffective at preventing nephrotoxicity in patients with renal impairment undergoing emergency contrast CT. The study was registered as Clinical trial (NCT01467154).

  5. Protective effects of N-acetylcysteine on aluminum phosphide-induced oxidative stress in acute human poisoning.

    Science.gov (United States)

    Tehrani, Hiva; Halvaie, Zahra; Shadnia, Shahin; Soltaninejad, Kambiz; Abdollahi, Mohammad

    2013-01-01

    Aluminum phosphide is used as a fumigant. It produces phosphine gas (PH₃). PH₃ is a mitochondrial poison which inhibits cytochrome c oxidase, it leads to generation of reactive oxygen species; so one of the most important suggested mechanisms for its toxicity is induction of oxidative stress. In this regard, it could be proposed that a drug like N-acetylcysteine (NAC) as an antioxidant would improve the tolerance of aluminum phosphide-intoxicated cases. The objective of this study was to evaluate the protective effects of NAC on acute aluminum phosphide poisoning. This was a prospective, randomized, controlled open-label trial. All patients received the same supportive treatments. NAC treatment group also received NAC. The blood thiobarbituric acid reactive substances as a marker of lipid peroxidation and total antioxidant capacity of plasma were analyzed. Mean ingested dose of aluminum phosphide in NAC treatment and control groups was 4.8 ± 0.9 g vs. 5.4 ± 3.3 g, respectively (p = 0.41). Significant increase in plasma malonyldialdehyde level in control group was observed (139 ± 28.2 vs. 149.6 ± 35.2 μmol/L, p = 0.02). NAC infusion in NAC treatment group significantly decreased malondialdehyde level (195.7 ± 67.4 vs. 174.6 ± 48.9 μmol/L, p = 0.03), duration of hospitalization (2.7 ± 1.8 days vs. 8.5 ± 8.2 days, p = 0.02), rate of intubation and ventilation (45.4% vs. 73.3%, p = 0.04). Mortality rate in NAC treatment and control groups were 36% and 60%, respectively with odds ratio 2.6 (0.7-10.1, 95% CI). NAC may have a therapeutic effect in acute aluminum phosphide poisoning.

  6. Effects of post-resuscitation treatment with N-acetylcysteine on cardiac recovery in hypoxic newborn piglets.

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    Jiang-Qin Liu

    Full Text Available AIMS: Although N-acetylcysteine (NAC can decrease reactive oxygen species and improve myocardial recovery after ischemia/hypoxia in various acute animal models, little is known regarding its long-term effect in neonatal subjects. We investigated whether NAC provides prolonged protective effect on hemodynamics and oxidative stress using a surviving swine model of neonatal asphyxia. METHODS AND RESULTS: Newborn piglets were anesthetized and acutely instrumented for measurement of systemic hemodynamics and oxygen transport. Animals were block-randomized into a sham-operated group (without hypoxia-reoxygenation [H-R, n = 6] and two H-R groups (2 h normocapnic alveolar hypoxia followed by 48 h reoxygenation, n = 8/group. All piglets were acidotic and in cardiogenic shock after hypoxia. At 5 min after reoxygenation, piglets were given either saline or NAC (intravenous 150 mg/kg bolus + 20 mg/kg/h infusion via for 24 h in a blinded, randomized fashion. Both cardiac index and stroke volume of H-R controls remained lower than the pre-hypoxic values throughout recovery. Treating the piglets with NAC significantly improved cardiac index, stroke volume and systemic oxygen delivery to levels not different from those of sham-operated piglets. Accompanied with the hemodynamic improvement, NAC-treated piglets had significantly lower plasma cardiac troponin-I, myocardial lipid hydroperoxides, activated caspase-3 and lactate levels (vs. H-R controls. The change in cardiac index after H-R correlated with myocardial lipid hydroperoxides, caspase-3 and lactate levels (all p<0.05. CONCLUSIONS: Post-resuscitation administration of NAC reduces myocardial oxidative stress and caused a prolonged improvement in cardiac function and in newborn piglets with H-R insults.

  7. In search of better spermatogonial preservation by supplementation of cryopreserved human immature testicular tissue xenografts with N-acetylcysteine and testosterone

    Directory of Open Access Journals (Sweden)

    Jonathan ePoels

    2014-12-01

    Full Text Available Controlled slow-freezing is the procedure currently applied for immature testicular tissue cryobanking in clinical practice. Vitrification has been proposed as a promising alternative, with a view to better preserving spermatogonial stem cells for future fertility restoration by autografting in young boys suffering from cancer. It appears that besides the potential influence of the cryopreservation technique used, the transplantation procedure itself has a significant impact on spermatogonial loss observed in ITT xenografts. Eighteen immature testicular tissue pieces issuing from 6 patients aged 2-15 years were used. Fragments of fresh tissue (serving as ungrafted controls, frozen-thawed tissue, frozen-thawed tissue supplemented with N-acetylcysteine and frozen-thawed tissue supplemented with testosterone xenografted to nude mice for 5 days were compared. Upon graft removal, histological and immunohistochemical analyses were performed to evaluate spermatogonia, intratubular proliferation and intrinsic and extrinsic apoptosis. A significant decrease in the integrity of intact seminiferous tubules was found in all three grafted groups. Spermatogonia were observed by immunohistochemistry in all grafted groups, with recovery rates of 67%, 63% and 53% respectively for slow-frozen tissue, slow-frozen tissue supplemented with N-acetylcysteine and slow-frozen tissue supplemented with testosterone. Apoptosis evidenced by active caspase-3 and TUNEL was similar in all grafts. The study is limited by the low availability of immature testicular tissue samples of human origin, and no clear impact of graft supplementation was found. The mouse xenotransplantation model needs to be refined to investigate human spermatogenesis in human immature testicular tissue grafts.

  8. Use of N-acetylcysteine plus simethicone to improve mucosal visibility during upper GI endoscopy: a double-blind, randomized controlled trial.

    Science.gov (United States)

    Monrroy, Hugo; Vargas, Jose Ignacio; Glasinovic, Esteban; Candia, Roberto; Azúa, Emilio; Gálvez, Camila; Rojas, Camila; Cabrera, Natalia; Vidaurre, Josefa; Álvarez, Natalia; González, Jessica; Espino, Alberto; González, Robinson; Parra-Blanco, Adolfo

    2018-04-01

    Upper GI endoscopy (UGE) is essential for the diagnosis of gastrointestinal diseases. Mucus and bubbles may decrease mucosal visibility. The use of mucolytics could improve visualization. Our aim was to determine whether premedication with simethicone or simethicone plus N-acetylcysteine is effective in improving visibility during UGE. This was a randomized, double-blinded, placebo-controlled trial with 2 control groups: no intervention and water 100 mL (W); and 3 intervention groups: simethicone 200 mg (S); S + N-acetylcysteine (NAC) 500 mg (S+NAC500); and S + NAC 1000 mg (S+NAC1000). The solution was ingested 20 minutes before UGE. Gastric visibility was evaluated in 4 segments with a previously described scale. A score of less than 7 points was defined as adequate visibility (AV). Water volume was used to improve visibility, and adverse reactions were evaluated as a secondary outcome. Multiple group comparison was performed using non-parametric one-way analysis of variance (ANOVA). Two hundred thirty patients were included in the study, 68% female, mean age 49 years. The most common indication for UGE was epigastric pain/dyspepsia (33%). AV was more frequent in the S+NAC500 and S+NAC1000 groups (65% and 67%) compared with no intervention (44%, P = .044) and water (41%, P = .022). The gastric total visibility scale (TVS) was significantly better in the S+NAC500 and S+NAC1000 groups compared with water (P = .03 and P = .008). Simethicone was not different from no intervention and water. S+NAC1000 required less water volume to improve visibility. No adverse reactions from the study drugs were observed. Premedication with S+NAC500 and S+NAC1000 improves visibility during UGE. The use of simethicone did not show improvements in gastric visibility. TVS was worse in patients using water alone. (Clinical trial registration number: NCT 01653171.). Copyright © 2018 American Society for Gastrointestinal Endoscopy. All rights reserved.

  9. Safety and pharmacokinetic studies of liposomal antioxidant formulations containing N-acetylcysteine, α-tocopherol or γ-tocopherol in beagle dogs.

    Science.gov (United States)

    Alipour, Misagh; Mitsopoulos, Panagiotis; Smith, Milton G; Bolger, Gordon; Pucaj, Kresimir; Suntres, Zacharias E

    2013-07-01

    The safety and pharmacokinetic profile of liposomal formulations containing combinations of the antioxidants α-tocopherol, γ-tocopherol or N-acetylcysteine in beagle dogs was examined. Each group consisted of beagle dogs of both genders with a control group receiving empty dipalmitoylphosphatidylcholine (DPPC) liposomes (330 mg/kg DPPC, EL), and test groups receiving liposomes prepared from DPPC lipids with (i) N-acetylcysteine (NAC) (60 mg/kg NAC [L-NAC]); (ii) NAC and α-tocopherol (αT) (60 mg/kg NAC and 25 mg/kg α-tocopherol [L-αT-NAC]) and (iii) NAC and γ-tocopherol (60 mg/kg NAC and 25 mg/kg γ-tocopherol (γT) [L-γT-NAC]). The dogs in the control group (EL) and three test groups exhibited no signs of toxicity during the dosing period or day 15 post treatment. Weight gain, feed consumption and clinical pathology findings (hematology, coagulation, clinical chemistry, urinalysis) were unremarkable in all dogs and in all groups. Results from the pharmacokinetic study revealed that the inclusion of tocopherols in the liposomal formulation significantly increased the area under the curve (AUC) and β-half life for NAC; the tocopherols had greater impact on the clearance of NAC, where reductions of central compartment clearance (CL) ranged from 56% to 60% and reductions of tissue clearance (CL2) ranged from 73% to 77%. In conclusion, there was no treatment-related toxicity in dogs at the maximum feasible dose level by a single bolus intravenous administration while the addition of tocopherols to the liposomal formulation prolonged the circulation of NAC in plasma largely due to a decreased clearance of NAC.

  10. Investigation of antioxidant defense mechanisms of Citrullus Colocynthis fruits and N-acetylcysteine in the diabetes mellitus model on rats

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    H. R. Lamazian

    2016-10-01

    Full Text Available The aim of study: to investigate the presence and mechanisms of antioxidant activity in dry extract of Citrullus Colocynthis fruits and N-acetylcysteine. Materials and methods. MDA, SOD, catalase, glutathione were studied in liver homogenate of streptozotocin-induced diabetic rats (group "model", groups X1 and X2 - rats with diabetes who were given a plant extract per os at a dose of 200 mg / kg and 400 mg / kg respectively, X3 - rats with diabetes who were given NAC per os at a dose of1.5 g / kg and healthy rats (group "Control". Fatty acid composition of erythrocyte and heart homogenate was determined by a gas chromatography. Results. In "Model" the growth of MDA, reduction of SOD and catalase were observed. In X1 and X2 groups MDA concentration and SOD activity decreased in relative to "Model" and "Control" and catalase activity, on the contrary, increased reaching the level of "Control" and even higher (X2. Glutathione concentration also decreased and this negative effect was increasing with increasing of plant extract dose. NAC caused a decrease of MDA in relative to "Model", normalized levels of SOD and catalase and effectively increased the concentration of glutathione compared with "Model". 9 fatty acids (FA, 4 of which belong to the unsaturated one (oleic, linoleic, linolenic, arachidonic and 5 - to saturated one (myristic, pentadecanoic, palmitic, margarine (heptadecanoic, stearic were identified in heart homogenate and erythrocytes of rats. The plant extract significantly changes the ratio of fatty acids in the myocardium (increases the level of stearic and linoleic FA and decreases the level of pentadecanoic and arachidonic FA and in erythrocytes (decreases the level of linoleic and linolenic FA and increases the level of saturated FA, practically without disturbing the balance between saturated and unsaturated FA. The quantitative composition of saturated FA doesn’t change statistically in the group X3 in relative to "Control

  11. Protective effects of N-acetylcysteine against cadmium-induced damage in cultured rat normal liver cells.

    Science.gov (United States)

    Odewumi, Caroline O; Badisa, Veera L D; Le, Uyen T; Latinwo, Lekan M; Ikediobi, Christopher O; Badisa, Ramesh B; Darling-Reed, Selina F

    2011-02-01

    In this study, the protective effects of N-acetylcysteine (NAC), a precursor of reduced glutathione, were studied by measuring the viability, the levels of antioxidant enzymes, and by analyzing the cell cycle in cadmium (Cd)-treated rat liver cells. The cells were treated with 150 µM CdCl2 alone or co-treated with 150 µM CdCl2 and 5 mM NAC (2 h pre-, simultaneous or 2 h post-treatment) for 24 h. The viability of the cells treated with 150 µM CdCl2 alone decreased to 40.1%, while that of the cells co-treated with 5 mM NAC (pre-, simultaneous and post-treatment) significantly increased to 83.7, 86.2 and 83.7%, respectively in comparison to the control cells (100%). The catalase enzyme level decreased to undetectable level in the cells treated with CdCl2 alone, while it significantly increased in the co-treated cells (pre-, simultaneous and post-treatment) to 40.1, 34.3 and 13.2%, respectively. In the cells treated with CdCl2 alone, the glutathione peroxidase enzyme level decreased to 78.3%, while it increased in the co-treated cells (pre-, simultaneous, and post-treatment) to 84.5, 83.3 and 87.9%, respectively. The glutathione reductase enzyme level decreased to 56.1% in the cells treated with cadmium alone, but significantly increased in the cells co treated with NAC (pre-, simultaneous and post-treatment) to 79.5, 78.5 and 78.2%, respectively. Cd caused cell cycle arrest at the S and G2/M phases. The co-treatment with NAC inhibited cell cycle arrest by shifting the cells to the G1 phase. These results clearly show the protective effects of NAC against Cd-induced damage in rat liver cells.

  12. N-acetylcysteine for prevention of acute renal failure in patients with chronic renal insufficiency undergoing cardiac surgery: a prospective, randomized, clinical trial.

    Science.gov (United States)

    Sisillo, Erminio; Ceriani, Roberto; Bortone, Franco; Juliano, Glauco; Salvi, Luca; Veglia, Fabrizio; Fiorentini, Cesare; Marenzi, Giancarlo

    2008-01-01

    To assess the preventive effect of the antioxidant N-acetylcysteine on postoperative acute renal failure in patients with renal insufficiency undergoing cardiac surgery. Randomized, placebo-controlled, prospective study. University cardiology center. Two hundred fifty-four consecutive patients with chronic renal insufficiency (estimated creatinine clearance acute renal failure (> 25% increase in serum creatinine from baseline) and the in-hospital clinical course were evaluated. Acute renal failure occurred in 46% of patients and was associated with increased in-hospital mortality (7% vs. 0.7%; p = .024). It occurred in 52% of control patients and 40% of N-acetylcysteine-treated patients (p = .06). In-hospital mortality and need for renal replacement therapy were not affected by N-acetylcysteine, but a lower percentage of N-acetylcysteine-treated patients required mechanical ventilation prolonged for > 48 hrs (3% vs. 18%; p 4 days (13% vs. 33%; p acute renal failure in patients with renal insufficiency undergoing cardiac surgery.

  13. N-acetylcysteine prevents the development of gastritis induced by Helicobacter pylori infection.

    Science.gov (United States)

    Jang, Sungil; Bak, Eun-Jung; Cha, Jeong-Heon

    2017-05-01

    Helicobacter pylori (H. pylori) is a human gastric pathogen, causing various gastric diseases ranging from gastritis to gastric adenocarcinoma. It has been reported that combining N-acetylcysteine (NAC) with conventional antibiotic therapy increases the success rate of H. pylori eradication. We evaluated the effect of NAC itself on the growth and colonization of H. pylori, and development of gastritis, using in vitro liquid culture system and in vivo animal models. H. pylori growth was evaluated in broth culture containing NAC. The H. pylori load and histopathological scores of stomachs were measured in Mongolian gerbils infected with H. pylori strain 7.13, and fed with NAC-containing diet. In liquid culture, NAC inhibited H. pylori growth in a concentration-dependent manner. In the animal model, 3-day administration of NAC after 1 week from infection reduced the H. pylori load; 6-week administration of NAC after 1 week from infection prevented the development of gastritis and reduced H. pylori colonization. However, no reduction in the bacterial load or degree of gastritis was observed with a 6-week administration of NAC following 6-week infection period. Our results indicate that NAC may exert a beneficial effect on reduction of bacterial colonization, and prevents the development of severe inflammation, in people with initial asymptomatic or mild H. pylori infection.

  14. Current evidence for the use of N-acetylcysteine following liver resection.

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    Kemp, Richard; Mole, Jonathan; Gomez, Dhanny

    2017-11-13

    N-acetylcysteine (NAC) has many uses in medicine; notable in the management of paracetamol toxicity, acute liver failure and liver surgery. The aim of this review was to critically appraise the published literature for the routine use of NAC in liver resection surgery. An electronic search was performed of EBSCOhost (Medline and CINAHL database), PubMed and the Cochrane Library for the period 1990-2016. MeSH headings: 'acetyl-cysteine', 'liver resection' and 'hepatectomy' were used to identify all relevant articles published in English. Following the search criteria used, three articles were included. Two of these studies were randomized controlled trials. All the studies collated data on morbidity and mortality. All three studies did not show a significant difference in overall complications rates in patients that underwent hepatic resection that had NAC infusion compared with patients that did not. In one study, NAC administration was associated with a higher frequency of grade A post-hepatectomy liver failure. In another study, a significantly higher incidence of delirium was observed in the NAC group, which led to the trial to be terminated early. The current published data do not support the routine use of NAC following liver resection. © 2017 Royal Australasian College of Surgeons.

  15. Systematic review of N-acetylcysteine in the treatment of addictions

    Directory of Open Access Journals (Sweden)

    Elson Asevedo

    2014-05-01

    Full Text Available Objective: To conduct the first systematic literature review of clinical trials of N-acetylcysteine (NAC for the treatment of substance abuse disorders and addictive behaviors. Methods: A search of the MEDLINE, Embase and PsycINFO databases was conducted. The inclusion criteria for the review were clinical trials that used NAC in the treatment of a disorder related to substance use and/or addictive behaviors, limited to texts in English, Spanish, or French. The selected studies were evaluated with respect to type of trial, sample size, diagnostic input, intervention, length of follow-up, outcome variables, and results. Results: Nine studies analyzing a total of 165 patients met the eligibility criteria and were included in qualitative analysis. These studies evaluated the role of NAC in cocaine dependence (three studies, cannabis dependence (two studies, nicotine dependence (two studies, methamphetamine addiction (one study, and pathological gambling (one study. Five of these trials were double-blind, randomized, and placebo-controlled. Conclusions: The studies analyzed suggest a potential role for NAC in the treatment of addiction, especially of cocaine and cannabis dependence. These results are concordant with the hypothesis of the involvement of glutamatergic pathways in the pathophysiology of addiction.

  16. N-Acetylcysteine in the treatment of trichotillomania: remarkable results in two patients.

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    Özcan, D; Seçkin, D

    2016-09-01

    The management of trichotillomania is challenging. The limited efficacy and side-effects of pharmacological medications and difficulty in long-term maintenance of behavioural therapies necessitates alternative treatment options. A dysregulated glutamatergic system has been implicated in the pathophysiology of trichotillomania. A limited number of reports indicate that N-acetylcysteine (NAC), a glutamate modulator, may be a promising treatment for this disorder. We report two patients with trichotillomania for whom treatment with NAC was successful. The first patient was a 30-year-old female, and the second patient was a 14-year-old girl, both who were diagnosed with trichotillomania and prescribed NAC (1200 mg/d, p.o.). Hair pulling behaviour subsided within 2 months and 2 weeks of initiating NAC in the first and second patient, respectively. Complete hair regrowth was observed after 4 and 6 months of NAC treatment in the first and second patient, respectively. No side-effects related to NAC were noted. NAC could be a well-tolerated and effective treatment option for trichotillomania. © 2016 European Academy of Dermatology and Venereology.

  17. Synergistic protective effect ofN-acetylcysteine and taurine against cisplatin-induced nephrotoxicity in rats.

    Science.gov (United States)

    Abdel-Wahab, Wessam M; Moussa, Farouzia I; Saad, Najwa A

    2017-01-01

    Cisplatin (cis-diaminedichloroplatinum II; CDDP) is an effective anticancer drug, but it has limitations because of its nephrotoxicity. This study investigates the protective effect of N -acetylcysteine (NAC) and taurine (TAU), both individually and in combination, against CDDP nephrotoxicity in rats. For this purpose, 48 male rats were assigned into eight groups (n=6) as follows: 1) control group, 2) NAC group, 3) TAU group, 4) NAC-TAU group, 5) CDDP group, 6) CDDP-NAC group, 7) CDDP-TAU group, and 8) CDDP-NAC-TAU group. Cisplatin was administered as a single intraperitoneal injection at a concentration of 6 mg/kg. Three days after CDDP administration, NAC (50 mg/kg) and/or TAU (50 mg/kg) were administered three times weekly for four consecutive weeks. Kidney function markers in serum, urinary glucose and protein, as well as oxidant and antioxidant parameters in renal tissue were assessed. Administration of CDDP significantly elevated urinary glucose and protein, as well as serum creatinine, urea, and uric acid. Moreover, CDDP enhanced lipid peroxidation and suppressed the major enzymatic antioxidants in the kidney tissue. Treatment with NAC or TAU protected against the alterations in the serum, urine, and renal tissue when used individually along with CDDP. Furthermore, a combined therapy of both was more effective in ameliorating CDDP-induced nephrotoxicity, which points out to their synergistic effect.

  18. N-acetylcysteine in the treatment of psychiatric disorders: current status and future prospects.

    Science.gov (United States)

    Minarini, Alessandro; Ferrari, Silvia; Galletti, Martina; Giambalvo, Nina; Perrone, Daniela; Rioli, Giulia; Galeazzi, Gian Maria

    2017-03-01

    N-acetylcysteine (NAC) is widely known for its role as a mucolytic and as an antidote to paracetamol overdose. There is increasing interest in the use of NAC in the treatment of several psychiatric disorders. The rationale for the administration of NAC in psychiatric conditions is based on its role as a precursor to the antioxidant glutathione, and its action as a modulating agent of glutamatergic, dopaminergic, neurotropic and inflammatory pathways. Areas covered: This study reviews the available data regarding the use of NAC in different psychiatric disorders including substance use disorders, autism, obsessive-compulsive spectrum disorders, schizophrenia, depression, bipolar disorder. Promising results were found in trials testing the use of NAC, mainly as an add-on treatment, in cannabis use disorder in young people, depression in bipolar disorder, negative symptoms in schizophrenia, and excoriation (skin-picking) disorder. Despite initial optimism, recent findings regarding NAC efficacy in autism have been disappointing. Expert opinion: These preliminary positive results require further confirmation in larger samples and with longer follow-ups. Given its high tolerability and wide availability, NAC represents an important target to investigate in the field of new adjunctive treatments for psychiatric conditions.

  19. Mechanisms of Antioxidant Induction with High-Dose N-Acetylcysteine in Childhood Cerebral Adrenoleukodystrophy.

    Science.gov (United States)

    Kartha, Reena V; Zhou, Jie; Basso, Lisa; Schröder, Henning; Orchard, Paul J; Cloyd, James

    2015-12-01

    Childhood cerebral adrenoleukodystrophy (CCALD), a progressive demyelinating disease affecting school-aged boys, causes death within a few years. Oxidative stress is an important contributing factor. N-acetylcysteine (NAC; 280 mg/kg/day) added as adjunctive therapy to reduced-intensity hematopoietic cell transplantation (HCT) improves survival in advanced cases. However, the mechanisms underlying the benefits of NAC are unclear. The aim of this study was to understand the mechanism of action of NAC in the setting of HCT in CCALD. Immunoassays were carried out to determine changes in heme oxygenase-1 (HO-1) and ferritin expression in plasma samples collected from boys with CCALD at three different timepoints during the course of transplantation. In addition, the induction of HO-1 was also confirmed in normal fibroblasts following incubation with 10-100 µmol/L NAC for 4 h. Following NAC therapy we observed an increase in expression of the antioxidants HO-1 (~4-fold) and its effector ferritin (~160-fold) in patient samples as compared with baseline. We also observed that NAC exposure significantly increased HO-1 expression in fibroblasts. Our data suggest that HO-1 is a possible target protein of NAC and a mediator of its cytoprotective effects in these patients.

  20. N-acetylcysteine advancement of surfactant therapy in experimental meconium aspiration syndrome: possible mechanisms.

    Science.gov (United States)

    Kopincová, J; Mokrá, D; Mikolka, P; Kolomazník, M; Čalkovská, A

    2014-01-01

    Meconium aspiration syndrome (MAS) is meconium-induced respiratory failure of newborns associated with activation of inflammatory and oxidative pathways. For severe MAS, exogenous surfactant treatment is used which improves respiratory functions but does not treat the inflammation. Oxidative process can lead to later surfactant inactivation; hence, surfactant combination with antioxidative agent may enhance the therapeutic effect. Young New Zealand rabbits were instilled by meconium suspension and treated by surfactant alone, N-acetylcysteine (NAC) alone or by their combination and oxygen-ventilated for 5 h. Blood samples were taken before and 30 min after meconium application and 30 min, 1, 3 and 5 h after the treatment for evaluating of oxidative damage, total leukocyte count, leukocyte differential count and respiratory parameters. Leukocyte differential was assessed also in bronchoalveolar lavage fluid. NAC alone had only mild therapeutic effect on MAS. However, the combination of NAC and surfactant facilitated rapid onset of therapeutic effect in respiratory parameters (oxygenation index, PaO(2)/FiO(2)) compared to surfactant alone and was the only treatment which prevented neutrophil migration into the lungs, oxidative damage and lung edema. Moreover, NAC suppressed IL-8 and IL-beta formation and thus seems to be favorable agent for improving surfactant therapy in MAS.

  1. Targeting oncogenic interleukin-7 receptor signalling with N-acetylcysteine in T cell acute lymphoblastic leukaemia.

    Science.gov (United States)

    Mansour, Marc R; Reed, Casie; Eisenberg, Amy R; Tseng, Jen-Chieh; Twizere, Jean-Claude; Daakour, Sarah; Yoda, Akinori; Rodig, Scott J; Tal, Noa; Shochat, Chen; Berezovskaya, Alla; DeAngelo, Daniel J; Sallan, Stephen E; Weinstock, David M; Izraeli, Shai; Kung, Andrew L; Kentsis, Alex; Look, A Thomas

    2015-01-01

    Activating mutations of the interleukin-7 receptor (IL7R) occur in approximately 10% of patients with T cell acute lymphoblastic leukaemia (T-ALL). Most mutations generate a cysteine at the transmembrane domain leading to receptor homodimerization through disulfide bond formation and ligand-independent activation of STAT5. We hypothesized that the reducing agent N-acetylcysteine (NAC), a well-tolerated drug used widely in clinical practice to treat acetaminophen overdose, would reduce disulfide bond formation, and inhibit mutant IL7R-mediated oncogenic signalling. We found that treatment with NAC disrupted IL7R homodimerization in IL7R-mutant DND-41 cells as assessed by non-reducing Western blot, as well as in a luciferase complementation assay. NAC led to STAT5 dephosphorylation and cell apoptosis at clinically achievable concentrations in DND-41 cells, and Ba/F3 cells transformed by an IL7R-mutant construct containing a cysteine insertion. The apoptotic effects of NAC could be rescued in part by a constitutively active allele of STAT5. Despite using doses lower than those tolerated in humans, NAC treatment significantly inhibited the progression of human DND-41 cells engrafted in immunodeficient mice. Thus, targeting leukaemogenic IL7R homodimerization with NAC offers a potentially effective and feasible therapeutic strategy that warrants testing in patients with T-ALL. © 2014 John Wiley & Sons Ltd.

  2. Evaluation of N-acetylcysteine treatment in acute pancreatitis-induced lung injury.

    Science.gov (United States)

    Yubero, Sara; Ramudo, Laura; Manso, Manuel A; Collía, Francisco; De Dios, Isabel

    2012-07-01

    Pulmonary complications are frequent during acute pancreatitis (AP). We investigate the effects of N-acetylcysteine (NAC) on lung injury in mild and severe AP. ANIMALS AND TREATMENT: Mild and severe AP was induced in rats by bile-pancreatic duct obstruction (BPDO) and infusion of 3.5 % sodium taurocholate (NaTc) into the bile-pancreatic duct, respectively. NAC (50 mg/kg) was given 1 h before and 1 h after AP. Amylase activity was measured in plasma. Lungs were harvested for mRNA expression analysis of monocyte chemoattractant protein-1 (MCP-1), cytokine-induced neutrophil chemoattractant (CINC), P-selectin and intercellular adhesion molecule-1 (ICAM-1), myeloperoxidase (MPO) activity and histological examination. Hyperamylasemia was reduced by NAC in both AP models. NAC down-regulated MCP-1, CINC and P-selectin in BPDO- but not in NaTc-induced AP. Pulmonary insults did not vary in mild AP and were exacerbated in severe AP by NAC treatment. NAC reduced lung MPO activity in mild but not in severe AP. Although NAC treatment down-regulated inflammatory mediators in lungs during AP it did not prevent leukocyte infiltration, which could be responsible for maintaining the lung injury. As a result, NAC aggravated the lung damage in severe AP and failed to exert beneficial effects in the mild disease model.

  3. Isolation of tissue layers in hermatypic corals by N-acetylcysteine: morphological and proteomic examinations

    Science.gov (United States)

    Peng, S.-E.; Luo, Y.-J.; Huang, H.-J.; Lee, I.-T.; Hou, L.-S.; Chen, W.-N. U.; Fang, L.-S.; Chen, C.-S.

    2008-03-01

    Corals are diploblastic in body pattern and include two tissue layers, the epidermis and gastrodermis, interconnected by an acellular matrix mesoglea. During development, cells in these tissue layers differentiate morphologically and functionally. In most hermatypic corals, the gastrodermis further develops an ability to associate with microalgae dinoflagellates. This endosymbiosis occurs inside specific host gastrodermal cells, and its mechanism still remains unclear notwithstanding decades of research. The delay in progress is partly due to the difficulty in separating the gastrodermis and its symbionts from the epidermis for detailed cellular and biochemical investigations. The present study reports a simple method to separate these two tissue layers in hermatypic corals using the reducing agent, N-acetylcysteine (NAC). Efficient tissue and proteomic isolations are demonstrated by microscopy and two-dimensional SDS polyacrylamide gel electrophoresis (2D SDS-PAGE). The NAC treatment was able to separate tissue layers without inducing protein degradation. Furthermore, the sensitivity of protein detection greatly increases in the isolated tissue layers. The application of the present technique provides future research on endosymbiosis and coral development with a tool for higher accuracy and sensitivity.

  4. Protective effects of N-acetylcysteine against monosodium glutamate-induced astrocytic cell death.

    Science.gov (United States)

    Park, Euteum; Yu, Kyoung Hwan; Kim, Do Kyung; Kim, Seung; Sapkota, Kumar; Kim, Sung-Jun; Kim, Chun Sung; Chun, Hong Sung

    2014-05-01

    Monosodium glutamate (MSG) is a flavor enhancer, largely used in the food industry and it was reported to have excitotoxic effects. Higher amounts of MSG consumption have been related with increased risk of many diseases, including Chinese restaurant syndrome and metabolic syndromes in human. This study investigated the protective effects of N-acetylcysteine (NAC) on MSG-induced cytotoxicity in C6 astrocytic cells. MSG (20 mM)-induced reactive oxygen species (ROS) generation and apoptotic cell death were significantly attenuated by NAC (500 μM) pretreatment. NAC effectively inhibited the MSG-induced mitochondrial membrane potential (MMP) loss and intracellular reduced glutathione (GSH) depletion. In addition, NAC significantly attenuated MSG-induced endoplasmic reticulum (ER) stress markers, such as XBP1 splicing and CHOP, PERK, and GRP78 up-regulation. Furthermore, NAC prevented the changes of MSG-induced Bcl-2 expression level. These results suggest that NAC can protect C6 astrocytic cells against MSG-induced oxidative stress, mitochondrial dysfunction, and ER stress. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Do Montelukast Sodium and N-Acetylcysteine Have a Nephroprotective Effect on Unilateral Ureteral Obstruction? A Placebo Controlled Trial in a Rat Model.

    Science.gov (United States)

    Sunay, Melih; Karakan, Tolga; Aydın, Arif; Koca, Gökhan; Börcek, Pınar; Öğüş, Elmas

    2015-10-01

    We assessed the nephroprotective effects of montelukast sodium and N-acetylcysteine on secondary renal damage due to unilateral ureteral obstruction in a rat model. In this study 30 Wistar albino male rats were randomized into 3 groups, including placebo, N-acetylcysteine and montelukast sodium. Three rats served as the control group. The left ureter of the rats was sutured with 4-zero polyglactin sutures. Medications were given 3 days before obstruction and continued for 15 days. Dimercaptosuccinic acid renal scintigraphy was performed before obstruction and on day 15. Rats were sacrificed on day 15 and histopathological examinations were done. We biochemically assessed oxidative stress markers (myeloperoxidase and malondialdehyde), sulfhydryl and total nitrite for lipid peroxidation, oxidative protein damage and antioxidant levels, respectively. On pathological examination inflammation and tubular epithelial damage in the N-acetylcysteine and montelukast sodium groups were less than in the placebo group (p placebo group (p 0.05) or among the N-acetylcysteine, montelukast sodium and placebo groups on scintigraphy (p >0.05). No pathological, chemical and scintigraphic differences were seen among the N-acetylcysteine, montelukast sodium and sham treated groups (p >0.05). N-acetylcysteine and montelukast sodium have a protective effect against obstructive damage of the kidney. However, further investigations are needed. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  6. Early treatment with N-acetylcysteine in children with acute liver failure secondary to hepatitis A.

    Science.gov (United States)

    Sotelo, Norberto; de los Angeles Durazo, María; Gonzalez, Alejandro; Dhanakotti, Nagasharmila

    2009-01-01

    Hepatitis A virus can evolve to acute liver failure with a fatal outcome if it is not reversed. We describe the clinical course of 12 children who presented with hepatitis A acute liver failure and received treatment with oral N-acetylcysteine (NAC). Of the seventy-two patients with viral hepatitis A, 12 patients who had acute hepatic failure were included. The variables evaluated were age, sex, duration of clinical features prior to hospitalization, signs and symptoms, laboratory parameters [alanine aminotransferase (ALT), aspartate aminotransferase (AST), prothrombin time (PT), partial thromboplastin time (PTT), internal normalization ratio and ammonia], treatment (oral NAC 100 mg/kg/day, lactulose, neomycin and general measures) and clinical course during hospitalization. Six males and six females were included. School-aged and adolescent children predominated. All presented with jaundice, nausea, vomiting and hepatomegaly. Two had stage 2 neurological signs as per the West-Haven scale. All had altered laboratory parameters. All received NAC, six patients for a week and the remaining six for 9-36 days. Treatment was not ceased until patients showed clinical and laboratory improvement. All data were analyzed using both student's t test and Wilcoxon signed rank with alpha = 0.05, the ALT with P = 0.0003 and 0.005, AST with P = 0.0001 and 0.0005, PT with P = 0.0237 and 0.0005, PTT with P = 0.0515 and 0.0039, ammonia with P = 0.0197 and 0.0015 and direct bilirubin with P = 0.0190 and 0.068. There was good tolerance to medications and a satisfactory clinical course. The use of oral NAC appears to be an effective therapeutic alternative for hepatitis A-induced liver failure if it is offered appropriately. It can modify the clinical course to a favorable one and prevent the fatal outcome of hepatic encephalopathy.

  7. A randomized placebo-controlled trial of N-acetylcysteine for cannabis use disorder in adults.

    Science.gov (United States)

    Gray, Kevin M; Sonne, Susan C; McClure, Erin A; Ghitza, Udi E; Matthews, Abigail G; McRae-Clark, Aimee L; Carroll, Kathleen M; Potter, Jennifer S; Wiest, Katharina; Mooney, Larissa J; Hasson, Albert; Walsh, Sharon L; Lofwall, Michelle R; Babalonis, Shanna; Lindblad, Robert W; Sparenborg, Steven; Wahle, Aimee; King, Jacqueline S; Baker, Nathaniel L; Tomko, Rachel L; Haynes, Louise F; Vandrey, Ryan G; Levin, Frances R

    2017-08-01

    Cannabis use disorder (CUD) is a prevalent and impairing condition, and established psychosocial treatments convey limited efficacy. In light of recent findings supporting the efficacy of N-acetylcysteine (NAC) for CUD in adolescents, the objective of this trial was to evaluate its efficacy in adults. In a 12-week double-blind randomized placebo-controlled trial, treatment-seeking adults ages 18-50 with CUD (N=302), enrolled across six National Drug Abuse Treatment Clinical Trials Network-affiliated clinical sites, were randomized in a 1:1 ratio to a 12-week course of NAC 1200mg (n=153) or placebo (n=149) twice daily. All participants received contingency management (CM) and medical management. The primary efficacy measure was the odds of negative urine cannabinoid tests during treatment, compared between NAC and placebo participants. There was not statistically significant evidence that the NAC and placebo groups differed in cannabis abstinence (odds ratio=1.00, 95% confidence interval 0.63-1.59, p=0.984). Overall, 22.3% of urine cannabinoid tests in the NAC group were negative, compared with 22.4% in the placebo group. Many participants were medication non-adherent; exploratory analysis within medication-adherent subgroups revealed no significant differential abstinence outcomes by treatment group. In contrast with prior findings in adolescents, there is no evidence that NAC 1200mg twice daily plus CM is differentially efficacious for CUD in adults when compared to placebo plus CM. This discrepant finding between adolescents and adults with CUD may have been influenced by differences in development, cannabis use profiles, responses to embedded behavioral treatment, medication adherence, and other factors. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Therapeutic potential of N-acetylcysteine as an antiplatelet agent in patients with type-2 diabetes

    Directory of Open Access Journals (Sweden)

    MacRury Sandra M

    2011-05-01

    Full Text Available Abstract Background Platelet hyperaggregability is a pro-thrombotic feature of type-2 diabetes, associated with low levels of the antioxidant glutathione (GSH. Clinical delivery of N-acetylcysteine (NAC, a biosynthetic precursor of GSH, may help redress a GSH shortfall in platelets, thereby reducing thrombotic risk in type-2 diabetes patients. We investigated the effect of NAC in vitro, at concentrations attainable with tolerable oral dosing, on platelet GSH concentrations and aggregation propensity in blood from patients with type-2 diabetes. Methods Blood samples (n = 13 were incubated (2 h, 37°C with NAC (10-100 micromolar in vitro. Platelet aggregation in response to thrombin and ADP (whole blood aggregometry was assessed, together with platelet GSH concentration (reduced and oxidized, antioxidant status, reactive oxygen species (ROS generation, and plasma NOx (a surrogate measure of platelet-derived nitric oxide; NO. Results At therapeutically relevant concentrations (10-100 micromolar, NAC increased intraplatelet GSH levels, enhanced the antioxidant effects of platelets, and reduced ROS generation in blood from type-2 diabetes patients. Critically, NAC inhibited thrombin- and ADP-induced platelet aggregation in vitro. Plasma NOx was enhanced by 30 micromolar NAC. Conclusions Our results suggest that NAC reduces thrombotic propensity in type-2 diabetes patients by increasing platelet antioxidant status as a result of elevated GSH synthesis, thereby lowering platelet-derived ROS. This may increase bioavailability of protective NO in a narrow therapeutic range. Therefore, NAC might represent an alternative or additional therapy to aspirin that could reduce thrombotic risk in type-2 diabetes.

  9. N-acetylcysteine reverses diastolic dysfunction and hypertrophy in familial hypertrophic cardiomyopathy.

    Science.gov (United States)

    Wilder, Tanganyika; Ryba, David M; Wieczorek, David F; Wolska, Beata M; Solaro, R John

    2015-11-15

    S-glutathionylation of cardiac myosin-binding protein C (cMyBP-C) induces Ca(2+) sensitization and a slowing of cross-bridge kinetics as a result of increased oxidative signaling. Although there is evidence for a role of oxidative stress in disorders associated with hypertrophic cardiomyopathy (HCM), this mechanism is not well understood. We investigated whether oxidative myofilament modifications may be in part responsible for diastolic dysfunction in HCM. We administered N-acetylcysteine (NAC) for 30 days to 1-mo-old wild-type mice and to transgenic mice expressing a mutant tropomyosin (Tm-E180G) and nontransgenic littermates. Tm-E180G hearts demonstrate a phenotype similar to human HCM. After NAC administration, the morphology and diastolic function of Tm-E180G mice was not significantly different from controls, indicating that NAC had reversed baseline diastolic dysfunction and hypertrophy in our model. NAC administration also increased sarco(endo)plasmic reticulum Ca(2+) ATPase protein expression, reduced extracellular signal-related kinase 1/2 phosphorylation, and normalized phosphorylation of phospholamban, as assessed by Western blot. Detergent-extracted fiber bundles from NAC-administered Tm-E180G mice showed nearly nontransgenic (NTG) myofilament Ca(2+) sensitivity. Additionally, we found that NAC increased tension cost and rate of cross-bridge reattachment. Tm-E180G myofilaments were found to have a significant increase in S-glutathionylation of cMyBP-C, which was returned to NTG levels upon NAC administration. Taken together, our results indicate that oxidative myofilament modifications are an important mediator in diastolic function, and by relieving this modification we were able to reverse established diastolic dysfunction and hypertrophy in HCM. Copyright © 2015 the American Physiological Society.

  10. N-acetylcysteine protects against star fruit-induced acute kidney injury.

    Science.gov (United States)

    Shimizu, Maria Heloisa Massola; Gois, Pedro Henrique França; Volpini, Rildo Aparecido; Canale, Daniele; Luchi, Weverton Machado; Froeder, Leila; Heilberg, Ita Pfeferman; Seguro, Antonio Carlos

    2017-11-01

    Star fruit (SF) is a popular fruit, commonly cultivated in many tropical countries, that contains large amount of oxalate. Acute oxalate nephropathy and direct renal tubular damage through release of free radicals are the main mechanisms involved in SF-induced acute kidney injury (AKI). The aim of this study was to evaluate the protective effect of N-acetylcysteine (NAC) on SF-induced nephrotoxicity due to its potent antioxidant effect. Male Wistar rats received SF juice (4 mL/100 g body weight) by gavage after a 12 h fasting and water deprivation. Fasting and water deprivation continued for 6 h thereafter to warrant juice absorption. Thereafter, animals were allocated to three experimental groups: SF (n = 6): received tap water; SF + NAC (n = 6): received NAC (4.8 g/L) in drinking water for 48 h after gavage; and Sham (n = 6): no interventions. After 48 h, inulin clearance studies were performed to determine glomerular filtration rate. In a second series of experiment, rats were housed in metabolic cages for additional assessments. SF rats showed markedly reduced inulin clearance associated with hyperoxaluria, renal tubular damage, increased oxidative stress and inflammation. NAC treatment ameliorated all these alterations. Under polarized light microscopy, SF rats exhibited intense calcium oxalate birefringence crystals deposition, dilation of renal tubules and tubular epithelial degeneration, which were attenuate by NAC therapy. Our data show that therapeutic NAC attenuates renal dysfunction in a model of acute oxalate nephropathy following SF ingestion by reducing oxidative stress, oxaluria, and inflammation. This might represent a novel indication of NAC for the treatment of SF-induced AKI.

  11. N-Acetylcysteine as a chemical scavenger for sulfur mustard: New insights by mass spectrometry.

    Science.gov (United States)

    Siegert, Markus; Kranawetvogl, Andreas; Thiermann, Horst; John, Harald

    2018-02-01

    The vesicant sulfur mustard (SM) is a banned chemical warfare agent. Although, SM has been used in combat since WWI, there is no causal therapy currently available. Accordingly, development and investigation of antidotes and scavengers targeting SM are of high clinical relevance. N-acetylcysteine (NAC) was shown to mitigate symptoms of SM intoxications in vitro and in vivo. However, it is still unclear whether the beneficial effects of NAC are only due to physiological processes or also due to chemical scavenging of SM. Therefore, in this study, we examined the scavenging potential of NAC toward SM. Co-incubations of SM and different NAC concentrations in human serum were performed to monitor diverse adducts (covalent reaction products) of human serum albumin (HSA), NAC, and SM. After proteolytic cleavage of HSA with proteinase K the alkylated tripeptide hydroxyethylthioethyl-CysProPhe (HETE-CPF) and the disulfide bridged tripeptide NAC-CPF were detected. Samples were analyzed by microbore liquid chromatography-electrospray ionization-high-resolution tandem-mass spectrometry (μLC-ESI MS/HR MS). Furthermore, degradation kinetics of SM in phosphate buffered saline were measured in the presence and absence of NAC. Although NAC-CPF was identified and characterized for the first time by mass spectrometry and reaction products of NAC and SM were detected and identified by MS/HR MS, analyses clearly documented minor reactivity not significantly contributing to reduction of SM concentrations. Therefore, we conclude that chemical scavenging of SM by NAC does not play the key role in NAC therapy of SM poisoning. Copyright © 2017 John Wiley & Sons, Ltd.

  12. l-N-acetylcysteine protects outer hair cells against TNFα initiated ototoxicity in vitro.

    Science.gov (United States)

    Tillinger, Joshua A; Gupta, Chhavi; Ila, Kadri; Ahmed, Jamal; Mittal, Jeenu; Van De Water, Thomas R; Eshraghi, Adrien A

    2018-03-07

    The present study is aimed at determining the efficacy and exploring the mechanisms by which l-N-acetylcysteine (l-NAC) provides protection against tumor necrosis factor-alpha (TNFα)-induced oxidative stress damage and hair cell loss in 3-day-old rat organ of Corti (OC) explants. Previous work has demonstrated a high level of oxidative stress in TNFα-challenged OC explants. TNFα can potentially play a significant role in hair cell loss following an insult to the inner ear. l-NAC has shown to provide effective protection against noise-induced hearing loss in laboratory animals but mechanisms of this otoprotective effect are not well-defined. Rat OC explants were exposed to either: (1) saline control (N = 12); (2) TNFα (2 μg/ml, N = 12); (3) TNFα+l-NAC (5 mM, N = 12); (4) TNFα+l-NAC (10 mM, N = 12); or (5) l-NAC (10 mM, N = 12). Outer hair cell (OHC) density, levels of reactive oxygen species (ROS), lipid peroxidation of cell membranes, gluthathione activity, and mitochondrial viability were assayed. l-NAC (5 and 10 mM) provided protection for OHCs from ototoxic level of TNFα in OC explants. Groups treated with TNFα+l-NAC (5 mM) showed a highly significant reduction of both ROS (p < 0.01) and 4-hydroxy-2-nonenal immunostaining (p < 0.001) compared to TNFα-challenged explants. Total glutathione levels were low in TNFα-challenged explants compared to control and TNFα+l-NAC (5 mM) treated explants (p < 0.001). l-NAC is a promising treatment for protecting auditory HCs from TNFα-induced oxidative stress and subsequent loss via programmed cell death.

  13. Topical N-acetylcysteine reduces interleukin-1-alpha in tear fluid after laser subepithelial keratectomy.

    Science.gov (United States)

    Urgancioglu, Berrak; Bilgihan, Kamil; Engin, Doruk; Cirak, Meltem Yalinay; Hondur, Ahmet; Hasanreisoglu, Berati

    2009-01-01

    To evaluate the effect of topical N-acetylcysteine (NAC) on interleukin 1-alpha (IL-1alpha) levels in tear fluid after myopic laser subepithelial keratectomy (LASEK) and its possible role in modulating corneal wound healing. Twenty-six eyes of 13 patients who underwent myopic LASEK were divided into 2 groups. Group 1 (n=10 eyes) was used as a control group. All patients received topical lomefloxacin and dexamethasone postoperatively. Additionally, patients in Group 2 received topical NAC for 1 month postoperatively. Tear fluid samples were collected with microcapillary tubes preoperatively, on the first and on the fifth postoperative day, and the release of IL-1alpha in tear fluid was calculated. Haze grading and confocal microscopic examination were performed at 1 and 3 months postoperatively. The mean IL-1-alpha release values were 0.285-/+0.159 pg/min in Group 1 and 0.235-/+0.142 pg/min in Group 2 preoperatively. In Group 1, the values were 0.243-/+0.155 pg/min on day 1 and 0.164-/+0.125 pg/min on day 5. In Group 2, the mean IL-1alpha release values were 0.220-/+0.200 pg/min on day 1 and 0.080-/+0.079 pg/min on day 5. The difference between the groups was significant only for day 5 (p0.05). NAC seems to have an additive effect to steroids in suppressing IL-1alpha levels in tear fluid and may be clinically advantageous in modulating corneal wound healing during the early postoperative period after LASEK.

  14. Effect of n-acetylcysteine on deranged renal functions in patient receiving non ionic radio contrast

    International Nuclear Information System (INIS)

    Faisal, A.; Kamal, M.

    2013-01-01

    Objective: To determine the effect of N-Acetylcysteine (NAC) on deranged renal functions in patients receiving non-ionic contrast. Study Design: Quasi- experimental study. Place and Duration of Study: The study was conducted in the Department of Radiology, DHQ Hospital Rawalpindi, RMC and Allied hospitals from August 2011 to January 2012. Methodology: Eighty consecutive patients with deranged renal function tests (RFTs) (creatinine level > 1.3 mg/dl and 50 mg/dl) were included in this study. These patients were advised to take at-least eight sachets of NAC to talling to 1,600 mg (one sachets is 200 mg) within two days with good hydration (6 to 8 glasses of water) prior to Contrast Enhanced Computer Tomographic (CECT) scan. After completion of NAC recommended dose, the RFTs are repeated to confirm the controlled range. The patients are allowed for CECT, if the serum urea level > 50 mg/dl (reference range 0-50 mg/dl) and serum creatinine level < 1.3 mg/dl (reference range 0.2-1.2 mg/dl). Results: The mean age of the patient is 53.98+-15.4 years. The use of NAC extensively improves the serum urea level of 73 out of 80 patients (91.3%) with a significance of 0.0001 to a normal level (<50 mg/dl). Similarly, serum creatinine level of 71 out of 80 patients (88.8%) with a significance of 0.0001 has an improved from reference range ( <=1. 2 mg/dl). Conclusion: Use of NAC resulted in improved serum urea and creatinine levels in the majority of patients. (author)

  15. N-acetylcysteine (NAC) ameliorates Epstein-Barr virus latent membrane protein 1 induced chronic inflammation.

    Science.gov (United States)

    Gao, Xiao; Lampraki, Eirini-Maria; Al-Khalidi, Sarwah; Qureshi, Muhammad Asif; Desai, Rhea; Wilson, Joanna Beatrice

    2017-01-01

    Chronic inflammation results when the immune system responds to trauma, injury or infection and the response is not resolved. It can lead to tissue damage and dysfunction and in some cases predispose to cancer. Some viruses (including Epstein-Barr virus (EBV)) can induce inflammation, which may persist even after the infection has been controlled or cleared. The damage caused by inflammation, can itself act to perpetuate the inflammatory response. The latent membrane protein 1 (LMP1) of EBV is a pro-inflammatory factor and in the skin of transgenic mice causes a phenotype of hyperplasia with chronic inflammation of increasing severity, which can progress to pre-malignant and malignant lesions. LMP1 signalling leads to persistent deregulated expression of multiple proteins throughout the mouse life span, including TGFα S100A9 and chitinase-like proteins. Additionally, as the inflammation increases, numerous chemokines and cytokines are produced which promulgate the inflammation. Deposition of IgM, IgG, IgA and IgE and complement activation form part of this process and through genetic deletion of CD40, we show that this contributes to the more tissue-destructive aspects of the phenotype. Treatment of the mice with N-acetylcysteine (NAC), an antioxidant which feeds into the body's natural redox regulatory system through glutathione synthesis, resulted in a significantly reduced leukocyte infiltrate in the inflamed tissue, amelioration of the pathological features and delay in the inflammatory signature measured by in vivo imaging. Reducing the degree of inflammation achieved through NAC treatment, had the knock on effect of reducing leukocyte recruitment to the inflamed site, thereby slowing the progression of the pathology. These data support the idea that NAC could be considered as a treatment to alleviate chronic inflammatory pathologies, including post-viral disease. Additionally, the model described can be used to effectively monitor and accurately measure

  16. A dosing regimen for immediate N-acetylcysteine treatment for acute paracetamol overdose.

    Science.gov (United States)

    Shen, Finna; Coulter, Carolyn V; Isbister, Geoffrey K; Duffull, Stephen B

    2011-08-01

    Current treatment of paracetamol (acetaminophen) poisoning involves initiating a 3-phase N-acetylcysteine (NAC) infusion after comparing a plasma concentration, taken ≥ 4 h post-overdose, to a nomogram. This may result in dosing errors, a delay in treatment, or possibly more adverse effects - due to the use of a high dose rate for the first infusion when treatment is initiated. Our aim was to investigate a novel dosing regimen for the immediate administration of NAC on admission at a lower infusion rate. We used a published population pharmacokinetic model of NAC to simulate a scenario where a patient presents to the hospital 2 h post-overdose. The conventional regimen is commenced 6 h post-overdose when the 4-h plasma paracetamol concentration is available. We investigated an NAC infusion using a lower dosing rate initiated immediately on presentation. We determined a dosing rate that gave an area under the curve (AUC) of the concentration-time curve that was the same or greater than that from the conventional regimen on 90% of occasions. Lower dosing rates of NAC initiated immediately resulted in a similar exposure to NAC. An infusion of 110 mg/kg over the first 5 h (22 mg/kg/h) followed by the last two phases of the conventional regimen, or 200 mg/kg over 9 h (22.6 mg/kg/h) followed by the last phase of the conventional regimen could be used. The novel dosing regimen allowed immediate treatment of a patient using a lower dosing rate. This greatly simplifies the current dosing regimen and may reduce NAC adverse effects while ensuring the same amount of NAC is delivered.

  17. N-acetylcysteine and meso-2,3 dimercaptosuccinic acid alleviate oxidative stress and hepatic dysfunction induced by sodium arsenite in male rats

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    Abu El-Saad AM

    2016-10-01

    Full Text Available Ahmed M Abu El-Saad,1,4 Mohammed A Al-Kahtani,2 Ashraf M Abdel-Moneim3,4 1Department of Biology, Faculty of Medicine, Dammam University, Dammam, Saudi Arabia; 2Department of Biology, Faculty of Science, King Khalid University, Abha, Saudi Arabia; 3Department of Biological Sciences, Faculty of Science, King Faisal University, Al-Ahsa, Saudi Arabia; 4Department of Zoology, Faculty of Science, Alexandria University, Alexandria, Egypt Abstract: Environmental exposure to arsenic represents a serious challenge to humans and other animals. The aim of the present study was to test the protective effect of antioxidant N-acetylcysteine (NAC either individually or in combination with a chelating agent, meso-2,3-dimercaptosuccinic acid (DMSA, against sodium arsenite oral toxicity in male rats. Five groups were used: control; arsenic group (orally administrated in a concentration of 2 mg/kg body weight [b.w.]; the other three groups were orally administrated sodium arsenite in a concentration of 2 mg/kg b.w. followed by either NAC (10 mg/kg b.w., intraperitoneally [i.p.], DMSA (50 mg/kg b.w., i.p. or NAC plus DMSA. Arsenic toxicity caused significant rise in serum aspartate aminotransferase, alanine aminotransferase and total bilirubin, and a significant decrease in total protein (TP and albumin levels after 3 weeks of experimental period. In addition, arsenic-treated rats showed significantly higher arsenic content in liver and significant rise in hepatic malondialdehyde level. By contrast, sharp decreases in glutathione content and catalase and glutathione reductase activities were discernible. NAC and/or DMSA counteracted most of these physiologic and biochemical defects. NAC monotherapy was more effective than DMSA in increasing TP, while DMSA was more effective in decreasing alanine aminotransferase. The combined treatment was superior over monotherapies in recovery of TP and glutathione. Biochemical data were well supported by histopathological and

  18. N-Acetylcysteine Supplementation Controls Total Antioxidant Capacity, Creatine Kinase, Lactate, and Tumor Necrotic Factor-Alpha against Oxidative Stress Induced by Graded Exercise in Sedentary Men

    Directory of Open Access Journals (Sweden)

    Donrawee Leelarungrayub

    2011-01-01

    Full Text Available Aim of this study was to evaluate the effects of short-term (7 days N-acetylcysteine (NAC at 1,200 mg daily supplementation on muscle fatigue, maximal oxygen uptake (VO2max, total antioxidant capacity (TAC, lactate, creatine kinase (CK, and tumor necrotic factor-alpha (TNF-α. Twenty-nine sedentary men (13 controls; 16 in the supplement group from a randomized control were included. At before and after supplementation, fatigue index (FI was evaluated in the quadriceps muscle, and performed a graded exercise treadmill test to induce oxidative stress, and as a measure of VO2max. Blood samples were taken before exercise and 20 minutes after it at before and after supplementation, to determine TAC, CK, lactate, and TNF-α levels. Results showed that FI and VO2max increased significantly in the supplement group. After exercise decreased the levels of TAC and increased lactate, CK, and TNF-α of both groups at before supplementation. After supplementation, lactate, CK, and TNF-α levels significantly increased and TAC decreased after exercise in the control group. Whereas the TAC and lactate levels did not change significantly, but CK and TNF-α increased significantly in the supplement group. Therefore, this results showed that NAC improved the muscle fatigue, VO2max, maintained TAC, controlled lactate production, but had no influence on CK and TNF-α.

  19. The effects of N-acetylcysteine and deferoxamine on plasma cytokine and oxidative damage parameters in critically ill patients with prolonged hypotension: a randomized controlled trial.

    Science.gov (United States)

    Fraga, Cassiana Mazon; Tomasi, Cristiane Damiani; Biff, Daiane; Topanotti, Maria Fernanda Locks; Felisberto, Francine; Vuolo, Francieli; Petronilho, Fabricia; Dal-Pizzol, Felipe; Ritter, Cristiane

    2012-09-01

    Reactive oxygen species and inflammation have been implicated in renal tubule cell injury. However, there is some controversy concerning whether antioxidants might attenuate oxidative damage and inflammation in humans after hypotension in the setting of critical illness. This study was a prospective, randomized, double-blinded, placebo-controlled study that included patients with hypotension. Patients were randomized to receive either N-acetylcysteine (NAC; 50 mg/kg by 4 hours followed by 100 mg/kg/d for 48 hours diluted in 5% glucose) and deferoxamine (DFX; at a single dose of 1000 mg diluted in 5% glucose) or placebo. The primary study outcome was the serum levels of markers of oxidative damage and inflammatory response. Secondary outcomes included the incidence of acute renal failure, serum creatinine at hospital discharge, intensive care unit length of stay, and length of hospital stay. Thirty patients were enrolled in the study. The use of NAC plus DFX decreased the oxidative damage parameters but not plasma interleukin-6 levels. In contrast, plasma nitrite levels increased 24 hours after NAC plus DFX administration. On analysis of secondary outcomes, it was observed that creatinine levels at hospital discharge were lower in patients receiving NAC plus DFX when compared with placebo. NAC plus DFX administration was able to decrease plasma markers of oxidative damage and creatinine levels at hospital discharge.

  20. The effect of N-acetylcysteine supplementation on serum homocysteine levels and hepatic and renal oxidative stress in homocysteine thiolactone-treated rats.

    Science.gov (United States)

    Kondakçı, Gamze; Aydın, A Fatih; Doğru-Abbasoğlu, Semra; Uysal, Müjdat

    2017-05-01

    The effect of N-acetylcysteine (NAC) (1 g/kg body weight/day) on serum homocysteine (Hcy) levels, insulin resistance (IR), and hepatic and renal prooxidant-antioxidant balance was evaluated in rats treated with homocysteine thiolactone (HcyT) (500 mg/kg body weight/day for 6 weeks). Reactive oxygen species (ROS), malondialdehyde (MDA), glutathione, ferric reducing antioxidant power, and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were determined in the liver and kidney. HcyT elevated serum Hcy levels and caused IR, but liver and kidney function tests remained unchanged. HcyT increased ROS and MDA without any change in hepatic antioxidants, but it elevated renal SOD and GSH-Px activities. NAC decreased serum Hcy, hepatic and renal ROS and MDA levels, and renal SOD and GSH-Px activities in rats with high Hcy levels. However, it did not ameliorate IR. Our results indicate that NAC supplementation may be effective in decreasing Hcy levels and Hcy-induced hepatic and renal oxidative stress.

  1. The influence of single application of paracetamol and/or N-acetylcysteine on rats in subchronic exposition to trichloroethylene vapours. II. Effect on hepatic glutathione level

    Directory of Open Access Journals (Sweden)

    Danuta Plewka

    2012-09-01

    Full Text Available Background: Feature of modern existing hazards both environmental and occupational is cumulative exposure often leading to unexpected response of the organism resulting, among other things, in interactions with cytochrome P450 system involved in biotransformation of trichloroethylene and paracetamol. Hepatotoxity of paracetamol is closely connected with hepatic glutathione level. „In therapy of acute paracetamol poisoning application of N-acetylcysteine as a factor, which protects GSH level in cells, is recommended.” Materials and method: Tests were performed on rats which were treated with trichloroethylene, paracetamol and/or N-acetylcysteine. In rat liver total level of glutathione was determined i.e. reduced and oxidized form. Results: Paracetamol just after completion of the exposure affected the glutathione level. Trichloroethylene throughout the period of observation stimulated growth of glutathione level in liver. N-acetylcysteine didn’t have any influence on the level of investigated tripeptyde. Conclusions: N-acetylcysteine removes negative effect of paracetamol especially when it’s applied with 2-hour delay. After exposure for trichloethylene immediate application of N-acetylcysteine caused noticeable lowering of glutathione level. Cumulative exposure for three xenobiotics had positive influence for glutathione level in rat liver.

  2. Effect of N-Acetylcysteine on Antioxidant Defense, Oxidative Modification, and Salivary Gland Function in a Rat Model of Insulin Resistance

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    Piotr Żukowski

    2018-01-01

    Full Text Available Oxidative stress plays a crucial role in the salivary gland dysfunction in insulin resistance (IR. It is not surprising that new substances are constantly being sought that will protect against the harmful effects of IR in the oral cavity environment. The purpose of this study was to evaluate the effect of N-acetylcysteine (NAC on oxidative stress and secretory function of salivary glands in a rat model of insulin resistance. Rats were divided into 4 groups: C—normal diet, C + NAC—normal diet + NAC, HFD—high-fat diet, and HFD + NAC. We have demonstrated that NAC elevated enzymatic (superoxide dismutase, catalase, and peroxidase and nonenzymatic antioxidants (reduced glutathione (GSH and total antioxidant capacity (TAS in the parotid glands of HFD + NAC rats, while in the submandibular glands increased only GSH and TAS levels. NAC protects against oxidative damage only in the parotid glands and increased stimulated salivary secretion; however, it does not increase the protein secretion in the both salivary glands. Summarizing, NAC supplementation prevents the decrease of stimulated saliva secretion, seen in the HFD rats affected. NAC improves the antioxidative capacity of the both glands and protects against oxidative damage to the parotid glands of IR rats.

  3. Evaluation of Oxidative Stress in Combination Therapy with D-penicillamine and N-Acetylcysteine (NAC in Lead Poisoning in Opium Addicts

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    Saeedeh Shojaeepour

    2017-12-01

    Full Text Available Background: N-acetylcysteine (NAC is a putative antioxidant and has gained attention as a promising agent for chelating heavy metals including lead. Considering the animal studies results, we hypothesized that adding NAC to the treatment regimen may improve the success of treatment with lead chelators. Methods: A total of 46 patients who were lead-poisoned opioid addicts were divided into two groups randomly and treated with d-penicillamine (DP, 1g/day in four equal divided doses and NAC+DP (1 g/day + 150 mg/kg/day. The efficacy of treatment was evaluated by hospitalization period. Meanwhile, the oxidative stress parameters including lipid peroxidation, protein carbonyl, total antioxidant capacity (TAC, glutathione concentration and super oxide dismutase (SOD activity were determined on admission and discharge and compared with healthy normal controls. Results: Hospitalization period was not different between the two groups. Treatment with DP and DP+NAC significantly decreased oxidative stress in patients. On the discharge day, the SOD activity and TAC were significantly higher in DP+NAC group in comparison with the DP group. Conclusion: Although NAC recovers antioxidant capacity, the advantages of NAC in improvement of DP efficacy in lead poisoning is questionable. Further studies with larger sample size and combination with other chelators are recommended.

  4. Inhibition of rotavirus ECwt infection in ICR suckling mice by N-acetylcysteine, peroxisome proliferator-activated receptor gamma agonists and cyclooxygenase-2 inhibitors

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    Carlos Arturo Guerrero

    2013-09-01

    Full Text Available Live attenuated vaccines have recently been introduced for preventing rotavirus disease in children. However, alternative strategies for prevention and treatment of rotavirus infection are needed mainly in developing countries where low vaccine coverage occurs. In the present work, N-acetylcysteine (NAC, ascorbic acid (AA, some nonsteroidal anti-inflammatory drugs (NSAIDs and peroxisome proliferator-activated receptor gamma (PPARγ agonists were tested for their ability to interfere with rotavirus ECwt infectivity as detected by the percentage of viral antigen-positive cells of small intestinal villi isolated from ECwt-infected ICR mice. Administration of 6 mg NAC/kg every 8 h for three days following the first diarrhoeal episode reduced viral infectivity by about 90%. Administration of AA, ibuprofen, diclofenac, pioglitazone or rosiglitazone decreased viral infectivity by about 55%, 90%, 35%, 32% and 25%, respectively. ECwt infection of mice increased expression of cyclooxygenase-2, ERp57, Hsc70, NF-κB, Hsp70, protein disulphide isomerase (PDI and PPARγ in intestinal villus cells. NAC treatment of ECwt-infected mice reduced Hsc70 and PDI expression to levels similar to those observed in villi from uninfected control mice. The present results suggest that the drugs tested in the present work could be assayed in preventing or treating rotaviral diarrhoea in children and young animals.

  5. N-Acetylcysteine in the Treatment of Pediatric Trichotillomania: A Randomized, Double-Blind, Placebo-Controlled Add-On Trial

    Science.gov (United States)

    Bloch, Michael H.; Panza, Kaitlyn E.; Grant, Jon E.; Pittenger, Christopher; Leckman, James F.

    2013-01-01

    Objective: To examine the efficacy of N-acetylcysteine (NAC) for the treatment of pediatric trichotillomania (TTM) in a double-blind, placebo-controlled, add-on study. Method: A total of 39 children and adolescents aged 8 to 17 years with pediatric trichotillomania were randomly assigned to receive NAC or matching placebo for 12 weeks. Our primary…

  6. The effect of N-acetylcysteine and working memory training on cocaine use, craving and inhibition in regular cocaine users: correspondence of lab assessments and Ecological Momentary Assessment

    NARCIS (Netherlands)

    Schulte, Mieke H. J.; Wiers, Reinout W.; Boendermaker, Wouter J.; Goudriaan, Anna E.; van den Brink, Wim; van Deursen, Denise S.; Friese, Malte; Brede, Emily; Waters, Andrew J.

    2017-01-01

    Effective treatment for cocaine use disorder should dampen hypersensitive cue-induced motivational processes and/or strengthen executive control. Using a randomized, double-blind, placebo-controlled intervention, the primary aim of this study was to investigate the effect of N-Acetylcysteine (NAC)

  7. Prevention of Contrast-Induced Nephropathy With N-Acetylcysteine or Sodium Bicarbonate in Patients With ST-Segment-Myocardial Infarction

    DEFF Research Database (Denmark)

    Thayssen, Per; Lassen, Jens Flensted; Jensen, Svend Eggert

    2014-01-01

    (CINSTEMI) trial. Patients were randomly assigned in a 1:1:1:1 ratio to receive hydration with sodium chloride together with 1 of 4 prophylactic regimes (1) N-acetylcysteine (NAC), (2) sodium bicarbonate (NaHCO3) infusion, (3) NAC in combination with NaHCO3, or (4) hydration with sodium chloride infusion...

  8. Chemical Changes in Nonthermal Plasma-Treated N-Acetylcysteine (NAC) Solution and Their Contribution to Bacterial Inactivation

    Science.gov (United States)

    Ercan, Utku K.; Smith, Josh; Ji, Hai-Feng; Brooks, Ari D.; Joshi, Suresh G.

    2016-01-01

    In continuation of our previous reports on the broad-spectrum antimicrobial activity of atmospheric non-thermal dielectric barrier discharge (DBD) plasma treated N-Acetylcysteine (NAC) solution against planktonic and biofilm forms of different multidrug resistant microorganisms, we present here the chemical changes that mediate inactivation of Escherichia coli. In this study, the mechanism and products of the chemical reactions in plasma-treated NAC solution are shown. UV-visible spectrometry, FT-IR, NMR, and colorimetric assays were utilized for chemical characterization of plasma treated NAC solution. The characterization results were correlated with the antimicrobial assays using determined chemical species in solution in order to confirm the major species that are responsible for antimicrobial inactivation. Our results have revealed that plasma treatment of NAC solution creates predominantly reactive nitrogen species versus reactive oxygen species, and the generated peroxynitrite is responsible for significant bacterial inactivation. PMID:26832829

  9. The Influence of N-acetylcysteine and Gender-Related Differences on the Radiosensitivity of Mouse Lymphocytes

    International Nuclear Information System (INIS)

    El-Shamy, E.; El-Kabany, H.

    2012-01-01

    The objective of the present study is to evaluate the possible efficiency of 200 mg/kg body weight N-acetylcysteine (NAC) on the radiosensitivity of mouse lymphocytes considering gender factor. The half of blood sample from mice was exposed to gamma-radiation (2 Gy). The time course of lymphocyte apotosis of irradiated samples was examined in vitro by flow cytometry and compared with lymphocytes from non-irradiated remaining half of samples. Kinetics of radiation-induced apoptosis was similar among groups, which peaked at 8 h. NAC protected irradiated lymphocytes in male mice. Lymphocytes from female mice were highly radiation resistant compared to males and the NAC provided no additional benefit at the doses used in this study. These results highlight that radiation-induced apoptosis is complex and is modified by the radio protector and gender.

  10. Risk factors in the development of adverse reactions to N-acetylcysteine in patients with paracetamol poisoning

    DEFF Research Database (Denmark)

    Schmidt, L E; Dalhoff, K

    2001-01-01

    AIMS: To identify risk factors in the development of side-effects to N-acetylcysteine (NAC) in patients with paracetamol poisoning. METHODS: A retrospective study was carried out based upon the hospital charts of 529 consecutive patients admitted with paracetamol poisoning, all treated with NAC...... 2.9 times (95% CI 2.1, 4.7) more likely to develop side-effects (Chi-square: P = 0.004). Side-effects were of similar severity in asthmatics and nonasthmatics. A history of medical allergy was not a risk factor. Serum paracetamol was lower in patients with side-effects than in those without (Mann......-Whitney: P = 0.00006). CONCLUSIONS: Asthma must be considered a risk factor in the development of side-effects to NAC. However, the side-effects are easily managed and there is no reason to withhold NAC from any patient with paracetamol poisoning. Paracetamol itself seems to offer some protection against...

  11. N-acetylcysteine versus Dopamine to Prevent Acute Kidney Injury after Cardiac Surgery in Patients with Preexisting Moderate Renal Insufficiency.

    Science.gov (United States)

    Savluk, Omer Faruk; Guzelmeric, Fusun; Yavuz, Yasemin; Cevirme, Deniz; Gurcu, Emre; Ogus, Halide; Orki, Tulay; Kocak, Tuncer

    2017-01-01

    Acute kidney injury after cardiac surgery is associated with mortality and morbidity. Therefore, strategies to prevent acute kidney injury are very important. The aim of this placebo-controlled randomized double-blind study was to compare the prophylactic efficacy of N-Acetylcysteine and dopamine administration in patients with pre-existing moderate renal insufficiency who were undergoing cardiopulmonary bypass. This study included 135 patients with pre-existing moderate renal insufficiency who were scheduled for coronary artery bypass grafting surgery. Serum creatinine and GFR were recorded preoperatively and on the first and second postoperative days. On the first and second postoperative days, the drugs used showed statistically significant differences among the creatinine groups (Prenal function, whereas the application of renal dose dopamine did not have a protective effect in patients with pre-existing moderate renal failure.

  12. Update on the pathological processes, molecular biology, and clinical utility of N-acetylcysteine in chronic obstructive pulmonary disease

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    Tse HN

    2014-08-01

    Full Text Available Hoi Nam Tse, Cee Zhung Steven TsengMedical and Geriatric Department, Kwong Wah Hospital, Hong Kong Special Administrative RegionAbstract: Chronic obstructive pulmonary disease (COPD is a common and morbid disease characterized by high oxidative stress. Its pathogenesis is complex, and involves excessive oxidative stress (redox imbalance, protease/antiprotease imbalance, inflammation, apoptosis, and autoimmunity. Among these, oxidative stress has a pivotal role in the pathogenesis of COPD by initiating and mediating various redox-sensitive signal transduction pathways and gene expression. The protective physiological mechanisms of the redox balance in the human body, their role in the pathogenesis of COPD, and the clinical correlation between oxidative stress and COPD are reviewed in this paper. N-acetylcysteine (NAC is a mucolytic agent with both antioxidant and anti-inflammatory properties. This paper also reviews the use of NAC in patients with COPD, especially the dose-dependent properties of NAC, eg, its effects on lung function and the exacerbation rate in patients with the disease. Earlier data from BRONCUS (the Bronchitis Randomized on NAC Cost-Utility Study did not suggest that NAC was beneficial in patients with COPD, only indicating that it reduced exacerbation in an "inhaled steroid-naïve" subgroup. With regard to the dose-dependent properties of NAC, two recent randomized controlled Chinese trials suggested that high-dose NAC (1,200 mg daily can reduce exacerbations in patients with COPD, especially in those with an earlier (moderately severe stage of disease, and also in those who are at high risk of exacerbations. However, there was no significant effect on symptoms or quality of life in patients receiving NAC. Further studies are warranted to investigate the effect of NAC at higher doses in non-Chinese patients with COPD.Keywords: N-acetylcysteine, antioxidant, anti-inflammatory, chronic obstructive pulmonary disease

  13. Manipulation of energy and redox states in the C6 glioma cells by buthionine sulfoxamine and N-acetylcysteine and the effect on cell survival to cadmium toxicity.

    Science.gov (United States)

    Yang, M S; Yu, L C; Pat, S W

    2007-04-15

    Changes in cellular energy and redox states were studied in the C6 glioma cells following exposure to chemicals that affect glutathione metabolism. It was demonstrated that treatment with sublethal concentrations (25, 50 and 100 microM) of buthionine sulfoxamine (BSO) did not affect cellular energy state as measured by total adenosine nucleotides (TAN=ATP+ADP+ AMP), ATP:ADP:AMP and energy charge potential (ECP=[ATP + 0.5 (ADP)]/TAN). However, there was a significantly decrease in cellular GSH/GSSG and total glutathione (TG=[GSH+GSSG]/ TAN). The change was due to a significant decrease in intracellular GSH level without significant change in [GSSG]. Cells exposed to BSO for 24 hr were much more sensitive to subsequent injuries caused by Cd (0.6 mM for 3 hr). The results indicated that while a significant reduction of intracellular redox state did not affect cell viability, it could increase the susceptibility of cells to subsequent chemical stress. N-acetylcysteine (NAC), on the other hand, caused a dose (1, 5 and 10 mM)-dependent increase in GSH/GSSG without significant changes in intracellular energy state. Improvement of intracellular GSH/GSSG offered no protection against subsequent Cd induced cell death unless NAC was present at the time Cd was added. The pattern of cell death also correlated with the increase in intracellular free radial generation as measured by the fluorescence labeling with 27- dichlorofluorescin. Results of the present study demonstrated that intracellular redox states could be manipulated by addition of chemicals that affect glutathione metabolism. While the redox state may not be the sufficient condition to cause cell death, it could modulate the response of cells to subsequent Cd treatment. Furthermore, the action of NAC against Cd cytotoxicity may not be related to intracellular redox status.

  14. The Efficacy of Umbelliferone, Arbutin, and N-Acetylcysteine to Prevent Microbial Colonization and Biofilm Development on Urinary Catheter Surface: Results from a Preliminary Study

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    Tommaso Cai

    2016-01-01

    Full Text Available We evaluated, in a preliminary study, the efficacy of umbelliferone, arbutin, and N-acetylcysteine to inhibit biofilm formation on urinary catheter. We used 20 urinary catheters: 5 catheters were incubated with Enterococcus faecalis (control group; 5 catheters were incubated with E. faecalis in presence of umbelliferone (150 mg, arbutin (60 mg, and N-acetylcysteine (150 mg (group 1; 5 catheters were incubated with E. faecalis in presence of umbelliferone (150 mg, arbutin (60 mg, and N-acetylcysteine (400 mg (group 2; and 5 catheters were incubated with E. faecalis in presence of umbelliferone (300 mg, arbutin (60 mg, and N-acetylcysteine (150 mg (group 3. After 72 hours, planktonic microbial growth and microorganisms on catheter surface were assessed. In the control group, we found a planktonic load of ≥105 CFU/mL in the inoculation medium and retrieved 3.69 × 106 CFU/cm from the sessile cells adherent to the catheter surface. A significantly lower amount in planktonic (p<0.001 and sessile (p=0.004 bacterial load was found in group 3, showing <100 CFU/mL and 0.12 × 106 CFU/cm in the incubation medium and on the catheter surface, respectively. In groups 1 and 2, 1.67 × 106 CFU/cm and 1.77 × 106 CFU/cm were found on catheter surface. Our results document that umbelliferone, arbutin, and N-acetylcysteine are able to reduce E. faecalis biofilm development on the surface of urinary catheters.

  15. Effect of treatment with N-acetylcysteine on non-enzymatic antioxidant reserves and lipid peroxidation in workers exposed to lead

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    Sławomir Kasperczyk

    2014-06-01

    Full Text Available There are no published studies examining the effects of N-acetylcysteine (NAC administration on the non-enzymatic defence systems in humans exposed to lead. In view of this, it was decided to measure the levels of uric acid (UA, albumin, bilirubin and alpha-tocopherol before and after treatment with NAC. An estimation was also made of the degree of oxidative stress by measuring the ferric reducing ability of plasma (FRAP, the levels of conjugated dienes (CD and lipid hydroperoxides (LHP. Male employees who worked with lead were randomized into two groups. The first group included workers who were not administered any drugs (n=49, while the second group (n=122 consisted of workers who were treated with NAC at three different doses (200 mg, 400 mg and 800 mg for 12 weeks. The administration of NAC (400 mg, 800 mg resulted in significant decreases in the LHP levels. Similarly, a strong tendency toward lower levels of CD was observed in the same groups. The UA levels were significantly lower only in the group receiving the 200 mg dose of NAC. However, the alpha-tocopherol levels were significantly elevated after treatment with NAC (400 mg, 800 mg. NAC administration did not significantly affect the levels of bilirubin and albumin, but a tendency toward higher values was observed for FRAP. NAC reduced the extent of lipid peroxidation in a dose-dependent manner. Elevated concentrations of alpha-tocopherol may have enhanced the beneficial effects of NAC. Treatment with NAC may contribute to the restoration of non-enzymatic antioxidant reserves when administered to lead-exposed workers.

  16. Effect of fraxetin on antioxidant defense and stress proteins in human neuroblastoma cell model of rotenone neurotoxicity. Comparative study with myricetin and N-acetylcysteine

    International Nuclear Information System (INIS)

    Molina-Jimenez, Maria Francisca; Sanchez-Reus, Maria Isabel; Cascales, Maria; Andres, David; Benedi, Juana

    2005-01-01

    Mitochondrial complex I inhibitor rotenone induces apoptosis through enhancing mitochondrial reactive oxygen species production. Recently, it has been shown that fraxetin (coumarin) and myricetin (flavonoid) have significant neuroprotective effects against apoptosis induced by rotenone, increase the total glutathione levels in vitro, and inhibit lipid peroxidation. Thus, these considerations prompted us to investigate the way in which fraxetin and myricetin affect the endogenous antioxidant defense system, such as Mn and CuZn superoxide dismutase (MnSOD, CuZnSOD), catalase, glutathione reductase (GR), and glutathione peroxidase (GPx) on rotenone neurotoxicity in neuroblastoma cells. N-acetylcysteine (NAC), a potent antioxidant, was employed as a comparative agent. Also, the expression and protein levels of HSP70 by Northern and Western blot analysis were assayed in SH-SY5Y cells. After incubation for 16 h, rotenone significantly increased the expression and activity of MnSOD, GPx, and catalase. When cells were preincubated with fraxetin, there was a decrease in the protein levels and activity of both MnSOD and catalase, in comparison with the rotenone treatment. The myricetin effect was less pronounced. Activity and expression of GPx were increased by rotenone and pre-treatment with fraxetin did not modify significantly these levels. The significant enhancement in HSP70 expression at mRNA and protein levels induced by fraxetin was observed by pre-treatment of cells 0.5 h before rotenone insult. These data suggest that major features of rotenone-induced neurotoxicity are partially mediated by free radical formation and oxidative stress, and that fraxetin partially protects against rotenone toxicity affecting the main protection system of the cells against oxidative injury

  17. The role of prophylactic ibuprofen and N-acetylcysteine on the level of cytokines in periapical exudates and the post-treatment pain

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    Ehsani Maryam

    2012-09-01

    Full Text Available Abstract Background Periapical lesions are inflammatory diseases that result in periapical bone destruction because of host defensive–microbial disturbances. Objective To evaluate the role of prophylactic ibuprofen and N-acetylcysteine (NAC on the levels of tumor necrosis factor alpha (TNF- α, interleukin- 6(IL-6 and IL-17 and post-treatment pain level in chronic periapical lesions. Materials and methods Eighty patients with chronic apical lesions less than 1 cm were randomly assigned to receive NAC tablets (400 mg, ibuprofen tablets (400 mg, NAC (400 mg/ibuprofen (200 mg combination and placebo 90 minutes prior to sampling. Periapical exudates were collected from root canals. TNF- α, IL-6 and IL-17 levels were determined by ELISA and post-treatment pain was assessed using a visual analog scale (VAS. Results There was a significant difference in IL-6 level between ibuprofen group and placebo (p = 0.019. Significant difference in IL-17 level was observed between NAC/ibuprofen combination group and placebo (p = 0.043. Four hours after treatment, a significant difference was observed in VAS pain score between ibuprofen group and placebo (p = 0.017. Eight hours post-treatment, VAS pain score for NAC group was statistically lower than placebo group (p = 0.033. After 12 hours VAS pain score showed a significant decrease in NAC group compared to placebo (p = 0.049. Conclusion The prophylactic ibuprofen and NAC failed to clearly reflect their effect on cytokines levels in exudates of chronic periapical lesions. On the other hand it seems that NAC can be a substitute for ibuprofen in the management of post endodontic pain.

  18. N-Acetylcysteine, a glutathione precursor, reverts vascular dysfunction and endothelial epigenetic programming in intrauterine growth restricted guinea pigs.

    Science.gov (United States)

    Herrera, Emilio A; Cifuentes-Zúñiga, Francisca; Figueroa, Esteban; Villanueva, Cristian; Hernández, Cherie; Alegría, René; Arroyo-Jousse, Viviana; Peñaloza, Estefania; Farías, Marcelo; Uauy, Ricardo; Casanello, Paola; Krause, Bernardo J

    2017-02-15

    Intrauterine growth restriction (IUGR) is associated with vascular dysfunction, oxidative stress and signs of endothelial epigenetic programming of the umbilical vessels. There is no evidence that this epigenetic programming is occurring on systemic fetal arteries. In IUGR guinea pigs we studied the functional and epigenetic programming of endothelial nitric oxide synthase (eNOS) (Nos3 gene) in umbilical and systemic fetal arteries, addressing the role of oxidative stress in this process by maternal treatment with N-acetylcysteine (NAC) during the second half of gestation. The present study suggests that IUGR endothelial cells have common molecular markers of programming in umbilical and systemic arteries. Notably, maternal treatment with NAC restores fetal growth by increasing placental efficiency and reverting the functional and epigenetic programming of eNOS in arterial endothelium in IUGR guinea pigs. In humans, intrauterine growth restriction (IUGR) is associated with vascular dysfunction, oxidative stress and signs of endothelial programming in umbilical vessels. We aimed to determine the effects of maternal antioxidant treatment with N-acetylcysteine (NAC) on fetal endothelial function and endothelial nitric oxide synthase (eNOS) programming in IUGR guinea pigs. IUGR was induced by implanting ameroid constrictors on uterine arteries of pregnant guinea pigs at mid gestation, half of the sows receiving NAC in the drinking water (from day 34 until term). Fetal biometry and placental vascular resistance were followed by ultrasound throughout gestation. At term, umbilical arteries and fetal aortae were isolated to assess endothelial function by wire-myography. Primary cultures of endothelial cells (ECs) from fetal aorta, femoral and umbilical arteries were used to determine eNOS mRNA levels by quantitative PCR and analyse DNA methylation in the Nos3 promoter by pyrosequencing. Doppler ultrasound measurements showed that NAC reduced placental vascular resistance

  19. P2X(7) receptor in the kidneys of diabetic rats submitted to aerobic training or to N-acetylcysteine supplementation [corrected].

    Science.gov (United States)

    Rodrigues, Adelson M; Bergamaschi, Cassia T; Fernandes, Maria Jose S; Paredes-Gamero, Edgar J; Buri, Marcus V; Curi, Marcus V; Ferreira, Alice T; Araujo, Sergio R R; Punaro, Giovana R; Maciel, Fabiane R; Nogueira, Guilherme B; Higa, Elisa M S

    2014-01-01

    Previous studies in our laboratory showed that N-acetylcysteine supplementation or aerobic training reduced oxidative stress and the progression of diabetic nephropathy in rats. The P2X(7 receptor is up-regulated in pathological conditions, such as diabetes mellitus. This up-regulation is related to oxidative stress and induces tissue apoptosis or necrosis. The aim of the present study is to assess the role of P2X(7) receptor in the kidneys of diabetic rats submitted to aerobic training or N-acetylcysteine supplementation. Diabetes was induced in male Wistar rats by streptozotocin (60 mg/kg, i.v.) and the training was done on a treadmill; N-acetylcysteine was given in the drinking water (600 mg/L). By confocal microscopy, as compared to control, the kidneys of diabetic rats showed increased P2 × 7 receptor expression and a higher activation in response to 2'(3')-O-(4-benzoylbenzoyl) adenosine5'-triphosphate (specific agonist) and adenosine triphosphate (nonspecific agonist) (all p<0.05). All these alterations were reduced in diabetic rats treated with N-acetylcysteine, exercise or both. We also observed measured proteinuria and albuminuria (early marker of diabetic nephropathy) in DM groups. Lipoperoxidation was strongly correlated with P2X(7) receptor expression, which was also correlated to NO•, thus associating this receptor to oxidative stress and kidney lesion. We suggest that P2X(7) receptor inhibition associated with the maintenance of redox homeostasis could be useful as coadjuvant treatment to delay the progression of diabetic nephropathy.

  20. P2X(7 receptor in the kidneys of diabetic rats submitted to aerobic training or to N-acetylcysteine supplementation [corrected].

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    Adelson M Rodrigues

    Full Text Available Previous studies in our laboratory showed that N-acetylcysteine supplementation or aerobic training reduced oxidative stress and the progression of diabetic nephropathy in rats. The P2X(7 receptor is up-regulated in pathological conditions, such as diabetes mellitus. This up-regulation is related to oxidative stress and induces tissue apoptosis or necrosis. The aim of the present study is to assess the role of P2X(7 receptor in the kidneys of diabetic rats submitted to aerobic training or N-acetylcysteine supplementation. Diabetes was induced in male Wistar rats by streptozotocin (60 mg/kg, i.v. and the training was done on a treadmill; N-acetylcysteine was given in the drinking water (600 mg/L. By confocal microscopy, as compared to control, the kidneys of diabetic rats showed increased P2 × 7 receptor expression and a higher activation in response to 2'(3'-O-(4-benzoylbenzoyl adenosine5'-triphosphate (specific agonist and adenosine triphosphate (nonspecific agonist (all p<0.05. All these alterations were reduced in diabetic rats treated with N-acetylcysteine, exercise or both. We also observed measured proteinuria and albuminuria (early marker of diabetic nephropathy in DM groups. Lipoperoxidation was strongly correlated with P2X(7 receptor expression, which was also correlated to NO•, thus associating this receptor to oxidative stress and kidney lesion. We suggest that P2X(7 receptor inhibition associated with the maintenance of redox homeostasis could be useful as coadjuvant treatment to delay the progression of diabetic nephropathy.

  1. Chronic N-acetylcysteine administration prevents development of hypertension in Nomega-nitro-L-arginine methyl ester-treated rats: the role of reactive oxygen species

    Czech Academy of Sciences Publication Activity Database

    Rauchová, Hana; Pecháňová, O.; Kuneš, Jaroslav; Vokurková, Martina; Dobešová, Zdenka; Zicha, Josef

    2005-01-01

    Roč. 28, č. 5 (2005), s. 475-482 ISSN 0916-9636 R&D Projects: GA ČR(CZ) GA305/03/0769; GA MZd(CZ) NR7786 Grant - others:VEGA(SK) 02/3185/24; SAV(SK) APVT-51-017902 Institutional research plan: CEZ:AV0Z5011922 Keywords : N-acetylcysteine * nitric oxide synthase * superoxide anions Subject RIV: ED - Physiology Impact factor: 2.786, year: 2005

  2. Inhibition with N-acetylcysteine of enhanced production of tumor necrosis factor in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Sagara, M; Satoh, J; Zhu, X P; Takahashi, K; Fukuzawa, M; Muto, G; Muto, Y; Toyota, T

    1994-06-01

    We previously reported that the in vivo production of the tumor necrosis factor alpha (TNF) was significantly enhanced after the onset of diabetes in spontaneous type 1 and 2 diabetic animals. In this report we confirmed the enhanced production of TNF in streptozotocin (STZ)-induced diabetes and then attempted to suppress the enhanced TNF production with N-acetylcysteine (NAC), a precursor of glutathione synthesis. The lipopolysaccharide-induced serum TNF activities were significantly enhanced in STZ-induced diabetic rats (6-18 weeks of age) compared with those of nondiabetic rats throughout the 12-week experiment. A single, oral administration of NAC (200 or 1000 mg/kg body wt) significantly suppressed the enhanced TNF production in the diabetic rats compared with that in untreated rats in a dose-dependent manner. On the other hand, in the long-term (6 or 12 weeks) administrations, smaller doses of NAC (50 or 200 mg/kg/day) also significantly inhibited the enhanced production of TNF regardless of the dose of NAC. NAC administration, however, did not suppress the TNF production of nondiabetic rats. The long-term NAC administration affected neither body weight nor levels of serum glucose, fructosamine, albumin, and triglyceride. These results show that NAC administration significantly suppressed the enhanced TNF production in diabetic rats and indicate that NAC might be useful in preventing TNF-mediated pathological conditions in diabetes.

  3. N-Acetylcysteine enhances the action of anti-inflammatory drugs as suppressors of prostaglandin production in monocytes

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    Erica Hoffer

    2002-01-01

    Full Text Available The anti-inflammatory effect of non-steroidal anti-inflammatory drugs (NSAIDs is associated with inhibition of cyclooxygenase (COX, the rate-limiting enzyme responsible for the synthesis of prostaglandins. Since oxygen free radicals can act as second cellular messengers, especially to modulate the metabolism of arachidonic acid and the prostaglandin tract, it seems plausible that antioxidants might affect the production of prostaglandin by activated cells. This research is focused on the effect of the antioxidant N-acetylcysteine (NAC on the inhibition of prostaglandin E2 formation in activated monocytes by specific and non-specific COX inhibitors. We found that lipopolysaccharide-induced prostaglandin E2 formation was significantly reduced by rofecoxib and by diclofenac, two NSAIDs. Addition of NAC to each of these drugs enhanced the effect of the NSAIDs. These results suggest that one might expect either a potentiation of the anti-inflammatory effect of COX inhibitors by their simultaneous administration with NAC, or obtaining the same anti-inflammatory at lower drug levels.

  4. N-Acetylcysteine Prevents Hypertension via Regulation of the ADMA-DDAH Pathway in Young Spontaneously Hypertensive Rats

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    Nai-Chia Fan

    2013-01-01

    Full Text Available Asymmetric dimethylarginine (ADMA reduces nitric oxide (NO, thus causing hypertension. ADMA is metabolized by dimethylarginine dimethylaminohydrolase (DDAH, which can be inhibited by oxidative stress. N-Acetylcysteine (NAC, an antioxidant, can facilitate glutathione (GSH synthesis. We aimed to determine whether NAC can prevent hypertension by regulating the ADMA-DDAH pathway in spontaneously hypertensive rats (SHR. Rats aged 4 weeks were assigned into 3 groups (n=8/group: control Wistar Kyoto rats (WKY, SHR, and SHR receiving 2% NAC in drinking water. All rats were sacrificed at 12 weeks of age. SHR had higher blood pressure than WKY, whereas NAC-treated animals did not. SHR had elevated plasma ADMA levels, which was prevented by NAC therapy. SHR had lower renal DDAH activity than WKY, whereas NAC-treated animals did not. Renal superoxide production was higher in SHR than in WKY, whereas NAC therapy prevented it. NAC therapy was also associated with higher GSH-to-oxidized GSH ratio in SHR kidneys. Moreover, NAC reduced oxidative stress damage in SHR. The observed antihypertensive effects of NAC in young SHR might be due to restoration of DDAH activity to reduce ADMA, leading to attenuation of oxidative stress. Our findings highlight the impact of NAC on the development of hypertension by regulating ADMA-DDAH pathway.

  5. N-acetylcysteine modulates angiogenesis and vasodilation in stomach such as DNA damage in blood of portal hypertensive rats.

    Science.gov (United States)

    Licks, Francielli; Hartmann, Renata Minuzzo; Marques, Camila; Schemitt, Elizângela; Colares, Josieli Raskopf; Soares, Mariana do Couto; Reys, Juliana; Fisher, Camila; da Silva, Juliana; Marroni, Norma Possa

    2015-11-21

    To evaluate the antioxidant effect of N-acetylcysteine (NAC) on the stomach of rats with portal hypertension. Twenty-four male Wistar rats weighing ± 250 g were divided into four experimental groups (n = 6 each): Sham-operated (SO), SO + NAC, partial portal vein ligation (PPVL), and PPVL + NAC. Treatment with NAC in a dose of 10 mg/kg (i.p.) diluted in 0.6 mL of saline solution was administered daily for 7 d starting 8 d after the surgery. Animals from the PPVL and SO group received saline solution (0.6 mL) for the same period of time as the PPVL + NAC and SO + NAC group. On the 15(th) day the animals were anesthetized and we evaluated portal pressure by cannulating mesenteric artery. After, we removed the stomach for further analysis. We performed immunohistochemical analysis for endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), and nitrotirosine (NTT) proteins in stomach. We also evaluated eNOS and VEGF by Western blot analysis and assessed DNA damage in blood samples by the comet assay. The portal hypertension group exhibited increases in portal pressure when compared to SO group (29.8 ± 1.8 vs 12.0 ± 0.3 mmHg) (P stomach from the alterations induced by the PPVL procedure.

  6. Minocycline synergizes with N-acetylcysteine and improves cognition and memory following traumatic brain injury in rats.

    Science.gov (United States)

    Abdel Baki, Samah G; Schwab, Ben; Haber, Margalit; Fenton, André A; Bergold, Peter J

    2010-08-31

    There are no drugs presently available to treat traumatic brain injury (TBI). A variety of single drugs have failed clinical trials suggesting a role for drug combinations. Drug combinations acting synergistically often provide the greatest combination of potency and safety. The drugs examined (minocycline (MINO), N-acetylcysteine (NAC), simvastatin, cyclosporine A, and progesterone) had FDA-approval for uses other than TBI and limited brain injury in experimental TBI models. Drugs were dosed one hour after injury using the controlled cortical impact (CCI) TBI model in adult rats. One week later, drugs were tested for efficacy and drug combinations tested for synergy on a hierarchy of behavioral tests that included active place avoidance testing. As monotherapy, only MINO improved acquisition of the massed version of active place avoidance that required memory lasting less than two hours. MINO-treated animals, however, were impaired during the spaced version of the same avoidance task that required 24-hour memory retention. Co-administration of NAC with MINO synergistically improved spaced learning. Examination of brain histology 2 weeks after injury suggested that MINO plus NAC preserved white, but not grey matter, since lesion volume was unaffected, yet myelin loss was attenuated. When dosed 3 hours before injury, MINO plus NAC as single drugs had no effect on interleukin-1 formation; together they synergistically lowered interleukin-1 levels. This effect on interleukin-1 was not observed when the drugs were dosed one hour after injury. These observations suggest a potentially valuable role for MINO plus NAC to treat TBI.

  7. Oxidative stress determined through the levels of antioxidant enzymes and the effect of N-acetylcysteine in aluminum phosphide poisoning.

    Science.gov (United States)

    Agarwal, Avinash; Robo, Roto; Jain, Nirdesh; Gutch, Manish; Consil, Shuchi; Kumar, Sukriti

    2014-10-01

    The primary objective of this study was to determine the serum level of antioxidant enzymes and to correlate them with outcome in patients of aluminum phosphide (ALP) poisoning and, secondly, to evaluate the effect of N-acetylcysteine (NAC) given along with supportive treatment of ALP poisoning. We conducted a cohort study in patients of ALP poisoning hospitalized at a tertiary care center of North India. The treatment group and control group were enrolled during the study period of 1 year from May 2011 to April 2012. Oxidative stress was evaluated in each subject by estimating the serum levels of the enzymes, viz. catalase, superoxide dismutase (SOD) and glutathione reductase (GR). The treatment group comprised of patients who were given NAC in addition to supportive treatment (magnesium sulfate and vasopressors, if required), while in the control group, only supportive treatment was instituted. The primary endpoint of the study was the survival of the patients. The baseline catalase (P = 0.008) and SOD (P poisoning, but baseline GR level has not suppressed but is rather increasing with due time, and more so in the treatment group. NAC along with supportive treatment may have improved survival in ALP poisoning.

  8. Evaluation of N-acetylcysteine and methylprednisolone as therapies for oxygen and acrolein-induced lung damage

    Energy Technology Data Exchange (ETDEWEB)

    Critchley, J.A.J.H. (Univ. of Edinburgh (England)); Beeley, J.M.; Clark, R.J.; Buchanan, J.D. (Royal Naval Hospital Hoslar, Gosport (England)); Summerfield, M.; Bell, S. (Admiralty Research Establishment, Alverstoke (England)); Spurlock, M.S.; Edginton, J.A.G. (Chemical Defence Establishment, Porton Down (England))

    1990-04-01

    Reactive oxidizing species are implicated in the etiology of a range of inhalational pulmonary injuries. Consequently, various free radical scavengers have been tested as potential prophylactic agents. The sulfydryl compound, N-acetylcysteine (NAC) is the only such compound clinically available for use in realistic dosages, and it is well established as an effective antidote for the hepatic and renal toxicity of paracetamol. Another approach in pulmonary injury prophylaxis is methylprednisolone therapy. The authors evaluated NAC and methylprednisolone in two rats models of inhalation injury: 40-hr exposure to >97% oxygen at 1.1 bar and 15-min exposure to acrolein vapor (210 ppm). The increases in lung wet/dry weight ratios, seen with both oxygen and acrolein toxicity were reduced with both treatments. However, with oxygen, NAC therapy was associated with considerably increased mortality and histological changes. Furthermore, IP NAC administration resulted in large volumes of ascitic fluid. With acrolein, IV, NAC had no significant effect on mortality or pulmonary histological damage. Methylprednisolone had no beneficial effects on either the mortality or histological damage observed in either toxicity model. They caution against the ad hoc use of NAC in the management of inhalational pulmonary injury.

  9. Successful use of N-acetylcysteine to treat severe hepatic injury caused by a dietary fitness supplement.

    Science.gov (United States)

    El Rahi, Cynthia; Thompson-Moore, Nathaniel; Mejia, Patricia; De Hoyos, Patricio

    2015-06-01

    In the absence of adequate premarketing efficacy and safety evaluations, adverse events from over-the-counter supplements are emerging as a public health concern. Specifically, bodybuilding products are being identified as a frequent cause of drug-induced liver injury. We present a case of a 20-year-old Hispanic male who presented with acute nausea and vomiting accompanied by severe right upper quadrant abdominal pain, shivering, and shortness of breath. Laboratory data pointed to mixed cholestatic and hepatocellular damage, and after exclusion of known alternate etiologies, the patient was diagnosed with acute drug-induced liver injury secondary to the use of "Friction," a bodybuilding supplement. Treatment with N-acetylcysteine (NAC) 20% oral solution was initiated empirically at a dose of 4000 mg [DOSAGE ERROR CORRECTED] (70 mg/kg) every 4 hours and was continued once the diagnosis was made. Within 48 hours of admission to our hospital, the patient began to show clinical resolution of right abdominal pain and tolerance to oral diet associated with a significant decline toward normal in his liver function tests and coagulopathy. The WHO-UMC causality assessment system suggested a "certain causality" between exposure to the supplement and the acute liver injury. In the event of suspected drug-induced liver injury, treatment with NAC should be considered given its favorable risk-benefit profile. © 2015 Pharmacotherapy Publications, Inc.

  10. Protective effect of N-Acetylcysteine against ethanol-induced gastric ulcer: a pharmacological assessment in mice

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    Ausama Ayoob Jaccob

    2015-06-01

    Aim: Since there is an increasing need for gastric ulcer therapies with optimum benefit-risk profile. This study was conducted to investigate gastro-protective effects of N-Acetylcysteine (NAC against ethanol-induced gastric ulcer models in mice. Materials and Methods: Forty-two mice were allocated into six groups consisting of 7 mice each. Groups 1 (normal control and 2 (ulcer control received distilled water at a dose of 10 ml/kg, groups 3, 4 and 5 were given NAC at doses 100, 300 and 500 mg/kg, respectively, and the 6th group received ranitidine (50 mg/kg. All drugs administered orally once daily for 7 days, on the 8th day absolute ethanol (7 ml/kg was administrated orally to all mice to induce the acute ulcer except normal control group. Then 3 h after, all animals were sacrificed then consequently the stomachs were excised for examination. Results: NAC administration at the tested doses showed a dose-related potent gastro-protective effect with significant increase in curative ratio, PH of gastric juice and mucus content viscosity seen with the highest dose of NAC and it is comparable with that observed in ranitidine group. Conclusion: The present findings demonstrate that, oral NAC shows significant gastro-protective effects comparable to ranitidine confirmed by antisecretory, cytoprotective, histological and biochemical data but the molecular mechanisms behind such protection are complex. [J Intercult Ethnopharmacol 2015; 4(2.000: 90-95

  11. N-Acetylcysteine for Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials

    Directory of Open Access Journals (Sweden)

    Divyesh Thakker

    2015-01-01

    Full Text Available Objective. To review the benefits and harms of N-acetylcysteine (NAC in women with polycystic ovary syndrome (PCOS. Method. Literature search was conducted using the bibliographic databases, MEDLINE (Ovid, CINAHL, EMBASE, Scopus, PsyInfo, and PROQUEST (from inception to September 2013 for the studies on women with PCOS receiving NAC. Results. Eight studies with a total of 910 women with PCOS were randomized to NAC or other treatments/placebo. There were high risk of selection, performance, and attrition bias in two studies and high risk of reporting bias in four studies. Women with NAC had higher odds of having a live birth, getting pregnant, and ovulation as compared to placebo. However, women with NAC were less likely to have pregnancy or ovulation as compared to metformin. There was no significant difference in rates of the miscarriage, menstrual regulation, acne, hirsutism, and adverse events, or change in body mass index, testosterone, and insulin levels with NAC as compared to placebo. Conclusions. NAC showed significant improvement in pregnancy and ovulation rate as compared to placebo. The findings need further confirmation in well-designed randomized controlled trials to examine clinical outcomes such as live birth rate in longer follow-up periods. Systematic review registration number is CRD42012001902.

  12. Pilot study demonstrating metabolic and anti-proliferative effects of in vivo anti-oxidant supplementation with N-Acetylcysteine in Breast Cancer.

    Science.gov (United States)

    Monti, Daniel; Sotgia, Federica; Whitaker-Menezes, Diana; Tuluc, Madalina; Birbe, Ruth; Berger, Adam; Lazar, Melissa; Cotzia, Paolo; Draganova-Tacheva, Rossitza; Lin, Zhao; Domingo-Vidal, Marina; Newberg, Andrew; Lisanti, Michael P; Martinez-Outschoorn, Ubaldo

    2017-06-01

    High oxidative stress as defined by hydroxyl and peroxyl activity is often found in the stroma of human breast cancers. Oxidative stress induces stromal catabolism, which promotes cancer aggressiveness. Stromal cells exposed to oxidative stress release catabolites such as lactate, which are up-taken by cancer cells to support mitochondrial oxidative phosphorylation. The transfer of catabolites between stromal and cancer cells leads to metabolic heterogeneity between these cells and increased cancer cell proliferation and reduced apoptosis in preclinical models. N-Acetylcysteine (NAC) is an antioxidant that reduces oxidative stress and reverses stromal catabolism and stromal-carcinoma cell metabolic heterogeneity, resulting in reduced proliferation and increased apoptosis of cancer cells in experimental models of breast cancer. The purpose of this clinical trial was to determine if NAC could reduce markers of stromal-cancer metabolic heterogeneity and markers of cancer cell aggressiveness in human breast cancer. Subjects with newly diagnosed stage 0 and I breast cancer who were not going to receive neoadjuvant therapy prior to surgical resection were treated with NAC before definitive surgery to assess intra-tumoral metabolic markers. NAC was administered once a week intravenously at a dose of 150 mg/kg and 600 mg twice daily orally on the days not receiving intravenous NAC. Histochemistry for the stromal metabolic markers monocarboxylate transporter 4 (MCT4) and caveolin-1 (CAV1) and the Ki67 proliferation assay and TUNEL apoptosis assay in carcinoma cells were performed in pre- and post-NAC specimens. The range of days on NAC was 14-27 and the mean was 19 days. Post-treatment biopsies showed significant decrease in stromal MCT4 and reduced Ki67 in carcinoma cells. NAC did not significantly change stromal CAV1 and carcinoma TUNEL staining. NAC was well tolerated. NAC as a single agent reduces MCT4 stromal expression, which is a marker of glycolysis in breast cancer

  13. Pre-treatment with N-acetylcysteine upregulates superoxide dismutase 2 and catalase genes in cadmium-induced oxidative stress in the chick omphalocele model.

    Science.gov (United States)

    Doi, Takashi; Puri, Prem; Bannigan, John; Thompson, Jennifer

    2011-02-01

    In the chick embryo, administration of the heavy metal Cadmium (Cd) induces omphalocele phenotype. Cd is a potent inhibitor of antioxidant enzymes and causes accumulation of reactive oxygen species (ROSs) such as hydrogen peroxide. Previous work with the Cd chick model has demonstrated that increased levels of MDA, as a marker for oxidative stress, 24 h post Cd treatment (24H) are identical in chick embryos exposed to Cd. Furthermore, of the several antioxidants assessed, only N-acetylcysteine (NAC) has been shown to reduce MDA levels to control values in the Cd-treated chick embryo. However, the molecular mechanisms by which NAC acts to maintain oxidative stress in the Cd-induced ventral body wall defect chick model remains to be unclear. We designed this study to investigate the hypothesis that gene expression levels of antioxidant enzymes are downregulated in malformed embryos exposed to Cd compared to controls and to determine the effect of pre-treatment with NAC on the expression levels of genes encoding antioxidant enzymes. After 60 h incubation, chick embryos were pre-treated with NAC and exposed to either chick saline or Cd. Chicks were then harvested at 24H and divided into five groups: control, Cd group without malformation [Cd(-)], Cd group with malformation [Cd(+)], NAC + Cd(-) and NAC + Cd(+). Real-time PCR was performed to evaluate the relative mRNA expression levels of antioxidant enzymes, including superoxide dismutase (SOD)-1, SOD2, catalase (CAT) and glutathione peroxidase (GPX)-4. Differences between five groups were tested by Tukey-Kramer post-hoc test following one-way ANOVA. Statistical significance was accepted at p < 0.05. Immunohistochemistry was also performed to evaluate protein expression. The mRNA expression levels of SOD2 and CAT were significantly decreased in Cd(+) as compared to controls, whereas there was no significant difference between controls and Cd(-) (p < 0.05 vs. controls). In addition, gene expression levels of

  14. Probenecid and N-Acetylcysteine Prevent Loss of Intracellular Glutathione and Inhibit Neuronal Death after Mechanical Stretch Injury In Vitro.

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    Du, Lina; Empey, Philip E; Ji, Jing; Chao, Honglu; Kochanek, Patrick M; Bayır, Hülya; Clark, Robert S B

    2016-10-15

    Probenecid and N-acetylcysteine (NAC) can preserve intracellular levels of the vital antioxidant glutathione (GSH) via two distinct biochemical pathways. Probenecid inhibits transporter-mediated GSH efflux and NAC serves as a cysteine donor for GSH synthesis. We hypothesized that probenecid and NAC alone would maintain intracellular GSH concentrations and inhibit neuronal death after traumatic stretch injury, and that the drugs in combination would produce additive effects. Sex-segregated rat primary cortical neurons were treated with probenecid (100 μM) and NAC (50 μM), alone and in combination (Pro-NAC), then subjected to mechanical stretch (10s -1 strain rate, 50% membrane deformation). At 24 h, both probenecid and NAC inhibited trauma-induced intracellular GSH depletion, lactate dehydrogenase (LDH) release, and propidium iodide (PI) uptake in both XY- and XX-neurons. Combined Pro-NAC treatment was superior to probenecid or NAC alone in maintenance of intracellular GSH and neuronal death assessed by PI uptake. Interestingly, caspase 3 activity 24 h after mechanical trauma was more prominent in XX-neurons, and treatment effects (probenecid, NAC, and Pro-NAC) were observed in XX- but not XY-neurons; however, XY-neurons were ultimately more vulnerable to mechanical stretch-induced injury than their XX counterparts, as was evidenced by more neuronal death detected by LDH release and PI uptake. In addition, after stretch injury in HT22 hippocampal cells, both NAC and probenecid were highly effective at reducing oxidative stress detected by dichlorofluorescein fluorescence. These in vitro data support further testing of this drug combination in models of traumatic neuronal injury in vivo.

  15. Outlining adequate protocols for Lidia bull epididymal storage and sperm cryopreservation: use of glycerol, dimethylformamide and N-acetylcysteine

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    Elvira Matilla

    2017-12-01

    Full Text Available The Lidia bovine breed is an important hallmark of the Spanish cattle industry. Bulls are selected based upon aggressiveness and epididymal sperm cryopreservation is the way to obtain and store their genetics. There are not specifically designed protocols yet to perform Lidia bull sperm cryopreservation. The present study aimed to determine if a tris-fructose-citrate-egg yolk (20% v/v; TFY extender supplemented with 7% glycerol (TFY1 or 3.5% glycerol plus 3.5% dimethylformamide (DMF; TFY2 are suitable media for cryopreservation of epididymal Lidia bull sperm. Moreover, the effect of N-acetylcysteine (NAC, a potent antioxidant, was evaluated. The epididymis were stored at 4°C for 24, 48, 72 or 96 h, and both freezing media were tested as such or supplemented with 1 or 2.5 mM of NAC. Our data demonstrated that post-thaw viability was well maintained (TFY1: 50.8% ± 1.9 at 24 h and 52.4% ± 0.8 at 96 h and TFY2: 52.6% ± 1.6 at 24 h and 56.1% ± 1.8 at 96 h; mean % ± SEM; p>0.05 as also were total and progressive sperm motility, high mitochondrial membrane potential, ROS production, DNA status and acrosomal intactness of Lidia bull sperm up to 96 h of epididymal storage, all extender variations being similar (p>0.05. In conclusion, the use of TFY medium supplemented either with 7% glycerol alone or the combination of 3.5% glycerol and 3.5% DMF were equally safe choices for epididymal Lidia bull sperm cryopreservation, and NAC addition did not significantly improve sperm post-thaw quality.

  16. Evaluation of the Effect of Nebulized N-Acetylcysteine on Respiratory Secretions in Mechanically Ventilated Patients: Randomized Clinical Trial

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    Seyed Masoom Masoompour

    2015-07-01

    Full Text Available Background: The purpose of our study was to evaluate an inexpensive and available method to reduce mucous impactions in mechanically ventilated patients. Methods: This randomized clinical trial was conducted on 40 mechanically ventilated patients aged 15-90 years. The patients were randomly allocated into two arms; 20 cases and 20 controls. The cases received N-acetylcysteine via their nebulizers, and the control group received normal saline three times a day for one day. We measured the density of respiratory secretion, plateau and peak airway pressures, and O2 saturation at baseline, 12 and 24 hours later. Results: Although the mean secretion density was significantly lower in the NAC group (F (1, 38=8.61, P=0.006, but a repeated measures ANOVA with a Greenhouse-Geisser correction determined that the effect of NAC on mean secretion density did not differ significantly between time points (F (1, 38=3.08, P=0.087. NAC increased O2 saturation significantly between time points (F (1.92, 73.1=4.6, P=0.014. The plateau airway pressures were relatively stable throughout the study in the normal saline and NAC groups (F (1.95, 37.1=0.67, P=0.513. The peak airway pressure did not change significantly during the study in the normal saline and NAC groups (F (1.52, 56.4=0.91, P=0.384. Conclusion: Considering the limitations of the study, nebulized NAC in mechanically ventilated patients was not effective more than normal saline nebulization in reducing the density of mucous plugs. The peak and plateau airway pressures were relatively stable throughout the study in both groups. Trial Registration Number: IRCT201104276312N1.

  17. Intravenous N-acetylcysteine in pediatric patients with nonacetaminophen acute liver failure: a placebo-controlled clinical trial.

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    Squires, Robert H; Dhawan, Anil; Alonso, Estella; Narkewicz, Michael R; Shneider, Benjamin L; Rodriguez-Baez, Norberto; Olio, Dominic Dell; Karpen, Saul; Bucuvalas, John; Lobritto, Steven; Rand, Elizabeth; Rosenthal, Philip; Horslen, Simon; Ng, Vicky; Subbarao, Girish; Kerkar, Nanda; Rudnick, David; Lopez, M James; Schwarz, Kathleen; Romero, Rene; Elisofon, Scott; Doo, Edward; Robuck, Patricia R; Lawlor, Sharon; Belle, Steven H

    2013-04-01

    N-acetylcysteine (NAC) was found to improve transplantation-free survival in only those adults with nonacetaminophen (non-APAP) acute liver failure (ALF) and grade 1-2 hepatic encephalopathy (HE). Because non-APAP ALF differs significantly between children and adults, the Pediatric Acute Liver Failure (PALF) Study Group evaluated NAC in non-APAP PALF. Children from birth through age 17 years with non-APAP ALF enrolled in the PALF registry were eligible to enter an adaptively allocated, doubly masked, placebo-controlled trial using a continuous intravenous infusion of NAC (150 mg/kg/day in 5% dextrose in water [D5W]) or placebo (D5W) for up to 7 days. The primary outcome was 1-year survival. Secondary outcomes included liver transplantation-free survival, liver transplantation (LTx), length of intensive care unit (ICU) and hospital stays, organ system failure, and maximum HE score. A total of 184 participants were enrolled in the trial with 92 in each arm. The 1-year survival did not differ significantly (P = 0.19) between the NAC (73%) and placebo (82%) treatment groups. The 1-year LTx-free survival was significantly lower (P = 0.03) in those who received NAC (35%) than those who received placebo (53%), particularly, but not significantly so, among those less than 2 years old with HE grade 0-1 (NAC 25%; placebo 60%; P = 0.0493). There were no significant differences between treatment arms for hospital or ICU length of stay, organ systems failing, or highest recorded grade of HE. NAC did not improve 1-year survival in non-APAP PALF. One-year LTx-free survival was significantly lower with NAC, particularly among those pediatric drug trials, regardless of results in adults. Copyright © 2012 American Association for the Study of Liver Diseases.

  18. Minocycline synergizes with N-acetylcysteine and improves cognition and memory following traumatic brain injury in rats.

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    Samah G Abdel Baki

    Full Text Available BACKGROUND: There are no drugs presently available to treat traumatic brain injury (TBI. A variety of single drugs have failed clinical trials suggesting a role for drug combinations. Drug combinations acting synergistically often provide the greatest combination of potency and safety. The drugs examined (minocycline (MINO, N-acetylcysteine (NAC, simvastatin, cyclosporine A, and progesterone had FDA-approval for uses other than TBI and limited brain injury in experimental TBI models. METHODOLOGY/PRINCIPAL FINDINGS: Drugs were dosed one hour after injury using the controlled cortical impact (CCI TBI model in adult rats. One week later, drugs were tested for efficacy and drug combinations tested for synergy on a hierarchy of behavioral tests that included active place avoidance testing. As monotherapy, only MINO improved acquisition of the massed version of active place avoidance that required memory lasting less than two hours. MINO-treated animals, however, were impaired during the spaced version of the same avoidance task that required 24-hour memory retention. Co-administration of NAC with MINO synergistically improved spaced learning. Examination of brain histology 2 weeks after injury suggested that MINO plus NAC preserved white, but not grey matter, since lesion volume was unaffected, yet myelin loss was attenuated. When dosed 3 hours before injury, MINO plus NAC as single drugs had no effect on interleukin-1 formation; together they synergistically lowered interleukin-1 levels. This effect on interleukin-1 was not observed when the drugs were dosed one hour after injury. CONCLUSIONS/SIGNIFICANCE: These observations suggest a potentially valuable role for MINO plus NAC to treat TBI.

  19. Beneficial Effects of N-acetylcysteine and N-mercaptopropionylglycine on Ischemia Reperfusion Injury in the Heart.

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    Bartekova, Monika; Barancik, Miroslav; Ferenczyova, Kristina; Dhalla, Naranjan S

    2018-01-30

    Ischemia-reperfusion (I/R) injury of the heart as a consequence of myocardial infarction or cardiac surgery represents a serious clinical problem. One of the most prominent mechanisms of I/R injury is the development of oxidative stress in the heart. In this regard, I/R has been shown to enhance the production of reactive oxygen/nitrogen species in the heart which lead to the imbalance between the pro-oxidants and antioxidant capacities of the endogenous radical-scavenging systems. Increasing the antioxidant capacity of the heart by the administration of exogenous antioxidants is considered beneficial for the heart exposed to I/R. N-acetylcysteine (NAC) and Nmercaptopropionylglycine (MPG) are two sulphur containing amino acid substances, which belong to the broad category of exogenous antioxidants that have been tested for their protective potential in cardiac I/R injury. Pretreatment of hearts with both NAC and MPG has demonstrated that these agents attenuate the I/R-induced alterations in sarcolemma, sarcoplasmic reticulum, mitochondria and myofibrils in addition to improving cardiac function. While experimental studies have revealed promising data suggesting beneficial effects of NAC and MPG in cardiac I/R injury, the results of clinical trials are not conclusive because both positive and no effects of these substances have been reported on the post-ischemic recovery of heart following cardiac surgery or myocardial infarction. It is concluded that both NAC and MPG exert beneficial effects in preventing the I/Rinduced injury; however, further studies are needed to establish their effectiveness in reversing the I/R-induced abnormalities in the heart. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Global research productivity of N-acetylcysteine use in paracetamol overdose: A bibliometric analysis (1976-2012).

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    Zyoud, S H; Al-Jabi, S W; Sweileh, W M; Awang, R; Waring, W S

    2015-10-01

    The main objective of this study was to examine the publication pattern of N-acetylcysteine (NAC) research output for paracetamol overdose at the global level. Data were searched for documents that contained specific words regarding NAC and paracetamol as keywords in the title and/or abstract and/or keywords. Scientific output was evaluated based on a methodology developed and used in other bibliometric studies. Research productivity was adjusted to the national population and nominal gross domestic product per capita. The criteria were met by 367 publications from 33 countries. The highest number of articles associated with the use of NAC in paracetamol overdose was from the United States of America (USA; 39.78%), followed by the United Kingdom (UK; 11.99%). After adjusting for economy and population power, USA (2.822), Iran (1.784) and UK (1.125) had the highest research productivity. The total number of citations at the time of data analysis (14 March 2014) was 8785 with an average of 23.9 citations per document and a median (interquartile range) of 6 (1-22). The h-index of the retrieved documents was 48. The highest h-index was 32 for USA, followed by 20 for UK. Furthermore, the highest number of collaborations with international authors for each country was held by USA with 11 countries, followed by Canada with 7 countries. The amount of NAC-based research activity was low in some countries, and more effort is needed to bridge this gap and to promote better evaluation of NAC use worldwide. Our findings demonstrate that NAC use for paracetamol overdose remains a hot issue in scientific research and may have a larger audience compared with other toxicological aspects. Editors and authors in the field of toxicology might usefully promote the submission of work on NAC in future to improve their journal's impact. © The Author(s) 2015.

  1. Incidence and management of N-acetylcysteine-related anaphylactoid reactions during the management of acute paracetamol overdose.

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    Yamamoto, Takahiro; Spencer, Tanya; Dargan, Paul I; Wood, David M

    2014-02-01

    Adverse drug reactions (ADRs) to N-acetylcysteine (NAC) treatment for paracetamol overdose are typically anaphylactoid in origin and occur in 2-48% of treated patients. We explored the incidence and management of NAC ADR in our unit. Case notes of patients who presented with paracetamol overdose and had ADR to NAC between February 2005 and June 2011 were reviewed. A total of 1648 patients presented with suspected paracetamol overdose and 660 received NAC treatment. Within this group, 82 patients had documented NAC-related ADR. ADR developed in 12.4% (82/660) of patients receiving intravenous NAC and 59 had full documentation available and were included in this study (34 women, 25 men). ADR occurred in the 15-min (150 mg/kg) bag in 36 cases (61%), 22 in the 4-h (50 mg/kg) bag (37%) and one in the 16-h (100 mg/kg) bag (2%). Symptoms were classified as minimal (n=16, 27%), moderate (n=26, 44%) and severe (n=17, 29%). Asthma and female sex, which are reported risk factors for ADR, did not lead to the development of more severe ADR (P=0.771 and 0.330, respectively). Treatments administered included stopping the NAC infusion (n=32, 54%), administration of antiemetics (n=36, 61%), H1 antihistamines (n=26, 44%), steroids (n=16, 27%), inhaled B2 agonists (n=6, 10%) and adrenaline (n=3, 5%). The incidence of ADR to NAC was comparable with published studies, although there was no association of severity with asthma or female sex. The management of ADRs is variable, with frequent, inappropriate use of steroids. Education about the pathophysiology of these ADRs may improve management.

  2. Vitamin E and N-Acetylcysteine as Antioxidant Adjuvant Therapy in Children with Acute Lymphoblastic Leukemia

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    Al-Tonbary, Youssef; Al-Haggar, Mohammad; EL-Ashry, Rasha; EL-Dakroory, Sahar; Azzam, Hanan; Fouda, Ashraf

    2009-01-01

    Although cancer therapies have experienced great success nowadays, yet the associated toxic response and free radicals formation have resulted in significant number of treatment-induced deaths rather than disease-induced fatalities. Complications of chemotherapy have forced physicians to study antioxidant use as adjunctive treatment in cancer. This study aimed to evaluate the antioxidant role of vitamin E and N-acetyl cysteine (NAC) in overcoming treatment-induced toxicity in acute lymphoblastic leukaemia (ALL) during the intensive period of chemo-/radiotherapy, almost the first two months of treatment. Forty children newly diagnosed with ALL were enrolled in this study. Twenty children (group I) have taken vitamin E and NAC supplementations with chemotherapy and the other twenty children (group II) have not taken any adjuvant antioxidant therapy. They were evaluated clinically for the occurrence of complications and by the laboratory parameters (blood levels of glutathione peroxidase (Glu.PX) antioxidant enzyme, malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), liver enzymes, and bone marrow picture). Results revealed reduced chemotherapy and radiotherapy toxicity as evidenced by decreasing level of MDA, increasing level of Glu.Px and decreased occurrence of toxic hepatitis, haematological complications, and need for blood and platelet transfusions in group I compared to group II. We can conclude that vitamin E and NAC have been shown to be effective as antioxidant adjuvant therapy in children with ALL to reduce chemo-/radiotherapy-related toxicities during the initial period of treatment. PMID:19960046

  3. Vitamin E and N-Acetylcysteine as Antioxidant Adjuvant Therapy in Children with Acute Lymphoblastic Leukemia

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    Youssef Al-Tonbary

    2009-01-01

    Full Text Available Although cancer therapies have experienced great success nowadays, yet the associated toxic response and free radicals formation have resulted in significant number of treatment-induced deaths rather than disease-induced fatalities. Complications of chemotherapy have forced physicians to study antioxidant use as adjunctive treatment in cancer. This study aimed to evaluate the antioxidant role of vitamin E and N-acetyl cysteine (NAC in overcoming treatment-induced toxicity in acute lymphoblastic leukaemia (ALL during the intensive period of chemo-/radiotherapy, almost the first two months of treatment. Forty children newly diagnosed with ALL were enrolled in this study. Twenty children (group I have taken vitamin E and NAC supplementations with chemotherapy and the other twenty children (group II have not taken any adjuvant antioxidant therapy. They were evaluated clinically for the occurrence of complications and by the laboratory parameters (blood levels of glutathione peroxidase (Glu.PX antioxidant enzyme, malondialdehyde (MDA, tumor necrosis factor- (TNF-, liver enzymes, and bone marrow picture. Results revealed reduced chemotherapy and radiotherapy toxicity as evidenced by decreasing level of MDA, increasing level of Glu.Px and decreased occurrence of toxic hepatitis, haematological complications, and need for blood and platelet transfusions in group I compared to group II. We can conclude that vitamin E and NAC have been shown to be effective as antioxidant adjuvant therapy in children with ALL to reduce chemo-/radiotherapy-related toxicities during the initial period of treatment.

  4. Inflammatory bowel and oxidative stress changes in an experimental model of portal hypertension: action of N-acetylcysteine

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    Francielli Licks

    2016-10-01

    Full Text Available Introduction: Portal hypertension (PH is characterized by vasodilatation in the portal system and the bowel is one of the severely affected organs. N-acetylcysteine (NAC is a molecule with important properties and widely used in clinical practice. Objective: To evaluate NAC action in the bowel of animals submitted to the animal model of partial portal vein ligation (PPVL. Methods: 18 male Wistar rats were divided into three experimental groups (n = 6: sham-operated (SO, PPVL, and PPVL + NAC. On the 8th day after surgery, N-acetylcysteine (10 mg/kg, ip was administered daily for 7 days. On the 15th day the animals’ bowel was collected for oxidative stress analysis, immunohistochemistry and Western blot. We evaluated the expression of NF-KB and TNF-α by immunohistochemistry and of iNOS by Western blot. Lipid peroxidation was assessed by TBARS technique, and the activities of antioxidant enzymes superoxide dismutase (SOD and glutation peroxidase (GPx were checked. Results: We observed an increased expression of NF-KB and TNF-α in PPVL group, and an increased iNOS expression assessed by Western blot. NAC reduced the expression of all proteins evaluated. We also observed an increase in oxidative stress in the bowel of mice PPVL group compared to controls (SO, and NAC was effective in reducing these values in PPVL + NAC group. Also, a reduction in the activity of SOD and GPx enzymes was observed in the diseased group, and NAC was able to restore the activity of the enzymes assessed. Conclusion: We suggest the anti-inflammatory and antioxidant action of NAC in the bowel of animals submitted to PPVL model. Resumo: Introdução: A Hipertensão Portal (HP é caracterizada por uma vasodilatação no sistema portal, e o intestino é um dos órgãos gravemente acometidos. A N-acetilcisteína (NAC é uma molécula com importantes propriedades, amplamente utilizada na clínica. Objetivo: Avaliar a ação da NAC no intestino de animais submetidos ao

  5. N-acetylcysteine regimens for paracetamol overdose: Time for a change?

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    Wong, Anselm; Graudins, Andis

    2016-12-01

    Paracetamol overdose is one of the commonest pharmaceutical poisonings in the world. For nearly four decades, intravenous acetylcysteine regimens have been used to treat most patients successfully and prevent or mitigate hepatotoxicity. However, the rate of occurrence of adverse reactions to acetylcysteine is quite high, and there is a potential for these to be reduced. Recent studies show that distributing the loading-dose of acetylcysteine over the first few hours of treatment may decrease the incidence of adverse reactions. In addition, varying the duration of acetylcysteine administration may potentially benefit certain cohorts of poisoned patients, depending on their risk of developing hepatotoxicity. © 2016 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

  6. Decreased Expression of Arginine-Phenylalanine-Amide-Related Peptide-3 Gene in Dorsomedial Hypothalamic Nucleus of Constant Light Exposure Model of Polycystic Ovarian Syndrome

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    Zahra Shaaban

    2018-01-01

    Full Text Available Background An abnormality in pulse amplitude and frequency of gonadotropin releasing hormone (GnRH secretion is the most characteristics of polycystic ovarian syndrome (PCOS. On the other hand, arginine-phenylalanine-amide (RFamide-related peptide-3 (RFRP3 inhibits the secretion of GnRH in mammalian hypothalamus. The current study performed in order to investigate the expression of RFRP3 mRNA in the dorsomedial hypothalamic nucleus (DMH after the induction of PCOS in a rat model of constant light exposure, and the possible role of parity on occurrence of PCOS. Materials and Methods In the experimental study, female nulliparous (n=12 and primiparous (n=12 rats were randomly subdivided into control and PCOS subgroups (n=6. PCOS were induced by 90 days exposure to constant light. After 90 days, blood, brain, and ovaries were sampled. Serum levels of follicle stimulating hormone (FSH, luteinizing hormone (LH, and testosterone were evaluated. In addition, six adult female ovariectomized rats as a control of real-time polymerase chain reaction (PCR tests were prepared and in the DMH of all rats, the relative mRNA expression of RFRP3 was assessed. Results Histological evaluation of ovaries represented the polycystic features. In addition, serum concentrations of testosterone in the PCOS subgroups were more than the controls (P<0.05. Furthermore, the relative expression of RFRP3 mRNA in PCOS subgroups was lower than the controls (P<0.05. Conclusion Constant light model of the PCOS-induced rats decreased the gene expression of RFRP3 in the DMH that suggests the decrease of RFRP3 may reduce its inhibitory effect on GnRH during the PCOS pathogenesis. This effect was stronger in the nulliparous rats than the primiparous.

  7. Protective Effects of Erythropoietin and N-Acetylcysteine on Methotrexate-Induced Lung Injury in Rats

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    Hasan Kahraman

    2013-03-01

    Full Text Available Objective: Methotrexate (MTX is known to have deleterious side effects on lung tissue. We aimed to investigate the effects of erythropoietin (EPO and N-acetyl-cysteine (NAC on MTX-induced lung injury in rats. Study Design: Animal experiment. Material and Methods: Twenty-six female Sprague-Dawley rats were divided into 4 groups. Sham group, 0.3 mL saline; MTX group, 5 mg/kg MTX; EPO group, 5mg/kg MTX and 2000 IU/kg EPO; NAC group, 5 mg/kg MTX and 200 mg/kg NAC were administered once daily for 4 consecutive days. Malondialdehyde (MDA, superoxide dismutase (SOD, catalase (CAT and inflammation and congestion scores in lung tissues were evaluated. Results: In MTX group MDA were significantly higher, CAT and SOD were significantly lower than in sham, EPO and NAC groups (p0.005. In group MTX both scores were significantly higher than in sham (p<0.005. The congestion score of group MTX was significantly higher than those of group EPO and NAC (p<0.005. Conclusion: EPO and NAC have significant preventive effects on MTX-induced lung injury in rats. Decreased antioxidant capacity and increased MDA level may cause the oxidative damage in MTX group. Also, higher antioxidant capacity and lower MDA level may be a response to oxidative stress in EPO and NAC groups.

  8. Protective Effect of N-Acetylcystein and Resveratrol on Ischemia-Reperfusion Injury in Rat Ovary

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    Avni Kılıç

    2016-06-01

    Full Text Available Objective: The aim of this study is evaluating the protective activity of N-acetyl cysteine and resveratrol treatment against ischemia - reperfusion damage created experimentally in rat ovaries. Methods: 42 female Wistar rats were used in our study. Rats were separated randomly into six groups consisting of seven rats as sham, torsion, torsion- detorsion, torsion-detorsion+saline, torsion-detorsion+resveretrol (20 mg/kg and torsion- detorsion+N-acetyl cysteine (150 mg/kg. Except Sham, ovarian torsion procedure was implemented to all other groups for 2 hours. Detorsion procedure was implemented to other groups for 2 hours, except the torsion group. Medications were given through intraperitoneal way half an hour before the detorsion procedure in saline (two milliliter, resveratrol (20 mg/kg and N-acetyl cysteine (150 mg/kg groups. Then, 2 ml of blood samples were drawn for markers of oxidative stress and tumour necrosis factor-alpha (TNF-α work and the ovaries, which were torsioned for the histologic examination, were ex­tracted from all rats. Edema, congestion, hemorrhage, leuko­cyte infiltration and degeneration of follicles were evaluated by histopathological examination. Results: According to histopathologic damage scores, the least damage was seen in sham group and the most damage was seen T-DT group (1.00±0.81 vs. 11.00±1.15, respectively; p<0.001. It was seen that resveratrol and N-acetyl cysteine treatments were effective in decreasing tissue damage (total damage score average 83.85±0.89 vs. 3.85±0.89, respec­tively; p<0.001, and on the other hand there was not any dif­ference between resveratrol and N-acetyl cysteine treatments (p=0.966. Besides, it was determined that oxidative stress levels were higher in torsion - detorsion group and the resve­ratrol and N-acetyl cysteine treatment caused a significant de­crease in oxidative stress levels. In additionally, the reductions of TNF-α levels were found to be equally effective in

  9. N-acetylcysteine Counteracts Adipose Tissue Macrophage Infiltration and Insulin Resistance Elicited by Advanced Glycated Albumin in Healthy Rats

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    Karolline S. da Silva

    2017-09-01

    Full Text Available Background: Advanced glycation endproducts elicit inflammation. However, their role in adipocyte macrophage infiltration and in the development of insulin resistance, especially in the absence of the deleterious biochemical pathways that coexist in diabetes mellitus, remains unknown. We investigated the effect of chronic administration of advanced glycated albumin (AGE-albumin in healthy rats, associated or not with N-acetylcysteine (NAC treatment, on insulin sensitivity, adipose tissue transcriptome and macrophage infiltration and polarization.Methods: Male Wistar rats were intraperitoneally injected with control (C or AGE-albumin alone, or, together with NAC in the drinking water. Biochemical parameters, lipid peroxidation, gene expression and protein contents were, respectively, determined by enzymatic techniques, reactive thiobarbituric acid substances, RT-qPCR and immunohistochemistry or immunoblot. Carboxymethyllysine (CML and pyrraline (PYR were determined by LC/mass spectrometry (LC-MS/MS and ELISA.Results: CML and PYR were higher in AGE-albumin as compared to C. Food consumption, body weight, systolic blood pressure, plasma lipids, glucose, hepatic and renal function, adipose tissue relative weight and adipocyte number were similar among groups. In AGE-treated animals, insulin resistance, adipose macrophage infiltration and Col12a1 mRNA were increased with no changes in M1 and M2 phenotypes as compared to C-albumin-treated rats. Total GLUT4 content was reduced by AGE-albumin as compared to C-albumin. NAC improved insulin sensitivity, reduced urine TBARS, adipose macrophage number and Itgam and Mrc mRNA and increased Slc2a4 and Ppara. CD11b, CD206, Ager, Ddost, Cd36, Nfkb1, Il6, Tnf, Adipoq, Retn, Arg, and Il12 expressions were similar among groups.Conclusions: AGE-albumin sensitizes adipose tissue to inflammation due to macrophage infiltration and reduces GLUT4, contributing to insulin resistance in healthy rats. NAC antagonizes AGE

  10. N-acetylcysteine prevents HIV gp 120-related damage of human cultured astrocytes: correlation with glutamine synthase dysfunction

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    Costa Nicola

    2007-12-01

    Full Text Available Abstract Background HIV envelope gp 120 glycoprotein is released during active HIV infection of brain macrophages thereby generating inflammation and oxidative stress which contribute to the development of the AIDS-Dementia Complex (ADC. Gp120 has also been found capable to generate excitotoxic effect on brain tissue via enhancement of glutamatergic neurotransmission, leading to neuronal and astroglial damage, though the mechanism is still to be better understood. Here we investigated on the effect of N-acetylcysteine (NAC, on gp120-induced damage in human cultured astroglial cells and the possible contribution of gp120-related reacting oxygen species (ROS in the imbalanced activity of glutamine synthase (GS, the enzyme that metabolizes glutamate into glutamine within astroglial cells playing a neuroprotective role in brain disorders. Results Incubation of Lipari human cultured astroglial cells with gp 120 (0.1–10 nM produced a significant reduction of astroglial cell viability and apoptosis as evaluated by TUNEL reaction and flow cytometric analysis (FACS. This effect was accompanied by lipid peroxidation as detected by means of malondialdehyde assay (MDA. In addition, gp 120 reduced both glutamine concentration in astroglial cell supernatants and GS expression as detected by immunocytochemistry and western blotting analysis. Pre-treatment of cells with NAC (0.5–5 mM, dose-dependently antagonised astroglial apoptotic cell death induced by gp 120, an effect accompanied by significant attenuation of MDA accumulation. Furthermore, both effects were closely associated with a significant recovery of glutamine levels in cell supernatants and by GS expression, thus suggesting that overproduction of free radicals might contribute in gp 120-related dysfunction of GS in astroglial cells. Conclusion In conclusion, the present experiments demonstrate that gp 120 is toxic to astroglial cells, an effect accompanied by lipid peroxidation and by altered

  11. N-acetylcysteine prevents spatial memory impairment induced by chronic early postnatal glutaric acid and lipopolysaccharide in rat pups.

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    Fernanda S Rodrigues

    Full Text Available BACKGROUND AND AIMS: Glutaric aciduria type I (GA-I is characterized by accumulation of glutaric acid (GA and neurological symptoms, such as cognitive impairment. Although this disease is related to oxidative stress and inflammation, it is not known whether these processes facilitate the memory impairment. Our objective was to investigate the performance of rat pups chronically injected with GA and lipopolysaccharide (LPS in spatial memory test, antioxidant defenses, cytokines levels, Na+, K+-ATPase activity, and hippocampal volume. We also evaluated the effect of N-acetylcysteine (NAC on theses markers. METHODS: Rat pups were injected with GA (5 umol g of body weight-1, subcutaneously; twice per day; from 5th to 28th day of life, and were supplemented with NAC (150 mg/kg/day; intragastric gavage; for the same period. LPS (2 mg/kg; E.coli 055 B5 or vehicle (saline 0.9% was injected intraperitoneally, once per day, from 25th to 28th day of life. Oxidative stress and inflammatory biomarkers as well as hippocampal volume were assessed. RESULTS: GA caused spatial learning deficit in the Barnes maze and LPS potentiated this effect. GA and LPS increased TNF-α and IL-1β levels. The co-administration of these compounds potentiated the increase of IL-1β levels but not TNF-α levels in the hippocampus. GA and LPS increased TBARS (thiobarbituric acid-reactive substance content, reduced antioxidant defenses and inhibited Na+, K+-ATPase activity. GA and LPS co-administration did not have additive effect on oxidative stress markers and Na+, K+ pump. The hippocampal volume did not change after GA or LPS administration. NAC protected against impairment of spatial learning and increase of cytokines levels. NAC Also protected against inhibition of Na+,K+-ATPase activity and oxidative markers. CONCLUSIONS: These results suggest that inflammatory and oxidative markers may underlie at least in part of the neuropathology of GA-I in this model. Thus, NAC could

  12. N-Acetylcysteine an Allium Plant Compound Improves High-Sucrose Diet-Induced Obesity and Related Effects

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    Gisele A. Souza

    2011-01-01

    Full Text Available This study was designed to determine whether N-acetylcysteine (NAC, C5H9–NO3S, a compound from Allium species may be used as a complementary therapeutic agent, to inhibit high-sucrose induced-obesity and its effects on glucose tolerance, in vivo low-density lipoprotein (LDL-oxidation and serum oxidative stress in rats. Initially, 24 male Wistar rats were divided into two groups: controls receiving standard chow (C, n = 6 and those receiving high-sucrose diet (HS, n = 18. After 22 days, (HS group was divided into three groups (n = 6/group; (HS-HS continued to eat high-sucrose diet and water; (HS-N continued to eat high-sucrose diet and received 2 mg l−1-NAC in its drinking water; (HS-CN changing high-sucrose to standard chow and receiving 2 mg l­1-NAC in its drinking water. After 22 days of the HS-group division (44 days of experimental period body weight, body mass index and surface area were enhanced in HS-HS rats (P < .001. HS-HS rats had glucose intolerance, increased serum triacylglycerol (TG, very low-density lipoprotein (VLDL, oxidized-LDL (ox-LDL and lipid-hydroperoxide (LH than the others (P < .01. NAC in HS-N and HS-CN rats reduced the obesity markers, feed efficiency, LH and ox-LDL, as well normalized glucose response, TG and VLDL (P < .01 in these groups compared with HS-HS. Total antioxidant substances, GSH/GSSG ratio and glutathione-reductase, were higher in HS-N than in HS-HS (P < .01. In conclusion, NAC improved high-sucrose diet-induced obesity and its effects on glucose tolerance, lipid profile, in vivo LDL-oxidation and serum oxidative stress, enhancing antioxidant defences. The application of this agent may be feasible and beneficial for high-sucrose diet-induced obesity, which certainly would bring new insights on obesity-related adverse effects control.

  13. Tratamento de pacientes com úlceras isquêmicas secundárias à esclerose sistêmica com N-acetilcisteína endovenosa Treatment of patients with isquemic ulcers secondary to systemic sclerosis with intravenous N-acetylcysteine

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    Cristiane Kayser

    2006-04-01

    Full Text Available Os repetidos episódios de isquemia-reperfusão observados na esclerose sistêmica (ES acarretam aumento na atividade de radicais livres, o que pode estar implicado nas anormalidades vasculares e inflamatórias descritas nessa enfermidade. A N-acetilcisteína sob forma endovenosa é uma potente droga antioxidante e, como tal, poderia ter efeito benéfico para o tratamento das lesões vasculares da ES. Relatamos o tratamento com N-acetilcisteína endovenosa de três pacientes com diagnóstico de ES e com úlceras ativas de extremidades (dígitos ou artelhos. Dois pacientes apresentavam duas úlceras digitais e o terceiro paciente, três úlceras em artelhos no início do tratamento. Todos os pacientes apresentaram diminuição no diâmetro de pelo menos uma úlcera após o tratamento. Duas pacientes apresentaram cicatrização de uma úlcera. Esses resultados preliminares sugerem que a N-acetilcisteína endovenosa parece ser uma boa opção terapêutica para o tratamento de úlceras de extremidades em pacientes com ES e justificam a elaboração de ensaios controlados duplo-cego com placebo.The repetitive ischemic-reperfusion episodes in patients with systemic sclerosis (SSc cause an increase in free radical activity, which may be implicated in the inflammatory and vascular lesions observed in this illness. Endovenous N-acetylicysteine is a potent anti-oxidant agent and might be beneficial to the treatment of vascular events in SSc. This communication reports on the use of endovenous N-acetylcysteine in three SSc patients with active ulcers in fingers and toes. At baseline, two patients presented two finger ulcers each, and a third patient had three ulcers in the toes. All patients presented a decrease in the dimensions of at least one ulcer. Two patients presented complete healing of one ulcer. These preliminary results suggest that endovenous N-acetylcysteine may be an efficient therapeutic option for extremity ulcers in SSc patients and

  14. Protective Role of N-Acetylcysteine on Isoprenaline-Induced Myocardial Injury: Histological, Immunohistochemical and Morphometric Study.

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    Zaki, Sherif Mohamed; Abdalla, Ibrahim Labib; Sadik, Abir Oueida El; Mohamed, Enas Ahmad; Kaooh, Sarah

    2018-02-01

    Several researchers studied the protective effect of the N-acetylcysteine (NAC) when it was given before the induction of myocardial infarction (MI). Other researchers studied such protective effect when it was before done and after done of the MI. The missing data are the comparison between the protective effect of NAC before myocardial injury with its protective effect both before and after myocardial injury. The aim of the study was to compare the cardioprotective effect of NAC on the isoprenaline-induced myocardial injury before the isoprenaline (ISP) injection with its protective effect both before and after the ISP injection. This study was applied over both short and long time periods. A total of 90 male adult Wistar albino rats were used in the study. The rats were divided into four groups: control group, ISP-treated group, NAC-pretreated group and NAC-pre-& posttreated group. Based on the duration of the experiment, the second and third groups were further subdivided into a and b groups. Histological, immunohistochemical and histomorphometric analysis were used. The myocytes in the ISP-treated groups were fragmented, disrupted with karyolysis. The blood vessels were dilated, congested and associated with blood extravasation, interstitial edema and cellular inflammatory infiltration. Much improvement was observed in the NAC-pretreated group. Focal degeneration was detected in the muscle fibers. The capillaries were normal. Minimal blood extravasation and cellular infiltration were seen. The cardiac muscle fibers in the NAC-pre-& posttreated group were regularly arranged. The mean collagen fiber area percent of the ISP-treated groups was significantly higher by 8.3-folds and 10.1-folds as compared with that of the control group and was also higher by 5.5-folds and 6.8-folds as compared with that of the NAC-pre-&posttreated groups. The α-SMA area percent in the ISP-treated groups was significantly higher by 12.2-folds and 23.9-folds as compared with that of

  15. The influence of single application of paracetamol and/or N-acetylcysteine on rats subchronic exposed to trichloroethylene vapours. I. Effect on hepatic moonooxygenase system dependent of cytochrome P450

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    Andrzej Plewka

    2012-06-01

    Full Text Available Background: There is a number of factors which potentially affect occurrence of toxic change in liver after overdosing of paracetamol. Hepatic metabolism of trichloroethylene has primary impact on hepatotoxic effect of this solvent. This means that the combined exposure to these xenobiotics can be particularly harmful for human. The influence of N-acetylcysteine (NAC as a protective factor after paracetamol intoxication was studies. Materials and method: Tests were carried out on rats which were treated with trichloroethylene, paracetamol and/or N-acetylcysteine. In the hepatic microsomal fraction activity of the components of cytochrome P450- dependent monooxygenases was determined Results: Paracetamol slightly stimulated cytochrome P450 having no effect on reductase activity cooperating with it. Cytochrome b5 and its reductase were inhibited by this compound. Trichloroethylene was the inhibitor of compounds of II microsomal electron transport chain. N-acetylcysteine inhibited activity of reductase of NADH-cytochrome b5. Conclusions: Tested doses of the xenobiotics influenced on II microsomal electron transport chain. Protective influence of N-acetylcysteine was better if this compound was applied 2 hours after exposure on xenobiotics

  16. Efficacy of Ascorbic Acid (Vitamin C) and/N-Acetylcysteine (NAC) Supplementation on Nutritional and Antioxidant Status of Male Chronic Obstructive Pulmonary Disease (COPD) Patients.

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    Pirabbasi, Elham; Shahar, Suzana; Manaf, Zahara Abdul; Rajab, Nor Fadilah; Manap, Roslina Abdul

    2016-01-01

    Antioxidant therapy has a potential to be introduced as therapeutic modality for chronic obstructive pulmonary disease (COPD) patients. This study aimed to determine the effect of antioxidant supplementation [ascorbic acid and N-Acetylcysteine (NAC)] on nutritional and antioxidant status in male COPD patients. A parallel and single blind randomised controlled clinical trial (RCT) was conducted at two medical centers in Kuala Lumpur, Malaysia. Seventy-nine subjects were recruited and randomly divided into four trial arms (i.e., NAC, vitamin C, NAC+vitamin C and control groups) for six mo. The primary outcome was changes in body mass index by estimating power of 90% and significance level of psupplementation of NAC or vitamin C improved nutritional and antioxidant status of subjects.

  17. The effect of adjuvant N-acetylcysteine effervescent tablets therapy on cardiopulmonary function and airway remodeling in patients with stable COPD

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    Gui-Fang Hu1

    2017-05-01

    Full Text Available Objective: To study the effect of adjuvant N-acetylcysteine (NAC effervescent tablets therapy on cardiopulmonary function and airway remodeling in patients with stable chronic obstructive pulmonary disease (COPD. Methods: Patients with stable COPD treated in Zigong Third People’s Hospital and West China Hospital, Sichuan University between May 2014 and October 2016 were selected and randomly divided into two groups, NAC group received N-acetylcysteine effervescent tablets combined with routine treatment, and control group received routine treatment. Before treatment as well as 2 weeks and 4 weeks after treatment, oxidative stress indexes and airway remodeling indexes in serum as well as inflammatory response indexes in peripheral blood were determined. Results: MDA, PC, 8-OHdG, MMP2, MMP3 and MMP9 contents in serum as well as NLRP3, ASC, p38MAPK and TREM-1 mRNA expression levels in peripheral blood mononuclear cells of both groups of patients after treatment were significantly lower than those before treatment while TAC levels as well as TIMP1 and TIMP2 contents in serum were significantly higher than those before treatment, and MDA, PC, 8-OHdG, MMP2, MMP3 and MMP9 contents in serum a well as NLRP3, ASC, p38MAPK and TREM-1 mRNA expression levels in peripheral blood mononuclear cells of NAC group after treatment were significantly lower than those of control group while TAC levels as well as TIMP1 and TIMP2 contents in serum were significantly higher than those of control group. Conclusion: Adjuvant NAC effervescent tablets treatment of stable COPD can improve the effect of oxidative stress and inflammatory response on cardiopulmonary function, and inhibit the airway remodeling caused by protease activation.

  18. Effect of N-acetylcysteine on lung injury induced by skeletal muscle ischemia-reperfusion: histopathological study in rat model Efeito de N-acetilcisteína em dano pulmonar induzido por isquemia-reperfusão de músculo esquelético: estudo histopatólogico em modelo de rato

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    Amir Sotoudeh

    2012-02-01

    Full Text Available PURPOSE: To investigate whether N-acetylcysteine, a free radicals scavenger has a protective effect against lung injury as a remote organ after skeletal muscle ischemia-reperfusion. METHODS: Twenty Wistar male rats were divided randomly into two experimental groups: group ischemia-reperfusion (group I and group ischemia-reperfusion + N-acetylcysteine (group II. All animals were undergone two hours of ischemia by occlusion femoral artery and 24h of reperfusion. Before clamped the femoral artery, 250 IU heparin was administered via the jugular vein to prevent clotting. Rats that were treated with N-acetylcysteine given IV at a dose of 150 mgkg-¹, immediately before reperfusion. After 24h of reperfusion, animals were euthanized and left lung harvested for histopathological analysis under light microscopy. RESULTS: In the group I, tissues showed histological changes with intra-alveolar edema, intra-alveolar hemorrhage and neutrophilic infiltration. Histopathologically, there was a significant difference (P = 0.005 between two groups. CONCLUSION: Administration of N-acetylcysteine treatment significantly decreased lung injury induced by skeletal muscle ischemia reperfusion according to histological findings.OBJETIVO: Investigar se N-acetilcisteína, neutralizador de radicais livres, tem efeito protetor contra dano pulmonar como um órgão remoto após isquemia-reperfusão de músculo esquelético. MÉTODOS: Vinte ratos machos Wistar, foram aleatóriamente distribuídos em dois grupos: grupo isquemia-reperfusão (grupo I e grupo isquemia-reperfusão +N-acetilcisteína (grupo II. Todos os animais foram submetidos a duas horas de ischemia pela oclusão artéria femoral e 24 horas de reperfusão. Antes de ocluir a artéria femoral, foi administrado 250 IU de heparina pela veia jugular para prevenir coagulação. A N-acetilcisteína foi administrada por via intravenosa, na uma dose de 150 mgkg-1, imediatamente antes de reperfusão. Após 24 horas de

  19. Early blockade of joint inflammation with a fatty acid amide hydrolase inhibitor decreases end-stage osteoarthritis pain and peripheral neuropathy in mice.

    Science.gov (United States)

    McDougall, Jason J; Muley, Milind M; Philpott, Holly T; Reid, Allison; Krustev, Eugene

    2017-05-25

    The endocannabinoid system has been shown to reduce inflammatory flares and pain in rodent models of arthritis. A limitation of endocannabinoids is that they are rapidly denatured by hydrolysing enzymes such as fatty acid amide hydrolase (FAAH) which renders them physiologically inert. Osteoarthritis (OA) is primarily a degenerative joint disease; however, it can incorporate mild inflammation and peripheral neuropathy. The aim of this study was to determine whether early blockade of FAAH bioactivity could reduce OA-associated inflammation and joint neuropathy. The ability of this treatment to prevent end-stage OA pain development was also tested. Physiological saline or sodium monoiodoacetate (MIA; 0.3 mg) was injected into the right knee of male C57Bl/6 mice (20-42 g) and joint inflammation (oedema, blood flow and leukocyte trafficking) was measured over 14 days. Joint inflammation was also measured in a separate cohort of animals treated on day 1 with either saline or the FAAH inhibitor URB597 (0.03-0.3 mg/kg topical onto the knee joint). In other experiments, von Frey hair tactile sensitivity was determined on days 1 and 14 in MIA-injected mice treated prophylactically with URB597 (0.3 mg/kg s.c. over the knee joint on days 0-3). Saphenous nerve myelination was also assessed in these animals on day 14 by G-ratio analysis. Intra-articular injection of MIA caused an increase in joint oedema (P pain was also attenuated. These data indicate that local inhibition of FAAH in MIA-injected knees can reduce acute inflammatory changes associated with the model. Prophylactic treatment of OA mice with the endocannabinoid hydrolysis inhibitor URB597 was also shown to be neuroprotective and prevented the development of joint pain at later time points.

  20. N-Acetylcysteine Combined with Home Based Physical Activity: Effect on Health Related Quality of Life in Stable COPD Patients- A Randomised Controlled Trial.

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    Salve, Vijay Tukaram; Atram, Jitesh S

    2016-12-01

    Quality of life is adversely affected in Chronic Obstructive Pulmonary Disease (COPD), due to irreversible, progressive nature of the disease and limitations of current treatment options available. One of the important aim of treatment of COPD is to improve Quality of Life (QoL). Cigarette smoke contains numerous free radicals and other oxidants. Oxidative stress has been implicated in pathogenesis, progression of disease and exacerbation in COPD. Pulmonary tuberculosis, outdoor and indoor air pollution and many others are aetiologies of COPD in non-smokers. N-Acetylcysteine (NAC) is a precursor of endogenous anti-oxidant, Glutathione (GSH) and both agents act as free radical scavengers. Exercise limitation results in poor physical performance and eventually poor QoL in COPD. To observe the combined effect of 600mg of NAC once daily and physical activity (home based) in addition to standard treatment for ten weeks, compared with placebo as control group with standard treatment. This randomised controlled trial was conducted at a tertiary care centre in Mumbai for two years from December 2011 to December 2013. Hundred patients diagnosed as stable COPD (as per Global Initiative against Obstructive Lung Disease (GOLD) 2010 guidelines) were enrolled in the study. There were 50 patients in study group and control group each. The QoL was assessed using Saint George Respiratory Questionnaire-C (SGRQ-C) initially and at the end of ten weeks. The study group was treated with NAC 600mg once a day combined with daily physical activity in addition to standard treatment. Control group patients were treated with placebo and standard treatment. At the end of 10 weeks, it was observed that, mean change in SGRQ-C was significant in "study group" as compared to "control group". Mean change in score among study group was 4.72 and the same in control was 1.32, p-value=0.007. There was significant improvement in SGRQ-C score at the end of 10 weeks and QoL in the study group (p-value-0

  1. Comparative Effects of Phosphoenolpyruvate, a Glycolytic Intermediate, as an Organ Preservation Agent with Glucose and N-Acetylcysteine against Organ Damage during Cold Storage of Mouse Liver and Kidney

    OpenAIRE

    Ishitsuka, Yoichi; Fukumoto, Yusuke; Kondo, Yuki; Irikura, Mitsuru; Kadowaki, Daisuke; Narita, Yuki; Hirata, Sumio; Moriuchi, Hiroshi; Maruyama, Toru; Hamasaki, Naotaka; Irie, Tetsumi

    2013-01-01

    We evaluated the usefulness of phosphoenolpyruvate (PEP), a glycolytic intermediate with antioxidative and energy supplementation potentials, as an organ preservation agent. Using ex vivo mouse liver and kidney of a static cold storage model, we compared the effects of PEP against organ damage and oxidative stress during cold preservation with those of glucose or N-acetylcysteine (NAC). Lactate dehydrogenase (LDH) leakage, histological changes, and oxidative stress parameters (measured as thi...

  2. [Oral N-acetylcysteine in the treatment of Raynaud's phenomenon secondary to systemic sclerosis: a randomized, double-blind, placebo-controlled clinical trial].

    Science.gov (United States)

    Correa, Marcelo José Uchoa; Mariz, Henrique Ataíde; Andrade, Luís Eduardo Coelho; Kayser, Cristiane

    2014-01-01

    To evaluate the safety and efficacy of N-acetylcysteine (NAC) orally on digital microcirculation blood flow in patients with Raynaud's phenomenon (RP) secondary to systemic sclerosis (SSc). This was a randomized, double-blind, placebo-controlled trial in which 42 patients with SSc received oral NAC at a dose of 600mg tid (21 patients, mean age 45.6±9.5 years) or placebo (21 patients, mean age 45.0±12.7 years) for four weeks. The primary endpoint was the change in cutaneous microcirculation blood flow before and after cold stimulation measured by laser Doppler imaging (LDI) at weeks 0 and 4. The frequency and severity of RP and the number of digital ulcers were also measured at weeks 0 and 4. The adverse events were recorded in the fourth week. There was no significant change in digital blood flow assessed by LDI before or after cold stimulus after four weeks of NAC or placebo. Both groups showed significant improvement in the frequency and severity of RP attacks, with no difference between the two groups. At the end of the study, the placebo group had three digital ulcers, while the NAC group showed no ulcers. NAC was well tolerated and no patient discontinued the treatment. NAC orally at a dose of 1800mg/day showed no vasodilator effect on hands' microcirculation after four weeks of treatment in patients with RP secondary to SSc. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

  3. Flame retardant tris(1,3-dichloro-2-propylphosphate (TDCPP toxicity is attenuated by N-acetylcysteine in human kidney cells

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    David W. Killilea

    Full Text Available Prolonged exposure to the flame retardants found in many household products and building materials is associated with adverse developmental, reproductive, and carcinogenic consequences. While these compounds have been studied in numerous epidemiological and animal models, less is known about the effects of flame retardant exposure on cell function. This study evaluated the toxicity of the commonly used fire retardant tris(1,3-dichloro-2-propylphosphate (TDCPP in cell line derived from the kidney, a major tissue target of organohalogen toxicity. TDCPP inhibited cell growth at lower concentrations (IC50 27 μM, while cell viability and toxicity were affected at higher concentrations (IC50 171 μM and 168 μM, respectively. TDCPP inhibited protein synthesis and caused cell cycle arrest, but only at higher concentrations. Additionally, the antioxidant N-acetylcysteine (NAC reduced cell toxicity in cells treated with TDCPP, suggesting that exposure to TDCPP increased oxidative stress in the cells. In summary, these data show that low concentrations of TDCPP result in cytostasis in a kidney cell line, whereas higher concentrations induce cell toxicity. Furthermore, TDCPP toxicity can be attenuated by NAC, suggesting that antioxidants may be effective countermeasures to some organohalogen exposures. Keywords: flame retardant, cytostasis, cell toxicity, antioxidant, cell cycle

  4. Flame retardant tris(1,3-dichloro-2-propyl)phosphate (TDCPP) toxicity is attenuated by N-acetylcysteine in human kidney cells.

    Science.gov (United States)

    Killilea, David W; Chow, Darryl; Xiao, Sheng Qi; Li, Charles; Stoller, Marshall L

    2017-01-01

    Prolonged exposure to the flame retardants found in many household products and building materials is associated with adverse developmental, reproductive, and carcinogenic consequences. While these compounds have been studied in numerous epidemiological and animal models, less is known about the effects of flame retardant exposure on cell function. This study evaluated the toxicity of the commonly used fire retardant tris(1,3-dichloro-2-propyl)phosphate (TDCPP) in cell line derived from the kidney, a major tissue target of organohalogen toxicity. TDCPP inhibited cell growth at lower concentrations (IC 50 27 μM), while cell viability and toxicity were affected at higher concentrations (IC 50 171 μM and 168 μM, respectively). TDCPP inhibited protein synthesis and caused cell cycle arrest, but only at higher concentrations. Additionally, the antioxidant N -acetylcysteine (NAC) reduced cell toxicity in cells treated with TDCPP, suggesting that exposure to TDCPP increased oxidative stress in the cells. In summary, these data show that low concentrations of TDCPP result in cytostasis in a kidney cell line, whereas higher concentrations induce cell toxicity. Furthermore, TDCPP toxicity can be attenuated by NAC, suggesting that antioxidants may be effective countermeasures to some organohalogen exposures.

  5. A double-blinded, placebo-controlled, multicenter clinical trial of N-acetylcysteine for preventing amphotericin B-induced nephrotoxicity.

    Science.gov (United States)

    Karimzadeh, Iman; Khalili, Hossein; Sagheb, Mohammad Mahdi; Farsaei, Shadi

    2015-01-01

    To evaluate the effectiveness of oral N-acetylcysteine (NAC) co-treatment in preventing amphotericin B (AmB)-induced nephrotoxicity (AIN), including creatinine clearance and biomarkers of renal function (cystatin C [Cys C] and kidney injury molecule-1 [KIM-1]). Either placebo or 600 mg oral NAC was given twice daily during the treatment course of AmB. Renal function test, serum as well as urinary level of Cys C and urinary KIM-1 were determined. Among the study population (n = 54), 23 (42.59%) patients developed AmB nephrotoxicity during their treatment course. NAC co-treatment was significantly associated with mitigating AmB nephrotoxicity (OR = 0.286, 95% CI: 0.082 - 0.993; p = 0.049). No statistically significant difference regarding accuracy of measured biomarkers including serum creatinine, serum and urine Cys C and urine KIM-1 at days 0 and 7 of treatment in predicting and detecting AmB nephrotoxicity was identified. The changes in mean serum and urine Cys C and urine KIM during AmB treatment within and between treatment groups were not statistically significant. Co-treatment with 600 mg oral NAC twice a day during AmB treatment, after adjusting for multiple variables, was associated with prevention of AIN. However, significantly higher adverse reactions developed in the patients who were treated with NAC.

  6. The adjuvant effect of metformin and N-acetylcysteine to clomiphene citrate in induction of ovulation in patients with Polycystic Ovary Syndrome.

    Science.gov (United States)

    Maged, Ahmed M; Elsawah, Heba; Abdelhafez, Aly; Bakry, Ahmed; Mostafa, Walaa Ai

    2015-01-01

    To assess the adjuvant effect of metformin and N-acetylcysteine (NAC) to clomiphene citrate (CC) in induction of ovulation in Polycystic Ovary Syndrome (PCOS) patients. 120 women with PCOS were randomly divided into three equal groups: group I received CC only, group II received CC plus NAC and group III received CC plus metformin. There was a significant difference between group II and other two groups regarding average number of ovulatory follicles >18 mm (2.25 versus 1.75 and 1.89, respectively), but no significant difference between the three study groups regarding number of intermediate follicles 14-18 mm (4, 10 and 4, respectively). There was no significant difference between the three study groups regarding occurrence and laterality of ovulation, pregnancy rate per cycle but a significant difference between group II and other two groups regarding pregnancy rate per patient (20% versus 10% and 10%, respectively, p value 0.05). There was a highly statistically significant difference between group II and other two groups regarding peak endometrial thickness (7.3 ± 1.1 versus 5.4 ± 0.6 and 5.3 ± 0.6, respectively). NAC as an adjuvant to CC for induction of ovulation improves ovulation and pregnancy rates in PCOS patients with beneficial impacts on endometrial thickness.

  7. Ameliorative effects of dimetylthiourea and N-acetylcysteine on nanoparticles induced cyto-genotoxicity in human lung cancer cells-A549.

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    Ritesh Kumar Srivastava

    Full Text Available We study the ameliorative potential of dimetylthiourea (DMTU, an OH• radical trapper and N-acetylcysteine (NAC, a glutathione precursor/H₂O₂ scavenger against titanium dioxide nanoparticles (TiO₂-NPs and multi-walled carbon nanotubes (MWCNTs induced cyto-genotoxicity in cultured human lung cancer cells-A549. Cytogenotoxicity was induced by exposing the cells to selected concentrations (10 and 50 µg/ml of either of TiO₂-NPs or MWCNTs for 24 h. Anti-cytogenotoxicity effects of DMTU and NAC were studied in two groups, i.e., treatment of 30 minutes prior to toxic insult (short term exposure, while the other group received DMTU and NAC treatment during nanoparticles exposure, i.e., 24 h (long term exposure. Investigations were carried out for cell viability, generation of reactive oxygen species (ROS, micronuclei (MN, and expression of markers of oxidative stress (HSP27, CYP2E1, genotoxicity (P⁵³ and CYP2E1 dependent n- nitrosodimethylamine-demethylase (NDMA-d activity. In general, the treatment of both DMTU and NAC was found to be effective significantly against TiO₂-NPs and MWCNTs induced cytogenotoxicity in A549 cells. Long-term treatment of DMTU and NAC during toxic insults has shown better prevention than short-term pretreatment. Although, cells responded significantly to both DMTU and NAC, but responses were chemical specific. In part, TiO₂-NPs induced toxic responses were mediated through OH• radicals generation and reduction in the antioxidant defense system. While in the case of MWCNTs, adverse effects were primarily due to altering/hampering the enzymatic antioxidant system. Data indicate the applicability of human lung cancer cells-A549 as a pre-screening tool to identify the target specific prophylactic and therapeutic potential of drugs candidate molecules against nanoparticles induced cellular damages.

  8. Pro-oxidant and antioxidant effects of N-acetylcysteine regulate doxorubicin-induced NF-kappa B activity in leukemic cells†

    Science.gov (United States)

    Finn, Nnenna Adimora

    2012-01-01

    Clinical debate has arisen over the consequences of antioxidant supplementation during cancer chemotherapy. While antioxidants may impede the efficacy of chemotherapy by scavenging reactive oxygen species and free radicals, it is also possible that antioxidants alleviate unwanted chemotherapy-induced toxicity, thus allowing for increased chemotherapy doses. These contradictory assertions suggest that antioxidant supplementation during chemotherapy treatment can have varied outcomes depending on the cellular context. To gain a more robust understanding of the role that antioxidants play in chemotherapy, we investigated the dose-dependent effects of the antioxidant, N-acetylcysteine (NAC), on the redox-mediated regulation of intracellular signaling. In this study, we systematically evaluated the effect of Dox-induced ROS on the NF-κB pathway in a pediatric acute lymphoblastic leukemia (ALL) cell line by measuring the thiol-based oxidative modifications of redox-sensitive proteins within the pathway. We report a functional consequence of NAC supplementation during doxorubicin (Dox) chemotherapy administration via the NF-kappa B (NF-κB) signal transduction pathway. The ability of NAC to alter Dox-induced NF-κB activity is contingent on the ROS-mediated S-glutathionylation of IKK-β. Moreover, the NAC-dependent alteration of intracellular glutathione redox balance, through pro-oxidant and antioxidant mechanisms, can be exploited to either promote or inhibit Dox-induced NF-κB activity in an NAC-concentration-dependent manner. We developed an electron-transfer-based computational model that predicts the effect of NAC pretreatment on Dox-induced NF-κB signaling for a range of NAC and Dox treatment combinations. PMID:22134636

  9. I.v. N-acetylcysteine and emergency CT: use of serum creatinine and cystatin C as markers of radiocontrast nephrotoxicity.

    Science.gov (United States)

    Poletti, Pierre-Alexandre; Saudan, Patrick; Platon, Alexandra; Mermillod, Bernadette; Sautter, Anna-Maria; Vermeulen, Bernard; Sarasin, François P; Becker, Christoph D; Martin, Pierre-Yves

    2007-09-01

    The purpose of this study was to assess the effect of i.v. administration of N-acetylcysteine (NAC) on serum levels of creatinine and cystatin C, two markers of renal function, in patients with renal insufficiency who undergo emergency contrast-enhanced CT. Eighty-seven adult patients with renal insufficiency who underwent emergency CT were randomized to two groups. In the first group, in addition to hydration, patients received a 900-mg injection of NAC 1 hour before and another immediately after injection of iodine contrast medium. Patients in the second group received hydration only. Serum levels of creatinine and cystatin C were measured at admission and on days 2 and 4 after CT. Nephrotoxicity was defined as a 25% or greater increase in serum creatinine or cystatin C concentration from baseline value. A 25% or greater increase in serum creatinine concentration was found in nine (21%) of 43 patients in the control group and in two (5%) of 44 patients in the NAC group (p = 0.026). A 25% or greater increase in serum cystatin C concentration was found in nine (22%) of 40 patients in the control group and in seven (17%) of 41 patients in the NAC group (p = 0.59). On the basis of serum creatinine concentration only, i.v. administration of NAC appears protective against the nephrotoxicity of contrast medium. No effect is found when serum cystatin C concentration is used to assess renal function. The effect of NAC on serum creatinine level remains unclear and may not be related to a renoprotective action.

  10. The role of N-acetylcysteine in the management of acute and chronic pulmonary complications of sulfur mustard: a literature review.

    Science.gov (United States)

    Shohrati, Majid; Karimzadeh, Iman; Saburi, Amin; Khalili, Hossein; Ghanei, Mostafa

    2014-08-01

    Sulfur mustard exposure, as the most widely used chemical weapon, can lead to acute and long-term pulmonary complications via various pathways, such as triggering an imbalance between the oxidant and antioxidant system. Currently, there is no validated antidote, chemoprophylaxis and curative modality for pulmonary toxicities secondary to sulfur mustard exposure. The aim of this literature review is to collect available experimental and clinical data on the efficacy of N-acetylcysteine (NAC), as a prominent antioxidant agent, in the prevention and/or treatment of sulfur mustard-induced acute and chronic pulmonary toxicities. A literature search was performed by the relevant keywords like "N-acetyl cysteine", "Sulfur mustard" and "Lung injury" in databases such as Scopus, Medline, Embase and ISI Web of Knowledge. No time limitation was considered. Nineteen articles were selected for review. A number of in vitro and experimental studies concluded that oral, intravenous, intraperitoneal and intra-tracheal administration of NAC is effective in the management of sulfur mustard-induced acute lung injury, in a time-dependent manner, via direct scavenging, inhibition of oxidative stress, inflammatory responses and apoptosis. In addition, oral NAC alone (1200 or 1800 mg/day for 4 months) or at a dose 600 mg/day for 6 months in combination with clarithromycin (500 mg/day) have led to improvements of clinical and paraclinical pulmonary parameters of patients with bronchiolitis obliterans due to sulfur mustard, through undetermined mechanisms. Despite limitations of relevant experimental and clinical studies, NAC can be considered as a candidate agent for prevention and/or treatment of sulfur mustard-induced acute lung injuries, as well as its long-term pulmonary toxicities, especially bronchiolitis obliterans.

  11. Role of direct reactivity with metals in chemoprotection by N-acetylcysteine against chromium(VI), cadmium(II), and cobalt(II).

    Science.gov (United States)

    Luczak, Michal W; Zhitkovich, Anatoly

    2013-12-01

    The antioxidant N-acetylcysteine (NAC) is widely used for the assessment of the role of reactive oxygen species (ROS) in various biological processes and adverse drug reactions. NAC has been found to effectively inhibit the toxicity of carcinogenic metals, which was attributed to its potent ROS-suppressive properties. However, the absence of redox activity among some metals and findings from genetic models suggested a more diverse, smaller role of oxidative stress in metal toxicity. Here, we examined mechanisms of chemoprotection by NAC against Cd(II), Co(II), and Cr(VI) in human cells. We found that NAC displayed a broad-spectrum chemoprotective activity against all three metals, including suppression of cytotoxicity, apoptosis, p53 activation, and HSP72 and HIF-1α upregulation. Cytoprotection by NAC was independent of cellular glutathione. NAC strongly inhibited the uptake of all three metals in histologically different types of human cells, explaining its high chemoprotective potential. A loss of Cr(VI) accumulation by cells was caused by NAC-mediated extracellular reduction of chromate to membrane-impermeative Cr(III). Suppression of Co(II) uptake resulted from a rapid formation of Co(II)-NAC conjugates that were unable to enter cells. Our results demonstrate that NAC acts through more than one mechanism in preventing metal toxicity and its chemoprotective activity can be completely ROS-independent. Good clinical safety and effectiveness in Co(II) sequestration suggest that NAC could be useful in the prevention of tissue accumulation and toxic effects of Co ions released by cobalt-chromium hip prostheses. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. N-acetylcysteine in agriculture, a novel use for an old molecule: focus on controlling the plant-pathogen Xylella fastidiosa.

    Directory of Open Access Journals (Sweden)

    Lígia S Muranaka

    Full Text Available Xylella fastidiosa is a plant pathogen bacterium that causes diseases in many different crops. In citrus, it causes Citrus Variegated Chlorosis (CVC. The mechanism of pathogenicity of this bacterium is associated with its capacity to colonize and form a biofilm in the xylem vessels of host plants, and there is not yet any method to directly reduce populations of this pathogen in the field. In this study, we investigated the inhibitory effect of N-Acetylcysteine (NAC, a cysteine analogue used mainly to treat human diseases, on X. fastidiosa in different experimental conditions. Concentrations of NAC over 1 mg/mL reduced bacterial adhesion to glass surfaces, biofilm formation and the amount of exopolysaccharides (EPS. The minimal inhibitory concentration of NAC was 6 mg/mL. NAC was supplied to X. fastidiosa-infected plants in hydroponics, fertigation, and adsorbed to organic fertilizer (NAC-Fertilizer. HPLC analysis indicated that plants absorbed NAC at concentrations of 0.48 and 2.4 mg/mL but not at 6 mg/mL. Sweet orange plants with CVC symptoms treated with NAC (0.48 and 2.4 mg/mL in hydroponics showed clear symptom remission and reduction in bacterial population, as analyzed by quantitative PCR and bacterial isolation. Experiments using fertigation and NAC-Fertilizer were done to simulate a condition closer to that normally is used in the field. For both, significant symptom remission and a reduced bacterial growth rate were observed. Using NAC-Fertilizer the lag for resurgence of symptoms on leaves after interruption of the treatment increased to around eight months. This is the first report of the anti-bacterial effect of NAC against a phytopathogenic bacterium. The results obtained in this work together with the characteristics of this molecule indicate that the use of NAC in agriculture might be a new and sustainable strategy for controlling plant pathogenic bacteria.

  13. N-Acetylcysteine in Agriculture, a Novel Use for an Old Molecule: Focus on Controlling the Plant–Pathogen Xylella fastidiosa

    Science.gov (United States)

    Muranaka, Lígia S.; Giorgiano, Thais E.; Takita, Marco A.; Forim, Moacir R.; Silva, Luis F. C.; Coletta-Filho, Helvécio D.; Machado, Marcos A.; de Souza, Alessandra A.

    2013-01-01

    Xylella fastidiosa is a plant pathogen bacterium that causes diseases in many different crops. In citrus, it causes Citrus Variegated Chlorosis (CVC). The mechanism of pathogenicity of this bacterium is associated with its capacity to colonize and form a biofilm in the xylem vessels of host plants, and there is not yet any method to directly reduce populations of this pathogen in the field. In this study, we investigated the inhibitory effect of N-Acetylcysteine (NAC), a cysteine analogue used mainly to treat human diseases, on X. fastidiosa in different experimental conditions. Concentrations of NAC over 1 mg/mL reduced bacterial adhesion to glass surfaces, biofilm formation and the amount of exopolysaccharides (EPS). The minimal inhibitory concentration of NAC was 6 mg/mL. NAC was supplied to X. fastidiosa-infected plants in hydroponics, fertigation, and adsorbed to organic fertilizer (NAC-Fertilizer). HPLC analysis indicated that plants absorbed NAC at concentrations of 0.48 and 2.4 mg/mL but not at 6 mg/mL. Sweet orange plants with CVC symptoms treated with NAC (0.48 and 2.4 mg/mL) in hydroponics showed clear symptom remission and reduction in bacterial population, as analyzed by quantitative PCR and bacterial isolation. Experiments using fertigation and NAC-Fertilizer were done to simulate a condition closer to that normally is used in the field. For both, significant symptom remission and a reduced bacterial growth rate were observed. Using NAC-Fertilizer the lag for resurgence of symptoms on leaves after interruption of the treatment increased to around eight months. This is the first report of the anti-bacterial effect of NAC against a phytopathogenic bacterium. The results obtained in this work together with the characteristics of this molecule indicate that the use of NAC in agriculture might be a new and sustainable strategy for controlling plant pathogenic bacteria. PMID:24009716

  14. N-acetylcysteine in agriculture, a novel use for an old molecule: focus on controlling the plant-pathogen Xylella fastidiosa.

    Science.gov (United States)

    Muranaka, Lígia S; Giorgiano, Thais E; Takita, Marco A; Forim, Moacir R; Silva, Luis F C; Coletta-Filho, Helvécio D; Machado, Marcos A; de Souza, Alessandra A

    2013-01-01

    Xylella fastidiosa is a plant pathogen bacterium that causes diseases in many different crops. In citrus, it causes Citrus Variegated Chlorosis (CVC). The mechanism of pathogenicity of this bacterium is associated with its capacity to colonize and form a biofilm in the xylem vessels of host plants, and there is not yet any method to directly reduce populations of this pathogen in the field. In this study, we investigated the inhibitory effect of N-Acetylcysteine (NAC), a cysteine analogue used mainly to treat human diseases, on X. fastidiosa in different experimental conditions. Concentrations of NAC over 1 mg/mL reduced bacterial adhesion to glass surfaces, biofilm formation and the amount of exopolysaccharides (EPS). The minimal inhibitory concentration of NAC was 6 mg/mL. NAC was supplied to X. fastidiosa-infected plants in hydroponics, fertigation, and adsorbed to organic fertilizer (NAC-Fertilizer). HPLC analysis indicated that plants absorbed NAC at concentrations of 0.48 and 2.4 mg/mL but not at 6 mg/mL. Sweet orange plants with CVC symptoms treated with NAC (0.48 and 2.4 mg/mL) in hydroponics showed clear symptom remission and reduction in bacterial population, as analyzed by quantitative PCR and bacterial isolation. Experiments using fertigation and NAC-Fertilizer were done to simulate a condition closer to that normally is used in the field. For both, significant symptom remission and a reduced bacterial growth rate were observed. Using NAC-Fertilizer the lag for resurgence of symptoms on leaves after interruption of the treatment increased to around eight months. This is the first report of the anti-bacterial effect of NAC against a phytopathogenic bacterium. The results obtained in this work together with the characteristics of this molecule indicate that the use of NAC in agriculture might be a new and sustainable strategy for controlling plant pathogenic bacteria.

  15. Role of direct reactivity with metals in chemoprotection by N-acetylcysteine against chromium(VI), cadmium(II) and cobalt(II)

    Science.gov (United States)

    Luczak, Michal W.; Zhitkovich, Anatoly

    2013-01-01

    The antioxidant N-acetylcysteine (NAC) is widely used for the assessment of the role of reactive oxygen species (ROS) in various biological processes and adverse drug reactions. NAC has been found to effectively inhibit toxicity of carcinogenic metals, which was attributed to its potent ROS-suppressive properties. However, the absence of redox activity among some metals and findings from genetic models suggested a more diverse, smaller role of oxidative stress in metal toxicity. Here, we examined mechanisms of chemoprotection by NAC against Cd(II), Co(II) and Cr(VI) in human cells. We found that NAC displayed a broad-spectrum chemoprotective activity against all three metals, including suppression of cytotoxicity, apoptosis, p53 activation and HSP72 and HIF-1α upregulation. Cytoprotection by NAC was independent of cellular glutathione. NAC strongly inhibited uptake of all three metals in histologically different types of human cells, explaining its high chemoprotective potential. A loss of Cr(VI) accumulation by cells was caused by NAC-mediated extracellular reduction of chromate to membrane-impermeable Cr(III). Suppression of Co(II) uptake resulted from a rapid formation of Co(II)-NAC conjugates that were unable to enter cells. Our results demonstrate that NAC acts through more than one mechanism in preventing metal toxicity and its chemoprotective activity can be completely ROS-independent. A good clinical safety and effectiveness in Co(II) sequestration suggest that NAC could be useful for prevention of tissue accumulation and toxic effects of Co ions released by cobalt-chromium hip prostheses. PMID:23792775

  16. Calcium-dependent nitric oxide production is involved in the cytoprotective properties of n-acetylcysteine in glycochenodeoxycholic acid-induced cell death in hepatocytes

    International Nuclear Information System (INIS)

    Gonzalez-Rubio, Sandra; Linares, Clara I.; Bello, Rosario I.; Gonzalez, Raul; Ferrin, Gustavo; Hidalgo, Ana B.; Munoz-Gomariz, Elisa; Rodriguez, Blanca A.; Barrera, Pilar; Ranchal, Isidora; Duran-Prado, Mario; Aguilar-Melero, Patricia; De la Mata, Manuel; Muntane, Jordi

    2010-01-01

    The intracellular oxidative stress has been involved in bile acid-induced cell death in hepatocytes. Nitric oxide (NO) exerts cytoprotective properties in glycochenodeoxycholic acid (GCDCA)-treated hepatocytes. The study evaluated the involvement of Ca 2+ on the regulation of NO synthase (NOS)-3 expression during N-acetylcysteine (NAC) cytoprotection against GCDCA-induced cell death in hepatocytes. The regulation of Ca 2+ pools (EGTA or BAPTA-AM) and NO (L-NAME or NO donor) production was assessed during NAC cytoprotection in GCDCA-treated HepG2 cells. The stimulation of Ca 2+ entrance was induced by A23187 in HepG2. Cell death, Ca 2+ mobilization, NOS-1, -2 and -3 expression, AP-1 activation, and NO production were evaluated. GCDCA reduced intracellular Ca 2+ concentration and NOS-3 expression, and enhanced cell death in HepG2. NO donor prevented, and L-NAME enhanced, GCDCA-induced cell death. The reduction of Ca 2+ entry by EGTA, but not its release from intracellular stores by BAPTA-AM, enhanced cell death in GCDCA-treated cells. The stimulation of Ca 2+ entrance by A23187 reduced cell death and enhanced NOS-3 expression in GCDCA-treated HepG2 cells. The cytoprotective properties of NAC were related to the recovery of intracellular Ca 2+ concentration, NOS-3 expression and NO production induced by GCDCA-treated HepG2 cells. The increase of NO production by Ca 2+ -dependent NOS-3 expression during NAC administration reduces cell death in GCDCA-treated hepatocytes.

  17. Phase I randomized clinical trial of N-acetylcysteine in combination with an adjuvant probenecid for treatment of severe traumatic brain injury in children.

    Directory of Open Access Journals (Sweden)

    Robert S B Clark

    Full Text Available There are no therapies shown to improve outcome after severe traumatic brain injury (TBI in humans, a leading cause of morbidity and mortality. We sought to verify brain exposure of the systemically administered antioxidant N-acetylcysteine (NAC and the synergistic adjuvant probenecid, and identify adverse effects of this drug combination after severe TBI in children.IRB-approved, randomized, double-blind, placebo controlled Phase I study in children 2 to 18 years-of-age admitted to a Pediatric Intensive Care Unit after severe TBI (Glasgow Coma Scale [GCS] score ≤8 requiring an externalized ventricular drain for measurement of intracranial pressure (ICP. Patients were recruited from November 2011-August 2013. Fourteen patients (n = 7/group were randomly assigned after obtaining informed consent to receive probenecid (25 mg/kg load, then 10 mg/kg/dose q6h×11 doses and NAC (140 mg/kg load, then 70 mg/kg/dose q4h×17 doses, or placebos via naso/orogastric tube. Serum and CSF samples were drawn pre-bolus and 1-96 h after randomization and drug concentrations were measured via UPLC-MS/MS. Glasgow Outcome Scale (GOS score was assessed at 3 months.There were no adverse events attributable to drug treatment. One patient in the placebo group was withdrawn due to adverse effects. In the treatment group, NAC concentrations ranged from 16,977.3±2,212.3 to 16,786.1±3,285.3 in serum and from 269.3±113.0 to 467.9±262.7 ng/mL in CSF, at 24 to 72 h post-bolus, respectively; and probenecid concentrations ranged from 75.4.3±10.0 to 52.9±25.8 in serum and 5.4±1.0 to 4.6±2.1 μg/mL in CSF, at 24 to 72 h post-bolus, respectively (mean±SEM. Temperature, mean arterial pressure, ICP, use of ICP-directed therapies, surveillance serum brain injury biomarkers, and GOS at 3 months were not different between groups.Treatment resulted in detectable concentrations of NAC and probenecid in CSF and was not associated with undesirable effects after TBI in children

  18. Phase I randomized clinical trial of N-acetylcysteine in combination with an adjuvant probenecid for treatment of severe traumatic brain injury in children.

    Science.gov (United States)

    Clark, Robert S B; Empey, Philip E; Bayır, Hülya; Rosario, Bedda L; Poloyac, Samuel M; Kochanek, Patrick M; Nolin, Thomas D; Au, Alicia K; Horvat, Christopher M; Wisniewski, Stephen R; Bell, Michael J

    2017-01-01

    There are no therapies shown to improve outcome after severe traumatic brain injury (TBI) in humans, a leading cause of morbidity and mortality. We sought to verify brain exposure of the systemically administered antioxidant N-acetylcysteine (NAC) and the synergistic adjuvant probenecid, and identify adverse effects of this drug combination after severe TBI in children. IRB-approved, randomized, double-blind, placebo controlled Phase I study in children 2 to 18 years-of-age admitted to a Pediatric Intensive Care Unit after severe TBI (Glasgow Coma Scale [GCS] score ≤8) requiring an externalized ventricular drain for measurement of intracranial pressure (ICP). Patients were recruited from November 2011-August 2013. Fourteen patients (n = 7/group) were randomly assigned after obtaining informed consent to receive probenecid (25 mg/kg load, then 10 mg/kg/dose q6h×11 doses) and NAC (140 mg/kg load, then 70 mg/kg/dose q4h×17 doses), or placebos via naso/orogastric tube. Serum and CSF samples were drawn pre-bolus and 1-96 h after randomization and drug concentrations were measured via UPLC-MS/MS. Glasgow Outcome Scale (GOS) score was assessed at 3 months. There were no adverse events attributable to drug treatment. One patient in the placebo group was withdrawn due to adverse effects. In the treatment group, NAC concentrations ranged from 16,977.3±2,212.3 to 16,786.1±3,285.3 in serum and from 269.3±113.0 to 467.9±262.7 ng/mL in CSF, at 24 to 72 h post-bolus, respectively; and probenecid concentrations ranged from 75.4.3±10.0 to 52.9±25.8 in serum and 5.4±1.0 to 4.6±2.1 μg/mL in CSF, at 24 to 72 h post-bolus, respectively (mean±SEM). Temperature, mean arterial pressure, ICP, use of ICP-directed therapies, surveillance serum brain injury biomarkers, and GOS at 3 months were not different between groups. Treatment resulted in detectable concentrations of NAC and probenecid in CSF and was not associated with undesirable effects after TBI in children. Clinical

  19. 1,4-Anthraquinone: A new useful pre-column reagent for the determination of N-acetylcysteine and captopril in pharmaceuticals by high performance liquid chromatography.

    Science.gov (United States)

    Gatti, Rita; Morigi, Rita

    2017-09-05

    1,4-Anthraquinone (ANQ) is proposed as a novel pre-column reagent for high performance liquid chromatography (HPLC) determination of N-acetylcysteine (NAC) and captopril (CAP) in pharmaceutical formulations. The derivatization reactions were carried out at room temperature: NAC at pH 8 for 1min, while CAP at pH 7.5 for 20min. Both reactions reached completeness at a reagent to thiol molar ratio of about 2.5. The synthesised derivatives were characterized by 1 H NMR and IR. The chromatographic separations were performed on a C 18 Phenomenex Synergi Fusion 4μm (250mm×4.6mm I.D.) stainless steel column with detection at λ=300nm. The mobile phase consisted of methanol/triethylammonium (TEA) phosphate buffer (pH 3; 0.05mol/L) 75:25 (v/v) at a flow-rate of 0.4mL/min for NAC and 88:12 (v/v), at a flow-rate of 0.6mL/min for CAP. The validation parameters (linearity, sensitivity, accuracy, precision, specificity and stability) were highly satisfactory. Linear response was observed (determination coefficient ≥0.9996). Detection limits were about 8 and 18ng/mL for NAC and CAP, respectively. Intra-day precision (relative standard deviation, R.S.D.) was ≤1.58%, for thiol to internal standard (IS) peak area ratio and ≤0.33%, for thiol and IS retention times (t R ), without significant differences between intra- and inter-day data. Thiol recovery studies were satisfactory (99.50%) with R.S.D. ≤0.56%. The results highlight the high sensitivity of the method and the remarkable reactivity and selectivity of the reagent towards the thiol function. The developed method is suitable for the quality control of both thiols in commercial products. The method can be applied in any analytical laboratory not requiring a sophisticated instrumentation. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Effect of amides on lithium tetraborate solubility

    International Nuclear Information System (INIS)

    Tsekhanskij, R.S.; Skvortsov, V.C.; Molodkin, A.K.; Sadetdi- pov, Sh.V.

    1983-01-01

    Using the methods of solubility, densi- and refractometry at 25 deg C, it has been established that the systemS lithium tetraborate-formamide (acetamide, dimethyl-formamide)-water are of a simple eutonic type. Amides decrease the salt solubility. Lyotropic effect, as calculated for molar concentrations (-Lsub(M)) relative to the absolute value, increases from formamide to dimethylformamide. The sequence is determined by the fact that, when there is one or two hydrophilic methyl groups in amide molecules which are in contact with tetraborate, they decrease the hydration energy of lithium cations

  1. Backbone amide linker strategy

    DEFF Research Database (Denmark)

    Shelton, Anne Pernille Tofteng; Jensen, Knud Jørgen

    2013-01-01

    In the backbone amide linker (BAL) strategy, the peptide is anchored not at the C-terminus but through a backbone amide, which leaves the C-terminal available for various modifications. This is thus a very general strategy for the introduction of C-terminal modifications. The BAL strategy...... to assemble the final peptide. One useful application of this strategy is in the synthesis of C-terminal peptide aldehydes. The C-terminal aldehyde is masked as an acetal during synthesis and then conveniently demasked in the final cleavage step to generate the free aldehyde. Another application...

  2. Labelling, biodistribution and compartmental analysis of N-acetylcysteine labelled with Tc-99m. Comparative investigation with with sup 9 sup 9 sup m Tc-MIBI in an in vivo tumoral model

    CERN Document Server

    Faintuch, B L

    1997-01-01

    Labelling and biodistribution studies were done with two different ligands, respectively Methoxy isobutyl isonitrile (MIBI) and N-acetylcysteine (NAC), employing Tc-99m as a tracer. The main objective was to assess the pharmacokinetic properties of the second substance, aiming at its possible application in cancer diagnosis. To this purpose an in vivo investigation was done using healthy and tumor-bearing rats with experimental cancer. Images of tumor-bearing rats registered in a scintillation camera indicated that with sup 9 sup 9 sup m Tc-MIBI none of the two selected times was adequate for visualization of the cancer mass. In contrast, sup 9 sup 9 sup m Tc-NAC permitted clear identification of the humor, four hours after injection. The results have demonstrated that sup 9 sup 9 sup m Tc-NAC is a radiopharmaceutical with affinity for cancer tissue and promising for further investigation concerning imaging diagnosis of tumors.

  3. Labelling, biodistribution and compartmental analysis of N-acetylcysteine labelled with Tc-99m. Comparative investigation with with 99m Tc-MIBI in an in vivo tumoral model

    International Nuclear Information System (INIS)

    Faintuch, Bluma Linkowski

    1997-01-01

    Labelling and biodistribution studies were done with two different ligands, respectively Methoxy isobutyl isonitrile (MIBI) and N-acetylcysteine (NAC), employing Tc-99m as a tracer. The main objective was to assess the pharmacokinetic properties of the second substance, aiming at its possible application in cancer diagnosis. To this purpose an in vivo investigation was done using healthy and tumor-bearing rats with experimental cancer. Images of tumor-bearing rats registered in a scintillation camera indicated that with 99m Tc-MIBI none of the two selected times was adequate for visualization of the cancer mass. In contrast, 99m Tc-NAC permitted clear identification of the humor, four hours after injection. The results have demonstrated that 99m Tc-NAC is a radiopharmaceutical with affinity for cancer tissue and promising for further investigation concerning imaging diagnosis of tumors. (author)

  4. Maternal melatonin or N-acetylcysteine therapy regulates hydrogen sulfide-generating pathway and renal transcriptome to prevent prenatal NG-Nitro-L-arginine-methyl ester (L-NAME)-induced fetal programming of hypertension in adult male offspring.

    Science.gov (United States)

    Tain, You-Lin; Lee, Chien-Te; Chan, Julie Y H; Hsu, Chien-Ning

    2016-11-01

    Pregnancy is a critical time for fetal programming of hypertension. Nitric oxide deficiency during pregnancy causes hypertension in adult offspring. We examined whether maternal melatonin or N-acetylcysteine therapy can prevent N G -nitro-L-arginine-methyl ester-induced fetal programming of hypertension in adult offspring. Next, we aimed to identify potential gatekeeper pathways that contribute to N G -nitro-L-arginine-methyl ester -induced programmed hypertension using the next generation RNA sequencing technology. Pregnant Sprague-Dawley rats were assigned to 4 groups: control, N G -nitro-L-arginine-methyl ester, N G -nitro-L-arginine-methyl ester +melatonin, and N G -nitro-L-arginine-methyl ester+N-acetylcysteine. Pregnant rats received N G -nitro-L-arginine-methyl ester administration at 60 mg/kg/d subcutaneously during pregnancy alone, with additional 0.01% melatonin in drinking water, or with additional 1% N-acetylcysteine in drinking water during the entire pregnancy and lactation. Male offspring (n=8/group) were killed at 12 weeks of age. N G -nitro-L-arginine-methyl ester exposure during pregnancy induced programmed hypertension in adult male offspring, which was prevented by maternal melatonin or N-acetylcysteine therapy. Protective effects of melatonin and N-acetylcysteine against N G -nitro-L-arginine-methyl ester-induced programmed hypertension were associated with an increase in hydrogen sulfide-generating enzymes and hydrogen sulfide synthesis in the kidneys. Nitric oxide inhibition by N G -nitro-L-arginine-methyl ester in pregnancy caused >2000 renal transcripts to be modified during nephrogenesis stage in 1-day-old offspring kidney. Among them, genes belong to the renin-angiotensin system, and arachidonic acid metabolism pathways were potentially involved in the N G -nitro-L-arginine-methyl ester-induced programmed hypertension. However, melatonin and N-acetylcysteine reprogrammed the renin-angiotensin system and arachidonic acid pathway

  5. Amides in Nature and Biocatalysis.

    Science.gov (United States)

    Pitzer, Julia; Steiner, Kerstin

    2016-10-10

    Amides are widespread in biologically active compounds with a broad range of applications in biotechnology, agriculture and medicine. Therefore, as alternative to chemical synthesis the biocatalytic amide synthesis is a very interesting field of research. As usual, Nature can serve as guide in the quest for novel biocatalysts. Several mechanisms for carboxylate activation involving mainly acyl-adenylate, acyl-phosphate or acyl-enzyme intermediates have been discovered, but also completely different pathways to amides are found. In addition to ribosomes, selected enzymes of almost all main enzyme classes are able to synthesize amides. In this review we give an overview about amide synthesis in Nature, as well as biotechnological applications of these enzymes. Moreover, several examples of biocatalytic amide synthesis are given. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Cytochrome bd-I in Escherichia coli is less sensitive than cytochromes bd-II or bo'' to inhibition by the carbon monoxide-releasing molecule, CORM-3: N-acetylcysteine reduces CO-RM uptake and inhibition of respiration.

    Science.gov (United States)

    Jesse, Helen E; Nye, Tacita L; McLean, Samantha; Green, Jeffrey; Mann, Brian E; Poole, Robert K

    2013-09-01

    CO-releasing molecules (CO-RMs) are potential therapeutic agents, able to deliver CO - a critical gasotransmitter - in biological environments. CO-RMs are also effective antimicrobial agents; although the mechanisms of action are poorly defined, haem-containing terminal oxidases are primary targets. Nevertheless, it is clear from several studies that the effects of CO-RMs on biological systems are frequently not adequately explained by the release of CO: CO-RMs are generally more potent inhibitors than is CO gas and other effects of the molecules are evident. Because sensitivity to CO-RMs cannot be predicted by sensitivity to CO gas, we assess the differential susceptibilities of strains, each expressing only one of the three terminal oxidases of E. coli - cytochrome bd-I, cytochrome bd-II and cytochrome bo', to inhibition by CORM-3. We present the first sensitive measurement of the oxygen affinity of cytochrome bd-II (Km 0.24μM) employing globin deoxygenation. Finally, we investigate the way(s) in which thiol compounds abolish the inhibitory effects of CORM-2 and CORM-3 on respiration, growth and viability, a phenomenon that is well documented, but poorly understood. We show that a strain expressing cytochrome bd-I as the sole oxidase is least susceptible to inhibition by CORM-3 in its growth and respiration of both intact cells and membranes. Growth studies show that cytochrome bd-II has similar CORM-3 sensitivity to cytochrome bo'. Cytochromes bo' and bd-II also have considerably lower affinities for oxygen than bd-I. We show that the ability of N-acetylcysteine to abrogate the toxic effects of CO-RMs is not attributable to its antioxidant effects, or prevention of CO targeting to the oxidases, but may be largely due to the inhibition of CO-RM uptake by bacterial cells. A strain expressing cytochrome bd-I as the sole terminal oxidase is least susceptible to inhibition by CORM-3. N-acetylcysteine is a potent inhibitor of CO-RM uptake by E. coli. Rational design

  7. Potencialização do efeito metemoglobinizante da dapsona em ratos pela N-acetilcisteína Potentiation of dapsone induced methemoglobinemia by N-acetylcysteine in rats

    Directory of Open Access Journals (Sweden)

    Natália Valadares de Moraes

    2008-03-01

    Full Text Available Dapsona (DDS (4,4'diaminodifenilsulfona, fármaco de escolha para o tratamento da hanseníase, freqüentemente induz anemia hemolítica e metemoglobinemia. A N-hidroxilação, uma de suas principais vias de biotransformação, é constantemente relacionada com a metemoglobinemia observada com o uso do fármaco. Com o objetivo de prevenir a hemotoxicidade induzida pela DDS, N-acetilcisteína, fármaco precursor de glutationa, foi administrada em associação com DDS em ratos machos Wistar pesando 220-240 g. Os animais foram anestesiados e o sangue coletado da aorta para determinação da concentração plasmática de DDS por CLAE, determinação dos níveis de metemoglobina e de glutationa eritrocitária por espectrofotometria, e avaliação de parâmetros bioquímicos e hematológicos. Os resultados obtidos mostraram que a N-acetilcisteína potenciou o efeito metemoglobinizante da dapsona devido ao aumento de sua concentração plasmática e conseqüente aumento da formação da N-hidroxilamina. Concluímos que as interações medicamentosas com a dapsona exigem estudos individualizados a fim de evitar os efeitos adversos do fármaco.Dapsone (DDS (4,4'diaminodiphenylsulfone, the drug of choice for the treatment of leprosy, frequently induces hemolytic anemia and methemoglobinemia. N-hydroxylation, one of the major pathways of biotransformation, has been constantly related to the methemoglobinemia after the use of the drug. In order to prevent the dapsone-induced hemotoxicity, N-acetylcysteine, a drug precursor of glutathione, was administered in combination with DDS to male Wistar rats, weighting 220-240 g. The animals were then anaesthetized and blood was collected from the aorta for determination of plasma DDS concentration by HPLC, determination of methemoglobinemia and glutathione by spectrophotometry, and for biochemical and hematological parameters. Our results showed that N-acetylcysteine enhanced dapsone-induced methemoglobinemia due to

  8. Amides in Nature and Biocatalysis

    NARCIS (Netherlands)

    Pitzer, J.; Steiner, K.

    2016-01-01

    Amides are widespread in biologically active compounds with a broad range of applications in biotechnology, agriculture and medicine. Therefore, as alternative to chemical synthesis the biocatalytic amide synthesis is a very interesting field of research. As usual, Nature can serve as guide in the

  9. 3-Methyl-1-phenyl-2-pyrazolin-5-one or N-acetylcysteine prevents hippocampal mossy fiber sprouting and rectifies subsequent convulsive susceptibility in a rat model of kainic acid-induced seizure ceased by pentobarbital.

    Science.gov (United States)

    Nomura, Shohei; Shimakawa, Shuichi; Miyamoto, Ryohei; Fukui, Miho; Tamai, Hiroshi

    2014-11-24

    There is accumulating evidence that reactive oxygen species are involved in the development of seizures under pathological conditions, and antioxidant treatments are a novel therapeutic approach for epilepsy. The kainic acid (KA) model of induced seizures has been widely used to study temporal lobe epilepsy. However, research on the use of free radical scavengers following KA-induced status epilepticus (SE) is limited. We examined whether antioxidants already used in humans could reduce hippocampal neuronal cell loss, mossy fiber sprouting and the acquisition of hyperexcitability when administered as a single dose after SE. The antioxidant 3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone) (30mg/kg) or N-acetylcysteine (NAC) (30mg/kg) was administered after KA-induced SE ceased by pentobarbital. We evaluated neuronal cell viability 1 week after SE, determined the threshold for seizures induced by inhalation of flurothyl ether 12 weeks after SE, and examined the extent of mossy fiber sprouting 12 weeks after SE. We found that edaravone or NAC prevented neuronal cell loss and mossy fiber sprouting, and increased the threshold for seizures induced by flurothyl ether, even when administered after KA-induced SE. These results demonstrate that a single dose of edaravone or NAC can protect against neuronal cell loss and epileptogenesis when administered after SE ceased by pentobarbital. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Phase space investigation of the lithium amide halides

    Energy Technology Data Exchange (ETDEWEB)

    Davies, Rosalind A. [Hydrogen Storage Chemistry Group, School of Chemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT (United Kingdom); Hydrogen and Fuel Cell Group, School of Chemical Engineering, University of Birmingham, Edgbaston B15 2TT (United Kingdom); Hewett, David R.; Korkiakoski, Emma [Hydrogen Storage Chemistry Group, School of Chemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT (United Kingdom); Thompson, Stephen P. [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0QX (United Kingdom); Anderson, Paul A., E-mail: p.a.anderson@bham.ac.uk [Hydrogen Storage Chemistry Group, School of Chemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT (United Kingdom)

    2015-10-05

    Highlights: • The lower limits of halide incorporation in lithium amide have been investigated. • The only amide iodide stoichiometry observed was Li{sub 3}(NH{sub 2}){sub 2}I. • Solid solutions were observed in both the amide chloride and amide bromide systems. • A 46% reduction in chloride content resulted in a new phase: Li{sub 7}(NH{sub 2}){sub 6}Cl. • New low-chloride phase maintained improved H{sub 2} desorption properties of Li{sub 4}(NH{sub 2}){sub 3}Cl. - Abstract: An investigation has been carried out into the lower limits of halide incorporation in lithium amide (LiNH{sub 2}). It was found that the lithium amide iodide Li{sub 3}(NH{sub 2}){sub 2}I was unable to accommodate any variation in stoichiometry. In contrast, some variation in stoichiometry was accommodated in Li{sub 7}(NH{sub 2}){sub 6}Br, as shown by a decrease in unit cell volume when the bromide content was reduced. The amide chloride Li{sub 4}(NH{sub 2}){sub 3}Cl was found to adopt either a rhombohedral or a cubic structure depending on the reaction conditions. Reduction in chloride content generally resulted in a mixture of phases, but a new rhombohedral phase with the stoichiometry Li{sub 7}(NH{sub 2}){sub 6}Cl was observed. In comparison to LiNH{sub 2}, this new low-chloride phase exhibited similar improved hydrogen desorption properties as Li{sub 4}(NH{sub 2}){sub 3}Cl but with a much reduced weight penalty through addition of chloride. Attempts to dope lithium amide with fluoride ions have so far proved unsuccessful.

  11. Gender differences among treatment-seeking adults with cannabis use disorder: Clinical profiles of women and men enrolled in the achieving cannabis cessation-evaluating N-acetylcysteine treatment (ACCENT) study.

    Science.gov (United States)

    Sherman, Brian J; McRae-Clark, Aimee L; Baker, Nathaniel L; Sonne, Susan C; Killeen, Therese K; Cloud, Kasie; Gray, Kevin M

    2017-03-01

    Recent evidence suggests that women may fare worse than men in cannabis trials with pharmacologic interventions. Identifying baseline clinical profiles of treatment-seeking cannabis-dependent adults could inform gender-specific treatment planning and development. The current study compared baseline demographic, cannabis use, and psychiatric factors between women (n = 86) and men (n = 216) entering the Achieving Cannabis Cessation-Evaluating N-acetylcysteine Treatment (ACCENT) study, a multi-site, randomized controlled trial conducted within the National Drug Abuse Treatment Clinical Trials Network. Women reported greater withdrawal intensity (p = .001) and negative impact of withdrawal (p = .001), predominantly due to physiological and mood symptoms. Women were more likely to have lifetime panic disorder (p = .038) and current agoraphobia (p = .022), and reported more days of poor physical health (p = .006) and cannabis-related medical problems (p = .023). Women reporting chronic pain had greater mean pain scores than men with chronic pain (p = .006). Men and women did not differ on any measures of baseline cannabis use. Cannabis-dependent women may present for treatment with more severe and impairing withdrawal symptoms and psychiatric conditions compared to cannabis-dependent men. This might help explain recent evidence suggesting that women fare worse than men in cannabis treatment trials of pharmacologic interventions. Baseline clinical profiles of treatment-seeking adults can inform gender-specific treatment planning and development. Cannabis-dependent women may benefit from integrated treatment focusing on co-occurring psychiatric disorders and targeted treatment of cannabis withdrawal syndrome.(Am J Addict 2017;26:136-144). © 2017 American Academy of Addiction Psychiatry.

  12. The effects of n-acetylcysteine and/or deferoxamine on manic-like behavior and brain oxidative damage in mice submitted to the paradoxal sleep deprivation model of mania.

    Science.gov (United States)

    Arent, Camila O; Valvassori, Samira S; Steckert, Amanda V; Resende, Wilson R; Dal-Pont, Gustavo C; Lopes-Borges, Jéssica; Amboni, Rafaela T; Bianchini, Guilherme; Quevedo, João

    2015-06-01

    Bipolar disorder (BD) is a severe psychiatric disorder associated with social and functional impairment. Some studies have strongly suggested the involvement of oxidative stress in the pathophysiology of BD. Paradoxal sleep deprivation (PSD) in mice has been considered a good animal model of mania because it induces similar manic-like behavior, as well as producing the neurochemical alterations which have been observed in bipolar patients. Thus, the objective of the present study was to evaluate the effects of the antioxidant agent's n-acetylcysteine (Nac) and/or deferoxamine (DFX) on behavior and the oxidative stress parameters in the brains of mice submitted to the animal model of mania induced by PSD. The mice were treated for a period of seven days with saline solution (SAL), Nac, DFX or Nac plus DFX. The animals were subject to the PSD protocol for 36 h. Locomotor activity was then evaluated using the open-field test, and the oxidative stress parameters were subsequently evaluated in the hippocampus and frontal cortex of mice. The results showed PSD induced hyperactivity in mice, which is considered a manic-like behavior. In addition to this, PSD increased lipid peroxidation and oxidative damage to proteins, as well as causing alterations to antioxidant enzymes in the frontal cortex and hippocampus of mice. The Nac plus DFX adjunctive treatment prevented both the manic-like behavior and oxidative damage induced by PSD. Improving our understanding relating to oxidative damage in biomolecules, and the antioxidant mechanisms presented in the animal models of mania are important in helping to improve our knowledge concerning the pathophysiology and development of new therapeutical treatments for BD. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. A randomized controlled trial comparing hydration therapy to additional hemodialysis or N-acetylcysteine for the prevention of contrast medium-induced nephropathy: the Dialysis-versus-Diuresis (DVD) Trial.

    Science.gov (United States)

    Reinecke, H; Fobker, M; Wellmann, J; Becke, B; Fleiter, J; Heitmeyer, C; Breithardt, G; Hense, H-W; Schaefer, R M

    2007-03-01

    Contrast medium-induced nephropathy (CIN) is a serious complication with increasing frequency and an unfavorable prognosis. Previous analyses of surrogate parameters have suggested beneficial effects of hemodialysis that are assessed in this randomized clinical trial. We performed a prospective single-center trial in 424 consecutive patients with serum creatinine concentrations between 1.3- 3.5 mg/dl who underwent elective coronary angiography. Patients were randomized to one of three treatment strategies with all patients receiving pre- and postprocedural hydration: One group received no additional therapy, patients in the second group were hemodialyzed once, and the third group received oral N-acetylcysteine. The frequency of CIN (defined as an increase in serum creatinine>or=0.5 mg/dl) from 48 to 72 h after catheterization was 6.1% in the hydration-only group, 15.9% with hemodialysis treatment, and 5.3% in the N-ACC group (intention-to-treat analysis; P=0.008). There were no differences between the treatment groups with regard to increased (>or=0.5 mg/dl) serum creatinine concentrations after 30-60 days (4.8%, 5.1%, and 3.1%, respectively; P=0.700). Analyses of long-term follow-up (range 63 to 1316 days) by Cox regressions models of the study groups found quite similar survival rates (P=0.500). In contrast to other (retrospective) studies, long-term survival of patients with vs those without CIN within 72 h was not different, but patients who still had elevated creatinine concentrations at 30-60 days suffered from a markedly higher 2-year mortality (46% vs 17%, P=0.002). In conclusion, hemodialysis in addition to hydration therapy for the prevention of CIN provided no evidence for any outcome benefit but evidence for probable harm. Increased creatinine concentrations at 30-60 days, but not within 72 h, were associated with markedly reduced long-term survival.

  14. Acrylamide-induced oxidative stress and inflammatory response are alleviated by N-acetylcysteine in PC12 cells: Involvement of the crosstalk between Nrf2 and NF-κB pathways regulated by MAPKs.

    Science.gov (United States)

    Pan, Xiaoqi; Wu, Xu; Yan, Dandan; Peng, Cheng; Rao, Chaolong; Yan, Hong

    2018-05-15

    Acrylamide (ACR) is a classic neurotoxin in animals and humans. However, the mechanism underlying ACR neurotoxicity remains controversial, and effective prevention and treatment measures against this condition are scarce. This study focused on clarifying the crosstalk between the involved signaling pathways in ACR-induced oxidative stress and inflammatory response and investigating the protective effect of antioxidant N-acetylcysteine (NAC) against ACR in PC12 cells. Results revealed that ACR exposure led to oxidative stress characterized by significant increase in reactive oxygen species (ROS) and malondialdehyde (MDA) levels and glutathione (GSH) consumption. Inflammatory response was observed based on the dose-dependently increased levels of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6). NAC attenuated ACR-induced enhancement of MDA and ROS levels and TNF-α generation. In addition, ACR activated nuclear transcription factor E2-related factor 2 (Nrf2) and nuclear factor-κB (NF-κB) signaling pathways. Knockdown of Nrf2 by siRNA significantly blocked the increased NF-κB p65 protein expression in ACR-treated PC12 cells. Down-regulation of NF-κB by specific inhibitor BAY11-7082 similarly reduced ACR-induced increase in Nrf2 protein expression. NAC treatment increased Nrf2 expression and suppressed NF-κB p65 expression to ameliorate oxidative stress and inflammatory response caused by ACR. Further results showed that mitogen-activated protein kinases (MAPKs) pathway was activated prior to the activation of Nrf2 and NF-κB pathways. Inhibition of MAPKs blocked Nrf2 and NF-κB pathways. Collectively, ACR activated Nrf2 and NF-κB pathways which were regulated by MAPKs. A crosstalk between Nrf2 and NF-κB pathways existed in ACR-induced cell damage. NAC protected against oxidative damage and inflammatory response induced by ACR by activating Nrf2 and inhibiting NF-κB pathways in PC12 cells. Copyright © 2018 Elsevier B

  15. N-acetylcysteine and fructose-1,6-bisphosphate: immunomodulatory effects on mononuclear cell culture N-acetilcisteína e frutose-1,6-bisfosfato: efeito imunomodulador em cultura de células mononucleares

    Directory of Open Access Journals (Sweden)

    Ricardo Obalski de Mello

    2012-04-01

    Full Text Available INTRODUCTION: Sepsis is a complex syndrome caused by an uncontrolled systemic inflammatory response. Inflammatory cytokines play a pivotal role in septic shock pathogenesis. Therapeutic strategies have been tested in order to modulate the excessive generation or function of sepsis mediators. OBJECTIVE: The objective of the present study was to investigate the therapeutic effect of N-acetylcysteine (NAC and its association with fructose-1,6-bisphosphate (FBP on T-lymphocytes proliferation, interleukin-1β (IL-1β and monocyte chemotactic protein-1 (MCP-1 levels. MATERIAL AND METHODS: Peripheral blood mononuclear cell samples were isolated from healthy individuals. T-lymphocytes were stimulated with phytohemagglutinin for 96 hours and submitted to different concentrations of NAC or NAC associated with FBP. RESULTS: NAC (10 and 15 mM and NAC (15 mM associated with FBP reduced T-lymphocytes proliferation. IL-1β levels rose in the presence of both NAC (15 mM and NAC with FBP (1.25 mM. MCP-1 levels were reduced only by NAC (15 mM associated with FBP (1.25 mM. CONCLUSION: The results suggest that both NAC itself and NAC associated with FBP inhibit cellular proliferation, acting as potent immunomodulatory agents, which corroborates its use in the treatment of inflammatory diseases.INTRODUÇÃO: A sepse é uma síndrome complexa causada pela resposta inflamatória sistêmica descontrolada. As citocinas inflamatórias representam papel central na patogênese do choque séptico. Têm sido testadas estratégias terapêuticas a fim de modular a geração ou a função excessiva de mediadores na sepse. OBJETIVO: O objetivo deste estudo foi investigar o efeito terapêutico da N-acetilcisteína (NAC e sua associação com a frutose-1,6-bisfosfato (FBP sobre a proliferação de linfócitos T e a geração de interleucina-1β (IL-1β e proteína quimiotática de monócitos 1 (MCP-1 em cultura celular. MATERIAL E MÉTODOS: Foram isoladas células mononucleares de

  16. Efeitos da N-acetilcisteína no precondicionamento isquêmico: estudo em corações isolados de ratos Effects of n-acetylcysteine on ischemic preconditioning: study in isolated rat hearts

    Directory of Open Access Journals (Sweden)

    Denoel Marcelino de Oliveira

    2009-03-01

    Full Text Available OBJETIVO: Avaliar se a N-Acetilcisteína (NAC altera o Precondicionamento Isquêmico (PC em corações isolados de ratos usando apenas um ciclo de PC. MÉTODOS: Freqüência Cardíaca (FC, Fluxo Coronariano (FLC e Contratilidade Miocárdica (dP/dt foram registradas em 30 corações de ratos Wistar. Após anestesia, os corações foram perfundidos em sistema de Langendorff com solução de Krebs-Hensleit (K-H, equilibrada (95% de O2 e 5% de CO2. GI: Controle (n=6; GII: 20 min. isquemia (n=6; GIII: PC (n=6; GIV 50 µg/ml/min NAC antes do PC (n =6; GV: 100 µg/ml/min NAC antes do PC (n=6. Todos os parâmetros foram mensurados após 15 minutos de estabilização (T0 e T3, T5, T10, T15, T20, T25 e T30 minutos de reperfusão. Significância estatística foi considerada quando P0,05. dP/dt foi maior no GV comparado com GIV, mas com diferença estatisticamente significativa somente em T30. CONCLUSÃO: Os corações precondicionados tiveram melhor dP/dt, sendo alteradas pelo uso de NAC no GIV e não alteradas no GV.OBJECTIVE: The aim of this study is to assess if N-Acetylcysteine (NAC changes the Ischemic Preconditioning (IP in isolated rat hearts using only one cycle of IP. METHODS: Heart Rate (HR, Coronary Flow (CF and Myocardial Contractility (dP/dt were registered in 30 Wistar rat's hearts. After anesthesia the hearts were removed and perfused with Krebes-Hensleit equilibrated solution with 95% of O2 and 5% of CO2 according Langendorff's method. GI: Control (n=6; GII: 20 min. ischemia (n=6; GIII: IP (n=6; GIV 50 µg/ml/min NAC before IP (n =6; GV: 100 µg/ ml/min NAC before IP (n=6. Parameters were measured after 15 min. of stabilization (T 0 and T3, T5, T10, T15, T20, T25 and T30 min. after reperfusion. Statistical significance was considered when P0.05. dP/dt was higher in GV than GIV but with statistically significant difference only at T30. CONCLUSION: dP/dt was better in preconditioned hearts and was changed if using NAC in GIV. The use of NAC

  17. Labelling, biodistribution and compartmental analysis of N-acetylcysteine labelled with Tc-99m. Comparative investigation with with {sup 99m} Tc-MIBI in an in vivo tumoral model; Estudo de marcacao, biodistribuicao e analise compartimental da N-acetil cisteina marcada com Tc-99m. Investigacao comparativa com MIBI-{sup 99m}Tc em modelo tumoral in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Faintuch, Bluma Linkowski

    1997-07-01

    Labelling and biodistribution studies were done with two different ligands, respectively Methoxy isobutyl isonitrile (MIBI) and N-acetylcysteine (NAC), employing Tc-99m as a tracer. The main objective was to assess the pharmacokinetic properties of the second substance, aiming at its possible application in cancer diagnosis. To this purpose an in vivo investigation was done using healthy and tumor-bearing rats with experimental cancer. Images of tumor-bearing rats registered in a scintillation camera indicated that with {sup 99m} Tc-MIBI none of the two selected times was adequate for visualization of the cancer mass. In contrast, {sup 99m} Tc-NAC permitted clear identification of the humor, four hours after injection. The results have demonstrated that {sup 99m} Tc-NAC is a radiopharmaceutical with affinity for cancer tissue and promising for further investigation concerning imaging diagnosis of tumors. (author)

  18. Hydrogen abstraction reactions by amide electron adducts

    International Nuclear Information System (INIS)

    Sevilla, M.D.; Sevilla, C.L.; Swarts, S.

    1982-01-01

    Electron reactions with a number of peptide model compounds (amides and N-acetylamino acids) in aqueous glasses at low temperature have been investigated using ESR spectroscopy. The radicals produced by electron attachment to amides, RC(OD)NDR', are found to act as hydrogen abstracting agents. For example, the propionamide electron adduct is found to abstract from its parent propionamide. Electron adducts of other amides investigated show similar behavior except for acetamide electron adduct which does not abstract from its parent compound, but does abstract from other amides. The tendency toward abstraction for amide electron adducts are compared to electron adducts of several carboxylic acids, ketones, aldehydes and esters. The comparison suggests the hydrogen abstraction tendency of the various deuterated electron adducts (DEAs) to be in the following order: aldehyde DEA > acid DEA = approximately ester DEA > ketone DEA > amide DEA. In basic glasses the hydrogen abstraction ability of the amide electron adducts is maintained until the concentration of base is increased sufficiently to convert the DEA to its anionic form, RC(O - )ND 2 . In this form the hydrogen abstracting ability of the radical is greatly diminished. Similar results were found for the ester and carboxylic acid DEA's tested. (author)

  19. Dynamics of urokinase receptor interaction with Peptide antagonists studied by amide hydrogen exchange and mass spectrometry

    DEFF Research Database (Denmark)

    Jørgensen, Thomas J D; Gårdsvoll, Henrik; Danø, Keld

    2004-01-01

    Using amide hydrogen exchange combined with electrospray ionization mass spectrometry, we have in this study determined the number of amide hydrogens on several peptides that become solvent-inaccessible as a result of their high-affinity interaction with the urokinase-type plasminogen activator...... receptor (uPAR). These experiments reveal that at least six out of eight amide hydrogens in a synthetic nine-mer peptide antagonist (AE105) become sequestered upon engagement in uPAR binding. Various uPAR mutants with decreased affinity for this peptide antagonist gave similar results, thereby indicating...... that deletion of the favorable interactions involving the side chains of these residues in uPAR does not affect the number of hydrogen bonds established by the main chain of the peptide ligand. The isolated growth factor-like domain (GFD) of the cognate serine protease ligand for uPAR showed 11 protected amide...

  20. Metal extraction by amides of carboxylic acids

    International Nuclear Information System (INIS)

    Skorovarov, D.I.; Chumakova, G.M.; Rusin, L.I.; Ul'anov, V.S.; Sviridova, R.A.; Sviridov, A.L.

    1988-01-01

    Extraction ability of various amides was studied. Data on extraction of rare earths, vanadium, molybdenum, rhenium, uranium, niobium, tantalum by N,N-dibutyl-amides of acetic, nonanic acids and fatly synthetic acids of C 7 -C 9 fractions are presented. Effect of salting-out agents, inorganic acid concentrations on extraction process was studied. Potential ability of using amides of carboxylic acids for extractional concentration of rare earths as well as for recovery and separation of iron, rhenium, vanadium, molybdenum, uranium, niobium, and tantalum was shown

  1. Dissecting Hofmeister Effects: Direct Anion-Amide Interactions Are Weaker than Cation-Amide Binding.

    Science.gov (United States)

    Balos, Vasileios; Kim, Heejae; Bonn, Mischa; Hunger, Johannes

    2016-07-04

    Whereas there is increasing evidence for ion-induced protein destabilization through direct ion-protein interactions, the strength of the binding of anions to proteins relative to cation-protein binding has remained elusive. In this work, the rotational mobility of a model amide in aqueous solution was used as a reporter for the interactions of different anions with the amide group. Protein-stabilizing salts such as KCl and KNO3 do not affect the rotational mobility of the amide. Conversely, protein denaturants such as KSCN and KI markedly reduce the orientational freedom of the amide group. Thus these results provide evidence for a direct denaturation mechanism through ion-protein interactions. Comparing the present findings with results for cations shows that in contrast to common belief, anion-amide binding is weaker than cation-amide binding. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Solvent extraction of uranium(VI) and thorium(IV) from nitrate media by carboxylic acid amides

    International Nuclear Information System (INIS)

    Preston, J.S.; Preez, A.C. du

    1995-01-01

    A series of nineteen N-alkyl carboxylic acid amides (R.CO.NHR') has been prepared, in which the alkyl groups R and R' have been varied in order to introduce different degrees of steric complexity into the compounds. A smaller number of N,N-dialkyl amides (R.CO.NR 2 ') and non-substituted amides (R.CO.NH 2 ) has also been prepared for comparison purposes. These amides were characterized by measurement of their boiling points, melting points, refractive indices and densities. The solvent extraction of uranium(VI) and thorium(IV) from sodium nitrate media by solutions of the amides in toluene was studied. Increasing steric bulk of the alkyl groups R and R' was found to cause a marked decrease in the extraction of thorium, with a much smaller effect on the extraction of uranium, thus considerably enhancing the separation between these metals. Vapour pressure osmometry studies indicate that the N-alkyl amides are self-associated in toluene solution, with aggregation numbers up to about 2.5 for 0.6 M solutions at 35 degree C. In contrast, the N,N-dialkyl amides behave as monomers under these conditions. The distribution ratios for the extraction of uranium and thorium show second- and third-order dependences, respectively, on the extractant concentration for both the N-alkyl and N,N-dialkyl amides. 15 refs., 8 figs., 8 tabs

  3. Suplementação de N-acetilcisteína em pacientes infectados pelo HIV submetidos ao primeiro tratamento anti-retroviral: Avaliação do efeito sobre a carga viral, TNF-α, IL-6, IL-8, β2-microglobulina, IgA, IgG e IgM, haptoglobina e α1-glicoproteína ácida N-acetylcysteine supplementation of HIV-infected patients under the first anti-retroviral treatment: Evaluation of the effect on viral load, TNF-α, IL-6, IL-8, β2-microglobulin, IgA, IgG, IgM, haptoglobin and α1-acid glycoprotein

    Directory of Open Access Journals (Sweden)

    Aricio Treitinger

    2002-03-01

    alterations are characterized by elevated levels of tumor necrosis factor alpha (TNF-α, interleukin 8 (IL-8, β2-microglobulin, IgA, IgG, IgM, haptoglobin and a1-acid glycoprotein. The goal of this double blind placebo-controlled study was to evaluate the effect of N-acetylcysteine supplementation on virological, immunological and inflammatory markers in 24 HIVinfected individuals who were taking their first anti-retroviral therapy. Eleven individuals were treated with anti-retroviral therapy plus placebo supplementation and thirteen were treated with anti-retroviral therapy plus 600 mg/day of Nacetylcysteine. The levels of the studied markers were evaluated at the day before and after 60, 120 and 180 days of treatment. In both groups a significant decrease in serum levels of TNF-α (p=0.0001, IL-6 (p>0.05, IL-8 (p=0.0001, b2 microglobulin (p=0.0005, IgA (p=0.007, IgG (p=0.001, IgM (p=0.0001, haptoglobin (p=0.0001 e α1-acid glycoprotein (p=0.012 was found due to anti-retroviral therapy. N-acetylcysteine supplementation had no additive or synergistic effects on the studied parameters. In conclusion, N-acetylcysteine had no additional beneficial effects, at least at the dose used in this study, on the treatment of HIV-infected patients under anti-retroviral therapy.

  4. Effect of amides on sodium tetraborate solubility

    International Nuclear Information System (INIS)

    Tsekhanskij, R.S.; Skvortsov, V.G.; Molodkin, A.K.; Sadetdinov, Sh.V.

    1986-01-01

    Methods of solubility and refractometry at 25 deg C were applied to investigate sodium tetraborate - formamide (dimethylformamide) - water systems. It is stated that they are of simple eutonic type as well as the earlier described sodium tetraborate-acetamide-water system. Amides reduce solubility of the salt. The effect of contact interaction between dissolved substances on salt cation hydration and thus on the value of liotropic amide effect is confirmed. This value is found to be also depend on the number of molecules of coordination water in the initial crystalline hydrate

  5. Steroids linked with amide bond - extended cholesterol

    Czech Academy of Sciences Publication Activity Database

    Černý, Ivan; Buděšínský, Miloš; Pouzar, Vladimír; Drašar, P.

    2009-01-01

    Roč. 74, č. 1 (2009), s. 88-94 ISSN 0039-128X R&D Projects: GA MŠk(CZ) LC06077; GA AV ČR KAN200200651 Institutional research plan: CEZ:AV0Z40550506 Keywords : synthesis * oligomers * amides Subject RIV: CC - Organic Chemistry Impact factor: 2.905, year: 2009

  6. Amides and an alkaloid from Portulaca oleracea.

    Science.gov (United States)

    Kokubun, Tetsuo; Kite, Geoffrey C; Veitch, Nigel C; Simmonds, Monique S J

    2012-08-01

    A total of 16 phenolic compounds, including one new and five known N-cinnamoyl phenylethylamides, one new pyrrole alkaloid named portulacaldehyde, five phenylpropanoid acids and amides, and derivatives of benzaldehyde and benzoic acid, were isolated and identified from a polar fraction of an extract of Portulaca oleracea. Their structures were determined through spectroscopic analyses.

  7. Cp*Rh(III)/Bicyclic Olefin Cocatalyzed C-H Bond Amidation by Intramolecular Amide Transfer.

    Science.gov (United States)

    Wang, Xiaoming; Gensch, Tobias; Lerchen, Andreas; Daniliuc, Constantin G; Glorius, Frank

    2017-05-10

    A bicyclic olefin was discovered as a cocatalyst in a Cp*Rh(III)-catalyzed C-H bond amidation proceeding by an intramolecular amide transfer in N-phenoxyacetamide derivatives. Combining experimental and theoretical studies, we propose that the olefin promotes a Rh(III) intermediate to undergo oxidative addition into the O-N bond to form a Rh(V) nitrenoid species and subsequently direct the nitrenoid to add to the ortho position. The amide directing group plays a dual role as a cleavable coordinating moiety as well as an essential coupling partner for the C-H amidation. This methodology was successfully applied to the late-stage diversification of natural products and a marketed drug under mild conditions.

  8. Metabolism of amino acid amides in Pseudomonas putida ATCC 12633

    NARCIS (Netherlands)

    Hermes, H.F.M.; Croes, L.M.; Peeters, W.P.H.; Peters, P.J.H.; Dijkhuizen, L.

    1993-01-01

    The metabolism of the natural amino acid L-valine, the unnatural amino acids D-valine, and D-, L-phenylglycine (D-, L-PG), and the unnatural amino acid amides D-, L-phenylglycine amide (D, L-PG-NH2) and L-valine amide (L-Val-NH2) was studied in Pseudomonas putida ATCC 12633. The organism possessed

  9. Self-assembly and antimicrobial activity of long-chain amide-functionalized ionic liquids in aqueous solution.

    Science.gov (United States)

    Garcia, M Teresa; Ribosa, Isabel; Perez, Lourdes; Manresa, Angeles; Comelles, Francesc

    2014-11-01

    Surface active amide-functionalized ionic liquids (ILs) consisting of a long alkyl chain (C6C14) connected to a polar head group (methylimidazolium or pyridinium cation) via an amide functional group were synthesized and their thermal stability, micellar properties and antimicrobial activity in aqueous solution investigated. The incorporation of an amide group increased the thermal stability of the functionalized ionic liquids compared to simple alkyl chain substituted ionic liquids. The surface activity and aggregation behaviour in aqueous solution of amide-functionalized ionic liquids were examined by tensiometry, conductivity and spectrofluorimetry. Amide-functionalized ILs displayed surface activity and their critical micelle concentration (cmc) in aqueous media decreased with the elongation of the alkyl side chain as occurs for typical surfactants. Compared to non-functionalized ILs bearing the same alkyl chain, ionic liquids with an amide moiety possess higher surface activity (pC20) and lower cmc values. The introduction of an amide group in the hydrophobic chain close to the polar head enhances adsorption at the air/water interface and micellization which could be attributed to the H-bonding in the headgroup region. The antimicrobial activity was evaluated against a panel of representative Gram-negative and Gram-positive bacteria and fungi. Amide-functionalized ILs with more than eight carbon atoms in the side chain showed broad antimicrobial activity. Antibacterial activities were found to increase with the alkyl chain length being the C12 homologous the most effective antimicrobial agents. The introduction of an amide group enhanced significantly the antifungal activity as compared to non-functionalized ILs. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. The effect of short-term, high-dose oral N-acetylcysteine treatment on oxidative stress markers in cystic fibrosis patients with chronic P-aeruginosa infection - A pilot study

    DEFF Research Database (Denmark)

    Skov, Marianne; Pressler, Tacjana; Lykkesfeldt, Jens

    2015-01-01

    ascorbic acid (p = 0.037) and a significant decrease in the levels of the oxidized form of ascorbic. acid (dehydroascorbate) (p = 0.004) compared to baseline were achieved after NAC treatment. No significant differences were observed in the control group. The parameters of oxidative burden did not change...

  11. Effect of N-acetylcysteine on the accuracy of the prothrombin time assay of plasma coagulation factor II plus VII plus X activity in subjects infused with the drug. Influence of time and temperature

    DEFF Research Database (Denmark)

    Thorsen, S.; Teisner, A.; Jensen, S.A.

    2009-01-01

    Objectives: The prothrombin time (PT) assay of factor II+VII+X activity is an important predictor of liver damage in paracetamol poisoned patients. It complicates interpretation of results that the antidote, acetylcysteine (NAC) depresses this activity. The aim was to investigate if NAC influences...... added to plasma in vitro decreased factor II+VII+X activity at 37 degrees C in a time-dependent manner. This effect was quenched at temperatures 24 degrees C. Activity lost at 37 degrees C could partly be recovered by subsequent incubation at 5 or 20 degrees C. Incubation at 37 degrees C prior to assay...... led to a significant additional depression of factor II+VII+X activity in plasma from subjects infused with NAC during the first 3h of infusion indicating that it contained reactive NAC. The risk that this NAC interfered with the accuracy of the PT assay was considered minimal with samples stored...

  12. Synthesis and uses of the amides extractants

    International Nuclear Information System (INIS)

    Musikas, C.

    1989-01-01

    Carboxylic acids amides (RR'NCOCR''), malonic acid amides (RR'NCOCH 2 CONRR') and substituted malonic acid amides (RR'NCOCHR'' CONRR') are extractants of the actinides ions. They show good prospects for use in the nuclear industry because of their complete incinerability. In addition, their degradation products interfer much more less in the separation processes when compared with organophosphorus extractants. The synthesis and the purification of two typical extractants: N-N-di (2-ethylhexyl) butyramide (C 4 H 9 CHC 2 H 5 CH 2 ) 2 NCOC 3 H 7 and N,N'-dimethyl N,N'-dibutyl 1.3 diamide 2(3-oxa)nonyl propane (C 4 H 9 CH 3 NCO) 2 CHC 2 H 4 OC 6 H 13 are described. The purities, checked by NMR, elemental analysis and potentiometry, were in the range 98 to 99.5%. The yields for monoamides were in the range 70 to 90% and for the diamides 20 to 40%. 3 figs, 3 tabs, 10 refs

  13. New Umami Amides: Structure-Taste Relationship Studies of Cinnamic Acid Derived Amides and the Natural Occurrence of an Intense Umami Amide in Zanthoxylum piperitum.

    Science.gov (United States)

    Frerot, Eric; Neirynck, Nathalie; Cayeux, Isabelle; Yuan, Yoyo Hui-Juan; Yuan, Yong-Ming

    2015-08-19

    A series of aromatic amides were synthesized from various acids and amines selected from naturally occurring structural frameworks. These synthetic amides were evaluated for umami taste in comparison with monosodium glutamate. The effect of the substitution pattern of both the acid and the amine parts on umami taste was investigated. The only intensely umami-tasting amides were those made from 3,4-dimethoxycinnamic acid. The amine part was more tolerant to structural changes. Amides bearing an alkyl- or alkoxy-substituted phenylethylamine residue displayed a clean umami taste as 20 ppm solutions in water. Ultraperformance liquid chromatography coupled with a high quadrupole-Orbitrap mass spectrometer (UPLC/MS) was subsequently used to show the natural occurrence of these amides. (E)-3-(3,4-Dimethoxyphenyl)-N-(4-methoxyphenethyl)acrylamide was shown to occur in the roots and stems of Zanthoxylum piperitum, a plant of the family Rutaceae growing in Korea, Japan, and China.

  14. Analytical applications of resins containing amide and polyamine functional groups

    International Nuclear Information System (INIS)

    Orf, G.M.

    1977-12-01

    A dibutyl amide resin is used for the separation of uranium(VI), thorium(IV), and zirconium(IV) from each other and several other metal ions. Uranium(VI) and thorium(IV) are determined in the presence of large excesses of foreign metal ions and anions. A practical application of the amide resin is studied by determining uranium in low grade uranium ores. The amide resin is also used for the selective concentration of gold(III) from sea water

  15. SOLID-PHASE PEPTIDE SYNTHESIS OF ISOTOCIN WITH AMIDE ...

    African Journals Online (AJOL)

    SOLID-PHASE PEPTIDE SYNTHESIS OF ISOTOCIN WITH AMIDE OF ASPARAGINE PROTECTED WITH 1-TETRALINYL. TRIFLUOROMETHANESULPHONIC ACID (TFMSA) DEPROTECTION, CLEAVAGE AND AIR OXIDATION OF MERCAPTO GROUPS TO DISULPHIDE.

  16. Decreased Libido

    Science.gov (United States)

    ... causes decreased libido? Decreased libido often accompanies other sexual disorders. Although most men with erectile dysfunction do not complain of decreased libido, after time, persistent failure with erections and sexual performance can lead to reduced sex drive in ...

  17. Pharmacodynamic Effect of N-Acetylcysteine as Adjunctive Therapy ...

    African Journals Online (AJOL)

    Erah

    8. Alves JD, Ames PR. Atherosclerosis, oxidative stress and auto-antibodies in systemic lupus erythematosus and primary antiphospholipid syndrome. Immunobiology 2003; 207(1): 23-. 28. 9. Kurien BT. Scofield RH. Free radical mediated peroxidative damage in systemic lupus erythematosus. Life Science 2003; 73: 1655-.

  18. Polymer amide as an early topology.

    Science.gov (United States)

    McGeoch, Julie E M; McGeoch, Malcolm W

    2014-01-01

    Hydrophobic polymer amide (HPA) could have been one of the first normal density materials to accrete in space. We present ab initio calculations of the energetics of amino acid polymerization via gas phase collisions. The initial hydrogen-bonded di-peptide is sufficiently stable to proceed in many cases via a transition state into a di-peptide with an associated bound water molecule of condensation. The energetics of polymerization are only favorable when the water remains bound. Further polymerization leads to a hydrophobic surface that is phase-separated from, but hydrogen bonded to, a small bulk water complex. The kinetics of the collision and subsequent polymerization are discussed for the low-density conditions of a molecular cloud. This polymer in the gas phase has the properties to make a topology, viz. hydrophobicity allowing phase separation from bulk water, capability to withstand large temperature ranges, versatility of form and charge separation. Its flexible tetrahedral carbon atoms that alternate with more rigid amide groups allow it to deform and reform in hazardous conditions and its density of hydrogen bonds provides adhesion that would support accretion to it of silicon and metal elements to form a stellar dust material.

  19. Polymer amide as an early topology.

    Directory of Open Access Journals (Sweden)

    Julie E M McGeoch

    Full Text Available Hydrophobic polymer amide (HPA could have been one of the first normal density materials to accrete in space. We present ab initio calculations of the energetics of amino acid polymerization via gas phase collisions. The initial hydrogen-bonded di-peptide is sufficiently stable to proceed in many cases via a transition state into a di-peptide with an associated bound water molecule of condensation. The energetics of polymerization are only favorable when the water remains bound. Further polymerization leads to a hydrophobic surface that is phase-separated from, but hydrogen bonded to, a small bulk water complex. The kinetics of the collision and subsequent polymerization are discussed for the low-density conditions of a molecular cloud. This polymer in the gas phase has the properties to make a topology, viz. hydrophobicity allowing phase separation from bulk water, capability to withstand large temperature ranges, versatility of form and charge separation. Its flexible tetrahedral carbon atoms that alternate with more rigid amide groups allow it to deform and reform in hazardous conditions and its density of hydrogen bonds provides adhesion that would support accretion to it of silicon and metal elements to form a stellar dust material.

  20. Oxidative activation of dihydropyridine amides to reactive acyl donors

    DEFF Research Database (Denmark)

    Funder, Erik Daa; Trads, Julie Brender; Gothelf, Kurt Vesterager

    2015-01-01

    Amides of 1,4-dihydropyridine (DHP) are activated by oxidation for acyl transfer to amines, alcohols and thiols. In the reduced form the DHP amide is stable towards reaction with amines at room temperature. However, upon oxidation with DDQ the acyl donor is activated via a proposed pyridinium...

  1. Preparation of different amides via Ritter reaction from alcohols and ...

    Indian Academy of Sciences (India)

    Ritter reaction; SBNPSA; alcohol; nitrile; amide. 1. Introduction. The conversion of nitriles to amides by reaction with alcohols or alkenes in the presence of sulphuric acid is named Ritter reaction. Acidification of the appro- priate alcohol or alkene generates a carbenium ion which reacts with nitrile. While the successful ...

  2. synthesis and characterization of new optically active poly(amide ...

    African Journals Online (AJOL)

    Preferred Customer

    such as poly(amide-imide)s and poly(acrylat-imide)s, have been developed [3-7]. Poly(amide- imide)s (PAIs) are well known as a class of polymers with good compromise between thermal stability and processability. There is a growing interest in PAIs for a variety of applications as they retain good mechanical properties at ...

  3. Synthesis, morphology, and properties of segmented poly(ether amide)s with uniform oxalamide-based hard segments

    NARCIS (Netherlands)

    Sijbrandi, N.J.; Kimenai, A.J.; Mes, E.P.C.; Broos, R.; Bar, G.; Rosenthal, M.; Odarchenko, Y.; Ivanov, D.A.; Dijkstra, Pieter J.; Feijen, Jan

    2012-01-01

    The synthesis, morphology, and properties of segmented poly(ether amide)s based on flexible PTHF segments (Mn = 1.1 × 103 g mol–1) and uniform rigid oxalamide segments were investigated. The amount of oxalamide groups in the hard segment and the spacer length of bisoxalamide-based hydrogen bonded

  4. Amide to Alkyne Interconversion via a Nickel/Copper-Catalyzed Deamidative Cross-Coupling of Aryl and Alkenyl Amides

    KAUST Repository

    Srimontree, Watchara

    2017-06-05

    A nickel-catalyzed deamidative cross-coupling reaction of amides with terminal alkynes as coupling partners was disclosed. This newly developed methodology allows the direct interconversion of amides to alkynes and enables a facile route for C(sp2)-C(sp) bond formation in a straightforward and mild fashion.

  5. Naturally occurring antifungal aromatic esters and amides

    International Nuclear Information System (INIS)

    Ali, M.S.; Shahnaz; Tabassum, S.; Ogunwande, I.A.; Pervez, M.K.

    2010-01-01

    During the search of antifungal natural products from terrestrial plants, a new long chained aromatic ester named grandiflorate along with spatazoate from Portulaca grandiflora and N-[2-methoxy-2-(4-methoxyphenyl) ethyl]-trans-cinnamide and aegeline from Solanum erianthum of Nigeria were isolated and tested against six fungal species. The known constituents have not been reported so far from mentioned investigated plants. Structures of the isolated compounds were elucidated with the aid of spectroscopic techniques including two dimensional NMR experiments. Among the compounds, the esters found more potent than amides against Candida albicans and Aspergillus flavus. The new compound grandiflorate gave response against all tested fungal species while aegeline was found to give lowest inhibition during this study. (author)

  6. Influence of Amide/Amine vs Nis-Amide Coordination in Nickel Superoxide Dismutase

    Energy Technology Data Exchange (ETDEWEB)

    Neupane,K.; Shearer, J.

    2006-01-01

    Nickel superoxide dismutase (NiSOD) is a mononuclear nickel-containing metalloenzyme that catalyzes the disproportionation of superoxide by cycling between Ni{sup II} and Ni{sup III} oxidation states. In the reduced Ni{sup II} oxidation state, the metal center is ligated by two cysteinate sulfurs, one amide nitrogen, and one amine nitrogen (from the N-terminus), while in the oxidized Ni{sup III} state, an imidazole nitrogen coordinates to the metal center. Herein, we expand on a previous report in which we described a functional metallopeptide-based NiSOD model compound [Ni{sup II}(SOD{sup M1})] (SOD{sup M1} = H{sub 2}N-HCDLPCGVYDPA-COOH) by exploring how acylation of the N-terminus (producing [Ni{sup II}(SOD{sup M1}-Ac)]) influences the properties of the metallopeptide. Titration results, GPC data, and mass-spectrometry data demonstrate that Ni{sup II} coordinates to SOD{sup M1}-Ac in a 1:1 ratio, while variable pH studies show that Ni{sup II} coordination is strong at a pH of 7.5 and above but not observed below a pH of 6.2. This is higher than [Ni{sup II}(SOD{sup M1})] by {approx}1.0 pH unit consistent with bisamide ligation. Ni K-edge XAS demonstrates that the Ni{sup II} center is coordinated in a square-planar NiN{sub 2}S{sub 2} coordination environment with Ni-N distances of 1.846(4) {angstrom} and Ni-S distances of 2.174(3) {angstrom}. Comparison of the electronic absorption and CD spectrum of [Ni{sup II}(SOD{sup M1})] versus [Ni{sup II}(SOD{sup M1}-Ac)] in conjunction with time-dependent DFT calculations suggests a decrease in Ni covalency in the acylated versus unacylated metallopeptide. This decrease in covalency was also supported by DFT calculations and Ni L-edge XAS. [Ni{sup II}(SOD{sup M1}-Ac)] has a quasireversible Ni{sup II}/Ni{sup III} redox couple of 0.49(1) V vs Ag/AgCl, which represents a -0.2 V shift compared with [Ni{sup II}(SOD{sup M1})], while the peak separation suggests a change in the coordination environment upon oxidation (i.e., axial

  7. An efficient synthetic protocol for amide derivatives of Boc-2-aminoisobutyrate.

    Science.gov (United States)

    Jo, Minmi; Won, Sun-Woo; Lee, Dong Guk; Jung, Jae-Kyung; Kim, Sunhong; Kwak, Young-Shin

    2018-03-01

    Aminoisobutyric acid (AIB) is an important building block widely incorporated by medicinal chemists in molecular design. Owing to the steric challenge, elaborating AIB's carboxylic acid using conventional amidation protocols is often problematic. We discovered that an amidation protocol utilizing methyl Boc-aminoisobutyrate and magnesium amidates of various reactivities produces the corresponding amide derivatives in good to excellent yields.

  8. Dielectric behaviour of some amides and formamides dissolved in ...

    Indian Academy of Sciences (India)

    2011-08-02

    frequency relative per- mittivity ε∞ij and static experimental parameter Xij of different amides dissolved in nonpolar solvents at 35. ◦. C. System. Weight. Static relative. High-. Static fraction permittivity frequency relative.

  9. MICROBIAL DEGRADATION OF SEVEN AMIDES BY SUSPENDED BACTERIAL POPULATIONS

    Science.gov (United States)

    Microbial transformation rate constants were determined for seven amides in natural pond water. A second-order mathematical rate expression served as the model for describing the microbial transformation. Also investigated was the relationship between the infrared spectra and the...

  10. Silver-catalyzed synthesis of amides from amines and aldehydes

    Science.gov (United States)

    Madix, Robert J; Zhou, Ling; Xu, Bingjun; Friend, Cynthia M; Freyschlag, Cassandra G

    2014-11-18

    The invention provides a method for producing amides via the reaction of aldehydes and amines with oxygen adsorbed on a metallic silver or silver alloy catalyst. An exemplary reaction is shown in Scheme 1: (I), (II), (III). ##STR00001##

  11. Total synthesis of resorcinol amide Hsp90 inhibitor AT13387.

    Science.gov (United States)

    Patel, Bhavesh H; Barrett, Anthony G M

    2012-12-21

    The synthesis of C-5-substituted resorcinol amide AT13387, a known Hsp90 inhibitor currently in clinical trials, is reported without the use of phenolic protection in an overall yield of 13.4%. Biomimetic aromatization and Suzuki-Miyaura cross coupling approach were employed to synthesize the resorcinol and iso-indoline units, respectively, which were efficiently coupled using Grignard-mediated amidation.

  12. A new phenylethyl alkyl amide from the Ambrostoma quadriimpressum Motschulsky

    Directory of Open Access Journals (Sweden)

    Guolei Zhao

    2011-09-01

    Full Text Available A new phenylethyl alkyl amide, (10R-10-hydroxy-N-phenethyloctadecanamide (1, was isolated from the beetle Ambrostoma quadriimpressum Motschulsky. The structure of the amide was determined by NMR and MS. The absolute configuration of compound 1 was confirmed by an asymmetric total synthesis, which was started from L-glutamic acid. The construction of the aliphatic chain was accomplished by the selective protection of the hydroxy groups and two-time implementation of the Wittig olefination reaction.

  13. Synthesis and biological activity of pyridazine amides, hydrazones and hydrazides.

    Science.gov (United States)

    Buysse, Ann M; Yap, Maurice Ch; Hunter, Ricky; Babcock, Jonathan; Huang, Xinpei

    2017-04-01

    Optimization studies on compounds initially designed to be herbicides led to the discovery of a series of [6-(3-pyridyl)pyridazin-3-yl]amides exhibiting aphicidal properties. Systematic modifications of the amide moiety as well as the pyridine and pyridazine rings were carried out to determine if these changes could improve insecticidal potency. Structure-activity relationship (SAR) studies showed that changes to the pyridine and pyridazine rings generally resulted in a significant loss of insecticidal potency against green peach aphids [Myzus persicae (Sulzer)] and cotton aphids [(Aphis gossypii (Glover)]. However, replacement of the amide moiety with hydrazines, hydrazones, or hydrazides appeared to be tolerated, with small aliphatic substituents being especially potent. A series of aphicidal [6-(3-pyridyl)pyridazin-3-yl]amides were discovered as a result of random screening of compounds that were intially investigated as herbicides. Follow-up studies of the structure-activity relationship of these [6-(3-pyridyl)pyridazin-3-yl]amides showed that biosteric replacement of the amide moiety was widely tolerated suggesting that further opportunities for exploitation may exist for this new area of insecticidal chemistry. Insecticidal efficacy from the original hit, compound 1, to the efficacy of compound 14 produced greater than 10-fold potency improvement against Aphis gossypii and greater than 14-fold potency improvement against Myzus persicae. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  14. Electrical behavior of amide functionalized graphene oxide and graphene oxide films annealed at different temperatures

    Energy Technology Data Exchange (ETDEWEB)

    Rani, Sumita; Kumar, Mukesh, E-mail: kumarmukesh@gmail.com; Kumar, Dinesh; Sharma, Sumit

    2015-06-30

    Films of graphene oxide (GO) and amide functionalized graphene oxides (AGOs) were deposited on SiO{sub 2}/Si(100) by spin coating and were thermally annealed at different temperatures. Sheet resistance of GO and AGOs films was measured using four probe resistivity method. GO an insulator at room temperature, exhibits decrease in sheet resistance with increase in annealing temperature. However, AGOs' low sheet resistance (250.43 Ω) at room temperature further decreases to 39.26 Ω after annealing at 800 °C. It was observed that the sheet resistance of GO was more than AGOs up to 700 °C, but effect was reversed after annealing at higher temperature. At higher annealing temperatures the oxygen functionality reduces in GO and sheet resistance decreases. Sheet resistance was found to be annealing time dependent. Longer duration of annealing at a particular temperature results in decrease of sheet resistance. - Highlights: • Amide functionalized graphene oxides (AGOs) were synthesized at room temperature (RT). • AGO films have low sheet resistance at RT as compared to graphene oxide (GO). • Fast decrease in the sheet resistance of GO with annealing as compared to AGOs • AGOs were found to be highly dispersible in polar solvents.

  15. NMR Analysis of Amide Hydrogen Exchange Rates in a Pentapeptide-Repeat Protein from A. thaliana.

    Science.gov (United States)

    Xu, Shenyuan; Ni, Shuisong; Kennedy, Michael A

    2017-05-23

    At2g44920 from Arabidopsis thaliana is a pentapeptide-repeat protein (PRP) composed of 25 repeats capped by N- and C-terminal α-helices. PRP structures are dominated by four-sided right-handed β-helices typically consisting of mixtures of type II and type IV β-turns. PRPs adopt repeated five-residue (Rfr) folds with an Rfr consensus sequence (STAV)(D/N)(L/F)(S/T/R)(X). Unlike other PRPs, At2g44920 consists exclusively of type II β-turns. At2g44920 is predicted to be located in the thylakoid lumen although its biochemical function remains unknown. Given its unusual structure, we investigated the biophysical properties of At2g44920 as a representative of the β-helix family to determine if it had exceptional global stability, backbone dynamics, or amide hydrogen exchange rates. Circular dichroism measurements yielded a melting point of 62.8°C, indicating unexceptional global thermal stability. Nuclear spin relaxation measurements indicated that the Rfr-fold core was rigid with order parameters ranging from 0.7 to 0.9. At2g44920 exhibited a striking range of amide hydrogen exchange rates spanning 10 orders of magnitude, with lifetimes ranging from minutes to several months. A weak correlation was found among hydrogen exchange rates, hydrogen bonding energies, and amino acid solvent-accessible areas. Analysis of contributions from fast (approximately picosecond to nanosecond) backbone dynamics to amide hydrogen exchange rates revealed that the average order parameter of amides undergoing fast exchange was significantly smaller compared to those undergoing slow exchange. Importantly, the activation energies for amide hydrogen exchange were found to be generally higher for the slowest exchanging amides in the central Rfr coil and decreased toward the terminal coils. This could be explained by assuming that the concerted motions of two preceding or following coils required for hydrogen bond disruption and amide hydrogen exchange have a higher activation energy

  16. Amide and Ester-Functionalized Humic Acid for Fuel Combustion Enhancement

    Science.gov (United States)

    Riggs, Mark

    . The modified humic acid samples were diluted with kerosene to identify the influence on combustion properties. Butyl-modified humic acid samples decreased the molar enthalpy of combustion. Hexyl, octyl, and decyl-modified humic acids improved the combustion values. Decyl amide-modified humic acid showed the largest improvement of these mixtures with a 0.9% increase from the expected molar enthalpy of combustion with a loading percentage of 0.36% in kerosene. Octyl amide-modified and octyl ester-modified humic acid mixtures were prepared in 0.05, 0.1, and 1% loading percentage dilutions to study the effect of modified humic acid loading percent on combustion properties. The 0.1% dilution showed the largest increase of the expected molar enthalpy of combustion by 1.14% and 0.4% for amide-modified HA and ester-modified HA, respectively.

  17. Mapping temperature-induced conformational changes in the Escherichia coli heat shock transcription factor sigma 32 by amide hydrogen exchange

    DEFF Research Database (Denmark)

    Rist, Wolfgang; Jørgensen, Thomas J D; Roepstorff, Peter

    2003-01-01

    Stress conditions such as heat shock alter the transcriptional profile in all organisms. In Escherichia coli the heat shock transcription factor, sigma 32, out-competes upon temperature up-shift the housekeeping sigma-factor, sigma 70, for binding to core RNA polymerase and initiates heat shock...... gene transcription. To investigate possible heat-induced conformational changes in sigma 32 we performed amide hydrogen (H/D) exchange experiments under optimal growth and heat shock conditions combined with mass spectrometry. We found a rapid exchange of around 220 of the 294 amide hydrogens at 37...... promoters. The correlated exchange is shown to constitute a reversible unfolding with a half-life of about 30 min due to a temperature-dependent decrease in stabilization energy. We propose that this gradual decrease in stabilization energy of domain sigma 2 with increasing temperatures facilitates...

  18. Biosynthesis of amidated joining peptide from pro-adrenocorticotropin-endorphin

    Energy Technology Data Exchange (ETDEWEB)

    Cullen, E.I.; Mains, R.E. (Johns Hopkins Univ. School of Medicine, Baltimore, MD (USA))

    1987-09-01

    Joining peptide is the major alpha-amidated product of pro-ACTH/endorphin (PAE) in AtT-20 corticotropic tumor cells. To study intracellular joining peptide synthesis, affinity purified antibodies directed against gamma-MSH, joining peptide, and ACTH were used to immunoprecipitate extracts from biosynthetically labeled AtT-20 cells. Immunoprecipitates were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by tryptic peptide mapping on HPLC. In steady labeling experiments, radioactivity in amidated joining peptide (JP) increased roughly linearly with time, in the manner of a final product, whereas radioactivity associated with PAE (1-94)NH2 reached a constant value after 2-4 h, indicating that PAE(1-94)NH2 is an intermediate in the biosynthesis of JP. Radioactivity appeared in ACTH(1-39) well before JP, consistent with a cleavage order in which ACTH is cleaved from PAE(1-95) before JP sequences are cleaved from PAE(1-74). This conclusion was supported by tryptic peptide analyses of immunoprecipitates, which indicated that less than 5% of JP-related material is cleaved from PAE(1-74) before being cleaved from ACTH-related sequences. After a pulse label, radioactivity in PAE(1-94)NH2 reached a peak value after 1 h of chase and declined with a half-life of less than 1 h. Amidated JP increased to a constant level after 2 h of chase. Enough radiolabeled PAE(1-94)NH2 was detected to account for about half of the radioactivity found in amidated JP, indicating that about half of JP-related material is first cleaved from PAE(1-95) before being amidated. This result was corroborated using HPLC purification to determine both amidated and glycine-extended forms of JP.

  19. Amide synthesis by nucleophilic attack of vinyl azides.

    Science.gov (United States)

    Zhang, Feng-Lian; Wang, Yi-Feng; Lonca, Geoffroy Hervé; Zhu, Xu; Chiba, Shunsuke

    2014-04-22

    A method for the synthesis of amide-containing molecules was developed using vinyl azides as an enamine-type nucleophile towards carbon electrophiles, such as imines, aldehydes, and carbocations that were generated from alcohols in the presence of BF3 ⋅OEt2 . After nucleophilic attack of the vinyl azide, a substituent of the resulting iminodiazonium ion intermediate migrates to form a nitrilium ion, which is hydrolyzed to afford the corresponding amide. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Amide-modified poly(butylene terepthalate): thermal stability

    NARCIS (Netherlands)

    van Bennekom, A.C.M.; van Bennekom, A.C.M.; Willemsen, P.A.A.T.; Willemsen, P.A.A.T.; Gaymans, R.J.

    1996-01-01

    The thermal stability of a poly(ester amide) copolymer (PBTA) based on poly(butylene terephthalate) (PBT) and nylon-4,T with the diamide of butanediamine and dimethyl terephthalate (N,N′-bis(p-carbomethoxybenzoyl)butanediamine) and homopolymer PBT was studied. The development of inherent viscosity

  1. Polyurethanes elastomers with amide chain extenders of uniform length

    NARCIS (Netherlands)

    van der Schuur, J.M.; Noordover, B.A.J.; Noordover, Bart; Gaymans, R.J.

    2006-01-01

    Toluene diisocyanate based polyurethanes with amide extenders were synthesized poly(propylene oxide) with a number average molecular weight of 2000 and endcapped with toluene diisocyanate was used as the polyether segment. The chain extenders were based on poly(hexamethylene terephthalamide):

  2. Proximity effect on the general base catalysed hydrolysis of amide ...

    Indian Academy of Sciences (India)

    A constant value of absorbance could not be achieved even after 3 days. However, independent measurements. (by mixing the corresponding amines, salicylic acid and. NaOH, I = 0.5 mol dm. −3) showed that a reaction mix- ture for the complete hydrolysis of the amides (I–IV) to the corresponding amines and salicylate had ...

  3. Method for enhancing amidohydrolase activity of fatty acid amide hydrolase

    Energy Technology Data Exchange (ETDEWEB)

    John, George; Nagarajan, Subbiah; Chapman, Kent; Faure, Lionel; Koulen, Peter

    2017-12-26

    A method for enhancing amidohydrolase activity of Fatty Acid Amide Hydrolase (FAAH) is disclosed. The method comprising administering a phenoxyacyl-ethanolamide that causes the enhanced activity. The enhanced activity can have numerous effects on biological organisms including, for example, enhancing the growth of certain seedlings.

  4. Straightforward uranium-catalyzed dehydration of primary amides to nitriles

    International Nuclear Information System (INIS)

    Enthaler, Stephan

    2011-01-01

    The efficient uranium-catalyzed dehydration of a variety of primary amides, using N-methyl-N-(trimethylsilyl)trifluoroacetamide (MSTFA) as a dehydration reagent, to the corresponding nitriles has been investigated. With this catalyst system, extraordinary catalyst activities and selectivities were feasible. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  5. Synthesis and characterization of thermally stable poly(amide-imide ...

    African Journals Online (AJOL)

    ... polymeric chains on the properties of nanocomposites films were investigated by using UV-Vis spectroscopy, thermal gravimetry analysis (TGA) and water uptake measurements. KEYWORDS: Bis(4-carboxyphenyl)-N,N'-pyromellitimide acid moiety, Poly(amide-imide)-montmorillonite nanocomposite, Thermal properties.

  6. Synthesis, characterization and photo behavior of new poly(amide ...

    African Journals Online (AJOL)

    ... and the interaction between clay and polymeric chains on the properties of nanocomposites films were investigated by using UV-Vis spectroscopy, thermogravimetric analysis (TGA) and water uptake measurements. KEY WORDS: Nanocomposite, Poly(amide-imide), Silicate particle, Polycondensation, Thermal behavior.

  7. Effect of Thiazolidinedione Amide on Insulin Resistance, Creactive ...

    African Journals Online (AJOL)

    Effect of Thiazolidinedione Amide on Insulin Resistance, Creactive Protein and Endothelial Function in Young Women with Polycystic Ovary Syndrome. Wen-Yu Zhong, Hui Peng, Hua Li, Hui Shang, Yong-Qing Wei, Zheng-Hui Fang, Xing-Bo Zhao ...

  8. Proximity effect on the general base catalysed hydrolysis of amide ...

    Indian Academy of Sciences (India)

    the solution state kinetics and equilibria involving poly- dentate phenol–amide ligands and transition metal ions. ∗ ... itored with a Cecil spectrophotometer model CE 7200. (U.K.). The cell block was thermostatted to the .... then acidified with HClO4 to pH 1 and extracted with. CHCl3 at least thrice. All the CHCl3 extracts were.

  9. Synthesis of novel nanostructured chiral poly(amide-imide)s ...

    Indian Academy of Sciences (India)

    Synthesis of novel nanostructured chiral poly(amide-imide)s containing dopamine and natural amino acids. SHADPOUR MALLAKPOURa,b,∗ and AMIN ZADEHNAZARIa. aOrganic Polymer Chemistry Research Laboratory, Department of Chemistry,. bNanotechnology and Advanced Materials Institute, Isfahan University of ...

  10. Citral derived amides as potent bacterial NorA efflux pump inhibitors

    DEFF Research Database (Denmark)

    Thota, Niranjan; Koul, Surrinder; Reddy, Mallepally V

    2008-01-01

    Monoterpene citral and citronellal have been used as starting material for the preparation of 5,9-dimethyl-deca-2,4,8-trienoic acid amides and 9-formyl-5-methyl-deca-2,4,8-trienoic acid amides. The amides on bioevaluation as efflux pump inhibitors (EPIs) against Staphylococcus aureus 1199 and Nor...

  11. Use of triphenyl phosphate as risk mitigant for metal amide hydrogen storage materials

    Energy Technology Data Exchange (ETDEWEB)

    Cortes-Concepcion, Jose A.; Anton, Donald L.

    2016-04-26

    A process in a resulting product of the process in which a hydrogen storage metal amide is modified by a ball milling process using an additive of TPP. The resulting product provides for a hydrogen storage metal amide having a coating that renders the hydrogen storage metal amide resistant to air, ambient moisture, and liquid water while improving useful hydrogen storage and release kinetics.

  12. In vitro evaluation of N-methyl amide tripeptidomimetics as substrates for the human intestinal di-/tri-peptide transporter hPEPT1

    DEFF Research Database (Denmark)

    Andersen, Rikke; Nielsen, Carsten Uhd; Begtrup, Mikael

    2006-01-01

    of structural properties of 6859 N-methyl amide tripeptidomimetics. In vitro extracellular degradation of the selected tripeptidomimetics as well as affinity for and transepithelial transport via hPEPT1 were investigated in Caco-2 cells. Decreased apparent degradation was observed for all tripeptidomimetics...

  13. Physical attributes of some clouds amid a forest ecosystem's trees

    Science.gov (United States)

    DeFelice, Thomas P.

    2002-01-01

    Cloud or fog water collected by forest canopies of any elevation could represent significant sources of required moisture and nutrients for forest ecosystems, human consumption, and as an alternative source of water for agriculture and domestic use. The physical characteristics of fogs and other clouds have been well studied, and this information can be useful to water balance or canopy–cloud interaction model verification and to calibration or training of satellite-borne sensors to recognize atmospheric attributes, such as optical thickness, albedo, and cloud properties. These studies have taken place above-canopy or within canopy clearings and rarely amid the canopy. Simultaneous physical and chemical characteristics of clouds amid and above the trees of a mountain forest, located about 3.3 km southwest of Mt. Mitchell, NC, were collected between 13 and 22 June 1993. This paper summarizes the physical characteristics of the cloud portions amid the trees. The characteristic cloud amid the trees (including cloud and precipitation periods) contained 250 droplet/cm3 with a mean diameter of 9.5 μm and liquid water content (LWC) of 0.11 g m−3. The cloud droplets exhibited a bimodal distribution with modes at about 2 and 8 μm and a mean diameter near 5 μm during precipitation-free periods, whereas the concurrent above-canopy cloud droplets had a unimodal distribution with a mode near 6 μm and a mean diameter of 6 μm. The horizontal cloud water flux is nonlinearly related to the rate of collection onto that surface amid the trees, especially for the Atmospheric Sciences Research Center (ASRC) sampling device, whereas it is linear when the forward scattering spectrometer probe (FSSP) are is used. These findings suggest that statements about the effects clouds have on surfaces they encounter, which are based on above-canopy or canopy-clearing data, can be misleading, if not erroneous.

  14. Carryover potassium amide in cracker at HWP, Hazira - a case study (Paper No. 1.5)

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    The liquid ammonia fed to cracker is made available from potassium amide catalyst recovery unit, where catalyst potassium amide is separated by distillation. Extreme care is taken to ensure that ammonia is totally free from potassium. Also the gas used for catalyst heating during start up, should be free of any possible amide contamination and should be pure and dry as moisture is a poison for the catalyst. In order to prevent the recurrence of amide carryover to cracker tubes from start up gas line, certain modifications were carried out besides removal of amide from pipings. Details are discussed. (author)

  15. Solvent Exchange Rates of Side-chain Amide Protons in Proteins

    International Nuclear Information System (INIS)

    Rajagopal, Ponni; Jones, Bryan E.; Klevit, Rachel E.

    1998-01-01

    Solvent exchange rates and temperature coefficients for Asn/Gln side-chain amide protons have been measured in Escherichia coli HPr. The protons of the eight side-chain amide groups (two Asn and six Gln) exhibit varying exchange rates which are slower than some of the fast exchanging backbone amide protons. Differences in exchange rates of the E and Z protons of the same side-chain amide group are obtained by measuring exchange rates at pH values > 8. An NOE between a side-chain amide proton and a bound water molecule was also observed

  16. Adsorption equilibrium of uranium from seawater on chelating resin containing amide oxime group

    International Nuclear Information System (INIS)

    Hori, Takahiro; Saito, Kyoichi; Furusaki, Shintaro; Sugo, Takanobu; Okamoto, Jiro.

    1987-01-01

    Chelating resins containing amide oxime group were synthesized by radiation-induced graft polymerization. The amount of the amide oxime groups was controlled below about 0.1 mol per kg of base polymer. The adsorption equilibrium of uranium from seawater on this resin was investigated. It was suggested that two neighboring amide oxime groups on the grafted chain captured one uranyl ion, and that single amide oxime ligand had little capacity for the adsorption of uranium. The adsorption equilibrium was correlated by a Langmuir-type equation. The content of neighboring amide oxime groups was 0.406 x 10 -3 mol per kg of base polymer, which corresponded to 0.39 % of the total amount of amide oxime groups. The apparent stoichiometric stability constant for the complex of uranyl ion with the neighboring amide oxime groups in seawater was calculated to be 10 -21.7 . (author)

  17. Simple Synthesis Hydrogenated Castor Oil Fatty Amide Wax and Its Coating Characterization.

    Science.gov (United States)

    Yu, Xiuzhu; Wang, Ning; Zhang, Rui; Zhao, Zhong

    2017-07-01

    A simple method for incorporating amine groups in hydrogenated castor oil (HCO) to produce wax for beeswax or carnauba wax substitution in packaging and coating was developed. From the conversion rate of the products, HCO was reacted with ethanolamine at 150°C for 5 h, and the molar ratio of HCO and ethanolamine was 1:4. The hardness of the final product was seven times higher than that of beeswax, the cohesiveness of the final product was 1.3 times higher than that of beeswax and approximately one half of that of carnauba wax, and the melting point of the final product is 98°C. The Fourier transform Infrared spectroscopy showed that the amide groups were incorporated to form the amide products. In coating application, the results showed that the force of the final product coating cardboard was higher than that of beeswax and paraffin wax and less than that of carnauba wax. After 24 h soaking, the compression forces were decreased. HCO fatty acid wax can be an alternative wax for carnauba wax and beeswax in coating applications.

  18. Cinnamic acid amides from Tribulus terrestris displaying uncompetitive α-glucosidase inhibition.

    Science.gov (United States)

    Song, Yeong Hun; Kim, Dae Wook; Curtis-Long, Marcus J; Park, Chanin; Son, Minky; Kim, Jeong Yoon; Yuk, Heung Joo; Lee, Keun Woo; Park, Ki Hun

    2016-05-23

    The α-glucosidase inhibitory potential of Tribulus terrestris extracts has been reported but as yet the active ingredients are unknown. This study attempted to isolate the responsible metabolites and elucidate their inhibition mechanism of α-glucosidase. By fractionating T. terristris extracts, three cinnamic acid amide derivatives (1-3) were ascertained to be active components against α-glucosidase. The lead structure, N-trans-coumaroyltyramine 1, showed significant inhibition of α-glucosidase (IC50 = 0.42 μM). Moreover, all active compounds displayed uncompetitive inhibition mechanisms that have rarely been reported for α-glucosidase inhibitors. This kinetic behavior was fully demonstrated by showing a decrease of both Km and Vmax, and Kik/Kiv ratio ranging between 1.029 and 1.053. We progressed to study how chemical modifications to the lead structure 1 may impact inhibition. An α, β-unsaturation carbonyl group and hydroxyl group in A-ring of cinnamic acid amide emerged to be critical functionalities for α-glucosidase inhibition. The molecular modeling study revealed that the inhibitory activities are tightly related to π-π interaction as well as hydrogen bond interaction between enzyme and inhibitors. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  19. Coumarin amide derivatives as fluorescence chemosensors for cyanide anions

    International Nuclear Information System (INIS)

    Wu, Qianqian; Liu, Zhiqiang; Cao, Duxia; Guan, Ruifang; Wang, Kangnan; Shan, Yanyan; Xu, Yongxiao; Ma, Lin

    2015-01-01

    Four coumarin amide derivatives with 4-methyl coumarin or pyrene as terminal group have been synthesized. Their photophysical properties and recognition properties for cyanide anions have been examined. The results indicate that the compounds can recognize cyanide anions with obvious absorption and fluorescence spectra change, at the same time, obvious color and fluorescence change can be observed by naked eye. The in situ hydrogen nuclear magnetic resonance spectra and photophysical properties change confirm that Michael additions between the chemosensors and cyanide anions take place at the 4-position of coumarin. - Highlights: • Four coumarin amide derivatives with 4-methyl coumarin or pyrene as terminal group were synthesized. • The compounds can recognize cyanide anions with obvious absorption and fluorescence spectra change. • Michael additions between the chemosensors and cyanide anions take place at the 4-position of coumarin

  20. Actinide extraction by substituted amides or diamides from carboxylic acids

    International Nuclear Information System (INIS)

    Cuillerdier, C.; Musikas, C.; Morisseau, J.C.; Hoel, P.; Guillaume, B.

    1987-01-01

    Amides are studied for use in reprocessing, these solvents can be incinerated and radiolytic degradation have no effect on the process. Main research fields are: 1) Monoamides type RCONR 2 allow U (VI) and Pu (IV) extraction like TBP. Ramified R and R' increase the amount of U extracted, the selectivity U/Pu and U + Pu/Fission products. A counter current test gave encouraging results. 2) Diamides for trivalent actinide extraction from radioactive wastes and especially malonamides. Extraction coefficient in function of HNO 3 concentration are measured for Am (III), En (III), Pu (IV), U (VI) and Zr (IV). Zr should be complexed in aqueous phase to avoid extraction with actinides. Selection of solvent is not yet possible but amides are interesting as alternate extractants [fr

  1. Electronic structure effects of amide group: Vince lactam

    Science.gov (United States)

    Novak, Igor; Kovač, Branka

    2005-03-01

    HeI photoelectron spectrum of 2-azabicyclo[2.2.1]hept-5-en-3-one (Vince lactam) has been measured. The assignment of the spectrum was made by comparison with photoelectron spectra of related compounds and by taking into account the lactam's molecular structure. The analysis of the electronic structure of amide group, in terms of inductive and conjugative effects, is presented on the basis of photoelectron spectroscopic data.

  2. Toxocara canis: Larvicidal activity of fatty acid amides.

    Science.gov (United States)

    Mata-Santos, Taís; D'Oca, Caroline da Ros Montes; Mata-Santos, Hílton Antônio; Fenalti, Juliana; Pinto, Nitza; Coelho, Tatiane; Berne, Maria Elisabeth; da Silva, Pedro Eduardo Almeida; D'Oca, Marcelo Gonçalves Montes; Scaini, Carlos James

    2016-02-01

    Considering the therapeutic potential of fatty acid amides, the present study aimed to evaluate their in vitro activity against Toxocara canis larvae and their cytotoxicity for the first time. Linoleylpyrrolidilamide was the most potent, with a minimal larvicidal concentration (MLC) of 0.05 mg/mL and 27% cytotoxicity against murine peritoneal macrophages C57BL/6 mice, as assessed by the MTT assay. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. [Amides of amino acids and peptides as antifungal agents].

    Science.gov (United States)

    Giori, P; Vertuani, G; Mazzotta, D; Guarneri, M; Pancaldi, D; Brunelli, A

    1982-07-01

    The synthesis of pyrazolyl-amides of aminoacids and peptides is described. The chemicals were tested for antifungal activity against wheat powdery mildew (Erysiphe graminis DC.), cucumber powdery mildew (Erysiphe cichoracearum DC.), wheat brown rust (Puccinia recondita Rob. ex Desm. f. sp. tritici Erikss et Henn.), celery leaf spot (Septoria Apii Briosi ed Cav. Chest.) and collar rot (Rhizoctonia solani Kuhn). Some of these compounds showed antifungal activity.

  4. Interacting Blends of Novel Unsaturated Polyester Amide Resin with Styrene

    OpenAIRE

    Patel, Hasmukh S.; Panchal, Kumar K.

    2004-01-01

    Novel unsaturated poly (ester-amide) resins (UPEAs) were prepared by the reaction between an epoxy resin, namely diglycidyl ether of bisphenol–A (DGEBA) and unsaturated aliphatic bisamic acids using a base catalyst. These UPEAs were then blended with a vinyl monomer namely, Styrene (STY.) to produce a homogeneous resin syrup. The curing of these UPEAs-STY. resin blends was carried out by using benzoyl peroxide (BPO) as a catalyst and was monitored by using a differential scanning calorimeter ...

  5. The professional agency of teacher educators amid academic discourses

    OpenAIRE

    Hökkä, Päivi; Eteläpelto, Anneli; Rasku-Puttonen, Helena

    2012-01-01

    Agency has been seen as fundamental in the renegotiation of professional identities. However, it is unclear how teacher educators exercise their professional agency in their work, and how multiple discourses frame and restrict the practice of their professional agency. This study examines how teacher educators practise agency in negotiating their professional identities amid the multiple discourses emerging from the academic context of their work. The aim was to investigate educators’ locally...

  6. Effect of structure on extraction ability of phosphoric acid amides

    International Nuclear Information System (INIS)

    Laskorin, B.N.; Buchikhin, E.P.; Yakshin, V.V.

    1976-01-01

    Effective constants of uranium (6) extraction with amides and esteroamides based on the acids of phosphorus of various structures have been determined. The component analysis of the complexes obtained points to the formation of a compound with the metal/ligand ratio = 2. The introduction of alkyl amine substituents in the molecule of the neutral esters of organophosphoric acids is shown to lead to a substantial increase in their extraction capacity [ru

  7. Yeast AMID homologue Ndi1p displays respiration-restricted apoptotic activity and is involved in chronological aging.

    Science.gov (United States)

    Li, Wei; Sun, Libo; Liang, Qiuli; Wang, Juan; Mo, Weike; Zhou, Bing

    2006-04-01

    Apoptosis-inducing factor (AIF) and AIF-homologous mitochondrion-associated inducer of death (AMID) are both mitochondrial flavoproteins that trigger caspase-independent apoptosis. Phylogenetic analysis suggests that these two proteins evolutionarily diverge back from their common prokaryote ancestor. Compared with AIF, the proapoptotic nature of AMID and its mode of action are much less clarified. Here, we show that overexpression of yeast AMID homologue internal NADH dehydrogenase (NDI1), but not external NADH dehydrogenase (NDE1), can cause apoptosis-like cell death, and this effect can be repressed by increased respiration on glucose-limited media. This result indicates that the regulatory network of energy metabolism, in particular the cross-talk between mitochondria and the rest of the cell, is involved in Ndi1p-induced yeast cell apoptosis. The apoptotic effect of NDI1 overexpression is associated with increased production of reactive oxygen species (ROS) in mitochondria. In addition, NDI1 overexpression in sod2 background causes cell lethality in both fermentable and semifermentable media. Interruption of certain components in the electron transport chain can suppress the growth inhibition from Ndi1p overexpression. We finally show that disruption of NDI1 or NDE1 decreases ROS production and elongates the chronological life span of yeast, accompanied by the loss of survival fitness. Implication of these findings for Ndi1p-induced apoptosis is discussed.

  8. Enzymatically and reductively degradable α-amino acid-based poly(ester amide)s: Synthesis, cell compatibility, and intracellular anticancer drug delivery

    NARCIS (Netherlands)

    Sun, H.; Cheng, Ru; Deng, Chao; Meng, Fenghua; Dias, Aylvin A.; Hendriks, Marc; Feijen, Jan; Zhong, Zhiyuan

    2015-01-01

    A novel and versatile family of enzymatically and reductively degradable α-amino acid-based poly(ester amide)s (SS-PEAs) were developed from solution polycondensation of disulfide-containing di-p-toluenesulfonic acid salts of bis-l-phenylalanine diesters (SS-Phe-2TsOH) with di-p-nitrophenyl adipate

  9. The implications of (2S,4S)-hydroxyproline 4-O-glycosylation for prolyl amide isomerization.

    Science.gov (United States)

    Owens, Neil W; Lee, Adrian; Marat, Kirk; Schweizer, Frank

    2009-10-12

    The conformations of peptides and proteins are often influenced by glycans O-linked to serine (Ser) or threonine (Thr). (2S,4R)-4-Hydroxyproline (Hyp), together with L-proline (Pro), are interesting targets for O-glycosylation because they have a unique influence on peptide and protein conformation. In previous work we found that glycosylation of Hyp does not affect the N-terminal amide trans/cis ratios (K(trans/cis)) or the rates of amide isomerization in model amides. The stereoisomer of Hyp--(2S,4S)-4-hydroxyproline (hyp)--is rarely found in nature, and has a different influence both on the conformation of the pyrrolidine ring and on K(trans/cis). Glycans attached to hyp would be expected to be projected from the opposite face of the prolyl side chain relative to Hyp; the impact this would have on K(trans/cis) was unknown. Measurements of (3)J coupling constants indicate that the glycan has little impact on the C(gamma)-endo conformation produced by hyp. As a result, it was found that the D-galactose residue extending from a C(gamma)-endo pucker affects both K(trans/cis) and the rate of isomerization, which is not found to occur when it is projected from a C(gamma)-exo pucker; this reflects the different environments delineated by the proline side chain. The enthalpic contributions to the stabilization of the trans amide isomer may be due to disruption of intramolecular interactions present in hyp; the change in enthalpy is balanced by a decrease in entropy incurred upon glycosylation. Because the different stereoisomers--Hyp and hyp--project the O-linked carbohydrates in opposite spatial orientations, these glycosylated amino acids may be useful for understanding of how the projection of a glycan from the peptide or protein backbone exerts its influence.

  10. Effect of Amidated Low Methoxyl Pectin on the Mechanical Properties and Colour Attributes of Fish Mince

    Directory of Open Access Journals (Sweden)

    Rocio M. Uresti

    2003-01-01

    Full Text Available Pectins have been unsuccessfully applied to improve functionality of meat and fish products. Effect of amidated low methoxyl pectin (ALM pectin levels on functionality of Mexican flounder (Cyclopsetta chittendenii mince was studied. Changes in the firmness and work of extrusion of pastes, texture profile analysis (TPA of gels, and colour parameters were determined. ALM pectin at 1 % decreased firmness and work of extrusion of fish pastes but increased hardness, chewiness and cohesiveness of the gels (P<0.05. The addition of ALM pectin increased slightly the whiteness and yellowness of mince gels. Chrome parameter indicated that gels remained in the grayish achromatic region. Therefore ALM pectin at 1 % could be employed to modify the textural properties of fish mince.

  11. FMRF-amide-like immunoreactivity in brain and pituitary of the hagfish Eptatretus burgeri (Cyclostomata)

    DEFF Research Database (Denmark)

    Jirikowski, G; Erhart, G; Grimmelikhuijzen, C J

    1984-01-01

    Paraffin sections of brain and pituitary of the hagfish Eptatretus burgeri were immunostained with an antiserum to FMRF-amide. Immunoreactivity was visible in a large number of neurons in the posterior part of the ventromedial hypothalamus and in long neuronal processes extending cranially from...... the hypothalamus to the olfactory system and caudally to the medulla oblongata. FMRF-amide-like immunoreactivity was also found in cells of the adenohypophysis. These observations suggest that the hagfish possesses a brain FMRF-amide-like transmitter system and pituitary cells containing FMRF-amide-like material...

  12. Synthesis of new fatty acids amides from aminolysis of fatty acid methyl esters (FAMEs)

    International Nuclear Information System (INIS)

    Lopes, Carolina R.; Montes D'Oca, Caroline da Ros; Duarte, Rodrigo da C.; Kurz, Marcia H.S.; Primel, Ednei G.; Clementin, Rosilene M.; Villarreyes, Joaquin Ariel M.; Montes D'Oca, Marcelo G.

    2010-01-01

    Recent biochemical and pharmacological studies have led to the characterization of different fatty acid amides as a new family of biologically active lipids. Here, we describe the synthesis of new amides from C16:0, 18:0, 18:1 and 18:1, OH fatty acids (FFA) families with cyclic and acyclic amines and demonstrate for the first time that these compounds produce cytotoxic effects. Application of this method to the synthesis of fatty acid amides was performed using the esters aminolysis as a key step and various carboxylic amides were prepared in good yield from fatty acid methyl esters (FAMEs). (author)

  13. Coordination compounds of cobalt and cadmium with isobutyric acid amide

    International Nuclear Information System (INIS)

    Tsivadze, A.Yu.; Ivanova, I.S.; Solovkina, O.A.

    1983-01-01

    Coordination compounds of cobalt and cadmium with isobutyric acid amide (IBAA) of Co(NCS) 2 x(IBAA) 2 (H 2 O) 2 , CoCl 2 (IBAA) 4 , CoI 2 (IBAA) 8 (H 2 O) 2 , CdI 2 (IBAA) 2 composition have been synthesized and characterized. Their infrared absorption spectra (200-400 cm -1 ), electron reflection spectra (200-750 nm) were studied. It is shown that in all compounds there are IBAA molecUles coordinated through an oxygen atom. Thiocyanogroups are coordinated throUgh nitrogen atoms

  14. Antiproliferative activity of synthetic fatty acid amides from renewable resources.

    Science.gov (United States)

    dos Santos, Daiane S; Piovesan, Luciana A; D'Oca, Caroline R Montes; Hack, Carolina R Lopes; Treptow, Tamara G M; Rodrigues, Marieli O; Vendramini-Costa, Débora B; Ruiz, Ana Lucia T G; de Carvalho, João Ernesto; D'Oca, Marcelo G Montes

    2015-01-15

    In the work, the in vitro antiproliferative activity of a series of synthetic fatty acid amides were investigated in seven cancer cell lines. The study revealed that most of the compounds showed antiproliferative activity against tested tumor cell lines, mainly on human glioma cells (U251) and human ovarian cancer cells with a multiple drug-resistant phenotype (NCI-ADR/RES). In addition, the fatty methyl benzylamide derived from ricinoleic acid (with the fatty acid obtained from castor oil, a renewable resource) showed a high selectivity with potent growth inhibition and cell death for the glioma cell line-the most aggressive CNS cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Antifungal activity of natural and synthetic amides from Piper species

    Energy Technology Data Exchange (ETDEWEB)

    Marques, Joaquim V.; Oliveira, Alberto de; Kato, Massuo J., E-mail: majokato@iq.usp.b [Universidade de Sao Paulo (IQ/USP), SP (Brazil). Inst. de Quimica; Raggi, Ludmila; Young, Maria C. [Instituto de Botanica, Sao Paulo, SP (Brazil). Secao de Fisiologia e Bioquimica de Plantas

    2010-07-01

    The antifungal leaves extract from Piper scutifolium was submitted to bioactivity-guided chromatographic separation against Cladosporium cladosporioides and C. sphaerospermum yielding piperine, piperlonguminine and corcovadine as the active principles which displayed a detection limit of 1 {mu}g. Structure-activity relationships were investigated with the preparation of twelve analogs having differences in the number of unsaturations, aromatic ring substituents and in the amide moiety. Analogs having a single double-bond and no substituent in the aromatic ring displayed higher activity, while N,N,-diethyl analogs displayed higher dose-dependent activity. (author)

  16. A new phenolic amide glycoside from Cimicifuga dahurica.

    Science.gov (United States)

    Zhang, Fan; Han, Li-Feng; Pan, Gui-Xiang; Peng, Shuang; Andre, Ndagijimana

    2013-08-01

    A new phenolic amide glycoside, cimicifugamide A (1) along with four known compounds, trans-feruloyl tyramine 4-O-beta-D-glucopyranoside (2), (+)-isolariciresinol 3-O-beta-D-glucopyranoside (3), cimidahurine (4), and 24-epi-7, 8-didehydrocimigenol-3-O-beta-D-xylopyranoside (5) were isolated from the rhizomes of Cimicifuga dahurica. Compound 3 was identified as a lignan and has been obtained from Cimicifuga genus for the first time. The structure of compound 1 was elucidated by IR, UV, HR-MS and NMR spectroscopic methods.

  17. Quantitative structure-activity relationship study of amide mosquito repellents.

    Science.gov (United States)

    Wang, P; Xu, X; Liao, S; Song, J; Fan, G; Chen, S; Wang, Z

    2017-04-01

    A quantitative structure-activity relationship (QSAR) study on 43 amide repellents was carried out by the heuristic method in order to reveal the correlations between molecular parameters of these amides and their repellency against Aedes aegypti. Sketches and optimizations of molecular structures were achieved by the Gaussian software package. Generation and screening of molecular parameters were accomplished using CODESSA 2.7.10 software. The leave-one-out method was applied for the model validation. The results showed that a four-descriptor QSAR model with r 2 of 0.897 was obtained. The average r 2 values of the training set and test set of the QSAR model were 0.901 and 0.863, respectively, which suggested that the stability and predictability of the model were confirmed. Analysis of the implications of the descriptors that constitute the QSAR model indicated that all the descriptors were related to the charge distribution over the molecule and affect the dipole moment of the repellents.

  18. Poly(ester amide)s based on (L)-lactic acid oligomers and α-amino acids: influence of the α-amino acid side chain in the poly(ester amide)s properties.

    Science.gov (United States)

    Fonseca, Ana C; Coelho, Jorge F J; Valente, Joana F A; Correia, Tiago R; Correia, Ilídio J; Gil, Maria H; Simões, Pedro N

    2013-01-01

    Novel biodegradable and low cytotoxic poly(ester amide)s (PEAs) based on α-amino acids and (L)-lactic acid (L-LA) oligomers were successfully synthesized by interfacial polymerization. The chemical structure of the new polymers was confirmed by spectroscopic analyses. Further characterization suggests that the α-amino acid plays a critical role on the final properties of the PEA. L-phenylalanine provides PEAs with higher glass transition temperature, whereas glycine enhances the crystallinity. The hydrolytic degradation in PBS (pH = 7.4) at 37 °C also depends on the α-amino acid, being faster for glycine-based PEAs. The cytotoxic profiles using fibroblast human cells indicate that the PEAs did not elicit an acute cytotoxic effect. The strategy presented in this work opens the possibility of synthesizing biodegradable PEAs with low citotoxicity by an easy and fast method. It is worth to mention also that the properties of these materials can be fine-tuned only by changing the α-amino acid.

  19. Effervescent N-Acetylcysteine Tablets versus Oral Solution N-Acetylcysteine in Fasting Healthy Adults: An Open-Label, Randomized, Single-Dose, Crossover, Relative Bioavailability Study

    Directory of Open Access Journals (Sweden)

    Spencer C. Greene, MD, FACEP, FACMT

    2016-01-01

    Conclusions: Data from this study of a single dose of 11 g oral NAC demonstrated that effervescent NAC tablets and oral solution NAC met the regulatory criteria for bioequivalence in fasting healthy adult subjects. Effervescent NAC tablets appear to be a more palatable alternative for treatment of acetaminophen overdose. ClinicalTrials.gov identifier: NCT02723669.

  20. Functional aspects of cHH C-terminal amidation in crayfish species.

    Science.gov (United States)

    Mosco, Alessandro; Edomi, Paolo; Guarnaccia, Corrado; Lorenzon, Simonetta; Pongor, Sándor; Ferrero, Enrico A; Giulianini, Piero G

    2008-04-10

    The crustacean hyperglycemic hormone is the most abundant neuropeptide present in the eyestalk of Crustacea and its main role is to control the glucose level in the hemolymph. Our study was aimed at assessing the importance of C-terminal amidation for its biological activity. Two recombinant peptides were produced, Asl-rcHH-Gly with a free carboxyl terminus and Asl-rcHH-amide with an amidated C-terminus. Homologous bioassays performed on the astacid crayfish Astacus leptodactylus showed that the amidated peptide had a stronger hyperglycemic effect compared to the non-amidated peptide. To assess the relevance of amidation also in other decapods and how much the differences in the cHH amino acid sequence can affect the functionality of the peptides, we carried out heterologous bioassays on the cambarid Procambarus clarkii and palaemonid Palaemon elegans. The Asl-rcHH-amide elicited a good response in P. clarkii and in P. elegans. The injection of Asl-rcHH-Gly evoked a weak response in both species. These results prove the importance of C-terminal amidation for the biological activity of cHH in crayfish as well as the role of the peptide primary sequence for the species-specificity hormone-receptor recognition.

  1. Comparing Amide-Forming Reactions Using Green Chemistry Metrics in an Undergraduate Organic Laboratory

    Science.gov (United States)

    Fennie, Michael W.; Roth, Jessica M.

    2016-01-01

    In this laboratory experiment, upper-division undergraduate chemistry and biochemistry majors investigate amide-bond-forming reactions from a green chemistry perspective. Using hydrocinnamic acid and benzylamine as reactants, students perform three types of amide-forming reactions: an acid chloride derivative route; a coupling reagent promoted…

  2. Biomimetic L-aspartic acid-derived functional poly(ester amide)s for vascular tissue engineering.

    Science.gov (United States)

    Knight, Darryl K; Gillies, Elizabeth R; Mequanint, Kibret

    2014-08-01

    Functionalization of polymeric biomaterials permits the conjugation of cell signaling molecules capable of directing cell function. In this study, l-phenylalanine and l-aspartic acid were used to synthesize poly(ester amide)s (PEAs) with pendant carboxylic acid groups through an interfacial polycondensation approach. Human coronary artery smooth muscle cell (HCASMC) attachment, spreading and proliferation was observed on all PEA films. Vinculin expression at the cell periphery suggested that HCASMCs formed focal adhesions on the functional PEAs, while the absence of smooth muscle α-actin (SMαA) expression implied the cells adopted a proliferative phenotype. The PEAs were also electrospun to yield nanoscale three-dimensional (3-D) scaffolds with average fiber diameters ranging from 130 to 294nm. Immunoblotting studies suggested a potential increase in SMαA and calponin expression from HCASMCs cultured on 3-D fibrous scaffolds when compared to 2-D films. X-ray photoelectron spectroscopy and immunofluorescence demonstrated the conjugation of transforming growth factor-β1 to the surface of the functional PEA through the pendant carboxylic acid groups. Taken together, this study demonstrates that PEAs containing aspartic acid are viable biomaterials for further investigation in vascular tissue engineering. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  3. Synthesis of amide-functionalized cellulose esters by olefin cross-metathesis.

    Science.gov (United States)

    Meng, Xiangtao; Edgar, Kevin J

    2015-11-05

    Cellulose esters with amide functionalities were synthesized by cross-metathesis (CM) reaction of terminally olefinic esters with different acrylamides, catalyzed by Hoveyda-Grubbs 2nd generation catalyst. Chelation by amides of the catalyst ruthenium center caused low conversions using conventional solvents. The effects of both solvent and structure of acrylamide on reaction conversion were investigated. While the inherent tendency of acrylamides to chelate Ru is governed by the acrylamide N-substituents, employing acetic acid as a solvent significantly improved the conversion of certain acrylamides, from 50% to up to 99%. Homogeneous hydrogenation using p-toluenesulfonyl hydrazide successfully eliminated the α,β-unsaturation of the CM products to give stable amide-functionalized cellulose esters. The amide-functionalized product showed higher Tg than its starting terminally olefinic counterpart, which may have resulted from strong hydrogen bonding interactions of the amide functional groups. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Food emulsions with amidated pectin from celery (Apium graveolens var. rapaceum D.C. tubers

    Directory of Open Access Journals (Sweden)

    Iv. Petrova

    2017-09-01

    Full Text Available Abstract. Hydrocolloids, especially polysaccharides from traditional plant sources and their derivatives possessed significant emulsifying properties. Pectin was isolated from celery tubers by accelerated “green” method for extraction based on ultrasonic irradiation. Further chemical modification of celery pectin was performed with 4 mol/L NH The amidated celery pectin was obtained with the following characteristics: the degree of esterification (DE 31%, the degree of 3. amidation (DA 16%, degree of acetylation (DAc 2% and anhydrouronic acid content (AUAC 68%. This modified pectin was incorporated in preparation of model 30, 40 and 50% oil-in-water emulsions. The effect of amidation of celery pectin on the stability of emulsions was investigated. The results showed that amidation increased the emulsifying properties of pectic polysaccharides. It affected also the rheological characteristics of model emulsion. The current study demonstrated preparation of emulsion with low-caloric amidated pectin as proper alternative to the traditional emulsifiers.

  5. Nickel-catalysed retro-hydroamidocarbonylation of aliphatic amides to olefins

    Science.gov (United States)

    Hu, Jiefeng; Wang, Minyan; Pu, Xinghui; Shi, Zhuangzhi

    2017-05-01

    Amide and olefins are important synthetic intermediates with complementary reactivity which play a key role in the construction of natural products, pharmaceuticals and manmade materials. Converting the normally highly stable aliphatic amides into olefins directly is a challenging task. Here we show that a Ni/NHC-catalytic system has been established for decarbonylative elimination of aliphatic amides to generate various olefins via C-N and C-C bond cleavage. This study not only overcomes the acyl C-N bond activation in aliphatic amides, but also encompasses distinct chemical advances on a new type of elimination reaction called retro-hydroamidocarbonylation. This transformation shows good functional group compatibility and can serve as a powerful synthetic tool for late-stage olefination of amide groups in complex compounds.

  6. α-Halo Amides as Competent Latent Enolates: Direct Catalytic Asymmetric Mannich-Type Reaction.

    Science.gov (United States)

    Sun, Bo; Balaji, Pandur Venkatesan; Kumagai, Naoya; Shibasaki, Masakatsu

    2017-06-21

    α-Halogenated carbonyl compounds are susceptible to dehalogenation and thus largely neglected as enolate precursors in catalytic enantioselective C-C bond-forming reactions. By merging the increased stability of the α-C-halogen bond of amides and the direct enolization methodology of the designed amide, we explored a direct catalytic asymmetric Mannich-type reaction of α-halo 7-azaindoline amides with N-carbamoyl imines. All α-halo substituents, α-F, -Cl, -Br, -I amides, were tolerated to provide the Mannich-adducts in a highly stereoselective manner without undesirable dehalogenation. The diastereoselectivity switched intriguingly depending on the substitution pattern of the aromatic imines, which is ascribed to stereochemical differentiation based on the open transition-state model. Functional group interconversion of the 7-azaindoline amide moiety of the Mannich-adducts and further elaboration into a diamide without dehalogenation highlight the synthetic utility of the present protocol for accessing enantioenriched halogenated chemical entities.

  7. Anti-Neoplastic Cytotoxicity of Gemcitabine-(C4-amide)-[anti-HER2/neu] in Combination with Griseofulvin against Chemotherapeutic-Resistant Mammary Adenocarcinoma (SKBr-3)

    Science.gov (United States)

    Coyne, CP; Jones, Toni; Bear, Ryan

    2015-01-01

    Introduction Gemcitabine is a pyrimidine nucleoside analog that becomes triphosphorylated and in this form it competitively inhibits cytidine incorporation into DNA strands. Diphosphorylated gemcitabine irreversibly inhibits ribonucleotide reductase thereby preventing deoxyribonucleotide synthesis. Functioning as a potent chemotherapeutic, gemcitabine decreases neoplastic cell proliferation and induces apoptosis which accounts for its effectiveness in the clinical treatment of several leukemia and carcinoma cell types. A brief plasma half-life due to rapid deamination, chemotherapeuticresistance and sequelae restricts gemcitabine utility in clinical oncology. Selective “targeted” gemcitabine delivery represents a molecular strategy for prolonging its plasma half-life and minimizing innocent tissue/organ exposure. Methods A previously described organic chemistry scheme was applied to synthesize a UV-photoactivated gemcitabine intermediate for production of gemcitabine-(C4-amide)-[anti-HER2/neu]. Immunodetection analysis (Western-blot) was applied to detect the presence of any degradative fragmentation or polymerization. Detection of retained binding-avidity for gemcitabine-(C4-amide)-[anti-HER2/neu] was determined by cell-ELISA using populations of chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3) that highly over-express the HER2/neu trophic membrane receptor. Anti-neoplastic cytotoxicity of gemcitabine-(C4-amide)-[anti-HER2/neu] and the tubulin/microtubule inhibitor, griseofulvin was established against chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3). Related investigations evaluated the potential for gemcitabine-(C4-amide)-[anti-HER2/neu] in dual combination with griseofulvin to evoke increased levels of anti-neoplastic cytotoxicity compared to gemcitabine-(C4-amide)-[anti-HER2/neu]. Results Covalent gemcitabine-(C4-amide)-[anti-HER2/neu] immunochemotherapeutic and griseofulvin exerted anti-neoplastic cytotoxicity against chemotherapeutic

  8. Characterization of FdmV as an Amide Synthetase for Fredericamycin A Biosynthesis in Streptomyces griseus ATCC 43944*

    OpenAIRE

    Chen, Yihua; Wendt-Pienkowski, Evelyn; Ju, Jianhua; Lin, Shuangjun; Rajski, Scott R.; Shen, Ben

    2010-01-01

    Fredericamycin (FDM) A is a pentadecaketide natural product that features an amide linkage. Analysis of the fdm cluster from Streptomyces griseus ATCC 43944, however, failed to reveal genes encoding the types of amide synthetases commonly seen in natural product biosynthesis. Here, we report in vivo and in vitro characterizations of FdmV, an asparagine synthetase (AS) B-like protein, as an amide synthetase that catalyzes the amide bond formation in FDM A biosynthesis. This is supported by the...

  9. Interception of amide ylides with sulfonamides: synthesis of (E)-N-sulfonyl amidines catalyzed by Zn(OTf)2.

    Science.gov (United States)

    Chen, Jijun; Long, Wenhao; Fang, Shangwen; Yang, Yonggang; Wan, Xiaobing

    2017-12-12

    Through the interception of amide ylides with sulfonamides, we herein report the first general example of an intermolecular condensation reaction between sulfonamides and amides. Beyond formamides, this approach was successfully applied to a variety of lactams and linear amides, giving rise to a broad array of (E)-N-sulfonyl amidines.

  10. Coordination compounds of cobalt and cadmium with isobutyric acid amide

    Energy Technology Data Exchange (ETDEWEB)

    Tsivadze, A.Yu.; Ivanova, I.S.; Solovkina, O.A. (AN SSSR, Moscow. Inst. Obshchej i Neorganicheskoj Khimii)

    1983-06-01

    Coordination compounds of cobalt and cadmium with isobutyric acid amide (IBAA) of Co(NCS)/sub 2/x(IBAA)/sub 2/(H/sub 2/O)/sub 2/, CoCl/sub 2/(IBAA)/sub 4/, CoI/sub 2/(IBAA)/sub 8/(H/sub 2/O)/sub 2/, CdI/sub 2/(IBAA)/sub 2/ composition have been synthesized and characterized. Their infrared absorption spectra (200-400 cm/sup -1/), electron reflection spectra (200-750 nm) were studied. It is shown that in all compounds there are IBAA molecUles coordinated through an oxygen atom. Thiocyanogroups are coordinated through nitrogen atoms.

  11. Synthesis and antifungal evaluation of PCA amide analogues.

    Science.gov (United States)

    Qin, Chuan; Yu, Di-Ya; Zhou, Xu-Dong; Zhang, Min; Wu, Qing-Lai; Li, Jun-Kai

    2018-04-18

    To improve the physical and chemical properties of phenazine-1-carboxylic acid (PCA) and find higher antifungal compounds, a series of PCA amide analogues were designed and synthesized and their structures were confirmed by 1 H NMR, HRMS, and X-ray. Most compounds showed some antifungal activities in vitro. Particularly, compound 3d exhibited inhibition effect against Pyriculariaoryzac Cavgra with EC 50 value of 28.7 μM and compound 3q exhibited effect against Rhizoctonia solani with EC 50 value of 24.5 μM, more potently active than that of the positive control PCA with its EC 50 values of 37.3 μM (Pyriculariaoryzac Cavgra) and 33.2 μM (Rhizoctonia solani), respectively.

  12. Three new amides from streptomyces sp. H7372

    Energy Technology Data Exchange (ETDEWEB)

    Cheenpracha, Sarot; Borris, Robert P.; Tran, Tammy T.; Chang, Leng Chee, E-mail: lengchee@hawaii.ed [University of Hawaii Hilo, HI (United States). College of Pharmacy. Dept. of Pharmaceutical Sciences; Jee, Jap Meng; Seow, Heng Fong; Cheah, Hwen-Yee [Universiti Putra Malaysia, Selangor (Malaysia). Faculty of Medicine and Health Sciences. Department of Pathology. bImmunology Unit; Hoc, Coy Choke [University Malaysia Sabah (Malaysia). School of Science and Technology. Biotechnology Program

    2011-07-01

    Three new amides, methyl phenatate A (1), actiphenamide (2) and actiphenol 1-beta-D-glucopyranoside (3), along with thirteen known compounds, were isolated from the organic extract of a fermentation culture of Streptomyces sp. H7372. The structures were elucidated by spectroscopic methods including 1D- and 2D-NMR techniques, and MS analyses. Cycloheximide (6) and cyclo({Delta}Ala-L-Val) (8) gave a clear zone of inhibition of Ras-Raf-1 interaction in the yeast two hybrid assay which showed high potency with 10 and 25 mm clear ZOIs on SD His{sup -} and inactive on SD His{sup +} at 2.5 mug per disk, respectively. (author)

  13. Restricted amide rotation with steric hindrance induced multiple conformations

    Science.gov (United States)

    Krishnan, V. V.; Vazquez, Salvador; Maitra, Kalyani; Maitra, Santanu

    2017-12-01

    The Csbnd N bond character is dependent directly upon the resonance-contributor structure population driven by the delocalized nitrogen lone-pair of electrons. In the case of N, N-dibenzyl-ortho-toluamide (o-DBET), the molecule adopts subpopulations of conformers with distinct NMR spectral features, particularly at low temperatures. This conformational adaptation is unique to o-DBET, while the corresponding meta- and para- forms do not show such behavior. Variable-temperature (VT) NMR, two-dimensional exchange spectroscopy (EXSY), and qualitative molecular modeling studies are used to demonstrate how multiple competing interactions such as restricted amide rotation and steric hindrance effects can lead to versatile molecular adaptations in the solution state.

  14. Interacting Blends of Novel Unsaturated Polyester Amide Resin with Styrene

    Directory of Open Access Journals (Sweden)

    Hasmukh S. Patel

    2004-01-01

    Full Text Available Novel unsaturated poly (ester-amide resins (UPEAs were prepared by the reaction between an epoxy resin, namely diglycidyl ether of bisphenol–A (DGEBA and unsaturated aliphatic bisamic acids using a base catalyst. These UPEAs were then blended with a vinyl monomer namely, Styrene (STY. to produce a homogeneous resin syrup. The curing of these UPEAs-STY. resin blends was carried out by using benzoyl peroxide (BPO as a catalyst and was monitored by using a differential scanning calorimeter (DSC. The glass fibre reinforced composites (i.e. laminates of these UPEA-STY. resin blends were fabricated using the DSC data. The chemical, mechanical and electrical properties of the glass fibre composites have also been evaluated. The unreinforced cured samples of the UPEA-STY. resin blends were also analyzed by thermogravimetry (TGA.

  15. Proposed Chevron Tengiz venture stalls amid Soviet political squabble

    International Nuclear Information System (INIS)

    Anon.

    1991-01-01

    This paper reports on the status of foreign investment in Soviet oil and gas joint ventures which has reached a critical juncture. Just as the U.S. is considering granting most favored nation trade status to the U.S.S.R., the joint venture petroleum deal seen as the litmus test for such deals-Chevron Corp.'s proposed addition of supergiant Tengiz oil field to its Caspian Sea joint venture-has stalled amid controversy. Unconfirmed reports from Soviet officials and other foreign joint venture participants in the U.S.S.R. have Chevron pulling out of the long negotiated, multibillion dollar project after the Soviets rejected the company's terms. Chevron, however, insists the project is still alive

  16. Conformational analysis of amide extractants by NMR in organic phase

    International Nuclear Information System (INIS)

    Berthon, C.

    1993-08-01

    This study deals with nuclear fuel reprocessing. We have essentially used NMR spectroscopy. We want to understand which kind of conformational parameters control selectivity and efficiency of amide extractant. The symmetric monoamides used are DOBA (C 3 H 7 CON (CH 2 CH(C 2 H 5 ) C 4 H 9 ) 2 ), DOiBA ((CH 3 ) 2 CCHON (CH 2 CH(C 2 H 5 )C 4 H 9 ) 2 ) and DOTA ((CH 3 ) 3 CCH 2 CON(CH 2 CH(C 2 H 5 )C 4 H 9 ) 2 ). Each gives two quasi equivalent conformers (cis and trans) in organic phases. The selected malonamide DMDBTDMA ((C 4 H 9 (CH 3 )NCO) 2 CHC 14 H 29 ) has four conformers because of its twice disymmetric amide functions. Weak interactions between monoamides which yield to dimer formation. The malonamide also gives dimers but forms aggregates too. Nitric acid extraction is due to the competitive formation of six species L, L 2 , L 2 (HNO 3 ), L(HNO 3 ), L(HNO 3 ) 2 , L(HNO 3 ) 3 (L: monoamide). Complexation between lanthanides (III) and monoamides yields to the stoichiometries L 3 Ln(NO 3 ) 3 and L 2 Ln(NO 3 ) 3 . Their ratio depend of steric hindrance on the carbonyl and the metal ionic radius. The same thing is observed of Pu 4+ and Th 4+ extraction in non acidic media. L 2 An(NO 3 ) 4 is the main stoichiometric except for the Th 4+ - DOBA system where the species (DOBA) 3 Th(NO 3 ) 4 appear. Exchange rates between the ligand and the complex are pointed out. The monoamide conformations obtained with lanthanide and plutonium nitrate can explain the difference in extracting power of this molecule between An 4+ and Ln 3+ . (author). 162 refs., 87 figs., 44 tabs., 7 annexes

  17. Ground-State Distortion in N-Acyl-tert-butyl-carbamates (Boc) and N-Acyl-tosylamides (Ts): Twisted Amides of Relevance to Amide N-C Cross-Coupling.

    Science.gov (United States)

    Szostak, Roman; Shi, Shicheng; Meng, Guangrong; Lalancette, Roger; Szostak, Michal

    2016-09-02

    Amide N-C(O) bonds are generally unreactive in cross-coupling reactions employing low-valent transition metals due to nN → π*C═O resonance. Herein we demonstrate that N-acyl-tert-butyl-carbamates (Boc) and N-acyl-tosylamides (Ts), two classes of acyclic amides that have recently enabled the development of elusive amide bond N-C cross-coupling reactions with organometallic reagents, are intrinsically twisted around the N-C(O) axis. The data have important implications for the design of new amide cross-coupling reactions with the N-C(O) amide bond cleavage as a key step.

  18. Amide Proton Transfer (APT) MR imaging and Magnetization Transfer (MT) MR imaging of pediatric brain development

    International Nuclear Information System (INIS)

    Zhang, Hong; Kang, Huiying; Peng, Yun; Zhao, Xuna; Jiang, Shanshan; Zhang, Yi; Zhou, Jinyuan

    2016-01-01

    To quantify the brain maturation process during childhood using combined amide proton transfer (APT) and conventional magnetization transfer (MT) imaging at 3 Tesla. Eighty-two neurodevelopmentally normal children (44 males and 38 females; age range, 2-190 months) were imaged using an APT/MT imaging protocol with multiple saturation frequency offsets. The APT-weighted (APTW) and MT ratio (MTR) signals were quantitatively analyzed in multiple brain areas. Age-related changes in MTR and APTW were evaluated with a non-linear regression analysis. The APTW signals followed a decreasing exponential curve with age in all brain regions measured (R 2 = 0.7-0.8 for the corpus callosum, frontal and occipital white matter, and centrum semiovale). The most significant changes appeared within the first year. At maturation, larger decreases in APTW and lower APTW values were found in the white matter. On the contrary, the MTR signals followed an increasing exponential curve with age in the same brain regions measured, with the most significant changes appearing within the initial 2 years. There was an inverse correlation between the MTR and APTW signal intensities during brain maturation. Together with MT imaging, protein-based APT imaging can provide additional information in assessing brain myelination in the paediatric population. (orig.)

  19. Amide Proton Transfer (APT) MR imaging and Magnetization Transfer (MT) MR imaging of pediatric brain development

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Hong; Kang, Huiying; Peng, Yun [Beijing Children' s Hospital, Capital Medical University, Imaging Center, Department of Radiology, Beijing (China); Zhao, Xuna [Philips Healthcare, Beijing (China); Jiang, Shanshan; Zhang, Yi; Zhou, Jinyuan [Johns Hopkins University, Division of MR Research, Department of Radiology, Baltimore, MD (United States)

    2016-10-15

    To quantify the brain maturation process during childhood using combined amide proton transfer (APT) and conventional magnetization transfer (MT) imaging at 3 Tesla. Eighty-two neurodevelopmentally normal children (44 males and 38 females; age range, 2-190 months) were imaged using an APT/MT imaging protocol with multiple saturation frequency offsets. The APT-weighted (APTW) and MT ratio (MTR) signals were quantitatively analyzed in multiple brain areas. Age-related changes in MTR and APTW were evaluated with a non-linear regression analysis. The APTW signals followed a decreasing exponential curve with age in all brain regions measured (R{sup 2} = 0.7-0.8 for the corpus callosum, frontal and occipital white matter, and centrum semiovale). The most significant changes appeared within the first year. At maturation, larger decreases in APTW and lower APTW values were found in the white matter. On the contrary, the MTR signals followed an increasing exponential curve with age in the same brain regions measured, with the most significant changes appearing within the initial 2 years. There was an inverse correlation between the MTR and APTW signal intensities during brain maturation. Together with MT imaging, protein-based APT imaging can provide additional information in assessing brain myelination in the paediatric population. (orig.)

  20. Hydrogen bond stabilities in membrane-reconstituted alamethicin from amide-resolved hydrogen-exchange measurements.

    Science.gov (United States)

    Dempsey, C E; Handcock, L J

    1996-01-01

    Amide-resolved hydrogen-deuterium exchange-rate constants were measured for backbone amides of alamethicin reconstituted in dioleoylphosphatidylcholine vesicles by an exchange-trapping method combined with high-resolution nuclear magnetic resonance spectroscopy. In vesicles containing alamethicin at molar ratios between 1:20 and 1:100 relative to lipid, the exchange-rate constants increased with increasing volume of the D20 buffer in which the vesicles were suspended, indicating that exchange under these conditions is dominated by partitioning of the peptide into the aqueous phase. This was supported by observation of a linear relationship between the exchange-rate constants for amides in membrane-reconstituted alamethicin and those for amides in alamethicin dissolved directly into D2O buffer. Significant protection of amides from exchange with D2O buffer in membrane-reconstituted alamethicin is interpreted in terms of stabilization by helical hydrogen bonding. Under conditions in which amide exchange occurred by partitioning of the peptide into solution, only lower limits for hydrogen-bond stabilities in the membrane were determined; all the potentially hydrogen-bonded amides of alamethicin are at least 1000-fold exchange protected in the membrane-bound state. When partitioning of alamethicin into the aqueous phase was suppressed by hydration of reconstituted vesicles in a limiting volume of water [D2O:dioleoylphosphatidylcholine:alamethicin; 220:1:0.05; (M:M:M)], the exchange-protection factors exhibited helical periodicity with highly exchange-protected, and less well-protected, amides on the nonpolar and polar helix faces, respectively. The exchange data indicate that, under the conditions studied, alamethicin adopts a stable helical structure in DOPC bilayers in which all the potentially hydrogen-bonded amides are stabilized by helical hydrogen bonds. The protection factors define the orientation of the peptide helix with respect to an aqueous phase, which is

  1. Probing the production of amidated peptides following genetic and dietary copper manipulations.

    Directory of Open Access Journals (Sweden)

    Ping Yin

    Full Text Available Amidated neuropeptides play essential roles throughout the nervous and endocrine systems. Mice lacking peptidylglycine α-amidating monooxygenase (PAM, the only enzyme capable of producing amidated peptides, are not viable. In the amidation reaction, the reactant (glycine-extended peptide is converted into a reaction intermediate (hydroxyglycine-extended peptide by the copper-dependent peptidylglycine-α-hydroxylating monooxygenase (PHM domain of PAM. The hydroxyglycine-extended peptide is then converted into amidated product by the peptidyl-α-hydroxyglycine α-amidating lyase (PAL domain of PAM. PHM and PAL are stitched together in vertebrates, but separated in some invertebrates such as Drosophila and Hydra. In addition to its luminal catalytic domains, PAM includes a cytosolic domain that can enter the nucleus following release from the membrane by γ-secretase. In this work, several glycine- and hydroxyglycine-extended peptides as well as amidated peptides were qualitatively and quantitatively assessed from pituitaries of wild-type mice and mice with a single copy of the Pam gene (PAM(+/- via liquid chromatography-mass spectrometry-based methods. We provide the first evidence for the presence of a peptidyl-α-hydroxyglycine in vivo, indicating that the reaction intermediate becomes free and is not handed directly from PHM to PAL in vertebrates. Wild-type mice fed a copper deficient diet and PAM(+/- mice exhibit similar behavioral deficits. While glycine-extended reaction intermediates accumulated in the PAM(+/- mice and reflected dietary copper availability, amidated products were far more prevalent under the conditions examined, suggesting that the behavioral deficits observed do not simply reflect a lack of amidated peptides.

  2. Hydrogen bond stabilities in membrane-reconstituted alamethicin from amide-resolved hydrogen-exchange measurements.

    Science.gov (United States)

    Dempsey, C E; Handcock, L J

    1996-04-01

    Amide-resolved hydrogen-deuterium exchange-rate constants were measured for backbone amides of alamethicin reconstituted in dioleoylphosphatidylcholine vesicles by an exchange-trapping method combined with high-resolution nuclear magnetic resonance spectroscopy. In vesicles containing alamethicin at molar ratios between 1:20 and 1:100 relative to lipid, the exchange-rate constants increased with increasing volume of the D20 buffer in which the vesicles were suspended, indicating that exchange under these conditions is dominated by partitioning of the peptide into the aqueous phase. This was supported by observation of a linear relationship between the exchange-rate constants for amides in membrane-reconstituted alamethicin and those for amides in alamethicin dissolved directly into D2O buffer. Significant protection of amides from exchange with D2O buffer in membrane-reconstituted alamethicin is interpreted in terms of stabilization by helical hydrogen bonding. Under conditions in which amide exchange occurred by partitioning of the peptide into solution, only lower limits for hydrogen-bond stabilities in the membrane were determined; all the potentially hydrogen-bonded amides of alamethicin are at least 1000-fold exchange protected in the membrane-bound state. When partitioning of alamethicin into the aqueous phase was suppressed by hydration of reconstituted vesicles in a limiting volume of water [D2O:dioleoylphosphatidylcholine:alamethicin; 220:1:0.05; (M:M:M)], the exchange-protection factors exhibited helical periodicity with highly exchange-protected, and less well-protected, amides on the nonpolar and polar helix faces, respectively. The exchange data indicate that, under the conditions studied, alamethicin adopts a stable helical structure in DOPC bilayers in which all the potentially hydrogen-bonded amides are stabilized by helical hydrogen bonds. The protection factors define the orientation of the peptide helix with respect to an aqueous phase, which is

  3. Acceleration of Amide Bond Rotation by Encapsulation in the Hydrophobic Interior of a Water-Soluble Supramolecular Assembly

    Energy Technology Data Exchange (ETDEWEB)

    Pluth, Michael D.; Bergman, Robert G.; Raymond, Kenneth N.

    2008-04-08

    The hydrophobic interior cavity of a self-assembled supramolecular assembly exploits the hydrophobic effect for the encapsulation of tertiary amides. Variable temperature 1H NMR experiments reveal that the free energy barrier for rotation around the C-N amide bond is lowered by up to 3.6 kcal/mol upon encapsulation. The hydrophobic cavity of the assembly is able to stabilize the less polar transition state of the amide rotation process. Carbon-13 labeling studies showed that the {sup 13}C NMR carbonyl resonance increases with temperature for the encapsulated amides which suggests that the assembly is able to favor a twisted for of the amide.

  4. Mesoporous Niobium Oxide Spheres as an Effective Catalyst for the Transamidation of Primary Amides with Amines

    KAUST Repository

    Ghosh, Subhash Chandra

    2014-02-06

    Mesoporous niobium oxide spheres (MNOS), conveniently prepared by a novel antisolvent precipitation approach, have been shown to be an effective catalyst for the transamidation of primary amides with amines. This novel transamidation can be efficiently carried out under solvent-free conditions and is applicable to a wide range of primary amides and amines to provide N-alkyl amides in good to excellent yields. The catalyst is highly stable and reusable. The application of this transamidation reaction has been demonstrated in the synthesis of antidepressant drug moclobemide and other druglike compounds. © 2014 Wiley-VCH Verlag GmbH&Co. KGaA, Weinheim.

  5. Synthesis of an Acyltrifluoroborate and its Fusion with Azides to Form Amides

    Science.gov (United States)

    Raushel, Jessica; Ellis, Noel M.

    2010-01-01

    A uniquely stable acyl potassium trifluoroborate, potassium (2-phenylacetyl) trifluoroborate, has been synthesized and isolated. In the presence of an activating Lewis acid, this reagent reacts with azides to form amides in good yields. PMID:20481486

  6. Tf2NH-Catalyzed Amide Synthesis from Vinyl Azides and Alcohols.

    Science.gov (United States)

    Zhang, Feng-Lian; Zhu, Xu; Chiba, Shunsuke

    2015-06-19

    Triflimide (Tf2NH) specifically catalyzed reactions of alcohols and vinyl azides, enabling efficient construction of amides with C-C bond formation through nucleophilic attack of vinyl azides onto the putative carbocation intermediates derived from alcohols are described.

  7. Copper-mediated amidation of alkenylzirconocenes with acyl azides: formation of enamides.

    Science.gov (United States)

    Liu, Hailan; Zhou, Yiqing; Yan, Xiaoyu; Chen, Chao; Liu, Qingbin; Xi, Chanjuan

    2013-10-18

    Copper-mediated amidation of alkenylzirconocenes generated in situ from alkynes and zirconocenes with acyl azides is accomplished under mild conditions. The reaction can be used to prepare various enamides.

  8. Enantioselective synthesis of almorexant via iridium-catalysed intramolecular allylic amidation

    NARCIS (Netherlands)

    Fananas Mastral, Martin; Teichert, Johannes F.; Fernandez-Salas, Jose Antonio; Heijnen, Dorus; Feringa, Ben L.

    2013-01-01

    An enantioselective synthesis of almorexant, a potent antagonist of human orexin receptors, is presented. The chiral tetrahydroisoquinoline core structure was prepared via iridium-catalysed asymmetric intramolecular allylic amidation. Further key catalytic steps of the synthesis include an oxidative

  9. First Novozym 435 lipase-catalyzed Morita-Baylis-Hillman reaction in the presence of amides.

    Science.gov (United States)

    Tian, Xuemei; Zhang, Suoqin; Zheng, Liangyu

    2016-03-01

    The first Novozym 435 lipase-catalyzed Morita-Baylis-Hillman (MBH) reaction with amides as co-catalyst was realized. Results showed that neither Novozym 435 nor amide can independently catalyze the reaction. This co-catalytic system that used a catalytic amount of Novozym 435 with a corresponding amount of amide was established and optimized. The MBH reaction strongly depended on the structure of aldehyde substrate, amide co-catalyst, and reaction additives. The optimized reaction yield (43.4%) was achieved in the Novozym 435-catalyzed MBH reaction of 2, 4-dinitrobenzaldehyde and cyclohexenone with isonicotinamide as co-catalyst and β-cyclodextrin as additive only in 2 days. Although enantioselectivity of Novozym 435 was not found, the results were still significant because an MBH reaction using lipase as biocatalyst was realized for the first time. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Synthesis, characterization and pharmacological evaluation of amide prodrugs of Flurbiprofen

    Energy Technology Data Exchange (ETDEWEB)

    Mishra, Ashutosh; Veerasamy, Ravichandran; Jain, Prateek Kumar; Dixit, Vinod Kumar; Agrawal, Ram Kishor [Dr. H. S. Gour Vishwavidyalaya, Sagar (India). Dept. of Pharmaceutical Sciences. Pharmaceutical Chemistry Research Lab.]. E-mail: dragrawal2001@yahoo.co.in

    2008-07-01

    Flurbiprofen (FB) suffers from the general side effects of NSAIDs, owing to presence of free carboxylic acid group. The study was aimed to retard the adverse effects of gastrointestinal origin. Ten prodrugs of FB were synthesized by amidation with ethyl esters of amino acids, namely, glycine, L-phenylalanine, L-tryptophan, L-valine, L-isoleucine, L-alanine, L-leucine, L-glutamic acid, L-aspartic acid and {beta} alanine. Purified synthesized prodrugs were characterized by m.p., TLC, solubility, partition coefficients, elemental analyses, UV, FTIR, NMR and MS. Synthesized prodrugs were subjected for bioavailability studies, analgesic, anti-inflammatory activities and ulcerogenic index. Marked reduction of ulcerogenic index and comparable analgesic, antiinflammatory activities were obtained in all cases as compared to FB. Among synthesized prodrugs AR-9, AR-10 and AR-2 showing excellent pharmacological response and encouraging hydrolysis rate both in (Simulated Intestinal Fluid) SIF and in 80% human plasma. Prodrugs with increased aliphatic side chain length or introduction of aromatic substituent resulted in enhanced partition coefficient but diminished dissolution and hydrolysis rate. Such prodrugs can be considered for sustained release purpose. (author)

  11. Effectors of Filamentous Plant Pathogens: Commonalities amid Diversity.

    Science.gov (United States)

    Franceschetti, Marina; Maqbool, Abbas; Jiménez-Dalmaroni, Maximiliano J; Pennington, Helen G; Kamoun, Sophien; Banfield, Mark J

    2017-06-01

    Fungi and oomycetes are filamentous microorganisms that include a diversity of highly developed pathogens of plants. These are sophisticated modulators of plant processes that secrete an arsenal of effector proteins to target multiple host cell compartments and enable parasitic infection. Genome sequencing revealed complex catalogues of effectors of filamentous pathogens, with some species harboring hundreds of effector genes. Although a large fraction of these effector genes encode secreted proteins with weak or no sequence similarity to known proteins, structural studies have revealed unexpected similarities amid the diversity. This article reviews progress in our understanding of effector structure and function in light of these new insights. We conclude that there is emerging evidence for multiple pathways of evolution of effectors of filamentous plant pathogens but that some families have probably expanded from a common ancestor by duplication and diversification. Conserved folds, such as the oomycete WY and the fungal MAX domains, are not predictive of the precise function of the effectors but serve as a chassis to support protein structural integrity while providing enough plasticity for the effectors to bind different host proteins and evolve unrelated activities inside host cells. Further effector evolution and diversification arise via short linear motifs, domain integration and duplications, and oligomerization. Copyright © 2017 American Society for Microbiology.

  12. Copper-catalyzed C(sp2)-H amidation with azides as amino sources.

    Science.gov (United States)

    Peng, Jiangling; Xie, Zeqiang; Chen, Ming; Wang, Jian; Zhu, Qiang

    2014-09-19

    A copper-catalyzed C-H amidation process, with azides as amino sources under oxidant-free conditions, has been developed. When N-heterocycles were employed as directing groups, sulfonylazide and benzoylazide could be used as amidating reagents to provide corresponding N-arylamides. When amidines or imine were used, tandem C-N/N-N bond formation occurred to afford indazole derivatives in one pot.

  13. A protocol for amide bond formation with electron deficient amines and sterically hindered substrates

    DEFF Research Database (Denmark)

    Due-Hansen, Maria E; Pandey, Sunil K; Christiansen, Elisabeth

    2016-01-01

    A protocol for amide coupling by in situ formation of acyl fluorides and reaction with amines at elevated temperature has been developed and found to be efficient for coupling of sterically hindered substrates and electron deficient amines where standard methods failed.......A protocol for amide coupling by in situ formation of acyl fluorides and reaction with amines at elevated temperature has been developed and found to be efficient for coupling of sterically hindered substrates and electron deficient amines where standard methods failed....

  14. Barbier Continuous Flow Preparation and Reactions of Carbamoyllithiums for Nucleophilic Amidation.

    Science.gov (United States)

    Ganiek, Maximilian A; Becker, Matthias R; Berionni, Guillaume; Zipse, Hendrik; Knochel, Paul

    2017-08-01

    An ambient temperature continuous flow method for nucleophilic amidation and thioamidation is described. Deprotonation of formamides by lithium diisopropylamine (LDA) affords carbamoyllithium intermediates that are quenched in situ with various electrophiles such as ketones, allyl bromides, Weinreb and morpholino amides. The nature of the reactive lithium intermediates and the thermodynamics of the metalation were further investigated by ab initio calculations and kinetic experiments. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Preparation and phytotoxicity of novel kaurane diterpene amides with potential use as herbicides.

    Science.gov (United States)

    Boaventura, Maria Amélia Diamantino; Pereira, Rondinelle Gomes; de Oliveira Freitas, Luiza B; Dos Reis, Leandro Alves; da Silva Vieira, Henriete

    2008-05-14

    Novel kaurane ditepene monoamides were synthesized in good yields directly from kaurenoic ( 1) and grandiflorenic ( 2) acids and unprotected symmetrical diamines, using a modified protocol for monoacylation. Amides from 1 and 2 and monoamines were also obtained and tested against seed germination and growth of radicle and shoot of Lactuca sativa (lettuce), at 10 (-3), 10 (-5), and 10 (-7) M. Amides from symmetrical diamines showed significant inhibitory activity at higher concentrations.

  16. Paracellular permeation-enhancing effect of AT1002 C-terminal amidation in nasal delivery

    Directory of Open Access Journals (Sweden)

    Song KH

    2015-03-01

    Full Text Available Keon-Hyoung Song,1 Sang-Bum Kim,2 Chang-Koo Shim,2 Suk-Jae Chung,2 Dae-Duk Kim,2 Sang-Ki Rhee,1 Guang J Choi,1 Chul-Hyun Kim,3 Kiyoung Kim4 1Department of Pharmaceutical Engineering, Soonchunhyang University, Asan, Republic of Korea; 2College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea; 3Department of Sports Medicine, 4Department of Medical Biotechnology, Soonchunhyang University, Asan, Republic of Korea Background: The identification of permeation enhancers has gained interest in the development of drug delivery systems. A six-mer peptide, H-FCIGRL-OH (AT1002, is a tight junction modulator with promising permeation-enhancing activity. AT1002 enhances the transport of molecular weight markers or agents with low bioavailability with no cytotoxicity. However, AT1002 is not stable in neutral pH or after incubation under physiological conditions, which is necessary to fully uncover its permeation-enhancing effect. Thus, we increased the stability or mitigated the instability of AT1002 by modifying its terminal amino acids and evaluated its subsequent biological activity.Methods: C-terminal-amidated (FCIGRL-NH2, Pep1 and N-terminal-acetylated (Ac-FCIGRL, Pep2 peptides were analyzed by liquid chromatography–mass spectrometry. We further assessed cytotoxicity on cell monolayers, as well as the permeation-enhancing activity following nasal administration of the paracellular marker mannitol.Results: Pep1 was nontoxic to cell monolayers and showed a relatively low decrease in peak area compared to AT1002. In addition, administration of mannitol with Pep1 resulted in significant increases in the area under the plasma concentration–time curve and peak plasma concentration at 3.63-fold and 2.68-fold, respectively, compared to mannitol alone. In contrast, no increase in mannitol concentration was shown with mannitol/AT1002 or mannitol/Pep2 compared to the control. Thus, Pep1 increased

  17. ZSM-5 Filled Polyether Block Amide Membranes for Separating EA from Aqueous Solution by Pervaporation

    Directory of Open Access Journals (Sweden)

    Jin Gu

    2013-01-01

    Full Text Available ZSM-5 filled polyether block amide membranes (PEBA, PEBA/ZSM-5, were prepared and used to recover aroma, ethyl acetate (EA, from aqueous solution by pervaporation (PV. The membranes demonstrated high EA permselectivity, and with the increase of ZSM-5 loading, the separation factor increased initially and then decreased, while the total flux demonstrated the similar variation until the ZSM-5 loading was 10 wt%, at which it reached the lowest value. After that, it began to increase again. On the other hand, the separation factor, and total flux of the PEBA/ZSM-5 membrane containing 10 wt% ZSM-5, PEBA/ZSM-5-10, increased with the increase of feed concentration and temperature. The best PV performance, separation factor and total flux of PEBA/ZSM-5-10 membrane were 185.5 and 199.5 gm−2h−1, respectively, with feed concentration of 5 wt% EA at 50°C.

  18. Transport and partitioning of CO2 fixed by root nodules of ureide and amide producing legumes

    International Nuclear Information System (INIS)

    Vance, C.P.; Boylan, K.L.M.; Maxwell, C.A.; Heichel, G.H.; Hardman, L.L.

    1985-01-01

    Nodulated and denodulated roots of adzuki bean (Vigna angularis), soybean (Glycine max), and alfalfa (Medicago sativa) were exposed to 14 CO 2 to investigate the contribution of nodule CO 2 fixation to assimilation and transport of fixed nitrogen. The distribution of radioactivity in xylem sap and partitioning of carbon fixed by nodules to the whole plant were measured. Radioactivity in the xylem sap of nodulated soybean and adzuki bean was located primarily (70 to 87%) in the acid fraction while the basic (amino acid) fraction contained 10 to 22%. In contrast radioactivity in the xylem sap of nodulated alfalfa was primarily in amino acids with about 20% in organic acids. Total ureide concentration was 8.1, 4.7, and 0.0 micromoles per milliliter xylem sap for soybean, adzuki bean, and alfalfa, respectively. While the major nitrogen transport products in soybeans and adzuki beans are ureides, this class of metabolites contained less than 20% of the the total radioactivity. When nodules of plants were removed, radioactivity in xylem sap decreased by 90% or more. Pulse-chase experiments indicated that CO 2 fixed by nodules was rapidly transported to shoots and incorporated into acid stable constituents. The data are consistent with a role for nodule CO 2 fixation providing carbon for the assimilation and transport of fixed nitrogen in amide-based legumes. In contrast, CO 2 fixation by nodules of ureide transporting legumes appears to contribute little to assimilation and transport of fixed nitrogen. 19 references, 2 figures, 5 tables

  19. Computational Amide I Spectroscopy for Refinement of Disordered Peptide Ensembles: Maximum Entropy and Related Approaches

    Science.gov (United States)

    Reppert, Michael; Tokmakoff, Andrei

    The structural characterization of intrinsically disordered peptides (IDPs) presents a challenging biophysical problem. Extreme heterogeneity and rapid conformational interconversion make traditional methods difficult to interpret. Due to its ultrafast (ps) shutter speed, Amide I vibrational spectroscopy has received considerable interest as a novel technique to probe IDP structure and dynamics. Historically, Amide I spectroscopy has been limited to delivering global secondary structural information. More recently, however, the method has been adapted to study structure at the local level through incorporation of isotope labels into the protein backbone at specific amide bonds. Thanks to the acute sensitivity of Amide I frequencies to local electrostatic interactions-particularly hydrogen bonds-spectroscopic data on isotope labeled residues directly reports on local peptide conformation. Quantitative information can be extracted using electrostatic frequency maps which translate molecular dynamics trajectories into Amide I spectra for comparison with experiment. Here we present our recent efforts in the development of a rigorous approach to incorporating Amide I spectroscopic restraints into refined molecular dynamics structural ensembles using maximum entropy and related approaches. By combining force field predictions with experimental spectroscopic data, we construct refined structural ensembles for a family of short, strongly disordered, elastin-like peptides in aqueous solution.

  20. Smart synthesis of high performance thermosets based on ortho-(amide-co-imide functional benzoxazines

    Directory of Open Access Journals (Sweden)

    Hatsuo eIshida

    2015-02-01

    Full Text Available High performance thermosets via amide-imide functional benzoxazine resins as precursors have been synthesized. The structures of synthesized monomers have been confirmed by 1H NMR and FT-IR. Among these two benzoxazine monomers, the ortho-amide-imide functional benzoxazine resin shows powerful features both in the synthesis of benzoxazine monomers and the properties of the corresponding thermosets. For the cross-linked poly(amide-co-imide based on ortho-amide-imide functional benzoxazine, a smart route is adopted to develop a more thermally stable cross-linked poly(benzoxazole-co-imide. Besides, the poly(benzoxazole-co-imide can also undergo a further thermal treatment to form polybenzoxazole. Furthermore, a main-chain type ortho-functional polybenzoxazine with amide-co-imide and benzoxazine groups as repeating units has also been prepared. Both the ortho-amide-imide functional benzoxazine and main-chain type polybenzoxazine resins show the possibility to form high performance thermosets with low cost and easy processability .

  1. Direct effects of exendin-(9,39) and GLP-1-(9,36)amide on insulin action, β-cell function, and glucose metabolism in nondiabetic subjects.

    Science.gov (United States)

    Sathananthan, Matheni; Farrugia, Luca P; Miles, John M; Piccinini, Francesca; Dalla Man, Chiara; Zinsmeister, Alan R; Cobelli, Claudio; Rizza, Robert A; Vella, Adrian

    2013-08-01

    Exendin-(9,39) is a competitive antagonist of glucagon-like peptide-1 (GLP-1) at its receptor. However, it is unclear if it has direct and unique effects of its own. We tested the hypothesis that exendin-(9,39) and GLP-1-(9,36)amide have direct effects on hormone secretion and β-cell function as well as glucose metabolism in healthy subjects. Glucose containing [3-(3)H]glucose was infused to mimic the systemic appearance of glucose after a meal. Saline, GLP-1-(9,36)amide, or exendin-(9,39) at 30 pmol/kg/min (Ex 30) or 300 pmol/kg/min (Ex 300) were infused in random order on separate days. Integrated glucose concentrations were slightly but significantly increased by exendin-(9,39) (365 ± 43 vs. 383 ± 35 vs. 492 ± 49 vs. 337 ± 50 mmol per 6 h, saline, Ex 30, Ex 300, and GLP-1-[9,36]amide, respectively; P = 0.05). Insulin secretion did not differ among groups. However, insulin action was lowered by exendin-(9,39) (25 ± 4 vs. 20 ± 4 vs. 18 ± 3 vs. 21 ± 4 10(-4) dL/kg[min per μU/mL]; P = 0.02), resulting in a lower disposition index (DI) during exendin-(9,39) infusion (1,118 ± 118 vs. 816 ± 83 vs. 725 ± 127 vs. 955 ± 166 10(-14) dL/kg/min(2) per pmol/L; P = 0.003). Endogenous glucose production and glucose disappearance did not differ significantly among groups. We conclude that exendin-(9,39), but not GLP-1-(9,36)amide, decreases insulin action and DI in healthy humans.

  2. Poly(amic acid)s and their poly(amide imide) counterparts containing azobenzene moieties: Characterization, imidization kinetics and photochromic properties

    Energy Technology Data Exchange (ETDEWEB)

    Konieczkowska, Jolanta [Centre of Polymer and Carbon Materials, Polish Academy of Sciences, 34 M. Curie-Sklodowska Str., 41-819 Zabrze (Poland); Institute of Chemistry, University of Silesia, 9 Szkolna Str., 40-006 Katowice (Poland); Janeczek, Henryk [Centre of Polymer and Carbon Materials, Polish Academy of Sciences, 34 M. Curie-Sklodowska Str., 41-819 Zabrze (Poland); Kozanecka-Szmigiel, Anna, E-mail: annak@if.pw.edu.pl [Faculty of Physics, Warsaw University of Technology, 75 Koszykowa Str., 00-662 Warszawa (Poland); Schab-Balcerzak, Ewa, E-mail: eschab-balcerzak@cmpw-pan.edu.pl [Centre of Polymer and Carbon Materials, Polish Academy of Sciences, 34 M. Curie-Sklodowska Str., 41-819 Zabrze (Poland)

    2016-09-01

    We report on a series of novel photochromic poly(amide imide)s and their poly(amic acid) precursors bearing azobenzene chromophores as the side groups. The chemical structures of the polymers were designed so that they exhibited an enhanced thermal stability combined with a large and stable birefringence photogenerated by light of the wavelengths belonging to a wide spectral range. The polymers possessed rigidly attached azochromophores in the content of either one or two per a repeating unit, which in the latter case differed in their structures. The imidization kinetics of the poly(amic acid)s was investigated by differential scanning calorimetry and the kinetic parameters were estimated using Ozawa and Kissinger methods. Measurements of the selected physical properties of the polymers, such as solubility, supramolecular structure, linear absorption, thermal stability, glass transition and photochromic response were performed and used for determination of the structure-property relations. The measurements of photochromic properties showed a very efficient generation of optical anisotropy upon blue and violet irradiation, for both the poly(amide imide)s containing two different chromophores in the repeating unit and for their precursors. For these poly(amide imide)s and for their precursors an exceptionally slow decrease in the photoinduced optical anisotropy in the dark was also observed. - Highlights: • Three azopoly(amide imide)s were obtained from azopoly(amic acid)s. • Chosen physicochemical properties and photochromic responses were measured. • Desired optical response was found for polymers with two azo-dyes in repeating unit. • Structure-property relations were shown.

  3. Catalytic Ester and Amide to Amine Interconversion: Nickel-Catalyzed Decarbonylative Amination of Esters and Amides by C−O and C−C Bond Activation

    KAUST Repository

    Yue, Huifeng

    2017-03-15

    An efficient nickel-catalyzed decarbonylative amination reaction of aryl and heteroaryl esters has been achieved for the first time. The new amination protocol allows the direct interconversion of esters and amides into the corresponding amines and represents a good alternative to classical rearrangements as well as cross coupling reactions.

  4. Detection and qualitative analysis of fatty acid amides in the urine of alcoholics using HPLC-QTOF-MS.

    Science.gov (United States)

    Dabur, Rajesh; Mittal, Ashwani

    2016-05-01

    Fatty acid amides (FAAs) in alcoholism lead to liver diseases. These amides have been reported in plasma and in other organs of the body, while their detection or presence in the urine is still unknown. Therefore, the focus of the current study was to detect and analyze FAAs qualitatively in urine samples of alcoholics. Furthermore, the effects of Tinospora cordifolia (hepatoprotective medicinal plant) intervention on FAA levels in moderate alcoholics were also analyzed. In the study, asymptomatic chronic alcoholics (n = 22) without chronic liver disease and nonalcoholic healthy volunteers (n = 24) with a mean age of 39 ± 2.0 years were selected. The first-pass urine and fasting blood samples were collected in the morning on day 0 and day 14 after T. cordifolia water extract (TCE) treatment and analyzed using automated biochemistry analyzer and HPLC-QTOF-MS. Results indicated the increased levels of serum triglycerides, cholesterol, and liver function enzymes in alcoholic subjects, which were significantly down-regulated by TCE intervention. Multivariate discrimination analysis of QTOF-MS data showed increased urinary levels of oleoamide (2.55-fold), palmitamide (5.6-fold), and erucamide (1.6-fold) in alcoholics as compared to control subjects. Levels of oleamide (1.8-fold), palmitamide (1.7-fold), and linoleamide (1.5-fold) were found to be increased in plasma. Treatment with TCE in alcoholics (3.0 g lyophilized water extract/day) significantly decreased the plasma and urinary levels of all FAAs except linoleamide. The HPLC-QTOF-MS approach for FAAs analysis in both urinary and plasma samples of alcoholics worked very well. Moreover, findings (i.e., increased levels of FAAs in urine and in plasma) further support other findings that these amides play a very important role in alcoholism. Further, like our previous findings, TCE proved its hepatoprotective effect against alcoholism not only by lowering the levels of these detected FAAs, but also by decreasing the

  5. Epigenetic regulation of fatty acid amide hydrolase in Alzheimer disease.

    Directory of Open Access Journals (Sweden)

    Claudio D'Addario

    Full Text Available OBJECTIVE: Alzheimer disease (AD is a progressive, degenerative and irreversible neurological disorder with few therapies available. In search for new potential targets, increasing evidence suggests a role for the endocannabinoid system (ECS in the regulation of neurodegenerative processes. METHODS: We have studied the gene expression status and the epigenetic regulation of ECS components in peripheral blood mononuclear cells (PBMCs of subjects with late-onset AD (LOAD and age-matched controls (CT. RESULTS: We found an increase in fatty acid amide hydrolase (faah gene expression in LOAD subjects (2.30 ± 0.48 when compared to CT (1.00 ± 0.14; *p<0.05 and no changes in the mRNA levels of any other gene of ECS elements. Consistently, we also observed in LOAD subjects an increase in FAAH protein levels (CT: 0.75 ± 0.04; LOAD: 1.11 ± 0.15; *p<0.05 and activity (pmol/min per mg protein CT: 103.80 ± 8.73; LOAD: 125.10 ± 4.00; *p<0.05, as well as a reduction in DNA methylation at faah gene promoter (CT: 55.90 ± 4.60%; LOAD: 41.20 ± 4.90%; *p<0.05. CONCLUSIONS: Present findings suggest the involvement of FAAH in the pathogenesis of AD, highlighting the importance of epigenetic mechanisms in enzyme regulation; they also point to FAAH as a new potential biomarker for AD in easily accessible peripheral cells.

  6. Pb(II)-promoted amide cleavage: mechanistic comparison to a Zn(II) analogue.

    Science.gov (United States)

    Elton, Eric S; Zhang, Tingting; Prabhakar, Rajeev; Arif, Atta M; Berreau, Lisa M

    2013-10-07

    Two new Pb(II) complexes of the amide-appended nitrogen/sulfur epppa (N-((2-ethylthio)ethyl)-N-((6-pivaloylamido-2-pyridyl)methyl)-N-((2-pyridyl)methyl)amine) chelate ligand, [(epppa)Pb(NO3)2] (4-NO3) and [(epppa)Pb(ClO4)2] (4-ClO4), were prepared and characterized. In the solid state, 4-NO3 exhibits κ(5)-epppa chelate ligand coordination as well as the coordination of two bidentate nitrate ions. In acetonitrile, 4-NO3 is a 1:1 electrolyte with a coordinated NO3(-), whereas 4-ClO4 is a 1:2 electrolyte. Treatment of 4-ClO4 with 1 equiv Me4NOH·5H2O in CH3CN:CH3OH (3:5) results in amide methanolysis in a reaction that is akin to that previously reported for the Zn(II) analogue [(epppa)Zn](ClO4)2 (3-ClO4). (1)H NMR kinetic studies of the amide methanolysis reactions of 4-ClO4 and 3-ClO4 as a function of temperature revealed free energies of activation of 21.3 and 24.5 kcal/mol, respectively. The amide methanolysis reactions of 4-ClO4 and 3-ClO4 differ in terms of the effect of the concentration of methanol (saturation kinetics for 4-ClO4; second-order behavior for 3-ClO4), the observation of a small solvent kinetic isotope effect (SKIE) only for the reaction of the Zn(II)-containing 3-ClO4, and the properties of an initial intermediate isolated from each reaction upon treatment with Me4NOH·5H2O. These experimental results, combined with computational studies of the amide methanolysis reaction pathways of 4-ClO4 and 3-ClO4, indicate that the Zn(II)-containing 3-ClO4 initially undergoes amide deprotonation upon treatment with Me4NOH·5H2O. Subsequent amide protonation from coordinated methanol yields a structure containing a coordinated neutral amide and methoxide anion from which amide cleavage can then proceed. The rate-determining step in this pathway is either amide protonation or protonation of the leaving group. The Pb(II)-containing 4-ClO4 instead directly forms a neutral amide-containing, epppa-ligated Pb(II)-OH/Pb(II)-OCH3 equilibrium mixture upon treatment

  7. 7-N-Acetylcysteine-pyrrole conjugate—A potent DNA reactive metabolite of pyrrolizidine alkaloids

    OpenAIRE

    Xiaobo He; Liang Ma; Qingsu Xia; Peter P. Fu

    2016-01-01

    Plants containing pyrrolizidine alkaloids (PAs) are widespread throughout the world and are the most common poisonous plants affecting livestock, wildlife, and humans. PAs require metabolic activation to form reactive dehydropyrrolizidine alkaloids (dehydro-PAs) that are capable of alkylating cellular DNA and proteins, form (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-DNA and DHP-protein adducts, and lead to cytotoxicity, genotoxicity, and tumorigenicity. In this study, we d...

  8. Antihypertensive Mechanisms of Chronic Captopril or N-Acetylcysteine Treatment in L-NAME Hypertensive Rats

    Czech Academy of Sciences Publication Activity Database

    Zicha, Josef; Dobešová, Zdenka; Kuneš, Jaroslav

    2006-01-01

    Roč. 29, č. 12 (2006), s. 1021-1027 ISSN 0916-9636 R&D Projects: GA MZd NR7786 Institutional research plan: CEZ:AV0Z50110509 Keywords : NO-dependent vasodilation * sympathetic vasoconstriction * endothelium-derived hyperpolarizing factor Subject RIV: ED - Physiology Impact factor: 3.177, year: 2006

  9. The effect of N-acetylcysteine and melatonin in adult spontaneously hypertensive rats with established hypertension

    Czech Academy of Sciences Publication Activity Database

    Pecháňová, Olga; Zicha, Josef; Paulis, Ĺudovít; Zenebe, W.; Dobešová, Zdenka; Kojšová, S.; Jendeková, L.; Sládková, M.; Dovinová, I.; Šimko, F.; Kuneš, Jaroslav

    2007-01-01

    Roč. 561, 1-3 (2007), s. 129-136 ISSN 0014-2999 R&D Projects: GA MZd(CZ) NR7786; GA ČR GA305/03/0769 Grant - others:VEGA(SK) 2/6148/26; VEGA(SK) 1/3429/06; VEGA(SK) 1/3442/26; APVT(SK) 51-027404; APVT(SK) 51-017902 Institutional research plan: CEZ:AV0Z5011922 Keywords : NO synthase * oxidative load * genetic hypertension Subject RIV: ED - Physiology Impact factor: 2.376, year: 2007

  10. Minocycline and N-acetylcysteine: A Synergistic Drug Combination to Treat Traumatic Brain Injury

    Science.gov (United States)

    2013-10-01

    TBI (“Multidrug treatment of traumatic brain injury”, PT073028) from the Fiscal Year 2007 CDMRP program for Psychological Health/Traumatic Brain...ncbi.nlm.nih.gov/pubmed/20166806). Inman, C.F., et al., 2005. Validation of computer-assisted, pixel-based analysis of multiple- colour immunofluorescence

  11. N-acetylcysteine improves arterial vascular reactivity in patients with chronic kidney disease

    DEFF Research Database (Denmark)

    Wittstock, Antje; Burkert, Magdalena; Zidek, Walter

    2009-01-01

    Patients with stage 5 chronic kidney disease show increased cardiovascular morbidity and mortality that are partly related to impaired arterial vascular reactivity. We investigated whether intravenous administration of the antioxidant acetylcysteine improves arterial vascular reactivity...

  12. Observing reducing effect of N-acetylcysteine in the metabolism of yeast

    Directory of Open Access Journals (Sweden)

    Sebastián Chapela

    2016-06-01

    Full Text Available The research focuses on the design of experimental teaching using readily available materials and simple methods to implement. It arises as an example for learning, using baker's yeast Saccharomyces cerevisiae, because it has many of the metabolic pathways existing in mammalian cells. In this paper it was developed an essay that allow students to observe macroscopically the capacity of N- Acetyl cysteine (NAC to stimulate the reducing power of yeast using indicator Methylene Blue (MB color change.

  13. N-acetylcysteine and hemodialysis treatment of a severe case of methyl ethyl ketone peroxide intoxication

    NARCIS (Netherlands)

    van Enckevort, C C G; Touw, D J; Vleming, L-J

    The plastic hardener methyl ethyl ketone peroxide (MEKP) is an unstable peroxide that releases free oxygen radicals. Ingestion of this compound induces widespread liver necrosis that is often fatal, extensive ulceration with subsequent scarring, and stenosis of the proximal digestive tract in

  14. {sup 99m} Tc-N-acetylcysteine: Biodistribution in rats with tumor

    Energy Technology Data Exchange (ETDEWEB)

    Faintuch, Bluma; Almeida, Maria A.T.M. de; Muramoto, Amiko; Carvalho, Olga G.; Araujo, Elaine B. [Instituto de Pesquisas Energeticas e Nucleares (IPEN), Sao Paulo, SP (Brazil)

    1997-12-01

    The amino acid N-Acetycysteine was labelled with Tc-99m by a simple and convenient technique with more than 98 % of radiochemical purity. The biodistribution and the uptake of the radiopharmaceutical was ascertained in healthy controls and in Walker 256 carcinosarcoma-bearing rats between 1 and 1440 minutes. Biodistribution results indicates rapid blood clearance and significant radioactivity in small principal organs and tissues, without marked differences between controls and tumor-bearing organisms. The highest uptake corresponded to the kidneys, but sufficient tropism for experimental mammary cancer tissue (Walker carcinosarcoma) was confirmed. (author). 5 refs., 1 figs.

  15. Interaction of amidated single-walled carbon nanotubes with protein by multiple spectroscopic methods

    Energy Technology Data Exchange (ETDEWEB)

    Li, Lili [China Pharmaceutical University, Nanjing 210009 (China); The Nursing College of Pingdingshan University, Pingdingshan 467000 (China); Lin, Rui [Yancheng Health Vocational and Technical College, Yancheng 224005 (China); He, Hua, E-mail: dochehua@163.com [China Pharmaceutical University, Nanjing 210009 (China); Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing 210009 (China); Sun, Meiling, E-mail: sml-nir@sohu.com [China Pharmaceutical University, Nanjing 210009 (China); Jiang, Li; Gao, Mengmeng [China Pharmaceutical University, Nanjing 210009 (China)

    2014-01-15

    The aim of this work was to investigate the detailed interaction between BSA and amidated single walled carbon nanotubes (e-SWNTs) in vitro. Ethylenediamine (EDA) was successfully linked on the surface of single-walled carbon nanotubes (SWNTs) via acylation to improve their dispersion and to introduce active groups. Bovine serum albumin (BSA) was selected as the template protein to inspect the interaction of e-SWNTs with protein. Decreases in fluorescence intensity of BSA induced by e-SWNTs demonstrated the occurrence of interaction between BSA and e-SWNTs. Quenching parameters and different absorption spectra for e-SWNTs–BSA show that the quenching effect of e-SWNTs was static quenching. Hydrophobic force had a leading contribution to the binding roles of BSA on e-SWNTs, which was confirmed by positive enthalpy change and entropy change. The interference of Na{sup +} with the quenching effect of e-SWNTs authenticated that electrostatic force existed in the interactive process simultaneously. The hydrophobicity of amino acid residues markedly increased with the addition of e-SWNTs viewed from UV spectra of BSA. The content of α-helix structure in BSA decreased by 6.8% due to the addition of e-SWNTs, indicating that e-SWNTs have an effect on the secondary conformation of BSA. -- Highlights: • The interaction between e-SWNTs and BSA was investigated by multiple spectroscopic methods. • Quenching mechanism was static quenching. • Changes in structure of BSA were inspected by synchronous fluorescence, UV–vis and CD spectrum.

  16. Influences of hyperbranched poly(amide-ester) on the properties of poly(butylene succinate)

    International Nuclear Information System (INIS)

    Run, Mingtao; Wang, Jian; Yao, Meng; Guo, Lijie; Wang, Hai-jun; Ba, Xinwu

    2013-01-01

    The polymer blends of hyperbranched poly(amide-ester) and poly(butylene succinate) (HBP/PBS) were prepared by melt-blending method. The molecular interaction within the blends, phase morphology, crystal morphology, mechanical, rheological and dynamic mechanical properties were investigated by using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), tensile machine, polarized optical microscopy, rotational rheometer and dynamic mechanical analyzer (DMA), respectively. The results suggest that PBS and HBP have a certain compatibility at amorphous state. A certain number of H-bonding was detected between PBS and HBP phases and it influences the material properties. HBP not only serves partially as a nucleating agent for the crystallization of PBS but also plays a role of plasticizer for the rheology of PBS. The glass transition temperatures of the blends slightly decrease with increasing HBP content. The proper amount of HBP (4–6%) has a reinforcement effect on the PBS matrix at glassy state. However, the blend with 10%HBP content has an improved impact strength mainly due to the plasticization effect or H-bonding effect of HBP on PBS matrix. The storage modulus is increased with increasing HBP contents, and the loss modulus is much smaller than the storage modulus in each blend at glassy state. At rubbery state the storage modulus of different samples is independent of HBP content. The complex viscosity of the melt decreases with increasing HBP content; however, the blend with 10%HBP is a special sample because of its abnormal larger complex viscosity at low shear frequencies. In addition, the melt’s elasticity behavior increases slightly with increasing HBP content. - Highlights: ► H-bonding was detected between PBS and HBP phases by FTIR. ► HBP serves partly as a nucleating agent for the crystallization of PBS. ► HBP plays a role of plasticizer for PBS. ► The blend with 10%HBP has abnormal larger complex viscosity

  17. Decreasing relative risk premium

    DEFF Research Database (Denmark)

    Hansen, Frank

    2007-01-01

    such that the corresponding relative risk premium is a decreasing function of present wealth, and we determine the set of associated utility functions. We find a new characterization of risk vulnerability and determine a large set of utility functions, closed under summation and composition, which are both risk vulnerable...... and have decreasing relative risk premium. We finally introduce the notion of partial risk neutral preferences on binary lotteries and show that partial risk neutrality is equivalent to preferences with decreasing relative risk premium...

  18. Cis/Trans Isomerization in Secondary Amides: Reaction Paths, Nitrogen Inversion, and Relevance to Peptidic Systems.

    Science.gov (United States)

    Thakkar, Balmukund S; Svendsen, John-Sigurd M; Engh, Richard A

    2017-09-14

    Cis/trans isomerization of 2°-amide bonds is a key step in a wide range of important processes. Here we present a theoretical assessment of cis/trans isomerization of 2°-amide bonds using B3LYP density functional methods, describing two reaction paths and corresponding geometry changes during isomerization of N-methylacetamide (NMA) and glycylglycine methyl ester (GGMe). The isomerization begins via a common path, as the extended π-bonding of the amide bond maintains approximate planarity of the O-C-N-H dihedral angle, with only gradually increasing pyramidalization of the nitrogen atom, until a bifurcation point is reached. Both subsequent paths comprise two phases, an "ω phase" (characterized by a major change in C-C-N-C dihedral) and a "θ phase" (characterized by major change in O-C-N-H dihedral), with two distinct transition states. The θ phase involves inversion of the pyramidal amide-nitrogen geometry. Both reaction paths converge at another bifurcation point near the opposite geometry. Studies on the larger GGMe show in addition that the multiple additional rotamers do not change the qualitative properties of the isomerization, but do affect the energies of the differing transition states. These detailed results provide significant new insights into cis/trans isomerization paths in 2°-amides, and serve as a basis for theoretical studies on larger peptidic systems.

  19. On the determinants of amide backbone exchange in proteins: a neutron crystallographic comparative study.

    Science.gov (United States)

    Bennett, Brad C; Gardberg, Anna S; Blair, Matthew D; Dealwis, Chris G

    2008-07-01

    The hydrogen/deuterium-exchange (HDX) method, coupled with neutron diffraction, is a powerful probe for investigating molecular dynamics. In the present report, general determinants of HDX are proposed based on 12 deposited neutron protein structures. The parameters that correlate best with HDX are the depth within the protein structure of the amide N atom and the secondary-structure type. Both the B factor of the amide N atom and the ratio B/B correlate moderately. However, solvent accessibility only correlates strongly for one molecule and hydrogen-bonding distance correlates for two molecules with respect to amide HDX. In addition to the relatively small number of neutron structures available, the limitations to this type of analysis, namely resolution, data completeness and the data-to-parameter ratio, are discussed briefly. A global analysis of HDX was performed to overcome some of these obstacles, damping the effects of outliers and the extreme variation of the data sets arising from resolution limitations. From this, amide depth and hydrogen-bonding distance to the amide (a measure of interaction strength) show strong global correlation with HDX. For some structures, the constituents of the hydrophobic protein core could be identified based on contiguous regions that are resistant to exchange and have significant depth. These may, in fact, constitute minimal folding domains.

  20. Alpha-amidated peptides derived from pro-opiomelanocortin in normal human pituitary

    DEFF Research Database (Denmark)

    Fenger, M; Johnsen, A H

    1988-01-01

    Normal human pituitaries were extracted in boiling water and acetic acid, and the alpha-amidated peptide products of pro-opiomelanocortin (POMC), alpha-melanocyte-stimulating hormone (alpha MSH), gamma-melanocyte-stimulating hormone (gamma 1MSH), and amidated hinge peptide (HP-N), as well...... as their glycine-extended precursors, were characterized by sequence-specific radioimmunoassays, gel-chromatography, h.p.l.c. and amino acid sequencing. alpha MSH and gamma 1MSH constituted 0.27-1.32% and 0.10-5.10%, respectively, of the POMC-derived products [calculated as the sum of adrenocorticotropic hormone...... (ACTH)-(1-39), ACTH-(1-14) and alpha MSH immunoreactivity]. alpha MSH and ACTH-(1-14) were only present in non- or mono-acetylated forms. Only large forms of gamma 1MSH and gamma 2MSH were present in partly glycosylated states. The hinge peptides were amidated to an extent two to three orders...

  1. Lipase-catalyzed synthesis of fatty acid amide (erucamide) using fatty acid and urea.

    Science.gov (United States)

    Awasthi, Neeraj Praphulla; Singh, R P

    2007-01-01

    Ammonolysis of fatty acids to the corresponding fatty acid amides is efficiently catalysed by Candida antartica lipase (Novozym 435). In the present paper lipase-catalysed synthesis of erucamide by ammonolysis of erucic acid and urea in organic solvent medium was studied and optimal conditions for fatty amides synthesis were established. In this process erucic acid gave 88.74 % pure erucamide after 48 hour and 250 rpm at 60 degrees C with 1:4 molar ratio of erucic acid and urea, the organic solvent media is 50 ml tert-butyl alcohol (2-methyl-2-propanol). This process for synthesis is economical as we used urea in place of ammonia or other amidation reactant at atmospheric pressure. The amount of catalyst used is 3 %.

  2. Alpha-amidated peptides derived from pro-opiomelanocortin in human pituitary tumours

    DEFF Research Database (Denmark)

    Fenger, M; Johnsen, A H

    1988-01-01

    Human pituitary tumours, obtained at surgery for Cushing's disease and Nelson's syndrome, were extracted and the content and molecular forms of pro-opiomelanocortin (POMC)-derived peptides determined by radioimmunoassay, gel chromatography, reversed-phase high-performance liquid chromatography...... (HPLC) and sequence analysis. In the tumours from patients with Cushing's disease the mean concentrations of amidated peptides relative to the total amount of POMC were as follows: alpha-MSH, 1.7%; amidated gamma-MSH (gamma 1-MSH), 8.5% and the peptide linking gamma-MSH and ACTH in the precursor (hinge....... In conclusion, all the molecular forms of the amidated peptides detected in tumours from patients with Cushing's disease and Nelson's syndrome were similar to the molecular forms found in the normal human pituitary. The main difference between the tumours and the normal pituitary was the greater amount...

  3. Redução de amidas por boranos Reduction of amides by boranes

    Directory of Open Access Journals (Sweden)

    Antônio Flávio de Carvalho Alcântara

    2002-05-01

    Full Text Available Despite the fact that boranes are frequently used in amide reductions, the reaction mechanisms of the involved are note well known. This work presents the results of a bibliographic search on probable amide reduction mechanisms and an analysis of the existing literature. Steric and electronic effects were considered in light of reactivity since it could be concluded that the formation of intermediates and products depends mainly on the substitution patterns of both the boron and nitrogen atoms. Otherwise, results described in the literature for the reactions of boranes, sodium borohydride, lithium aluminum hydride, alkylboranes or haloboranes with others functional groups such as carboxylic acids, esters, ketones and alkenes were analysed with the aim to obtain something about the N-substituted amide reactions employing boranes.

  4. PrAS: Prediction of amidation sites using multiple feature extraction.

    Science.gov (United States)

    Wang, Tong; Zheng, Wei; Wuyun, Qiqige; Wu, Zhenfeng; Ruan, Jishou; Hu, Gang; Gao, Jianzhao

    2017-02-01

    Amidation plays an important role in a variety of pathological processes and serious diseases like neural dysfunction and hypertension. However, identification of protein amidation sites through traditional experimental methods is time consuming and expensive. In this paper, we proposed a novel predictor for Prediction of Amidation Sites (PrAS), which is the first software package for academic users. The method incorporated four representative feature types, which are position-based features, physicochemical and biochemical properties features, predicted structure-based features and evolutionary information features. A novel feature selection method, positive contribution feature selection was proposed to optimize features. PrAS achieved AUC of 0.96, accuracy of 92.1%, sensitivity of 81.2%, specificity of 94.9% and MCC of 0.76 on the independent test set. PrAS is freely available at https://sourceforge.net/p/praspkg. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Synthesis, Anticancer and Antibacterial Activity of Salinomycin N-Benzyl Amides

    Directory of Open Access Journals (Sweden)

    Michał Antoszczak

    2014-11-01

    Full Text Available A series of 12 novel monosubstituted N-benzyl amides of salinomycin (SAL was synthesized for the first time and characterized by NMR and FT-IR spectroscopic methods. Molecular structures of three salinomycin derivatives in the solid state were determined using single crystal X-ray method. All compounds obtained were screened for their antiproliferative activity against various human cancer cell lines as well as against the most problematic bacteria strains such as methicillin-resistant Staphylococcus aureus (MRSA and Staphylococcus epidermidis (MRSE, and Mycobacterium tuberculosis. Novel salinomycin derivatives exhibited potent anticancer activity against drug-resistant cell lines. Additionally, two N-benzyl amides of salinomycin revealed interesting antibacterial activity. The most active were N-benzyl amides of SAL substituted at -ortho position and the least anticancer active derivatives were those substituted at the -para position.

  6. Synthesis and Characterization of Novel Polyurethanes Based on Vegetable Oils Amide and Ester Polyols

    Directory of Open Access Journals (Sweden)

    Vladimir YAKUSHIN

    2014-09-01

    Full Text Available Amide and ester type polyols were synthesized from rapeseed, sunflower and castor oils, and two types of ethanolamine (diethanolamine and triethanolamine at different molar ratio. Poly(urethane amides and polyester urethanes based on the synthesized polyols were prepared. The effect of the chemical structure of the obtained polyurethanes on density, glass transition temperature, thermal stability and mechanical properties was investigated. The influence of the content of OH groups in the synthesized polyols on the specified characteristics was estimated. It has been found that poly(urethane amides have better mechanical characteristics, but their thermal stability is lower than that of polyester urethanes. The chemical structure of the synthesized polyols and polyurethanes is qualitatively confirmed by IR-spectroscopy data. DOI: http://dx.doi.org/10.5755/j01.ms.20.3.4532

  7. Pyroglutamylated RF-amide peptide (QRFP) gene is regulated by metabolic endotoxemia.

    Science.gov (United States)

    Jossart, Christian; Mulumba, Mukandila; Granata, Riccarda; Gallo, Davide; Ghigo, Ezio; Marleau, Sylvie; Servant, Marc J; Ong, Huy

    2014-01-01

    Pyroglutamylated RF-amide peptide (QRFP) is involved in the regulation of food intake, thermogenesis, adipogenesis, and lipolysis. The expression of QRFP in adipose tissue is reduced in diet-induced obesity, a mouse model in which plasma concentrations of endotoxins are slightly elevated. The present study investigated the role of metabolic endotoxemia (ME) on QRFP gene regulation. Our results uncovered the expression of QRFP in murine macrophages and cell lines. This expression has been found to be decreased in mice with ME. Low doses of lipopolysaccharide (LPS) transiently down-regulated QRFP by 59% in RAW264.7 macrophages but not in 3T3-L1 adipocytes. The effect of LPS on QRFP expression in macrophages was dependent on the inhibitor of kB kinase and TIR-domain-containing adapter-inducing interferon (IFN)-β (TRIF) but not myeloid differentiation primary response gene 88. IFN-β was induced by ME in macrophages. IFN-β sustainably reduced QRFP expression in macrophages (64%) and adipocytes (49%). IFN-γ down-regulated QRFP (74%) in macrophages only. Both IFNs inhibited QRFP secretion from macrophages. LPS-stimulated macrophage-conditioned medium reduced QRFP expression in adipocytes, an effect blocked by IFN-β neutralizing antibody. The effect of IFN-β on QRFP expression was dependent on phosphoinositide 3-kinase, p38 MAPK, and histone deacetylases. The effect of IFN-γ was dependent on MAPK/ERK kinase 1/2 and histone deacetylases. Macrophage-conditioned medium containing increased amounts of QRFP preserved adipogenesis in adipocytes. In conclusion, LPS induces IFN-β release from macrophages, which reduces QRFP expression in both macrophages and adipocytes in an autocrine/paracrine-dependent manner, suggesting QRFP as a potential biomarker in ME.

  8. Fatty acid amide hydrolase inhibitors confer anti-invasive and antimetastatic effects on lung cancer cells

    Science.gov (United States)

    Winkler, Katrin; Ramer, Robert; Dithmer, Sophie; Ivanov, Igor; Merkord, Jutta; Hinz, Burkhard

    2016-01-01

    Inhibition of endocannabinoid degradation has been suggested as tool for activation of endogenous tumor defense. One of these strategies lies in blockade of fatty acid amide hydrolase (FAAH) which catalyzes the degradation of endocannabinoids (anandamide [AEA], 2-arachidonoylglycerol [2-AG]) and endocannabinoid-like substances (N-oleoylethanolamine [OEA], N-palmitoylethanolamine [PEA]). This study addressed the impact of two FAAH inhibitors (arachidonoyl serotonin [AA-5HT], URB597) on A549 lung cancer cell metastasis and invasion. LC-MS analyses revealed increased levels of FAAH substrates (AEA, 2-AG, OEA, PEA) in cells incubated with either FAAH inhibitor. In athymic nude mice FAAH inhibitors were shown to elicit a dose-dependent antimetastatic action yielding a 67% and 62% inhibition of metastatic lung nodules following repeated administration of 15 mg/kg AA-5HT and 5 mg/kg URB597, respectively. In vitro, a concentration-dependent anti-invasive action of either FAAH inhibitor was demonstrated, accompanied with upregulation of tissue inhibitor of matrix metalloproteinases-1 (TIMP-1). Using siRNA approaches, a causal link between the TIMP-1-upregulating and anti-invasive action of FAAH inhibitors was confirmed. Moreover, knockdown of FAAH by siRNA was shown to confer decreased cancer cell invasiveness and increased TIMP-1 expression. Inhibitor experiments point toward a role of CB2 and transient receptor potential vanilloid 1 in conferring anti-invasive effects of FAAH inhibitors and FAAH siRNA. Finally, antimetastatic and anti-invasive effects were confirmed for all FAAH substrates with AEA and OEA causing a TIMP-1-dependent anti-invasive action. Collectively, the present study provides first-time proof for an antimetastatic action of FAAH inhibitors. As mechanism of its anti-invasive properties an upregulation of TIMP-1 was identified. PMID:26930716

  9. Asparagine: an amide of particular distinction in the regulation of symbiotic nitrogen fixation of legumes.

    Science.gov (United States)

    Sulieman, Saad; Tran, Lam-Son Phan

    2013-09-01

    Symbiotic nitrogen fixation is tightly regulated by a range of fine processes at the nodule level, over which the host plant has overall control through the whole life of the plant. The operation of this control at the nodule level is not yet fully understood, but greater knowledge will ultimately lead to a better improvement of N2 fixation through the use of crop legumes and genetic engineering of crop plants for higher performance. It has been suggested that, nodule responses to the nutritional complexity of the rhizosphere environment involve a great deal of coordination of sensing and signal transduction. This regulation can be achieved through several mechanisms, including changes in carbon metabolism, oxygen supply and/or overproduction of reactive oxygen and nitrogen species. Recently, the cycling of amino acids observed between the plant and bacteroid fractions suggests a new and important regulatory mechanism involved in nodule responses. Most of the recent transcriptional findings are consistent with the earlier biochemical and physiological reports. Current research revealed unique advances for nodule metabolism, especially on the regulation of asparagine synthetase gene expression and the control of asparagine (ASN) to N2 fixing activity. A large amount of ASN is found accumulating in the root nodules of the symbiotic plants under restricted environments, such as drought, salinity and nutrient deficiency. Exceptionally, ASN phloem feeding has resulted in an increased concentration of the ASN amide in nodules followed by a remarkable decrease in nodule activity. In this review, recent progress concerning the possible role of ASN in whole-plant-based down-regulation of symbiotic N2 fixation will be reviewed.

  10. Synthesis and characterization of alternating poly(amide urea)s and poly(amide urethane urethane)s from ε-caprolactam, diamines, and diphenyl carbonate or ethylene carbonate

    NARCIS (Netherlands)

    Ubaghs, Luc; Sharma, Bhaskar; Keul, Helmut; Höcker, Hartwig; Loontjens, Ton; Benthem, Rolf van

    2003-01-01

    Alternating poly(amide urea)s from ε-caprolactam, diamines H2N-(CH2)x-NH2 (x = 2 - 4), and diphenyl carbonate were prepared in two steps. The microstructure of the poly(amide urea)s, as determined by means of 1H NMR spectroscopy, reveals a strictly alternating sequence of the building blocks. The

  11. Synthesis, properties and applications of biodegradable polymers derived from diols and dicarboxylic acids: from polyesters to poly(ester amide)s.

    Science.gov (United States)

    Díaz, Angélica; Katsarava, Ramaz; Puiggalí, Jordi

    2014-04-25

    Poly(alkylene dicarboxylate)s constitute a family of biodegradable polymers with increasing interest for both commodity and speciality applications. Most of these polymers can be prepared from biobased diols and dicarboxylic acids such as 1,4-butanediol, succinic acid and carbohydrates. This review provides a current status report concerning synthesis, biodegradation and applications of a series of polymers that cover a wide range of properties, namely, materials from elastomeric to rigid characteristics that are suitable for applications such as hydrogels, soft tissue engineering, drug delivery systems and liquid crystals. Finally, the incorporation of aromatic units and α-amino acids is considered since stiffness of molecular chains and intermolecular interactions can be drastically changed. In fact, poly(ester amide)s derived from naturally occurring amino acids offer great possibilities as biodegradable materials for biomedical applications which are also extensively discussed.

  12. Synthesis, Properties and Applications of Biodegradable Polymers Derived from Diols and Dicarboxylic Acids: From Polyesters to Poly(ester amide)s

    Science.gov (United States)

    Díaz, Angélica; Katsarava, Ramaz; Puiggalí, Jordi

    2014-01-01

    Poly(alkylene dicarboxylate)s constitute a family of biodegradable polymers with increasing interest for both commodity and speciality applications. Most of these polymers can be prepared from biobased diols and dicarboxylic acids such as 1,4-butanediol, succinic acid and carbohydrates. This review provides a current status report concerning synthesis, biodegradation and applications of a series of polymers that cover a wide range of properties, namely, materials from elastomeric to rigid characteristics that are suitable for applications such as hydrogels, soft tissue engineering, drug delivery systems and liquid crystals. Finally, the incorporation of aromatic units and α-amino acids is considered since stiffness of molecular chains and intermolecular interactions can be drastically changed. In fact, poly(ester amide)s derived from naturally occurring amino acids offer great possibilities as biodegradable materials for biomedical applications which are also extensively discussed. PMID:24776758

  13. [Aminomethyl derivatives of (benzisothiazolin-3-one-2-yl)acetic acid amides and 2-(1,2-benzisothiazoline-3-one-2-yl)propionic acid amides].

    Science.gov (United States)

    Sławik, T

    1991-11-01

    In the search for pharmacological active new derivatives of 1,2-benzisothiazolin-3-on amides of (3-oxo-1,2-benzisothiazolin-2-yl)acetic acid and 3-(3-oxo-1,2-benzisothiazolin-2-yl)propionic acid were obtained. In the reaction of these amides with formaldehyde and various second aryl amines the title compounds are formed. Morpholinmethylamide of (3-oxo-1,2-benzisothiazolin-2-yl)acetic acid showed activity against Trichomonas vaginalis. In the reaction of ethyl esters of (3-oxo-1,2-benzisothiazolin-2-yl) acetic- and -propionic acids with hydrazine hydrate products of ring-opening of isothiazole-2,2'-dithio-bis [N- (ethoxycarbonylmethyl)benzamide] and 2,2'-dithio-bis[N-(ethoxycarbonylethyl)benzamide are formed.

  14. Decreasing Relative Risk Premium

    DEFF Research Database (Denmark)

    Hansen, Frank

    We consider the risk premium demanded by a decision maker with wealth x in order to be indifferent between obtaining a new level of wealth y1 with certainty, or to participate in a lottery which either results in unchanged present wealth or a level of wealth y2 > y1. We define the relative risk...... premium as the quotient between the risk premium and the increase in wealth y1–x which the decision maker puts on the line by choosing the lottery in place of receiving y1 with certainty. We study preferences such that the relative risk premium is a decreasing function of present wealth, and we determine...... relative risk premium in the small implies decreasing relative risk premium in the large, and decreasing relative risk premium everywhere implies risk aversion. We finally show that preferences with decreasing relative risk premium may be equivalently expressed in terms of certain preferences on risky...

  15. N,N-Diethylurea-Catalyzed Amidation between Electron-Defficient Aryl Azides and Phenylacetaldehydes

    Science.gov (United States)

    Xie, Sheng; Ramström, Olof; Yan, Mingdi

    2015-01-01

    Urea structures, of which N,N-diethylurea (DEU) proved to be the most efficient, were discovered to catalyze amidation reactions between electron-defficient aryl azides and phenylacetaldehydes. Experimental data support 1,3-dipolar cycloaddition between DEU-activated enols and electrophilic phenyl azides, especially perfluoroaryl azides, followed by rearrangement of the triazoline intermediate. The activation of the aldehyde under near-neutral conditions was of special importance in inhibiting dehydration/aromatization of the triazoline intermediate, thus promoting the rearrangement to form aryl amides. PMID:25616121

  16. N,N-diethylurea-catalyzed amidation between electron-deficient aryl azides and phenylacetaldehydes.

    Science.gov (United States)

    Xie, Sheng; Ramström, Olof; Yan, Mingdi

    2015-02-06

    Urea structures, of which N,N-diethylurea (DEU) proved to be the most efficient, were discovered to catalyze amidation reactions between electron-deficient aryl azides and phenylacetaldehydes. Experimental data support 1,3-dipolar cycloaddition between DEU-activated enols and electrophilic phenyl azides, especially perfluoroaryl azides, followed by rearrangement of the triazoline intermediate. The activation of the aldehyde under near-neutral conditions was of special importance in inhibiting dehydration/aromatization of the triazoline intermediate, thus promoting the rearrangement to form aryl amides.

  17. Hydrolysis of ibuprofen nitrile and ibuprofen amide and deracemisation of ibuprofen using Nocardia corallina B-276.

    Science.gov (United States)

    Lievano, Ricardo; Pérez, Herminia Inés; Manjarrez, Norberto; Solís, Aida; Solís-Oba, Myrna

    2012-03-12

    A novel application of whole cells of Nocardia corallina B-276 for the deracemisation of ibuprofen is reported. This microorganism successfully hydrolysed ibuprofen nitrile to ibuprofen amide, and ibuprofen amide to ibuprofen, using a suspension of cells in a potassium phosphate buffer solution (0.1 M, pH = 7.0). These results can be explained by the presence of NHase and amidase enzymes, but the reactions are not enantioselective and low ee values were obtained. However, (R)-ibuprofen was isolated with > 99% ee by a deracemisation process catalysed by N. corallina B-276. This is the first report of this kind of catalysis with this microorganism.

  18. Hydrolysis of Ibuprofen Nitrile and Ibuprofen Amide and Deracemisation of Ibuprofen Using Nocardia corallina B-276

    Directory of Open Access Journals (Sweden)

    Myrna Solís-Oba

    2012-03-01

    Full Text Available A novel application of whole cells of Nocardia corallina B-276 for the deracemisation of ibuprofen is reported. This microorganism successfully hydrolysed ibuprofen nitrile to ibuprofen amide, and ibuprofen amide to ibuprofen, using a suspension of cells in a potassium phosphate buffer solution (0.1 M, pH = 7.0. These results can be explained by the presence of NHase and amidase enzymes, but the reactions are not enantioselective and low ee values were obtained. However, (R-ibuprofen was isolated with >99% ee by a deracemisation process catalysed by N. corallina B-276. This is the first report of this kind of catalysis with this microorganism.

  19. Safety Assessment of Amino Acid Alkyl Amides as Used in Cosmetics.

    Science.gov (United States)

    Burnett, Christina L; Heldreth, Bart; Bergfeld, Wilma F; Belsito, Donald V; Hill, Ronald A; Klaassen, Curtis D; Liebler, Daniel C; Marks, James G; Shank, Ronald C; Slaga, Thomas J; Snyder, Paul W; Andersen, F Alan

    The Cosmetic Ingredient Review Expert Panel (Panel) reviewed the product use, formulation, and safety data of 115 amino acid alkyl amides, which function as skin and hair conditioning agents and as surfactants-cleansing agents in personal care products. Safety test data on dermal irritation and sensitization for the ingredients with the highest use concentrations, lauroyl lysine and sodium lauroyl glutamate, were reviewed and determined to adequately support the safe use of the ingredients in this report. The Panel concluded that amino acid alkyl amides are safe in the present practices of use and concentration in cosmetics, when formulated to be nonirritating.

  20. Occurrence, biological activities and {sup 13}C NMR data of amides from Piper (Piperaceae)

    Energy Technology Data Exchange (ETDEWEB)

    Nascimento, Jeferson C. do; Paula, Vanderlucia F. de [Universidade Estadual do Sudoeste da Bahia, Jequie, BA (Brazil). Dept. de Quimica e Exatas; David, Jorge M. [Universidade Federal da Bahia (UFBA), Salvador, BA (Brazil). Inst. de Quimica; David, Juceni P., E-mail: jmdavid@ufba.br [Universidade Federal da Bahia (UFBA), Salvador, BA (Brazil). Fac. de Farmacia

    2012-07-01

    This manuscript describes an update review with up to 285 references concerning the occurrence of amides from a variety of species of the genus Piper (Piperaceae). Besides addressing occurrence, this review also describes the biological activities attributed to extracts and pure compounds, a compiled {sup 13}C NMR data set, the main correlations between structural and NMR spectroscopic data of these compounds, and employment of hyphened techniques such as LC-MS, GC-MS and NMR for analysis of amides from biological samples and crude Piper extracts. (author)

  1. Uranyl Photocleavage of Phosphopeptides Yields Truncated C-Terminally Amidated Peptide Products

    DEFF Research Database (Denmark)

    Elnegaard, Rasmus L B; Møllegaard, Niels Erik; Zhang, Qiang

    2017-01-01

    The uranyl ion (UO2(2+) ) binds phosphopeptides with high affinity, and when irradiated with UV-light, it can cleave the peptide backbone. In this study, high-accuracy tandem mass spectrometry and enzymatic assays were used to characterise the photocleavage products resulting from the uranyl phot...... challenges in green pharmaceutical chemistry....... photocleavage reaction of a tetraphosphorylated β-casein model peptide. We show that the primary photocleavage products of the uranyl-catalysed reaction are C-terminally amidated. This could be of great interest to the pharmaceutical industry, as efficient peptide amidation reactions are one of the top...

  2. Shear and dielectric responses of propylene carbonate, tripropylene glycol, and a mixture of two secondary amides

    DEFF Research Database (Denmark)

    Gainaru, Catalin; Hecksher, Tina; Olsen, Niels Boye

    2012-01-01

    to calculate the dielectric from the mechanical response and vice versa. Using a single parameter for a given system, good agreement between model calculations and experimental data is achieved for the entire relaxation spectra, including secondary relaxations and the Debye-like dielectric peak......Propylene carbonate and a mixture of two secondary amides, N-ethylformamide and Nethylacetamide, are investigated by means of broadband dielectric and mechanical shear spectroscopy. The similarities between the rheological and the dielectric responses of these liquids and of the previously...... in the secondary amides. In addition, the predictions of the shoving model are confirmed for the investigated liquids...

  3. Synthesis and Characterization of Ethylene DiamineTetera Acetic Acid Polyester-amides polymer with Aminoalcohol

    Directory of Open Access Journals (Sweden)

    Dakhil Nasser Taha

    2017-02-01

    Full Text Available linear aromatic and aliphatic polyester-amides (PEAs have been synthesized by polycondensation of aliphatic and aromatic aminoalcohol (Ethanol amine, 2-amino-2-methyl-propan-1-ol, m-amino phenol with Ethylenediaminetetraacetic acid (EDTA as a favorable and combined complexing compound was joined into the polymer backbone with poly addition reactions. These polymers were characterized by FTIR, 1H NMR, solubility studies , elemental analysis, , Thermal analyses such as TGA were measured, intrinsic viscosity. The poly(ester-amides obtained show good thermal stability.

  4. Occurrence, biological activities and 13C NMR data of amides from Piper (Piperaceae

    Directory of Open Access Journals (Sweden)

    Jeferson C. do Nascimento

    2012-01-01

    Full Text Available This manuscript describes an update review with up to 285 references concerning the occurrence of amides from a variety of species of the genus Piper (Piperaceae. Besides addressing occurrence, this review also describes the biological activities attributed to extracts and pure compounds, a compiled 13C NMR data set, the main correlations between structural and NMR spectroscopic data of these compounds, and employment of hyphened techniques such as LC-MS, GC-MS and NMR for analysis of amides from biological samples and crude Piper extracts.

  5. Mechanistic insight into benzenethiol catalyzed amide bond formations from thioesters and primary amines

    DEFF Research Database (Denmark)

    Stuhr-Hansen, Nicolai; Bork, Nicolai; Strømgaard, Kristian

    2014-01-01

    in the aromatic thioester amidation reaction. Under similar conditions, cysteine-free ligation was achieved by coupling a fully side-chain protected 15 amino acid phosphopeptide thioester to the free N-terminal of a side-chain protected 9 amino acid peptide producing the corresponding 24 amino acid phosphopeptide.......The influence of arylthiols on cysteine-free ligation, i.e. the reaction between an alkyl thioester and a primary amine forming an amide bond, was studied in a polar aprotic solvent. We reacted the ethylthioester of hippuric acid with cyclohexylamine in the absence or presence of various quantities...

  6. Hydrolysis of Ibuprofen Nitrile and Ibuprofen Amide and Deracemisation of Ibuprofen Using Nocardia corallina B-276

    OpenAIRE

    Myrna Solís-Oba; Norberto Manjarrez; Aida Solís; Ricardo Lievano; Herminia Inés Pérez

    2012-01-01

    A novel application of whole cells of Nocardia corallina B-276 for the deracemisation of ibuprofen is reported. This microorganism successfully hydrolysed ibuprofen nitrile to ibuprofen amide, and ibuprofen amide to ibuprofen, using a suspension of cells in a potassium phosphate buffer solution (0.1 M, pH = 7.0). These results can be explained by the presence of NHase and amidase enzymes, but the reactions are not enantioselective and low ee values were obtained. However, (R)-ibuprofen was is...

  7. Decreasing serial cost sharing

    DEFF Research Database (Denmark)

    Hougaard, Jens Leth; Østerdal, Lars Peter Raahave

    2009-01-01

    The increasing serial cost sharing rule of Moulin and Shenker (Econometrica 60:1009-1037, 1992) and the decreasing serial rule of de Frutos (J Econ Theory 79:245-275, 1998) are known by their intuitive appeal and striking incentive properties. An axiomatic characterization of the increasing serial...... rule was provided by Moulin and Shenker (J Econ Theory 64:178-201, 1994). This paper gives an axiomatic characterization of the decreasing serial rule....

  8. Decreasing Serial Cost Sharing

    DEFF Research Database (Denmark)

    Hougaard, Jens Leth; Østerdal, Lars Peter

    The increasing serial cost sharing rule of Moulin and Shenker [Econometrica 60 (1992) 1009] and the decreasing serial rule of de Frutos [Journal of Economic Theory 79 (1998) 245] have attracted attention due to their intuitive appeal and striking incentive properties. An axiomatic characterization...... of the increasing serial rule was provided by Moulin and Shenker [Journal of Economic Theory 64 (1994) 178]. This paper gives an axiomatic characterization of the decreasing serial rule...

  9. Ru(II)-catalyzed amidation reactions of 8-methylquinolines with azides via C(sp(3))-H activation.

    Science.gov (United States)

    Liu, Bingxian; Li, Bin; Wang, Baiquan

    2015-11-25

    Ru(II)-catalyzed amidation reactions of 8-methylquinolines with azides have been developed. They are the first examples of [(p-cymene)RuCl2]2-catalyzed C(sp(3))-H bond intermolecular amidation reactions which give quinolin-8-ylmethanamines under mild reaction conditions in good yields.

  10. Studies on peptide amidase-catalysed C-terminal peptide amidation in organic media with respect to its substrate specificity

    Czech Academy of Sciences Publication Activity Database

    Čeřovský, Václav; Kula, M. R.

    2001-01-01

    Roč. 33, - (2001), s. 183-187 ISSN 0885-4513 R&D Projects: GA ČR GA203/99/1458 Keywords : enzymic amidation * peptide amides * peptide synthesis Subject RIV: CC - Organic Chemistry Impact factor: 1.408, year: 2001

  11. Non-amidated and amidated members of the C-type allatostatin (AST-C) family are differentially distributed in the stomatogastric nervous system of the American lobster, Homarus americanus.

    Science.gov (United States)

    Christie, Andrew E; Miller, Alexandra; Fernandez, Rebecca; Dickinson, Evyn S; Jordan, Audrey; Kohn, Jessica; Youn, Mina C; Dickinson, Patsy S

    2018-01-13

    The crustacean stomatogastric nervous system (STNS) is a well-known model for investigating neuropeptidergic control of rhythmic behavior. Among the peptides known to modulate the STNS are the C-type allatostatins (AST-Cs). In the lobster, Homarus americanus, three AST-Cs are known. Two of these, pQIRYHQCYFNPISCF (AST-C I) and GNGDGRLYWRCYFNAVSCF (AST-C III), have non-amidated C-termini, while the third, SYWKQCAFNAVSCFamide (AST-C II), is C-terminally amidated. Here, antibodies were generated against one of the non-amidated peptides (AST-C I) and against the amidated isoform (AST-C II). Specificity tests show that the AST-C I antibody cross-reacts with both AST-C I and AST-C III, but not AST-C II; the AST-C II antibody does not cross-react with either non-amidated peptide. Wholemount immunohistochemistry shows that both subclasses (non-amidated and amidated) of AST-C are distributed throughout the lobster STNS. Specifically, the antibody that cross-reacts with the two non-amidated peptides labels neuropil in the CoGs and the stomatogastric ganglion (STG), axons in the superior esophageal (son) and stomatogastric (stn) nerves, and ~ 14 somata in each commissural ganglion (CoG). The AST-C II-specific antibody labels neuropil in the CoGs, STG and at the junction of the sons and stn, axons in the sons and stn, ~ 42 somata in each CoG, and two somata in the STG. Double immunolabeling shows that, except for one soma in each CoG, the non-amidated and amidated peptides are present in distinct sets of neuronal profiles. The differential distributions of the two AST-C subclasses suggest that the two peptide groups are likely to serve different modulatory roles in the lobster STNS.

  12. Effect of polyethyleneglycol on CH{sub 4} permeation through poly(amide-b-ethylene oxide)-based nanocomposite membranes

    Energy Technology Data Exchange (ETDEWEB)

    Asghari, Morteza, E-mail: asghari@kashanu.ac.ir [Separation Processes Research Group (SPRG), University of Kashan, Kashan (Iran, Islamic Republic of); Energy Research Institute, University of Kashan, Ghotb-e-Ravandi Avenue, Kashan (Iran, Islamic Republic of); Mahmudi, Amir; Zargar, Vida [Separation Processes Research Group (SPRG), University of Kashan, Kashan (Iran, Islamic Republic of); Khanbabaei, Ghader [Polymer Science and Technology Division, Research Institute of Petroleum Industry, Tehran (Iran, Islamic Republic of)

    2014-11-01

    Graphical abstract: - Highlights: • A three-phase polymer/liquid/solid (PEBA/PEG/zeolite X) membrane was fabricated. • Nanocrystalline zeolite X was used as filler to stabilize membrane polymeric matrix. • Introducing zeolite to PEBA matrix caused its total free volume to decrease. • A gradual decrease with pressure was observed in CH{sub 4} permeability for the membranes. • In all the experiments, operating pressures varied from 2 to 8 bar. - Abstract: A three-phase polymer/liquid/solid poly(amide-b-ethylene oxide) (PEBA)/polyethylene glycol (PEG)/zeolite X was fabricated and its gas permeability was investigated. CH{sub 4} permeability of neat PEBA, two-phase PEBA/NaX and three-phase PEBA/PEG/NaX were compared for different pressures within the range of 2–8 bar. The fabricated membranes were structurally characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and atomic force microscope (AFM). SEM images showed that the zeolite grain size was homogeneously smaller than 2 μm. They also revealed the dense structures of the membranes and no pores were observed at these magnifications. AFM surface images indicated that the membranes surface roughness increased significantly with increasing zeolite loading. CH{sub 4} permeability for single-, two- and three-phase membranes decreased from 3.13 to 2.81, from 3.96 to 2.31 and from 2.67 to 2.14 barrer, respectively.

  13. Dynamic kinetic resolution of amino acid amide catalyzed by D-aminopeptidase and alpha-amino-epsilon-caprolactam racemase.

    Science.gov (United States)

    Asano, Yasuhisa; Yamaguchi, Shigenori

    2005-06-01

    Amino acid amide racemizing activity was discovered in alpha-amino-epsilon-caprolactam (ACL) racemase (EC 5. 1. 1. 15) from Achromobacter obae. The enzymatic synthesis of d-alanine from l-alanine amide has been demonstrated by use of d-aminopeptidase (DAP; EC 3. 4. 11. 19) from Ochrobactrum anthropi C1-38 and ACL racemase. The conversion of 45 mM l-alanine amide was carried out at 30 degrees C for 7 h; l-alanine amide was completely converted to d-alanine, and no l-alanine was detected. The result of successive enzymatic reaction shows that the combination of ACL racemase and DAP can be applied for dynamic kinetic resolution of dl-amino acid amides to yield d-amino acids.

  14. Decreasing asthma morbidity

    African Journals Online (AJOL)

    1994-12-12

    Dec 12, 1994 ... Apart from the optimal use of drugs, various supplementary methods have been tested to decrease asthma morbidity, usually in patients from reiatively affluent socio-economic backgrounds. A study of additional measures taken in a group of moderate to severe adult asthmatics from very poor socio- ...

  15. Synthesis of a-amino amides via a-amino imidoylbenzotriazoles

    Directory of Open Access Journals (Sweden)

    ALAN R. KATRITZKY

    2005-03-01

    Full Text Available Reactions of isonitriles 11a-c with N-(a-aminoalkylbenzotriazoles 10a-k afford N-(a-aminoimidoylbenzotriazoles 12a-q which on hydrolysis by dilute hydrochloric acid gave a-amino amides 14a-j.

  16. Ru(II)-catalyzed intermolecular ortho-C-H amidation of aromatic ketones with sulfonyl azides.

    Science.gov (United States)

    Bhanuchandra, M; Yadav, M Ramu; Rit, Raja K; Rao Kuram, Malleswara; Sahoo, Akhila K

    2013-06-07

    Ru(II)-catalyzed intermolecular ortho-C-H amidation of weakly coordinating aromatic ketones with sulfonyl azides is reported. The developed reaction protocol can be extended to various substituted aromatic ketones to afford a wide range of desired C-N bond formation products in good yields.

  17. Rhodium(III)-catalyzed intermolecular amidation with azides via C(sp³)-H functionalization.

    Science.gov (United States)

    Wang, Nuancheng; Li, Renhe; Li, Liubo; Xu, Shansheng; Song, Haibin; Wang, Baiquan

    2014-06-06

    The amidation reactions of 8-methylquinolines with azides catalyzed by a cationic rhodium(III) complex proceed efficiently to give quinolin-8-ylmethanamine derivatives in good yields via C(sp(3))-H bond activation under external oxidant-free conditions. A catalytically competent five-membered rhodacycle has been isolated and characterized, revealing a key intermediate in the catalytic cycle.

  18. Quantum calculations of the electro-optical parameters of haloid ethers, esters, amides and carbamates

    Science.gov (United States)

    Furer, V. L.

    1992-03-01

    Force and electro-optical parameters of haloid ethers, esters, amides and carbamates were calculated using the MINDO/3 method. The obtained values of parameters, frequencies and intensities of bands in IR spectra are in good accordance with experiment. The changes of molecular parameters due to the electronic interactions and conformational transitions are discussed.

  19. Amide Synthesis from Alcohols and Amines by the Extrusion of Dihydrogen

    DEFF Research Database (Denmark)

    Nordstrøm, Lars Ulrik Rubæk; Vogt, Henning; Madsen, R.

    2008-01-01

    An environmentally friendly method for synthesis of amides is presented where a simple ruthenium catalyst mediates the direct coupling between an alcohol and an amine with the liberation of two molecules of dihydrogen. The active catalyst is generated in situ from an easily available ruthenium co...

  20. The Migration Security in Russian Society amid Ethnic and Social Conflicts Aggravation

    Directory of Open Access Journals (Sweden)

    N А Tkacheva

    2011-03-01

    Full Text Available National security protection emerges as an indispensable factor for the development of personality, society, and state amid the increasing complexity of international migration processes. The article touches upon the peculiarities of ethnic and social relations between migrants and members of the host country providing insight into the novel category of "migration security".

  1. Synthesis of Peptide Amides using Sol-Gel Immobilized Alcalase in Batch and Continuous Reaction System

    NARCIS (Netherlands)

    Corici, L.N.; Frissen, A.E.; Zoelen, van D.J.; Eggen, I.F.; Peter, F.; Davidescu, C.; Boeriu, C.G.

    2011-01-01

    Two commercial proteases from Bacillus licheniformis (Alcalase 2.4 L FG and Alcalase 2.5 L, Type DX) were screened for the production of Z-Ala-Phe-NH2 in batch reaction. Alcalase 2.4 L FG was the most efficient enzyme for the C-terminal amidation of Z-Ala-Phe-OMe using ammonium carbamate as ammonium

  2. Direct Lactamization of Azido Amides via Staudinger-Type Reductive Cyclization

    International Nuclear Information System (INIS)

    Heo, In Jung; Lee, Su Jeong; Cho, Chang Woo

    2012-01-01

    The direct lactamization of 1,3- and 1,4-azido amides has been achieved using triphenylphosphine and water, affording various γ- and δ-lactams in good to excellent yields. The direct lactamization of the azido amides was performed via the Staudinger-type reductive cyclization in which the amide group acts as the electrophile for lactam synthesis. This lactamization provides a mild, functional group tolerant and efficient route for the synthesis of various γ- and δ-lactams found in natural products and pharmaceuticals. Further studies will be conducted to develop new synthetic routes for the synthesis of various lactams. The lactam ring system is one of the most ubiquitous structural motifs found in natural products and pharmaceuticals. Owing to the prevalence of lactams, their synthesis has attracted considerable attention. Lactams are usually prepared by the coupling of activated carboxylic acid derivatives with amines. Alternative routes include the Beckmann rearrangement of oximes, the Schmidt reaction of cyclic ketones and hydrazoic acid, the Kinugasa reaction of nitrones and terminal acetylenes, the Diels-Alder reaction of cyclopentadiene and chlorosulfonyl isocyanate, transition metal catalyzed lactamization of amino alcohols, and iodolactamization of amides and alkenes. In particular, the intramolecular Staudinger ligation of azides and activated carboxy acids, including esters, is well known as an environmentally friendly and mild protocol for lactam synthesis

  3. Amide hydrogen-deuterium exchange kinetics as a test of structural states of proteins

    International Nuclear Information System (INIS)

    Popescu, Aurel I.; Craescu, Constantin

    2000-01-01

    The amide hydrogen-deuterium exchange (AHD EX ) method gives information about the accessibility degree of amide protons, on their interaction with the physico-chemical microenvironment, and implicitly, on the 3D structure of proteins. This method as useful both for the characterisation of the native state and of conformational modifications induced by protein interaction with different physico-chemical agents. The rate of the amide proton exchange for deuterium can be measured by various physical methods (NMR, MS, pulsed H/D exchange, etc.) evaluating the so-called protection factor, P, defined as the ratio between the exchange constant, k RC , experimentally determined on model peptides in a random coil conformation and the actual exchange constant, k EX , derived from the NMR spectra (e.g. the heteronuclear multiple-quantum correlation spectroscopy, HMQC). In this work, the NMR spectra of the immunophilin domain of FKBP59-I protein (both in unligated state and when it is ligated with FK506 immunosuppressor) recorded at corrected pH = 7.2, T= 308 K, are interpreted. The results show a large variety of kinetic constant values, spanning from those of very rapidly exchanging protons (non-protected) to those of very slow exchanging once (highly protected). After binding FK506, the protection factor of FKBP59-I amide protons, are significantly increased. (authors)

  4. Effects of indole amides on lettuce and onion germination and growth.

    Science.gov (United States)

    Borgati, Thiago F; Boaventura, Maria Amelia D

    2011-01-01

    Auxins, such as indole-3-acetic acid (IAA), are important in plant germination and growth, while physiological polyamines, such as putrescine, are involved in cell proliferation and differentiation, and their concentrations increase during germination. In this work, novel indole amides were synthesized in good yields by monoacylation of morpholine and unprotected symmetrical diamines with indole-3-carboxylic acid, a putative metabolite of IAA, possessing no auxin-like activity. These amides were tested for their effects on seed germination and growth of the radicles and shoots of Lactuca sativa (lettuce) and Allium cepa (onion) seedlings, at 100.0, 1.0, and 0.01 microM concentrations. Germination was generally stimulated, with the exception of amide 3, derived from morpholine, at 100 microM. On radicle and shoot growth, the effect of these compounds was predominantly inhibitory. Compound 3 was the best inhibitor of growth of lettuce and onion, at the highest concentration. Amides, such as propanil, among others, are described as having herbicidal activity.

  5. Investigation of the complex reaction coordinate of acid catalyzed amide hydrolysis from molecular dynamics simulations

    International Nuclear Information System (INIS)

    Zahn, Dirk

    2004-01-01

    The rate-determining step of acid catalyzed peptide hydrolysis is the nucleophilic attack of a water molecule to the carbon atom of the amide group. Therein the addition of the hydroxyl group to the amide carbon atom involves the association of a water molecule transferring one of its protons to an adjacent water molecule. The protonation of the amide nitrogen atom follows as a separate reaction step. Since the nucleophilic attack involves the breaking and formation of several bonds, the underlying reaction coordinate is rather complex. We investigate this reaction step from path sampling Car-Parrinello molecular dynamics simulations. This approach does not require the predefinition of reaction coordinates and is thus particularly suited for investigating reaction mechanisms. From our simulations the most relevant components of the reaction coordinate are elaborated. Though the C···O distance of the oxygen atom of the water molecule performing the nucleophilic attack and the corresponding amide carbon atom is a descriptor of the reaction progress, a complete picture of the reaction coordinate must include all three molecules taking part in the reaction. Moreover, the proton transfer is found to depend on favorable solvent configurations. Thus, also the arrangement of non-reacting, i.e. solvent water molecules needs to be considered in the reaction coordinate

  6. Vitamin E amides, a new class of vitamin E analogues with enhanced proapoptotic activity

    Czech Academy of Sciences Publication Activity Database

    Tomic-Vatic, A.; EyTina, J.; Chapmann, J.; Mahdavian, E.; Neužil, Jiří; Salvatore, B.A.

    2005-01-01

    Roč. 117, č. 2 (2005), s. 118-193 ISSN 0020-7136 Institutional research plan: CEZ:AV0Z5052915; CEZ:AV0Z50520514 Keywords : vitamin E amides * apoptosis * anticancer agents Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.700, year: 2005

  7. Fe(III) complex of biuret-amide based macrocyclic ligand as peroxidase enzyme mimic.

    Science.gov (United States)

    Panda, Chakadola; Ghosh, Munmun; Panda, Tamas; Banerjee, Rahul; Sen Gupta, Sayam

    2011-07-28

    An Fe(III) complex of a biuret-amide based macrocyclic ligand that exhibits both excellent reactivity for the activation of H(2)O(2) and high stability, especially at low pH and high ionic strength, is reported.

  8. High Performance Liquid Chromatographic Analysis of Phytoplankton Pigments Using a C16-Amide Column

    Science.gov (United States)

    A reverse-phase high performance liquid chromatographic (RP-HPLC) method was developed to analyze in a single run, most polar and non-polar chlorophylls and carotenoids from marine phytoplankton. The method is based on a RP-C16-Amide column and a ternary gradient system consistin...

  9. Nonplanar Tertiary Amides in Rigid Chiral Tricyclic Dilactams. Peptide Group Distortions and Vibrational Optical Activity

    Czech Academy of Sciences Publication Activity Database

    Pazderková, Markéta; Profant, V.; Hodačová, J.; Šebestík, Jaroslav; Pazderka, T.; Novotná, P.; Urbanová, M.; Šafařík, Martin; Buděšínský, Miloš; Tichý, Miloš; Bednárová, Lucie; Baumruk, V.; Maloň, Petr

    2013-01-01

    Roč. 117, č. 33 (2013), s. 9626-9642 ISSN 1520-6106 R&D Projects: GA ČR GAP205/10/1276 Institutional support: RVO:61388963 Keywords : spirodilactams * amide bond * vibrational circular dichroism * non-planarity * Raman optical activity Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.377, year: 2013

  10. Novel amide derivatives as inhibitors of histone deacetylase: design, synthesis and SAR

    DEFF Research Database (Denmark)

    Andrianov, V.; Gailite, V.; Lola, D.

    2009-01-01

    Enzymatic inhibition of histone deacetylase (HDAC) activity is emerging as an innovative and effective approach for the treatment of cancer. A series of novel amide derivatives have been synthesized and evaluated for their ability to inhibit human HDACs. Multiple compounds were identified as potent...

  11. Picolyl amides of betulinic acid as antitumor agents causing tumor cell apoptosis

    Czech Academy of Sciences Publication Activity Database

    Bildziukevich, Uladzimir; Rárová, L.; Šaman, David; Wimmer, Zdeněk

    2018-01-01

    Roč. 145, FEB 10 (2018), s. 41-50 ISSN 0223-5234 R&D Projects: GA MPO(CZ) FV10599 Institutional support: RVO:61389030 ; RVO:61388963 Keywords : Amide * Betulinic acid * Cytotoxicity * Picolyl amine * Therapeutic index Subject RIV: CC - Organic Chemistry OBOR OECD: Organic chemistry Impact factor: 4.519, year: 2016

  12. Synthesis and characterization of new copoly(amide-imide)s based ...

    African Journals Online (AJOL)

    ... solubility tests and UV-vis spectroscopy. Thermal stabilities of resulted polymers (7a-c) containing three different second diacids were compared by using TGA and DTG thermograms. KEY WORDS: Highperformance polymers, Copoly(amide-imide)s, Direct polycondensation, Thermal properties. Bull. Chem. Soc. Ethiop.

  13. The Preparations and Water Vapor Barrier Properties of Polyimide Films Containing Amide Moieties

    Directory of Open Access Journals (Sweden)

    Kai Zhang

    2017-12-01

    Full Text Available Flexible displays are a systematic revolution in the field of display, in which high-performance and high-barrier polymer substrates are considered to be one of the most important key materials. In this work, high water vapor barrier polyimides containing amide moieties were synthesized via the ternary polymerization of 4,4′-diaminobenzailide (DABA, 4,4′-diaminodipheny ether (ODA, and 3,3′,4,4′-biphenyl-tetracarboxylic acid dianhydride (BPDA followed by thermal imidization. The relationship between the content of amide moieties and the water vapor barrier property of the prepared polyimides was studied by means of density test, water absorbing test, water contact angle test, water vapor permeation test, fourier transform infrared spectroscopy (FT-IR, thermogravimetric analysis (TGA, thermogravimetry coupled with fourier transform infrared spectrometry (TG-FTIR, wide-angle X-ray diffraction analysis (WXRD, mechanical performance test, etc. The results show that the introduction of amide groups into polyimide (PI main chains can improve the water vapor barrier properties of the polyimides effectively. The water vapor transmission rate (WVTR of the polyimide films can be improved from 8.2365 g·(m2·24 h−1 to 0.8670 g·(m2·24 h−1 with the increasing content of amide moieties.

  14. Ruthenium on chitosan: A recyclable heterogeneous catalyst for aqueous hydration of nitriles to amides

    Science.gov (United States)

    Ruthenium has been immobilized over chitosan by simply stirring an aqueous suspension of chitosan in water with ruthenium chloride and has been utilized for the oxidation of nitriles to amides; the hydration of nitriles occurs in high yield and excellent selectivity, which procee...

  15. Process for chemical reaction of amino acids and amides yielding selective conversion products

    Science.gov (United States)

    Holladay, Jonathan E [Kennewick, WA

    2006-05-23

    The invention relates to processes for converting amino acids and amides to desirable conversion products including pyrrolidines, pyrrolidinones, and other N-substituted products. L-glutamic acid and L-pyroglutamic acid provide general reaction pathways to numerous and valuable selective conversion products with varied potential industrial uses.

  16. Characterization and dispersibility of improved thermally stable amide functionalized graphene oxide

    Energy Technology Data Exchange (ETDEWEB)

    Rani, Sumita [Electronic Science Department, Kurukshetra University, Kurukshetra, Haryana 136119 (India); Kumar, Mukesh, E-mail: kumarmukesh@gmail.com [Electronic Science Department, Kurukshetra University, Kurukshetra, Haryana 136119 (India); Kumar, Rajiv [Department of Chemistry, Kurukshetra University, Kurukshetra, Haryana 136119 (India); Kumar, Dinesh; Sharma, Sumit [Electronic Science Department, Kurukshetra University, Kurukshetra, Haryana 136119 (India); Singh, Gulshan [Department of Chemistry, Kurukshetra University, Kurukshetra, Haryana 136119 (India)

    2014-12-15

    Graphical abstract: Improved thermal stability and surface study of amide functionalized graphene oxide. - Highlights: • Amide functionalized graphene oxides (AGOs) were synthesized from aniline, 2-aminothiazole and 2-aminopyrimidine. • Achieved enhancement in thermal stability of AGOs as compare to GO. • AGOs are found to be highly dispersible in water, DMSO and DMF. • Dispersibility is stable for more than two and half months. - Abstract: Amidation of graphene oxide (GO) with aniline, 2-aminothiazole and 2-aminopyrimidine results in the synthesis of amide functionalized graphene oxides (AGOs). Scanning electron microscopy, X-ray diffraction, thermogravimetric analysis (TGA), UV–vis and Raman spectroscopy were used to investigate the properties of AGOs. It was found that, contrary to GO, AGOs are soluble in water, dimethyl sulfoxide, dimethylformamide and can be stabilized for months. TGA of AGOs shows the major weight loss above 670 °C as compared to GO in which significant weight loss occurs near 200 °C. Thus AGOs show strong improvement in thermal properties.

  17. Protein structure validation and refinement using amide proton chemical shifts derived from quantum mechanics

    DEFF Research Database (Denmark)

    Christensen, Anders Steen; Linnet, Troels Emtekær; Borg, Mikael

    2013-01-01

    We present the ProCS method for the rapid and accurate prediction of protein backbone amide proton chemical shifts - sensitive probes of the geometry of key hydrogen bonds that determine protein structure. ProCS is parameterized against quantum mechanical (QM) calculations and reproduces high level...

  18. Indoline Amide Glucosides from Portulaca oleracea: Isolation, Structure, and DPPH Radical Scavenging Activity.

    Science.gov (United States)

    Jiao, Ze-Zhao; Yue, Su; Sun, Hong-Xiang; Jin, Tian-Yun; Wang, Hai-Na; Zhu, Rong-Xiu; Xiang, Lan

    2015-11-25

    A polyamide column chromatography method using an aqueous ammonia mobile phase was developed for large-scale accumulation of water-soluble indoline amide glucosides from a medicinal plant, Portulaca oleracea. Ten new [oleraceins H, I, K, L, N, O, P, Q, R, S (1-10)] and four known [oleraceins A-D (11-14)] indoline amide glucosides were further purified and structurally characterized by various chromatographic and spectroscopic methods. The DPPH radical scavenging activities of oleraceins K (5) and L (6), with EC50 values of 15.30 and 16.13 μM, respectively, were twice that of a natural antioxidant, vitamin C; the EC50 values of the 12 other indoline amides, which ranged from 29.05 to 43.52 μM, were similar to that of vitamin C. Structure-activity relationships indicated that the DPPH radical scavenging activities of these indoline amides correlate with the numbers and positions of the phenolic hydroxy groups.

  19. An efficient and convenient synthesis of N-substituted amides under ...

    Indian Academy of Sciences (India)

    scopic reagents, low yield, tedious product isolation, longer reaction time and competing side reactions. In this paper we wish to report a comprehensive study of the reactions between various organic nitriles and alcohols in the presence of catalytic amount of Al(HSO4)3 to provide N-substituted amides via Ritter fashion.

  20. One pot direct synthesis of amides or oxazolines from carboxylic acids using Deoxo-Fluor reagent.

    Science.gov (United States)

    Kangani, Cyrous O; Kelley, David E

    2005-12-19

    A mild and highly efficient one pot-one step condensation and/or condensation-cyclization of various acids to amides and/or oxazolines using Deoxo-Fluor reagents is described. Parallel syntheses of various free fatty acids with 2-amino-2, 2-dimethyl-1-propanol resulted with excellent yields.

  1. Protein topology determines cysteine oxidation fate: the case of sulfenyl amide formation among protein families.

    Science.gov (United States)

    Defelipe, Lucas A; Lanzarotti, Esteban; Gauto, Diego; Marti, Marcelo A; Turjanski, Adrián G

    2015-03-01

    Cysteine residues have a rich chemistry and play a critical role in the catalytic activity of a plethora of enzymes. However, cysteines are susceptible to oxidation by Reactive Oxygen and Nitrogen Species, leading to a loss of their catalytic function. Therefore, cysteine oxidation is emerging as a relevant physiological regulatory mechanism. Formation of a cyclic sulfenyl amide residue at the active site of redox-regulated proteins has been proposed as a protection mechanism against irreversible oxidation as the sulfenyl amide intermediate has been identified in several proteins. However, how and why only some specific cysteine residues in particular proteins react to form this intermediate is still unknown. In the present work using in-silico based tools, we have identified a constrained conformation that accelerates sulfenyl amide formation. By means of combined MD and QM/MM calculation we show that this conformation positions the NH backbone towards the sulfenic acid and promotes the reaction to yield the sulfenyl amide intermediate, in one step with the concomitant release of a water molecule. Moreover, in a large subset of the proteins we found a conserved beta sheet-loop-helix motif, which is present across different protein folds, that is key for sulfenyl amide production as it promotes the previous formation of sulfenic acid. For catalytic activity, in several cases, proteins need the Cysteine to be in the cysteinate form, i.e. a low pKa Cys. We found that the conserved motif stabilizes the cysteinate by hydrogen bonding to several NH backbone moieties. As cysteinate is also more reactive toward ROS we propose that the sheet-loop-helix motif and the constraint conformation have been selected by evolution for proteins that need a reactive Cys protected from irreversible oxidation. Our results also highlight how fold conservation can be correlated to redox chemistry regulation of protein function.

  2. Contribution of the study of the radiolysis of amide compounds Tc the knowledge of the electron-molecule interaction in various gas and liquid phases. An attempt of correlation with the molecular orbital theory calculations

    International Nuclear Information System (INIS)

    Tran Thi Thu Hoa.

    1985-08-01

    A study of electron attachment processes on selected amides, respectively at low pressure or under pressure inert gas (C 2 H 4 , N 2 , Ar) has been carried out. The results were compared with presolvated electron scavenging reactions in various polar liquids. The effect of the environment and density of the medium on the stabilisation of anionic transient species has been determined, which led us to propose a generalized electron attachment scheme for the liquid and gas phases, taking into account the different energy levels of the attaching electrons. A quanto-chemical approach using the ''effective charge'' model has demonstrated that the solvation increases the amide electron affinity and decreases the vertical attachment energy which is in agreement with the gas phase experimental results [fr

  3. Enzymatically and reductively degradable α-amino acid-based poly(ester amide)s: synthesis, cell compatibility, and intracellular anticancer drug delivery.

    Science.gov (United States)

    Sun, Huanli; Cheng, Ru; Deng, Chao; Meng, Fenghua; Dias, Aylvin A; Hendriks, Marc; Feijen, Jan; Zhong, Zhiyuan

    2015-02-09

    A novel and versatile family of enzymatically and reductively degradable α-amino acid-based poly(ester amide)s (SS-PEAs) were developed from solution polycondensation of disulfide-containing di-p-toluenesulfonic acid salts of bis-l-phenylalanine diesters (SS-Phe-2TsOH) with di-p-nitrophenyl adipate (NA) in N,N-dimethylformamide (DMF). SS-PEAs with Mn ranging from 16.6 to 23.6 kg/mol were obtained, depending on NA/SS-Phe-2TsOH molar ratios. The chemical structures of SS-PEAs were confirmed by (1)H NMR and FTIR spectra. Thermal analyses showed that the obtained SS-PEAs were amorphous with a glass transition temperature (Tg) in the range of 35.2-39.5 °C. The in vitro degradation studies of SS-PEA films revealed that SS-PEAs underwent surface erosion in the presence of 0.1 mg/mL α-chymotrypsin and bulk degradation under a reductive environment containing 10 mM dithiothreitol (DTT). The preliminary cell culture studies displayed that SS-PEA films could well support adhesion and proliferation of L929 fibroblast cells, indicating that SS-PEAs have excellent cell compatibility. The nanoparticles prepared from SS-PEA with PVA as a surfactant had an average size of 167 nm in phosphate buffer (PB, 10 mM, pH 7.4). SS-PEA nanoparticles while stable under physiological environment undergo rapid disintegration under an enzymatic or reductive condition. The in vitro drug release studies showed that DOX release was accelerated in the presence of 0.1 mg/mL α-chymotrypsin or 10 mM DTT. Confocal microscopy observation displayed that SS-PEA nanoparticles effectively transported DOX into both drug-sensitive and -resistant MCF-7 cells. MTT assays revealed that DOX-loaded SS-PEA nanoparticles had a high antitumor activity approaching that of free DOX in drug-sensitive MCF-7 cells, while more than 10 times higher than free DOX in drug-resistant MCF-7/ADR cells. These enzymatically and reductively degradable α-amino acid-based poly(ester amide)s have provided an appealing platform for

  4. Effect of inhibition of fatty acid amide hydrolase on MPTP-induced dopaminergic neuronal damage.

    Science.gov (United States)

    Viveros-Paredes, J M; Gonzalez-Castañeda, R E; Escalante-Castañeda, A; Tejeda-Martínez, A R; Castañeda-Achutiguí, F; Flores-Soto, M E

    2017-01-16

    Parkinson's disease (PD) is a neurodegenerative disorder characterised by balance problems, muscle rigidity, and slow movement due to low dopamine levels and loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The endocannabinoid system is known to modulate the nigrostriatal pathway through endogenous ligands such as anandamide (AEA), which is hydrolysed by fatty acid amide hydrolase (FAAH). The purpose of this study was to increase AEA levels using FAAH inhibitor URB597 to evaluate the modulatory effect of AEA on dopaminergic neuronal death induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Our study included 4 experimental groups (n = 6 mice per group): a control group receiving no treatment, a group receiving URB597 (0.2mg/kg) every 3 days for 30 days, a group treated with MPTP (30mg/kg) for 5 days, and a group receiving URB597 and subsequently MPTP injections. Three days after the last dose, we conducted a series of behavioural tests (beam test, pole test, and stride length test) to compare motor coordination between groups. We subsequently analysed immunoreactivity of dopaminergic cells and microglia in the SNpc and striatum. Mice treated with URB597 plus MPTP were found to perform better on behavioural tests than mice receiving MPTP only. According to the immunohistochemistry study, mice receiving MPTP showed fewer dopaminergic cells and fibres in the SNpc and striatum. Animals treated with URB597 plus MPTP displayed increased tyrosine hydroxylase immunoreactivity compared to those treated with MPTP only. Regarding microglial immunoreactivity, the group receiving MPTP showed higher Iba1 immunoreactivity in the striatum and SNpc than did the group treated with URB597 plus MPTP. Our results show that URB597 exerts a protective effect since it inhibits dopaminergic neuronal death, decreases microglial immunoreactivity, and improves MPTP-induced motor alterations. Copyright © 2016 Sociedad Española de Neurología. Publicado

  5. Quantum chemical studies of a model for peptide bond formation. 3. Role of magnesium cation in formation of amide and water from ammonia and glycine

    Science.gov (United States)

    Oie, T.; Loew, G. H.; Burt, S. K.; MacElroy, R. D.

    1984-01-01

    The SN2 reaction between glycine and ammonia molecules with magnesium cation Mg2+ as a catalyst has been studied as a model reaction for Mg(2+)-catalyzed peptide bond formation using the ab initio Hartree-Fock molecular orbital method. As in previous studies of the uncatalyzed and amine-catalyzed reactions between glycine and ammonia, two reaction mechanisms have been examined, i.e., a two-step and a concerted reaction. The stationary points of each reaction including intermediate and transition states have been identified and free energies calculated for all geometry-optimized reaction species to determine the thermodynamics and kinetics of each reaction. Substantial decreases in free energies of activation were found for both reaction mechanisms in the Mg(2+)-catalyzed amide bond formation compared with those in the uncatalyzed and amine-catalyzed amide bond formation. The catalytic effect of the Mg2+ cation is to stabilize both the transition states and intermediate, and it is attributed to the neutralization of the developing negative charge on the electrophile and formation of a conformationally flexible nonplanar five-membered chelate ring structure.

  6. Novel endogenous N-acyl amides activate TRPV1-4 receptors, BV-2 microglia, and are regulated in brain in an acute model of inflammation

    Directory of Open Access Journals (Sweden)

    Siham eRaboune

    2014-08-01

    Full Text Available A family of endogenous lipids, structurally analogous to the endogenous cannabinoid, N-arachidonoyl ethanolamine (Anandamide, and called N-acyl amides have emerged as a family of biologically active compounds at TRP receptors. N-acyl amides are constructed from an acyl group and an amine via an amide bond. This same structure can be modified by changing either the fatty acid or the amide to form potentially hundreds of lipids. More than 70 N-acyl amides have been identified in nature. We have ongoing studies aimed at isolating and characterizing additional members of the family of N-acyl amides in both central and peripheral tissues in mammalian systems. Here, using a unique in-house library of over 70 N-acyl amides we tested the following three hypotheses: 1 Additional N-acyl amides will have activity at TRPV1-4, 2 Acute peripheral injury will drive changes in CNS levels of N-acyl amides, and 3 N-acyl amides will regulate calcium in CNS-derived microglia. Through these studies, we have identified 20 novel N-acyl amides that collectively activate (stimulating or inhibiting TRPV1-4. Using lipid extraction and HPLC coupled to tandem mass spectrometry we showed that levels of at least 10 of these N-acyl amides that activate TRPVs are regulated in brain after intraplantar carrageenan injection. We then screened the BV2 microglial cell line for activity with this N-acyl amide library and found overlap with TRPV receptor activity as well as additional activators of calcium mobilization from these lipids. Together these data provide new insight into the family of N-acyl amides and their roles as signaling molecules at ion channels, in microglia, and in the brain in the context of inflammation.

  7. Decreased oxygen permeability of EVOH through molecular interactions

    Directory of Open Access Journals (Sweden)

    Zs. Peter

    2014-10-01

    Full Text Available Poly(ethylene-co-vinyl alcohol of 48 mol% ethylene content was modified with N,N'-bis(2,2,6,6-tetramethyl-4-piperidyl-isophthalamide (Nylostab SEED to decrease the oxygen permeability of the polymer. The additive was added in a wide concentration range from 0 to 10 wt%. The structure and properties of the polymer were characterized with various methods including differential scanning calorimetry, X-ray diffraction, mechanical testing, optical measurements and oxygen permeation. Interactions were estimated by molecular modeling and infrared spectroscopy. The results showed that oxygen permeation decreased considerably when the additive was added at less than 2.0 wt% concentration. The decrease resulted from the interaction of the hydroxyl groups of the polymer and the amide groups of the additive. The dissolution of the additive in the polymer led to decreased crystallinity, but also to decreased mobility of amorphous molecules. Stiffness and strength, but also deformability increased as a result. Above 2 wt% the additive forms a separate phase leading to the deterioration of properties. The success of the approach represents a novel way to control oxygen permeation in EVOH and in other polymers with similar functional groups capable of strong interactions.

  8. Nanoporous amide networks based on tetraphenyladamantane for selective CO2capture

    KAUST Repository

    Zulfiqar, Sonia

    2016-04-19

    Reduction of anthropogenic CO2 emissions and CO2 separation from post-combustion flue gases are among the imperative issues in the spotlight at present. Hence, it is highly desirable to develop efficient adsorbents for mitigating climate change with possible energy savings. Here, we report the design of a facile one pot catalyst-free synthetic protocol for the generation of three different nitrogen rich nanoporous amide networks (NANs) based on tetraphenyladamantane. Besides the porous architecture, CO2 capturing potential and high thermal stability, these NANs possess notable CO2/N2 selectivity with reasonable retention while increasing the temperature from 273 K to 298 K. The quantum chemical calculations also suggest that CO2 interacts mainly in the region of polar amide groups (-CONH-) present in NANs and this interaction is much stronger than that with N2 thus leading to better selectivity and affirming them as promising contenders for efficient gas separation. © The Royal Society of Chemistry 2016.

  9. Spectroscopic and structural studies of a new para-iodo-N-benzyl amide of salinomycin

    Science.gov (United States)

    Antoszczak, Michał; Janczak, Jan; Rutkowski, Jacek; Brzezinski, Bogumił; Huczyński, Adam

    2017-11-01

    A new para-iodo-N-benzyl amide of salinomycin was synthesized and characterized by NMR, FT-IR, DFT, single crystal X-ray diffraction and theoretical methods. The results obtained for the crystal, in solution and in gas phase provided evidence of pseudo-cyclic structure of this compound stabilized by intramolecular hydrogen bonds. It was shown that the compound studied forms stable 1:1 complexes with monovalent (Li+, Na+, K+, Rb+ and Cs+) and divalent (Mg2+, Ca2+, Sr2+ and Ba2+) cations demonstrating that the chemical modification of salinomycin carboxyl group considerably changes the ionophoretic properties of this antibiotic. For the first time, the ESI MS fragmentations of the complex of para-iodo-N-benzyl amide of salinomycin with Na+ are also discussed in details.

  10. Intramolecular migration of amide hydrogens in protonated peptides upon collisional activation

    DEFF Research Database (Denmark)

    Jørgensen, Thomas J D; Gårdsvoll, Henrik; Ploug, Michael

    2005-01-01

    if collision-induced dissociation (CID) should provide reliable site-specific information from (1)H/(2)H exchange experiments. We have explored a series of unique, regioselectively deuterium-labeled peptides as model systems to probe for intramolecular amide hydrogen migration under low-energy collisional...... are protected against exchange with the solvent, while the amide hydrogens of the nonbinding sequences exchange rapidly with the solvent. We have utilized such long-lived complexes to generate peptides labeled with deuterium in either the binding or nonbinding region, and the expected regioselectivity...... of this labeling was confirmed after pepsin proteolysis. CID of such deuterated peptides, [M + 2H](2+), yielded fragment ions (b- and y-ions) having a deuterium content that resemble the theoretical values calculated for 100% scrambling. Thus, complete randomization of all hydrogen atoms attached to nitrogen...

  11. Amides from Piper capense with CNS Activity – A Preliminary SAR Analysis

    Directory of Open Access Journals (Sweden)

    Hasse B. Rasmussen

    2009-09-01

    Full Text Available Piper capense L.f. (Piperaceae is used traditionally in South Africa as a sleep inducing remedy. Bioassay-guided fractionation of the roots of P. capense led to the isolation of piperine (1 and 4,5-dihydropiperine (2, which showed moderate affinity for the benzodiazepine site on the GABAA receptor (IC50 values of 1.2 mM and 1.0 mM, respectively. The present study suggests that strict structural properties of the amides are essential for affinity. Taken together, these observations suggest that the carbon chain must contain not less than four carbons, and that a conjugated double bond, adjacent to the amide group, is necessary for binding to the receptor and that the amine part should be bulky.

  12. Fatty Amides from Crude Rice Bran Oil as Green Corrosion Inhibitors

    Directory of Open Access Journals (Sweden)

    E. Reyes-Dorantes

    2017-01-01

    Full Text Available Due to its high oil content, this research proposes the use of an agroindustrial byproduct (rice bran as a sustainable option for the synthesis of corrosion inhibitors. From the crude rice bran oil, the synthesis of fatty amide-type corrosion inhibitors was carried out. The corrosion inhibitory capacity of the fatty amides was evaluated on an API X-70 steel using electrochemical techniques such as real-time corrosion monitoring and potentiodynamic polarization curves. As a corrosive medium, a CO2-saturated solution (3.5% NaCl was used at three temperatures (30, 50, and 70°C and different concentrations of inhibitor (0, 5, 10, 25, 50, and 100 ppm. The results demonstrate that the sustainable use of agroindustrial byproducts is a good alternative to the synthesis of environmentally friendly inhibitors with high corrosion inhibition efficiencies.

  13. Chemical constituents from red algae Bostrychia radicans (Rhodomelaceae): new amides and phenolic compounds

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Ana Ligia Leandrini de; Silva, Denise B. da; Lopes, Norberto P.; Debonsi, Hosana M. [Universidade de Sao Paulo (FCFRP/USP), Ribeirao Preto, SP (Brazil). Fac. de Ciencias Farmaceuticas de Ribeirao Preto. Dept. de Quimica e Fisica; Yokoya, Nair S., E-mail: hosana@fcfrp.usp.br [Instituto de Botanica, Sao Paulo, SP (Brazil). Secao de Ficologia

    2012-07-01

    This study describes the isolation and structural determination of two amides, isolated for the first time: N,4-dihydroxy-N-(2'-hydroxyethyl)-benzamide (0.019%) and N,4-dihydroxy-N-(2'-hydroxyethyl)-benzeneacetamide (0.023%). These amides, produced by the red macroalgae Bostrychia radicans, had their structures assigned by NMR spectral data and MS analyses. In addition, this chemical study led to the isolation of cholesterol, heptadecane, squalene, trans-phytol, neophytadiene, tetradecanoic and hexadecanoic acids, methyl hexadecanoate and methyl 9-octadecenoate, 4-(methoxymethyl)-phenol, 4-hydroxybenzaldehyde, methyl 4-hydroxybenzeneacetate, methyl 2-hydroxy-3-(4-hydroxyphenyl)-propanoate, hydroquinone, methyl 4-hydroxymandelate, methyl 4-hydroxybenzoate, 4-hydroxybenzeneacetic acid and (4-hydroxyphenyl)-oxo-acetaldehyde. This is the first report concerning these compounds in B. radicans, contributing by illustrating the chemical diversity within the Rhodomelaceae family. (author)

  14. Synthesis and characterization of poly(ester amide from remewable resources through melt polycondensation

    Directory of Open Access Journals (Sweden)

    B. B. Wang

    2014-01-01

    Full Text Available Biodegradable poly(ester amides (PEAs were synthesized from lactic acid and 11-aminoundecanoic acid via melt polycondensation. Molecular weights, chemical structures and thermal properties of the poly(ester amides were characterized in terms of gel permeation chromatography (GPC, Fourier transform infrared spectroscopy (FTIR, 1H nuclear magnetic resonance (1H NMR, differential scanning calorimetry (DSC and thermogravimetric analysis (TGA, respectively. The PEAs have low molecular weights and display a lower cold crystallization temperature as well as smaller crystallinity by comparison with the pure poly(lactic acid (PLA. The incorporation of the 11-aminoundecanoic acid into the PLA chain not only improved the thermal stability but changed the decomposition process.

  15. Mechanical characterization of porous asphalt mixes modified with fatty acid amides -FAA-

    Directory of Open Access Journals (Sweden)

    Vanessa Senior Arrieta

    2017-01-01

    Full Text Available Porous asphalt mixes (PAM, form a special road surface for asphalt pavement structures, have a special particle size distribution that lets infiltrate to the runoff storm water through of it because of its voids content about 20 %. Many researchers conducted studies and have concluded that the use of modified asphalts is completely necessary to design PAM. Organic and chemical additives and special procedures as foamed asphalt have enhanced the performance of PAM, during their service life. This paper is focused on the mechanical characterization of PAM and how the asphalt modified with fatty acid amides, influenced on their behavior and performance. Based on an experimental methodology with laboratory tests aimed at establishing a comparison between porous asphalt mixes, using for its design and production a penetration 60-70 pure asphalt and another one asphalt modified with fatty acid amides.

  16. Drinking amid abundant illicit drugs. The Vietnam case.

    Science.gov (United States)

    Goodwin, D W; Davis, D H; Robins, L N

    1975-02-01

    We studied drinking patterns and problems of 451 US Army enlisted men after their return from Vietnam. Before Vietnam, nearly half were regular drinkers and one quarter had drinking problems. Problem drinking declined in Vietnam as opiate use rose sharply; half had tried opiates and 20% were opiate dependent. After Vietnam, opiate use decreased (now less than 2% opiate dependent) and problem drinking again became ascendant. At time of interview, 17% had drunk in an alcoholic pattern at some period in their lives and another 41% had had problems from drinking. The younger men were more likely to have had problems. Alcholism predictors included:becoming intoxicated at an early age; dropping out of school; truancy and expulsion from school; and having a father with a history of alcoholism or arrests.

  17. Safety of intradiscal injection and biocompatibility of polyester amide microspheres in a canine model predisposed to intervertebral disc degeneration

    NARCIS (Netherlands)

    Willems, Nicole; Mihov, George; Grinwis, Guy C M; van Dijk, Maarten; Schumann, Detlef; Bos, Clemens; Strijkers, Gustav J; Dhert, Wouter J A; Meij, Björn P; Creemers, Laura B.; Tryfonidou, Marianna A

    Repair of degenerated intervertebral discs (IVD) might be established via intradiscal delivery of biologic therapies. Polyester amide polymers (PEA) were evaluated for in vitro cytotoxicity and in vivo biocompatibility, and thereafter intradiscal application of PEA microspheres (PEAMs) in a canine

  18. Tissue and plasma concentrations of amidated and glycine-extended glucagon-like peptide I in humans

    DEFF Research Database (Denmark)

    Orskov, C; Rabenhøj, L; Wettergren, A

    1994-01-01

    Using specific radioimmunoassays, we studied the occurrence of amidated and glycine-extended glucagon-like peptide I (GLP-I) molecules in the human small intestine and pancreas and in the circulation system in response to a breakfast meal. Through gel permeation chromatography of extracts...... plasma were 7 +/- 1 and 6 +/- 1 pM, respectively (n = 6). In response to a breakfast meal, the concentration of amidated GLP-I rose significantly amounting to 41 +/- 5 pM 90 min after the meal ingestion, whereas the concentration of glycine-extended GLP-I only rose slightly to a maximum of 10 +/- 1 p......M. Thus, both amidated and glycine-extended GLP-I molecules are produced in the small intestine and in the pancreas in humans. Both amidated and glycine-extended GLP-I are measurable in fasting plasma.(ABSTRACT TRUNCATED AT 250 WORDS)...

  19. N-acetyl lysyltyrosylcysteine amide inhibits myeloperoxidase, a novel tripeptide inhibitor1[S

    OpenAIRE

    Zhang, Hao; Jing, Xigang; Shi, Yang; Xu, Hao; Du, Jianhai; Guan, Tongju; Weihrauch, Dorothee; Jones, Deron W.; Wang, Weiling; Gourlay, David; Oldham, Keith T.; Hillery, Cheryl A.; Pritchard, Kirkwood A.

    2013-01-01

    Myeloperoxidase (MPO) plays important roles in disease by increasing oxidative and nitrosative stress and oxidizing lipoproteins. Here we report N-acetyl lysyltyrosylcysteine amide (KYC) is an effective inhibitor of MPO activity. We show KYC inhibits MPO-mediated hypochlorous acid (HOCl) formation and nitration/oxidation of LDL. Disulfide is the major product of MPO-mediated KYC oxidation. KYC (⩽4,000 μM) does not induce cytotoxicity in bovine aortic endothelial cells (BAECs). KYC inhibits HO...

  20. Plasma-enabled sensing of urea and related amides on polyaniline

    Czech Academy of Sciences Publication Activity Database

    Puliyalil, H.; Slobodian, P.; Sedlacik, M.; Benlikaya, R.; Říha, Pavel; Ostrikov, K.; Cvelbar, U.

    2016-01-01

    Roč. 10, č. 2 (2016), s. 265-272 ISSN 2095-0179 Grant - others:Ministerstvo školství, mládeže a tělovýchovy (MŠMT)(CZ) LO1504 Institutional support: RVO:67985874 Keywords : gas sensing * urea * PANI * amides * plasma Subject RIV: BK - Fluid Dynamics Impact factor: 1.712, year: 2016

  1. Ruthenium-catalyzed C7 amidation of indoline C-H bonds with sulfonyl azides.

    Science.gov (United States)

    Pan, Changduo; Abdukader, Ablimit; Han, Jie; Cheng, Yixiang; Zhu, Chengjian

    2014-03-24

    A ruthenium-catalyzed direct C7 amidation of indoline C-H bonds with sulfonyl azides was developed. This procedure allows the synthesis of a variety of 7-amino-substituted indolines, which are useful in pharmaceutical. The good functional tolerances, as well as the mild conditions, are prominent feature of this method. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Plasma-enabled sensing of urea and related amides on polyaniline

    Czech Academy of Sciences Publication Activity Database

    Puliyalil, H.; Slobodian, P.; Sedlacik, M.; Benlikaya, R.; Říha, Pavel; Ostrikov, K.; Cvelbar, U.

    2016-01-01

    Roč. 10, č. 2 (2016), s. 265-272 ISSN 2095-0179 Grant - others:Ministerstvo školství, mládeže a tělovýchovy (MŠMT)(CZ) LO1504 Institutional support: RVO:67985874 Keywords : gas sensing * urea * PANI * amides * plasma Subject RIV: BK - Fluid Dynamics Impact factor : 1.712, year: 2016

  3. Nitrotriazole- and imidazole-based amides and sulfonamides as antitubercular agents.

    Science.gov (United States)

    Papadopoulou, Maria V; Bloomer, William D; Rosenzweig, Howard S; Arena, Alexander; Arrieta, Francisco; Rebolledo, Joseph C J; Smith, Diane K

    2014-11-01

    Twenty-three 3-nitrotriazole-based and 2-nitroimidazole-based amides and sulfonamides were screened for antitubercular (anti-TB) activity in aerobic Mycobacterium tuberculosis H37Rv by using the BacTiter-Glo (BTG) microbial cell viability assay. In general, 3-nitrotriazole-based sulfonamides demonstrated anti-TB activity, whereas 3-nitrotriazole-based amides and 2-nitroimidazole-based amides and sulfonamides were inactive. Three 3-nitrotriazole-based sulfonamides (compounds 4, 2, and 7) demonstrated 50% inhibitory concentration (IC50), IC90, and MIC values of 0.38, 0.43, and 1.56 μM (compound 4), 0.57, 0.98, and 3.13 μM (compound 2), and 0.79, 0.87, and 3.13 μM (compound 7), respectively. For 3-nitrotriazole-based sulfonamides, anti-TB activity increased with lipophilicity, whereas the one-electron reduction potential (E1/2) did not play a role. 2-Nitroimidazole-based analogs, which were inactive in the BTG assay, were significantly more active in the low-oxygen assay and more active than the 3-nitrotriazoles. All active nitrotriazoles in the BTG assay were similarly active or more potent (lower MIC values) against resistant strains, with the exception of compounds 2, 3, 4, and 8, which demonstrated greater MIC values against isoniazid-resistant strains. Five 3-nitrotriazole-based sulfonamides demonstrated activity in infected murine J774 macrophages, causing log reductions similar to those seen with rifampin. However, some compounds caused toxicity in uninfected macrophages. In conclusion, the classes of 3-nitrotriazole-based amides and sulfonamides merit further investigation as potential antitubercular agents. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  4. Susceptibility of Apis mellifera (Hymenoptera: Apidae) to pellitorine, an amide isolated from Piper tuberculatum (Piperaceae)

    OpenAIRE

    Miranda, José; Hosana Maria Debonsi Navickiene,; Nogueira-Couto, Regina; Sérgio Antônio De Bortoli,; Kato, Massuo; Vanderlan Da Silva Bolzani,; Furlan, Maysa

    2003-01-01

    International audience; The acute toxicity of pellitorine, an amide isolated from Piper tuberculatum (Piperaceae) which is studied as a biopesticide in European corner borer, was evaluated on larvae and newly emerged adults of honeybee Apis mellifera by means of contact and ingestion bioassays. Workers in the larval and adult phase were separated in groups, which received pellitorine in different concentrations. The larvae were maintained in their own original cells, receiving feeding and nor...

  5. Uranium and plutonium extraction by N,N-dialkyl-amides using multistage mixer-settler extractors

    Energy Technology Data Exchange (ETDEWEB)

    Ban, Y.; Hotoku, S.; Tsutsui, N.; Suzuki, A.; Tsubata, Y.; Matsumura, T.

    2016-07-01

    N,N-Dialkyl-amides (mono-amides) are known as extractants for U and Pu, and many studies have been carried out mainly by single-stage batch method. We have focused on two mono amides: N,N-di(2-ethylhexyl)-2,2-dimethylpropanamide (DEHDMPA) and N,N-di(2-ethylhexyl)butanamide (DEHBA), and proposed a multistage extraction process for recovering U and Pu by these mono-amides. A continuous counter-current experiment was carried out to demonstrate the validity of this process. This process consisted of two cycles, and the first cycle and the second cycle employed DEHDMPA and DEHBA as extractants, respectively. The feed solution for the first cycle was 5.1 mol/dm{sup 3} (M) nitric acid containing 0.92 M U, 1.6 mM Pu, and 0.6 mM Np. The raffinate collected in the first cycle was used as the feed for the second cycle. The ratios of U recovered in the U fraction and U-Pu fraction were 99.1% and 0.8%, respectively, and the ratios of U in the used solvents were <0.04%. The ratio of Pu recovered in the U-Pu fraction was 99.7%, and the ratio of Pu in the used solvents was in the order of 10{sup -3} - 10{sup -4}%. The concentration ratio of U with respect to Pu in the U-Pu fraction was 9, and this indicated that Pu was not isolated. The decontamination factor of U with respect to Pu in the U fraction was obtained as 4.5*10{sup 5}. These results supported the validity of the proposed process. (authors)

  6. Interacting Blends of Novel Unsaturated Polyester Amide Resin with Vinyl Acetate

    OpenAIRE

    Patel, H. S.; Panchal, K. K.; Patel, S. R.; Desai, S. N.

    2004-01-01

    Novel unsaturated poly (ester- amide) resins (UPEAs) were prepared by the reaction between an epoxy resin, namely diglycidyl ether of bisphenol–A (DGEBA) and unsaturated aliphatic bisamic acids using a base catalyst. These UPEAs were then blended with a vinyl monomer namely, Vinyl acetate (VA) to produce a homogeneous resin syrup. The curing of these UPEAs-VA resin blends was carried out by using benzoyl peroxide (BPO) as an initiator for the radical polymerization and was monitored by using ...

  7. solid-phase peptide synthesis of isotocin with amide of asparagine ...

    African Journals Online (AJOL)

    Isotocin, a nonapeptide amide, was synthesised on a benzhydryl-resin using the Boc-strategy. Benzyl group was used in the protection of the side-chains of tyrosine, serine and cysteine. Tetralinyl group was used to protect asparagine side-chain. TFMSA-TFA-thioanisole-1,2-ethanedithiol (2:20:2:1 v/v) was used on the ...

  8. Direct enantioselective conjugate addition of carboxylic acids with chiral lithium amides as traceless auxiliaries.

    Science.gov (United States)

    Lu, Ping; Jackson, Jeffrey J; Eickhoff, John A; Zakarian, Armen

    2015-01-21

    Michael addition is a premier synthetic method for carbon-carbon and carbon-heteroatom bond formation. Using chiral dilithium amides as traceless auxiliaries, we report the direct enantioselective Michael addition of carboxylic acids. A free carboxyl group in the product provides versatility for further functionalization, and the chiral reagent can be readily recovered by extraction with aqueous acid. The method has been applied in the enantioselective total synthesis of the purported structure of pulveraven B.

  9. Direct Catalytic Asymmetric Mannich-Type Reaction of α-N3 Amide.

    Science.gov (United States)

    Sun, Zhongdong; Weidner, Karin; Kumagai, Naoya; Shibasaki, Masakatsu

    2015-12-01

    An α-N3 7-azaindoline amide serves as a latent enolate to directly engage in an asymmetric Mannich-type reaction with N-thiophosphinoyl imines by the action of a cooperative catalyst. The thus-obtained highly enantioenriched anti-adduct was transformed into β-amino-α-azido acid in high yield by simple acidic treatment. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. A new feruloyl amide derivative from the fruits of Tribulus terrestris.

    Science.gov (United States)

    Zhang, Xiaopo; Wei, Na; Huang, Jian; Tan, Yinfeng; Jin, Dejun

    2012-01-01

    A new feruloyl amide derivative, named tribulusamide C, was isolated from the fruits of Tribulus terrestris. Its structure was determined on the basis of spectroscopic analysis including IR, 1-D-, 2-D-NMR and HR-ESI-MS. The structure of tribulusamide C was characterised by a unit of pyrrolidine-2,5-dione, which distinguished it from other lignanamides previously isolated from the fruits of T. terrestris.

  11. Arg-Phe-amide-like peptides in the primitive nervous systems of coelenterates

    DEFF Research Database (Denmark)

    Grimmelikhuijzen, C J; Ebbesen, Ditte Graff

    1985-01-01

    By using immunocytochemistry and radioimmunoassays, several substances resembling vertebrate or invertebrate neuropeptides have been found in the nervous systems of coelenterates. The most abundant neuropeptides were those related to the molluscan neuropeptide Phe-Met-Arg-Phe-amide (FMRFamide......). Of antisera against different fragments of FMRFamide, those against RFamide were superior in recognizing the coelenterate peptide. Incubation of whole mounts with these RFamide antisera visualized the coelenterate nervous system in such a detail as has previously not been possible. By using a radioimmunoassay...

  12. Synthesis of Amidines from Amides Using a Nickel-Catalyzed Decarbonylative Amination through CO Extrusion Intramolecular Recombination Fragment Coupling.

    Science.gov (United States)

    Liu, Xiangqian; Yue, Huifeng; Jia, Jiaqi; Guo, Lin; Rueping, Magnus

    2017-09-04

    A catalytic synthesis of amidines from amides has been established for the first time. The newly developed CO extrusion recombination process takes advantage of an inexpensive nickel(II) catalyst and provides the corresponding amidines with high efficiency. The intramolecular fragment coupling shows excellent chemoselectivity, starts from readily available amides, and provides a valuable alternative amidine synthesis protocol. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Biodegradable gadolinium-chelated cationic poly(urethane amide) copolymers for gene transfection and magnetic resonance imaging

    International Nuclear Information System (INIS)

    Gao, Xiaolong; Wang, Gangmin; Shi, Ting; Shao, Zhihong; Zhao, Peng; Shi, Donglu; Ren, Jie; Lin, Chao; Wang, Peijun

    2016-01-01

    Theranostic nano-polyplexes containing gene and imaging agents hold a great promise for tumor diagnosis and therapy. In this work, we develop a group of new gadolinium (Gd)-chelated cationic poly(urethane amide)s for gene delivery and T 1 -weighted magnetic resonance (MR) imaging. Cationic poly(urethane amide)s (denoted as CPUAs) having multiple disulfide bonds, urethane and amide linkages were synthesized by stepwise polycondensation reaction between 1,4-bis(3-aminopropyl)piperazine and a mixture of di(4-nitrophenyl)-2, 2′-dithiodiethanocarbonate (DTDE-PNC) and diethylenetriaminepentaacetic acid (DTPA) dianhydride at varied molar ratios. Then, Gd-chelated CPUAs (denoted as GdCPUAs) were produced by chelating Gd(III) ions with DTPA residues of CPUAs. These GdCPUAs could condense gene into nanosized and positively-charged polyplexes in a physiological condition and, however, liberated gene in an intracellular reductive environment. In vitro transfection experiments revealed that the GdCPUA at a DTDE-PNC/DTPA residue molar ratio of 85/15 induced the highest transfection efficiency in different cancer cells. This efficiency was higher than that yielded with 25 kDa branched polyethylenimine as a positive control. GdCPUAs and their polyplexes exhibited low cytotoxicity when an optimal transfection activity was detected. Moreover, GdCPUAs may serve as contrast agents for T 1 -weighted magnetic resonance imaging. The results of this work indicate that biodegradable Gd-chelated cationic poly(urethane amide) copolymers have high potential for tumor theranostics. - Highlights: • Novel cationic gadolinium-chelated poly(urethane amide)s (GdCPUAs) are prepared. • GdCPUAs can induce a high transfection efficacy in different cancer cells. • GdCPUAs reveal good cyto-compatibility against cancer cells. • GdCPUAs may be applied as T 1 -contrast agents for magnetic resonance imaging. • GdCPUAs hold high potential for cancer theranostics.

  14. A comprehensive study of the complexation of alkali metal cations by lower rim calix[4]arene amide derivatives.

    Science.gov (United States)

    Horvat, Gordan; Frkanec, Leo; Cindro, Nikola; Tomišić, Vladislav

    2017-09-13

    The complexation of alkali metal cations by lower rim N,N-dihexylacetamide (L1) and newly synthesized N-hexyl-N-methylacetamide (L2) calix[4]arene tertiary-amide derivatives was thoroughly studied at 25 °C in acetonitrile (MeCN), benzonitrile (PhCN), and methanol (MeOH) by means of direct and competitive microcalorimetric titrations, and UV and 1 H NMR spectroscopies. In addition, by measuring the ligands' solubilities, the solution (transfer) Gibbs energies of the ligands and their alkali metal complexes were obtained. The inclusion of solvent molecules in the free and complexed calixarene hydrophobic cavities was also investigated. Computational (classical molecular dynamics) investigations of the studied systems were also carried out. The obtained results were compared with those previously obtained by studying the complexation ability of an N-hexylacetamidecalix[4]arene secondary-amide derivative (L3). The stability constants of 1 : 1 complexes were determined in all solvents used (the values obtained by different methods being in excellent agreement), as were the corresponding complexation enthalpies and entropies. Almost all of the examined reactions were enthalpically controlled. The most striking exceptions were reactions of Li + with both ligands in methanol, for which the entropic contribution to the reaction Gibbs energy was substantial due the entropically favourable desolvation of the smallest lithium cation. The thermodynamic stabilities of the complexes were quite solvent dependent (the stability decreased in the solvent order: MeCN > PhCN ≫ MeOH), which could be accounted for by considering the differences in the solvation of the ligand and free and complexed alkali metal cations in the solvents used. Comparison of the stability constants of the ligand L1 and L2 complexes clearly revealed that the higher electron-donating ability of the hexyl with respect to the methyl group is of considerable importance in determining the equilibria of the

  15. Synthesis and thermal degradation characterization of novel poly(phosphazene-aryl amides

    Directory of Open Access Journals (Sweden)

    Z. P. Zhao

    2012-04-01

    Full Text Available New fully aromatic poly(phosphazene-aryl amides were prepared by polycondensation reaction of our synthesized aromatic diamine: 1,1,3,5-tetraphenoxy-4,6-bis(4-aminophenoxyoligocyclotriphosphazene (monomer 1 with terephthaloyl dichloride. Their chemical structure and composition were characterized by elemental analysis, 1H and 31P NMR (Nuclear Magnetic Resonance, and FT-IR (Fourier transform infrared spectroscopy, whereas their thermal degradation properties were determined by DSC (Differential Scanning Calorimetry and TGA (Thermal Gravimertic Analysis techniques. The solid residues of all samples were analysed by FT-IR and SEM (Scanning Electron Microscopy. Compared to conventional PPTA (poly(p-phenylene terephthamide, PPAA (poly(phosphazene-aryl amide shows excellent thermal stability and solubility in polar protic solvents. All poly(phosphazene-aryl amides show two thermal degradation in the temperature range 150–600°C. The monomer 1, due to its structure, shows the first maximum rate of thermal decomposition temperature around 150–350°C, which may be due to the decomposition of the P–O–C bone. Morphology of the solid residues by Scanning Electron Microscope exhibit that the granular of the solid residues gradual disappearance with the increase of monomer 1 content. The surface layer of PPAA solid residues has been grumous, for the syneresis of P–O–P took place.

  16. Substituted Amides of Pyrazine-2-carboxylic acids: Synthesis and Biological Activity

    Directory of Open Access Journals (Sweden)

    Katarina Kralova

    2002-03-01

    Full Text Available Condensation of 6-chloro-, 5-tert-butyl- or 6-chloro-5-tert-butylpyrazine-2-carboxylic acid chloride with ring substituted anilines yielded a series of amides, which were tested for their in vitro antimycobacterial, antifungal and photosynthesis-inhibiting activities. The highest antituberculotic activity (72% inhibition against Mycobacterium tuberculosis and the highest lipophilicity (log P = 6.85 were shown by the 3,5-bistrifluoromethylphenyl amide of 5-tert-butyl-6-chloropyrazine-2-carboxylic acid (2o. The 3-methylphenyl amides of 6-chloro- and 5-tert-butyl-6-chloro-pyrazine-2-carboxylic acid (2d and 2f exhibited only a poor in vitro antifungal effect (MIC = 31.25-500 μmol·dm-3 against all strains tested, although the latter was the most active antialgal compound (IC50 = 0.063 mmol·dm-3. The most active inhibitor of oxygen evolution rate in spinach chloroplasts was the (3,5-bis-trifluoromethylphenylamide of 6-chloropyrazine-2-carboxylic acid (2m, IC50 = 0.026 mmol·dm-3.

  17. Synthesis and evaluation of bile acid amides of [Formula: see text]-cyanostilbenes as anticancer agents.

    Science.gov (United States)

    Agarwal, Devesh S; Singh, Rajnish Prakash; Lohitesh, K; Jha, Prabhat N; Chowdhury, Rajdeep; Sakhuja, Rajeev

    2017-12-13

    A series of amino-substituted [Formula: see text]-cyanostilbene derivatives and their bile acid (cholic and deoxycholic acid) amides were designed and synthesized. A comparative study on the anticancer and antibacterial activity evaluation on the synthesized analogs was carried against the human osteosarcoma (HOS) cancer cell line, and two gram -ve (E. coli and S. typhi) and two gram [Formula: see text]ve (B. subtilis and S. aureus) bacterial strains. All the cholic acid [Formula: see text]-cyanostilbene amides showed an [Formula: see text] in the range 2-13 [Formula: see text] against human osteosarcoma cells (HOS) with the most active analog (6g) possessing an [Formula: see text] of [Formula: see text]. One of the amino-substituted [Formula: see text]-cyanostilbene, 4e, was found to possess an [Formula: see text] of [Formula: see text]. An increase in the number of cells at the sub-[Formula: see text] phase of the cell was observed in the in vitro cell cycle analysis of two most active compounds in the series (4e, 6g) suggesting a clear indication toward induction of apoptotic cascade. With respect to antibacterial screening, amino-substituted [Formula: see text]-cyanostilbenes were found to be more active than their corresponding bile acid amides. The synthesized compounds were also subjected to in silico study to predict their physiochemical properties and drug-likeness score.

  18. On the relationship between NMR-derived amide order parameters and protein backbone entropy changes.

    Science.gov (United States)

    Sharp, Kim A; O'Brien, Evan; Kasinath, Vignesh; Wand, A Joshua

    2015-05-01

    Molecular dynamics simulations are used to analyze the relationship between NMR-derived squared generalized order parameters of amide NH groups and backbone entropy. Amide order parameters (O(2) NH ) are largely determined by the secondary structure and average values appear unrelated to the overall flexibility of the protein. However, analysis of the more flexible subset (O(2) NH  entropy than that reported by the side chain methyl axis order parameters, O(2) axis . A calibration curve for backbone entropy vs. O(2) NH is developed, which accounts for both correlations between amide group motions of different residues, and correlations between backbone and side chain motions. This calibration curve can be used with experimental values of O(2) NH changes obtained by NMR relaxation measurements to extract backbone entropy changes, for example, upon ligand binding. In conjunction with our previous calibration for side chain entropy derived from measured O(2) axis values this provides a prescription for determination of the total protein conformational entropy changes from NMR relaxation measurements. © 2015 Wiley Periodicals, Inc.

  19. Amide group anchored glucose oxidase based anodic catalysts for high performance enzymatic biofuel cell

    Science.gov (United States)

    Chung, Yongjin; Ahn, Yeonjoo; Kim, Do-Heyoung; Kwon, Yongchai

    2017-01-01

    A new enzyme catalyst is formed by fabricating gold nano particle (GNP)-glucose oxidase (GOx) clusters that are then attached to polyethyleneimine (PEI) and carbon nanotube (CNT) with cross-linkable terephthalaldehyde (TPA) (TPA/[CNT/PEI/GOx-GNP]). Especially, amide bonds belonging to TPA play an anchor role for incorporating rigid bonding among GNP, GOx and CNT/PEI, while middle size GNP is well bonded with thiol group of GOx to form strong GNP-GOx cluster. Those bonds are identified by chemical and electrochemical characterizations like XPS and cyclic voltammogram. The anchording effect of amide bonds induces fast electron transfer and strong chemical bonding, resulting in enhancements in (i) catalytic activity, (ii) amount of immobilized GOx and (ii) performance of enzymatic biofuel cell (EBC) including the catalyst. Regarding the catalytic activity, the TPA/[CNT/PEI/GOx-GNP] produces high electron transfer rate constant (6 s-1), high glucose sensitivity (68 μA mM-1 cm-2), high maximum current density (113 μA cm-2), low charge transfer resistance (17.0 Ω cm2) and long-lasting durability while its chemical structure is characterized by XPS confirming large portion of amide bond. In EBC measurement, it has high maximum power density (0.94 mW cm-2) compatible with catalytic acitivity measurements.

  20. Amides from Piper nigrum L. with dissimilar effects on melanocyte proliferation in-vitro.

    Science.gov (United States)

    Lin, Zhixiu; Liao, Yonghong; Venkatasamy, Radhakrishnan; Hider, Robert C; Soumyanath, Amala

    2007-04-01

    Melanocyte proliferation stimulants are of interest as potential treatments for the depigmentary skin disorder, vitiligo. Piper nigrum L. (Piperaceae) fruit (black pepper) water extract and its main alkaloid, piperine (1), promote melanocyte proliferation in-vitro. A crude chloroform extract of P. nigrum containing piperine was more stimulatory than an equivalent concentration of the pure compound, suggesting the presence of other active components. Piperine (1), guineensine (2), pipericide (3), N-feruloyltyramine (4) and N-isobutyl-2E, 4E-dodecadienamide (5) were isolated from the chloroform extract. Their activity was compared with piperine and with commercial piperlongumine (6) and safrole (7), and synthetically prepared piperettine (8), piperlonguminine (9) and 1-(3, 4-methylenedioxyphenyl)-decane (10). Compounds 6-10 either occur in P. nigrum or are structurally related. Compounds 1, 2, 3, 8 and 9 stimulated melanocyte proliferation, whereas 4, 5, 6, 7 and 10 did not. Comparison of structures suggests that the methylenedioxyphenyl function is essential for melanocyte stimulatory activity. Only those compounds also possessing an amide group were active, although the amino component of the amide group and chain linking it to the methylenedioxyphenyl group can vary. P. nigrum, therefore, contains several amides with the ability to stimulate melanocyte proliferation. This finding supports the traditional use of P. nigrum extracts in vitiligo and provides new lead compounds for drug development for this disease.

  1. Dysfunction in fatty acid amide hydrolase is associated with depressive-like behavior in Wistar Kyoto rats.

    Directory of Open Access Journals (Sweden)

    K Yaragudri Vinod

    Full Text Available BACKGROUND: While the etiology of depression is not clearly understood at the present time, this mental disorder is thought be a complex and multifactorial trait with important genetic and environmental contributing factors. METHODOLOGY/PRINCIPAL FINDINGS: The role of the endocannabinoid (eCB system in depressive behavior was examined in Wistar Kyoto (WKY rat strain, a genetic model of depression. Our findings revealed selective abnormalities in the eCB system in the brains of WKY rats compared to Wistar (WIS rats. Immunoblot analysis indicated significantly higher levels of fatty acid amide hydrolase (FAAH in frontal cortex and hippocampus of WKY rats with no alteration in the level of N-arachidonyl phosphatidyl ethanolamine specific phospholipase-D (NAPE-PLD. Significantly higher levels of CB1 receptor-mediated G-protein coupling and lower levels of anandamide (AEA were found in frontal cortex and hippocampus of WKY rats. While the levels of brain derived neurotropic factor (BDNF were significantly lower in frontal cortex and hippocampus of WKY rats compared to WIS rats, pharmacological inhibition of FAAH elevated BDNF levels in WKY rats. Inhibition of FAAH enzyme also significantly increased sucrose consumption and decreased immobility in the forced swim test in WKY rats. CONCLUSIONS/SIGNIFICANCE: These findings suggest a critical role for the eCB system and BDNF in the genetic predisposition to depressive-like behavior in WKY rats and point to the potential therapeutic utility of eCB enhancing agents in depressive disorder.

  2. Grafting of methacryl amide onto γ-irradiated silk fiber and several physical properties of the grafted-silk

    International Nuclear Information System (INIS)

    Tsukada, Masuhio; Aoki, Akira

    1985-01-01

    Strength-strain measurement and DSC were carried out in order to analyze the physical properties of Methacryl amide (MAA)-grafted silk fibers, which had been degummed and irradiated with gamma rays (total dose of gamma rays 1.05 Mrad) prior to the MAA graft processing. Strength, elongation, initile tensile resistance and tensile elasticity of MAA-grafted silk fibers were very similar to those of untreated silk fibers. The degree of grafting for MAA-grafted silk was about 40-42 % regardless of gamma irradiation treatment, while the denier of grafted silk was about 30 % greater than that of untreated silk fiber. Water content and humidity absorption power of the silk fiber markedly increased by the MAA grafting. However, strength and elongation of MAA-grafted silk fiber decreased appeciably compared with the untreated silk fiber. Initial tensile resistance and tensile elasticity of MAA-grafted silk fiber remained uncharged even after MAA grafting. Tensile elasticity of MAA-grafted silk fiber which had been irradiated with gamma rays and successively degummed slightly increased with the other MAA-grafted silk fibers. (author)

  3. Development of analytical method used for the estimation of potassium amide in liquid ammonia at HWP (Tuticorin)

    International Nuclear Information System (INIS)

    Ramanathan, A.V.

    2007-01-01

    Potassium amide in liquid ammonia is used as a homogeneous catalyst in mono-thermal ammonia-hydrogen isotopic chemical exchange process employed for the manufacture of heavy water. Estimation of concentration of potassium amide in liquid ammonia is vital for checking whether it is sufficient for catalysis in isotopic exchange towers or for purification in purifiers in the Heavy Water Plants. This estimation was carried out earlier by the conventional method involving evaporation of ammonia, decomposition of potassium amide with water and titration of liberated ammonia with sulphuric acid. This method has been replaced by a newly developed method involving direct titration of potassium amide in ammonia with ammonium bromide. This new method is based on the principle that ammonium bromide and potassium amide act as acid and base respectively in the non-aqueous solvent medium, liquid ammonia. This method has not only proved to be an alternative method of estimation of potassium amide in liquid ammonia but also has been serving as a developed analytical method, because it is faster (with fewer steps), more accurate, safer (as it excludes the use of corrosive sulphuric acid needed for the conventional method) and more convenient (as it doesn't need specially designed apparatus and inert gas like dry nitrogen used in the conventional method). (author)

  4. Fragrance Release from the Surface of Branched Poly (Amide S

    Directory of Open Access Journals (Sweden)

    T. Youngs

    2005-01-01

    Full Text Available Enzymes are powerful tools in organic synthesis that are able to catalyse a wide variety of selective chemical transformations under mild and environmentally friendly conditions. Enzymes such as the lipases have also found applications in the synthesis and degradation of polymeric materials. However, the use of these natural catalysts in the synthesis and the post-synthetic modification of dendrimers and hyperbranched molecules is an application of chemistry yet to be explored extensively. In this study the use of two hydrolytic enzymes, a lipase from Candida cylindracea and a cutinase from Fusarium solani pisii, were investigated in the selective cleavage of ester groups situated on the peripheral layer of two families of branched polyamides. These branched polyamides were conjugated to simple fragrances citronellol and L-menthol via ester linkages. Hydrolysis of the ester linkage between the fragrances and the branched polyamide support was carried out in aqueous buffered systems at slightly basic pH values under the optimum operative conditions for the enzymes used. These preliminary qualitative investigations revealed that partial cleavage of the ester functionalities from the branched polyamide support had occurred. However, the ability of the enzymes to interact with the substrates decreased considerably as the branching density, the rigidity of the structure and the bulkiness of the polyamide-fragrance conjugates increased.

  5. LABOUR MARKET AMID THE CHANGES IN LIGHT INDUSTRY

    Directory of Open Access Journals (Sweden)

    Jemboiu George-Nicolae

    2013-06-01

    Full Text Available The Romanian economy has undergone a number of changes after 1989, their effects being present all over the areas and causing chain reactions. An eloquent example is light industry, whose internal supply market has known a significant decrease due to the reducing activity in agriculture, animal husbandry, etc., while internal outlets had to face imports, usually of a low quality. In this respect, light industry has turned to international trade, given the cheap labour force, over time has been developed the lohn production system. The gross labour was among the most required in this area, the design and sales activities were often external customer's responsibility. The old factories were not able to adapt to the new conditions, so many of them reduced the activity. In the end it led to a major layoff of labour force both in light industry, as well as in associated areas. Only a part of it has managed to reintegrate in the new enterprises which were more adapted to current market conditions. Solving the problem of excess labour force, given its presence especially in rural areas and in mono-industrial towns, representative areas and the developing Region South-West Oltenia, also involves the relaunching of light industry. There is need to support the internal sources of supply of raw materials, as well as a new view related to the selling of products, based on creative activities and exploration of markets. These marks can lead to occupational integration of the excess labour force and to ensure the social balance in the areas affected by the restructuring of national economy.

  6. A catalytic antibody programmed for torsional activation of amide bond hydrolysis.

    Science.gov (United States)

    Aggarwal, Ranjana; Benedetti, Fabio; Berti, Federico; Buchini, Sabrina; Colombatti, Alfonso; Dinon, Francesca; Galasso, Vinicio; Norbedo, Stefano

    2003-07-07

    Amidase antibody 312d6, obtained against the sulfonamide hapten 4 a that mimics the transition state for hydrolysis of a distorted amide, accelerates the hydrolysis of the corresponding amides 1 a-3 a by a factor of 10(3) at pH 8. The mechanisms of both the uncatalyzed and antibody-catalyzed reactions were studied. Between pH 8 and 12 the uncatalyzed hydrolysis of N-toluoylindoles 1 a and 3 a shows a simple first-order dependence on [OH(-)], while hydrolysis of 3 a is zeroth-order in [OH(-)] below pH 8. The pH profile for hydrolysis of the corresponding tryptophan amide 2 a is more complex due to the dissociation of the zwitterion into an anion with pK(a) 9.74; hydrolysis of the zwitterionic and the anionic form of 2 a both show simple first-order dependence on [OH(-)]. Absence of (18)O exchange between H(2) (18)O/(18)OH(-) and the substrate, a normal SKIE for both 1 a (k(H)/k(D)=1.12) and 3 a (k(H)/k(D)=1.24) and the value of the Hammett constant rho for hydrolysis of p-substituted amides 3 a-e are consistent with an ester-like mechanism in which formation of the tetrahedral intermediate is rate-determining and the amine departs as anion. The 312d6-catalyzed hydrolysis of 3 a was studied between pH 7.5 and 9, and its independence of pH in this range indicates that water is the reacting nucleophile. Hydrolysis of 3 a is only partially inhibited by the sulfonamide hapten, and this indicates that non-specific catalysis by the protein accompanies the specific process. Only the nonspecific process is observed in the hydrolysis of amides 3 with para substituents other than methyl. Binding studies on the corresponding series of p-substituted sulfonamides 5 a-e confirm the high specificity of antibody 312d6 for p-methyl substituted substrates.

  7. Aromatic amide and hydrazide foldamer-based responsive host-guest systems.

    Science.gov (United States)

    Zhang, Dan-Wei; Zhao, Xin; Li, Zhan-Ting

    2014-07-15

    CONSPECTUS: In host-guest chemistry, a larger host molecule selectively and noncovalently binds to a smaller guest molecule or ion. Early studies of host-guest chemistry focused on the recognition of spherical metal or ammonium ions by macrocyclic hosts, such as cyclic crown ethers. In these systems, preorganization enables their binding sites to cooperatively contact and attract a guest. Although some open-chain crown ether analogues possess similar, but generally lower, binding affinities, the design of acyclic molecular recognition hosts has remained challenging. One of the most successful examples was rigid molecular tweezers, acyclic covalently bonded preorganized host molecules with open cavities that bind tightly as they stiffen. Depending on the length of the atomic backbones, hydrogen bonding-driven aromatic amide foldamers can form open or closed cavities. Through rational design of the backbones and the introduction of added functional groups, researchers can regulate the shape and size of the cavity. The directionality of hydrogen bonding and the inherent rigidity of aromatic amide units allow researchers to predict both the shape and size of the cavity of an aromatic amide foldamer. Therefore, researchers can then design guest molecules with structure that matches the cavity shape, size, and binding sites of the foldamer host. In addition, because hydrogen bonds are dynamic, researchers can design structures that can adapt to outside stimuli to produce responsive supramolecular architectures. In this Account, we discuss how aromatic amide and hydrazide foldamers induced by hydrogen bonding can produce responsive host-guest systems, based on research by our group and others. First we highlight the helical chirality induced as binding occurs in solution, which includes the induction of helicity by chiral guests in oligomeric and polymeric foldamers, the formation of diastereomeric complexes between chiral foldamer hosts and guests, and the induction of

  8. Cobalt chloride decreases fibroblast growth factor-21 expression dependent on oxidative stress but not hypoxia-inducible factor in Caco-2 cells

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yanlong [School of Pharmacy, Wenzhou Medical College, Wenzhou (China); Department of Medicine, University of Louisville, Louisville, KY (United States); Wang, Chunhong [Second Hospital, Jilin University, Changchun (China); Department of Medicine, University of Louisville, Louisville, KY (United States); Wang, Yuhua [College of Food Science and Engineering, Jilin Agricultural University, Changchun (China); Department of Medicine, University of Louisville, Louisville, KY (United States); Ma, Zhenhua [First Hospital, Xi' an Jiaotong University, Xi' an (China); Department of Medicine, University of Louisville, Louisville, KY (United States); Xiao, Jian [School of Pharmacy, Wenzhou Medical College, Wenzhou (China); McClain, Craig [Department of Medicine, University of Louisville, Louisville, KY (United States); Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY (United States); Alcohol Research Center, University of Louisville, Louisville, KY (United States); Robley Rex Veterans Affairs Medical Center, Louisville, KY (United States); Li, Xiaokun [School of Pharmacy, Wenzhou Medical College, Wenzhou (China); Feng, Wenke, E-mail: wenke.feng@louisville.edu [School of Pharmacy, Wenzhou Medical College, Wenzhou (China); Department of Medicine, University of Louisville, Louisville, KY (United States); Alcohol Research Center, University of Louisville, Louisville, KY (United States)

    2012-10-15

    Fibroblast growth factor-21 (FGF21) is a potential metabolic regulator with multiple beneficial effects on metabolic diseases. FGF21 is mainly expressed in the liver, but is also found in other tissues including the intestine, which expresses β-klotho abundantly. The intestine is a unique organ that operates in a physiologically hypoxic environment, and is responsible for the fat absorption processes including triglyceride breakdown, re-synthesis and absorption into the portal circulation. In the present study, we investigated the effects of hypoxia and the chemical hypoxia inducer, cobalt chloride (CoCl{sub 2}), on FGF21 expression in Caco-2 cells and the consequence of fat accumulation. Physical hypoxia (1% oxygen) and CoCl{sub 2} treatment decreased both FGF21 mRNA and secreted protein levels. Gene silence and inhibition of hypoxia-inducible factor-α (HIFα) did not affect the reduction of FGF21 mRNA and protein levels by hypoxia. However, CoCl{sub 2} administration caused a significant increase in oxidative stress. The addition of n-acetylcysteine (NAC) suppressed CoCl{sub 2}-induced reactive oxygen species (ROS) formation and completely negated CoCl{sub 2}-induced FGF21 loss. mRNA stability analysis demonstrated that the CoCl{sub 2} administration caused a remarkable reduction in FGF21 mRNA stability. Furthermore, CoCl{sub 2} increased intracellular triglyceride (TG) accumulation, along with a reduction in mRNA levels of lipid lipase, hormone sensitive lipase (HSL) and adipose triglyceride lipase (ATGL), and an increase of sterol regulatory element-binding protein-1c (SREBP1c) and stearoyl-coenzyme A (SCD1). Addition of both NAC and recombinant FGF21 significantly attenuated the CoCl{sub 2}-induced TG accumulation. In conclusion, the decrease of FGF21 in Caco-2 cells by chemical hypoxia is independent of HIFα, but dependent on an oxidative stress-mediated mechanism. The regulation of FGF21 by hypoxia may contribute to intestinal lipid metabolism and

  9. Cobalt chloride decreases fibroblast growth factor-21 expression dependent on oxidative stress but not hypoxia-inducible factor in Caco-2 cells

    International Nuclear Information System (INIS)

    Liu, Yanlong; Wang, Chunhong; Wang, Yuhua; Ma, Zhenhua; Xiao, Jian; McClain, Craig; Li, Xiaokun; Feng, Wenke

    2012-01-01

    Fibroblast growth factor-21 (FGF21) is a potential metabolic regulator with multiple beneficial effects on metabolic diseases. FGF21 is mainly expressed in the liver, but is also found in other tissues including the intestine, which expresses β-klotho abundantly. The intestine is a unique organ that operates in a physiologically hypoxic environment, and is responsible for the fat absorption processes including triglyceride breakdown, re-synthesis and absorption into the portal circulation. In the present study, we investigated the effects of hypoxia and the chemical hypoxia inducer, cobalt chloride (CoCl 2 ), on FGF21 expression in Caco-2 cells and the consequence of fat accumulation. Physical hypoxia (1% oxygen) and CoCl 2 treatment decreased both FGF21 mRNA and secreted protein levels. Gene silence and inhibition of hypoxia-inducible factor-α (HIFα) did not affect the reduction of FGF21 mRNA and protein levels by hypoxia. However, CoCl 2 administration caused a significant increase in oxidative stress. The addition of n-acetylcysteine (NAC) suppressed CoCl 2 -induced reactive oxygen species (ROS) formation and completely negated CoCl 2 -induced FGF21 loss. mRNA stability analysis demonstrated that the CoCl 2 administration caused a remarkable reduction in FGF21 mRNA stability. Furthermore, CoCl 2 increased intracellular triglyceride (TG) accumulation, along with a reduction in mRNA levels of lipid lipase, hormone sensitive lipase (HSL) and adipose triglyceride lipase (ATGL), and an increase of sterol regulatory element-binding protein-1c (SREBP1c) and stearoyl-coenzyme A (SCD1). Addition of both NAC and recombinant FGF21 significantly attenuated the CoCl 2 -induced TG accumulation. In conclusion, the decrease of FGF21 in Caco-2 cells by chemical hypoxia is independent of HIFα, but dependent on an oxidative stress-mediated mechanism. The regulation of FGF21 by hypoxia may contribute to intestinal lipid metabolism and absorption. -- Graphical abstract: Physical

  10. Structure elucidation and in vitro cytotoxicity of ochratoxin α amide, a new degradation product of ochratoxin A.

    Science.gov (United States)

    Bittner, Andrea; Cramer, Benedikt; Harrer, Henning; Humpf, Hans-Ulrich

    2015-05-01

    The mycotoxin ochratoxin A is a secondary metabolite occurring in a wide range of commodities. During the exposure of ochratoxin A to white and blue light, a cleavage between the carbon atom C-14 and the nitrogen atom was described. As a reaction product, the new compound ochratoxin α amide has been proposed based on mass spectrometry (MS) experiments. In the following study, we observed that this compound is also formed at high temperatures such as used for example during coffee roasting and therefore represents a further thermal ochratoxin A degradation product. To confirm the structure of ochratoxin α amide, the compound was prepared in large scale and complete structure elucidation via nuclear magnetic resonance (NMR) and MS was performed. Additionally, first studies on the toxicity of ochratoxin α amide were performed using immortalized human kidney epithelial (IHKE) cells, a cell line known to be sensitive against ochratoxin A with an IC50 value of 0.5 μM. Using this system, ochratoxin α amide revealed no cytotoxicity up to concentrations of 50 μM. Thus, these results propose that the thermal degradation of ochratoxin A to ochratoxin α amide might be a detoxification process. Finally, we present a sample preparation and a HPLC-tandem mass spectrometry (HPLC-MS/MS) method for the analysis of ochratoxin α amide in extrudates and checked its formation during the extrusion of artificially contaminated wheat grits at 150 and 180 °C, whereas no ochratoxin α amide was detectable under these conditions.

  11. Functional and structural study comparing the C-terminal amidated β-neurotoxin Ts1 with its isoform Ts1-G isolated from Tityus serrulatus venom.

    Science.gov (United States)

    Coelho, V A; Cremonez, C M; Anjolette, F A P; Aguiar, J F; Varanda, W A; Arantes, E C

    2014-06-01

    Mature Ts1, the main neurotoxin from Tityus serrulatus venom, has its C-terminal Cys amidated, while the isolated isoform of Ts1, named Ts1-G, keeps the non-amidated Gly residue at the C-terminal region, allowing the study of the comparative functional importance of amidation at the C-terminal between these two native toxins. Voltage dependent sodium current measurements showed that the affinity of Ts1-G for sodium channels is smaller than that of the mature Ts1, confirming the important role played by the C-terminal amidation in determining Ts1 activity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Synthesis of new fatty acids amides from aminolysis of fatty acid methyl esters (FAMEs); Sintese de novas amidas graxas a partir da aminolise de esteres metilicos

    Energy Technology Data Exchange (ETDEWEB)

    Lopes, Carolina R.; Montes D' Oca, Caroline da Ros; Duarte, Rodrigo da C.; Kurz, Marcia H.S.; Primel, Ednei G.; Clementin, Rosilene M.; Villarreyes, Joaquin Ariel M.; Montes D' Oca, Marcelo G., E-mail: dqmdoca@furg.b [Universidade Federal do Rio Grande, RS (Brazil). Escola de Quimica e Alimentos

    2010-07-01

    Recent biochemical and pharmacological studies have led to the characterization of different fatty acid amides as a new family of biologically active lipids. Here, we describe the synthesis of new amides from C16:0, 18:0, 18:1 and 18:1, OH fatty acids (FFA) families with cyclic and acyclic amines and demonstrate for the first time that these compounds produce cytotoxic effects. Application of this method to the synthesis of fatty acid amides was performed using the esters aminolysis as a key step and various carboxylic amides were prepared in good yield from fatty acid methyl esters (FAMEs). (author)

  13. Steric effects in release of amides from linkers in solid-phase synthesis. Molecular mechanics modeling of key step in peptide and combinatorial chemistry

    DEFF Research Database (Denmark)

    Norrby, Per-Ola; Jensen, Knud Jørgen

    2006-01-01

    -lability of the backbone amide linkage (BAL), which releases sec. amides, compared to C-terminal amide anchoring, which releases primary amides, was rationalized by steric relief upon cleavage. Thus, the relative stability of the carbenium ion formed from the linker in the acidolytic release is an insufficient measure...... of the lability of a linkage. In addition, predictions indicated that steric effects from the C-alpha-substituent in a BAL anchored amino acid residue should accelerate the acidolytic release. The finding that steric crowding leads to increased acid-lability will be important for further development and use...

  14. A Two-Step Procedure for the Overall Transamidation of 8-Aminoquinoline Amides Proceeding via the Intermediate N-Acyl-Boc-Carbamates.

    Science.gov (United States)

    Verho, Oscar; Pourghasemi Lati, Monireh; Oschmann, Michael

    2018-04-03

    Herein a two-step strategy for achieving overall transamidation of 8-aminoquinoline amides has been explored. In this protocol, the 8-aminoquinoline amides were first treated with Boc 2 O and DMAP to form the corresponding N-acyl-Boc-carbamates, which were found to be sufficiently reactive to undergo subsequent aminolysis with different amines in the absence of any additional reagents or catalysts. To demonstrate the utility of this approach, it was applied on a number of 8-aminoquinoline amides from the recent C-H functionalization literature, enabling access to a range of elaborate amide derivatives in good to high yields.

  15. Conformational properties of amphotericin B amide derivatives - impact on selective toxicity

    Science.gov (United States)

    Resat, Haluk; Sungur, F. Aylin; Baginski, Maciej; Borowski, Edward; Aviyente, Viktorya

    2000-10-01

    Even though it is highly toxic, Amphotericin B (AmB), an amphipathic polyene macrolide antibiotic, is used in the treatment of severe systemic fungal infections as a life-saving drug. To examine the influence of conformational factors on selective toxicity of these compounds, we have investigated the conformational properties of five AmB amide derivatives. It was found that the extended conformation with torsional angles (φ,ψ)=(290°,180° ) is a common minimum of the potential energy surfaces (PES) of unsubstituted AmB and its amide derivatives. The extended conformation of the studied compounds allows for the formation of an intermolecular hydrogen bond network between adjacent antibiotic molecules in the open channel configuration. Therefore, the extended conformation is expected to be the dominant conformer in an open AmB (or its amide derivatives) membrane channel. The derivative compounds for calculations were chosen according to their selective toxicity compared to AmB and they had a wide range of selective toxicity. Except for two AmB derivatives, the PES maps of the derivatives reveal that the molecules can coexist in more than one conformer. Taking into account the cumulative conclusions drawn from the earlier MD simulation studies of AmB membrane channel, the results of the potential energy surface maps, and the physical considerations of the molecular structures, we hypothesize a new model of structure-selective toxicity of AmB derivatives. In this proposed model the presence of the extended conformation as the only well defined global conformer for AmB derivatives is taken as the indicator of their higher selective toxicity. This model successfully explains our results. To further test our model, we also investigated an AmB derivative whose selective toxicity has not been experimentally measured before. Our prediction for the selective toxicity of this compound can be tested in experiments to validate or invalidate the proposed model.

  16. Amide proton solvent protection in amylin fibrils probed by quenched hydrogen exchange NMR.

    Directory of Open Access Journals (Sweden)

    Andrei T Alexandrescu

    Full Text Available Amylin is an endocrine hormone that accumulates in amyloid plaques in patients with advanced type 2 diabetes. The amyloid plaques have been implicated in the destruction of pancreatic β-cells, which synthesize amylin and insulin. To better characterize the secondary structure of amylin in amyloid fibrils we assigned the NMR spectrum of the unfolded state in 95% DMSO and used a quenched hydrogen-deuterium exchange technique to look at amide proton solvent protection in the fibrils. In this technique, partially exchanged fibrils are dissolved in 95% DMSO and information about amide proton occupancy in the fibrils is determined from DMSO-denatured monomers. Hydrogen exchange lifetimes at pH 7.6 and 37°C vary between ∼5 h for the unstructured N-terminus to 600 h for amide protons in the two β-strands that form inter-molecular hydrogen bonds between amylin monomers along the length of the fibril. Based on the protection data we conclude that residues A8-H18 and I26-Y37 comprise the two β-strands in amylin fibrils. There is variation in protection within the β-strands, particularly for strand β1 where only residues F15-H18 are strongly protected. Differences in protection appear to be due to restrictions on backbone dynamics imposed by the packing of two-layers of C2-symmetry-related β-hairpins in the protofilament structure, with strand β1 positioned on the surface and β2 in the interior.

  17. A polarizable QM/MM approach to the molecular dynamics of amide groups solvated in water

    Energy Technology Data Exchange (ETDEWEB)

    Schwörer, Magnus; Wichmann, Christoph; Tavan, Paul, E-mail: tavan@physik.uni-muenchen.de [Lehrstuhl für BioMolekulare Optik, Ludwig-Maximilians Universität München, Oettingenstr. 67, 80538 München (Germany)

    2016-03-21

    The infrared (IR) spectra of polypeptides are dominated by the so-called amide bands. Because they originate from the strongly polar and polarizable amide groups (AGs) making up the backbone, their spectral positions sensitively depend on the local electric fields. Aiming at accurate computations of these IR spectra by molecular dynamics (MD) simulations, which derive atomic forces from a hybrid quantum and molecular mechanics (QM/MM) Hamiltonian, here we consider the effects of solvation in bulk liquid water on the amide bands of the AG model compound N-methyl-acetamide (NMA). As QM approach to NMA we choose grid-based density functional theory (DFT). For the surrounding MM water, we develop, largely based on computations, a polarizable molecular mechanics (PMM) model potential called GP6P, which features six Gaussian electrostatic sources (one induced dipole, five static partial charge distributions) and, therefore, avoids spurious distortions of the DFT electron density in hybrid DFT/PMM simulations. Bulk liquid GP6P is shown to have favorable properties at the thermodynamic conditions of the parameterization and beyond. Lennard-Jones (LJ) parameters of the DFT fragment NMA are optimized by comparing radial distribution functions in the surrounding GP6P liquid with reference data obtained from a “first-principles” DFT-MD simulation. Finally, IR spectra of NMA in GP6P water are calculated from extended DFT/PMM-MD trajectories, in which the NMA is treated by three different DFT functionals (BP, BLYP, B3LYP). Method-specific frequency scaling factors are derived from DFT-MD simulations of isolated NMA. The DFT/PMM-MD simulations with GP6P and with the optimized LJ parameters then excellently predict the effects of aqueous solvation and deuteration observed in the IR spectra of NMA. As a result, the methods required to accurately compute such spectra by DFT/PMM-MD also for larger peptides in aqueous solution are now at hand.

  18. Tuning the bimetallic amide-imide precursor system to make paramagnetic GaMnN nanopowders

    Energy Technology Data Exchange (ETDEWEB)

    Drygas, Mariusz [AGH University of Science and Technology, Faculty of Energy and Fuels, Al. Mickiewicza 30, 30-059 Krakow (Poland); Janik, Jerzy F., E-mail: janikj@agh.edu.pl [AGH University of Science and Technology, Faculty of Energy and Fuels, Al. Mickiewicza 30, 30-059 Krakow (Poland); Musial, Michal [AGH University of Science and Technology, Faculty of Energy and Fuels, Al. Mickiewicza 30, 30-059 Krakow (Poland); Gosk, Jacek [Warsaw University of Technology, Faculty of Physics, Koszykowa 75, 00-662 Warszawa (Poland); Twardowski, Andrzej, E-mail: andrzej.twardowski@fuw.edu.pl [University of Warsaw, Faculty of Physics, Pasteura 5, 02-093 Warszawa (Poland)

    2016-09-01

    A bimetallic molecular system made of gallium (III) tris(dimethyl)amide Ga(NMe{sub 2}){sub 3} and manganese (II) bis(trimethylsilyl)amide Mn[N(SiMe{sub 3}){sub 2}]{sub 2} (Me = CH{sub 3}, fixed initial Mn-content 10 at.%) was subjected to ammonolysis in refluxing/liquid ammonia. Upon isolation at room temperature, the amide-imide mixed metal precursor was pyrolyzed at elevated temperatures under an ammonia flow by two different routes. Route 1 consisted of a direct nitridation at high temperatures of 500, 700 or 900 °C. In route 2, a low temperature pyrolysis at 150 °C was applied prior to nitridation at the same final temperatures as in route 1. All nanopowders were characterized by XRD diffraction, FT-IR spectroscopy, and SEM/EDX microscopy and analysis. Thorough magnetization measurements in function of magnetic field and temperature were carried out with a SQUID magnetometer. In all samples, the paramagnetic phase of GaMnN was accompanied by an antiferromagnetic by-product linked to a Mn-containing species from decomposition and oxidation of Mn-precursor excess. The Mn-contents in the crystalline GaMnN, i.e., Mn-incorporated in GaN crystal lattice, were of the order of 2–3 at.% mostly independent on the nitridation route whereas the latter had a pronounced effect on amounts of the antiferromagnetic by-product. - Highlights: • New bimetallic precursor system for conversion to GaN/Mn nanopowders was designed. • Two conversion routes were applied with precursor nitridation at 500, 700 or 900 °C. • Prepared nanopowders were thoroughly characterized including magnetic measurements. • The major product was the gallium nitride Mn-doped phase GaMnN with 2–3 at.% of Mn.

  19. A polarizable QM/MM approach to the molecular dynamics of amide groups solvated in water.

    Science.gov (United States)

    Schwörer, Magnus; Wichmann, Christoph; Tavan, Paul

    2016-03-21

    The infrared (IR) spectra of polypeptides are dominated by the so-called amide bands. Because they originate from the strongly polar and polarizable amide groups (AGs) making up the backbone, their spectral positions sensitively depend on the local electric fields. Aiming at accurate computations of these IR spectra by molecular dynamics (MD) simulations, which derive atomic forces from a hybrid quantum and molecular mechanics (QM/MM) Hamiltonian, here we consider the effects of solvation in bulk liquid water on the amide bands of the AG model compound N-methyl-acetamide (NMA). As QM approach to NMA we choose grid-based density functional theory (DFT). For the surrounding MM water, we develop, largely based on computations, a polarizable molecular mechanics (PMM) model potential called GP6P, which features six Gaussian electrostatic sources (one induced dipole, five static partial charge distributions) and, therefore, avoids spurious distortions of the DFT electron density in hybrid DFT/PMM simulations. Bulk liquid GP6P is shown to have favorable properties at the thermodynamic conditions of the parameterization and beyond. Lennard-Jones (LJ) parameters of the DFT fragment NMA are optimized by comparing radial distribution functions in the surrounding GP6P liquid with reference data obtained from a "first-principles" DFT-MD simulation. Finally, IR spectra of NMA in GP6P water are calculated from extended DFT/PMM-MD trajectories, in which the NMA is treated by three different DFT functionals (BP, BLYP, B3LYP). Method-specific frequency scaling factors are derived from DFT-MD simulations of isolated NMA. The DFT/PMM-MD simulations with GP6P and with the optimized LJ parameters then excellently predict the effects of aqueous solvation and deuteration observed in the IR spectra of NMA. As a result, the methods required to accurately compute such spectra by DFT/PMM-MD also for larger peptides in aqueous solution are now at hand.

  20. Anti-biofilm Properties of Bacterial Di-Rhamnolipids and Their Semi-Synthetic Amide Derivatives.

    Science.gov (United States)

    Aleksic, Ivana; Petkovic, Milos; Jovanovic, Milos; Milivojevic, Dusan; Vasiljevic, Branka; Nikodinovic-Runic, Jasmina; Senerovic, Lidija

    2017-01-01

    A new strain, namely Lysinibacillus sp. BV152.1 was isolated from the rhizosphere of ground ivy ( Glechoma hederacea L.) producing metabolites with potent ability to inhibit biofilm formation of an important human pathogens Pseudomonas aeruginosa PAO1, Staphylococcus aureus , and Serratia marcescens . Structural characterization revealed di-rhamnolipids mixture containing rhamnose (Rha)-Rha-C10-C10, Rha-Rha-C8-C10, and Rha-Rha-C10-C12 in the ratio 7:2:1 as the active principle. Purified di-rhamnolipids, as well as commercially available di-rhamnolipids (Rha-Rha-C10-C10, 93%) were used as the substrate for the chemical derivatization for the first time, yielding three semi-synthetic amide derivatives, benzyl-, piperidine-, and morpholine. A comparative study of the anti-biofilm, antibacterial and cytotoxic properties revealed that di-Rha from Lysinibacillus sp. BV152.1 were more potent in biofilm inhibition, both cell adhesion and biofilm maturation, than commercial di-rhamnolipids inhibiting 50% of P. aeruginosa PAO1 biofilm formation at 50 μg mL -1 and 75 μg mL -1 , respectively. None of the di-rhamnolipids exhibited antimicrobial properties at concentrations of up to 500 μg mL -1 . Amide derivatization improved inhibition of biofilm formation and dispersion activities of di-rhamnolipids from both sources, with morpholine derivative being the most active causing more than 80% biofilm inhibition at concentrations 100 μg mL -1 . Semi-synthetic amide derivatives showed increased antibacterial activity against S. aureus , and also showed higher cytotoxicity. Therefore, described di-rhamnolipids are potent anti-biofilm agents and the described approach can be seen as viable approach in reaching new rhamnolipid based derivatives with tailored biological properties.

  1. Kinetics of Free Radical Polymerization of N-Substituted Amides and Their Structural Implications

    Directory of Open Access Journals (Sweden)

    Anca Aldea

    2016-01-01

    Full Text Available Two N-substituted amides (N-acryloyl morpholine and N-methyl-N-vinylacetamide were polymerized in different solvents using radical initiator. The tacticity of obtained polymers was determined by 400 MHz 1H-NMR and 13C-NMR. At a given temperature, the syndiotacticity increased with increasing the solvent polarity. This solvent effect may be related to the hydrogen bonding interaction among solvent, monomer, and/or growing species. A peculiar aspect regards the steric hindrance at the nitrogen atom.

  2. Kinetics of the mechanochemical synthesis of alkaline-earth metal amides

    Science.gov (United States)

    Garroni, Sebastiano; Takacs, Laszlo; Leng, Haiyan; Delogu, Francesco

    2014-07-01

    A phenomenological framework is developed to model the kinetics of the formation of alkaline-earth metal amides by the ball milling induced reaction of their hydrides with gaseous ammonia. It is shown that the exponential character of the kinetic curves is modulated by the increase of the total volume of the powder inside the reactor due to the substantially larger molar volume of the products compared to the reactants. It is claimed that the volume of powder effectively processed during each collision connects the transformation rate to the physical and chemical processes underlying the mechanochemical transformations.

  3. Rapid and accurate processing method for amide proton exchange rate measurement in proteins

    International Nuclear Information System (INIS)

    Koskela, Harri; Heikkinen, Outi; Kilpelaeinen, Ilkka; Heikkinen, Sami

    2007-01-01

    Exchange between protein backbone amide hydrogen and water gives relevant information about solvent accessibility and protein secondary structure stability. NMR spectroscopy provides a convenient tool to study these dynamic processes with saturation transfer experiments. Processing of this type of NMR spectra has traditionally required peak integration followed by exponential fitting, which can be tedious with large data sets. We propose here a computer-aided method that applies inverse Laplace transform in the exchange rate measurement. With this approach, the determination of exchange rates can be automated, and reliable results can be acquired rapidly without a need for manual processing

  4. Mechanistic Investigation of the Ruthenium–N-Heterocyclic-Carbene-Catalyzed Amidation of Alcohols and Amines

    DEFF Research Database (Denmark)

    Makarov, Ilya; Fristrup, Peter; Madsen, Robert

    2012-01-01

    The mechanism of the ruthenium–N-heterocyclic-carbene-catalyzed formation of amides from alcohols and amines was investigated by experimental techniques (Hammett studies, kinetic isotope effects) and by a computational study by using dispersion-corrected density functional theory (DFT/ M06......, but that it is one of several slow steps in the catalytic cycle. Rapid scrambling of hydrogen and deuterium at the a position of the alcohol was observed with deuterium-labeled substrates, which implies that the catalytically active species is a ruthenium dihydride. The experimental results were supported...

  5. Synthesis of Peptide Amides using Sol-Gel Immobilized Alcalase in Batch and Continuous Reaction System

    OpenAIRE

    L. N. Corîci; A. E. Frissen; D -J. Van Zoelen; I. F. Eggen; F. Peter; C. M. Davidescu; C. G. Boeriu

    2011-01-01

    Two commercial proteases from Bacillus licheniformis (Alcalase 2.4 L FG and Alcalase 2.5 L, Type DX) were screened for the production of Z-Ala-Phe-NH2 in batch reaction. Alcalase 2.4 L FG was the most efficient enzyme for the C-terminal amidation of Z-Ala-Phe-OMe using ammonium carbamate as ammonium source. Immobilization of protease has been achieved by the sol-gel method, using dimethyldimethoxysilane (DMDMOS) and tetramethoxysilane (TMOS) as precursors (unpublished res...

  6. Ethyl malonate amides: a diketo acid offspring fragment for HIV integrase inhibition.

    Science.gov (United States)

    Serafin, Katarzyna; Mazur, Pawel; Bak, Andrzej; Laine, Elodie; Tchertanov, Luba; Mouscadet, Jean-François; Polanski, Jaroslaw

    2011-08-15

    While searching for new HIV integrase inhibitors we discovered that some ethyl malonate amides (EMA) are active against this enzyme. Surprisingly, the main function can only very rarely be found among the reported drug candidates. We synthesised a series of compounds in order to establish and analyse the structure-activity relationship. The similarity to the important classes of HIV integrase inhibitors as well as the synthetic availability of the different targets including this pharmacophore makes EMA compounds an interesting object of investigations. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Methods for attaching polymerizable ceragenins to water treatment membranes using amine and amide linkages

    Science.gov (United States)

    Hibbs, Michael; Altman, Susan J.; Jones, Howland D.T.; Savage, Paul B.

    2013-10-15

    This invention relates to methods for chemically grafting and attaching ceragenin molecules to polymer substrates; methods for synthesizing ceragenin-containing copolymers; methods for making ceragenin-modified water treatment membranes and spacers; and methods of treating contaminated water using ceragenin-modified treatment membranes and spacers. Ceragenins are synthetically produced antimicrobial peptide mimics that display broad-spectrum bactericidal activity. Alkene-functionalized ceragenins (e.g., acrylamide-functionalized ceragenins) can be attached to polyamide reverse osmosis membranes using amine-linking, amide-linking, UV-grafting, or silane-coating methods. In addition, silane-functionalized ceragenins can be directly attached to polymer surfaces that have free hydroxyls.

  8. Kinetic Modification on Hydrogen Desorption of Lithium Hydride and Magnesium Amide System

    OpenAIRE

    Miyaoka, Hiroki; Wang, Yongming; Hino, Satoshi; Isobe, Shigehito; Tokoyoda, Kazuhiko; Ichikawa, Takayuki; Kojima, Yoshitsugu

    2015-01-01

    Various synthesis and rehydrogenation processes of lithium hydride (LiH) and magnesium amide (Mg(NH2)2) system with 8:3 molar ratio are investigated to understand the kinetic factors and effectively utilize the essential hydrogen desorption properties. For the hydrogen desorption with a solid-solid reaction, it is expected that the kinetic properties become worse by the sintering and phase separation. In fact, it is experimentally found that the low crystalline size and the close contact of L...

  9. Recombinant production of peptide C-terminal α-amides using an engineered intein

    DEFF Research Database (Denmark)

    Albertsen, Louise; Shaw, Allan C; Norrild, Jens Chr.

    2013-01-01

    of the 198 amino acid intein with an eight amino acid linker. The optimized intein construct was used to produce the PYY derivative under high cell density cultivation conditions, generating the peptide thioester precursor in good yields and subsequent amidation provided the target peptide.......Peptides are of increasing interest as therapeutics in a wide range of diseases, including metabolic diseases such as diabetes and obesity. In the latter, peptide hormones such as peptide YY (PYY) and pancreatic peptide (PP) are important templates for drug design. Characteristic for these peptides...

  10. Mixed quantum-classical dynamics of an amide-I vibrational excitation in a protein α -helix

    Science.gov (United States)

    Freedman, Holly; Martel, Paulo; Cruzeiro, Leonor

    2010-11-01

    Adenosine triphosphate (ATP) is known to be the main energy currency of the living cell, and is used as a coenzyme to generate energy for many cellular processes through hydrolysis to adenosine diphosphate (ADP), although the mechanism of energy transfer is not well understood. It has been proposed that following hydrolysis of the ATP cofactor bound to a protein, up to two quanta of amide-I vibrational energy are excited and utilized to bring about important structural changes in the protein. To study whether, and how, amide-I vibrational excitations are capable of leading to protein structural changes, we have added components arising from quantum-mechanical amide-I vibrational excitations to the total energy and force terms within a molecular-dynamics simulation. This model is applied to helical deca-alanine as a test case to investigate how its dynamics differs in the presence or absence of an amide-I excitation. We find that the presence of an amide-I excitation can bias the structure toward a more helical state.

  11. The amide III vibrational circular dichroism band as a probe to detect conformational preferences of alanine dipeptide in water.

    Science.gov (United States)

    Mirtič, Andreja; Merzel, Franci; Grdadolnik, Jože

    2014-07-01

    The conformational preferences of blocked alanine dipeptide (ADP), Ac-Ala-NHMe, in aqueous solution were studied using vibrational circular dichroism (VCD) together with density functional theory (DFT) calculations. DFT calculations of three most representative conformations of ADP surrounded by six explicit water molecules immersed in a dielectric continuum have proven high sensitivity of amide III VCD band shape that is characteristic for each conformation of the peptide backbone. The polyproline II (PII ) and αR conformation of ADP are associated with a positive VCD band while β conformation has a negative VCD band in amide III region. Knowing this spectral characteristic of each conformation allows us to assign the experimental amide III VCD spectrum of ADP. Moreover, the amide III region of the VCD spectrum was used to determine the relative populations of conformations of ADP in water. Based on the interpretation of the amide III region of VCD spectrum we have shown that dominant conformation of ADP in water is PII which is stabilized by hydrogen bonded water molecules between CO and NH groups on the peptide backbone. Copyright © 2014 Wiley Periodicals, Inc.

  12. Studies on novel interpenetrating networks of urethane modified poly(ester-amide and vinyl ester of bisphenol-C

    Directory of Open Access Journals (Sweden)

    Pragnesh N. Dave

    2016-05-01

    Full Text Available Bisphthalamic acids were prepared by reaction of maleic anhydride and aromatic diamines. Novel poly(ester-amides (PEAs were prepared by reaction of DGEBF with bisphthalamic acids. Acrylation of PEAs was carried out using acryloyl chloride; products are called acrylated poly(ester-amides (APEAs. Epoxy resin based unsaturated poly(ester-amide resins (UPEAs can be prepared by many methods but here these were prepared by reported method. These UPEAs were then treated with acryloyl chloride to afford acrylated UPEAs resin (i.e. AUPEAs. Interpenetrating networks of equal proportional urethane modified poly(ester-amide and acrylated poly(ester-amide and vinyl ester of biaphenol c (VE resin were prepared. Urethane modified APEAs and AUPEAs were characterized by elemental analysis, molecular weight was determined by vapor pressure osmometer and by IR spectral study and by thermogravimetry. Based on DSC data in situ glass reinforced composites of the resultant blends have been prepared and characterized for mechanical, electrical and chemical properties. Unreinforced blends were characterized by thermogravimetry (TGA.

  13. Substitution of terminal amide with 1H-1,2,3-triazole: Identification of unexpected class of potent antibacterial agents.

    Science.gov (United States)

    Bi, Fangchao; Ji, Shengli; Venter, Henrietta; Liu, Jingru; Semple, Susan J; Ma, Shutao

    2018-03-01

    3-Methoxybenzamide (3-MBA) derivatives have been identified as novel class of potent antibacterial agents targeting the bacterial cell division protein FtsZ. As one of isosteres for the amide group, 1,2,3-triazole can mimic the topological and electronic features of the amide, which has gained increasing attention in drug discovery. Based on these considerations, we prepared a series of 1H-1,2,3-triazole-containing 3-MBA analogues via isosteric replacement of the terminal amide with triazole, which had increased antibacterial activity. This study demonstrated the possibility of developing the 1H-1,2,3-triazole group as a terminal amide-mimetic element which was capable of both keeping and modulating amide-related bioactivity. Surprisingly, a different action mode of these new 1H-1,2,3-triazole-containing analogues was observed, which could open new opportunities for the development of antibacterial agents. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. Acylated apelin-13 amide analogues exhibit enzyme resistance and prolonged insulin releasing, glucose lowering and anorexic properties.

    Science.gov (United States)

    O'Harte, Finbarr P M; Parthsarathy, Vadivel; Hogg, Christopher; Flatt, Peter R

    2017-12-15

    The adipokine, apelin has many biological functions but its activity is curtailed by rapid plasma degradation. Fatty acid derived apelin analogues represent a new and exciting avenue for the treatment of obesity-diabetes. This study explores four novel fatty acid modified apelin-13 analogues, namely, (Lys 8 GluPAL)apelin-13 amide, pGlu(Lys 8 GluPAL)apelin-13 amide, Lys 8 GluPAL(Tyr 13 )apelin-13 and Lys 8 GluPAL(Val 13 )apelin-13. Fatty acid modification extended the half-life of native apelin-13 to >24 h in vitro. pGlu(Lys 8 GluPAL)apelin-13 amide was the most potent insulinotropic analogue in BRIN-BD11 cells and isolated islets with maximal stimulatory effects of up to 2.7-fold (p glucose uptake in 3T3-L1 adipocytes (2.3-fold, p glucose (39-43%, p glucose tolerance tests in diet-induced obese mice. pGlu(Lys 8 GluPAL)apelin-13 amide and (Lys 8 GluPAL)apelin-13 amide also inhibited feeding (28-40%, p < .001), whereas Lys 8 GluPAL(Val 13 )apelin-13 increased food intake (8%, p < .05) in mice. These data indicate that novel enzymatically stable analogues of apelin-13 may be suitable for future development as therapeutic agents for obesity-diabetes. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Infrared spectroscopy of the amide I mode of N-methylacetamide in solid hydrogen at 2-4 K.

    Science.gov (United States)

    Paulson, Leif O; Anderson, David T

    2011-11-24

    We report high-resolution (0.05 cm(-1)) FTIR spectra of the fundamental and first overtone of the amide I mode of trans-N-methylacetamide (NMA) trapped in solid molecular hydrogen (SMH) at cryogenic temperatures with low (0.03%) and high (55%) ortho-hydrogen (oH(2)) concentrations. NMA-doped SMH samples with high oH(2) concentrations are nearly free from inhomogeneous broadening, permitting the measured amide I homogeneous line width of 1.268(8) cm(-1) to be used to place a lower limit on the vibrational lifetime of 4.19(3) ps. Direct observation of the amide I overtone allows the harmonic vibrational frequency ω(e) = 1726.6(5) cm(-1) and the anharmonicity constant ω(e)x(e) = 8.5(2) cm(-1) to be determined for NMA isolated in SMH samples with low oH(2) concentrations. © 2011 American Chemical Society

  16. (NHC)Cu-Catalyzed Mild C-H Amidation of (Hetero)arenes with Deprotectable Carbamates: Scope and Mechanistic Studies.

    Science.gov (United States)

    Xie, Weilong; Yoon, Jung Hee; Chang, Sukbok

    2016-09-28

    Primary arylamines are an important unit broadly found in synthetic, biological, and materials science. Herein we describe the development of a (NHC)Cu system that mediates a direct C-H amidation of (hetero)arenes by using N-chlorocarbamates or their sodio derivatives as the practical amino sources. A facile stoichiometric reaction of reactive copper-aryl intermediates with the amidating reagent led us to isolate key copper arylcarbamate species with the formation of a C-N bond. The use of (t)BuONa base made this transformation catalytic under mild conditions. The present (NHC)Cu-catalyzed C-H amidation works efficiently and selectively on a large scale over a range of arenes including polyfluorobenzenes, azoles, and quinoline N-oxides. Deprotection of the newly installed carbamate groups such as Boc and Cbz was readily performed to afford the corresponding primary arylamines.

  17. How Secondary and Tertiary Amide Moieties are Molecular Stations for Dibenzo-24-crown-8 in [2]Rotaxane Molecular Shuttles?

    Directory of Open Access Journals (Sweden)

    Benjamin Riss-Yaw

    2017-11-01

    Full Text Available Interlocked molecular machines like [2]rotaxanes are intriguing aesthetic molecules. The control of the localization of the macrocycle, which surrounds a molecular axle, along the thread leads to translational isomers of very different properties. Although many moieties have been used as sites of interactions for crown ethers, the very straightforwardly obtained amide motif has more rarely been envisaged as molecular station. In this article, we report the use of secondary and tertiary amide moieties as efficient secondary molecular station in pH-sensitive molecular shuttles. Depending on the N-substitution of the amide station, and on deprotonation or deprotonation-carbamoylation, the actuation of the molecular machinery differs accordingly to very distinct interactions between the axle and the DB24C8.

  18. How Secondary and Tertiary Amide Moieties are Molecular Stations for Dibenzo-24-crown-8 in [2]Rotaxane Molecular Shuttles?

    Science.gov (United States)

    Riss-Yaw, Benjamin; Morin, Justine; Clavel, Caroline; Coutrot, Frédéric

    2017-11-21

    Interlocked molecular machines like [2]rotaxanes are intriguing aesthetic molecules. The control of the localization of the macrocycle, which surrounds a molecular axle, along the thread leads to translational isomers of very different properties. Although many moieties have been used as sites of interactions for crown ethers, the very straightforwardly obtained amide motif has more rarely been envisaged as molecular station. In this article, we report the use of secondary and tertiary amide moieties as efficient secondary molecular station in pH-sensitive molecular shuttles. Depending on the N -substitution of the amide station, and on deprotonation or deprotonation-carbamoylation, the actuation of the molecular machinery differs accordingly to very distinct interactions between the axle and the DB24C8.

  19. Mammalian peptidylglycine alpha-amidating monooxygenase (PAM) mRNA expression can be modulated by the La autoantigen

    DEFF Research Database (Denmark)

    Brenet, Fabienne; Dussault, Nadège; Borch, Jonas

    2005-01-01

    Peptidylglycine alpha-amidating monooxygenase (PAM; EC 1.14.17.3) catalyzes the COOH-terminal alpha-amidation of peptidylglycine substrates, yielding amidated products. We have previously reported a putative regulatory RNA binding protein (PAM mRNA-BP) that binds specifically to the 3' untranslated...... region (UTR) of PAM-mRNA. Here, the PAM mRNA-BP was isolated and revealed to be La protein using affinity purification onto a 3' UTR PAM RNA, followed by tandem mass spectrometry identification. We determined that the core binding sequence is approximately 15-nucleotides (nt) long and is located 471 nt...... downstream of the stop codon. Moreover, we identified the La autoantigen as a protein that specifically binds the 3' UTR of PAM mRNA in vivo and in vitro. Furthermore, La protein overexpression caused a nuclear retention of PAM mRNAs and resulted in the down-regulation of endogenous PAM activity. Most...

  20. Polyunsaturated fatty acid amides from the Zanthoxylum genus - from culinary curiosities to probes for chemical biology.

    Science.gov (United States)

    Chruma, Jason J; Cullen, Douglas J; Bowman, Lydia; Toy, Patrick H

    2018-01-25

    Covering up to February 2017The pericarps of several species from the Zanthoxylum genus, a.k.a. the "prickly ash", have long been used for culinary purposes throughout Asia, most notably in the Sichuan (previously Szechuan) cuisine of Southwestern China, due to the unique tingling and numbing orosensations arising from a collection of polyunsaturated fatty acid amide (alkamide) constituents. The past decade has experienced dramatically increased academic and industrial interest in these pungent Zanthoxylum-derived alkamides, with a concomitant explosion in studies aimed at elucidating the specific biochemical mechanisms behind several medically-relevant biological activities exhibited by the natural products. This rapid increase in interest is partially fueled by advances in organic synthesis reported within the past few years that finally have allowed for the production of diastereomerically-pure Zanthoxylum alkamides and related analogs in multigram quantities. Herein is a comprehensive review of the discovery, total synthesis, and biological evaluation of Zanthoxylum-derived polyunsaturated fatty acid amides and synthetic analogues. Critical insights into how chemical synthesis can further benefit future chemical biology efforts in the field are also provided.