Effects of N-Acetylcysteine on Thresholds and Otoacoustic Emissions Following Noise Exposure

DTIC Science & Technology

2004-12-01

EFFECTS OF N- ACETYLCYSTEINE ON THRESHOLDS AND OTOACOUSTIC EMISSIONS FOLLOWING NOISE EXPOSURE Barbara Acker-Mills, Ph.D*., CPT Martin Robinette...wearing ear plugs, muffs, etc.. The current study evaluated the effectiveness of one antioxidant, N- acetylcysteine (NAC), on temporary cochlear changes...4. TITLE AND SUBTITLE Effects Of N- Acetylcysteine On Thresholds And Otoacoustic Emissions Following Noise Exposure 5a. CONTRACT NUMBER 5b

Efficacy of N-Acetylcysteine in Idiopathic Pulmonary Fibrosis

PubMed Central

Sun, Tong; Liu, Jing; Zhao, De Wei

2016-01-01

Abstract There are a number of conflicting reports describing the clinical outcomes of using N-acetylcysteine for the treatment of idiopathic pulmonary fibrosis. We have, therefore, performed a meta-analysis to evaluate the efficacy of N-acetylcysteine, compared with control, for the treatment of idiopathic pulmonary fibrosis. Original controlled clinical trials evaluating the efficacy of N-acetylcysteine for the treatment of idiopathic pulmonary fibrosis were included in the analysis. Searches for relevant articles were carried out in July 2014 by 2 independent researchers using PubMed, Embase, Cochrane Central, and Google Scholar. Change in forced vital capacity, change in percentage of predicted vital capacity, change in percentage of predicted carbon monoxide diffusing capacity, changes in 6 minutes walking test distance, rate of adverse events, and rate of death were expressed as outcomes using RevMan 5.0.1. Five trials, with a total of 564 patients, were included in this meta-analysis. The meta-analysis showed that the control group had significant decreases in percentage of predicted vital capacity (standardized mean difference [SMD] = 0.37; 95% confidence interval [CI]: 0.13 to −0.62; P = 0.003) and 6 minutes walking test distance (SMD = 0.25; 95% CI: 0.02–0.48; P = 0.04). There were no statistically significant differences in forced vital capacity (SMD = 0.07; 95% CI: −0.13–0.27; P = 0.52), percentage of predicted carbon monoxide diffusing capacity (SMD = 0.12; 95% CI: −0.06–0.30; P = 0.18), rates of adverse events (odd ratio = 4.50; 95% CI: 0.19–106.41; P = 0.35), or death rates (odd ratio = 1.79; 95% CI: 0.3–5.12; P = 0.28) between the N-acetylcysteine group and the control group. N-Acetylcysteine was found to have a significant effect only on decreases in percentage of predicted vital capacity and 6 minutes walking test distance. N-acetylcysteine showed no beneficial effect on changes

A double-blind randomized controlled trial of N-acetylcysteine in cannabis-dependent adolescents

PubMed Central

Gray, Kevin M.; Carpenter, Matthew J.; Baker, Nathaniel L.; DeSantis, Stacia M.; Kryway, Elisabeth; Hartwell, Karen J.; McRae-Clark, Aimee L.; Brady, Kathleen T.

2012-01-01

Objective Preclinical findings suggest that the over-the-counter supplement N-acetylcysteine, via glutamate modulation in the nucleus accumbens, holds promise as a pharmacotherapy targeting substance dependence. We sought to investigate N-acetylcysteine as a novel cannabis cessation treatment in adolescents, a vulnerable group for whom existing treatments have limited efficacy. Method In this 8-week double-blind randomized placebo-controlled trial, treatment-seeking cannabis-dependent adolescents (age 15-21, N = 116) received N-acetylcysteine (1200 mg) or placebo twice daily, each added to a contingency management intervention and brief (≤10 minute) weekly cessation counseling. The primary efficacy measure was the odds of negative weekly urine cannabinoid tests during treatment among participants receiving N-acetylcysteine versus placebo, via intent-to-treat analysis. The primary tolerability measure was frequency of adverse events, compared by treatment group. Results N-acetylcysteine was well tolerated with minimal adverse events. N-acetylcysteine participants had more than twice the odds, compared to placebo participants, of submitting negative urine cannabinoid tests during treatment (odds ratio = 2.4, [95% CI: 1.1-5.2], p = 0.029). Exploratory secondary abstinence outcomes numerically favored N-acetylcysteine, but were not statistically significant. Conclusions This is the first randomized trial of pharmacotherapy for cannabis dependence in any age group yielding a positive primary cessation outcome via intent-to-treat analysis. Findings support N-acetylcysteine as a pharmacotherapy to complement psychosocial treatment for cannabis dependence in adolescents. Further research is needed to replicate these findings and explore the efficacy of N-acetylcysteine across a variety of treatment contexts and outcomes. Trial Registration clinicaltrials.gov identifier: NCT 01005810 PMID:22706327

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

PubMed

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.

N-Methylamino Pyrimidyl Amides (MAPA): Highly Reactive, Electronically-Activated Amides in Catalytic N-C(O) Cleavage.

PubMed

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

2017-09-01

Despite recent progress in catalytic cross-coupling technologies, the direct activation of N-alkyl-N-aryl amides has been a challenging transformation. Here, we report the first Suzuki cross-coupling of N-methylamino pyrimidyl amides (MAPA) enabled by the controlled n N → π Ar conjugation and the resulting remodeling of the partial double bond character of the amide bond. The new mode of amide activation is suitable for generating acyl-metal intermediates from unactivated primary and secondary amides.

Structural Characterization of N-Alkylated Twisted Amides: Consequences for Amide Bond Resonance and N-C Cleavage.

PubMed

Hu, Feng; Lalancette, Roger; Szostak, Michal

2016-04-11

Herein, we describe the first structural characterization of N-alkylated twisted amides prepared directly by N-alkylation of the corresponding non-planar lactams. This study provides the first experimental evidence that N-alkylation results in a dramatic increase of non-planarity around the amide N-C(O) bond. Moreover, we report a rare example of a molecular wire supported by the same amide C=O-Ag bonds. Reactivity studies demonstrate rapid nucleophilic addition to the N-C(O) moiety of N-alkylated amides, indicating the lack of n(N) to π*(C=O) conjugation. Most crucially, we demonstrate that N-alkylation activates the otherwise unreactive amide bond towards σ N-C cleavage by switchable coordination. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Protective effects of N-acetylcysteine on experimentally undescended testis.

PubMed

Uyeturk, Ugur; Cetinkaya, Ayhan; Ozyalvacli, Gulzade; Tekce, Buket Kin; Ozyalvacli, Mehmet Emin; Kemahli, Eray; Gucuk, Adnan

2014-04-01

We evaluated the efficacy of N-acetylcysteine for testicular damage induced by undescended testes in rats. Flutamide was injected in the abdomen of pregnant rats daily from days 14 to 20 of gestation. Male offspring with cryptorchidism were randomly divided into 2 groups. Healthy male rats without undescended testes comprised the control group (group 1). Group 2 (undescended testes without N-acetylcysteine) received no treatment. Group 3 (undescended testes plus N-acetylcysteine) received intraperitoneal N-acetylcysteine daily. At 70 days after experiment initiation the testes were removed for histopathological and biochemical analysis. Mean malonyl dialdehyde values were lowest in group 1 and highest in group 2. In group 3 malonyl dialdehyde levels were significantly lower than in group 2 (p <0.001). Conversely, mean glutathione peroxidase was highest in group 1 and lowest in group 2. Glutathione peroxidase levels in group 3 were significantly higher than in group 2 (p <0.001). Histopathological differences between groups 1 and 3 in the modified Johnsen score were not significant (p = 0.041). However, the differences between these groups and group 2 were significant (p <0.001). The median apoptotic cell count did not differ between groups 1 and 3 but it was significantly higher in group 2 than in the other groups (p = 0.03 and <0.001, respectively). N-acetylcysteine may alleviate undescended testis induced damage to testes through its antioxidant effects. The underlying mechanism of these effects merits further investigation. Long-term studies are also needed as well as comparative animal and human studies. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Amide-N-oxide heterosynthon and amide dimer homosynthon in cocrystals of carboxamide drugs and pyridine N-oxides.

PubMed

Babu, N Jagadeesh; Reddy, L Sreenivas; Nangia, Ashwini

2007-01-01

The carboxamide-pyridine N-oxide heterosynthon is sustained by syn(amide)N-H...O-(oxide) hydrogen bond and auxiliary (N-oxide)C-H...O(amide) interaction (Reddy, L. S.; Babu, N. J.; Nangia, A. Chem. Commun. 2006, 1369). We evaluate the scope and utility of this heterosynthon in amide-containing molecules and drugs (active pharmaceutical ingredients, APIs) with pyridine N-oxide cocrystal former molecules (CCFs). Out of 10 cocrystals in this study and 7 complexes from previous work, amide-N-oxide heterosynthon is present in 12 structures and amide dimer homosynthon occurs in 5 structures. The amide dimer is favored over amide-N-oxide synthon in cocrystals when there is competition from another H-bonding functional group, e.g., 4-hydroxybenzamide, or because of steric factors, as in carbamazepine API. The molecular organization in carbamazepine.quinoxaline N,N'-dioxide 1:1 cocrystal structure is directed by amide homodimer and anti(amide)N-H...O-(oxide) hydrogen bond. Its X-ray crystal structure matches with the third lowest energy frame calculated in Polymorph Predictor (Cerius(2), COMPASS force field). Apart from generating new and diverse supramolecular structures, hydration is controlled in one substance. 4-Picoline N-oxide deliquesces within a day, but its cocrystal with barbital does not absorb moisture at 50% RH and 30 degrees C up to four weeks. Amide-N-oxide heterosynthon has potential utility in both amide and N-oxide type drug molecules with complementary CCFs. Its occurrence probability in the Cambridge Structural Database is 87% among 27 structures without competing acceptors and 78% in 41 structures containing OH, NH, H(2)O functional groups.

S-phenyl-N-acetylcysteine in urine of rats and workers after exposure to benzene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jongeneelen, F.J.; Dirven, H.A.; Leijdekkers, C.M.

1987-05-01

An HPLC method for the determination of S-phenyl-N-acetylcysteine in urine is described. The sensitivity is 6 mumol/L (CV = 9%) urine. Exposure of rats to six different concentrations of benzene, ranging from 0-30 ppm, was highly associated with urinary excretion of S-phenyl-N-acetylcysteine (r = 0.86) and with total phenol (r = 0.81). A background level of phenol was found in urine of both non-exposed rats and of non-exposed referents. However, no background excretion of S-phenyl-N-acetylcysteine was found, either in rats or in humans. In urine of exposed rats, the level of S-phenyl-N-acetylcysteine was approximately five times lower than the phenolmore » level. Workers occupationally exposed to benzene, showing high levels of urinary phenol, revealed low concentrations of urinary S-phenyl-N-acetylcysteine. The biological monitoring of industrial exposure to benzene by determination of S-phenyl-N-acetylcysteine in urine is not better than the determination of phenol in urine.« less

Topical N-acetylcysteine improves wound healing comparable to dexpanthenol: an experimental study.

PubMed

Oguz, Abdullah; Uslukaya, Omer; Alabalık, Ulas; Turkoglu, Ahmet; Kapan, Murat; Bozdag, Zubeyir

2015-04-01

In this study, we aimed to compare the effects of dexpanthenol and N-acetylcysteine on wound healing. The wound healing process is a multifaceted sequence of activities associated with tissue restoration process. A number of investigations and clinical studies have been performed to determine new approaches for the improvement of wound healing. A total of 30 rats were divided into 3 equal groups. A linear 2-cm incision was made in the rats' skin. No treatment was administered in the first (control) group. Dexpanthenol cream was administered to the rats in the second group and 3% N-acetylcysteine cream was administered to the rats in the third group. The wound areas of all of the rats were measured on certain days. On the 21st day, all wounds were excised and histologically evaluated. The epithelialization and granulation rates between the groups were revealed to be similar in microscopic evaluations. Although the fibrosis was remarkable in the control group as compared with the other groups, it was similar in N-acetylcysteine and dexpanthenol groups. Angiogenesis rate was remarkable in the N-acetylcysteine group compared with the others. In multiple-comparison analysis, Dexpanthenol and N-acetylcysteine groups had similar results in terms of wound healing rates (P < 0.05), which were both higher than in the control group (P > 0.05). The efficacy of N-acetylcysteine in wound healing is comparable to dexpanthenol, and both substances can be used to improve wound healing.

Topical N-Acetylcysteine Improves Wound Healing Comparable to Dexpanthenol: An Experimental Study

PubMed Central

Oguz, Abdullah; Uslukaya, Omer; Alabalık, Ulas; Turkoglu, Ahmet; Kapan, Murat; Bozdag, Zubeyir

2015-01-01

In this study, we aimed to compare the effects of dexpanthenol and N-acetylcysteine on wound healing. The wound healing process is a multifaceted sequence of activities associated with tissue restoration process. A number of investigations and clinical studies have been performed to determine new approaches for the improvement of wound healing. A total of 30 rats were divided into 3 equal groups. A linear 2-cm incision was made in the rats' skin. No treatment was administered in the first (control) group. Dexpanthenol cream was administered to the rats in the second group and 3% N-acetylcysteine cream was administered to the rats in the third group. The wound areas of all of the rats were measured on certain days. On the 21st day, all wounds were excised and histologically evaluated. The epithelialization and granulation rates between the groups were revealed to be similar in microscopic evaluations. Although the fibrosis was remarkable in the control group as compared with the other groups, it was similar in N-acetylcysteine and dexpanthenol groups. Angiogenesis rate was remarkable in the N-acetylcysteine group compared with the others. In multiple-comparison analysis, Dexpanthenol and N-acetylcysteine groups had similar results in terms of wound healing rates (P < 0.05), which were both higher than in the control group (P > 0.05). The efficacy of N-acetylcysteine in wound healing is comparable to dexpanthenol, and both substances can be used to improve wound healing. PMID:25583306

A potential role for N-acetylcysteine in the management of methamphetamine dependence.

PubMed

McKetin, Rebecca; Dean, Olivia M; Baker, Amanda L; Carter, Greg; Turner, Alyna; Kelly, Peter J; Berk, Michael

2017-03-01

Methamphetamine dependence is a growing problem in Australia and globally. Currently, there are no approved pharmacotherapy options for the management of methamphetamine dependence. N-acetylcysteine is one potential pharmacotherapy option. It has received growing attention as a therapy for managing addictions because of its capacity to restore homeostasis to brain glutamate systems disrupted in addiction and thereby reduce craving and the risk of relapse. N-acetylcysteine also has antioxidant properties that protect against methamphetamine-induced toxicity and it may therefore assist in the management of the neuropsychiatric and neurocognitive effects of methamphetamine. This commentary overviews the actions of N-acetylcysteine and evidence for its efficacy in treating addiction with a particular focus on its potential utility for methamphetamine dependence. We conclude that the preliminary evidence indicates a need for full-scale trials to definitively establish whether N-acetylcysteine has a therapeutic benefit and the nature of this benefit, for managing methamphetamine dependence. [McKetin R, Dean O, Baker A. L, Carter G, Turner A, Kelly P. J, Berk M. A potential role for N-acetylcysteine in the management of methamphetamine dependence. Drug Alcohol Rev 2017;36:153-159]. © 2016 Australasian Professional Society on Alcohol and other Drugs.

The effect of N-acetylcysteine on mechanical fatigue resistance of antibiotic-loaded bone cement.

PubMed

Sukur, Erhan; Akar, Abdulhalim; Topcu, Huseyin Nevzat; Cicekli, Ozgur; Kochai, Alauddin; Turker, Mehmet

2018-05-31

This biomechanical study evaluates the effect of N-acetylcysteine alone and in combination with the most commonly used antibiotic-loaded bone cement mixtures. We mixed eight bone cement mixture groups including combinations of N-acetylcysteine, gentamicin, teicoplanin, and vancomycin and applied a four-point bending test individually to each sample on days 1 and 15 using an MTS Acumen test device. The result was less than 50 MPa-the limit declared by the ISO (International Standards Organization)-in only the "gentamicin + bone cement + N-acetylcysteine" group. Mechanical fatigue resistance of the bone cement decreased significantly with the addition of N-acetylcysteine both on day 1 and day 15 (p <  0.001). With the addition of N-acetylcysteine into the "gentamicin + bone cement" and "vancomycin + bone cement" mixtures, a significant decrease in mechanical fatigue resistance was observed both on day 1 and day 15 (p <  0.001). In contrast, with the addition of N-acetylcysteine into the "teicoplanin + bone cement" mixture, no significant difference in mechanical fatigue resistance was observed on days 1 and 15 (p = 0.093, p = 0.356). Preliminary results indicate that adding N-acetylcysteine to teicoplanin-loaded bone cement does not significantly affect the cement's mechanical resistance, potentially leading to a new avenue for preventing and treating peri-prosthetic joint infection. N-acetylcysteine may, therefore, be considered as an alternative agent to be added to antibiotic-loaded bone cement mixtures used in the prevention of peri-prosthetic joint infection.

N-acetylcysteine prevents ketamine-induced adverse effects on development, heart rate and monoaminergic neurons in zebrafish.

PubMed

Robinson, Bonnie; Dumas, Melanie; Gu, Qiang; Kanungo, Jyotshna

2018-06-08

N-acetylcysteine, a precursor molecule of glutathione, is an antioxidant. Ketamine, a pediatric anesthetic, has been implicated in cardiotoxicity and neurotoxicity including modulation of monoaminergic systems in mammals and zebrafish. Here, we show that N-acetylcysteine prevents ketamine's adverse effects on development and monoaminergic neurons in zebrafish embryos. The effects of ketamine and N-acetylcysteine alone or in combination were measured on the heart rate, body length, brain serotonergic neurons and tyrosine hydroxylase-immunoreactive (TH-IR) neurons. In the absence of N-acetylcysteine, a concentration of ketamine that produces an internal embryo exposure level comparable to human anesthetic plasma concentrations significantly reduced heart rate and body length and those effects were prevented by N-acetylcysteine co-treatment. Ketamine also reduced the areas occupied by serotonergic neurons in the brain, whereas N-acetylcysteine co-exposure counteracted this effect. TH-IR neurons in the embryo brain and TH-IR cells in the trunk were significantly reduced with ketamine treatment, but not in the presence of N-acetylcysteine. In our continued search for compounds that can prevent ketamine toxicity, this study using specific endpoints of developmental toxicity, cardiotoxicity and neurotoxicity, demonstrates protective effects of N-acetylcysteine against ketamine's adverse effects. This is the first study that shows the protective effects of N-acetylcysteine on ketamine-induced developmental defects of monoaminergic neurons as observed in a whole organism. Published by Elsevier B.V.

N-Acetylcysteine in depressive symptoms and functionality: a systematic review and meta-analysis.

PubMed

Fernandes, Brisa S; Dean, Olivia M; Dodd, Seetal; Malhi, Gin S; Berk, Michael

2016-04-01

To assess the utility of N-acetylcysteine administration for depressive symptoms in subjects with psychiatric conditions using a systematic review and meta-analysis. A computerized literature search was conducted in MEDLINE, Embase, the Cochrane Library, SciELO, PsycINFO, Scopus, and Web of Knowledge. No year or country restrictions were used. The Boolean terms used for the electronic database search were (NAC OR N-acetylcysteine OR acetylcysteine) AND (depression OR depressive OR depressed) AND (trial). The last search was performed in November 2014. The literature was searched for double-blind, randomized, placebo-controlled trials using N-acetylcysteine for depressive symptoms regardless of the main psychiatric condition. Using keywords and cross-referenced bibliographies, 38 studies were identified and examined in depth. Of those, 33 articles were rejected because inclusion criteria were not met. Finally, 5 studies were included. Data were extracted independently by 2 investigators. The primary outcome measure was change in depressive symptoms. Functionality, quality of life, and manic and anxiety symptoms were also examined. A full review and meta-analysis were performed. Standardized mean differences (SMDs) and odds ratios (ORs) with 95% CIs were calculated. Five studies fulfilled our inclusion criteria for the meta-analysis, providing data on 574 participants, of whom 291 were randomized to receive N-acetylcysteine and 283 to placebo. The follow-up varied from 12 to 24 weeks. Two studies included subjects with bipolar disorder and current depressive symptoms, 1 included subjects with MDD in a current depressive episode, and 2 included subjects with depressive symptoms in the context of other psychiatric conditions (1 trichotillomania and 1 heavy smoking). Treatment with N-acetylcysteine improved depressive symptoms as assessed by Montgomery-Asberg Depression Rating Scale and Hamilton Depression Rating Scale when compared to placebo (SMD = 0.37; 95% CI = 0

Systemic inflammation and oxidative stress post-lung resection: Effect of pretreatment with N-acetylcysteine.

PubMed

Bastin, Anthony J; Davies, Nathan; Lim, Eric; Quinlan, Greg J; Griffiths, Mark J

2016-01-01

N-acetylcysteine has been used to treat a variety of lung diseases, where is it thought to have an antioxidant effect. In a randomized placebo-controlled double-blind study, the effect of N-acetylcysteine on systemic inflammation and oxidative damage was examined in patients undergoing lung resection, a human model of acute lung injury. Eligible adults were randomized to receive preoperative infusion of N-acetylcysteine (240 mg/kg over 12 h) or placebo. Plasma thiols, interleukin-6, 8-isoprostane, ischaemia-modified albumin, red blood cell glutathione and exhaled breath condensate pH were measured pre- and post-operatively as markers of local and systemic inflammation and oxidative stress. Patients undergoing lung resection and one-lung ventilation exhibited significant postoperative inflammation and oxidative damage. Postoperative plasma thiol concentration was significantly higher in the N-acetylcysteine-treated group. However, there was no significant difference in any of the measured biomarkers of inflammation or oxidative damage, or in clinical outcomes, between N-acetylcysteine and placebo groups. Preoperative administration of N-acetylcysteine did not attenuate postoperative systemic or pulmonary inflammation or oxidative damage after lung resection. NCT00655928 at ClinicalTrials.gov. © 2015 Asian Pacific Society of Respirology.

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

PubMed

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.

Structures of Highly Twisted Amides Relevant to Amide N-C Cross-Coupling: Evidence for Ground-State Amide Destabilization.

PubMed

Pace, Vittorio; Holzer, Wolfgang; Meng, Guangrong; Shi, Shicheng; Lalancette, Roger; Szostak, Roman; Szostak, Michal

2016-10-04

Herein, we show that acyclic amides that have recently enabled a series of elusive transition-metal-catalyzed N-C activation/cross-coupling reactions are highly twisted around the N-C(O) axis by a new destabilization mechanism of the amide bond. A unique effect of the N-glutarimide substituent, leading to uniformly high twist (ca. 90°) irrespective of the steric effect at the carbon side of the amide bond has been found. This represents the first example of a twisted amide that does not bear significant steric hindrance at the α-carbon atom. The (15) N NMR data show linear correlations between electron density at nitrogen and amide bond twist. This study strongly supports the concept of amide bond ground-state twist as a blueprint for activation of amides toward N-C bond cleavage. The new mechanism offers considerable opportunities for organic synthesis and biological processes involving non-planar amide bonds. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

N-Acetylcysteine Restores Sevoflurane Postconditioning Cardioprotection against Myocardial Ischemia-Reperfusion Injury in Diabetic Rats.

PubMed

Lin, Jiefu; Wang, Tingting; Li, Yalan; Wang, Mengxia; Li, Haobo; Irwin, Michael G; Xia, Zhengyuan

2016-01-01

The effect of sevoflurane postconditioning (sevo-postC) cardioprotection is compromised in diabetes which is associated with increased oxidative stress. We hypothesized that antioxidant N-Acetylcysteine may enhance or restore sevo-postC cardioprotection in diabetes. Control or streptozotocin-induced Type 1 diabetic rats were either untreated or treated with N-Acetylcysteine for four weeks starting at five weeks after streptozotocin injection and were subjected to myocardial ischemia-reperfusion injury (IRI), in the absence or presence of sevo-postC. Diabetes showed reduction of cardiac STAT3 activation (p-STAT3) and adiponectin with concomitantly increase of FoxO1 and CD36, which associated with reduced sevo-postC cardioprotection. N-Acetylcysteine and sevo-postC synergistically reduced the infarct size in diabetic groups. N-Acetylcysteine remarkably increased cardiac p-STAT3 which was further enhanced by sevo-postC. N-Acetylcysteine but not sevo-postC decreased myocardial FoxO1 while sevo-postC but not N-Acetylcysteine significantly increased myocardiac adiponectin in diabetic rats. It is concluded that late stage diabetic rats displayed reduction of cardiac p-STAT3, adiponectin deficiency, and increase of FoxO1 and CD36 expression, which may be responsible for the loss of myocardial responsiveness to sevo-postC cardioprotection. N-Acetylcysteine restored Sevo-postC cardioprotection in diabetes possibly through enhancing cardiac p-STAT3 and adiponectin and reducing Fox1 and CD36.

Acquired 5-oxoproline acidemia successfully treated with N-acetylcysteine.

PubMed

Hundemer, Gregory L; Fenves, Andrew Z

2017-04-01

Acquired 5-oxoprolinemia is increasingly recognized as a cause of anion gap metabolic acidosis. It predominantly occurs in chronically ill, malnourished women with impaired renal function and chronic acetaminophen ingestion. Depletion of glutathione and cysteine stores leads to elevated 5-oxoproline levels. N-acetylcysteine, given its effect in repleting glutathione and cysteine stores, has been proposed as a potential treatment for 5-oxoprolinemia, though reports of its successful use are lacking. We present a case of 5-oxoproline metabolic acidosis that persisted despite discontinuation of acetaminophen. However, the acidosis rapidly resolved with N-acetylcysteine administration.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

2006-06-15

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 hadmore » 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 {mu}mol/l prior to the procedure and 155.6 {+-} 48.6 {mu}mol/l (p = 0.49) after the procedure. Respective values for those without renal impairment were 79.6 {+-} 15.1 {mu}mol/l and 81.2 {+-} 20.0 {mu}mol/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 {mu}mol/l (p = 0.17) in patients with renal impairment and 79.7 {+-} 14.2 and 81.4 {+-} 15.4 {mu}mol/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.« less

N-acetylcysteine potentiates platelet inhibition by endothelium-derived relaxing factor.

PubMed

Stamler, J; Mendelsohn, M E; Amarante, P; Smick, D; Andon, N; Davies, P F; Cooke, J P; Loscalzo, J

1989-09-01

Recent evidence suggests that endothelium-derived relaxing factor exhibits properties of nitric oxide. Like nitric oxide, it inhibits platelet function and mediates its effects by elevating intracellular cyclic GMP. In this study we have investigated the role of reduced thiol in the mechanism of action of endothelium-derived relaxing factor on platelets. Bovine aortic endothelial cells were grown on microcarrier beads and pretreated with aspirin before use. Endothelial cells stimulated with bradykinin or exposed to stirred medium expressed a dose-dependent inhibition of platelet aggregation that was potentiated by the reduced thiol, N-acetylcysteine. Endothelial cell-mediated platelet inhibition was attenuated by methylene blue. Inhibition of platelet aggregation by endothelial cells was associated with a rise in platelet intracellular cyclic GMP, an effect that was enhanced by N-acetylcysteine. These data show that 1) the reduced thiol N-acetylcysteine potentiates platelet inhibition by endothelium-derived relaxing factor and 2) this effect is associated with increasing intracellular platelet cyclic GMP levels.

N-acetylcysteine in Acute Organophosphorus Pesticide Poisoning: A Randomized, Clinical Trial.

PubMed

El-Ebiary, Ahmad A; Elsharkawy, Rasha E; Soliman, Nema A; Soliman, Mohammed A; Hashem, Ahmed A

2016-08-01

Organophosphorus poisoning is a major global health problem with hundreds of thousands of deaths each year. Research interest in N-acetylcysteine has grown among increasing evidence of the role of oxidative stress in organophosphorus poisoning. We aimed to assess the safety and efficacy of N-acetylcysteine as an adjuvant treatment in patients with acute organophosphorus poisoning. This was a randomized, controlled, parallel-group trial on 30 patients suffering from acute organophosphorus poisoning, who were admitted to the Poison Control Center of Tanta University Emergency Hospital, Tanta, Egypt, between April and September 2014. Interventions included oral N-acetylcysteine (600 mg three times daily for 3 days) as an added treatment to the conventional measures versus only the conventional treatment. Outcome measures included mortality, total dose of atropine administered, duration of hospitalization and the need for ICU admission and/or mechanical ventilation. A total of 46 patients were screened and 30 were randomized. No significant difference was found between both groups regarding demographic characteristics and the nature or severity of baseline clinical manifestations. No major adverse effects to N-acetylcysteine therapy were reported. Malondialdehyde significantly decreased and reduced glutathione significantly increased only in the NAC-treated patients. The patients on NAC therapy required less atropine doses than those who received only the conventional treatment; however, the length of hospital stay showed no significant difference between both groups. The study concluded that the use of N-acetylcysteine as an added treatment was apparently safe, and it reduced atropine requirements in patients with acute organophosphorus pesticide poisoning. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Effect of N-Acetylcysteine on Adipose-Derived Stem Cell and Autologous Fat Graft Survival in a Mouse Model.

PubMed

Gillis, Joshua; Gebremeskel, Simon; Phipps, Kyle D; MacNeil, Lori A; Sinal, Christopher J; Johnston, Brent; Hong, Paul; Bezuhly, Michael

2015-08-01

Autologous fat grafting is a popular reconstructive technique, but is limited by inconsistent graft retention. The authors examined whether a widely available, clinically safe antioxidant, N-acetylcysteine, could improve adipose-derived stem cell survival and graft take when added to tumescent solution during fat harvest. Inguinal fat pads were harvested from C57BL/6 mice using tumescent solution with or without N-acetylcysteine. Flow cytometric, proliferation, and differentiation assays were performed on isolated primary adipose-derived stem cells and 3T3-L1 preadipocytes treated with or without hydrogen peroxide and/or N-acetylcysteine. N-Acetylcysteine-treated or control grafts were injected under recipient mouse scalps and assessed by serial micro-computed tomographic volumetric analysis. Explanted grafts underwent immunohistochemical analysis. In culture, N-acetylcysteine protected adipose-derived stem cells from oxidative stress and improved cell survival following hydrogen peroxide treatment. Combined exposure to both N-acetylcysteine and hydrogen peroxide led to a 200-fold increase in adipose-derived stem cell proliferation, significantly higher than with either agent alone. N-Acetylcysteine decreased differentiation of adipose-derived stem cells into mature adipocytes, as evidenced by decreased transcription of adipocyte differentiation markers and reduced Oil Red-O staining. In vivo, N-acetylcysteine treatment resulted in improved graft retention at 3 months compared with control (46 versus 17 percent; p = 0.027). N-Acetylcysteine-treated grafts demonstrated less fibrosis and inflammation, and a 33 percent increase in adipocyte density compared with controls (p < 0.001) that was not associated with increased vascularity. These findings provide proof of principle for the addition of N-acetylcysteine to tumescent harvest solution in the clinical setting to optimize fat graft yields.

Similarities between N-acetylcysteine and Glutathione in Binding to Lead(II) Ions

PubMed Central

Sisombath, Natalie S.; Jalilehvand, Farideh

2015-01-01

N -acetylcysteine is a natural thiol-containing antioxidant, a precursor for cysteine and glutathione, and a potential detoxifying agent for heavy metal ions. However, previous accounts of the efficiency of N-acetylcysteine (H2NAC) in excretion of lead are few and contradicting. Here we report results on the nature of lead(II) complexes formed with N-acetylcysteine in aqueous solution, which were obtained by combining information from several spectroscopic methods, including 207Pb, 13C and 1H NMR, Pb LIII-edge X-ray absorption, Ultraviolet-visible (UV-vis.) spectroscopy and electro-spray ionization mass spectrometry (ESI-MS). Two series of solutions were used containing CPb(II) = 10 and 100 mM, respectively, varying the H2NAC / Pb(II) mole ratios from 2.1 to 10.0 at pH = 9.1 – 9.4. The coordination environments obtained resemble those previously found for the Pb(II) glutathione system: at a ligand-to-lead mole ratio of 2.1 dimeric or oligomeric Pb(II) N-acetylcysteine complexes are formed, while a tri-thiolate [Pb(NAC)3]4− complex dominates in solutions with H2NAC/Pb(II) mole ratios > 3.0. PMID:26624959

Minocycline and N-acetylcysteine: A Synergistic Drug Combination to Treat Traumatic Brain Injury

DTIC Science & Technology

2011-10-01

AD_________________ Award Number: W81XWH-10-2-0171 TITLE: Minocycline and N-acetylcysteine: A... Minocycline and N-acetylcysteine: A Synergistic Drug Combination to Treat Traumatic Brain Injury 5b. GRANT NUMBER W81XWH-10-2-0171 5c. PROGRAM...combination of minocycline (MINO) and N-acetyl cysteine (NAC) synergistically improved brain function when dosed one hour following closed cortical

Efficacy and safety of inhaled N-acetylcysteine in idiopathic pulmonary fibrosis: A prospective, single-arm study.

PubMed

Okuda, Ryo; Matsushima, Hidekazu; Oba, Tomohiro; Kawabe, Rie; Matsubayashi, Minako; Amano, Masako; Nishizawa, Tomotaka; Honda, Koujiro

2016-05-01

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with few treatment options. The efficacy of N-acetylcysteine in patients with IPF remains controversial. The aim of this research was to investigate the efficacy of inhaled N-acetylcysteine. This study was designed as a single-center, single-arm, prospective clinical trial. Each patient who had IPF received 352.4mg of inhaled N-acetylcysteine twice daily. In total, 28 patients were enrolled. The mean values of the respiratory function parameters at the initiation of therapy were as follows: forced vital capacity (FVC), 2.27L and %FVC, 76.2%. The mean change in FVC during 26 weeks prior to the inhaled N-acetylcysteine therapy was -170mL, a significant decrease (p=0.019). The mean change in FVC during 26 weeks after the initiation of inhaled N-acetylcysteine therapy was -70mL (p=0.06). When the patients were classified into two groups according to the degree of decline in FVC (≥100mL vs. <100mL) during the 26-week period prior to the initiation of therapy, inhaled N-acetylcysteine showed a greater efficacy in attenuating FVC decline in the ≥100-mL group than in the <100-mL group. Inhaled N-acetylcysteine therapy was effective in patients with mild-to-moderate IPF and was more beneficial in patients who had greater declines in FVC before the initiation of therapy. (UMIN title: Efficacy and safety of inhaled N-acetylcysteine in idiopathic pulmonary fibrosis, UMIN000016706, 2015/03/04.). Copyright © 2015 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Precise determination of N-acetylcysteine in pharmaceuticals by microchip electrophoresis.

PubMed

Rudašová, Marína; Masár, Marián

2016-01-01

A novel microchip electrophoresis method for the rapid and high-precision determination of N-acetylcysteine, a pharmaceutically active ingredient, in mucolytics has been developed. Isotachophoresis separations were carried out at pH 6.0 on a microchip with conductivity detection. The methods of external calibration and internal standard were used to evaluate the results. The internal standard method effectively eliminated variations in various working parameters, mainly run-to-run fluctuations of an injected volume. The repeatability and accuracy of N-acetylcysteine determination in all mucolytic preparations tested (Solmucol 90 and 200, and ACC Long 600) were more than satisfactory with the relative standard deviation and relative error values <0.7 and <1.9%, respectively. A recovery range of 99-101% of N-acetylcysteine in the analyzed pharmaceuticals predetermines the proposed method for accurate analysis as well. This work, in general, indicates analytical possibilities of microchip isotachophoresis for the quantitative analysis of simplified samples such as pharmaceuticals that contain the analyte(s) at relatively high concentrations. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

PubMed

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.

Possible involvement of the JAK/STAT signaling pathway in N-acetylcysteine-mediated antidepressant-like effects.

PubMed

Al-Samhari, Marwa M; Al-Rasheed, Nouf M; Al-Rejaie, Salim; Al-Rasheed, Nawal M; Hasan, Iman H; Mahmoud, Ayman M; Dzimiri, Nduna

2016-03-01

Advances in depression research have targeted inflammation and oxidative stress to develop novel types of treatment. The JAK/STAT signaling pathway plays pivotal roles in immune and inflammatory responses. The present study was designed to investigate the effects of N-acetylcysteine, a putative precursor of the antioxidant glutathione, in an animal model of depression, with an emphasis on the JAK/STAT signaling pathway. Fluoxetine, a classical antidepressant drug was also under investigation. Male Wistar rats were subjected to forced swimming test and given N-acetylcysteine and fluoxetine immediately after the pre-test session, 5 h later and 1 h before the test session of the forced swimming test. N-acetylcysteine decreased immobility time (P < 0.05), serum corticosterone (P < 0.001), and hydrogen peroxide (P < 0.001), while restored glutathione concentration. Treatment of the rats with N-acetylcysteine produced significant (P < 0.001) down-regulation of STAT3 mRNA expression and protein phosphorylation. On the other hand, N-acetylcysteine significantly (P < 0.001) increased SOCS3 gene expression; however, SOCS3 protein was not changed. In conclusion, our study suggests that modulation of the JAK/STAT pathway might mediate the antidepressant-like effects of N-acetylcysteine. Therefore, depression research may target the JAK/STAT signaling pathway to provide a novel effective therapy. © 2015 by the Society for Experimental Biology and Medicine.

Possible involvement of the JAK/STAT signaling pathway in N-acetylcysteine-mediated antidepressant-like effects

PubMed Central

Al-Samhari, Marwa M; Al-Rasheed, Nouf M; Al-Rejaie, Salim; Al-Rasheed, Nawal M; Hasan, Iman H; Dzimiri, Nduna

2015-01-01

Advances in depression research have targeted inflammation and oxidative stress to develop novel types of treatment. The JAK/STAT signaling pathway plays pivotal roles in immune and inflammatory responses. The present study was designed to investigate the effects of N-acetylcysteine, a putative precursor of the antioxidant glutathione, in an animal model of depression, with an emphasis on the JAK/STAT signaling pathway. Fluoxetine, a classical antidepressant drug was also under investigation. Male Wistar rats were subjected to forced swimming test and given N-acetylcysteine and fluoxetine immediately after the pre-test session, 5 h later and 1 h before the test session of the forced swimming test. N-acetylcysteine decreased immobility time (P < 0.05), serum corticosterone (P < 0.001), and hydrogen peroxide (P < 0.001), while restored glutathione concentration. Treatment of the rats with N-acetylcysteine produced significant (P < 0.001) down-regulation of STAT3 mRNA expression and protein phosphorylation. On the other hand, N-acetylcysteine significantly (P < 0.001) increased SOCS3 gene expression; however, SOCS3 protein was not changed. In conclusion, our study suggests that modulation of the JAK/STAT pathway might mediate the antidepressant-like effects of N-acetylcysteine. Therefore, depression research may target the JAK/STAT signaling pathway to provide a novel effective therapy. PMID:26643864

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

PubMed

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.

Minocycline and N-acetylcysteine: A Synergistic Drug Combination to Treat Traumatic Brain Injury

DTIC Science & Technology

2012-10-01

W81XWH-10-2-0171 TITLE: Minocycline and N-acetylcysteine: a synergistic drug combination to treat traumatic brain injury PRINCIPAL INVESTIGATOR...TITLE AND SUBTITLE Minocycline and N-acetylcysteine: a synergistic drug combination to treat traumatic brain injury 5a. CONTRACT NUMBER 5b...The grantee previously found screened that the combination of minocycline (MINO) and N-acetyl cysteine (NAC) synergistically improved brain function

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

PubMed

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 < .001) and the Psychiatric Institute 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

Effects of histidine and n-acetylcysteine on experimental lesions induced by doxorubicin in sciatic nerve of rats.

PubMed

Farshid, Amir Abbas; Tamaddonfard, Esmaeal; Najafi, Sima

2015-10-01

In this study, the effect of separate and combined intraperitoneal (i.p.) injections of histidine and n-acetylcysteine were investigated on experimental damage induced by doxorubicin (DOX) in sciatic nerve of rats. DOX was i.p. injected at a dose of 4 mg/kg once weekly for four weeks. Histidine and n-acetylcysteine were i.p. injected at a same dose of 20 mg/kg. Cold and mechanical allodynia were recorded using acetone spray and von Frey filaments tests, respectively. The sciatic nerve damage was evaluated by light microscopy. Plasma levels of malondialdehyde (MDA) and total antioxidant capacity (TAC) were measured. Histidine and especially n-acetylcysteine at a same dose of 20 mg/kg suppressed cold and mechanical allodynia, improved sciatic nerve lesions and reversed MDA and TAC levels in DOX-treated groups. Combination treatment with histidine and n-acetylcysteine showed better responses when compared with them used alone. The results of the present study showed peripheral neuroprotective effects for histidine and n-acetylcysteine. Reduction of free radical-induced toxic effects may have a role in neuroprotective properties of histidine and n-acetylcysteine.

N-acetylcysteine improves coronary and peripheral vascular function.

PubMed

Andrews, N P; Prasad, A; Quyyumi, A A

2001-01-01

We investigated whether N-acetylcysteine (NAC), a reduced thiol that modulates redox state and forms adducts of nitric oxide (NO), improves endothelium-dependent vasomotion. Coronary atherosclerosis is associated with endothelial dysfunction and reduced NO activity. In 16 patients undergoing cardiac catheterization, seven with and nine without atherosclerosis, we assessed endothelium-dependent vasodilation with acetylcholine (ACH) and endothelium-independent vasodilation with nitroglycerin (NTG) and sodium nitroprusside (SNP) before and after intracoronary NAC. In 14 patients femoral vascular responses to ACH, NTG and SNP were measured before and after NAC. Intraarterial NAC did not change resting coronary or peripheral vascular tone. N-acetylcysteine potentiated ACH-mediated coronary vasodilation; coronary blood flow was 36 +/- 11% higher (p < 0.02), and epicardial diameter changed from -1.2 +/- 2% constriction to 4.7 +/- 2% dilation after NAC (p = 0.03). Acetylcholine-mediated femoral vasodilation was similarly potentiated by NAC (p = 0.001). Augmentation of the ACH response was similar in patients with or without atherosclerosis. N-acetylcysteine did not affect NTG-mediated vasodilation in either the femoral or coronary circulations and did not alter SNP responses in the femoral circulation. In contrast, coronary vasodilation with SNP was significantly greater after NAC (p < 0.05). Thiol supplementation with NAC improves human coronary and peripheral endothelium-dependent vasodilation. Nitroglycerin responses are not enhanced, but SNP-mediated responses are potentiated only in the coronary circulation. These NO-enhancing effects of thiols reflect the importance of the redox state in the control of vascular function and may be of therapeutic benefit in treating acute and chronic manifestations of atherosclerosis.

A gargantuan acetaminophen level in an acidemic patient treated solely with intravenous N-acetylcysteine.

PubMed

Zell-Kanter, Michele; Coleman, Patrick; Whiteley, Patrick M; Leikin, Jerrold B

2013-01-01

The objective of this report is to describe an acidemic patient with one of the largest recorded acetaminophen ingestions in a patient with acidemia who was treated with supportive care and intravenous (IV) N-acetylcysteine. A 59-year-old female with a history of depression was found comatose. In the Emergency Department, she was obtunded with agonal respirations and immediately intubated. Activated charcoal was given through a nasogastric tube. An initial acetaminophen serum level was 1141 mg/L. The patient was started on IV N-acetylcysteine. The acetaminophen level peaked 2 hours later at 1193 mg/L. She was continued on the IV N-acetylcysteine protocol. The next day her aspartate aminotransferase was 3150 U/L, alanine aminotransferase was 2780 U/L, and creatinine phosphokinase was 16,197 U/L. There was no elevation in bilirubin or international normalized ratio (INR). Transaminase levels decreased on day 3 and normalized by day 4 when she was transferred to a psychiatric unit. Few cases have been reported of strikingly elevated acetaminophen levels in poisoned patients who did not receive hemodialysis. These patients did have increased lactate levels, and some had normal liver function tests. All of these patients received N-acetylcysteine and survived the poisoning without sequelae. This patient in this report was unique in that she had the highest reported serum acetaminophen level with acidosis and was treated successfully with only IV N-acetylcysteine and supportive care.

Combination of tauroursodeoxycholic acid and N-acetylcysteine exceeds standard treatment for acetaminophen intoxication.

PubMed

Paridaens, Annelies; Raevens, Sarah; Colle, Isabelle; Bogaerts, Eliene; Vandewynckel, Yves-Paul; Verhelst, Xavier; Hoorens, Anne; van Grunsven, Leo A; Van Vlierberghe, Hans; Geerts, Anja; Devisscher, Lindsey

2017-05-01

Acetaminophen overdose in mice is characterized by hepatocyte endoplasmic reticulum stress, which activates the unfolded protein response, and centrilobular hepatocyte death. We aimed at investigating the therapeutic potential of tauroursodeoxycholic acid, a hydrophilic bile acid known to have anti-apoptotic and endoplasmic reticulum stress-reducing capacities, in experimental acute liver injury induced by acetaminophen overdose. Mice were injected with 300 mg/kg acetaminophen, 2 hours prior to receiving tauroursodeoxycholic acid, N-acetylcysteine or a combination therapy, and were euthanized 24 hours later. Liver damage was assessed by serum transaminases, liver histology, terminal deoxynucleotidyl transferase dUTP nick end labelling staining, expression profiling of inflammatory, oxidative stress, unfolded protein response, apoptotic and pyroptotic markers. Acetaminophen overdose resulted in a significant increase in serum transaminases, hepatocyte cell death, unfolded protein response activation, oxidative stress, NLRP3 inflammasome activation, caspase 1 and pro-inflammatory cytokine expressions. Standard of care, N-acetylcysteine and, to a lesser extent, tauroursodeoxycholic treatment were associated with significantly lower transaminase levels, hepatocyte death, unfolded protein response activation, oxidative stress markers, caspase 1 expression and NLRP3 levels. Importantly, the combination of N-acetylcysteine and tauroursodeoxycholic acid improved serum transaminase levels, reduced histopathological liver damage, UPR-activated CHOP, oxidative stress, caspase 1 expression, NLRP3 levels, IL-1β levels and the expression of pro-inflammatory cytokines and this to a greater extend than N-acetylcysteine alone. These findings indicate that a combination strategy of N-acetylcysteine and tauroursodeoxycholic acid surpasses the standard of care in acetaminophen-induced liver injury in mice and might represent an attractive therapeutic opportunity for acetaminophen

An Efficient Amide-Aldehyde-Alkene Condensation: Synthesis for the N-Allyl Amides.

PubMed

Quan, Zheng-Jun; Wang, Xi-Cun

2016-02-01

The allylamine skeleton represents a significant class of biologically active nitrogen compounds that are found in various natural products and drugs with well-recognized pharmacological properties. In this personal account, we will briefly discuss the synthesis of allylamine skeletons. We will focus on showing a general protocol for Lewis acid-catalyzed N-allylation of electron-poor N-heterocyclic amides and sulfonamide via an amide-aldehyde-alkene condensation reaction. The substrate scope with respect to N-heterocyclic amides, aldehydes, and alkenes will be discussed. This method is also capable of preparing the Naftifine motif from N-methyl-1-naphthamide or methyl (naphthalene-1-ylmethyl)carbamate, with paraformaldehyde and styrene in a one-pot manner. © 2016 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

PubMed

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.

[Decreasing reperfusion damage with N-acetylcysteine in experimental pancreas transplantion].

PubMed

Mayer, H; Thies, J; Schmidt, J; Gebhard, M M; Herfarth, C; Klar, E

1998-01-01

In this study we investigated the effect of donor and recipient conditioning with N-acetylcysteine on the ischemia/reperfusion injury after experimental pancreas-transplantation. We performed standardized pancreaticoduodenal transplantation in male lewis rats. The pancreas was perfused with UW-solution, harvested and conserved at 4 degrees C. Cold ischemia time was 1.5 hours and 16 hours respectively. The microcirculation in the transplanted organ was quantified by means of intravital microscopy 1.5 hours after implantation and reperfusion in the recipient. After 16 hours of cold ischemia we found a significant reduction in capillary erythrocyte velocity and a significantly enhanced leucocyte/endothelium interaction. The treatment with N-acetylcysteine resulted in a significant improvement of these microcirculatory disorders after prolonged cold ischemia.

SPICE/K2 Synthetic Marijuana-Induced Toxic Hepatitis Treated with N-Acetylcysteine

PubMed Central

Sheikh, Israr A.; Lukšič, Miha; Ferstenberg, Richard; Culpepper-Morgan, Joan A.

2014-01-01

Patient: Male, 45 Final Diagnosis: Spice/K2 induced liver injury Symptoms: Lethargy • somnolence • fatigue Medication: N-acetylcysteine Clinical Procedure: — Specialty: Gastroenterology Objective: Rare disease Background: Spice/K2 is one of several street names for synthetic marijuana. These hallucinogens are increasingly sold over the internet and in “head” shops. They are usually household herbs that are sprayed with chemicals that become centrally active compounds when burned together and inhaled by smoking. Case Report: We present a case of a 45-year-old male substance abuser who was admitted with evidence of hepatocellular necrosis and worsening liver failure. Tests for acetaminophen were negative, as were tests for alcohol. The patient was empirically treated with N-acetylcysteine. Hepatocellular damage was abated and the patient made a full recovery. Upon regaining consciousness, the patient admitted to smoking Spice/K2. Other toxicities have been reported with synthetic marijuana use, but not liver toxicity. Conclusions: Physicians need to have a high index of suspicion for unknown hepatotoxins in substance abusers. N-acetylcysteine can be given if there is no contraindication. PMID:25548903

N-acetylcysteine attenuates the development of cardiac fibrosis and remodeling in a mouse model of heart failure.

PubMed

Giam, Beverly; Chu, Po-Yin; Kuruppu, Sanjaya; Smith, A Ian; Horlock, Duncan; Kiriazis, Helen; Du, Xiao-Jun; Kaye, David M; Rajapakse, Niwanthi W

2016-04-01

Oxidative stress plays a central role in the pathogenesis of heart failure. We aimed to determine whether the antioxidantN-acetylcysteine can attenuate cardiac fibrosis and remodeling in a mouse model of heart failure. Minipumps were implanted subcutaneously in wild-type mice (n = 20) and mice with cardiomyopathy secondary to cardiac specific overexpression of mammalian sterile 20-like kinase 1 (MST-1;n = 18) to administerN-acetylcysteine (40 mg/kg per day) or saline for a period of 8 weeks. At the end of this period, cardiac remodeling and function was assessed via echocardiography. Fibrosis, oxidative stress, and expression of collagen types I andIIIwere quantified in heart tissues. Cardiac perivascular and interstitial fibrosis were greater by 114% and 209%, respectively, inMST-1 compared to wild type (P ≤ 0.001). InMST-1 mice administeredN-acetylcysteine, perivascular and interstitial fibrosis were 40% and 57% less, respectively, compared to those treated with saline (P ≤ 0. 03). Cardiac oxidative stress was 119% greater inMST-1 than in wild type (P < 0.001) andN-acetylcysteine attenuated oxidative stress inMST-1 by 42% (P = 0.005). These data indicate thatN-acetylcysteine can blunt cardiac fibrosis and related remodeling in the setting of heart failure potentially by reducing oxidative stress. This study provides the basis to investigate the role ofN-acetylcysteine in chronic heart failure. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Rebamipide increases the amount of mucin-like substances on the conjunctiva and cornea in the N-acetylcysteine-treated in vivo model.

PubMed

Urashima, Hiroki; Okamoto, Takashi; Takeji, Yasuhiro; Shinohara, Hisashi; Fujisawa, Shigeki

2004-08-01

Rebamipide increases the amount of mucin-like substances in the stomach. We aimed to determine the effects of rebamipide on the amount of mucin-like substances in the conjunctiva and cornea of N-acetylcysteine-treated eyes. Furthermore, we attempted to evaluate the effects of rebamipide on the wound healing of N-acetylcysteine-treated eyes. The model was created by instilling 10% N-acetylcysteine solutions into rabbit eyes. Rebamipide was then applied on the day following the completion of N-acetylcysteine treatment. The amount of mucin-like substances on the conjunctiva and cornea was measured using the Alcian-blue binding method. The degree of damage was evaluated using scores based on the areas and densities of the cornea and conjunctival after staining using a rose Bengal solution under blind conditions. Rebamipide increased the level of mucin-like substances on the conjunctiva of N-acetylcysteine-treated eyes when instilled at concentrations of 0.3% or higher, and 1% rebamipide increased the amount of mucin-like substances covering the cornea. Moreover, 1% rebamipide improved the rose Bengal scores of the cornea and conjunctiva in N-acetylcysteine-treated eyes. Rebamipide increased mucin-like substances on the cornea and conjunctiva of N-acetylcysteine-treated eyes. In accordance with the mucin-increasing effects, rebamipide improved the rose Bengal scores for the cornea and conjunctiva of N-acetylcysteine-treated eyes. However, the relevance of these findings to dry eyes is unclear because it is not known whether the change in mucus expression in the N-acetylcysteine model is similar to what occurs in aqueous tear deficiency. Consequently, it may be worth trying on an animal model of keratoconjunctivitis sicca.

Conversion of Amides to Esters by the Nickel-Catalyzed Activation of Amide C–N Bonds

PubMed Central

Hie, Liana; Fine Nathel, Noah F.; Shah, Tejas K.; Baker, Emma L.; Hong, Xin; Yang, Yun-Fang; Liu, Peng; Houk, K. N.; Garg, Neil K.

2015-01-01

Amides are common functional groups that have been well studied for more than a century.1 They serve as the key building blocks of proteins and are present in an broad range of other natural and synthetic compounds. Amides are known to be poor electrophiles, which is typically attributed to resonance stability of the amide bond.1,2 Whereas Nature can easily cleave amides through the action of enzymes, such as proteases,3 the ability to selectively break the C–N bond of an amide using synthetic chemistry is quite difficult. In this manuscript, we demonstrate that amide C–N bonds can be activated and cleaved using nickel catalysts. We have used this methodology to convert amides to esters, which is a challenging and underdeveloped transformation. The reaction methodology proceeds under exceptionally mild reaction conditions, and avoids the use of a large excess of an alcohol nucleophile. Density functional theory (DFT) calculations provide insight into the thermodynamics and catalytic cycle of this unusual transformation. Our results provide a new strategy to harness amide functional groups as synthons and are expected fuel the further use of amides for the construction of carbon–heteroatom or carbon–carbon bonds using non-precious metal catalysis. PMID:26200342

Chemoselective reductive nucleophilic addition to tertiary amides, secondary amides, and N-methoxyamides.

PubMed

Nakajima, Minami; Oda, Yukiko; Wada, Takamasa; Minamikawa, Ryo; Shirokane, Kenji; Sato, Takaaki; Chida, Noritaka

2014-12-22

As the complexity of targeted molecules increases in modern organic synthesis, chemoselectivity is recognized as an important factor in the development of new methodologies. Chemoselective nucleophilic addition to amide carbonyl centers is a challenge because classical methods require harsh reaction conditions to overcome the poor electrophilicity of the amide carbonyl group. We have successfully developed a reductive nucleophilic addition of mild nucleophiles to tertiary amides, secondary amides, and N-methoxyamides that uses the Schwartz reagent [Cp2 ZrHCl]. The reaction took place in a highly chemoselective fashion in the presence of a variety of sensitive functional groups, such as methyl esters, which conventionally require protection prior to nucleophilic addition. The reaction will be applicable to the concise synthesis of complex natural alkaloids from readily available amide groups. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Efficacy of N-Acetylcysteine in Idiopathic Pulmonary Fibrosis: A Systematic Review and Meta-Analysis.

PubMed

Sun, Tong; Liu, Jing; Zhao, De Wei

2016-05-01

There are a number of conflicting reports describing the clinical outcomes of using N-acetylcysteine for the treatment of idiopathic pulmonary fibrosis. We have, therefore, performed a meta-analysis to evaluate the efficacy of N-acetylcysteine, compared with control, for the treatment of idiopathic pulmonary fibrosis.Original controlled clinical trials evaluating the efficacy of N-acetylcysteine for the treatment of idiopathic pulmonary fibrosis were included in the analysis. Searches for relevant articles were carried out in July 2014 by 2 independent researchers using PubMed, Embase, Cochrane Central, and Google Scholar. Change in forced vital capacity, change in percentage of predicted vital capacity, change in percentage of predicted carbon monoxide diffusing capacity, changes in 6 minutes walking test distance, rate of adverse events, and rate of death were expressed as outcomes using RevMan 5.0.1.Five trials, with a total of 564 patients, were included in this meta-analysis. The meta-analysis showed that the control group had significant decreases in percentage of predicted vital capacity (standardized mean difference [SMD] = 0.37; 95% confidence interval [CI]: 0.13 to -0.62; P = 0.003) and 6 minutes walking test distance (SMD = 0.25; 95% CI: 0.02-0.48; P = 0.04). There were no statistically significant differences in forced vital capacity (SMD = 0.07; 95% CI: -0.13-0.27; P = 0.52), percentage of predicted carbon monoxide diffusing capacity (SMD = 0.12; 95% CI: -0.06-0.30; P = 0.18), rates of adverse events (odd ratio = 4.50; 95% CI: 0.19-106.41; P = 0.35), or death rates (odd ratio = 1.79; 95% CI: 0.3-5.12; P = 0.28) between the N-acetylcysteine group and the control group.N-Acetylcysteine was found to have a significant effect only on decreases in percentage of predicted vital capacity and 6 minutes walking test distance. N-acetylcysteine showed no beneficial effect on changes in forced vital capacity

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

PubMed

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.

The effect of N-acetylcysteine on cardiac contractility to dobutamine in rats with streptozotocin-induced diabetes.

PubMed

Cheng, Xing; Xia, Zhengyuan; Leo, Joyce M; Pang, Catherine C Y

2005-09-05

We examined if myocardial depression at the acute phase of diabetes (3 weeks after injection of streptozotocin, 60 mg/kg i.v.) is due to activation of inducible nitric oxide synthase and production of peroxynitrite, and if treatment with N-acetylcysteine (1.2 g/day/kg for 3 weeks, antioxidant) improves cardiac function. Four groups of rats were used: control, N-acetylcysteine-treated control, diabetic and N-acetylcysteine-treated diabetic. Pentobarbital-anaesthetized diabetic rats, relative to the controls, had reduced left ventricular contractility to dobutamine (1-57 microg/min/kg). The diabetic rats also had increased myocardial levels of thiobarbituric acid reactive substances, immunostaining of inducible nitric oxide synthase and nitrotyrosine, and similar baseline 15-F2t-isoprostane. N-acetylcysteine did not affect responses in the control rats; but increased cardiac contractility to dobutamine, reduced myocardial immunostaining of inducible nitric oxide synthase and nitrotyrosine and level of 15-F2t-isoprostane, and increased cardiac contractility to dobutamine in the diabetic rats. Antioxidant supplementation in diabetes reduces oxidative stress and improves cardiac function.

A Double-Blind, Randomized, Controlled Pilot Trial of N-Acetylcysteine in Veterans With Posttraumatic Stress Disorder and Substance Use Disorders.

PubMed

Back, Sudie E; McCauley, Jenna L; Korte, Kristina J; Gros, Daniel F; Leavitt, Virginia; Gray, Kevin M; Hamner, Mark B; DeSantis, Stacia M; Malcolm, Robert; Brady, Kathleen T; Kalivas, Peter W

2016-11-01

The antioxidant N-acetylcysteine is being increasingly investigated as a therapeutic agent in the treatment of substance use disorders (SUDs). This study explored the efficacy of N-acetylcysteine in the treatment of posttraumatic stress disorder (PTSD), which frequently co-occurs with SUD and shares impaired prefrontal cortex regulation of basal ganglia circuitry, in particular at glutamate synapses in the nucleus accumbens. Veterans with PTSD and SUD per DSM-IV criteria (N = 35) were randomly assigned to receive a double-blind, 8-week course of N-acetylcysteine (2,400 mg/d) or placebo plus cognitive-behavioral therapy for SUD (between March 2013 and April 2014). Primary outcome measures included PTSD symptoms (Clinician-Administered PTSD Scale, PTSD Checklist-Military) and craving (Visual Analog Scale). Substance use and depression were also assessed. Participants treated with N-acetylcysteine compared to placebo evidenced significant improvements in PTSD symptoms, craving, and depression (β values < -0.33; P values < .05). Substance use was low for both groups, and no significant between-group differences were observed. N-acetylcysteine was well tolerated, and retention was high. This is the first randomized controlled trial to investigate N-acetylcysteine as a pharmacologic treatment for PTSD and SUD. Although preliminary, the findings provide initial support for the use of N-acetylcysteine in combination with psychotherapy among individuals with co-occurring PTSD and SUD. ClinicalTrials.gov identifier: NCT02499029. © Copyright 2016 Physicians Postgraduate Press, Inc.

Ulcers caused by bullous morphea: successful therapy with N-acetylcysteine and topical wound care.

PubMed

Rosato, E; Veneziano, M L; Di Mario, A; Molinaro, I; Pisarri, S; Salsano, F

2013-01-01

Bullous morphea is an uncommon form of localized scleroderma. The pathogenesis is unknown and treatment of coexistent ulcers is difficult. The pathogenesis of bullae formation in morphea is multifactorial, but reactive oxygen species production appears to play a key role. We report a patient with bullous morphea with long-standing ulcers whom we successfully treated with N-acetylcysteine and topical wound care. N-acetylcysteine, an antioxidant sulfhydryl substance, promotes the healing of ulcers in patients with bullous morphea.

Oral administration of the antioxidant, N-acetylcysteine, abrogates diabetes-induced endothelial dysfunction.

PubMed

Pieper, G M; Siebeneich, W

1998-07-01

Oxidative stress is believed to play an important role in the development of vascular complications associated with diabetes mellitus. In this study, we examined the efficacy of long-term treatment with the antioxidant, N-acetylcysteine, in preventing the development of defective endothelium-dependent relaxation in streptozotocin-induced, Sprague-Dawley diabetic rats. At 48 h after injection of streptozotocin, a portion of diabetic rats received 250 mg/L N-acetylcysteine in drinking water for a total duration of 8 weeks. Oral administration did not alter the increase in blood glucose or the reduction in serum insulin but did modestly reduce total glycosylated hemoglobin. In precontracted thoracic aortic rings suspended in isolated tissue baths, endothelium-dependent relaxation to acetylcholine was impaired in diabetic rings compared with control rings. Endothelium-independent relaxation to nitroglycerin was unaltered. Long-term oral administration of N-acetylcysteine did not alter responses to nitroglycerin but completely prevented the defective relaxation to acetylcholine. These studies indicate a dissociation between glycemic control and correction of endothelial dysfunction and suggest that long-term exposure to reactive oxygen subsequent to diabetes rather than hyperglycemia per se is responsible for the development of endothelial dysfunction in diabetes mellitus.

Role of N-acetylcysteine on fibrosis and oxidative stress in cirrhotic rats.

PubMed

Pereira-Filho, Gustavo; Ferreira, Clarissa; Schwengber, Alex; Marroni, Cláudio; Zettler, Cláudio; Marroni, Norma

2008-01-01

Hepatic cirrhosis is the final stage of liver dysfunction, characterized by diffuse fibrosis which is the main response to the liver injury. The inhalatory carbon tetrachloride is an effective experimental model that triggers cirrhosis and allows to obtain histological and physiological modifications similar to the one seen in humans. To investigate the effects of N-acetylcysteine (NAC) on the fibrosis and oxidative stress in the liver of cirrhotic rats, analyzing liver function tests, lipoperoxidation, activity of glutathione peroxidase enzyme, collagen quantification, histopathology, as well as the nitric oxide role. The animals were randomly in three experimental groups: control (CO); cirrhotic (CCl4) and CCl4 + NAC. Evaluate the lipid peroxidation, the glutathione peroxidase enzyme, the collagen and the expression of inducible nitric oxide synthase (iNOS). The cirrhotic group treated with N-acetylcysteine showed trough the histological analysis and collagen quantification lower degrees of fibrosis. This group has also shown less damage to the cellular membranes, less decrease on the glutathione peroxidase levels and less expression of inducible nitric oxide synthase when matched with the cirrhotic group without treatment. N-acetylcysteine seams to offer protection against hepatic fibrosis and oxidative stress in cirrhotic rat livers.

Oxidative transformation of tunichromes - Model studies with 1,2-dehydro-N-acetyldopamine and N-acetylcysteine.

PubMed

Kuang, Qun F; Abebe, Adal; Evans, Jason; Sugumaran, Manickam

2017-08-01

Tunichromes are 1,2-dehydrodopa containing bioactive peptidyl derivatives found in blood cells of several tunicates. They have been implicated in metal sequestering, tunic formation, wound healing and defense reaction. Earlier studies conducted on these compounds indicate their extreme liability, high reactivity and easy oxidative polymerization. Their reactions are also complicated by the presence of multiple dehydrodopyl units. Since they have been invoked in crosslinking and covalent binding, to understand the reactivities of these novel compounds, we have taken a simple model compound that possess the tunichrome reactive group viz., 1,2-dehydro-N-acetyldopamine (Dehydro NADA) and examined its reaction with N-acetylcysteine in presence of oxygen under both enzymatic and nonenzymatic conditions. Ultraviolet and visible spectral studies of reaction mixtures containing dehydro NADA and N-acetylcysteine in different molar ratios indicated the production of side chain and ring adducts of N-acetylcysteine to dehydro NADA. Liquid chromatography and mass spectral studies supported this contention and confirmed the production of several different products. Mass spectral analysis of these products show the potentials of dehydro NADA to form side chain adducts that can lead to polymeric products. This is the first report demonstrating the ability of dehydro dopyl units to form adducts and crosslinks with amino acid side chains. Copyright © 2017 Elsevier Inc. All rights reserved.

Influence of N-acetylcysteine on indirect indicators of tissue oxygenation in septic shock patients: results from a prospective, randomized, double-blind study.

PubMed

Spies, C D; Reinhart, K; Witt, I; Meier-Hellmann, A; Hannemann, L; Bredle, D L; Schaffartzik, W

1994-11-01

Deactivation of endothelium-derived relaxing factor due to an increased oxygen radical load during sepsis may contribute to an impairment in microcirculatory blood flow. We investigated whether treatment with the sulfhydryl donor and oxygen radical scavenger, N-acetylcysteine, would improve whole-body oxygen consumption (VO2), gastric intramucosal pH, and veno-arterial CO2 gradient (veno-arterial PCO2) during septic shock. Prospective, randomized, double-blind study conducted over 2 yrs. Septic shock patients admitted to the intensive care unit. Fifty-eight patients requiring hemodynamic monitoring (radial and pulmonary artery catheters) due to septic shock, were included in this study. All patients were examined within 72 hrs after the onset of sepsis. They were optimally resuscitated by conventional means with volume and inotropic agents, and exhibited stable clinical conditions (hemodynamic values, body temperature, hemoglobin, FIO2). A gastric tonometer was inserted to measure the gastric intramucosal pH. Subjects randomly received either 150 mg/kg of intravenous N-acetylcysteine or placebo over a 15-min period, then a continuous infusion of 12.5 mg/hr of N-acetylcysteine or placebo over approximately 90 mins. Infusion measurements were begun 60 mins after the beginning of infusion and lasted approximately 30 mins. The infusion was then discontinued and 2 hrs later the final measurements were taken. Basic patient characteristics (age, sex, Acute Physiology and Chronic Health Evaluation [APACHE] II scores, Multiple Organ Failure scores) did not differ significantly, nor did pre- and 2-hr postinfusion measurements differ between any of the groups. Thirteen (45%) patients responded (i.e., showed an increase in VO2 > 10%, reaching a mean of 19%) to the N-acetylcysteine infusion. The N-acetylcysteine responders also showed an increase in gastric intramucosal pH, a decrease in veno-arterial PCO2, an increase in oxygen delivery, cardiac index, stroke index, and left

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

NASA Technical Reports Server (NTRS)

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.

N-acetylcysteine does not prevent post-endoscopic retrograde cholangiopancreatography hyperamylasemia and acute pancreatitis

PubMed Central

Milewski, Janusz; Rydzewska, Grazyna; Degowska, Malgorzata; Kierzkiewicz, Maciej; Rydzewski, Andrzej

2006-01-01

AIM: Acute pancreatitis (AP) is the most common and often severe complication of endoscopic retrograde cholangiopancreatography (ERCP). The early step in the pathogenesis of acute pancreatitis is probably the capillary endothelial injury mediated by oxygen-derived free radicals. N-acetylcysteine - a free radical scavenger may be potentially effective in preventing post-ERCP acute pancreatitis and it is also known that N-acetylcysteine (ACC) can reduce the severity of disease in experimental model of AP. METHODS: One hundred and six patients were randomly allocated to two groups. Fifty-five patients were given N-acetylcysteine (two 600 mg doses orally 24 and 12 h before ERCP and 600 mg was given iv, twice a day for two days after the ERCP). The control group consisted of 51 patients who were given iv. isotonic saline twice a day for two days after the ERCP. Serum and urine amylase activities were measured before ERCP and 8 and 24 h after the procedure. The primary outcome parameter was post-ERCP acute pancreatitis and the secondary outcome parameters were differences between groups in serum and urine amylase activity. RESULTS: There were no significant differences in the rate of post-ERCP pancreatitis between two groups (10 patients overall, 4 in the ACC group and 6 in the control group). There were also no significant differences in baseline and post-ERCP serum and urine amylase activity between ACC group and control group. CONCLUSION: N-acetylcysteine fails to demonstrate any significant preventive effect on post-ERCP pancreatitis, as well as on serum and urine amylase activity. PMID:16773694

N-acetylcysteine does not prevent post-endoscopic retrograde cholangiopancreatography hyperamylasemia and acute pancreatitis.

PubMed

Milewski, Janusz; Rydzewska, Grazyna; Degowska, Malgorzata; Kierzkiewicz, Maciej; Rydzewski, Andrzej

2006-06-21

Acute pancreatitis (AP) is the most common and often severe complication of endoscopic retrograde cholangiopancreatography (ERCP). The early step in the pathogenesis of acute pancreatitis is probably the capillary endothelial injury mediated by oxygen-derived free radicals. N-acetylcysteine - a free radical scavenger may be potentially effective in preventing post-ERCP acute pancreatitis and it is also known that N-acetylcysteine (ACC) can reduce the severity of disease in experimental model of AP. One hundred and six patients were randomly allocated to two groups. Fifty-five patients were given N-acetylcysteine (two 600 mg doses orally 24 and 12 h before ERCP and 600 mg was given iv, twice a day for two days after the ERCP). The control group consisted of 51 patients who were given iv. isotonic saline twice a day for two days after the ERCP. Serum and urine amylase activities were measured before ERCP and 8 and 24 h after the procedure. The primary outcome parameter was post-ERCP acute pancreatitis and the secondary outcome parameters were differences between groups in serum and urine amylase activity. There were no significant differences in the rate of post-ERCP pancreatitis between two groups (10 patients overall, 4 in the ACC group and 6 in the control group). There were also no significant differences in baseline and post-ERCP serum and urine amylase activity between ACC group and control group. N-acetylcysteine fails to demonstrate any significant preventive effect on post-ERCP pancreatitis, as well as on serum and urine amylase activity.

N-acetylcysteine attenuates endotoxin-induced leukocyte-endothelial cell adhesion and macromolecular leakage in vivo.

PubMed

Schmidt, H; Schmidt, W; Müller, T; Böhrer, H; Gebhard, M M; Martin, E

1997-05-01

To determine the influence of N-acetylcysteine on endotoxin-induced leukocyte-endothelial cell adhesion, vascular leakage, and venular microhemodynamics. Randomized, blinded, controlled trial. Experimental laboratory. Thirty male Wistar rats. After pretreatment with N-acetylcysteine (150 mg/kg; n = 40; group A) or 0.9% saline solution (n = 10; group B) animals were given an intravenous infusion of endotoxin (Escherichia coli lipopolysaccharide 026:B6; 2 mg/kg/hr) over 120 mins. Animals in the control group (n = 10; group C) received a volume-equivalent infusion of 0.9% saline solution. Leukocyte adherence, red cell velocity (VRBC), vessel diameters, venular wall shear rate, and macromolecular leakage were determined in mesenteric postcapillary venules using in vivo videomicroscopy at baseline and at 30, 50, 90, and 120 mins after the start of the endotoxin challenge. Endotoxin exposure induced a marked increase in adherent leukocytes (group B: baseline, 391 +/- 24 cells/mm2; 120 mins, 1268 +/- 131 cells/mm2; p < .01). N-acetylcysteine pretreatment attenuated the adherence of leukocytes during endotoxemia (baseline, 366 +/- 28 cells/mm2; 120 mins, 636 +/- 49 cells/mm2; p < .01 vs. baseline; p < .01 vs. group B). Leukocyte adherence in control animals (group C) did not increase significantly. Administration of N-acetylcysteine did not influence the decrease in VRBC observed during endotoxemia. In group B1 VRBC decreased during the infusion of endotoxin from 2.0 +/- 0.2 mm/sec at baseline to 1.1 +/- 0.2 mm/ sec after 120 mins (p < .01 vs. baseline; p < .05 vs. group C), and in group A from 2.2 +/- 0.2 mm/sec to 1.1 +/- 0.1 mm/sec after 120 mins (p < .01 vs. baseline; p < .05 vs. group C). In group C, VRBC remained unchanged (baseline, 1.7 +/- 0.2 mm/sec; at 120 mins, 1.5 +/- 0.2 mm/sec). The venular diameters remained unchanged in all groups during the entire study period. After 120 mins, the venular wall shear rate decreased from 502 +/- 62 secs-1 at baseline to 272

The protective effect of N-acetylcysteine on oxidative stress in the brain caused by the long-term intake of aspartame by rats.

PubMed

Finamor, Isabela A; Ourique, Giovana M; Pês, Tanise S; Saccol, Etiane M H; Bressan, Caroline A; Scheid, Taína; Baldisserotto, Bernardo; Llesuy, Susana F; Partata, Wânia A; Pavanato, Maria A

2014-09-01

Long-term intake of aspartame at the acceptable daily dose causes oxidative stress in rodent brain mainly due to the dysregulation of glutathione (GSH) homeostasis. N-Acetylcysteine provides the cysteine that is required for the production of GSH, being effective in treating disorders associated with oxidative stress. We investigated the effects of N-acetylcysteine treatment (150 mg kg(-1), i.p.) on oxidative stress biomarkers in rat brain after chronic aspartame administration by gavage (40 mg kg(-1)). N-Acetylcysteine led to a reduction in the thiobarbituric acid reactive substances, lipid hydroperoxides, and carbonyl protein levels, which were increased due to aspartame administration. N-Acetylcysteine also resulted in an elevation of superoxide dismutase, glutathione peroxidase, glutathione reductase activities, as well as non-protein thiols, and total reactive antioxidant potential levels, which were decreased after aspartame exposure. However, N-acetylcysteine was unable to reduce serum glucose levels, which were increased as a result of aspartame administration. Furthermore, catalase and glutathione S-transferase, whose activities were reduced due to aspartame treatment, remained decreased even after N-acetylcysteine exposure. In conclusion, N-acetylcysteine treatment may exert a protective effect against the oxidative damage in the brain, which was caused by the long-term consumption of the acceptable daily dose of aspartame by rats.

Twisted Amides: From Obscurity to Broadly Useful Transition-Metal-Catalyzed Reactions by N-C Amide Bond Activation.

PubMed

Liu, Chengwei; Szostak, Michal

2017-05-29

The concept of using amide bond distortion to modulate amidic resonance has been known for more than 75 years. Two classic twisted amides (bridged lactams) ingeniously designed and synthesized by Kirby and Stoltz to feature fully perpendicular amide bonds, and as a consequence emanate amino-ketone-like reactivity, are now routinely recognized in all organic chemistry textbooks. However, only recently the use of amide bond twist (distortion) has advanced to the general organic chemistry mainstream enabling a host of highly attractive N-C amide bond cross-coupling reactions of broad synthetic relevance. In this Minireview, we discuss recent progress in this area and present a detailed overview of the prominent role of amide bond destabilization as a driving force in the development of transition-metal-catalyzed cross-coupling reactions by N-C bond activation. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

40 CFR 721.10191 - Amides, coco, N-[3-(dibutylamino)propyl].

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Amides, coco, N-[3-(dibutylamino... Specific Chemical Substances § 721.10191 Amides, coco, N-[3-(dibutylamino)propyl]. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as amides, coco...

N-Acetylcysteine in the Treatment of Excoriation Disorder: A Randomized Clinical Trial.

PubMed

Grant, Jon E; Chamberlain, Samuel R; Redden, Sarah A; Leppink, Eric W; Odlaug, Brian L; Kim, Suck Won

2016-05-01

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. 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. A randomized, double-blind trial was conducted at ambulatory care centers at the University of Minnesota (September 12, 2011, to June 15, 2012) and the University of Chicago (December 17, 2012, to June 26, 2015) and included 66 adults with SPD. Data analysis was performed from July 16 to September 9, 2015. N-acetylcysteine (dosing range, 1200-3000 mg/d) or placebo was administered for 12 weeks. Participants were assessed using measures of skin-picking severity, including the modified Yale-Brown Obsessive Compulsive Scale (NE-YBOCS); total scores range from 0 to 40, with higher scores reflective of greater symptom severity. Another measure of skin-picking severity was the Clinical Global Impression-Severity Scale; total scores range from 1 (normal) to 7 (among the most extremely ill patients), and improvement ratings range from 7 (very much worse) to 1 (very much improved). Selected cognitive tasks included the Intra-dimensional/Extra-dimensional Shift Task to examine cognitive flexibility, with the key outcome measures being the number of errors, and Stop-Signal Reaction Time task, which evaluates motor inhibition. Outcomes were examined using a linear mixed-effects model. Of the 66 participants (31 randomized to placebo and 35 to N-acetylcysteine) included in the analysis, 59 (89%) were women; mean (SD) age was 34.8 (11.0) years. Compared with placebo, N-acetylcysteine treatment was associated with significant improvements in the NE-YBOCS. At baseline, NE-YBOCS scores were 18.9 and 17

A Convenient Approach to Synthesizing Peptide C-Terminal N-Alkyl Amides

PubMed Central

Fang, Wei-Jie; Yakovleva, Tatyana; Aldrich, Jane V.

2014-01-01

Peptide C-terminal N-alkyl amides have gained more attention over the past decade due to their biological properties, including improved pharmacokinetic and pharmacodynamic profiles. However, the synthesis of this type of peptide on solid phase by current available methods can be challenging. Here we report a convenient method to synthesize peptide C-terminal N-alkyl amides using the well-known Fukuyama N-alkylation reaction on a standard resin commonly used for the synthesis of peptide C-terminal primary amides, the PAL-PEG-PS (Peptide Amide Linker-polyethylene glycol-polystyrene) resin. The alkylation and oNBS deprotection were conducted under basic conditions and were therefore compatible with this acid labile resin. The alkylation reaction was very efficient on this resin with a number of different alkyl iodides or bromides, and the synthesis of model enkephalin N-alkyl amide analogs using this method gave consistently high yields and purities, demonstrating the applicability of this methodology. The synthesis of N-alkyl amides was more difficult on a Rink amide resin, especially the coupling of the first amino acid to the N-alkyl amine, resulting in lower yields for loading the first amino acid onto the resin. This method can be widely applied in the synthesis of peptide N-alkyl amides. PMID:22252422

Prebiotic formation of 'energy-rich' thioesters from glyceraldehyde and N-acetylcysteine

NASA Technical Reports Server (NTRS)

Weber, A. L.

1984-01-01

The 'energy-rich' thioester, N-acetyl-S-lactoylcysteine, is formed from low concentrations of glyceraldehyde and N-acetylcysteine under anaerobic conditions at ambient temperature in aqueous solutions of sodium phosphate (pH 7.0). Reactions with 2mM glyceraldehyde, 2mM N-acetylcysteine, and 500 mM sodium phosphate (pH 7.0) convert about 0.3 percent/day of the glyceraldehyde to lactoyl thioester. The formation of lactoyl thioester in similar reactions with 500 mM imidazole hydrochloride (pH 7.0) is supported by the thiol-dependence of lactate formation, which is 3-fold greater in the presence of thiol (0.11 percent/day) than in the absence of thiol (0.04 percent/day). The formation of lactoly thioester is thought to proceed by the phosphate (or imidazole)-catalyzed dehydration of glyceraldehyde, which adds to the thiol to form a hemithioacetal that rearranges to the thioester. A limited amount of a second thioester, N-acetyl-S-glyceroyl-cysteine, is also formed at the beginning of these reactions. The significance of these reactions to the origin of life is discussed.

Discovery of novel N-(5-(arylcarbonyl)thiazol-2-yl)amides and N-(5-(arylcarbonyl)thiophen-2-yl)amides as potent RORγt inhibitors.

PubMed

Wang, Yonghui; Cai, Wei; Zhang, Guifeng; Yang, Ting; Liu, Qian; Cheng, Yaobang; Zhou, Ling; Ma, Yingli; Cheng, Ziqiang; Lu, Sijie; Zhao, Yong-Gang; Zhang, Wei; Xiang, Zhijun; Wang, Shuai; Yang, Liuqing; Wu, Qianqian; Orband-Miller, Lisa A; Xu, Yan; Zhang, Jing; Gao, Ruina; Huxdorf, Melanie; Xiang, Jia-Ning; Zhong, Zhong; Elliott, John D; Leung, Stewart; Lin, Xichen

2014-01-15

Novel series of N-(5-(arylcarbonyl)thiazol-2-yl)amides and N-(5-(arylcarbonyl)thiophen-2-yl)amides were discovered as potent retinoic acid receptor-related orphan receptor-gamma-t (RORγt) inhibitors. SAR studies of the RORγt HTS hit 6a led to identification of thiazole ketone amide 8h and thiophene ketone amide 9g with high binding affinity and inhibitory activity of Th17 cell differentiation. Compound 8h showed in vivo efficacy in both mouse experimental autoimmune encephalomyelitis (EAE) and collagen induced arthritis (CIA) models via oral administration. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

PubMed

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.

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

PubMed

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.

External anal sphincter fatigue is not improved by N-acetylcysteine in an animal model.

PubMed

Healy, C F; McMorrow, C; O'Herlihy, C; O'Connell, P R; Jones, J F X

2008-06-01

Oxidative stress is associated with skeletal muscle fatigue. This study tests the hypotheses that N-acetylcysteine (NAC) reduces fatigue and accelerates recovery of the rat external anal sphincter (EAS). Fifteen female Wistar rats were killed humanely. The EAS was mounted as a ring preparation and electrically stimulated with 50 Hz trains of 200 ms in duration every 4 s for three and a half minutes. Three groups were analysed: a control group (n = 5), a group pretreated with NAC (10(-4) mol L(-1); n = 5) and a group pretreated with NAC (10(-3) mol L(-1); n = 5). A novel fatigue index was formulated and was compared to a conventional method of expressing fatigue. There was no significant difference at concentrations of NAC (10(-4) mol L(-1); P > 0.05). At high concentrations of NAC (10(-3) mol L(-1)) there was a significant depression in peak twitch amplitude before fatigue (P = 0.04). N-acetylcysteine in both concentrations used, did not alter fatigue or recovery of the rat EAS. There was a significant positive correlation between the two methods of expressing fatigue but the conventional method produced a higher fatigue index (22.4% on average). N-acetylcysteine does not ameliorate fatigue or accelerate recovery of the EAS and may not be a useful medical therapy for faecal incontinence.

40 CFR 721.10192 - Amides, coco, N-[3-(dibutylamino)propyl], acrylates.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Amides, coco, N-[3-(dibutylamino... Specific Chemical Substances § 721.10192 Amides, coco, N-[3-(dibutylamino)propyl], acrylates. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as amides...

N-acetylcysteine treatment blocks the development of ethanol-induced behavioural sensitization and related ΔFosB alterations.

PubMed

Morais-Silva, Gessynger; Alves, Gabrielle Cunha; Marin, Marcelo T

2016-11-01

Ethanol addiction is a serious public health problem that still needs more effective pharmacological treatment. A key factor in the development and maintenance of this disease is the advent of neuroadaptations in the mesocorticolimbic brain pathway upon chronic ethanol abuse. In general, these neuroadaptations are maladaptive and affect numerous neurotransmitter systems and intracellular molecules. One of these molecules is ΔFosB, a transcription factor that is altered after chronic drug use. Behavioural sensitization is a useful model for the study of the neuroadaptations related to addiction. Recent works have shown a role for the imbalance of glutamatergic neurotransmission in the symptoms found in addicted people. In this sense, the treatment with N-acetylcysteine, a l-cysteine prodrug that acts by restoring extrasynaptic concentrations of glutamate through the activation of cystine-glutamate antiporter, has shown promising results in the treatment of addiction. Thus, an animal model of behavioural sensitization was used to evaluate the effects of N-acetylcysteine treatment in the behavioural and molecular alterations induced by chronic ethanol administration. Swiss mice were subject to 13 days of daily ethanol administration to induce behavioural sensitization. Two hours before each ethanol administration and locomotor activity evaluation, the animals received intraperitoneally N-acetylcysteine injections. Immediately after the last test session, their brains were removed for ΔFosB and cystine-glutamate antiporter quantification. It was found that N-acetylcysteine treatment blocked ethanol-induced behavioural sensitization, the increase of ΔFosB content in the prefrontal cortex, and its reduction in the nucleus accumbens. The results suggest a possible use of N-acetylcysteine in ethanol-related disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effect of N-acetylcysteine on microcirculation of mucosa in rat ileum in a model of intestinal inflammation.

PubMed

Ruh, Joachim; Schmidt, Eduard; Vogel, Frank

2003-05-01

Oxygen radicals are formed by the endothelium and blood cells and have specific functions in various organs systems. On the level of the microcirculation, oxygen radicals take part in the regulation of the leukocyte-endothelial interaction. The involvement of oxygen radicals has previously been found in conditions such as sepsis, ischemia-reperfusion, and inflammation. Indomethacin is a clinically applied nonsteroidal antiphlogistic, and in previous studies in the rat, it has been found to induce an inflammatory reaction in the small intestine characterized by edema and reddening of the intestinal epithelium, ulceration, and dysregulation in the intestinal-epithelial barrier function. In the present study, we investigated the effect of N-acetylcysteine on erythrocyte velocity and the arteriolar diameter of the main arteriole in single villi, thus providing insight in the perfusion of the mucosa in indomethacin-induced intestinal inflammation. N-Acetylcysteine is known to inactivate superoxide and its precursors. Therefore, we used N-acetylcysteine to investigate whether superoxide and its precursors participate in the regulation of blood supply to single villi in this animal model. We found that indomethacin induced an increase in villous perfusion that was significantly reduced by N-acetylcysteine, indicating that superoxide and its precursors may participate in the regulation of blood supply to the mucosa in this animal model of intestinal inflammation.

Prebiotic formation of `energy-rich' thioesters from glyceraldehyde and N-acetylcysteine

NASA Astrophysics Data System (ADS)

Weber, Arthur L.

1984-03-01

The ‘energy-rich’ thioester, N-acetyl-S-lactoylcysteine, is formed from low concentrations of glyceraldehyde and N-acetylcysteine under anaerobic conditions at ambient temperature in aqueous solutions of sodium phosphate (pH 7.0). Reactions with 2 mM glyceraldehyde, 2 mM N-acetylcysteine, and 500 mM sodium phosphate (pH 7.0) convert about 0.3%/day of the glyceraldehyde to lactoyl thioester. The formation of lactoyl thioester in similar reactions with 500 mM imidazole hydrochloride (pH 7.0) is supported by the thiol-dependence of lactate formation, which is 3-fold greater in the presence of thiol (0.11%/day) than in the absence of thiol (0.04%/day). The formation of lactoyl thioester is thought to proceed by the phosphate (or imidazole)-catalyzed dehydration of glyceraldehyde to give pyruvaldehyde, which adds to the thiol to form a hemithioacetal that rearranges to the thioester. A limited amount of a second thioester, N-acetyl-S-glyceroyl-cysteine, is also formed at the beginning of these reactions. The significance of these reactions to the origin of life is discussed.

Biological Activities and Potential Oral Applications of N-Acetylcysteine: Progress and Prospects

PubMed Central

Pei, Yanping; Liu, Huan; Yang, Yi; Yang, Yanwei

2018-01-01

N-Acetylcysteine (NAC), a cysteine prodrug and glutathione (GSH) precursor, has been used for several decades in clinical therapeutic practices as a mucolytic agent and for the treatment of disorders associated with GSH deficiency. Other therapeutic activities of NAC include inhibition of inflammation/NF-κB signaling and expression of proinflammatory cytokines. N-Acetylcysteine is also a nonantibiotic compound possessing antimicrobial property and exerts anticarcinogenic and antimutagenic effects against certain types of cancer. Recently, studies describing potentially important biological and pharmacological activities of NAC have stimulated interests in using NAC-based therapeutics for oral health care. The present review focused on the biological activities of NAC and its potential oral applications. The potential side effects of NAC and formulations for drug delivery were also discussed, with the intent of advancing NAC-associated treatment modalities in oral medicine. PMID:29849877

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

PubMed

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 <0.05). No difference was seen in normal kidneys. Myeloperoxidase, malondialdehyde and total nitrite levels in the N-acetylcysteine group, and myeloperoxidase and malondialdehyde levels in the montelukast sodium group were lower than in the placebo group (p <0.05). No statistical difference was seen in sulfhydryl levels (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.

Effect of N-acetylcysteine on vascular endothelium function in aorta from oophorectomized rats.

PubMed

Delgado, J L; Landeras, J; Carbonell, L F; Parilla, J J; Abad, L; Quesada, T; Fiol, G; Hernández, I

1999-01-01

1. Experiments were performed to examine and to compare vascular endothelial function in aortic rings from oophorectomized and from ovary-intact rats and to test the effect of thiol compound as N-acetylcysteine on endothelial function. 2. In precontracted aortic rings from oophorectomized and intact rats, vascular endothelial function was evaluated by measuring changes in isometric force in response to cumulative doses of superoxide dismutase, acetylcholine and sodium nitroprusside. 3. In studies designed to assess the tone-related release of nitric oxide from aortic rings moderately precontracted with phenylephrine, superoxide dismutase produced a lower concentration-related relaxant response in aortic rings from oophorectomized rats than from ovary intact rats. 4. Acetylcholine caused a concentration- and endothelium-dependent relaxation of less magnitude in aortic rings from oophorectomized animals compared with those from ovary-intact rats. Addition of N-omega-nitro-L-arginine methyl ester eliminated the relaxation induced by both superoxide dismutase and acetylcholine. 5. No differences between groups were noticed in the concentration-relaxation curve induced by sodium nitroprusside. 6. Preincubation with N-acetylcysteine normalized the depressed vasorelaxant response to acetylcholine in the aortic rings from oophorectomized rats, whereas the concentration-response curve for acetylcholine in aortic rings from ovary-intact rats did not alter. 7. These results suggest that the absence of ovary estrogens is associated with a vascular endothelium dysfunction that can be reverted by addition of N-acetylcysteine, a thiol-containing compound with a free radical scavenger effect.

Mechanistic Studies on the Copper-Catalyzed N-Arylation of Amides

PubMed Central

Strieter, Eric R.; Bhayana, Brijesh; Buchwald, Stephen L.

2009-01-01

The copper-catalyzed N-arylation of amides, i.e., the Goldberg reaction, is an efficient method for the construction of products relevant to both industry and academic settings. Herein, we present mechanistic details concerning the catalytic and stoichiometric N-arylation of amides. In the context of the catalytic reaction, our findings reveal the importance of chelating diamine ligands in controlling the concentration of the active catalytic species. The consistency between the catalytic and stoichiometric results suggest that the activation of aryl halides occurs through a 1,2-diamine-ligated copper(I) amidate complex. Kinetic studies on the stoichiometric N-arylation of aryl iodides using 1,2-diamine ligated Cu(I) amidates also provide insights into the mechanism of aryl halide activation. PMID:19072233

A Randomised, Double Blind Trial of N-Acetylcysteine for Hearing Protection during Stapes Surgery

PubMed Central

Bagger-Sjöbäck, Dan; Strömbäck, Karin; Hakizimana, Pierre; Plue, Jan; Larsson, Christina; Hultcrantz, Malou; Papatziamos, Georgios; Smeds, Henrik; Danckwardt-Lillieström, Niklas; Hellström, Sten; Johansson, Ann; Tideholm, Bo; Fridberger, Anders

2015-01-01

Background 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. Methods 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. Findings 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. Conclusions N-Acetylcysteine has no effect on hearing thresholds, tinnitus, or balance disturbance after stapedotomy. Trial Registration ClinicalTrials.gov NCT00525551 PMID:25763866

Palladium-catalyzed Suzuki-Miyaura coupling of amides by carbon-nitrogen cleavage: general strategy for amide N-C bond activation.

PubMed

Meng, Guangrong; Szostak, Michal

2016-06-15

The first palladium-catalyzed Suzuki-Miyaura cross-coupling of amides with boronic acids for the synthesis of ketones by sterically-controlled N-C bond activation is reported. The transformation is characterized by operational simplicity using bench-stable, commercial reagents and catalysts, and a broad substrate scope, including substrates with electron-donating and withdrawing groups on both coupling partners, steric-hindrance, heterocycles, halides, esters and ketones. The scope and limitations are presented in the synthesis of >60 functionalized ketones. Mechanistic studies provide insight into the catalytic cycle of the cross-coupling, including the first experimental evidence for Pd insertion into the amide N-C bond. The synthetic utility is showcased by a gram-scale cross-coupling and cross-coupling at room temperature. Most importantly, this process provides a blueprint for the development of a plethora of metal catalyzed reactions of typically inert amide bonds via acyl-metal intermediates. A unified strategy for amide bond activation to enable metal insertion into N-C amide bond is outlined ().

N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action

PubMed Central

Dean, Olivia; Giorlando, Frank; Berk, Michael

2011-01-01

There is an expanding field of research investigating the benefits of alternatives to current pharmacological therapies in psychiatry. N-acetylcysteine (NAC) is emerging as a useful agent in the treatment of psychiatric disorders. Like many therapies, the clinical origins of NAC are far removed from its current use in psychiatry. Whereas the mechanisms of NAC are only beginning to be understood, it is likely that NAC is exerting benefits beyond being a precursor to the antioxidant, glutathione, modulating glutamatergic, neurotropic and inflammatory pathways. This review outlines the current literature regarding the use of NAC in disorders including addiction, compulsive and grooming disorders, schizophrenia and bipolar disorder. N-acetylcysteine has shown promising results in populations with these disorders, including those in whom treatment efficacy has previously been limited. The therapeutic potential of this acetylated amino acid is beginning to emerge in the field of psychiatric research. PMID:21118657

Nine of 16 stereoisomeric polyhydroxylated proline amides are potent β-N-acetylhexosaminidase inhibitors.

PubMed

Ayers, Benjamin J; Glawar, Andreas F G; Martínez, R Fernando; Ngo, Nigel; Liu, Zilei; Fleet, George W J; Butters, Terry D; Nash, Robert J; Yu, Chu-Yi; Wormald, Mark R; Nakagawa, Shinpei; Adachi, Isao; Kato, Atsushi; Jenkinson, Sarah F

2014-04-18

All 16 stereoisomeric N-methyl 5-(hydroxymethyl)-3,4-dihydroxyproline amides have been synthesized from lactones accessible from the enantiomers of glucuronolactone. Nine stereoisomers, including all eight with a (3R)-hydroxyl configuration, are low to submicromolar inhibitors of β-N-acetylhexosaminidases. A structural correlation between the proline amides is found with the ADMDP-acetamide analogues bearing an acetamidomethylpyrrolidine motif. The proline amides are generally more potent than their ADMDP-acetamide equivalents. β-N-Acetylhexosaminidase inhibition by an azetidine ADMDP-acetamide analogue is compared to an azetidine carboxylic acid amide. None of the amides are good α-N-acetylgalactosaminidase inhibitors.

Minocycline and N-acetylcysteine: A Synergistic Drug Combination to Treat Traumatic Brain Injury

DTIC Science & Technology

2013-10-01

Contract Number: W81XWH-10-2-0171 TITLE: Minocycline and...30September2012-29September2013 4. TITLE AND SUBTITLE Minocycline and N-acetylcysteine: a synergistic drug combination to treat...grantee previously found screened that the combination of minocycline (MINO) and N-acetyl cysteine (NAC) synergistically improved brain function when

The pharmacokinetics and extracorporeal removal of N-acetylcysteine during renal replacement therapies.

PubMed

Hernandez, Stephanie H; Howland, Maryann; Schiano, Thomas D; Hoffman, Robert S

2015-01-01

Acetaminophen-induced fulminant hepatic failure is associated with acute kidney injury, metabolic acidosis, and fluid and electrolyte imbalances, requiring treatment with renal replacement therapies. Although antidote, acetylcysteine, is potentially extracted by renal replacement therapies, pharmacokinetic data are lacking to guide potential dosing alterations. We aimed to determine the extracorporeal removal of acetylcysteine by various renal replacement therapies. Simultaneous urine, plasma and effluent specimens were serially collected to measure acetylcysteine concentrations in up to three stages: before, during and upon termination of renal replacement therapy. Alterations in pharmacokinetics were determined by applying standard pharmacokinetic equations. Over 2 years, 10 critically ill patients in fulminant hepatic failure requiring renal replacement therapy coincident with acetylcysteine were consecutively enrolled. All 10 patients required continuous venovenous hemofiltration (n = 10) and 2 of the 10 also required hemodialysis (n = 2). There was a significant alteration in the pharmacokinetics of acetylcysteine during hemodialysis; the area under the curve (AUC) decreased 41%, the mean extraction ratio was 51%, the mean hemodialytic clearance was 114.01 ml/kg/h, and a mean 166.75 mg/h was recovered in the effluent or 41% of the hourly dose. Alteration in the pharmacokinetics of acetylcysteine during continuous venovenous hemofiltration did not appear to be significant: the AUC decreased 13%, the mean clearance was 31.77 ml/kg/h and a mean 62.12 mg/h was recovered in the effluent or 14% of the hourly dose. There was no significant extraction of acetylcysteine from continuous venovenous hemofiltration. In contrast, there was significant extracorporeal removal of acetylcysteine during hemodialysis. A reasonable dose adjustment may be to double the IV infusion rate or possibly supplement with oral acetylcysteine during hemodialysis.

N-Acetylcysteine as adjunctive treatment in severe malaria: A randomized double blinded placebo controlled clinical trial

PubMed Central

Charunwatthana, Prakaykaew; Faiz, M. Abul; Ruangveerayut, Ronnatrai; Maude, Richard; Rahman, M. Ridwanur; Roberts, L. Jackson; Moore, Kevin; Yunus, Emran Bin; Hoque, M. Gofranul; Hasan, Mahatab Uddin; Lee, Sue J.; Pukrittayakamee, Sasithon; Newton, Paul N.; White, Nicholas J.; Day, Nicholas P.J.; Dondorp, Arjen M.

2009-01-01

Objective Markers of oxidative stress are reported to be increased in severe malaria. It has been suggested that the antioxidant N-acetylcysteine (NAC) may be beneficial in treatment. We studied the efficacy and safety of parenteral N-acetylcysteine as an adjunct to artesunate treatment of severe falciparum malaria. Design A randomized double-blind placebo controlled trial on the use of high dose intravenous NAC as adjunctive treatment to artesunate. Setting A provincial hospital in Western Thailand and a tertiary referral hospital in Chittagong, Bangladesh. Patients One hundred and eight adult patients with severe falciparum malaria. Interventions Patients were randomized to receive N-acetylcysteine or placebo as adjunctive treatment to intravenous artesunate. Measurements and main results A total of 56 patients were treated with NAC and 52 received placebo. NAC had no significant effect on mortality, lactate clearance times (p=0.74) or coma recovery times (p=0.46). Parasite clearance time was increased from 30h (range 6h to 144h) to 36h (range 6h to 120h) (p=0.03), but this could be explained by differences in admission parasitemia. Urinary F2-isoprostane metabolites, measured as a marker of oxidative stress, were increased in severe malaria compared to patients with uncomplicated malaria and healthy volunteers. Admission red cell rigidity correlated with mortality, but did not improve with NAC. Conclusion Systemic oxidative stress is increased in severe malaria. Treatment with N-acetylcysteine had no effect on outcome in patients with severe falciparum malaria in this setting. PMID:19114891

Spectroscopic study of N-acetylcysteine and N-acetylcystine/hydrogen peroxide complexation

NASA Astrophysics Data System (ADS)

Picquart, Michel; Abedinzadeh, Zohreh; Grajcar, Lydie; Baron, Marie Héléne

1998-03-01

A spectroscopic study of N-acetylcysteine (RSH) and N-acetylcystine (RSSR) has been performed using infrared absorption and Raman scattering in order to pinpoint the sites of complexation of these two species with H 2O 2. Molecules of RSH and RSSR were studied in KBr pellets, and in aqueous solutions of H 2O, D 2O and H 2O with H 2O 2 (1 mol l -1) to characterize the specific influence of the solvent molecules. A time-resolved Raman study was performed for RSH-H 2O 2 in aqueous solution at 1:1 molar ratio in order to observe the formation of RSSR and to discuss the mechanism of this redox reaction.

The effects of sildenafil and n-acetylcysteine on ischemia and reperfusion injury in gastrocnemius muscle and femoral artery endothelium.

PubMed

Aksu, Volkan; Yüksel, Volkan; Chousein, Serchat; Taştekin, Ebru; İşcan, Şahin; Sağiroğlu, Gönül; Canbaz, Suat; Sunar, Hasan

2015-02-01

We aimed to examine the effects of sildenafil and n-acetylcystein on ischemia/reperfusion injury in femoral artery endothelium and gastrocnemius muscle. 32 rats of Sprague-Dawley breed were randomly divided into four groups (n=8). Median laparotomy was performed, then a 120-minute ischemia was created by microvascular clamping of infrarenal aorta, followed by the release of clamping. In sildenafil group, 1 mg/kg of sildenafil infusion and in the n-acetylcystein group, 100 mg/kg of n-acetylcystein infusion was administered after release of clamps. Blood samples and tissue samples of femoral artery and gastrocnemius muscle were extracted for a histopathological evaluation. Serum levels of malondialdehyde in ischemia/reperfusion group (6.16±0.79) were higher compared to the control group (4.69±0.33), whereas a significant decrease was detected in sildenafil (5.17±0.50) and n-acetylcystein (4.96±0.49) groups. Femoral artery tissue sections of the control group, mean tumor necrosis factor alpha and hypoxy-induced factor-1 alpha immunoreactivity were found to be negative. In the ischemia/reperfusion group, mean tumor necrosis factor α immunoreactivity was intense and mean hypoxy-induced factor-1 alpha immunoreactivity was 51-75%. In the ischemia/reperfusion+Sildenafil and ischemia/reperfusion+NAS groups, mean tumor necrosis factor α immunoreactivity was slight and mean hypoxy-induced factor-1 alpha immunoreactivity was 26-50%. In conclusion, sildenafil and n-acetylcystein may reduce femoral artery endothelium and gastrocnemius muscle injury following lower extremity ischemia/reperfusion. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

N-acetylcysteine attenuates TNF-alpha-induced human vascular endothelial cell apoptosis and restores eNOS expression.

PubMed

Xia, Zhengyuan; Liu, Min; Wu, Yong; Sharma, Vijay; Luo, Tao; Ouyang, Jingping; McNeill, John H

2006-11-21

The circulatory inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) is increased in pathological conditions, such as diabetes, which initiate or exacerbate vascular endothelial injury. Both nitric oxide (NO) and reactive oxygen species may play a dual role (i.e., inhibiting or promoting) in TNF-alpha-induced endothelial cell apoptosis. We investigated the effects of the antioxidant N-acetylcysteine on TNF-alpha-induced apoptosis in human vascular endothelial cell (cell line ECV304) apoptosis, NO production and lipid peroxidation. Cultured vascular endothelial cell (ECV304) were either not treated (control), or treated with TNF-alpha (40 ng/ml) alone or TNF-alpha in the presence of N-acetylcysteine at 30 mmol/l or 1 mmol/l, respectively, for 24 h. Cell viability was measured by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. Cell apoptosis was assessed by flow cytometry. TNF-alpha-induced endothelial cell apoptosis was associated with increased inducible NO synthase but reduced endothelial NO synthase (eNOS) protein expression. NO production and the levels of the lipid peroxidation product malondialdehyde were concomitantly increased. Treatment with NAC at 30 mmol/l restored eNOS expression and further increased NO production as compared to TNF-alpha alone, resulting in improved cell viability and reduced apoptosis. This was accompanied by increased superoxide dismutase activity, increased glutathione peroxidase production and reduced malondialdehyde levels. N-acetylcysteine at 1 mmol/l, however, did not have significant effects on TNF-alpha-induced endothelial cell apoptosis and cell viability despite it slightly enhanced glutathione peroxidase production. N-acetylcysteine attenuation of TNF-alpha-induced human vascular endothelial cell apoptosis is associated with the restoration of eNOS expression.

40 CFR 721.10176 - Amides, peanut-oil, N-[3-(dimethylamino)propyl].

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Amides, peanut-oil, N-[3... Specific Chemical Substances § 721.10176 Amides, peanut-oil, N-[3-(dimethylamino)propyl]. (a) Chemical..., peanut-oil, N-[3-(dimethylamino)propyl] (PMN P-04-144; CAS No. 691400-76-7) is subject to reporting under...

40 CFR 721.10176 - Amides, peanut-oil, N-[3-(dimethylamino)propyl].

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Amides, peanut-oil, N-[3... Specific Chemical Substances § 721.10176 Amides, peanut-oil, N-[3-(dimethylamino)propyl]. (a) Chemical..., peanut-oil, N-[3-(dimethylamino)propyl] (PMN P-04-144; CAS No. 691400-76-7) is subject to reporting under...

The effects of N-Acetylcysteine on frontostriatal resting-state functional connectivity, withdrawal symptoms and smoking abstinence: A double-blind, placebo-controlled fMRI pilot study*

PubMed Central

Froeliger, B.; McConnell, P.A.; Stankeviciute, N.; McClure, E.A.; Kalivas, P.W.; Gray, K.M.

2015-01-01

BACKGROUND Chronic exposure to drugs of abuse disrupts frontostriatal glutamate transmission, which in turn meditates drug seeking. In animal models, N-acetylcysteine normalizes dysregulated frontostriatal glutamatergic neurotransmission and prevents reinstated drug seeking; however, the effects of N-Acetylcysteine on human frontostriatal circuitry function and maintaining smoking abstinence is unknown. Thus, the current study tested the hypothesis that N-Acetylcysteine would be associated with stronger frontostriatal resting-state functional connectivity (rsFC), attenuated nicotine withdrawal and would help smokers to maintain abstinence over the study period. METHODS The present study examined the effects of N-Acetylcysteine on frontostriatal rsFC, nicotine-withdrawal symptoms and maintaining abstinence. Healthy adult, non-treatment seeking smokers (N=16; mean (SD) age 36.5±11.9; cigs/day 15.8±6.1; yrs/smoking 15.7±8.9) were randomized to a double-blind course of 2400 mg N-Acetylcysteine (1200 mg b.i.d.) or placebo over the course of 3 ½ days of monetary-incentivized smoking abstinence. On each abstinent day, measures of mood and craving were collected digitally and participants attended a lab visit in order to assess smoking (i.e., expired-air carbon monoxide [CO]). On day 4, participants underwent fMRI scanning. RESULTS As compared to placebo (n=8), smokers in the N-Acetylcysteine group (n=8) maintained abstinence, reported less craving and higher positive affect (all p’s <.01), and concomitantly exhibited stronger rsFC between ventral striatal nodes, medial prefrontal cortex and precuneus—key default mode network nodes, and the cerebellum [p<.025; FWE]). CONCLUSIONS Taken together, these findings suggest that N-Acetylcysteine may positively affect potentially dysregulated corticostriatal connectivity, help to restructure reward processing, and help to maintain abstinence immediately following a quit attempt. PMID:26454838

The effects of N-Acetylcysteine on frontostriatal resting-state functional connectivity, withdrawal symptoms and smoking abstinence: A double-blind, placebo-controlled fMRI pilot study.

PubMed

Froeliger, B; McConnell, P A; Stankeviciute, N; McClure, E A; Kalivas, P W; Gray, K M

2015-11-01

Chronic exposure to drugs of abuse disrupts frontostriatal glutamate transmission, which in turn meditates drug seeking. In animal models, N-Acetylcysteine normalizes dysregulated frontostriatal glutamatergic neurotransmission and prevents reinstated drug seeking; however, the effects of N-Acetylcysteine on human frontostriatal circuitry function and maintaining smoking abstinence is unknown. Thus, the current study tested the hypothesis that N-Acetylcysteine would be associated with stronger frontostriatal resting-state functional connectivity (rsFC), attenuated nicotine withdrawal and would help smokers to maintain abstinence over the study period. The present study examined the effects of N-Acetylcysteine on frontostriatal rsFC, nicotine-withdrawal symptoms and maintaining abstinence. Healthy adult, non-treatment seeking smokers (N=16; mean (SD) age 36.5±11.9; cigs/day 15.8±6.1; years/smoking 15.7±8.9) were randomized to a double-blind course of 2400mg N-Acetylcysteine (1200mg b.i.d.) or placebo over the course of 3½ days of monetary-incentivized smoking abstinence. On each abstinent day, measures of mood and craving were collected and participants attended a lab visit in order to assess smoking (i.e., expired-air carbon monoxide [CO]). On day 4, participants underwent fMRI scanning. As compared to placebo (n=8), smokers in the N-Acetylcysteine group (n=8) maintained abstinence, reported less craving and higher positive affect (all p's<.01), and concomitantly exhibited stronger rsFC between ventral striatal nodes, medial prefrontal cortex and precuneus-key default mode network nodes, and the cerebellum [p<.025; FWE]). Taken together, these findings suggest that N-Acetylcysteine may positively affect dysregulated corticostriatal connectivity, help to restructure reward processing, and help to maintain abstinence immediately following a quit attempt. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

N-acetylcysteine neither lowers plasma homocysteine concentrations nor improves brachial artery endothelial function in cardiac transplant recipients.

PubMed

Miner, S E S; Cole, D E C; Evrovski, J; Forrest, Q; Hutchison, S J; Holmes, K; Ross, H J

2002-05-01

N-acetylcysteine is a novel antioxidant that has been reported to reduce plasma homocysteine concentrations and improve endothelial function. Cardiac transplant recipients have a high incidence of coronary endothelial dysfunction and hyperhomocysteinemia, both of which may lead to the development of transplantation coronary artery disease. It was hypothesized that N-acetylcysteine would reduce plasma homocysteine concentrations and improve brachial endothelial function in cardiac transplant recipients. A cohort of stable cardiac transplant recipients was recruited from the outpatient clinic at the Toronto General Hospital, Toronto, Ontario. Brachial artery endothelial functions were studied according to standard techniques to determine flow-mediated dilation of the brachial artery. Plasma homocysteine concentrations were assayed using high performance liquid chromatography with electrochemical detection and pulsed integrated amperometry. After baseline testing, patients were treated in an unblinded fashion with N-acetylcysteine 500 mg/day. After 10 weeks of therapy, patients returned for follow-up endothelial function and homocysteine testing. Thirty-one patients were initially enrolled. Two patients withdrew due to excessive gastrointestinal upset. Two patients did not return for follow-up testing. The remaining 27 patients tolerated the treatment well. At baseline, 85% of the patients had hyperhomocysteinemia (greater than 15 mol/L) with a mean plasma concentration of 18.6 4.7 mol/L. No changes in homocysteine concentrations were seen at follow-up. At baseline, the average flow-mediated dilation was only 4.7 6.3%. No changes were seen at follow-up. Hyperhomocysteinemia and brachial endothelial dysfunction are common in stable cardiac transplant recipients and are unaffected by supplementation with N-acetylcysteine.

N,N-Diethylurea-Catalyzed Amidation between Electron-Defficient Aryl Azides and Phenylacetaldehydes

PubMed Central

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

Transtympanic injections of N-acetylcysteine for the prevention of cisplatin-induced ototoxicity: a feasible method with promising efficacy.

PubMed

Riga, Maria G; Chelis, Leonidas; Kakolyris, Stylianos; Papadopoulos, Stergios; Stathakidou, Sofia; Chamalidou, Eleni; Xenidis, Nikolaos; Amarantidis, Kyriakos; Dimopoulos, Prokopios; Danielides, Vasilios

2013-02-01

Ototoxicity is a common and irreversible adverse effect of cisplatin treatment with great impact on the patients' quality of life. N-acetylcysteine is a low-molecular-weight agent which has shown substantial otoprotective activity. The role of transtympanic infusions of N-acetylcysteine was examined in a cohort of patients treated with cisplatin-based regimens. Twenty cisplatin-treated patients were subjected, under local anesthesia, to transtympanic N-acetylcysteine (10%) infusions in 1 ear, during the hydration procedure preceding intravenous effusion of cisplatin. The contralateral ear was used as control. The number of transtympanic infusions was respective to the number of administered cycles. Hearing acuity was evaluated before each cycle with pure tone audiometry by an audiologist blinded to the treated ear. A total of 84 transtympanic infusions were performed. In treated ears, no significant changes in auditory thresholds were recorded. In the control ears cisplatin induced a significant decrease of auditory thresholds at the 8000 Hz frequency band (P=0.008). At the same frequency (8000 Hz), the changes in auditory thresholds were significantly larger for the control ears than the treated ones (P=0.005). An acute pain starting shortly after the injection and lasting for a few minutes seemed to be the only significant adverse effect. Transtympanic injections of N-acetylcysteine seem to be a feasible and effective otoprotective strategy for the prevention of cisplatin-induced ototoxicity. Additional studies are required to further clarify the efficiency of this treatment and determine the optimal dosage and protocol.

N-Acetylcysteine supplementation reduces oxidative stress and DNA damage in children with β-thalassemia.

PubMed

Ozdemir, Zeynep Canan; Koc, Ahmet; Aycicek, Ali; Kocyigit, Abdurrahim

2014-01-01

There are several reports that increased oxidative stress and DNA damage were found in β-thalassemia major (β-TM) patients. In this study, we aimed to evaluate the effects of N-acetylcysteine (NAC) and vitamin E on total oxidative stress and DNA damage in children with β-TM. Seventy-five children with transfusion-dependent β-thalassemia (β-thal) were randomly chosen to receive 10 mg/kg/day of NAC or 10 IU/kg/day of vitamin E or no supplementation; 28 healthy controls were also included in the study. Serum total oxidant status (TOS) and total antioxidant capacity (TAC) were measured, oxidative stress index (OSI) was calculated, and mononuclear DNA damage was assessed by alkaline comet assay; they were determined before treatment and after 3 months of treatment. Total oxydent status, OSI, and DNA damage levels were significantly higher and TAC levels were significantly lower in the thalassemic children than in the healthy controls (p < 0.001). In both supplemented groups, mean TOS and OSI levels were decreased; TAC and pre transfusion hemoglobin (Hb) levels were significantly increased after 3 months (p ≤ 0.002). In the NAC group, DNA damage score decreased (p = 0.001). N-Acetylcysteine and vitamin E may be effective in reducing serum oxidative stress and increase pre transfusion Hb levels in children with β-thal. N-Acetylcysteine also can reduce DNA damage.

Computerized N-acetylcysteine physician order entry by template protocol for acetaminophen toxicity.

PubMed

Thompson, Trevonne M; Lu, Jenny J; Blackwood, Louisa; Leikin, Jerrold B

2011-01-01

Some medication dosing protocols are logistically complex for traditional physician ordering. The use of computerized physician order entry (CPOE) with templates, or order sets, may be useful to reduce medication administration errors. This study evaluated the rate of medication administration errors using CPOE order sets for N-acetylcysteine (NAC) use in treating acetaminophen poisoning. An 18-month retrospective review of computerized inpatient pharmacy records for NAC use was performed. All patients who received NAC for the treatment of acetaminophen poisoning were included. Each record was analyzed to determine the form of NAC given and whether an administration error occurred. In the 82 cases of acetaminophen poisoning in which NAC was given, no medication administration errors were identified. Oral NAC was given in 31 (38%) cases; intravenous NAC was given in 51 (62%) cases. In this retrospective analysis of N-acetylcysteine administration using computerized physician order entry and order sets, no medication administration errors occurred. CPOE is an effective tool in safely executing complicated protocols in an inpatient setting.

N-acetylcysteine in Cleistanthus collinus Poisoning: A Report of Two Cases in Children.

PubMed

Sharma, Shreya; Rameshkumar, Ramachandran; Mahadevan, Subramanian

2016-12-01

Cleistanthus collinus, also known as Oduvanthalai in Tamil, is the most commonly encountered plant poison in southern India. The leaves are used for poisoning humans (suicide or homicide) and animals (cattle and fish) and as an abortifacient, especially in rural south India. Although this poisoning is commonly reported in adults, data regarding the use of N-acetylcysteine in pediatric poisoning is lacking. We report two previously healthy male siblings of pediatric age group who ingested the liquid extracted from crushed leaves of this plant given to them by their mother as a means of deliberate harm. Both patients developed distal renal tubular acidosis, with hypokalemia. The younger sibling also developed myocardial toxicity. Other significant findings noted include hypocalcemia, hypomagnesemia and elevated liver enzymes. Both patients received supportive care along with N-acetylcysteine infusion, and showed complete recovery within 10 days. © The Author [2016]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A Biomedical Application of Activated Carbon Adsorption: An Experiment Using Acetaminophen and N-Acetylcysteine.

ERIC Educational Resources Information Center

Rybolt, Thomas R.; And Others

1988-01-01

Illustrates an interesting biomedical application of adsorption from solution and demonstrates some of the factors that influence the in vivo adsorption of drug molecules onto activated charcoal. Uses acetaminophen and N-acetylcysteine for the determination. Suggests several related experiments. (MVL)

Synthesis, anticancer and antibacterial activity of salinomycin N-benzyl amides.

PubMed

Antoszczak, Michał; Maj, Ewa; Napiórkowska, Agnieszka; Stefańska, Joanna; Augustynowicz-Kopeć, Ewa; Wietrzyk, Joanna; Janczak, Jan; Brzezinski, Bogumil; Huczyński, Adam

2014-11-25

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.

Synaptic and cellular changes induced by the schizophrenia susceptibility gene G72 are rescued by N-acetylcysteine treatment

PubMed Central

Pósfai, B; Cserép, C; Hegedüs, P; Szabadits, E; Otte, D M; Zimmer, A; Watanabe, M; Freund, T F; Nyiri, G

2016-01-01

Genetic studies have linked the primate-specific gene locus G72 to the development of schizophrenia and bipolar disorder. Transgenic mice carrying the entire gene locus express G72 mRNA in dentate gyrus (DG) and entorhinal cortex, causing altered electrophysiological properties of their connections. These transgenic mice exhibit behavioral alterations related to psychiatric diseases, including cognitive deficits that can be reversed by treatment with N-acetylcysteine, which was also found to be effective in human patients. Here, we show that G72 transgenic mice have larger excitatory synapses with an increased amount of N-methyl-d-aspartate (NMDA) receptors in the molecular layer of DG, compared with wild-type littermates. Furthermore, transgenic animals have lower number of dentate granule cells with a parallel, but an even stronger decrease in the number of excitatory synapses in the molecular layer. Importantly, we also show that treatment with N-acetylcysteine can effectively normalize all these changes in transgenic animals, resulting in a state similar to wild-type mice. Our results show that G72 transcripts induce robust alterations in the glutamatergic system at the synaptic level that can be rescued with N-acetylcysteine treatment. PMID:27163208

N-acetylcysteine inhibits muscle fatigue in humans.

PubMed Central

Reid, M B; Stokić, D S; Koch, S M; Khawli, F A; Leis, A A

1994-01-01

N-acetylcysteine (NAC) is a nonspecific antioxidant that selectively inhibits acute fatigue of rodent skeletal muscle stimulated at low (but not high) tetanic frequencies and that decreases contractile function of unfatigued muscle in a dose-dependent manner. The present experiments test the hypothesis that NAC pretreatment can inhibit acute muscular fatigue in humans. Healthy volunteers were studied on two occasions each. Subjects were pretreated with NAC 150 mg/kg or 5% dextrose in water by intravenous infusion. The subject then sat in a chair with surface electrodes positioned over the motor point of tibialis anterior, an ankle dorsiflexor of mixed-fiber composition. The muscle was stimulated to contract electrically (40-55 mA, 0.2-ms pulses) and force production was measured. Function of the unfatigued muscle was assessed by measuring the forces produced during maximal voluntary contractions (MVC) of ankle dorsiflexor muscle groups and during electrical stimulation of tibialis anterior at 1, 10, 20, 40, 80, and 120 Hz (protocol 1). Fatigue was produced using repetitive tetanic stimulations at 10 Hz (protocol 1) or 40 Hz (protocol 2); intermittent stimulations subsequently were used to monitor recovery from fatigue. The contralateral leg then was studied using the same protocol. Pretreatment with NAC did not alter the function of unfatigued muscle; MVC performance and the force-frequency relationship of tibialis anterior were unchanged. During fatiguing contractions stimulated at 10 Hz, NAC increased force output by approximately 15% (P < 0.0001), an effect that was evident after 3 min of repetitive contraction (P < 0.0125) and persisted throughout the 30-min protocol. NAC had no effect on fatigue induced using 40 Hz stimuli or on recovery from fatigue. N-acetylcysteine pretreatment can improve performance of human limb muscle during fatiguing exercise, suggesting that oxidative stress plays a causal role in the fatigue process and identifying antioxidant

NACA documents database project

NASA Technical Reports Server (NTRS)

Smith, Ruth S.

1991-01-01

The plan to get all the National Advisory Committee on Aeronautics (NACA) collection online, with quality records, led to the NACA Documents Data base Project. The project has a two fold purpose: (1) to develop the definitive bibliography of NACA produced and/or held documents; and (2) to make that bibliography and the associated documents available to the aerospace community. This study supports the first objective by providing an analysis of the NACA collection and its bibliographic records, and supports the second objective by defining the NACA archive and recommending methodologies for meeting the project objectives.

N-Acetylcysteine reverses cocaine-induced metaplasticity.

PubMed

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

2009-02-01

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

Wind-tunnel investigation of an N.A.C.A. 23012 airfoil with two arrangements of a wide-chord slotted flap

NASA Technical Reports Server (NTRS)

Harris, Thomas A

1939-01-01

An investigation has been made in the N.A.C.A. 7- by 10-foot wind tunnel of a large-chord N.A.C.A. 23012 airfoil with several arrangements of a 40-percent-chord slotted flap to determine the section aerodynamic characteristics of the airfoil as affected by slot shape, flap location, and flap deflection. The flap positions for maximum lift, the polar for arrangements considered favorable for take-off and climb, and the complete section aerodynamic characteristics for selected optimum arrangements were determined. A discussion is given of the relative merits of the various arrangements. A comparison is made of slotted flaps of different chords on the N.A.C.A. 23012 airfoil. The best 40-percent-chord slotted flap is only slightly superior to the 25-percent-chord slotted flap from considerations of maximum lift coefficient and low drag for take-off and initial climb.

Bromelain and N-acetylcysteine inhibit proliferation and survival of gastrointestinal cancer cells in vitro: significance of combination therapy.

PubMed

Amini, Afshin; Masoumi-Moghaddam, Samar; Ehteda, Anahid; Morris, David Lawson

2014-11-12

Bromelain and N-acetylcysteine are two natural, sulfhydryl-containing compounds with good safety profiles which have been investigated for their benefits and application in health and disease for more than fifty years. As such, the potential values of these agents in cancer therapy have been variably reported in the literature. In the present study, the efficacy of bromelain and N-acetylcysteine in single agent and combination treatment of human gastrointestinal carcinoma cells was evaluated in vitro and the underlying mechanisms of effect were explored. The growth-inhibitory effects of bromelain and N-acetylcysteine, on their own and in combination, on a panel of human gastrointestinal carcinoma cell lines, including MKN45, KATO-III, HT29-5F12, HT29-5M21 and LS174T, were assessed by sulforhodamine B assay. Moreover, the influence of the treatment on the expression of a range of proteins involved in the regulation of cell cycle and survival was investigated by Western blot. The presence of apoptosis was also examined by TUNEL assay. Bromelain and N-acetylcysteine significantly inhibited cell proliferation, more potently in combination therapy. Drug-drug interaction in combination therapy was found to be predominantly synergistic or additive. Mechanistically, apoptotic bodies were detected in treated cells by TUNEL assay. Furthermore, Western blot analysis revealed diminution of cyclins A, B and D, the emergence of immunoreactive subunits of caspase-3, caspase-7, caspase-8 and cleaved PARP, withering or cleavage of procaspase-9, overexpression of cytochrome c, reduced expression of anti-apoptotic Bcl-2 and pro-survival phospho-Akt, the emergence of the autophagosomal marker LC3-II and deregulation of other autophagy-related proteins, including Atg3, Atg5, Atg7, Atg12 and Beclin 1. These results were more prominent in combination therapy. We report for the first time to our knowledge the growth-inhibitory and cytotoxic effects of bromelain and N-acetylcysteine, in

Efficacy of simethicone and N-acetylcysteine as premedication in improving visibility during upper endoscopy.

PubMed

Chang, Wei-Kuo; Yeh, Ming-Kung; Hsu, Hsuang-Chun; Chen, Hsuan-Wei; Hu, Ming-Kuan

2014-04-01

Simethicone and N-acetylcysteine have been widely used in improving endoscopic visibility. However, the optimal dose, volume, and dosing time for the premedication regimen are still unclear. Our aim was to assess the efficacy of premedication in improving endoscopic visibility and determine the contributions of dose, volume, and premedication time. A total of 1849 patients were prospectively treated in three groups: group A: 100-mg simethicone suspension in 5 mL water; group B: 100-mg simethicone suspension in 100 mL water; and group C: 100-mg simethicone suspension in 100 mL water containing 200 mg N-acetylcysteine. Mucosa visibility was assessed at seven sites of upper gastrointestinal tract. The sum of scores was considered as total mucosal visibility score (TMVS). The upper body of stomach had the worst visibility score for all groups. TMVS of groups B and C were significantly lower than those of group A. Group C had a significantly fewer patients requiring endoscopic flushing than groups A and B. The TMVS for groups B and C were significantly lower than for group A within 30 min of beginning premedication. Beyond 30 min of premedication, there was no significant difference in the TMVS among groups. Premedication using 100 mg simethicone in 100 mL of water improves endoscopic visibility. Addition of N-acetylcysteine to simethicone in 100 mL of water reduces the need for endoscopic flushing. For patients unable to tolerate a large fluid volume, a 5-mL simethicone suspension administered more than 30 min prior to upper endoscopy is suggested. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Hydrodynamic Tests in the N.A.C.A. Tank of a Model of the Hull of the Short Calcutta Flying Boat

NASA Technical Reports Server (NTRS)

Ward, Kenneth E

1937-01-01

The hydrodynamic characteristics of a model of the hull of the Short Calcutta (N.A.C.A. Model 47) are presented in non-dimensional form. This model represents one of a series of hulls of successful foreign and domestic flying boats the characteristics of which are being obtained under similar test conditions in the N.A.C.A. tank. The take-off distance and time for a flying boat having the hull of the Calcutta are compared at two values of the gross load with the corresponding distances and times for the same flying boat having hulls of two representative American types, the Sikorsky S-40 and the N.A.C.A. 11-A. This comparison indicates that for hulls of the widely different forms compared, the differences in take-off time and distance are negligible.

Microorganisms hydrolyse amide bonds; knowledge enabling read-across of biodegradability of fatty acid amides.

PubMed

Geerts, Roy; Kuijer, Patrick; van Ginkel, Cornelis G; Plugge, Caroline M

2014-07-01

To get insight in the biodegradation and potential read-across of fatty acid amides, N-[3-(dimethylamino)propyl] cocoamide and N-(1-ethylpiperazine) tall oil amide were used as model compounds. Two bacteria, Pseudomonas aeruginosa PK1 and Pseudomonas putida PK2 were isolated with N-[3-(dimethylamino)propyl] cocoamide and its hydrolysis product N,N-dimethyl-1,3-propanediamine, respectively. In mixed culture, both strains accomplished complete mineralization of N-[3-(dimethylamino)propyl] cocoamide. Aeromonas hydrophila PK3 was enriched with N-(1-ethylpiperazine) tall oil amide and subsequently isolated using agar plates containing dodecanoate. N-(2-Aminoethyl)piperazine, the hydrolysis product of N-(1-ethylpiperazine) tall oil amide, was not degraded. The aerobic biodegradation pathway for primary and secondary fatty acid amides of P. aeruginosa and A. hydrophila involved initial hydrolysis of the amide bond producing ammonium, or amines, where the fatty acids formed were immediately metabolized. Complete mineralization of secondary fatty acid amides depended on the biodegradability of the released amine. Tertiary fatty acid amides were not transformed by P. aeruginosa or A. hydrophila. These strains were able to utilize all tested primary and secondary fatty acid amides independent of the amine structure and fatty acid. Read-across of previous reported ready biodegradability results of primary and secondary fatty acid amides is justified based on the broad substrate specificity and the initial hydrolytic attack of the two isolates PK1 and PK3.

NACA Conference on Helicopters

DTIC Science & Technology

1954-05-01

Louis S., Jr.: Summary of Airfoil Data. NACA Rep. 824, 1945. (Supersedes NACA WR L-560.) 2. Loftin, Laurence K., Jr., and Smith , Hamilton, A...F., and Smith , Hamilton A.: Aerodynamic Character- istics of the NACA 8-H-12 Airfoil Section at Six Reynold Numbers From 1.8 x 1u6 to 11.0 X 106...NACA TN 1998, 1949. 4. Smith , Hamilton A., and Schaefer, Raymond F.: Aerodynamic Character- 0 istics at Reynolds Numbers of 3.0 X 106 and 6.0 x 106 of

Complete NACA Muroc Staff of 1950, in front of original NACA building

NASA Technical Reports Server (NTRS)

1950-01-01

This group photo of National Advisory Committee for Aeronautics (NACA) employees was taken in 1950 in front of the NACA research building on South Base at Edwards Air Force Base, California. The team that had been established at Muroc Army Air Field in the later part of 1946 had grown to about 13 members at the beginning of 1947. In September of 1947 the group became known as the NACA Muroc Flight Test Unit with a complement of 27 employees by January 1948. In February 1948 the name of the base changed to Muroc Air Force Base and in 1949 would change again to Edwards Air Force Base. In November 1949 the NACA Muroc Flight Test Unit became the NACA High-Speed Flight Research Station. In January 1950 there were 132 employees with those numbers increasing to 196 by January 1952.

N-acetylcysteine administration does not improve patient outcome after liver resection

PubMed Central

Robinson, Stuart M; Saif, Rehan; Sen, Gourab; French, Jeremy J; Jaques, Bryon C; Charnley, Richard M; Manas, Derek M; White, Steven A

2013-01-01

Background Post-operative hepatic dysfunction is a major cause of concern when undertaking a liver resection. The generation of reactive oxygen species (ROS) as a result of hepatic ischaemia/reperfusion (I/R) injury can result in hepatocellular injury. Experimental evidence suggests that N-acetylcysteine may ameliorate ROS-mediated liver injury. Methods A cohort of 44 patients who had undergone a liver resection and receiving peri-operative N-acetylcysteine (NAC) were compared with a further cohort of 44 patients who did not. Liver function tests were compared on post-operative days 1, 3 and 5. Peri-operative outcome data were retrieved from a prospectively maintained database within our unit. ResultsAdministration of NAC was associated with a prolonged prothrombin time on the third post-operative day (18.4 versus 16.4 s; P = 0.002). The incidence of grades B and C liver failure was lower in the NAC group although this difference did not reach statistical significance (6.9% versus 14%; P = 0.287). The overall complication rate was similar between groups (32% versus 25%; P = ns). There were two peri-operative deaths in the NAC group and one in the control group (P = NS). ConclusionIn spite of promising experimental evidence, this study was not able to demonstrate any advantage in the routine administration of peri-operative NAC in patients undergoing a liver resection. PMID:23458723

Unexpected Hydrolytic Instability of N-Acylated Amino Acid Amides and Peptides

PubMed Central

2015-01-01

Remote amide bonds in simple N-acyl amino acid amide or peptide derivatives 1 can be surprisingly unstable hydrolytically, affording, in solution, variable amounts of 3 under mild acidic conditions, such as trifluoroacetic acid/water mixtures at room temperature. This observation has important implications for the synthesis of this class of compounds, which includes N-terminal-acylated peptides. We describe the factors contributing to this instability and how to predict and control it. The instability is a function of the remote acyl group, R2CO, four bonds away from the site of hydrolysis. Electron-rich acyl R2 groups accelerate this reaction. In the case of acyl groups derived from substituted aromatic carboxylic acids, the acceleration is predictable from the substituent’s Hammett σ value. N-Acyl dipeptides are also hydrolyzed under typical cleavage conditions. This suggests that unwanted peptide truncation may occur during synthesis or prolonged standing in solution when dipeptides or longer peptides are acylated on the N-terminus with electron-rich aromatic groups. When amide hydrolysis is an undesired secondary reaction, as can be the case in the trifluoroacetic acid-catalyzed cleavage of amino acid amide or peptide derivatives 1 from solid-phase resins, conditions are provided to minimize that hydrolysis. PMID:24617596

N-acetylcysteine prevents the geldanamycin cytotoxicity by forming geldanamycin-N-acetylcysteine adduct.

PubMed

Mlejnek, Petr; Dolezel, Petr

2014-09-05

Geldanamycin (GDN) is a benzoquinone ansamycin antibiotic with anti-proliferative activity on tumor cells. GDN cytotoxicity has been attributed to the disruption of heat shock protein 90 (Hsp90) binding and stabilizing client proteins, and by the induction of oxidative stress with concomitant glutathione (GSH) depletion. The later mechanism of cytotoxicity can be abrogated by N-acetylcysteine (NAC). It was suggested that NAC prevents GDN cytotoxicity mainly by the restoring of glutathione (GSH) level (Clark et al., 2009). Here we argue that NAC does not protect cells from the GDN cytotoxicity by restoring the level of GSH. A detailed LC/MS/MS analysis of cell extracts indicated formation of GDN adducts with GSH. The amount of the GDN-GSH adduct is proportional to the GDN concentration and increases with incubation time. While nanomolar and low micromolar GDN concentrations induce cell death without an apparent GSH decrease, only much higher micromolar GDN concentrations cause a significant GSH decrease. Therefore, only high micromolar GDN concentrations can cause cell death which might be related to GSH depletion. Addition of NAC leads to the formation of adducts with GDN which diminish formation of GDN adducts with GSH. NAC also forms stable adducts with GDN extracellularly. Although NAC induces an increase in the GSH pool, this effect is not crucial for abrogation of GDN cytotoxicity. Indeed, the presence of NAC in the growth medium causes a rapid conversion of GDN into the GDN-NAC adduct, which is the real cause of the abrogated GDN cytotoxicity. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

N-acetylcysteine restores nitric oxide-mediated effects in the fetoplacental circulation of preeclamptic patients.

PubMed

Bisseling, Tanya M; Maria Roes, Eva; Raijmakers, Maarten T M; Steegers, Eric A P; Peters, Wilbert H M; Smits, Paul

2004-07-01

Preeclampsia is associated with an imbalance between oxidants and antioxidants, resulting in reduced effects of the endothelium-derived, relaxing-factor nitric oxide (NO). Antioxidants, like N-acetylcysteine (NAC), remove reactive oxygen species, resulting in an improvement of endothelial function. We aimed to investigate the effect of NAC on the NO-pathway in the human fetoplacental circulation in preeclampsia and control pregnancies. The NO-pathway was investigated by use of the NO-synthase inhibitor L-NAME in an ex vivo cotyledon perfusion model. At baseline, fetoplacental arterial pressure was comparable in preeclamptic pregnancies (n=8) and control pregnancies (n=8), and increased dose-dependently after L-NAME. The maximal L-NAME-induced rise in fetoplacental arterial pressure was attenuated in preeclamptic versus control pregnancies (20.8 +/- 2.0 mm Hg vs 36.7 +/- 3.5 mm Hg, P<.05). Addition of NAC increased the L-NAME-induced rise in fetoplacental arterial pressure to 36.4 +/- 3.4 mm Hg in preeclampsia pregnancies (P<.05) and to 49.2 +/- 2.6 mm Hg in control pregnancies (P<.05). Preeclampsia is associated with a dysfunction of the NO-pathway. N-acetylcysteine increases NO-mediated effects in the fetoplacental circulation in preeclamptic placentas as well as in healthy control placentas.

Reduction of estrogen-induced transformation of mouse mammary epithelial cells by N-acetylcysteine

PubMed Central

Venugopal, Divya; Zahid, Muhammad; Mailander, Paula C; Meza, Jane L.; Rogan, Eleanor G.; Cavalieri, Ercole L.; Chakravarti, Dhrubajyoti

2009-01-01

A growing number of studies indicate that breast cancer initiation is related to abnormal estrogen oxidation to form an excess of estrogen-3,4-quinones, which react with DNA to form depurinating adducts and induce mutations. This mechanism is often called estrogen genotoxicity. 4-catechol estrogens, precursors of the estrogen-3,4-quinones, were previously shown to account for most of the transforming and tumorigenic activity. We examined whether estrogen-induced transformation can be reduced by inhibiting the oxidation of a 4-catechol estrogen to its quinone. We demonstrate that E6 cells (a normal mouse epithelial cell line) can be transformed by a single treatment with a catechol estrogen or its quinone. The transforming activities of 4-hydroxyestradiol and estradiol-3,4-quinone were comparable. N-acetylcysteine, a common antioxidant, inhibited the oxidation of 4-hydroxyestradiol to the quinone and consequent formation of DNA adducts. It also drastically reduced estrogen-induced transformation of E6 cells. These results strongly implicate estrogen genotoxicity in mammary cell transformation. Since N-acetylcysteine is well-tolerated in clinical studies, it may be a promising candidate for breast cancer prevention. PMID:18226522

The promise of N-acetylcysteine in neuropsychiatry.

PubMed

Berk, Michael; Malhi, Gin S; Gray, Laura J; Dean, Olivia M

2013-03-01

N-Acetylcysteine (NAC) targets a diverse array of factors germane to the pathophysiology of multiple neuropsychiatric disorders including glutamatergic transmission, the antioxidant glutathione, neurotrophins, apoptosis, mitochondrial function, and inflammatory pathways. This review summarises the areas where the mechanisms of action of NAC overlap with known pathophysiological elements, and offers a précis of current literature regarding the use of NAC in disorders including cocaine, cannabis, and smoking addictions, Alzheimer's and Parkinson's diseases, autism, compulsive and grooming disorders, schizophrenia, depression, and bipolar disorder. There are positive trials of NAC in all these disorders, and although many of these require replication and are methodologically preliminary, this makes it one of the most promising drug candidates in neuropsychiatric disorders. The efficacy pattern of NAC interestingly shows little respect for the current diagnostic systems. Its benign tolerability profile, its action on multiple operative pathways, and the emergence of positive trial data make it an important target to investigate. Copyright © 2013 Elsevier Ltd. All rights reserved.

Conversion of amides to esters by the nickel-catalysed activation of amide C-N bonds.

PubMed

Hie, Liana; Fine Nathel, Noah F; Shah, Tejas K; Baker, Emma L; Hong, Xin; Yang, Yun-Fang; Liu, Peng; Houk, K N; Garg, Neil K

2015-08-06

Amides are common functional groups that have been studied for more than a century. They are the key building blocks of proteins and are present in a broad range of other natural and synthetic compounds. Amides are known to be poor electrophiles, which is typically attributed to the resonance stability of the amide bond. Although amides can readily be cleaved by enzymes such as proteases, it is difficult to selectively break the carbon-nitrogen bond of an amide using synthetic chemistry. Here we demonstrate that amide carbon-nitrogen bonds can be activated and cleaved using nickel catalysts. We use this methodology to convert amides to esters, which is a challenging and underdeveloped transformation. The reaction methodology proceeds under exceptionally mild reaction conditions, and avoids the use of a large excess of an alcohol nucleophile. Density functional theory calculations provide insight into the thermodynamics and catalytic cycle of the amide-to-ester transformation. Our results provide a way to harness amide functional groups as synthetic building blocks and are expected to lead to the further use of amides in the construction of carbon-heteroatom or carbon-carbon bonds using non-precious-metal catalysis.

N-Acetylcysteine prevents congenital heart defects induced by pregestational diabetes

PubMed Central

2014-01-01

Background Pregestational diabetes is a major risk factor of congenital heart defects (CHDs). Glutathione is depleted and reactive oxygen species (ROS) production is elevated in diabetes. In the present study, we aimed to examine whether treatment with N-acetylcysteine (NAC), which increases glutathione synthesis and inhibits ROS production, prevents CHDs induced by pregestational diabetes. Methods Female mice were treated with streptozotocin (STZ) to induce pregestational diabetes prior to breeding with normal males to produce offspring. Some diabetic mice were treated with N-acetylcysteine (NAC) in drinking water from E0.5 to the end of gestation or harvesting of the embryos. CHDs were identified by histology. ROS levels, cell proliferation and gene expression in the fetal heart were analyzed. Results Our data show that pregestational diabetes resulted in CHDs in 58% of the offspring, including ventricular septal defect (VSD), atrial septal defect (ASD), atrioventricular septal defects (AVSD), transposition of great arteries (TGA), double outlet right ventricle (DORV) and tetralogy of Fallot (TOF). Treatment with NAC in drinking water in pregestational diabetic mice completely eliminated the incidence of AVSD, TGA, TOF and significantly diminished the incidence of ASD and VSD. Furthermore, pregestational diabetes increased ROS, impaired cell proliferation, and altered Gata4, Gata5 and Vegf-a expression in the fetal heart of diabetic offspring, which were all prevented by NAC treatment. Conclusions Treatment with NAC increases GSH levels, decreases ROS levels in the fetal heart and prevents the development of CHDs in the offspring of pregestational diabetes. Our study suggests that NAC may have therapeutic potential in the prevention of CHDs induced by pregestational diabetes. PMID:24533448

Therapeutic effect of budesonide/formoterol, montelukast and N-acetylcysteine for bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation.

PubMed

Kim, Sei Won; Rhee, Chin Kook; Kim, Yoo Jin; Lee, Seok; Kim, Hee Je; Lee, Jong Wook

2016-05-26

Bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (HSCT) is currently treated with systemic corticosteroids despite poor efficacy and side effects. This study investigated the therapeutic effect of budesonide/formoterol, montelukast and n-acetylcysteine, which are suggested as treatment options for BOS after HSCT. After diagnosis of BOS, 61 patients were treated with budesonide/formoterol, montelukast and n-acetylcysteine for 3 months. Pulmonary function test and COPD assessment test (CAT) were performed before and after the combination therapy. Therapeutic response was evaluated by changes in forced expiratory volume in 1 s (FEV1) or CAT score. After 3 months of combination treatment, mean FEV1 increased by 220 mL (p < 0.001) and residual volume decreased by 200 mL (p =0 .005). Median CAT score also significantly decreased from 15.5 to 11.0 (p = 0.001). The overall response rate to combination therapy was 82 %. Comparing the no-response group and the response group, the forced vital capacity (% predicted) decline between pre-HSCT and BOS diagnosis was significantly greater in the response group (p = 0.036). Combination treatment with budesonide/formoterol, montelukast and n-acetylcysteine significantly improved lung function and respiratory symptoms in patients with BOS after allogeneic HSCT without serious side effects.

Amide-induced phase separation of hexafluoroisopropanol-water mixtures depending on the hydrophobicity of amides.

PubMed

Takamuku, Toshiyuki; Wada, Hiroshi; Kawatoko, Chiemi; Shimomura, Takuya; Kanzaki, Ryo; Takeuchi, Munetaka

2012-06-21

Amide-induced phase separation of hexafluoro-2-propanol (HFIP)-water mixtures has been investigated to elucidate solvation properties of the mixtures by means of small-angle neutron scattering (SANS), (1)H and (13)C NMR, and molecular dynamics (MD) simulation. The amides included N-methylformamide (NMF), N-methylacetamide (NMA), and N-methylpropionamide (NMP). The phase diagrams of amide-HFIP-water ternary systems at 298 K showed that phase separation occurs in a closed-loop area of compositions as well as an N,N-dimethylformamide (DMF) system previously reported. The phase separation area becomes wider as the hydrophobicity of amides increases in the order of NMF < NMA < DMF < NMP. Thus, the evolution of HFIP clusters around amides due to the hydrophobic interaction gives rise to phase separation of the mixtures. In contrast, the disruption of HFIP clusters causes the recovery of the homogeneity of the ternary systems. The present results showed that HFIP clusters are evolved with increasing amide content to the lower phase separation concentration in the same mechanism among the four amide systems. However, the disruption of HFIP clusters in the NMP and DMF systems with further increasing amide content to the upper phase separation concentration occurs in a different way from those in the NMF and NMA systems.

Effects of N-Acetylcysteine Addition to University of Wisconsin Solution on the Rate of Ischemia-Reperfusion Injury in Adult Orthotopic Liver Transplant.

PubMed

Aliakbarian, Mohsen; Nikeghbalian, Saman; Ghaffaripour, Sina; Bahreini, Amin; Shafiee, Mohammad; Rashidi, Mohammad; Rajabnejad, Yaser

2017-08-01

One of the main concerns in liver transplant is the prolonged ischemia time, which may lead to primary graft nonfunction or delayed function. N-acetylcysteine is known as a hepato-protective agent in different studies, which may improve human hepatocyte viability in steatotic donor livers. This study investigated whether N-acetylcysteine can decrease the rate of ischemia-reperfusion syndrome and improve short-term outcome in liver transplant recipients. This was a double-blind, randomized, control clinical trial of 115 patients. Between April 2012 and January 2013, patients with orthotopic liver transplant were randomly divided into 2 groups; in 49 cases N-acetylcysteine was added to University of Wisconsin solution as the preservative liquid (experimental group), and in 66 cases standard University of Wisconsin solution was used (control group). We compared postreperfusion hypotension, inotrope requirement before and after portal reperfusion, intermittent arterial blood gas analysis and potassium measurement, pathological review of transplanted liver, in-hospital complications, morbidity, and mortality. There was no significant difference between the groups regarding time to hepatic artery reperfusion, hospital stay, vascular complications, inotrope requirement before and after portal declamping, and blood gas analysis. Hypotension after portal reperfusion was significantly more common in experimental group compared with control group (P = .005). Retransplant and in-hospital mortality were comparable between the groups. Preservation of the liver inside Univer-sity of Wisconsin solution plus N-acetylcysteine did not change the rate of ischemia reperfusion injury and short-term outcome in liver transplant recipients.

[A girl with self-harm treated with N-acetylcysteine (NAC)].

PubMed

Rus, C P

Deliberate and recurrent self-harm could be regarded as addictive behaviour that can be treated with medication. In addiction, the dopaminergic mesolimbic reward system is activated. Pain caused by cutting stimulates the reward system through the opioid system. Glutamatergic neurotransmission follows the same pathway and plays a role in addiction as well. In this case-study a 17-year-old girl was successfully treated with N-acetylcysteine (nac) in order to reduce the frequency of self-cutting. In addition, in this case nac reduced the symptoms of attention deficit/hyperactivity disorder and depression. nac modulates the glutamatergic neurotransmission. This article provides possible explanations for the effect of nac in this case.

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

PubMed Central

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. PMID:21584258

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

PubMed

Kemp, Richard; Mole, Jonathan; Gomez, Dhanny

2018-06-01

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.

C-terminal N-alkylated peptide amides resulting from the linker decomposition of the Rink amide resin: a new cleavage mixture prevents their formation.

PubMed

Stathopoulos, Panagiotis; Papas, Serafim; Tsikaris, Vassilios

2006-03-01

Decomposition of the resin linkers during TFA cleavage of the peptides in the Fmoc strategy leads to alkylation of sensitive amino acids. The C-terminal amide alkylation, reported for the first time, is shown to be a major problem in peptide amides synthesized on the Rink amide resin. This side reaction occurs as a result of the Rink amide linker decomposition under TFA treatment of the peptide resin. The use of 1,3-dimethoxybenzene in a cleavage cocktail prevents almost quantitatively formation of C-terminal N-alkylated peptide amides. Oxidized by-product in the tested Cys- and Met-containing peptides were not observed, even if thiols were not used in the cleavage mixture. Copyright (c) 2005 European Peptide Society and John Wiley & Sons, Ltd.

N-acetylcysteine supplementation decreases osteoclast differentiation and increases bone mass in mice fed a high-fat diet

USDA-ARS?s Scientific Manuscript database

Studies have demonstrated that obesity induced by high-fat diets increases bone resorption, decreases trabecular bone mass, and reduces bone strength in various animal models. This study investigated whether N-acetylcysteine (NAC), an antioxidant and a glutathione precursor, alters glutathione statu...

Energetically Unfavorable Amide Conformations for N6-Acetyllysine Side Chains in Refined Protein Structures

PubMed Central

Genshaft, Alexander; Moser, Joe-Ann S.; D'Antonio, Edward L.; Bowman, Christine M.; Christianson, David W.

2013-01-01

The reversible acetylation of lysine to form N6-acetyllysine in the regulation of protein function is a hallmark of epigenetics. Acetylation of the positively charged amino group of the lysine side chain generates a neutral N-alkylacetamide moiety that serves as a molecular “switch” for the modulation of protein function and protein-protein interactions. We now report the analysis of 381 N6-acetyllysine side chain amide conformations as found in 79 protein crystal structures and 11 protein NMR structures deposited in the Protein Data Bank (PDB) of the Research Collaboratory for Structural Bioinformatics. We find that only 74.3% of N6-acetyllysine residues in protein crystal structures and 46.5% in protein NMR structures contain amide groups with energetically preferred trans or generously trans conformations. Surprisingly, 17.6% of N6-acetyllysine residues in protein crystal structures and 5.3% in protein NMR structures contain amide groups with energetically unfavorable cis or generously cis conformations. Even more surprisingly, 8.1% of N6-acetyllysine residues in protein crystal structures and 48.2% in NMR structures contain amide groups with energetically prohibitive twisted conformations that approach the transition state structure for cis-trans isomerization. In contrast, 109 unique N-alkylacetamide groups contained in 84 highly-accurate small molecule crystal structures retrieved from the Cambridge Structural Database exclusively adopt energetically preferred trans conformations. Therefore, we conclude that cis and twisted N6-acetyllysine amides in protein structures deposited in the PDB are erroneously modeled due to their energetically unfavorable or prohibitive conformations. PMID:23401043

Amide-based inhibitors of p38alpha MAP kinase. Part 2: design, synthesis and SAR of potent N-pyrimidyl amides.

PubMed

Tester, Richland; Tan, Xuefei; Luedtke, Gregory R; Nashashibi, Imad; Schinzel, Kurt; Liang, Weiling; Jung, Joon; Dugar, Sundeep; Liclican, Albert; Tabora, Jocelyn; Levy, Daniel E; Do, Steven

2010-04-15

Optimization of a tri-substituted N-pyridyl amide led to the discovery of a new class of potent N-pyrimidyl amide based p38alpha MAP kinase inhibitors. Initial SAR studies led to the identification of 5-dihydrofuran as an optimal hydrophobic group. Additional side chain modifications resulted in the introduction of hydrogen bond interactions. Through extensive SAR studies, analogs bearing free amino groups and alternatives to the parent (S)-alpha-methyl benzyl moiety were identified. These compounds exhibited improved cellular activities and maintained balance between p38alpha and CYP3A4 inhibition. Copyright 2010 Elsevier Ltd. All rights reserved.

Determination of Structures and Energetics of Small- and Medium-Sized One-Carbon-Bridged Twisted Amides using ab Initio Molecular Orbital Methods: Implications for Amidic Resonance along the C-N Rotational Pathway.

PubMed

Szostak, Roman; Aubé, Jeffrey; Szostak, Michal

2015-08-21

Twisted amides containing nitrogen at the bridgehead position are attractive practical prototypes for the investigation of the electronic and structural properties of nonplanar amide linkages. Changes that occur during rotation around the N-C(O) axis in one-carbon-bridged twisted amides have been studied using ab initio molecular orbital methods. Calculations at the MP2/6-311++G(d,p) level performed on a set of one-carbon-bridged lactams, including 20 distinct scaffolds ranging from [2.2.1] to [6.3.1] ring systems, with the C═O bond on the shortest bridge indicate significant variations in structures, resonance energies, proton affinities, core ionization energies, frontier molecular orbitals, atomic charges, and infrared frequencies that reflect structural changes corresponding to the extent of resonance stabilization during rotation along the N-C(O) axis. The results are discussed in the context of resonance theory and activation of amides toward N-protonation (N-activation) by distortion. This study demonstrates that one-carbon-bridged lactams-a class of readily available, hydrolytically robust twisted amides-are ideally suited to span the whole spectrum of the amide bond distortion energy surface. Notably, this study provides a blueprint for the rational design and application of nonplanar amides in organic synthesis. The presented findings strongly support the classical amide bond resonance model in predicting the properties of nonplanar amides.

Reversible Twisting of Primary Amides via Ground State N-C(O) Destabilization: Highly Twisted Rotationally Inverted Acyclic Amides.

PubMed

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

2018-01-17

Since the seminal studies by Pauling in 1930s, planarity has become the defining characteristic of the amide bond. Planarity of amides has central implications for the reactivity and chemical properties of amides of relevance to a range of chemical disciplines. While the vast majority of amides are planar, nonplanarity has a profound effect on the properties of the amide bond, with the most common method to restrict the amide bond relying on the incorporation of the amide function into a rigid cyclic ring system. In a major departure from this concept, here, we report the first class of acyclic twisted amides that can be prepared, reversibly, from common primary amides in a single, operationally trivial step. Di-tert-butoxycarbonylation of the amide nitrogen atom yields twisted amides in which the amide bond exhibits nearly perpendicular twist. Full structural characterization of a range of electronically diverse compounds from this new class of twisted amides is reported. Through reactivity studies we demonstrate unusual properties of the amide bond, wherein selective cleavage of the amide bond can be achieved by a judicious choice of the reaction conditions. Through computational studies we evaluate structural and energetic details pertaining to the amide bond deformation. The ability to selectively twist common primary amides, in a reversible manner, has important implications for the design and application of the amide bond nonplanarity in structural chemistry, biochemistry and organic synthesis.

Limited theraputic effect of n-acetylcysteine on hepatic insulin resistance in an experimental model of alcohol-induced steatohepatitis

USDA-ARS?s Scientific Manuscript database

Alcohol-related steatohepatitis is associated with increased oxidative stress, DNA damage, lipotoxicity, and insulin resistance in liver. Hypothesis: Since inflammation and oxidative stress can promote insulin resistance, effective treatment with anti-oxidants, e.g. N-acetylcysteine (NAC), may rest...

Complete NACA Muroc Staff of 1954, in front of new NACA building (4800)

NASA Technical Reports Server (NTRS)

1954-01-01

The employees of the NACA High-Speed Flight Station are gathered for a 1954 photo shoot on the front steps of building 4800, the new NACA Facility at Main Base of Edwards Air Force Base, California. This new building was considerably larger than the earlier NACA buildings on South Base, but then the staff had increased and the extra space was needed. From 1950 when an earlier group picture was taken (E-33717) until 1954 the staff at NACA increased from 132 to 250. As the workload increased and more research flights were completed the complement of employees grew to 662 in 1966. More changes took place in 1954 with the Station being called the NACA High-Speed Flight Station. A further name change occurred in October 1958 to the National Aeronautics and Space Administration (NASA) High-Speed Flight Station and again in September 1959 to the NASA Flight Research Center. There would be two more name changes before the next group photo (EC85-33160-2) would be made. On March 1976 to NASA Hugh L. Dryden Flight Research Center and in October 1981 when the Center became the Ames-Dryden Flight Research Facility.

Intravenous N-Acetylcysteine for Prevention of Contrast-Induced Nephropathy: A Meta-Analysis of Randomized, Controlled Trials

PubMed Central

Sun, Zikai; Fu, Qiang; Cao, Longxing; Jin, Wen; Cheng, LingLing; Li, Zhiliang

2013-01-01

Background Contrast-induced nephropathy (CIN) is one of the common causes of acute renal insufficiency after contrast procedures. Whether intravenous N-acetylcysteine (NAC) is beneficial for the prevention of contrast-induced nephropathy is uncertain. In this meta-analysis of randomized controlled trials, we aimed to assess the efficacy of intravenous NAC for preventing CIN after administration of intravenous contrast media. Study Design Relevant studies published up to September 2012 that investigated the efficacy of intravenous N-acetylcysteine for preventing CIN were collected from MEDLINE, OVID, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, and the conference proceedings from major cardiology and nephrology meetings. The primary outcome was CIN. Secondary outcomes included renal failure requiring dialysis, mortality, and length of hospitalization. Data were combined using random-effects models with the performance of standard tests to assess for heterogeneity and publication bias. Meta-regression analyses were also performed. Results Ten trials involving 1916 patients met our inclusion criteria. Trials varied in patient demographic characteristics, inclusion criteria, dosing regimens, and trial quality. The summary risk ratio for contrast-induced nephropathy was 0.68 (95% CI, 0.46 to 1.02), a nonsignificant trend towards benefit in patients treated with intravenous NAC. There was evidence of significant heterogeneity in NAC effect across studies (Q = 17.42, P = 0.04; I2 = 48%). Meta-regression revealed no significant relation between the relative risk of CIN and identified differences in participant or study characteristics. Conclusion This meta-analysis showed that research on intravenous N-acetylcysteine and the incidence of CIN is too inconsistent at present to warrant a conclusion on efficacy. A large, well designed trial that incorporates the evaluation of clinically relevant outcomes in participants with different

Effect of Surface Roughness on Characteristics of Aerofoils N.A.C.A. 0012 and R.A.F. 34

DTIC Science & Technology

1936-02-13

TABLE 3 N.A.C.A. 0012. Hand finished R x 10-« 0-164 0-312 0-63 0-98 1-44 1-47J 1-99 302 3-94 5- 52 ’ 7-20 i P. atmos. 1 1 21 j 3-6 4-8...Roughened FF R x ’.0-* 0-308 103 201 311 5- 52 P. a>.::ios. 1 3-9 7-9 11 -6 18-3 V.f./s 76-2 65-4 63-7 67-8 79-2 TABLE 6 N.A.C.A. 0012. Chromium...4 70-5 78-9 781 TABLE 7 R.A.F. 34. Hand finished R x 10-« 0-31 i 1 25 2-56 3- 52 4 51 5-47 6-47 2- 52 2- 52 7-17 I*. atmos. I 4-3 8-3 13-2 14-7

Adverse reactions associated with acetylcysteine.

PubMed

Sandilands, E A; Bateman, D N

2009-02-01

Paracetamol (acetaminophen) is one of the most common agents deliberately ingested in self-poisoning episodes and a leading cause of acute liver failure in the western world. Acetylcysteine is widely acknowledged as the antidote of choice for paracetamol poisoning, but its use is not without risk. Adverse reactions, often leading to treatment delay, are frequently associated with both intravenous and oral acetylcysteine and are a common source of concern among treating physicians. A systematic literature review investigating the incidence, clinical features, and mechanisms of adverse effects associated with acetylcysteine. A variety of adverse reactions to acetylcysteine have been described ranging from nausea to death, most of the latter due to incorrect dosing. The pattern of reactions differs with oral and intravenous dosing, but reported frequency is at least as high with oral as intravenous. The reactions to the intravenous preparation result in similar clinical features to true anaphylaxis, including rash, pruritus, angioedema, bronchospasm, and rarely hypotension, but are caused by nonimmunological mechanisms. The precise nature of this reaction remains unclear. Histamine now seems to be an important mediator of the response, and there is evidence of variability in patient susceptibility, with females, and those with a history of asthma or atopy are particularly susceptible. Quantity of paracetamol ingestion, measured through serum paracetamol concentration, is also important as higher paracetamol concentrations protect patients against anaphylactoid effects. Most anaphylactoid reactions occur at the start of acetylcysteine treatment when concentrations are highest. Acetylcysteine also affects clotting factor activity, and this affects the interpretation of minor disturbances in the International Normalized Ratio in the context of paracetamol overdose. This review discusses the incidence, clinical features, underlying pathophysiological mechanisms, and

An Efficient Computational Model to Predict Protonation at the Amide Nitrogen and Reactivity along the C–N Rotational Pathway

PubMed Central

Szostak, Roman; Aubé, Jeffrey

2015-01-01

N-protonation of amides is critical in numerous biological processes, including amide bonds proteolysis and protein folding, as well as in organic synthesis as a method to activate amide bonds towards unconventional reactivity. A computational model enabling prediction of protonation at the amide bond nitrogen atom along the C–N rotational pathway is reported. Notably, this study provides a blueprint for the rational design and application of amides with a controlled degree of rotation in synthetic chemistry and biology. PMID:25766378

NACA Groundbreaking Ceremony

NASA Technical Reports Server (NTRS)

1953-01-01

The NACA High-Speed Flight Research Station, had initially been subordinate to the Langley Memorial Aeronautical Laboratory near Hampton, Virginia, but as the flight research in the Mojave Desert increasingly proved its worth after 1946, it made sense to make the Flight Research Station a separate entity reporting directly to the headquarters of the National Advisory Committee for Aeronautics. But an autonomous center required all the trappings of a major research facility, including good quarters. With the adoption of the Edwards 'Master Plan,' the Air Force had committed itself to moving from its old South Base to a new location midway between the South and North Bases. The NACA would have to move also--so why not take advantage of the situation and move into a full-blown research facility. The Air Force issued a lease to NACA for a location on the northwestern shore of the Roger Dry Lake. Construction started on the NACA station in early February 1953. On a windy day, January 27, 1953, at a groundbreaking ceremony stood left to right: Gerald Truszynski, Head of Instrumentation Division; Joseph Vensel, Head of the Operations Branch; Walter Williams, Head of the Station, scooping the first shovel full of dirt; Marion Kent, Head of Personnel; and California state official Arthur Samet.

Improvement of hepatic microhemodynamics by N-acetylcysteine after warm ischemia.

PubMed

Koeppel, T A; Thies, J C; Lehmann, T; Gebhard, M M; Herfarth, C; Otto, G; Post, S

1996-01-01

In this study we investigated the influence of N-acetylcysteine (NAC) on the hepatic microcirculation after warm ischemia by intravital fluorescence microscopy. Clamping of the left liver lobe was performed in 20 male Wistar rats for 70 min. The treatment group (n = 10) received 400 mg NAC/kg body weight 20 min prior to clamping. After reperfusion, acinar and sinusoidal perfusions were observed as well as the leukocyte-endothelium interaction. Phagocytic activity was assessed after application of latex beads. NAC reduced the number of nonperfused sinusoids in all acinar zones. A reduction in zone 1 (portal) was achieved from 15.5 to 7.1% (p < 0.0001), in zone 2 (midzonal) from 14.6 to 6.1% (p < 0.0001) and in zone 3 (central) from 11.9 to 2.9% (p < 0.0001). There were no significant differences in leukocyte adherence as well as in phagocytic activity detectable. We conclude that NAC improves hepatic microcirculation after warm ischemia by increasing sinusoidal blood flow.

N-acetylcysteine does not influence the activity of endothelium-derived relaxing factor in vivo.

PubMed

Creager, M A; Roddy, M A; Boles, K; Stamler, J S

1997-02-01

Nitric oxide forms complexes with an array of biomolecular carriers that retain biological activity. This reactivity of nitric oxide in physiological systems has led to some dispute as to whether endothelium-derived relaxing factors nitric oxide or a closely related adduct thereof, such as a nitrosothiol. In vitro bioassays used to address this question are limited by the exclusion of biological thiols that are requisite for nitrosothiol formation. Thus, the purpose of this study was to obtain insight into the identity of endothelium-derived relaxing factor in vivo. We reasoned that if endothelium-derived relaxing factor in nitric oxide, infusion of physiological concentrations of thiol would potentiate its bioactivity by analogy with effects seen in vitro, whereas nitrosothiol would be resistant to such modulation. We used venous-occlusion plethysmography to study forearm blood flow in normal subjects. Methacholine (0.3 to 10 micrograms/min) and nitroglycerin (1 to 30 micrograms/min) were infused via the brachial artery to elicit endothelium-dependent and endothelium-independent vasodilation, respectively. Dose-response determinations were made for each drug before and after an intra-arterial infusion of the reduced thiol, N-acetylcysteine, at rates estimated to achieve a physiological concentration of 1 mmol/L. Methacholine increased forearm blood flow in a dose-dependent manner. Infusion of N-acetylcysteine did not change the sensitivity (ED50, 1.7 versus 1.7 micrograms/min, P = NS) or maximal response to methacholine. In contrast, thiol increased the sensitivity to nitroglycerin (ED50, 4.7 versus 2.8 micrograms/min, P < .01). Thus, conflicting with reports in vitro, thiol does not modulate endothelium-derived relaxing factor responses in vivo. These data indicate that sulfhydryl groups are not a limiting factor for endothelium-derived relaxing factor responses in forearm resistance vessels in normal humans and are in keeping with reports that nitrosothiol

Design and Conformational Analysis of Peptoids Containing N-Hydroxy Amides Reveals a Unique Sheet-Like Secondary Structure

PubMed Central

Crapster, J. Aaron; Stringer, Joseph R.; Guzei, Ilia A.; Blackwell, Helen E.

2011-01-01

N-hydroxy amides can be found in many naturally occurring and synthetic compounds and are known to act as both strong proton donors and chelators of metal cations. We have initiated studies of peptoids, or N-substituted glycines, that contain N-hydroxy amide side chains to investigate the potential effects of these functional groups on peptoid backbone amide rotamer equilibria and local conformations. We reasoned that the propensity of these functional groups to participate in hydrogen bonding could be exploited to enforce intramolecular or intermolecular interactions that yield new peptoid structures. Here, we report the design, synthesis, and detailed conformational analysis of a series of model N-hydroxy peptoids. These peptoids were readily synthesized, and their structures were analyzed in solution by 1D and 2D NMR and in the solid-state by X-ray crystallography. The N-hydroxy amides were found to strongly favor trans conformations with respect to the peptoid backbone in chloroform. More notably, unique sheet-like structures held together via intermolecular hydrogen bonds were observed in the X-ray crystal structures of an N-hydroxy amide peptoid dimer, which to our knowledge represent the first structure of this type reported for peptoids. These results suggest that the N-hydroxy amide can be utilized to control both local backbone geometries and longer-range intermolecular interactions in peptoids, and represents a new functional group in the peptoid design toolbox. PMID:22180908

Coordinating Council. Fourth Meeting: NACA Documents Database Project

NASA Technical Reports Server (NTRS)

1991-01-01

This NASA Scientific and Technical Information Coordination Council meeting dealt with the topic 'NACA Documents Database Project'. The following presentations were made and reported on: NACA documents database project study plan, AIAA study, the Optimal NACA database, Deficiencies in online file, NACA documents: Availability and Preservation, the NARA Collection: What is in it? and What to do about it?, and NACA foreign documents and availability. Visuals are available for most presentations.

[The application of N-acetylcysteine in optimization of specific pharmacological therapies].

PubMed

Hołyńska-Iwan, Iga; Wróblewski, Marcin; Olszewska-Słonina, Dorota; Tyrakowski, Tomasz

2017-09-29

Based on the analysis of data from clinical trials it could be postulated that N-acetylcysteine has a positive impact on the treatment of various diseases. However, less is known about specific molecular and physiological mechanisms underlying the reported therapeutic effects. N-acetylcysteine (NAC, N-acetyl-L-cysteine) is an amino acid derivative containing a thiol group. It is a precursor of L-cysteine and glutathione. NAC is well absorbed and safe for the body at doses up to 300 mg per kg of body weight. Side effects are relatively rare. NAC is used as an mucolytic agent in adjunctive therapy of respiratory diseases causing the retention of secretions, as well as an antidote in the treatment of paracetamol poisoning. Moreover, NAC protects against the toxic effects of reactive oxygen species and their active metabolites. NAC is involved in free radical scavenging processes via several independent mechanisms, including a direct reduction of free radicals, providing substrates for oxidation-reduction reactions and activation of antioxidant enzymes. In the blood, NAC decreases the level of low density lipoprotein peroxidation. In various tissues, NAC may increase the levels of glutathione and cysteine and stimulate the superoxide dismutase action. NAC is used as a supplement in the treatment of various diseases associated with impaired exterior and intracellular oxidative balance. NAC increases the concentrations of amino acids and their derivatives, including cysteine, cystine, and glutathione. It also stabilizes the antioxidant status of the cells and the intercellular spaces. NAC changes the levels of transcription factors, modifying the transcription of selected genes and acting on the protein translation. It works on the activation of several enzymes in the cells and outside the cells. Based on the analysis of data from clinical trials it can be concluded, that an administration of NAC may be beneficial for these groups of patients, in whom the reversible

(Z)-N,N-Dimethyl-2-[phen­yl(pyridin-2-yl)methyl­idene]hydrazinecarbothio­amide

PubMed Central

Jayakumar, K.; Sithambaresan, M.; Prathapachandra Kurup, M. R.

2011-01-01

The title compound, C15H16N4S, exists in the Z conformation with the thionyl S atom lying cis to the azomethine N atom. The shortening of the N—N distance [1.3697 (17) Å] is due to extensive delocalization with the pyridine ring. The hydrazine–carbothio­amide unit is almost planar, with a maximum deviation of 0.013 (2) Å for the amide N atom. The stability of this conformation is favoured by the formation of an intra­molecular N—H⋯N hydrogen bond. The packing of the mol­ecules involves no classical inter­molecular hydrogen-bonding inter­actions; however, a C—H⋯π inter­action occurs. PMID:22199715

Pharmacokinetic modelling of modified acetylcysteine infusion regimens used in the treatment of paracetamol poisoning.

PubMed

Wong, Anselm; Landersdorfer, Cornelia; Graudins, Andis

2017-09-01

Paracetamol overdose is common and is treated with acetylcysteine to prevent the development of hepatotoxicity. N-acetyl-p-benzoquinone imine (NAPQI) is the toxic metabolite of paracetamol overdose. We aimed to assess the expected acetylcysteine concentration time profiles following delivery of modified acetylcysteine regimens proposed for those at high and low risk of hepatotoxicity. In addition, we will determine acetylcysteine concentrations post-cessation of abbreviated infusions. We performed pharmacokinetic simulations using Berkeley Madonna (version 8.3.23.0) comparing the time course of acetylcysteine concentration during and after the cessation of an abbreviated 12-h regimen (250 mg/kg) using a two-bag infusion and compared this to the standard 21-h three-bag (300 mg/kg) regimen. We also simulated extended duration acetylcysteine regimens and other increased dosing strategies that have been recommended in specific paracetamol poisoning scenarios. A more sustained serum concentration is achieved when the acetylcysteine loading dose is delivered over 4 h using the two-bag compared to the 1-h loading dose of the three-bag regimen. When administering an abbreviated 12-h acetylcysteine regimen, circulating acetylcysteine is detectable for 8 h after cessation of the infusion. This may provide a continued hepatoprotective effect if NAPQI is still being generated after the infusion is ceased. This pharmacokinetic simulation study is an important step in determining plasma acetylcysteine concentrations that are likely to be achieved using various modified treatment regimens. Importantly, for patients at low risk of liver injury after acute overdose, acetylcysteine is likely to be detectable many hours post-cessation of a 12-h regimen. This should provide a safety factor against development of hepatotoxicity for any ongoing paracetamol metabolism after cessation of the acetylcysteine infusion.

The Enlarged N.A.C.A. Tank, and Some of Its Work

NASA Technical Reports Server (NTRS)

Truscott, Starr

1939-01-01

The most conspicuous of the features of the enlarged N.A.C.A. tank are derived directly from those of the original tank and owe their present form not only to the reasons for their first use but also to the experience obtained with them. As in the original tank, there are: 1) A basin of great length (new 2,880 feet); 2) Rails made of structural H beams, without machining; 3) A towing carriage of very high speed (now 80 mph maximum); 4) Rubber tires on all the wheels, pneumatic on the running wheels and solid on the guide wheels.

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

ERIC Educational Resources Information Center

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…

Experimental and clinical evidence for modification of hepatic ischaemia–reperfusion injury by N-acetylcysteine during major liver surgery

PubMed Central

Jegatheeswaran, Santhalingam; Siriwardena, Ajith K

2011-01-01

Background Hepatic ischaemia–reperfusion (I/R) injury occurs in both liver resectional surgery and in transplantation. The biochemistry of I/R injury involves short-lived oxygen free radicals. N-acetylcysteine (NAC) is a thiol-containing synthetic compound used in the treatment of acetaminophen toxicity. The present study is a detailed overview of the experimental and clinical evidence for the use of NAC as a pharmaco-protection agent in patients undergoing major liver surgery or transplantation. Methods A computerized search of the Medline, Embase and SCI databases for the period from 1st January 1988 to 31st December 2008 produced 40 reports. For clinical studies, the quality of reports was assessed according to the criteria reported by the Cochrane communication review group. Results Nineteen studies evaluated NAC in experimental liver I/R injury. NAC was administered before induction of ischaemia in 13. The most widely used concentration was 150 mg/kg by intravenous bolus. Fifteen studies report an improvement in outcome, predominantly a reduction in transaminase. Seven studies used an isolated perfused liver model with all showing improvement (predominantly an improvement in bile production after N-acetylcysteine). Two out of four transplantation models showed an improvement in hepatic function. Clinical studies in transplantation show a modest improvement in transaminase levels with no beneficial effect on either patient or graft survival. Conclusion N-acetylcysteine, given before induction of a liver I/R injury in an experimental model can ameliorate liver injury. Clinical outcome data are limited and there is currently little evidence to justify use either in liver transplantation or in liver resectional surgery. PMID:21241423

Novel endogenous N-acyl amides activate TRPV1-4 receptors, BV-2 microglia, and are regulated in brain in an acute model of inflammation

PubMed Central

Raboune, Siham; Stuart, Jordyn M.; Leishman, Emma; Takacs, Sara M.; Rhodes, Brandon; Basnet, Arjun; Jameyfield, Evan; McHugh, Douglas; Widlanski, Theodore; Bradshaw, Heather B.

2014-01-01

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. PMID:25136293

Amide-transforming activity of Streptomyces: possible application to the formation of hydroxy amides and aminoalcohols.

PubMed

Yamada, Shinya; Miyagawa, Taka-Aki; Yamada, Ren; Shiratori-Takano, Hatsumi; Sayo, Noboru; Saito, Takao; Takano, Hideaki; Beppu, Teruhiko; Ueda, Kenji

2013-07-01

To develop an efficient bioconversion process for amides, we screened our collection of Streptomyces strains, mostly obtained from soil, for effective transformers. Five strains, including the SY007 (NBRC 109343) and SY435 (NBRC 109344) of Streptomyces sp., exhibited marked conversion activities from the approximately 700 strains analyzed. These strains transformed diverse amide compounds such as N-acetyltetrahydroquinoline, N-benzoylpyrrolidine, and N-benzoylpiperidine into alcohols or N,O-acetals with high activity and regioselectivity. N,O-acetal was transformed into alcohol by serial tautomerization and reduction reactions. As such, Streptomyces spp. can potentially be used for the efficient preparation of hydroxy amides and aminoalcohols.

Iron(II) cage complexes of N-heterocyclic amide and bis(trimethylsilyl)amide ligands: synthesis, structure, and magnetic properties.

PubMed

Sulway, Scott A; Collison, David; McDouall, Joseph J W; Tuna, Floriana; Layfield, Richard A

2011-03-21

Metallation of hexahydropyrimidopyrimidine (hppH) by [Fe{N(SiMe(3))(2)}(2)] (1) produces the trimetallic iron(II) amide cage complex [{(Me(3)Si)(2)NFe}(2)(hpp)(4)Fe] (2), which contains three iron(II) centers, each of which resides in a distorted tetrahedral environment. An alternative, one-pot route that avoids use of the highly air-sensitive complex 1 is described for the synthesis of the iron(II)-lithium complex [{(Me(3)Si)(2)N}(2)Fe{Li(bta)}](2) (3) (where btaH = benzotriazole), in which both iron(II) centers reside in 3-coordinated pyramidal environments. The structure of 3 is also interpreted in terms of the ring laddering principle developed for alkali metal amides. Magnetic susceptibility measurements reveal that both compounds display very weak antiferromagnetic exchange between the iron(II) centers, and that the iron(II) centers in 2 and 3 possess large negative axial zero-field splittings.

N-acetylcysteine for major depressive episodes in bipolar disorder.

PubMed

Magalhães, Pedro V; Dean, Olívia M; Bush, Ashley I; Copolov, David L; Malhi, Gin S; Kohlmann, Kristy; Jeavons, Susan; Schapkaitz, Ian; Anderson-Hunt, Murray; Berk, Michael

2011-12-01

In this report, we aimed to evaluate the effect of add-on N-acetylcysteine (NAC) on depressive symptoms and functional outcomes in bipolar disorder. To that end, we conducted a secondary analysis of all patients meeting full criteria for a depressive episode in a placebo controlled trial of adjunctive NAC for bipolar disorder. Twenty-four week randomised clinical trial comparing adjunctive NAC and placebo in individuals with bipolar disorder experiencing major depressive episodes. Symptomatic and functional outcome data were collected over the study period. Seventeen participants were available for this report. Very large effect sizes in favor of NAC were found for depressive symptoms and functional outcomes at endpoint. Eight of the ten participants on NAC had a treatment response at endpoint; the same was true for only one of the seven participants allocated to placebo. These results indicate that adjunctive NAC may be useful for major depressive episodes in bipolar disorder. Further studies designed to confirm this hypothesis are necessary.

[Effectiveness of N-acetylcysteine in the treatment of schizophrenia].

PubMed

Miyake, Nobumi; Miyamoto, Seiya

2016-04-01

Oxidative stress and neuroinflammation have recently been focused on the pathological hypotheses of schizophrenia. N-acetylcysteine (NAC) is a precursor of endogenous antioxidant glutathione and has antioxidant, anti-inflammatory, and neuroprotective properties. NAC is widely available as an over-the-counter nutritional supplement. Increasing lines of evidence suggest that NAC is effective for various mental disorders. In randomized controlled trials, treatment with NAC as an add-on to antipsychotics showed beneficial effects and safety profiles in patients with chronic schizophrenia. The results of a recent preclinical study using a neurodevelopmental model of schizophrenia suggest that NAC may have promising effects in an early stage of schizophrenia and an at-risk mental state. However, there is little clinical evidence for the efficacy and safety of NAC at these stages of schizophrenia. In this review, we summarize the evidence regarding the effectiveness of NAC for the treatment of schizophrenia and its prodromal stage. We also introduce the preliminary results of our research on NAC.

N-acetylcysteine for neuropsychiatric symptoms in a woman with Williams syndrome.

PubMed

Pineiro, Mildred Lopez; Roberts, Antoinette M; Waxler, Jessica L; Mullett, Jennifer E; Pober, Barbara R; McDougle, Christopher J

2014-11-01

Williams syndrome is a relatively rare genetic disorder caused by the hemizygous microdeletion of a region in chromosome 7q11.23. Individuals with Williams syndrome typically present with a highly social, overfriendly, and empathic personality. Comorbid medical and neuropsychiatric disorders are common. Reports of effective pharmacological treatment of associated neuropsychiatric disorders are limited. The authors describe the successful treatment of interfering anger, aggression, and hair-pulling with N-acetylcysteine in a 19-year-old woman with Williams syndrome. The neuropsychiatric symptoms emerged 1 week following an upper gastrointestinal endoscopy, for which fentanyl, midazolam, and propofol were used as anesthetics. The patient's treatment course and hypothesized mechanisms underlying the clinical presentation and symptom resolution are described. © The Author(s) 2014.

Evidence for the changing regimens of acetylcysteine.

PubMed

Chiew, Angela L; Isbister, Geoffrey K; Duffull, Stephen B; Buckley, Nicholas A

2016-03-01

Paracetamol overdose prior to the introduction of acetylcysteine was associated with significant morbidity. Acetylcysteine is now the mainstay of treatment for paracetamol poisoning and has effectively reduced rates of hepatotoxicity and death. The current three-bag intravenous regimen with an initial high loading dose was empirically derived four decades ago and has not changed since. This regimen is associated with a high rate of adverse effects due mainly to the high initial peak acetylcysteine concentration. Furthermore, there are concerns that the acetylcysteine concentration is not adequate for 'massive' overdoses and that the dose and duration may need to be altered. Various novel regimens have been proposed, looking to address these issues. Many of these modified regimens aim to decrease the rate of adverse reactions by slowing the loading dose and thereby decrease the peak concentration. We used a published population pharmacokinetic model of acetylcysteine to simulate these modified regimens. We determined mean peak and 20 h acetylcysteine concentrations and area under the under the plasma concentration-time curve to compare these regimens. Those regimens that resulted in a lower peak acetylcysteine concentration have been shown in studies to have a lower rate of adverse events. However, these studies were too small to show whether they are as effective as the traditional regimen. Further research is still needed to determine the optimum dose and duration of acetylcysteine that results in the fewest side-effects and treatment failures. Indeed, a more patient-tailored approach might be required, whereby the dose and duration are altered depending on the paracetamol dose ingested or paracetamol concentrations. © 2015 The British Pharmacological Society.

Antiinflammatory Effect of N-Acetylcysteine Combined with Exogenous Surfactant in Meconium-Induced Lung Injury.

PubMed

Mikolka, P; Kopincova, J; Mikusiakova, L Tomcikova; Kosutova, P; Calkovska, A; Mokra, D

2016-01-01

Neonatal meconium aspiration syndrome (MAS) can be treated by exogenous surfactant (S). However, aspirated meconium initiates local inflammation and oxidation which may inactivate surfactant and reduce its action. This experimental study estimated whether combined use of surfactant and the antioxidant N-acetylcysteine (NAC) can enhance effectiveness of therapy. Meconium-instilled rabbits were non-treated (M), treated with monotherapies (M + S, M + NAC), combined therapy (M + S + NAC), or received saline instead of meconium (controls, C). Surfactant therapy consisted of two lung lavages (BAL) with diluted Curosurf (5 mg phospholipids/ml, 10 ml/kg) followed by undiluted Curosurf (100 mg phospholipids/kg). N-acetylcysteine (Acc Injekt, 10 mg/kg) was given intravenously in M + S + NAC group 10 min after surfactant therapy. Animals were oxygen-ventilated for additional 5 h. Then, differential white cell count in the blood (WBC) was determined. Left lung was saline-lavaged and differential cell count in BAL was determined. In right lung tissue, wet/dry weight ratio, oxidation markers (TBARS, 3NT) and interleukines (IL-2, IL-6, IL-13, and TNFα) using ELISA and RT-PCR were estimated. Combined S + NAC therapy significantly decreased W/D ratio, TBARS, 3NT, and IL, whereas the effect of monotherapies (either S or NAC) was less obvious. In conclusion, addition of NAC to surfactant treatment may enhance the therapeutic outcome in MAS.

NACA Researcher Examines the Cyclotron

NASA Image and Video Library

1951-02-21

Researcher James Blue examines the new cyclotron at the National Advisory Committee for Aeronautics (NACA) Lewis Flight Propulsion Laboratory. Researchers at NACA Lewis began postulating about the use of atomic power for propulsion immediately after World War II. The NACA concentrated its efforts on the study of high temperature materials and heat transfer since it did not have access to the top secret fission information. The military studied the plausibility of nuclear propulsion for aircraft in the late 1940s. The military program was cancelled after four years without any breakthroughs, but the Atomic Energy Commission took on the effort in 1951. The NACA Lewis laboratory was expanding its nuclear-related research during this period. In 1948, Lewis engineers were assigned to the Oak Ridge National Laboratory to obtain expertise in high temperature heat transfer and advanced materials technology. The following year a new 80-person Nuclear Reactor Division was created, and an in-house nuclear school was established to train these researchers. The cyclotron was built behind the Materials and Structures Laboratory to support thermodynamic and materials research for both nuclear aircraft and nuclear rockets. The original NACA Lewis cyclotron was used to accelerate two kinds of particles. To better match the space radiation environment, the cyclotron was later modified to accelerate particles of the newly-discovered Van Allen radiation belts.

Potentiation of chemotherapeutics by bromelain and N-acetylcysteine: sequential and combination therapy of gastrointestinal cancer cells

PubMed Central

Amini, Afshin; Masoumi-Moghaddam, Samar; Ehteda, Anahid; Liauw, Winston; Morris, David Lawson

2016-01-01

Intraperitoneal chemotherapy together with cytoreductive surgery is the standard of care for a number of peritoneal surface malignancies. However, this approach fails to maintain the complete response and disease recurs due to microscopic residual disease. Although safer than systemic chemotherapy regimens, locoregional treatment with chemotherapeutics can induce toxicity which is a major concern affecting the patient’s treatment protocol and outcome. For an enhanced treatment efficacy, efforts should be made to maximize cytotoxic effects of chemotherapeutic agents on tumor cells while minimizing their toxic effects on host cells. Bromelain and N-acetylcysteine are two natural agents with good safety profiles shown to have anti-cancer effects. However, their interaction with chemotherapeutics is unknown. In this study, we investigated if these agents have the potential to sensitize in vitro gastrointestinal cancer models to cisplatin, paclitaxel, 5-fluorouracil, and vincristine. The drug-drug interaction was also analyzed. Our findings suggest that combination of bromelain and N-acetylcysteine with chemotherapeutic agents could give rise to an improved chemotherapeutic index in therapeutic approaches to peritoneal surface malignancies of gastrointestinal origin so that maximum benefits could result from less toxic and more patient-friendly doses. This represents a potentially efficacious strategy for the enhancement of microscopic cytoreduction and is a promising area for future research. PMID:27186409

Pd-Catalyzed N-Arylation of Secondary Acyclic Amides: Catalyst Development, Scope, and Computational Study

PubMed Central

Hicks, Jacqueline D.; Hyde, Alan M.; Cuezva, Alberto Martinez; Buchwald, Stephen L.

2009-01-01

We report the efficient N-arylation of acyclic secondary amides and related nucleophiles with aryl nonaflates, triflates, and chlorides. This method allows for easy variation of the aromatic component in tertiary aryl amides. A new biaryl phosphine with P-bound 3,5-(bis)trifluoromethylphenyl groups was found to be uniquely effective for this amidation. The critical aspects of the ligand were explored through synthetic, mechanistic, and computational studies. Systematic variation of the ligand revealed the importance of (1) a methoxy group on the aromatic carbon of the “top ring” ortho to the phosphorus and (2) two highly electron-withdrawing P-bound 3,5-(bis)trifluoromethylphenyl groups. Computational studies suggest the electron-deficient nature of the ligand is important in facilitating amide binding to the LPd(II)(Ph)(X) intermediate. PMID:19886610

Hydrodynamic and Aerodynamic Tests of Four Models of Outboard Floats : (N.A.C.A. Models 51-A, 51-B, 51-C, and 51-D)

NASA Technical Reports Server (NTRS)

Dawson, John R; Hartman, Edwin P

1938-01-01

Four models of outboard floats (N.A.C.A. models 51-A, 51-B, 51-C, and 51-D) were tested in the N.A.C.A. tank to determine their hydrodynamic characteristics and in the 20-foot wind tunnel to determine their aerodynamic drag. The results of the tests, together with comparisons of them, are presented in the form of charts. From the comparisons, the order of merit of the models is estimated for each factor considered. The best compromise between the various factors seems to be given by model 51-D. This model is the only one in the series with a transverse step.

Surgically Induced Necrotizing Scleritis Following Strabismus Surgery Treated Successfully with Topical N-acetylcysteine in a Child with Congenital Fibrosis of Extraocular Muscles and Varadi Papp Syndrome.

PubMed

Rajamani, Muralidhar; Nagasubramanian, Vidhya; Ayyavoo, Ahila; Raghupathy, Palany; Dandapani, Ramamurthy

2017-03-01

Surgically induced necrotizing scleritis (SINS) is a rare but serious disorder that can develop many years after strabismus surgery. It is generally treated with high-dose steroids or immunosuppression. We describe a patient with Varadi Papp syndrome and congenital fibrosis of the extraocular muscles, who developed surgically induced necrotizing scleritis a month after strabismus surgery and was successfully managed by oral vitamin C and topical N-acetylcysteine 10%. While SINS is conventionally treated with steroids/immunosuppression, a conservative approach may be tried in milder cases. The role of topical N-acetylcysteine in managing this complication needs to be explored.

Premedication with simethicone and N-acetylcysteine in improving visibility during upper endoscopy: a double-blind randomized trial.

PubMed

Elvas, Luís; Areia, Miguel; Brito, Daniel; Alves, Susana; Saraiva, Sandra; Cadime, Ana T

2017-02-01

Background and study aim  Upper endoscopy is the most common method for the diagnosis of upper gastrointestinal tract diseases. The aim of this study was to determine whether premedication with simethicone or N -acetylcysteine improves mucosal visualization during upper endoscopy. Patients and methods  This was a randomized, double-blind, placebo-controlled study of 297 patients scheduled for upper endoscopy who were premedicated 15 - 30 minutes before the procedure with: 100 mL of water (placebo, group A); water plus 100 mg simethicone (group B); water plus 100 mg simethicone plus 600 mg N -acetylcysteine (group C). The primary outcome measure was the quality of mucosal visualization (score: excellent, adequate or inadequate). Results  The addition of simethicone (group B) or simethicone plus N -acetylcysteine to the water (group C) improved the visualization scores of endoscopies compared with water alone (group A). In particular, groups B and C produced a significantly higher percentage of endoscopies with excellent visualization for the esophagus (91.1 % and 86.7 %, respectively, vs. 71.4 % in group A; P  < 0.001) and stomach (76.2 % and 74.5 % vs. 38.8 % in group A; P  < 0.001). For the duodenum, the use of simethicone also showed an increase in the endoscopies with excellent visualization compared with water alone (85.1 % vs. 73.5 %; P  = 0.042). There were no significant differences in scores between groups B and C or between gastric scores in patients with previous subtotal gastrectomy (B and C vs. A): 60.0 % and 42.1 % vs. 28.6 % ( P  = 0.14). The rate of reported lesions was higher in group B but without statistical significance. Conclusions  Premedication with simethicone resulted in better mucosal visibility. Such premedication might improve diagnostic yield, and should be considered for standard practice. Trial registered at ClinicalTrials.gov (NCT02357303). © Georg Thieme Verlag KG Stuttgart �

Antiatherogenic effects of S-nitroso-N-acetylcysteine in hypercholesterolemic LDL receptor knockout mice.

PubMed

Krieger, M H; Santos, K F R; Shishido, S M; Wanschel, A C B A; Estrela, H F G; Santos, L; De Oliveira, M G; Franchini, K G; Spadari-Bratfisch, R C; Laurindo, F R M

2006-02-01

The pathophysiology of the NO/NO synthase system and dysfunctional changes in the endothelium in the early phases of the atherogenic process are incompletely understood. In this study, we investigated the effects of the nitrosothiol NO donor S-nitroso-N-acetylcysteine (SNAC) in the early prevention of plaque development in the hypercholesterolemic LDLr-/- mice as well as the changes in endothelium-dependent relaxation and NO synthase expression. LDLr-/- mice were fed a 1.25% cholesterol-enriched diet for 15 days. Plasma cholesterol/triglyceride levels increased and this increase was accompanied by the development of aortic root lesions. Aortic vasorelaxation to acetylcholine was increased, although endothelium-independent relaxation in response to sodium nitroprusside did not change, which suggest stimulated NO release enhanced. This dysfunction was associated with enhanced aortic superoxide production and with increased levels of constitutive NOS isoform expression, particularly neuronal NOS. SNAC (S-nitroso-N-acetylcysteine) administration (0.51 micromol/kg/day i.p. for 15 days) decreased the extent of the plaque by 55% in hypercholesterolemic mice, but had no effects on vasomotor changes. It did, however, lead to a decrease in constitutive NOS expression. The SNAC induced only minor changes in plasma lipid profile. The present study has shown that, in early stages of plaque development in LDLr-/- mice, specific changes in NO/NO synthase system develop, that are characterized by increased endothelium-dependent vasorelaxation and increased constitutive NOS expression. Since the development of plaque and the indicator of endothelial cell dysfunction were prevented by SNAC, such treatment may constitute a novel strategy for the halting of progression of early plaque.

Electrogenic Na+/Ca2+ Exchange

PubMed Central

Danaceau, Jonathan P.; Lucero, Mary T.

2000-01-01

Olfactory receptor neurons (ORNs) from the squid, Lolliguncula brevis, respond to the odors l-glutamate or dopamine with increases in internal Ca2+ concentrations ([Ca2+]i). To directly asses the effects of increasing [Ca2+]i in perforated-patched squid ORNs, we applied 10 mM caffeine to release Ca2+ from internal stores. We observed an inward current response to caffeine. Monovalent cation replacement of Na+ from the external bath solution completely and selectively inhibited the caffeine-induced response, and ruled out the possibility of a Ca2+-dependent nonselective cation current. The strict dependence on internal Ca2+ and external Na+ indicated that the inward current was due to an electrogenic Na+/Ca2+ exchanger. Block of the caffeine-induced current by an inhibitor of Na+/Ca2+ exchange (50–100 μM 2′,4′-dichlorobenzamil) and reversibility of the exchanger current, further confirmed its presence. We tested whether Na+/Ca2+ exchange contributed to odor responses by applying the aquatic odor l-glutamate in the presence and absence of 2′,4′-dichlorobenzamil. We found that electrogenic Na+/Ca2+ exchange was responsible for ∼26% of the total current associated with glutamate-induced odor responses. Although Na+/Ca2+ exchangers are known to be present in ORNs from numerous species, this is the first work to demonstrate amplifying contributions of the exchanger current to odor transduction. PMID:10828249

N-acetylcysteine negatively regulates Notch3 and its malignant signaling

PubMed Central

Zhu, Juan-Juan; Liu, Xue-Xia; You, Hui; Gong, Mei-Ying; Zou, Ming; Cheng, Wen-Hsing; Zhu, Jian-Hong

2016-01-01

Notch3 receptor is expressed in a variety of cancers and the excised active intracellular domain (N3ICD) initiates its signaling cascade. N-acetylcysteine (NAC) as an antioxidant has been implicated in cancer prevention and therapy. In this study, we demonstrated a negative regulation of Notch3 by NAC in cancer cells. HeLa cells treated with NAC exhibited a time- and concentration-dependent decrease in Notch3 levels and its downstream effectors Hes1 and HRT1 in a manner independent of f-secretase or glutathione. In contrast, NAC did not affect protein levels of Notch1, the full length Notch3 precursor, or ectopically expressed N3ICD. Although SOD, catalase and NAC suppressed reactive oxygen species in HeLa cells, the first two antioxidants did not impact on Notch3 levels. While the mRNA expression of Notch3 was not altered by NAC, functional inhibition of lysosome, but not proteasome, blocked the NAC-dependent reduction of Notch3 levels. Furthermore, results from Notch3 silencing and N3ICD overexpression demonstrated that NAC prevented malignant phenotypes through down-regulation of Notch3 protein in multiple cancer cells. In summary, NAC reduces Notch3 levels through lysosome-dependent protein degradation, thereby negatively regulates Notch3 malignant signaling in cancer cells. These results implicate a novel NAC treatment in sensitizing Notch3-expressing tumors. PMID:27102435

N-acetylcysteine negatively regulates Notch3 and its malignant signaling.

PubMed

Zhang, Xiong; Wang, Ya-Nan; Zhu, Juan-Juan; Liu, Xue-Xia; You, Hui; Gong, Mei-Ying; Zou, Ming; Cheng, Wen-Hsing; Zhu, Jian-Hong

2016-05-24

Notch3 receptor is expressed in a variety of cancers and the excised active intracellular domain (N3ICD) initiates its signaling cascade. N-acetylcysteine (NAC) as an antioxidant has been implicated in cancer prevention and therapy. In this study, we demonstrated a negative regulation of Notch3 by NAC in cancer cells. HeLa cells treated with NAC exhibited a time- and concentration-dependent decrease in Notch3 levels and its downstream effectors Hes1 and HRT1 in a manner independent of f-secretase or glutathione. In contrast, NAC did not affect protein levels of Notch1, the full length Notch3 precursor, or ectopically expressed N3ICD. Although SOD, catalase and NAC suppressed reactive oxygen species in HeLa cells, the first two antioxidants did not impact on Notch3 levels. While the mRNA expression of Notch3 was not altered by NAC, functional inhibition of lysosome, but not proteasome, blocked the NAC-dependent reduction of Notch3 levels. Furthermore, results from Notch3 silencing and N3ICD overexpression demonstrated that NAC prevented malignant phenotypes through down-regulation of Notch3 protein in multiple cancer cells. In summary, NAC reduces Notch3 levels through lysosome-dependent protein degradation, thereby negatively regulates Notch3 malignant signaling in cancer cells. These results implicate a novel NAC treatment in sensitizing Notch3-expressing tumors.

Interactive effects of N-acetylcysteine and antidepressants.

PubMed

Costa-Campos, Luciane; Herrmann, Ana P; Pilz, Luísa K; Michels, Marcus; Noetzold, Guilherme; Elisabetsky, Elaine

2013-07-01

N-acetylcysteine (NAC), a glutathione precursor and glutamate modulator, has been shown to possess various clinically relevant psychopharmacological properties. Considering the role of glutamate and oxidative stress in depressive states, the poor effectiveness of antidepressant drugs (ADs) and the benefits of drug combination for treating depression, the aim of this study was to explore the possible benefit of NAC as an add on drug to treat major depression. For that matter we investigated the combination of subeffective and effective doses of NAC with subeffective and effective doses of several ADs in the mice tail suspension test. The key finding of this study is that a subeffective dose of NAC reduced the minimum effective doses of imipramine and escitalopram, but not those of desipramine and bupropion. Moreover, the same subeffective dose of NAC increased the minimum effective dose of fluoxetine in the same model. In view of the advantages associated with using the lowest effective dose of antidepressant, the results of this study suggest the potential of a clinically useful interaction of NAC with imipramine and escitalopram. Further studies are necessary to better characterize the molecular basis of such interactions, as well as to typify the particular drug combinations that would optimize NAC as an alternative for treating depression. Copyright © 2013 Elsevier Inc. All rights reserved.

NACA Wartime Safety Poster

NASA Image and Video Library

1945-04-21

One of many safety posters produced by NACA artists during World War II. The Aircraft Engine Research Laboratory established a Safety Office in 1942 to coordinate and oversee safety-related activities. The lab struggled to maintain a full staff during the war when military research projects were at a peak. NACA management mandated six-day work weeks without overtime and the elimination of holidays. As such, workplace injuries were a serious threat to maintaining productivity needed to sustain the military’s aeronautics efforts.

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.

PubMed

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

Delays during the administration of acetylcysteine for the treatment of paracetamol overdose

PubMed Central

Bailey, George P.; Najafi, Javad; Elamin, Muhammad E. M. O.; Waring, W. Stephen; Thomas, Simon H. L.; Archer, John R. H.; Wood, David M.

2016-01-01

Background The licensed intravenous acetylcysteine regimen for treating paracetamol overdose in most countries uses three separate infusions over 21 h. This complex regimen, requiring different infusion concentrations and rates, has been associated with administration errors. The aim of the present study was to assess the extent of administration delays occurring during this acetylcysteine regimen. Method A 6‐month retrospective observational study was conducted at three English teaching hospitals with clinical toxicology services from October 2014. Patients aged 16 years and over, treated with intravenous acetylcysteine for paracetamol overdose, were included. The start times for infusions were recorded and the delays compared with the prescribed infusion times were calculated. Anaphylactoid reactions, intravenous cannula problems, overdose intent and smoking status were recorded to assess their contribution to delays. Results From 263 cases identified, 198 met the study inclusion criteria. The median time between the start of infusions 1 and 3 was delayed from the intended 5 h by a median (interquartile range) of 90 (50–163) min, with 135 (68%) cases delayed by more than 1 h. Significantly longer delays were observed in patients with anaphylactoid reactions [median delay 267 (217–413) min, n = 8] and accidental/supratherapeutic overdose [median delay 170 (95–260) min, n = 29]. There were no significant differences between smokers and nonsmokers, or for patients with intravenous cannula problems. Conclusion Long delays were identified during the three‐infusion acetylcysteine regimen for the treatment of paracetamol overdose. These were of clinical significance and could lead to periods of subtherapeutic plasma acetylcysteine concentrations and potentially avoidable hepatotoxicity, as well as delaying hospital discharge. PMID:27412926

Delays during the administration of acetylcysteine for the treatment of paracetamol overdose.

PubMed

Bailey, George P; Najafi, Javad; Elamin, Muhammad E M O; Waring, W Stephen; Thomas, Simon H L; Archer, John R H; Wood, David M; Dargan, Paul I

2016-11-01

The licensed intravenous acetylcysteine regimen for treating paracetamol overdose in most countries uses three separate infusions over 21 h. This complex regimen, requiring different infusion concentrations and rates, has been associated with administration errors. The aim of the present study was to assess the extent of administration delays occurring during this acetylcysteine regimen. A 6-month retrospective observational study was conducted at three English teaching hospitals with clinical toxicology services from October 2014. Patients aged 16 years and over, treated with intravenous acetylcysteine for paracetamol overdose, were included. The start times for infusions were recorded and the delays compared with the prescribed infusion times were calculated. Anaphylactoid reactions, intravenous cannula problems, overdose intent and smoking status were recorded to assess their contribution to delays. From 263 cases identified, 198 met the study inclusion criteria. The median time between the start of infusions 1 and 3 was delayed from the intended 5 h by a median (interquartile range) of 90 (50-163) min, with 135 (68%) cases delayed by more than 1 h. Significantly longer delays were observed in patients with anaphylactoid reactions [median delay 267 (217-413) min, n = 8] and accidental/supratherapeutic overdose [median delay 170 (95-260) min, n = 29]. There were no significant differences between smokers and nonsmokers, or for patients with intravenous cannula problems. Long delays were identified during the three-infusion acetylcysteine regimen for the treatment of paracetamol overdose. These were of clinical significance and could lead to periods of subtherapeutic plasma acetylcysteine concentrations and potentially avoidable hepatotoxicity, as well as delaying hospital discharge. © 2016 The British Pharmacological Society.

2015 Summer Series - The NACA - A Hundred Year Legacy

NASA Image and Video Library

2015-07-09

Understanding the past provides insight into our identity and NASA's history lies within NACA, the National Advisory Committee for Aeronautics. NACA's culture of conducting cutting edge research became the spirit of NASA and laid the foundation for America's leap into space. NACA was established on March 3, 1915 in order to promote aeronautical research and was the source behind our air superiority during WWII. The Panel delves into the legacy of the NACA.

Ab initio study of the barrier to internal rotation in simple amides. 1. N, N-dimethylformamide and N, N-dimethylcarbamic halogenides

NASA Astrophysics Data System (ADS)

Vassilev, Nikolay G.; Dimitrov, Valentin S.

1999-06-01

Free energies of activation for rotation about the amide C-N bond in X-C(O)N(CH 3) 2 (X=H, F, Cl and Br) were calculated at the MP2(fc)/6-31+G*//6-31G* and MP2(fc)/6-311++G**//6-311++G** levels and compared with NMR gas-phase data. The results of calculations indicate that the repulsion between X and methyl group in ground state and the repulsion between X or oxygen and nitrogen lone pair in transition states (TS) are largely responsible for the difference in the free energies of the studied amides. For X=H (DMF), the anti TS is more stable; for the cases X=Cl, Br, the syn TS is more stable, while for the case X=F the two transition states are energetically almost equivalent.

Selected bibliography of NACA-NASA aircraft icing publications

NASA Technical Reports Server (NTRS)

Reinmann, J. J. (Compiler)

1981-01-01

A summary of NACA-NASA icing research from 1940 to 1962 is presented. It includes: the main results of the NACA icing program from 1940 to 1950; a selected bibliography of 132 NACA-NASA aircraft icing publications; a technical summary of each document cited in the selected bibliography; and a microfiche copy of each document cited in the selected bibliography.

Oral N-acetylcysteine and exercise tolerance in mild chronic obstructive pulmonary disease.

PubMed

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 < lower limit of normal (LLN) and FEV 1 ≥ LLN) were enrolled in a double-blind, randomized crossover study to receive NAC (1,800 mg/day) or placebo for 4 days. Severe-intensity constant-load 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 < 0.05), there were no differences in 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

Acetylcysteine for treatment of autism spectrum disorder symptoms.

PubMed

Stutzman, Danielle; Dopheide, Julie

2015-11-15

Successful use of acetylcysteine to control irritability and aggressive behaviors in a hospitalized adolescent patient with autism spectrum disorder (ASD) is described. A 17-year-old Hispanic male with ASD and intellectual disability was hospitalized for inpatient psychiatric treatment due to impulsive and violent behavior. Despite receiving various medications in the initial weeks of hospitalization, including intramuscular lorazepam and diphenhydramine injections (four days a week on average), the patient continued to exhibit aggressive and unpredictable behaviors. Treatment with 20% acetylcysteine oral solution was initiated at a dosage of 600 mg twice daily as an adjunct to quetiapine therapy. Over the next six weeks, reductions in the patient's aggressive behavior, tantrums, and irritability were noted. The use of as-needed medications to control aggression was decreased, and the dosage of quetiapine was lowered from 700 to 400 mg daily over the course of the hospitalization. Acetylcysteine was well tolerated, with no observed or reported adverse effects. Unlike clonidine or guanfacine (other medications used for ASD-related behavioral symptoms), acetylcysteine is not sedating; moreover, it lacks the metabolic, extrapyramidal, and endocrine adverse effects of atypical antipsychotics. Published data from small controlled trials and case reports suggest that acetylcysteine use is associated with improvements in irritability and aggression in prepubertal children with ASD; these therapeutic benefits may be associated with acetylcysteine's glutamatergic, dopaminergic, antioxidant, and anti-inflammatory properties. Treatment with acetylcysteine improved ASD symptoms, including irritability and aggression, in a teenage patient. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Wind-tunnel Tests of the NACA 45-125 Airfoil: A Thick Airfoil for High-Speed Airplanes

NASA Technical Reports Server (NTRS)

Delano, James B.

1940-01-01

Investigations of the pressure distribution, the profile drag, and the location of transition for a 30-inch-chord 25-percent-thick N.A,C.A. 45-125 airfoil were made in the N.A.C.A 8-foot high-speed wind tunnel for the purpose of aiding in the development of a thick wing for high-speed airplanes. The tests were made at a lift coefficient of 0.1 for Reynolds Numbers from 1,750,000 to 8,690,000, corresponding to speeds from 80 to 440 miles per hour at 59 F. The effect on the profile drag of fixing the transition point was also investigated. The effect of compressibility on the rate of increase of pressure coefficients was found to be greater than that predicted by a simplified theoretical expression for thin wings. The results indicated that, for a lift coefficient of 0.1, the critical speed of the N.A.C,A. 45-125 airfoil was about 460 miles per hour at 59 F,. The value of the profile-drag coefficient at a Reynolds Number of 4,500,000 was 0.0058, or about half as large as the value for the N.A,C,A. 0025 airfoil. The increase in the profile-drag coefficient for a given movement of the transition point was about three times as large as the corresponding increase for the N.A.C,A. 0012 airfoil. Transition determinations indicated that, for Reynolds Numbers up to ?,000,000, laminar boundary 1ayers were maintained over approximately 40 percent of the upper and the lower surfaces of the airfoil.

Hepatoprotective amide constituents from the fruit of Piper chaba: Structural requirements, mode of action, and new amides.

PubMed

Matsuda, Hisashi; Ninomiya, Kiyofumi; Morikawa, Toshio; Yasuda, Daisuke; Yamaguchi, Itadaki; Yoshikawa, Masayuki

2009-10-15

The 80% aqueous acetone extract from the fruit of Piper chaba (Piperaceae) was found to have hepatoprotective effects on D-galactosamine (D-GalN)/lipopolysaccharide-induced liver injury in mice. From the ethyl acetate-soluble fraction, three new amides, piperchabamides E, G, and H, 33 amides, and four aromatic constituents were isolated. Among the isolates, several amide constituents inhibited D-GalN/tumor necrosis factor-alpha (TNF-alpha)-induced death of hepatocytes, and the following structural requirements were suggested: (i) the amide moiety is essential for potent activity; and (ii) the 1,9-decadiene structure between the benzene ring and the amide moiety tended to enhance the activity. Moreover, a principal constituent, piperine, exhibited strong in vivo hepatoprotective effects at doses of 5 and 10 mg/kg, po and its mode of action was suggested to depend on the reduced sensitivity of hepatocytes to TNF-alpha.

Rocket Research Presentation at the NACA's 1947 Inspection

NASA Image and Video Library

1947-10-21

Researcher John Sloop briefs visitors on his latest rocket engine research during the 1947 Inspection at the National Advisory Committee for Aeronautics (NACA) Lewis Flight Propulsion Laboratory. The NACA had been hosting annual Aircraft Engineering Conferences, better known as Inspections, since 1926. Individuals from the manufacturing industry, military, and university settings were invited to tour the NACA laboratories. There were a series of stops on the tour, mostly at test facilities, where researchers would brief the group on the latest efforts in their particular field. The Inspections grew in size and scope over the years and by the mid-1940s required multiple days. The three-day 1947 Inspection was the first time the event was held at NACA Lewis. Over 800 scientists, industrialists, and military leaders attended the three-day event. Talks were given at the Altitude Wind Tunnel, Four Burner Area, Engine Research Building, and other facilities. An array of topics were discussed, including full-scale engine testing, ramjets, axial-flow compressors, turbojets, fuels, icing, and materials. The NACA Lewis staff and their families were able to view the same presentations after the Inspection was over. Sloop, a researcher in the Fuels and Thermodynamics Division, briefed visitors on NACA Lewis’ early research in rocket engine propellants, combustion, and cooling. This early NACA Lewis work led to the development of liquid hydrogen as a viable propellant in the late 1950s.

Use of N-Acetylcysteine in Psychiatric Conditions among Children and Adolescents: A Scoping Review.

PubMed

Naveed, Sadiq; Amray, Afshan; Waqas, Ahmed; Chaudhary, Amna M; Azeem, Muhammad W

2017-11-29

N-acetylcysteine (NAC) is a well-known antidote for acetaminophen toxicity and is easily available over the counter. It has antioxidant and anti-inflammatory properties and an established tolerance and safety profile. Owing to its neuroprotective effects, its clinical use has recently expanded to include the treatment of different psychiatric and non-psychiatric disorders. Although a number of randomized controlled trials have documented the clinical evidence for NAC, there are no reviews that summarize the evidence. The present scoping review summarizes the study designs, the patient characteristics, the evidence and the limitations in randomized controlled trials designed to explore the efficacy of NAC for psychiatric conditions in the pediatric population.

Targeted Lipidomics in Drosophila melanogaster Identifies Novel 2-Monoacylglycerols and N-acyl Amides

PubMed Central

Takacs, Sara M.; Stuart, Jordyn M.; Basnet, Arjun; Raboune, Siham; Widlanski, Theodore S.; Doherty, Patrick; Bradshaw, Heather B.

2013-01-01

Lipid metabolism is critical to coordinate organ development and physiology in response to tissue-autonomous signals and environmental cues. Changes to the availability and signaling of lipid mediators can limit competitiveness, adaptation to environmental stressors, and augment pathological processes. Two classes of lipids, the N-acyl amides and the 2-acyl glycerols, have emerged as important signaling molecules in a wide range of species with important signaling properties, though most of what is known about their cellular functions is from mammalian models. Therefore, expanding available knowledge on the repertoire of these lipids in invertebrates will provide additional avenues of research aimed at elucidating biosynthetic, metabolic, and signaling properties of these molecules. Drosophila melanogaster is a commonly used organism to study intercellular communication, including the functions of bioactive lipids. However, limited information is available on the molecular identity of lipids with putative biological activities in Drosophila. Here, we used a targeted lipidomics approach to identify putative signaling lipids in third instar Drosophila larvae, possessing particularly large lipid mass in their fat body. We identified 2-linoleoyl glycerol, 2-oleoyl glycerol, and 45 N-acyl amides in larval tissues, and validated our findings by the comparative analysis of Oregon-RS, Canton-S and w1118 strains. Data here suggest that Drosophila represent another model system to use for the study of 2-acyl glycerol and N-acyl amide signaling. PMID:23874457

Cytotoxicity and the induction of the stress protein Hsp 70 in Chang liver cells in response to zearalenone-induced oxidative stress.

PubMed

Lee, Hyungkyoung; Kang, Changgeun; Yoo, Yong-San; Hah, Do-Yun; Kim, Chung Hui; Kim, Euikyung; Kim, Jong Shu

2013-09-01

Zearalenone (ZEN) has been implicated in several cases of mycotoxicosis in farm animals and humans. The toxic effects of ZEN have been well characterized, but little is known regarding the mechanisms of ZEN toxicity, including the involvement of the oxidative stress pathway. Using Chang liver cells as a model, the aim of this study was to determine if ZEN could elevate the expression of the heat shock protein Hsp 70, induce cytotoxicity and modulate the levels of glutathione (GSH) and thiobarbituric acid reactive substance (TBARS). In addition, the cytoprotective effects of N-acetylcysteine amide (NACA) pre-treatment were assessed. Finally, the involvement of oxidative stress in ZEN-induced toxicity was confirmed. The results of this study demonstrated that ZEN-induced Hsp 70 expression in a dose- and time-dependent manners. This effect occurred at low-ZEN concentrations, and could therefore be considered a biomarker of ZEN-induced toxicity. The cytotoxicity was reduced when Chang liver cells were exposed to sub-lethal heat shock prior to ZEN treatment, demonstrating a cytoprotective effect of Hsp 70. This cytoprotective effect suggested that Hsp 70 might play a key role in the cellular defense mechanism. When cells were pre-treated with NACA prior to ZEN treatment, the cells were also protected from toxicity. This NACA cytoprotective effect suggested the involvement of oxidative stress in ZEN-induced toxicity, and this mechanism was supported by reduced Hsp 70 expression, inhibited cytolethality, increased GSH levels and decreased TBARS formation when cells were pre-treated with NACA prior to ZEN exposure. Our data clearly demonstrated that ZEN induced cytotoxicity in Chang liver cells by inhibiting cell proliferation, decreasing GSH levels and increasing TBARS formation in a dose-dependent manner. ZEN also, induced Hsp 70 expression, and the side effects of ZEN were significantly alleviated by pre-treatment with NACA. Oxidative stress is likely to be one of the

A restored NACA P-51D Mustang in flight

NASA Image and Video Library

2000-09-15

A white plate on the top of the wing of a restored National Advisory Committee for Aeronautics (NACA) P-51D Mustang mounts scale airfoil shapes as used by the NACA in the late 1940s for high-speed research. This former NACA testbed Mustang was rebuilt by John Muszala for Bill Allmon of Las Vegas, Nevada, who has been flying it since 1998. Allmon flew the vintage fighter to NASA's Dryden Flight Research Center at Edwards, California, Sept. 15, 2000 for a reunion of former NACA employees.

Protective Effect of N-acetylcysteine on Liver Damage During Chronic Intrauterine Hypoxia in Fetal Guinea Pig

PubMed Central

Hashimoto, Kazumasa; Pinkas, Gerard; Evans, LaShauna; Liu, Hongshan; Al-Hasan, Yazan

2012-01-01

Chronic exposure to hypoxia during pregnancy generates a stressed intrauterine environment that may lead to fetal organ damage. The objectives of the study are (1) to quantify the effect of chronic hypoxia in the generation of oxidative stress in fetal guinea pig liver and (2) to test the protective effect of antioxidant treatment in hypoxic fetal liver injury. Pregnant guinea pigs were exposed to either normoxia (NMX) or 10.5% O2 (HPX, 14 days) prior to term (65 days) and orally administered N-acetylcysteine ([NAC] 10 days). Near-term anesthetized fetuses were excised and livers examined by histology and assayed for malondialdehyde (MDA) and DNA fragmentation. Chronic HPX increased erythroid precursors, MDA (NMX vs HPX; 1.26 ± 0.07 vs 1.78 ± 0.07 nmol/mg protein; P < .001, mean ± standard error of the mean [SEM]) and DNA fragmentation levels in fetal livers (0.069 ± 0.01 vs 0.11 ± 0.005 OD/mg protein; P < .01). N-acetylcysteine inhibited erythroid aggregation and reduced (P < .05) both MDA and DNA fragmentation of fetal HPX livers. Thus, chronic intrauterine hypoxia generates cell and nuclear damage in the fetal guinea pig liver. Maternal NAC inhibited the adverse effects of fetal liver damage suggestive of oxidative stress. The suppressive effect of maternal NAC may implicate the protective role of antioxidants in the prevention of liver injury in the hypoxic fetus. PMID:22534333

NACA Subcommittee on Combustion Meeting

NASA Image and Video Library

1951-12-21

The National Advisory Committee for Aeronautics (NACA) Subcommittee on Combustion holds a meeting at Lewis Flight Propulsion Laboratory in Cleveland, Ohio. The NACA was managed by committees that included members of their own staff along with representatives from industry, the military, other government agencies, and universities. The 17-person Executive Committee was the NACA’s primary administrative body. They met several times a year at the NACA headquarters office in Washington DC to discuss broad issues confronting the US aeronautical community. Jerome Hunsaker, head of the Department of Aeronautical Engineering at the Massachusetts Institute of Technology, served as the NACA chairman from 1941 to 1956. George Lewis was not a member of the Executive Committee but served a key role as the NACA’s Director of Aeronautical Research. The NACA’s organizational chart also included 11 technical committees, several of which had specialized subcommittees. There were over 100 different subcommittees between World War I and 1958. The number of active subcommittees varied over the years. Most existed only for a few years, but some continued for over a decade. The subcommittees met three or four times per year, often at the laboratory most closely associated with the area of research. A team of laboratory researchers presented briefings on their recent activities and plans for the future. The Subcommittee on Combustion existed from 1945 to the NACA’s demise in 1958.

Acetylcysteine Oral Inhalation

MedlinePlus

... disease that causes problems with breathing, digestion, and reproduction). Acetylcysteine is in a class of medications called mucolytic agents. It works by thinning the mucus in the air passages to make it easier to cough up ...

Synthesis, Antifungal Evaluation and In Silico Study of N-(4-Halobenzyl)amides.

PubMed

Montes, Ricardo Carneiro; Perez, Ana Luiza A L; Medeiros, Cássio Ilan S; Araújo, Marianna Oliveira de; Lima, Edeltrudes de Oliveira; Scotti, Marcus Tullius; Sousa, Damião Pergentino de

2016-12-13

A collection of 32 structurally related N -(4-halobenzyl)amides were synthesized from cinnamic and benzoic acids through coupling reactions with 4-halobenzylamines, using (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP) as a coupling agent. The compounds were identified by spectroscopic methods such as infrared, ¹H- and 13 C- Nuclear Magnetic Resonance (NMR) and high-resolution mass spectrometry. The compounds were then submitted to antimicrobial tests by the minimum inhibitory concentration method (MIC) and nystatin was used as a control in the antifungal assays. The purpose of the tests was to evaluate the influence of structural changes in the cinnamic and benzoic acid substructures on the inhibitory activity against strains of Candida albicans , Candida tropicalis , and Candida krusei . A quantitative structure-activity relationship (QSAR) study with KNIME v. 3.1.0 and Volsurf v. 1.0.7 softwares were realized, showing that descriptors DRDRDR, DRDRAC, L4LgS, IW4 and DD2 influence the antifungal activity of the haloamides. In general, 10 benzamides revealed fungal sensitivity, especially a vanillic amide which enjoyed the lowest MIC. The results demonstrate that a hydroxyl group in the para position, and a methoxyl at the meta position enhance antifungal activity for the amide skeletal structure. In addition, the double bond as a spacer group appears to be important for the activity of amide structures.

N-acetylcysteine – passe-partout or much ado about nothing?

PubMed Central

Aitio, Mirja-Liisa

2006-01-01

In experimental studies, the old mucolytic agent N-acetylcysteine (NAC) has had beneficial effects in disorders supposedly linked to oxidative stress. Numerous, mainly small clinical trials with variable doses have yielded inconsistent results in a wide variety of diseases. NAC added to the conventional therapy of human immunodeficiency virus infection might be of benefit; in respect of chronic obstructive pulmonary disease, systematic reviews and meta-analyses suggested that prolonged treatment with NAC is efficacious, but a recent multicentre study has questioned this. In a large intervention trial on cancer recurrence, NAC was ineffective. NAC infusions have been widely used in acute hepatic failure but convincing evidence of its benefits is lacking. A preliminary study reported that NAC is effective in preventing radiocontrast-induced nephropathy but thereafter highly mixed results have been published, and even meta-analyses disagree on its efficacy. In intensive care NAC has mostly been a disappointment but recently it has ‘given promises’ in surgery with cardiopulmonary bypass. NAC therapy is routine only in paracetamol intoxication. PMID:16390346

Index of NACA Technical Publications, 1949 - May, 1951

NASA Technical Reports Server (NTRS)

1952-01-01

The Preface to the Index of NACA Technical Publications, 1915-1949, mentioned that regular supplements would be issued in the future. This is the first such Supplement and covers those documents issued through May of 1951. Similar arrangement is used in both Indexes. First, there is a classified listing of the subject categories; second, a chronological listing of NACA publications under each subject category; third, an alphabetical index to the subject categories; and finally, an author index. The latter feature was not included in the basic 1915-1949 Index but has been issued separately and is available upon request. Immediately following this Preface is an Explanatory Chart of NACA Publications Series Designations which may be of use in identifying references to NACA documents encountered in the literature.

N-Acetylcysteine as an antioxidant and disulphide breaking agent: the reasons why.

PubMed

Aldini, Giancarlo; Altomare, Alessandra; Baron, Giovanna; Vistoli, Giulio; Carini, Marina; Borsani, Luisa; Sergio, Francesco

2018-05-09

The main molecular mechanisms explaining the well-established antioxidant and reducing activity of N-acetylcysteine (NAC), the N-acetyl derivative of the natural amino acid l-cysteine, are summarised and critically reviewed. The antioxidant effect is due to the ability of NAC to act as a reduced glutathione (GSH) precursor; GSH is a well-known direct antioxidant and a substrate of several antioxidant enzymes. Moreover, in some conditions where a significant depletion of endogenous Cys and GSH occurs, NAC can act as a direct antioxidant for some oxidant species such as NO 2 and HOX. The antioxidant activity of NAC could also be due to its effect in breaking thiolated proteins, thus releasing free thiols as well as reduced proteins, which in some cases, such as for mercaptoalbumin, have important direct antioxidant activity. As well as being involved in the antioxidant mechanism, the disulphide breaking activity of NAC also explains its mucolytic activity which is due to its effect in reducing heavily cross-linked mucus glycoproteins. Chemical features explaining the efficient disulphide breaking activity of NAC are also explained.

A restored NACA P-51D Mustang in flight

NASA Image and Video Library

2000-09-15

The huge compass rose on Rogers Dry Lake formed a backdrop for a genuine NACA (National Advisory Committee for Aeronautics) P-51D Mustang owned and flown by William C. Allmon during a visit to the NASA Dryden Flight Research Center in California's Mojave Desert Sept. 15, 2000 for a reunion of former NACA employees. The NACA was the forerunner of NASA.

NACA Muroc Staff of 1949 at NACA barbecue

NASA Technical Reports Server (NTRS)

1949-01-01

On a nice day in November 1949 the NACA High-Speed Flight Station employees enjoy a break from a week of research by attending a barbecue on the Rawliegh Duntley ranch. The food was excellent and the camaraderie with friends and family members was welcome. Games were played with the winners applauded--fun for everyone before the start of another week.

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

PubMed

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.

Spectroscopic and structural studies of a new para-iodo-N-benzyl amide of salinomycin

NASA Astrophysics Data System (ADS)

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.

N-acetylcysteine modulates doxorubicin-induced oxidative stress and antioxidant vitamin concentrations in liver of rats.

PubMed

Koçkar, M Cem; Nazıroğlu, Mustafa; Celik, Omer; Tola, H Tahsin; Bayram, Dilek; Koyu, Ahmet

2010-12-02

Doxorubicin (DOX) is a chemotherapeutic agent, and is widely used in cancer treatment. The most common side effect of DOX was indicated on cardiovascular system by experimental studies. There are some studies suggesting oxidative stress-induced toxic changes on liver related to DOX administration. The aim of the present study was to evaluate whether antioxidant N-acetylcysteine (NAC) relieves oxidative stress in DOX- induced liver injury in rat. Twenty-four male rats were equally divided into three groups. First group was used as a control. Second group received single dose of DOX. NAC for 10 days was given to constituting the third group after giving one dose of DOX. After 10 days of the experiment, liver tissues were taken from all animals. Lipid peroxidation (LP) levels were higher in the DOX group than in control whereas LP levels were lower in the DOX+NAC group than in control. Vitamin C and vitamin E levels were lower in the DOX group than in control whereas vitamin C and vitamin E levels were higher in the DOX+NAC group than in the DOX group. Reduced glutathione levels were higher in the DOX+NAC group than in control and DOX group. Glutathione peroxidase, vitamin A and β-carotene values were not changed in the three groups by DOX and NAC administrations. In histopathological evaluation of DOX group, there were mononuclear cell infiltrations, vacuolar degeneration, hepatocytes with basophilic nucleus and sinusoidal dilatations. The findings were totally recovered by NAC administration. In conclusion, N-acetylcysteine induced modulator effects on the doxorubicin-induced hepatoxicity by inhibiting free radical production and supporting the antioxidant vitamin levels. Copyright © 2010 John Wiley & Sons, Ltd.

Hydrogen Bonding Interaction between Atmospheric Gaseous Amides and Methanol.

PubMed

Zhao, Hailiang; Tang, Shanshan; Xu, Xiang; Du, Lin

2016-12-30

Amides are important atmospheric organic-nitrogen compounds. Hydrogen bonded complexes of methanol (MeOH) with amides (formamide, N -methylformamide, N , N -dimethylformamide, acetamide, N -methylacetamide and N , N -dimethylacetamide) have been investigated. The carbonyl oxygen of the amides behaves as a hydrogen bond acceptor and the NH group of the amides acts as a hydrogen bond donor. The dominant hydrogen bonding interaction occurs between the carbonyl oxygen and the OH group of methanol as well as the interaction between the NH group of amides and the oxygen of methanol. However, the hydrogen bonds between the CH group and the carbonyl oxygen or the oxygen of methanol are also important for the overall stability of the complexes. Comparable red shifts of the C=O, NH- and OH-stretching transitions were found in these MeOH-amide complexes with considerable intensity enhancement. Topological analysis shows that the electron density at the bond critical points of the complexes fall in the range of hydrogen bonding criteria, and the Laplacian of charge density of the O-H∙∙∙O hydrogen bond slightly exceeds the upper value of the Laplacian criteria. The energy decomposition analysis further suggests that the hydrogen bonding interaction energies can be mainly attributed to the electrostatic, exchange and dispersion components.

Hydrogen Bonding Interaction between Atmospheric Gaseous Amides and Methanol

PubMed Central

Zhao, Hailiang; Tang, Shanshan; Xu, Xiang; Du, Lin

2016-01-01

Amides are important atmospheric organic–nitrogen compounds. Hydrogen bonded complexes of methanol (MeOH) with amides (formamide, N-methylformamide, N,N-dimethylformamide, acetamide, N-methylacetamide and N,N-dimethylacetamide) have been investigated. The carbonyl oxygen of the amides behaves as a hydrogen bond acceptor and the NH group of the amides acts as a hydrogen bond donor. The dominant hydrogen bonding interaction occurs between the carbonyl oxygen and the OH group of methanol as well as the interaction between the NH group of amides and the oxygen of methanol. However, the hydrogen bonds between the CH group and the carbonyl oxygen or the oxygen of methanol are also important for the overall stability of the complexes. Comparable red shifts of the C=O, NH- and OH-stretching transitions were found in these MeOH–amide complexes with considerable intensity enhancement. Topological analysis shows that the electron density at the bond critical points of the complexes fall in the range of hydrogen bonding criteria, and the Laplacian of charge density of the O–H∙∙∙O hydrogen bond slightly exceeds the upper value of the Laplacian criteria. The energy decomposition analysis further suggests that the hydrogen bonding interaction energies can be mainly attributed to the electrostatic, exchange and dispersion components. PMID:28042825

Aeronautics in NACA and NASA

NASA Technical Reports Server (NTRS)

1991-01-01

Initiated in 1915, the National Advisory Committee for Aeronautics/National Aeronautics and Space Administration (NACA/NASA) aeronautical programs have been the keystone of a sustained U.S. Government, industry, and university research effort which has been a primary factor in the development of our remarkable air transportation systems, the country's largest positive trade balance component, and the world's finest military Air Force. This overview summarizes the flow of events, and the major trends, that have led from the NACA origins to the present NASA Aeronautics program, and indicates some important directions for the years ahead.

Protective effect of N-acetylcysteine activated carbon release microcapsule on myocardial ischemia-reperfusion injury in rats

PubMed Central

Cai, Zhaobin; Shi, Tingting; Zhuang, Rangxiao; Fang, Hongying; Jiang, Xiaojie; Shao, Yidan; Zhou, Hongping

2018-01-01

With the development of science and technology, and development of artery bypass, methods such as cardiopulmonary cerebral resuscitation have been practiced in recent years. Despite this, some methods fail to promote or recover the function of tissues and organs, and in some cases, may aggravate dysfunction and structural damage to tissues. The latter is typical of ischemia-reperfusion (IR) injury. Lipid peroxidation mediated by free radicals is an important process of myocardial IR injury. Myocardial IR has been demonstrated to induce the formation of large numbers of free radicals in rats, which promotes the peroxidation of lipids within unsaturated fatty acids in the myocardial cell membrane. Markers of lipid peroxidation include malondialdehyde, superoxide dismutase and lactic dehydrogenase. Recent studies have demonstrated that N-acetylcysteine (NAC) is able to dilate blood vessels, prevent oxidative damage, improve immunity, inhibit apoptosis and the inflammatory response and promote glutathione synthesis in cells. NAC also improves the systolic function of myocardial cells and cardiac function, prevents myocardial apoptosis, protects ventricular remodeling and vascular remodeling, reduces opiomelanocortin levels in the serum and increases the content of nitric oxide in the serum, thus improving vascular endothelial function. Therefore, NAC has potent pharmacological activity; however, the relatively fast metabolism of NAC, along with its large clinical dose and low bioavailability, limit its applications. The present study combined NAC with medicinal activated carbons, and prepared N-acetylcysteine activated carbon sustained-release microcapsules (ACNACs) to overcome the limitations of NAC. It was demonstrated that ACNACs exerted greater effective protective effects than NAC alone on myocardial IR injury in rats. PMID:29434769

Groundbreaking Ceremony at the NACA's Plum Brook Station

NASA Image and Video Library

1956-09-21

Addison Rothrock, the National Advisory Committee for Aeronautics’s (NACA) Assistant Director of Research, speaks at the groundbreaking ceremony for the Lewis Flight Propulsion Laboratory’s new test reactor at Plum Brook Station. This dedication event was held almost exactly one year after the NACA announced that it would build its $4.5 million nuclear reactor on 500 acres of the army’s 9000-acre Plum Brook Ordnance Works. The site was located in Sandusky, Ohio, approximately 60 miles west of the NACA Lewis laboratory in Cleveland. Lewis Director Raymond Sharp is seated to the left of Rothrock, Congressman Albert Baumhart and NACA Secretary John Victory are to the right. Many government and local officials were on hand for the press conference and ensuing luncheon. In the wake of World War II the military, the Atomic Energy Commission, and the NACA became interested in the use of atomic energy for propulsion and power. A Nuclear Division was established at NACA Lewis in the early 1950s. The division’s request for a 60-megawatt research reactor was approved in 1955. The semi-remote Plum Brook location was selected over 17 other possible sites. Construction of the Plum Brook Reactor Facility lasted five years. By the time of its first trial runs in 1961 the aircraft nuclear propulsion program had been cancelled. The space age had arrived, however, and the reactor would be used to study materials for a nuclear powered rocket.

Beneficial effects of n-acetylcysteine on ischaemic brain injury

PubMed Central

Cuzzocrea, Salvatore; Mazzon, Emanuela; Costantino, Giuseppina; Serraino, Ivana; Dugo, Laura; Calabrò, Giusy; Cucinotta, Giovanni; De Sarro, Angela; Caputi, A P

2000-01-01

Nitric oxide (NO), peroxynitrite, formed from NO and superoxide anion, poly (ADP-ribole) synthetase have been implicated as mediators of neuronal damage following focal ischaemia. Here we have investigated the effects of n-acetylcysteine (NAC) treatment in Mongolian gerbils subjected to cerebral ischaemia.Treatment of gerbils with NAC (20 mg kg−1 30 min before reperfusion and 1, 2 and 6 h after reperfusion) reduced the formation of post-ischaemic brain oedema, evaluated by water content.NAC also attenuated the increase in the brain levels of malondialdehyde (MDA) and the increase in the hippocampus of myeloperoxidase (MPO) caused by cerebral ischaemia.Positive staining for nitrotyrosine was found in the hippocampus in Mongolian gerbils subjected to cerebral ischaemia. Hippocampus tissue sections from Mongolian gerbils subjected to cerebral ischaemia also showed positive staining for poly (ADP-ribose) synthetase (PARS). The degree of staining for nitrotyrosine and for PARS were markedly reduced in tissue sections obtained from animals that received NAC.NAC treatment increased survival and reduced hyperactivity linked to neurodegeneration induced by cerebral ischaemia and reperfusion.Histological observations of the pyramidal layer of CA1 showed a reduction of neuronal loss in animals that received NAC.These results show that NAC improves brain injury induced by transient cerebral ischaemia. PMID:10903958

Antimicrobial Activity of Penicillin G and N-acetylcystein on Planktonic and Sessile Cells of Streptococcus suis.

PubMed

Espinosa, Ivette; Báez, Michel; Lobo, Evelyn; Martínez, Siomara; Gottschalk, Marcelo

2016-01-01

The aim of this study was to investigate the capacity of Streptococcus suis strains to form biofilms and to evaluate the antimicrobial activity of Penicillin G and N-acetylcystein (NAC) on both S. suis sessile and planktonic forms. Only non-typeable isolates of S. suis were correlated with a greater biofilm formation capacity. The MCI of Penicillin G and NAC required for inhibiting biofilm growth were higher than the required concentration for inhibiting planktonic growth. The combinations of NAC and Penicillin G showed a strong synergistic activity that inhibited biofilm formation and disrupted the pre-formed biofilm of S. suis.

Synthesis of ketene N,N-acetals by copper-catalyzed double-amidation of 1,1-dibromo-1-alkenes.

PubMed

Coste, Alexis; Couty, François; Evano, Gwilherm

2009-10-01

An efficient procedure for the preparation of ketene N,N-acetals by copper-catalyzed double amidation of 1,1-dibromo-1-alkenes is reported. The reaction was found to be general, and ketene aminals could be obtained in good yields when potassium phosphate in toluene was used at 80 degrees C. The reaction was found to proceed through a regioselective monocoupling reaction followed by dehydrobromination and hydroamidation.

Primary fatty acid amide metabolism: conversion of fatty acids and an ethanolamine in N18TG2 and SCP cells.

PubMed

Farrell, Emma K; Chen, Yuden; Barazanji, Muna; Jeffries, Kristen A; Cameroamortegui, Felipe; Merkler, David J

2012-02-01

Primary fatty acid amides (PFAM) are important signaling molecules in the mammalian nervous system, binding to many drug receptors and demonstrating control over sleep, locomotion, angiogenesis, and many other processes. Oleamide is the best-studied of the primary fatty acid amides, whereas the other known PFAMs are significantly less studied. Herein, quantitative assays were used to examine the endogenous amounts of a panel of PFAMs, as well as the amounts produced after incubation of mouse neuroblastoma N(18)TG(2) and sheep choroid plexus (SCP) cells with the corresponding fatty acids or N-tridecanoylethanolamine. Although five endogenous primary amides were discovered in the N(18)TG(2) and SCP cells, a different pattern of relative amounts were found between the two cell lines. Higher amounts of primary amides were found in SCP cells, and the conversion of N-tridecanoylethanolamine to tridecanamide was observed in the two cell lines. The data reported here show that the N(18)TG(2) and SCP cells are excellent model systems for the study of PFAM metabolism. Furthermore, the data support a role for the N-acylethanolamines as precursors for the PFAMs and provide valuable new kinetic results useful in modeling the metabolic flux through the pathways for PFAM biosynthesis and degradation.

Re-Computation of Numerical Results Contained in NACA Report No. 496

NASA Technical Reports Server (NTRS)

Perry, Boyd, III

2015-01-01

An extensive examination of NACA Report No. 496 (NACA 496), "General Theory of Aerodynamic Instability and the Mechanism of Flutter," by Theodore Theodorsen, is described. The examination included checking equations and solution methods and re-computing interim quantities and all numerical examples in NACA 496. The checks revealed that NACA 496 contains computational shortcuts (time- and effort-saving devices for engineers of the time) and clever artifices (employed in its solution methods), but, unfortunately, also contains numerous tripping points (aspects of NACA 496 that have the potential to cause confusion) and some errors. The re-computations were performed employing the methods and procedures described in NACA 496, but using modern computational tools. With some exceptions, the magnitudes and trends of the original results were in fair-to-very-good agreement with the re-computed results. The exceptions included what are speculated to be computational errors in the original in some instances and transcription errors in the original in others. Independent flutter calculations were performed and, in all cases, including those where the original and re-computed results differed significantly, were in excellent agreement with the re-computed results. Appendix A contains NACA 496; Appendix B contains a Matlab(Reistered) program that performs the re-computation of results; Appendix C presents three alternate solution methods, with examples, for the two-degree-of-freedom solution method of NACA 496; Appendix D contains the three-degree-of-freedom solution method (outlined in NACA 496 but never implemented), with examples.

Physicochemical and electrochemical properties of N-methyl-N-methoxymethylpyrrolidinium bis(fluorosulfonyl)amide and its lithium salt composites

NASA Astrophysics Data System (ADS)

Horiuchi, Shunsuke; Yoshizawa-Fujita, Masahiro; Takeoka, Yuko; Rikukawa, Masahiro

2016-09-01

The ionic liquid (IL) N-Methyl-N-methoxymethylpyrrolidinium bis(fluorosulfonyl)amide ([Pyr1,1O1][FSA]) was synthesized, and its physicochemical and electrochemical properties were investigated with respect to its application as an electrolyte in lithium-ion secondary batteries operating over a wide temperature range. [Pyr1,1O1][FSA]/Li salt (0.34 mol kg-1) composites were prepared by adding lithium bis(trifluoromethylsulfonyl)amide (LiTFSA) into the IL. [Pyr1,1O1][FSA] and [Pyr1,1O1][FSA]/LiTFSA exhibited melting temperatures (Tm) below -30 °C. [Pyr1,1O1][FSA] exhibited a higher ionic conductivity value as compared with that of the corresponding IL with only alkyl substituents. The electrochemical window for both [Pyr1,1O1][FSA] and [Pyr1,1O1][FSA]/LiTFSA was 5.1 V. Stable lithium deposition and dissolution occurred on a Ni electrode at 25 °C.

Salt forms of the pharmaceutical amide dihydrocarbamazepine.

PubMed

Buist, Amanda R; Kennedy, Alan R

2016-02-01

Carbamazepine (CBZ) is well known as a model active pharmaceutical ingredient used in the study of polymorphism and the generation and comparison of cocrystal forms. The pharmaceutical amide dihydrocarbamazepine (DCBZ) is a less well known material and is largely of interest here as a structural congener of CBZ. Reaction of DCBZ with strong acids results in protonation of the amide functionality at the O atom and gives the salt forms dihydrocarbamazepine hydrochloride {systematic name: [(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)(hydroxy)methylidene]azanium chloride, C15H15N2O(+)·Cl(-)}, dihydrocarbamazepine hydrochloride monohydrate {systematic name: [(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)(hydroxy)methylidene]azanium chloride monohydrate, C15H15N2O(+)·Cl(-)·H2O} and dihydrocarbamazepine hydrobromide monohydrate {systematic name: [(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)(hydroxy)methylidene]azanium bromide monohydrate, C15H15N2O(+)·Br(-)·H2O}. The anhydrous hydrochloride has a structure with two crystallographically independent ion pairs (Z' = 2), wherein both cations adopt syn conformations, whilst the two hydrated species are mutually isostructural and have cations with anti conformations. Compared to neutral dihydrocarbamazepine structures, protonation of the amide group is shown to cause changes to both the molecular (C=O bond lengthening and C-N bond shortening) and the supramolecular structures. The amide-to-amide and dimeric hydrogen-bonding motifs seen for neutral polymorphs and cocrystalline species are replaced here by one-dimensional polymeric constructs with no direct amide-to-amide bonds. The structures are also compared with, and shown to be closely related to, those of the salt forms of the structurally similar pharmaceutical carbamazepine.

Stepwise microhydration of aromatic amide cations: water solvation networks revealed by the infrared spectra of acetanilide+-(H2O)n clusters (n ≤ 3).

PubMed

Klyne, Johanna; Schmies, Matthias; Miyazaki, Mitsuhiko; Fujii, Masaaki; Dopfer, Otto

2018-01-31

The structure and activity of peptides and proteins strongly rely on their charge state and the interaction with their hydration environment. Here, infrared photodissociation (IRPD) spectra of size-selected microhydrated clusters of cationic acetanilide (AA + , N-phenylacetamide), AA + -(H 2 O) n with n ≤ 3, are analysed by dispersion-corrected density functional theory calculations at the ωB97X-D/aug-cc-pVTZ level to determine the stepwise microhydration process of this aromatic peptide model. The IRPD spectra are recorded in the informative X-H stretch (ν OH , ν NH , ν CH , amide A, 2800-3800 cm -1 ) and fingerprint (amide I-II, 1000-1900 cm -1 ) ranges to probe the preferred hydration motifs and the cluster growth. In the most stable AA + -(H 2 O) n structures, the H 2 O ligands solvate the acidic NH proton of the amide by forming a hydrogen-bonded solvent network, which strongly benefits from cooperative effects arising from the excess positive charge. Comparison with neutral AA-H 2 O reveals the strong impact of ionization on the acidity of the NH proton and the topology of the interaction potential. Comparison with related hydrated formanilide clusters demonstrates the influence of methylation of the amide group (H → CH 3 ) on the shape of the intermolecular potential and the structure of the hydration shell.

Polyimides Containing Amide And Perfluoroisopropyl Links

NASA Technical Reports Server (NTRS)

Dezem, James F.

1993-01-01

New polyimides synthesized from reactions of aromatic hexafluoroisopropyl dianhydrides with asymmetric amide diamines. Soluble to extent of at least 10 percent by weight at temperature of about 25 degrees C in common amide solvents such as N-methylpyrrolidone, N,N-dimethylacetamide, and N,N-dimethylformamide. Polyimides form tough, flexible films, coatings, and moldings. Glass-transition temperatures ranged from 300 to 365 degrees C, and crystalline melting temperatures observed between 543 and 603 degrees C. Display excellent physical, chemical, and electrical properties. Useful as adhesives, laminating resins, fibers, coatings for electrical and decorative purposes, films, wire enamels, and molding compounds.

How amide hydrogens exchange in native proteins.

PubMed

Persson, Filip; Halle, Bertil

2015-08-18

Amide hydrogen exchange (HX) is widely used in protein biophysics even though our ignorance about the HX mechanism makes data interpretation imprecise. Notably, the open exchange-competent conformational state has not been identified. Based on analysis of an ultralong molecular dynamics trajectory of the protein BPTI, we propose that the open (O) states for amides that exchange by subglobal fluctuations are locally distorted conformations with two water molecules directly coordinated to the N-H group. The HX protection factors computed from the relative O-state populations agree well with experiment. The O states of different amides show little or no temporal correlation, even if adjacent residues unfold cooperatively. The mean residence time of the O state is ∼100 ps for all examined amides, so the large variation in measured HX rate must be attributed to the opening frequency. A few amides gain solvent access via tunnels or pores penetrated by water chains including native internal water molecules, but most amides access solvent by more local structural distortions. In either case, we argue that an overcoordinated N-H group is necessary for efficient proton transfer by Grotthuss-type structural diffusion.

N-acetylcysteine inhibits endothelial cell invasion and angiogenesis.

PubMed

Cai, T; Fassina, G; Morini, M; Aluigi, M G; Masiello, L; Fontanini, G; D'Agostini, F; De Flora, S; Noonan, D M; Albini, A

1999-09-01

The thiol N-acetylcysteine (NAC) is a chemopreventive agent that acts through a variety of mechanisms and can prevent in vivo carcinogenesis. We have previously shown that NAC inhibits invasion and metastasis of malignant cells as well as tumor take. Neovascularization is critical for tumor mass expansion and metastasis formation. We investigated whether a target of the anti-cancer activity of NAC could be the inhibition of the tumor angiogenesis-associated phenotype in vitro and in vivo using the potent angiogenic mixture of Kaposi's sarcoma cell products as a stimulus. Two endothelial (EAhy926 and human umbilical vein endothelial [HUVE]) cell lines were utilized in a panel of assays to test NAC ability in inhibiting chemotaxis, invasion, and gelatinolytic activity in vitro. NAC treatment of EAhy926 and HUVE cells in vitro dose-dependently reduced their ability to invade a reconstituted basement membrane, an indicator of endothelial cell activation. Invasion of HUVE cells was inhibited with an ID50 of 0.24 mM NAC, whereas inhibition of chemotaxis required a 10 fold higher doses, indicating that invasion is a preferential target. NAC inhibited the enzymatic activity and conversion to active forms of the gelatinase produced by endothelial cells. The matrigel in vivo assay was used for the evaluation of angiogenesis; NAC strongly inhibited neovascularization of the matrigel sponges in response to Kaposi's sarcoma cell products. NAC prevented angiogenesis while preserving endothelial cells, implying that it could be safely used as an anti-angiogenic treatment.

Electrochemical reduction of nitrate in the presence of an amide

DOEpatents

Dziewinski, Jacek J.; Marczak, Stanislaw

2002-01-01

The electrochemical reduction of nitrates in aqueous solutions thereof in the presence of amides to gaseous nitrogen (N.sub.2) is described. Generally, electrochemical reduction of NO.sub.3 proceeds stepwise, from NO.sub.3 to N.sub.2, and subsequently in several consecutive steps to ammonia (NH.sub.3) as a final product. Addition of at least one amide to the solution being electrolyzed suppresses ammonia generation, since suitable amides react with NO.sub.2 to generate N.sub.2. This permits nitrate reduction to gaseous nitrogen to proceed by electrolysis. Suitable amides include urea, sulfamic acid, formamide, and acetamide.

VCD Robustness of the Amide-I and Amide-II Vibrational Modes of Small Peptide Models.

PubMed

Góbi, Sándor; Magyarfalvi, Gábor; Tarczay, György

2015-09-01

The rotational strengths and the robustness values of amide-I and amide-II vibrational modes of For(AA)n NHMe (where AA is Val, Asn, Asp, or Cys, n = 1-5 for Val and Asn; n = 1 for Asp and Cys) model peptides with α-helix and β-sheet backbone conformations were computed by density functional methods. The robustness results verify empirical rules drawn from experiments and from computed rotational strengths linking amide-I and amide-II patterns in the vibrational circular dichroism (VCD) spectra of peptides with their backbone structures. For peptides with at least three residues (n ≥ 3) these characteristic patterns from coupled amide vibrational modes have robust signatures. For shorter peptide models many vibrational modes are nonrobust, and the robust modes can be dependent on the residues or on their side chain conformations in addition to backbone conformations. These robust VCD bands, however, provide information for the detailed structural analysis of these smaller systems. © 2015 Wiley Periodicals, Inc.

Effects of acetylcysteine and probucol on contrast medium-induced depression of intrinsic renal glutathione peroxidase activity in diabetic rats.

PubMed

Yen, Hsueh-Wei; Lee, Hsiang-Chun; Lai, Wen-Te; Sheu, Sheng-Hsiung

2007-04-01

Antioxidants such as N-acetylcysteine and probucol have been used to protect patients from contrast media-induced nephrotoxicity. The mechanisms underlying these protective effects are not well understood. We hypothesized that acetylcysteine and probucol alter the activity of endogenous antioxidant enzyme activity. Four weeks after induction of diabetes with streptozotocin, diabetic and nondiabetic rats were divided into three groups. Group 1 rats did not receive any antioxidant agents. Group 2 rats were treated with acetylcysteine and group 3 rats with probucol for 1 week before injection of the contrast medium diatrizoate (DTZ). We found that diabetic rats had higher renal glutathione peroxidase (GPx) activity than normal rats. DTZ suppressed renal GPx activity significantly in both group 1 diabetic and normal rats. Interestingly, renal GPx activity in both diabetic and normal rats pretreated with acetylcysteine or probucol was not inhibited by DTZ. Renal superoxide dismutase (SOD) increased significantly in normal rats after DTZ injection, but not in diabetic rats. Finally, acetylcysteine or probucol did not significantly influence renal SOD. These findings suggest that the renal protective effects of acetylcysteine and probucol against contrast-induced oxidative stress and nephrotoxicity may be mediated by altering endogenous GPx activity.

The effect of N-acetylcysteine on biofilms: Implications for the treatment of respiratory tract infections.

PubMed

Blasi, Francesco; Page, Clive; Rossolini, Gian Maria; Pallecchi, Lucia; Matera, Maria Gabriella; Rogliani, Paola; Cazzola, Mario

2016-08-01

In airway infections, biofilm formation has been demonstrated to be responsible for both acute and chronic events, and constitutes a genuine challenge in clinical practice. Difficulty in eradicating biofilms with systemic antibiotics has led clinicians to consider the possible role of non-antibiotic therapy. The aim of this review is to examine current evidence for the use of N-acetylcysteine (NAC) in the treatment of biofilm-related respiratory infections. Electronic searches of PUBMED up to September 2015 were conducted, searching for 'biofilm', 'respiratory tract infection', 'N-acetylcysteine', 'cystic fibrosis', 'COPD', 'bronchiectasis', 'otitis', and 'bronchitis' in titles and abstracts. Studies included for review were primarily in English, but a few in Italian were also selected. Biofilm formation may be involved in many infections, including ventilator-associated pneumonia, cystic fibrosis, bronchiectasis, bronchitis, and upper respiratory airway infections. Many in vitro studies have demonstrated that NAC is effective in inhibiting biofilm formation, disrupting preformed biofilms (both initial and mature), and reducing bacterial viability in biofilms. There are fewer clinical studies on the use of NAC in disruption of biofilm formation, although there is some evidence that NAC alone or in combination with antibiotics can decrease the risk of exacerbations of chronic bronchitis, chronic obstructive pulmonary disease, and rhinosinusitis. However, the usefulness of NAC in the treatment of cystic fibrosis and bronchiectasis is still matter of debate. Most of the studies published to date have used oral or intramuscular NAC formulations. Evidence from in vitro studies indicates that NAC has good antibacterial properties and the ability to interfere with biofilm formation and disrupt biofilms. Results from clinical studies have provided some encouraging findings that need to be confirmed and expanded using other routes of administration of NAC such as

Assessing the effects of melatonin and N-acetylcysteine on the McFarlane flap using a rat model

PubMed Central

Tunç, Süphan; Kesiktas, Erol; Yilmaz, Yeliz; Açikalin, Arbil; Oran, Gökçen; Yavuz, Metin; Gencel, Eyüphan; Eser, Cengiz

2016-01-01

OBJECTIVE To determine the effects of N-acetylcysteine (NAC) and melatonin, alone and in combination, on McFarlane flap viability in a rat model. METHODS Forty Wistar rats were divided into four groups and received daily intraperitoneal injections for one week before surgery: control (sham [n=10]); melatonin (n=10); NAC (n=10); and NAC+melatonin (n=10). One week after surgery, the experiment was terminated and photographs were taken for topographic studies. A transillumination study was performed to observe vascularization in the flaps and biopsies were obtained for histopathological studies. RESULTS Flap viability was significantly greater in the antioxidant- (ie, NAC and melatonin) treated groups compared with the control group; however, there were no significant differences among the groups that received antioxidants. CONCLUSIONS Melatonin and NAC are important antioxidants that can be used alone or in combination to increase flap viability and prevent distal necrosis in rats. PMID:28439512

Synthesis of Secondary Aromatic Amides via Pd-Catalyzed Aminocarbonylation of Aryl Halides Using Carbamoylsilane as an Amide Source.

PubMed

Tong, Wenting; Cao, Pei; Liu, Yanhong; Chen, Jianxin

2017-11-03

Using N-methoxymethyl-N-organylcarbamoyl(trimethyl)silanes as secondary amides source, the direct transformation of aryl halides into the corresponding secondary aromatic amides via palladium-catalyzed aminocarbonylation is described. The reactions tolerated a broad range of functional groups on the aryl ring except big steric hindrance of substituent. The types and the relative position of substituents on the aryl ring impact the coupling efficiency.

N-Acetylcysteine interacts with copper to generate hydrogen peroxide and selectively induce cancer cell death

PubMed Central

Zheng, Jie; Lou, Jessica R.; Zhang, Xiao-Xi; Benbrook, Doris M.; Hanigan, Marie H.; Lind, Stuart E.; Ding, Wei-Qun

2013-01-01

A variety of metal-binding compounds have been found to exert anti-cancer activity. We postulated that N-acetylcysteine (NAC), which is a membrane-permeable metal-binding compound, might have anti-cancer activity in the presence of metals. We found that NAC/Cu(II) significantly alters growth and induces apoptosis in human cancer lines, yet NAC/Zn(II) and NAC/Fe(III) do not. We further confirmed that this cytotoxicity of NAC/Cu(II) is attributed to reactive oxygen species (ROS). These findings indicate that the combination of Cu(II) and thiols generates cytotoxic ROS that induce apoptosis in cancer cells. They also indicate a fourth class of anti-neoplastic metal-binding compounds, the “ROS generator”. PMID:20667650

Ozone-induced impairment of mucociliary transport and its prevention with N-acetylcysteine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Allegra, L.; Moavero, N.E.; Rampoldi, C.

1991-09-30

The effects of an oxidizing gaseous pollutant on tracheal mucous velocity have been studied in conscious sheep. Acute (2 hours) exposure to 1.0 ppm of ozone showed an effect on tracheal mucous velocity that resulted in a significant decrease 40 minutes and 2 hours after exposure (35% and 40% of the baseline, respectively). Repeated exposure for longer periods (4 days, 5 hours/day) to 1.0 ppm of ozone also significantly decreased tracheal mucous velocity during the first and the second day (-47% and -70% of the baseline, respectively), but during the following days of exposure adaptation took place (tracheal mucous velocitymore » ranging from -42% to -55% of baseline). The tracheal mucous velocity still significantly decreased 5 days after the last exposure. N-Acetylcysteine, known both for its mucolytic and antioxidizing properties, has been demonstrated to prevent significantly all of the immediate effects of either short-term or long-term ozone exposures on mucociliary functions.« less

Index of Naca Technical Publications, June 1953 - May 1954

NASA Technical Reports Server (NTRS)

1954-01-01

The Preface to the Index of NACA Technical Publications, 1915 - 1949, mentioned that regular supplements would be issued in the future. This is the third such Supplement and covers those documents issued from June 1953 through May 1954. Also included are certain documents dated prior to June 1953 which have been declassified during the period covered by this supplement. Similar arrangement is used in these Indexes. First, there is a classified listing of the subject categories; second, a chronological listing of NACA publications under each subject category; third, an alphabetical index to the subject categories; and finally, an author index. Immediately following this Preface is an Explanatory Chart of NACA Publications Series Designations which may be of use in identifying references to NACA research reports encountered in the literature.

Stability of acetylcysteine solution repackaged in oral syringes and associated cost savings.

PubMed

Kiser, Tyree H; Oldland, Alan R; Fish, Douglas N

2007-04-01

The physical and chemical stability of repackaged acetylcysteine 600 mg/3 mL solution in oral syringes stored under refrigeration or at room temperature was studied for six months; a cost analysis was also conducted. Acetylcysteine 20% solution for inhalation was repackaged undiluted as 600 mg/3 mL in capped oral syringes and stored either under refrigeration or at room temperature exposed to fluorescent light. Four samples for each storage condition were analyzed in duplicate on day zero, weekly for the first month, and then every two weeks during months 2-6. Physical stability was assessed, and the chemical stability of acetylcysteine was evaluated by high-performance liquid chromatography. Acetylcysteine solution in syringes was physically stable during the entire six-month study period. When stored at room temperature, acetylcysteine retained 99% of the original concentration at three months and 95% at six months after preparation of the syringes. Loss of acetylcysteine was <2% at six months when stored under refrigeration. Packaging acetylcysteine in batches of 100 syringes instead of preparing individual syringes reduced wastage to zero syringes, saving an estimated $247 in drug costs. The estimated pharmacy time savings was 30 hours ($702). Acetylcysteine 20% solution repackaged as 600 mg/3 mL in oral syringes is both physically and chemically stable under refrigeration or at room temperature under normal fluorescent lighting for six months. The total loss of acetylcysteine was approximately 5% at room temperature under fluorescent lighting and <2% under refrigeration. Repackaging the solution in syringes in bulk rather than in single doses demonstrated a measurable cost saving.

NACA Photographer North American F-100A (NACA-200) Super Sabre Airplane take-off. The blowing-tupe

NASA Technical Reports Server (NTRS)

1957-01-01

NACA Photographer North American F-100A (NACA-200) Super Sabre Airplane take-off. The blowing-tupe boundary-layer control on the leading- and trailing-edge provided large reductions in takeoff and landing approach speeds. Approach speeds were reduced by about 10 knots (Mar 1960). Note: Used in publication in Flight Research at Ames; 57 Years of Development and Validation of Aeronautical Technology NASA SP-1998-3300 fig. 102 and and Memoirs of a Flight Test Engneer NASA SP-2002-4525

Multidrug Resistance-Associated Protein 1 (MRP1) mediated vincristine resistance: effects of N-acetylcysteine and Buthionine Sulfoximine

PubMed Central

Akan, Ilhan; Akan, Selma; Akca, Hakan; Savas, Burhan; Ozben, Tomris

2005-01-01

Background Multidrug resistance mediated by the multidrug resistance-associated protein 1 (MRP1) decreases cellular drug accumulation. The exact mechanism of MRP1 involved multidrug resistance has not been clarified yet, though glutathione (GSH) is likely to have a role for the resistance to occur. N-acetylcysteine (NAC) is a pro-glutathione drug. DL-Buthionine (S,R)-sulfoximine (BSO) is an inhibitor of GSH synthesis. The aim of our study was to investigate the effect of NAC and BSO on MRP1-mediated vincristine resistance in Human Embryonic Kidney (HEK293) and its MRP1 transfected 293MRP cells. Human Embryonic Kidney (HEK293) cells were transfected with a plasmid encoding whole MRP1 gene. Both cells were incubated with vincristine in the presence or absence of NAC and/or BSO. The viability of both cells was determined under different incubation conditions. GSH, Glutathione S-Transferase (GST) and glutathione peroxidase (GPx) levels were measured in the cell extracts obtained from both cells incubated with different drugs. Results N-acetylcysteine increased the resistance of both cells against vincristine and BSO decreased NAC-enhanced MRP1-mediated vincristine resistance, indicating that induction of MRP1-mediated vincristine resistance depends on GSH. Vincristine decreased cellular GSH concentration and increased GPx activity. Glutathione S-Transferase activity was decreased by NAC. Conclusion Our results demonstrate that NAC and BSO have opposite effects in MRP1 mediated vincristine resistance and BSO seems a promising chemotherapy improving agent in MRP1 overexpressing tumor cells. PMID:16042792

Premedication with N-acetylcysteine and simethicone improves mucosal visualization during gastroscopy: a randomized, controlled, endoscopist-blinded study.

PubMed

Neale, James R; James, Shirley; Callaghan, James; Patel, Praful

2013-07-01

Diagnostic gastroscopy provides a unique opportunity to diagnose early oesophagogastric neoplasia; however, intraluminal mucus and bile can obscure mucosal visualization. The aim of this study was to determine whether the use of a premedication solution containing the mucolytic agent N-acetylcysteine and the surfactant simethicone improves mucosal visualization within a UK diagnostic gastroscopy service. A total of 75 consecutive patients were recruited from a single (S.J.) endoscopist's diagnostic gastroscopy list. They were randomized into three treatment groups: (a) standard control=clear fluids only for 6 h, nil by mouth for 2 h; (b) water control=standard control+100 ml sterile water (given 20 min before gastroscopy); and (c) solution=standard control+100 ml investigated solution (20 min before gastroscopy). The endoscopist was blinded to patient preparation. Inadequate mucosal visualization was defined as fluid/mucus during gastroscopy that could not be suctioned and required flushing with water. The volume of flush, the site at which it was used and the total procedure times were recorded. All three groups showed no statistical difference for age, sex ratio, procedure priority or indication. The mean volume of flush required to obtain clear mucosa was significantly less in the solution group compared with the other groups. The mean overall procedure time was also less in the solution group compared with the other groups. Premedication with N-acetylcysteine and simethicone markedly improves mucosal visibility during gastroscopy. It also reduces the time taken for the procedure. This low-cost and well-tolerated intervention may improve detection of early neoplasia.

Pressure distribution over an NACA 23012 airfoil with an NACA 23012 external-airfoil flap

NASA Technical Reports Server (NTRS)

Wenzinger, Carl J

1938-01-01

Report presents the results of pressure-distribution tests of an NACA 23012 airfoil with an NACA 23012 external airfoil flap made in the 7 by 10-foot wind tunnel. The pressures were measured on the upper and lower surfaces at one chord section on both the main airfoil and on the flap for several different flap deflections and at several angles of attack. A test installation was used in which the airfoil was mounted horizontally in the wind tunnel between vertical end planes so that two-dimensional flow was approximated. The data are presented in the form of pressure-distribution diagrams and as graphs of calculated coefficients for the airfoil-and-flap combination and for the flap alone.

A clinical and pharmacoeconomic justification for intravenous acetylcysteine: a US perspective.

PubMed

Culley, Colleen M; Krenzelok, Edward P

2005-01-01

Paracetamol (acetaminophen) poisoning remains the most common exposure reported to US poison information centres and the leading cause of poisoning-related fatalities, despite the availability of an effective antidote, acetylcysteine. Oral acetylcysteine solution has been approved for the management of acetaminophen poisoning in the US for four decades. Until the recent approval of intravenous acetylcysteine in the US, it was necessary to compound the oral solution for intravenous administration. The effectiveness and tolerability of oral and intravenous acetylcysteine for the prevention of hepatotoxicity induced by paracetamol poisoning are well established in the literature. Intravenous acetylcysteine may be preferred over oral administration based on improved tolerability, ease of administration and the shortened course of therapy (20 hours intravenous vs 72 hours oral). The two intravenous acetylcysteine regimens documented in the literature, 48 hours and 20 hours, have similar efficacy when started within 8-10 hours of ingestion. Although there are no legal concerns with continuing the routine compounding of the oral solution to an intravenous product, new standards for pharmacy compounding of sterile preparations set forth by the US Pharmacopoeia highlight that the risk of compounding products for intravenous use must be assessed carefully. Changing the route of administration of a sterile oral solution to an intravenous preparation, when a commercial sterile and pyrogen-free product is available, may not be advisable. The best cost-containment strategies must be used for introduction of the more costly sterile, pyrogen-free intravenous acetylcysteine formulation by hospitals and healthcare systems. The intravenous acetylcysteine product is more cost effective when given for 20 hours than other treatment protocols based on the costs of acetylcysteine and hospitalisation. If used per protocol, the 20-hour intravenous acetylcysteine regimen may decrease

Reduced-Amide Inhibitor of Pin1 Binds in a Conformation Resembling a Twisted-Amide Transition State†

PubMed Central

Xu, Guoyan G.; Zhang, Yan; Mercedes-Camacho, Ana Y.; Etzkorn, Felicia A.

2011-01-01

The mechanism of the cell cycle regulatory peptidyl prolyl isomerase (PPIase), Pin1, was investigated using reduced-amide inhibitors designed to mimic the twisted-amide transition state. Inhibitors, R–pSer–Ψ[CH2N]–Pro–2-(indol-3-yl)-ethylamine, 1 (R = fluorenylmethoxycarbonyl, Fmoc), and 2 (R = Ac), of Pin1 were synthesized and bioassayed. Inhibitor 1 had an IC50 value of 6.3 μM, which is 4.5-fold better inhibition for Pin1 than our comparable ground state analogue, a cis-amide alkene isostere containing inhibitor. The change of Fmoc to Ac in 2 improved aqueous solubility for structural determination, and resulted in an IC50 value of 12 μM. The X-ray structure of the complex of 2 bound to Pin1 was determined to 1.76 Å resolution. The structure revealed that the reduced amide adopted a conformation similar to the proposed twisted-amide transition state of Pin1, with a trans-pyrrolidine conformation of the prolyl ring. A similar conformation of substrate would be destabilized relative to the planar amide conformation. Three additional reduced amides, with Thr replacing Ser, and l- or d-pipecolate (Pip) replacing Pro, were slightly weaker inhibitors of Pin1. PMID:21980916

N-acetylcysteine prevents stress-induced anxiety behavior in zebrafish.

PubMed

Mocelin, Ricieri; Herrmann, Ana P; Marcon, Matheus; Rambo, Cassiano L; Rohden, Aline; Bevilaqua, Fernanda; de Abreu, Murilo Sander; Zanatta, Leila; Elisabetsky, Elaine; Barcellos, Leonardo J G; Lara, Diogo R; Piato, Angelo L

2015-12-01

Despite the recent advances in understanding the pathophysiology of anxiety disorders, the pharmacological treatments currently available are limited in efficacy and induce serious side effects. A possible strategy to achieve clinical benefits is drug repurposing, i.e., discovery of novel applications for old drugs, bringing new treatment options to the market and to the patients who need them. N-acetylcysteine (NAC), a commonly used mucolytic and paracetamol antidote, has emerged as a promising molecule for the treatment of several neuropsychiatric disorders. The mechanism of action of this drug is complex, and involves modulation of antioxidant, inflammatory, neurotrophic and glutamate pathways. Here we evaluated the effects of NAC on behavioral parameters relevant to anxiety in zebrafish. NAC did not alter behavioral parameters in the novel tank test, prevented the anxiety-like behaviors induced by an acute stressor (net chasing), and increased the time zebrafish spent in the lit side in the light/dark test. These data may indicate that NAC presents an anti-stress effect, with the potential to prevent stress-induced psychiatric disorders such as anxiety and depression. The considerable homology between mammalian and zebrafish genomes invests the current data with translational validity for the further clinical trials needed to substantiate the use of NAC in anxiety disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

Entrance to the NACA's Flight Propulsion Research Laboratory

NASA Image and Video Library

1948-08-21

The sign near the entrance of the National Advisory Committee for Aeronautics (NACA) Flight Propulsion Research Laboratory. The name was changed several weeks later to the Lewis Flight Propulsion Laboratory in honor of the NACA’s former Director of Aeronautical Research, George W. Lewis. The research laboratory has had five different names since its inception in 1941. The Cleveland laboratory was originally known as the NACA Aircraft Engine Research Laboratory. In 1947 it was renamed the NACA Flight Propulsion Research Laboratory to reflect the expansion of the research activities beyond just engines. Following the death of George Lewis, the name was changed to the NACA Lewis Flight Propulsion Laboratory in September 1948. On October 1, 1958, the lab was incorporated into the new NASA space agency, and it was renamed the NASA Lewis Research Center. Following John Glenn’s flight on the space shuttle, the name was changed again to the NASA Glenn Research Center on March 1, 1999. From his office in Washington DC, George Lewis managed the aeronautical research conducted at the NACA for over 20 years. His most important accomplishment, however, may have been an investigative tour of German research facilities in the fall of 1936. The visit resulted in the broadening of the scope of the NACA’s research and the physical expansion that included the new engine laboratory in Cleveland.

Index of NACA Technical Publications: June, 1955 - June, 1956

NASA Technical Reports Server (NTRS)

1956-01-01

This Index of NACA Technical Publications covers those NACA research reports issued in the period of June 1955 through June 1956. It is the fifth supplement to the basic 1919-1949 Index. The res ear c h reports issued prior to June 1955 which have been declassified since that date have also been included. In addition, current announcement of newly declassified materials is regularly made in the NACA Research Abstracts and Reclassification Notice. The arrangement of the present Index follows that of its predecessors: (1) A listing of the subject categories by numerical classifications, (2) a chronological listing of the NACA research reports under each subject category, (3) an aIphabe ic a I index to the subject categories, and (4) an author index. An Explanatory Chart on page iii may be helpful in identifying references to NACA research reports encountered in the literature. Entries included herein duplicate in part the information of the index cards furnished with the individual research reports. Recipients maintaining card fiIes may wish to discard those index cards on hand for unclassified research reports issued during the June 1955-June 1956 period. Newly available research reports are currently announced in the NACA Research Abstracts and Reclassification Notice and are normally available for a period of five years after announcement. Most of the older research reports (those issued prior to May 1951) are thus available on a "loan only" basis within the United States

Tests of three tapered airfoils based on the N.A.C.A. 2200, the N.A.C.A.-M6, and the Clark Y sections

NASA Technical Reports Server (NTRS)

Anderson, Raymond F

1934-01-01

Three tapered airfoils based on the N.A.C.A. 2200, the N.A.C.A.-M6, and the Clark Y sections were tested in the variable-density wind tunnel at a Reynolds Number of approximately 3,100,000. The models, which were of aspect ratio 6, had constant core center sections and rounded tips, and tapered in thickness from 18 percent at the roots to 9 percent at the tips. The aerodynamic characteristics are given by the usual dimensionless coefficients plotted for both positive and negative angles of attack and by effective profile-drag coefficients plotted against lift coefficients.

Knock-Limited Power Outputs from a CFR Engine Using Internal Coolants. 3; Four Alkyl Amines, Three Alkanolamines, Six Amides, and Eight Heterocyclic Compounds

NASA Technical Reports Server (NTRS)

Imming, Harry S.; Bellman, Donald R.

1947-01-01

An investigation of the antiknock effectiveness of various additive-water solutions when used as internal coolants has been conducted at the NACA Cleveland laboratory. Nine compounds have been previously run in a CFR engine and the results are presented. In an effort to find a good anti-knock-coolant additive with more desirable physical properties than those of the nine compounds previously investigated, water solutions of four alkyl amines, three alkanolamines, six amides, and eight heterocyclic compounds were investigated and the results are presented.

Spatial and mineralogic variation of Na-Ca alteration in Laramide porphyry systems of Arizona

NASA Astrophysics Data System (ADS)

Runyon, S.; Seedorff, E.; Barton, M. D.; Mazdab, F. K.; Lecumberri-Sanchez, P.; Steele-MacInnis, M.

2017-12-01

Na-Ca alteration is characterized by the metasomatic addition of Ca ± Na and the loss of K. Minor volumes of Na-Ca alteration in Laramide porphyry systems develops from 3 to 8 km paleodepth. Mineral assemblages, mineral compositions, hydrogen isotopes, whole-rock analyses, and reconnaissance fluid inclusion characteristics have been documented for Na-Ca alteration in Laramide porphyry systems such as Tea Cup and Sierrita. Volumetrically minor Na-Ca alteration in Laramide porphyry systems documented in this study commonly takes the form of one of three mineral assemblages: albite-epidote-chlorite, Na-plagioclase-actinolite ± epidote, and garnet- or diopside-stable Na-plagioclase-actinolite ± epidote. These different Na-Ca mineral assemblages have broad spatial relationships, from shallow albite-chlorite-epidote to deeper Na-plagioclase-actinolite within a given district. Hydrogen isotope data on Na-Ca alteration minerals shows consistently distinct δD compositions of Na-Ca alteration minerals compared to igneous minerals in a given district. Further, calculated hydrogen isotope composition of fluids in equilibrium with Na-Ca alteration minerals are consistently enriched in δD compared to magmatic-hydrothermal fluids. Whole-rock analyses show consistent losses of K and variable addition of Na and Ca across different Na-Ca alteration assemblages. Na-Ca alteration has been well documented associated with the Jurassic arc. Previous studies demonstrated through mass balance, timing and spatial relationships, isotopic, and fluid inclusion studies that Na-Ca alteration associated with the Jurassic arc likely formed from the circulation of external, highly saline, non-magmatic fluids (e.g., Battles and Barton, 1995; Dilles et al., 1995). Na-Ca alteration documented in Laramide systems is generally similar to Na-Ca alteration documented along the Jurassic arc in mineral assemblages, compositions, and timing, but the volume of Na-Ca alteration in the Laramide systems is

A reduced-amide inhibitor of Pin1 binds in a conformation resembling a twisted-amide transition state.

PubMed

Xu, Guoyan G; Zhang, Yan; Mercedes-Camacho, Ana Y; Etzkorn, Felicia A

2011-11-08

The mechanism of the cell cycle regulatory peptidyl prolyl isomerase (PPIase), Pin1, was investigated using reduced-amide inhibitors designed to mimic the twisted-amide transition state. Inhibitors, R-pSer-Ψ[CH(2)N]-Pro-2-(indol-3-yl)ethylamine, 1 [R = fluorenylmethoxycarbonyl (Fmoc)] and 2 (R = Ac), of Pin1 were synthesized and bioassayed. Inhibitor 1 had an IC(50) value of 6.3 μM, which is 4.5-fold better for Pin1 than our comparable ground-state analogue, a cis-amide alkene isostere-containing inhibitor. The change of Fmoc to Ac in 2 improved aqueous solubility for structural determination and resulted in an IC(50) value of 12 μM. The X-ray structure of the complex of 2 bound to Pin1 was determined to 1.76 Å resolution. The structure revealed that the reduced amide adopted a conformation similar to the proposed twisted-amide transition state of Pin1, with a trans-pyrrolidine conformation of the prolyl ring. A similar conformation of substrate would be destabilized relative to the planar amide conformation. Three additional reduced amides, with Thr replacing Ser and l- or d-pipecolate (Pip) replacing Pro, were slightly weaker inhibitors of Pin1.

A restored NACA P-51D Mustang in flight

NASA Image and Video Library

2000-09-15

Bill Allmon of Las Vegas, Nevada, brought his restored NACA P-51D to a reunion of former NACA employees at the NASA Dryden Flight Research Center located at Edwards Air Force Base, Calif., on Sept. 15, 2000. Allmon's award-winning restoration is a genuine former NACA testbed that saw service at the Langley Research Center in Virginia in the late 1940s. Later this Mustang was put on outdoor static display as an Air National Guard monument in Pittsburgh, Pa., where exposure to the elements ravaged its metal structure, necessitating an extensive four-year rebuild.

Primary fatty acid amide metabolism: conversion of fatty acids and an ethanolamine in N18TG2 and SCP cells1[S

PubMed Central

Farrell, Emma K.; Chen, Yuden; Barazanji, Muna; Jeffries, Kristen A.; Cameroamortegui, Felipe; Merkler, David J.

2012-01-01

Primary fatty acid amides (PFAM) are important signaling molecules in the mammalian nervous system, binding to many drug receptors and demonstrating control over sleep, locomotion, angiogenesis, and many other processes. Oleamide is the best-studied of the primary fatty acid amides, whereas the other known PFAMs are significantly less studied. Herein, quantitative assays were used to examine the endogenous amounts of a panel of PFAMs, as well as the amounts produced after incubation of mouse neuroblastoma N18TG2 and sheep choroid plexus (SCP) cells with the corresponding fatty acids or N-tridecanoylethanolamine. Although five endogenous primary amides were discovered in the N18TG2 and SCP cells, a different pattern of relative amounts were found between the two cell lines. Higher amounts of primary amides were found in SCP cells, and the conversion of N-tridecanoylethanolamine to tridecanamide was observed in the two cell lines. The data reported here show that the N18TG2 and SCP cells are excellent model systems for the study of PFAM metabolism. Furthermore, the data support a role for the N-acylethanolamines as precursors for the PFAMs and provide valuable new kinetic results useful in modeling the metabolic flux through the pathways for PFAM biosynthesis and degradation. PMID:22095832

Early Use of N-acetylcysteine With Nitrate Therapy in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Segment-Elevation Myocardial Infarction Reduces Myocardial Infarct Size (the NACIAM Trial [N-acetylcysteine in Acute Myocardial Infarction]).

PubMed

Pasupathy, Sivabaskari; Tavella, Rosanna; Grover, Suchi; Raman, Betty; Procter, Nathan E K; Du, Yang Timothy; Mahadavan, Gnanadevan; Stafford, Irene; Heresztyn, Tamila; Holmes, Andrew; Zeitz, Christopher; Arstall, Margaret; Selvanayagam, Joseph; Horowitz, John D; Beltrame, John F

2017-09-05

Contemporary ST-segment-elevation myocardial infarction management involves primary percutaneous coronary intervention, with ongoing studies focusing on infarct size reduction using ancillary therapies. N-acetylcysteine (NAC) is an antioxidant with reactive oxygen species scavenging properties that also potentiates the effects of nitroglycerin and thus represents a potentially beneficial ancillary therapy in primary percutaneous coronary intervention. The NACIAM trial (N-acetylcysteine in Acute Myocardial Infarction) examined the effects of NAC on infarct size in patients with ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention. This randomized, double-blind, placebo-controlled, multicenter study evaluated the effects of intravenous high-dose NAC (29 g over 2 days) with background low-dose nitroglycerin (7.2 mg over 2 days) on early cardiac magnetic resonance imaging-assessed infarct size. Secondary end points included cardiac magnetic resonance-determined myocardial salvage and creatine kinase kinetics. Of 112 randomized patients with ST-segment-elevation myocardial infarction, 75 (37 in NAC group, 38 in placebo group) underwent early cardiac magnetic resonance imaging. Median duration of ischemia pretreatment was 2.4 hours. With background nitroglycerin infusion administered to all patients, those randomized to NAC exhibited an absolute 5.5% reduction in cardiac magnetic resonance-assessed infarct size relative to placebo (median, 11.0%; [interquartile range 4.1, 16.3] versus 16.5%; [interquartile range 10.7, 24.2]; P =0.02). Myocardial salvage was approximately doubled in the NAC group (60%; interquartile range, 37-79) compared with placebo (27%; interquartile range, 14-42; P <0.01) and median creatine kinase areas under the curve were 22 000 and 38 000 IU·h in the NAC and placebo groups, respectively ( P =0.08). High-dose intravenous NAC administered with low-dose intravenous nitroglycerin is associated with reduced

Hydrodynamic and Aerodynamic Tests of a Family of Models of Seaplane Floats with Varying Angles of Dead Rise - N.A.C.A. Models 57-A, 57-B, and 57-C

NASA Technical Reports Server (NTRS)

Parkinson, John B; Olson, Roland E; House, Rufus O

1939-01-01

Three models of V-bottom floats for twin-float seaplanes (N.A.C.A. models 57-A, 57-B, and 57-C) having angles of dead rise of 20 degrees, 25 degrees, and thirty degrees, respectively, were tested in the N.A.C.A. tank and in the N.A.C.A. 7- by 10-foot wind tunnel. Within the range investigated, the effect of angle of dead rise on water resistance was found to be negligible at speeds up to and including the hump speed, and water resistance was found to increase with angle of dead rise at planing speeds. The height of the spray at the hump speed decreased with increase in angle of dead rise and the aerodynamic drag increased with dead rise. Lengthening the forebody of model 57-B decreased the water resistance and the spray at speeds below the hump speed. Spray strips provided an effective means for the control of spray with the straight V sections used in the series but considerably increased the aerodynamic drag. Charts for the determination of the water resistance and the static properties of the model with 25 degrees dead rise and for the aerodynamic drag of all the models are included for use in design.

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

PubMed Central

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 outcome was change in severity of hairpulling as measured by the Massachusetts General Hospital–Hairpulling Scale (MGH-HPS). Secondary measures assessed hairpulling severity, automatic versus focused pulling, clinician-rated improvement, and comorbid anxiety and depression. Outcomes were examined using linear mixed models to test the treatment × time interaction in an intention-to-treat population. Results No significant difference between N-acetylcysteine and placebo was found on any of the primary or secondary outcome measures. On several measures of hairpulling, subjects significantly improved with time regardless of treatment assignment. In the NAC group, 25% of subjects were judged as treatment responders, compared to 21% in the placebo group. Conclusions We observed no benefit of NAC for the treatment of children with trichotillomania. Our findings stand in contrast to a previous, similarly designed trial in adults with TTM, which demonstrated a very large, statistically significant benefit of NAC. Based on the differing results of NAC in pediatric and adult TTM populations, the assumption that pharmacological interventions demonstrated to be effective in adults with TTM will be as effective in children, may be inaccurate. This trial highlights the importance of referring children with TTM to appropriate behavioral therapy before initiating pharmacological interventions, as behavioral therapy has demonstrated efficacy in both children and adults with trichotillomania. PMID:23452680

N-acetylcysteine prevents nitrosative stress-associated depression of blood pressure and heart rate in streptozotocin diabetic rats.

PubMed

Nagareddy, Prabhakara Reddy; Xia, Zhengyuan; MacLeod, Kathleen M; McNeill, John H

2006-04-01

Previous studies have indicated that cardiovascular abnormalities such as depressed blood pressure and heart rate occur in streptozotocin (STZ) diabetic rats. Chronic diabetes, which is associated with increased expression of inducible nitric oxide synthase (iNOS) and oxidative stress, may produce peroxynitrite/nitrotyrosine and cause nitrosative stress. We hypothesized that nitrosative stress causes cardiovascular depression in STZ diabetic rats and therefore can be corrected by reducing its formation. Control and STZ diabetic rats were treated orally for 9 weeks with N-acetylcysteine (NAC), an antioxidant and inhibitor of iNOS. At termination, the mean arterial blood pressure (MABP) and heart rate (HR) were measured in conscious rats. Nitrotyrosine and endothelial nitric oxide synthase (eNOS) and iNOS expression were assessed in the heart and mesenteric arteries by immunohistochemistry and Western blot experiments. Untreated diabetic rats showed depressed MABP and HR that was prevented by treatment with NAC. In untreated diabetic rats, levels of 15-F(2t)-isoprostane, an indicator of lipid peroxidation increased, whereas plasma nitric oxide and antioxidant concentrations decreased. Furthermore, decreased eNOS and increased iNOS expression were associated with elevated nitrosative stress in blood vessel and heart tissue of untreated diabetic rats. N-acetylcysteine treatment of diabetic rats not only restored the antioxidant capacity but also reduced the expression of iNOS and nitrotyrosine and normalized the expression of eNOS to that of control rats in heart and superior mesenteric arteries. The results suggest that nitrosative stress depress MABP and HR following diabetes. Further studies are required to elucidate the mechanisms involved in nitrosative stress mediated depression of blood pressure and heart rate.

A 2:1 co-crystal of p-nitro-benzoic acid and N,N'-bis-(pyridin-3-ylmeth-yl)ethanedi-amide: crystal structure and Hirshfeld surface analysis.

PubMed

Syed, Sabrina; Halim, Siti Nadiah Abdul; Jotani, Mukesh M; Tiekink, Edward R T

2016-01-01

The title 2:1 co-crystal, 2C7H5NO4·C14H14N4O2, in which the complete di-amide mol-ecule is generated by crystallographic inversion symmetry, features a three-mol-ecule aggregate sustained by hydroxyl-O-H⋯N(pyrid-yl) hydrogen bonds. The p-nitro-benzoic acid mol-ecule is non-planar, exhibiting twists of both the carb-oxy-lic acid and nitro groups, which form dihedral angles of 10.16 (9) and 4.24 (4)°, respectively, with the benzene ring. The di-amide mol-ecule has a conformation approximating to a Z shape, with the pyridyl rings lying to either side of the central, almost planar di-amide residue (r.m.s. deviation of the eight atoms being 0.025 Å), and forming dihedral angles of 77.22 (6)° with it. In the crystal, three-mol-ecule aggregates are linked into a linear supra-molecular ladder sustained by amide-N-H⋯O(nitro) hydrogen bonds and orientated along [10-4]. The ladders are connected into a double layer via pyridyl- and benzene-C-H⋯O(amide) inter-actions, which, in turn, are connected into a three-dimensional architecture via π-π stacking inter-actions between pyridyl and benzene rings [inter-centroid distance = 3.6947 (8) Å]. An evaluation of the Hirshfeld surfaces confirm the importance of inter-molecular inter-actions involving oxygen atoms as well as the π-π inter-actions.

NACA Engineer Examines Wind Tunnel Compressor Blades

NASA Image and Video Library

1955-09-21

An engineer examines the main compressor for the 10- by 10-Foot Supersonic Wind Tunnel at the National Advisory Committee for Aeronautics (NACA) Lewis Flight Propulsion Laboratory. The engineers were preparing the new wind tunnel for its initial runs in early 1956. The 10- by 10 was the most powerful propulsion wind tunnel in the nation. The facility was part of Congress’ Unitary Plan Act which coordinated wind tunnel construction at the NACA, Air Force, industry, and universities. The 10- by 10 was the largest of the three NACA tunnels built under the act. The 20-foot diameter eight-stage axial flow compressor, seen in this photograph, could generate air flows up to Mach 2.5 through the test section. The stainless steel compressor had 584 blades ranging from 1.8 to 3.25 feet in length. This main compressor was complemented by a secondary axial flow compressor. Working in tandem the two could generate wind streams up to Mach 3.5. The Cleveland Chamber of Commerce presented NACA Lewis photographer Bill Bowles with a second place award for this photograph in their Business and Professional category. The photograph was published in October 1955 edition of its periodical, The Clevelander, which highlighted local professional photographers. Fellow Lewis photographer Gene Giczy won second place in another category for a photograph of Cleveland Municipal Airport.

Missile on Display at the 1957 NACA Lewis Inspection

NASA Image and Video Library

1957-10-21

A researcher examines a model being installed in the test section of the 10- by 10-Foot Supersonic Wind Tunnel during the 1957 Inspection of the National Advisory Committee for Aeronautics (NACA) Lewis Flight Propulsion Laboratory. The NACA held its annual Inspection at one of its three research laboratories. Representatives from the military, aeronautical industry, universities, and the press were invited to the laboratory to be briefed on the NACA’s latest research efforts and tour the state- of- the- art test facilities. Over 1700 people visited the NACA Lewis in Cleveland, Ohio during the October 7 - 10, 1957 Inspection. NACA researchers Leonard Obery, seen here, James Connors, Leonard, Stitt, David Bowditch gave presentations on high Mach number turbojets at the 10- by 10 tunnel. It had been only 15 years since a jet aircraft had first flown in the US. Since then the sound barrier had been broken and speeds of Mach 2.5 had been achieved. In the late 1950s NACA researchers sought to create an engine that could achieve Mach 4. This type of engine would require an extremely long inlet and nozzle which would have to be capable of adjusting their diameter for different speeds. A Mach 4 engine would require new composite materials to withstand the severe conditions, modified airframes to hold the longer engines, and high temperature seals and lubricants. The 10- by 10-foot tunnel, which had only been in operation for a year and a half, would play a critical role in these studies. NACA researchers at other facilities discussed high energy aircraft fuels and rocket propellants, aircraft noise reduction, hypersonic flight, nuclear propulsion, and high temperature materials.

Induction of apoptosis by pyrrolidinedithiocarbamate and N-acetylcysteine in vascular smooth muscle cells.

PubMed

Tsai, J C; Jain, M; Hsieh, C M; Lee, W S; Yoshizumi, M; Patterson, C; Perrella, M A; Cooke, C; Wang, H; Haber, E; Schlegel, R; Lee, M E

1996-02-16

Pyrrolidinedithiocarbamate (PDTC) and N-acetylcysteine (NAC) have been used as antioxidants to prevent apoptosis in lymphocytes, neurons, and vascular endothelial cells. We report here that PDTC and NAC induce apoptosis in rat and human smooth muscle cells. In rat aortic smooth muscle cells, PDTC induced cell shrinkage, chromatin condensation, and DNA strand breaks consistent with apoptosis. In addition, overexpression of Bcl-2 suppressed vascular smooth muscle cell death caused by PDTC and NAC. The viability of rat aortic smooth muscle cells decreased within 3 h of treatment with PDTC and was reduced to 30% at 12 h. The effect of PDTC and NAC on smooth muscle cells was not species specific because PDTC and NAC both caused dose-dependent reductions in viability in rat and human aortic smooth muscle cells. In contrast, neither PDTC nor NAC reduced viability in human aortic endothelial cells. The use of antioxidants to induce apoptosis in vascular smooth muscle cells may help prevent their proliferation in arteriosclerotic lesions.

Clinical trials of N-acetylcysteine in psychiatry and neurology: A systematic review.

PubMed

Deepmala; Slattery, John; Kumar, Nihit; Delhey, Leanna; Berk, Michael; Dean, Olivia; Spielholz, Charles; Frye, Richard

2015-08-01

N-acetylcysteine (NAC) is recognized for its role in acetaminophen overdose and as a mucolytic. Over the past decade, there has been growing evidence for the use of NAC in treating psychiatric and neurological disorders, considering its role in attenuating pathophysiological processes associated with these disorders, including oxidative stress, apoptosis, mitochondrial dysfunction, neuroinflammation and glutamate and dopamine dysregulation. In this systematic review we find favorable evidence for the use of NAC in several psychiatric and neurological disorders, particularly autism, Alzheimer's disease, cocaine and cannabis addiction, bipolar disorder, depression, trichotillomania, nail biting, skin picking, obsessive-compulsive disorder, schizophrenia, drug-induced neuropathy and progressive myoclonic epilepsy. Disorders such as anxiety, attention deficit hyperactivity disorder and mild traumatic brain injury have preliminary evidence and require larger confirmatory studies while current evidence does not support the use of NAC in gambling, methamphetamine and nicotine addictions and amyotrophic lateral sclerosis. Overall, NAC treatment appears to be safe and tolerable. Further well designed, larger controlled trials are needed for specific psychiatric and neurological disorders where the evidence is favorable. Copyright © 2015 Elsevier Ltd. All rights reserved.

N-acetylcysteine (NAC) in neurological disorders: mechanisms of action and therapeutic opportunities

PubMed Central

Bavarsad Shahripour, Reza; Harrigan, Mark R; Alexandrov, Andrei V

2014-01-01

Background There is an expanding field of research investigating the benefits of medicines with multiple mechanisms of action across neurological disorders. N-acetylcysteine (NAC), widely known as an antidote to acetaminophen overdose, is now emerging as treatment of vascular and nonvascular neurological disorders. NAC as a precursor to the antioxidant glutathione modulates glutamatergic, neurotrophic, and inflammatory pathways. Aim and discussion Most NAC studies up to date have been carried out in animal models of various neurological disorders with only a few studies completed in humans. In psychiatry, NAC has been tested in over 20 clinical trials as an adjunctive treatment; however, this topic is beyond the scope of this review. Herein, we discuss NAC molecular, intracellular, and systemic effects, focusing on its potential applications in neurodegenerative diseases including spinocerebellar ataxia, Parkinson's disease, tardive dyskinesia, myoclonus epilepsy of the Unverricht–Lundbor type as well as multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer's disease. Conclusion Finally, we review the potential applications of NAC to facilitate recovery after traumatic brain injury, cerebral ischemia, and in treatment of cerebrovascular vasospasm after subarachnoid hemorrhage. PMID:24683506

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

PubMed

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.

Insecticidal, repellent and fungicidal properties of novel trifluoromethylphenyl amides.

PubMed

Tsikolia, Maia; Bernier, Ulrich R; Coy, Monique R; Chalaire, Katelyn C; Becnel, James J; Agramonte, Natasha M; Tabanca, Nurhayat; Wedge, David E; Clark, Gary G; Linthicum, Kenneth J; Swale, Daniel R; Bloomquist, Jeffrey R

2013-09-01

Twenty trifluoromethylphenyl amides were synthesized and evaluated as fungicides and as mosquito toxicants and repellents. Against Aedes aegypti larvae, N-(2,6-dichloro-4-(trifluoromethyl)phenyl)-3,5-dinitrobenzamide (1e) was the most toxic compound (24 h LC50 1940 nM), while against adults N-(2,6-dichloro-4-(trifluoromethyl)phenyl)-2,2,2-trifluoroacetamide (1c) was most active (24 h LD50 19.182 nM, 0.5 μL/insect). However, the 24 h LC50 and LD50 values of fipronil against Ae. aegypti larvae and adults were significantly lower: 13.55 nM and 0.787 × 10(-4) nM, respectively. Compound 1c was also active against Drosophila melanogaster adults with 24 h LC50 values of 5.6 and 4.9 μg/cm(2) for the Oregon-R and 1675 strains, respectively. Fipronil had LC50 values of 0.004 and 0.017 μg/cm(2) against the two strains of D. melanogaster, respectively. In repellency bioassays against female Ae. aegypti, 2,2,2-trifluoro-N-(2-(trifluoromethyl)phenyl)acetamide (4c) had the highest repellent potency with a minimum effective dosage (MED) of 0.039 μmol/cm(2) compared to DEET (MED of 0.091 μmol/cm(2)). Compound N-(2-(trifluoromethyl)phenyl)hexanamide (4a) had an MED of 0.091 μmol/cm(2) which was comparable to DEET. Compound 4c was the most potent fungicide against Phomopsis obscurans. Several trends were discerned between the structural configuration of these molecules and the effect of structural changes on toxicity and repellency. Para- or meta- trifluoromethylphenyl amides with an aromatic ring attached to the carbonyl carbon showed higher toxicity against Ae. aegypti larvae, than ortho- trifluoromethylphenyl amides. Ortho- trifluoromethylphenyl amides with trifluoromethyl or alkyl group attached to the carbonyl carbon produced higher repellent activity against female Ae. aegypti and Anopheles albimanus than meta- or para- trifluoromethylphenyl amides. The presence of 2,6-dichloro- substitution on the phenyl ring of the amide had an influence on larvicidal and repellent

Pressure response of protein backbone structure. Pressure-induced amide 15N chemical shifts in BPTI.

PubMed Central

Akasaka, K.; Li, H.; Yamada, H.; Li, R.; Thoresen, T.; Woodward, C. K.

1999-01-01

The effect of pressure on amide 15N chemical shifts was studied in uniformly 15N-labeled basic pancreatic trypsin inhibitor (BPTI) in 90%1H2O/10%2H2O, pH 4.6, by 1H-15N heteronuclear correlation spectroscopy between 1 and 2,000 bar. Most 15N signals were low field shifted linearly and reversibly with pressure (0.468 +/- 0.285 ppm/2 kbar), indicating that the entire polypeptide backbone structure is sensitive to pressure. A significant variation of shifts among different amide groups (0-1.5 ppm/2 kbar) indicates a heterogeneous response throughout within the three-dimensional structure of the protein. A tendency toward low field shifts is correlated with a decrease in hydrogen bond distance on the order of 0.03 A/2 kbar for the bond between the amide nitrogen atom and the oxygen atom of either carbonyl or water. The variation of 15N shifts is considered to reflect site-specific changes in phi, psi angles. For beta-sheet residues, a decrease in psi angles by 1-2 degrees/2 kbar is estimated. On average, shifts are larger for helical and loop regions (0.553 +/- 0.343 and 0.519 +/- 0.261 ppm/2 kbar, respectively) than for beta-sheet (0.295 +/- 0.195 ppm/2 kbar), suggesting that the pressure-induced structural changes (local compressibilities) are larger in helical and loop regions than in beta-sheet. Because compressibility is correlated with volume fluctuation, the result is taken to indicate that the volume fluctuation is larger in helical and loop regions than in beta-sheet. An important aspect of the volume fluctuation inferred from pressure shifts is that they include motions in slower time ranges (less than milliseconds) in which many biological processes may take place. PMID:10548039

Introducing the New Class of N-Phosphoryl Ynamides via Cu(I)-Catalyzed Amidations of Alkynyl Bromides

PubMed Central

Walton, Mary C.; North, Troy D.

2011-01-01

We describe here the first synthesis of N-phosphoryl ynamides featuring C- and P-chirality via copper(I)-catalyzed amidative cross-couplings between phosphoramidates and phosphordiamidates with alkynyl bromides. Also featured is a tandem aza-Claisen–hetero-[2+2] cycloaddition for the synthesis of N-phosphoryl azetidin-2-imines. PMID:21848304

Synthesis and biological activity of a new class of insecticides: the N-(5-aryl-1,3,4-thiadiazol-2-yl)amides.

PubMed

Eckelbarger, Joseph D; Parker, Marshall H; Yap, Maurice Ch; Buysse, Ann M; Babcock, Jonathan M; Hunter, Ricky; Adelfinskaya, Yelena; Samaritoni, Jack G; Garizi, Negar; Trullinger, Tony K

2017-04-01

Optimization studies on a high-throughput screening (HTS) hit led to the discovery of a series of N-(6-arylpyridazin-3-yl)amides with insecticidal activity. It was hypothesized that the isosteric replacement of the pyridazine ring with a 1,3,4-thiadiazole ring could lead to more potent biological activity and/or a broader sap-feeding pest spectrum. The resulting N-(5-aryl-1,3,4-thiadiazol-2-yl)amides were explored as a new class of insecticides. Several methods for 2-amino-1,3,4-thiadiazole synthesis were used for the preparation of key synthetic intermediates. Subsequent coupling to variously substituted carboxylic acid building blocks furnished the final targets, which were tested for insecticidal activity against susceptible strains of Aphis gossypii (Glover) (cotton aphid), Myzus persicae (Sulzer) (green peach aphid) and Bemisia tabaci (Gennadius) (sweetpotato whitefly). Structure-activity relationship (SAR) studies on both the amide tail and the aryl A-ring of novel N-(5-aryl-1,3,4-thiadiazol-2-yl)amides led to a new class of insecticidal molecules active against sap-feeding insect pests. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

A 2:1 co-crystal of 2-methyl-benzoic acid and N,N'-bis-(pyridin-4-ylmeth-yl)ethanedi-amide: crystal structure and Hirshfeld surface analysis.

PubMed

Syed, Sabrina; Jotani, Mukesh M; Halim, Siti Nadiah Abdul; Tiekink, Edward R T

2016-03-01

The asymmetric unit of the title 2:1 co-crystal, 2C8H8O2·C14H14N4O2, comprises an acid mol-ecule in a general position and half a di-amide mol-ecule, the latter being located about a centre of inversion. In the acid, the carb-oxy-lic acid group is twisted out of the plane of the benzene ring to which it is attached [dihedral angle = 28.51 (8)°] and the carbonyl O atom and methyl group lie approximately to the same side of the mol-ecule [hy-droxy-O-C-C-C(H) torsion angle = -27.92 (17)°]. In the di-amide, the central C4N2O2 core is almost planar (r.m.s. deviation = 0.031 Å), and the pyridyl rings are perpendicular, lying to either side of the central plane [central residue/pyridyl dihedral angle = 88.60 (5)°]. In the mol-ecular packing, three-mol-ecule aggregates are formed via hy-droxy-O-H⋯N(pyrid-yl) hydrogen bonds. These are connected into a supra-molecular layer parallel to (12[Formula: see text]) via amide-N-H⋯O(carbon-yl) hydrogen bonds, as well as methyl-ene-C-H⋯O(amide) inter-actions. Significant π-π inter-actions occur between benzene/benzene, pyrid-yl/benzene and pyrid-yl/pyridyl rings within and between layers to consolidate the three-dimensional packing.

Amide Bond Formation Assisted by Vicinal Alkylthio Migration in Enaminones: Metal- and CO-Free Synthesis of α,β-Unsaturated Amides.

PubMed

Liu, Zhuqing; Huang, Fei; Wu, Ping; Wang, Quannan; Yu, Zhengkun

2018-05-18

Amide bond formation is one of the most important transformations in organic synthesis, drug development, and materials science. Efficient construction of amides has been among the most challenging tasks for organic chemists. Herein, we report a concise methodology for amide bond (-CONH-) formation assisted by vicinal group migration in alkylthio-functionalized enaminones (α-oxo ketene N, S-acetals) under mild conditions. Simple treatment of such enaminones with PhI(OAc) 2 at ambient temperature in air afforded diverse multiply functionalized α,β-unsaturated amides including β-cyclopropylated acrylamides, in which a wide array of functional groups such as aryl, (hetero)aryl, alkenyl, and alkyl can be conveniently introduced to a ketene moiety. The reaction mechanism was investigated by exploring the origins of the amide oxygen and carbon atoms as well as isolation and structural characterization of the reaction intermediates. The amide bond formation reactions could also be efficiently performed under solventless mechanical milling conditions.

Oleoyl serine, an endogenous N-acyl amide, modulates bone remodeling and mass.

PubMed

Smoum, Reem; Bar, Arik; Tan, Bo; Milman, Garry; Attar-Namdar, Malka; Ofek, Orr; Stuart, Jordyn M; Bajayo, Alon; Tam, Joseph; Kram, Vardit; O'Dell, David; Walker, Michael J; Bradshaw, Heather B; Bab, Itai; Mechoulam, Raphael

2010-10-12

Bone mass is determined by a continuous remodeling process, whereby the mineralized matrix is being removed by osteoclasts and subsequently replaced with newly formed bone tissue produced by osteoblasts. Here we report the presence of endogenous amides of long-chain fatty acids with amino acids or with ethanolamine (N-acyl amides) in mouse bone. Of these compounds, N-oleoyl-l-serine (OS) had the highest activity in an osteoblast proliferation assay. In these cells, OS triggers a Gi-protein-coupled receptor and Erk1/2. It also mitigates osteoclast number by promoting osteoclast apoptosis through the inhibition of Erk1/2 phosphorylation and receptor activator of nuclear-κB ligand (RANKL) expression in bone marrow stromal cells and osteoblasts. In intact mice, OS moderately increases bone volume density mainly by inhibiting bone resorption. However, in a mouse ovariectomy (OVX) model for osteoporosis, OS effectively rescues bone loss by increasing bone formation and markedly restraining bone resorption. The differential effect of exogenous OS in the OVX vs. intact animals is apparently a result of an OVX-induced decrease in skeletal OS levels. These data show that OS is a previously unexplored lipid regulator of bone remodeling. It represents a lead to antiosteoporotic drug discovery, advantageous to currently available therapies, which are essentially either proformative or antiresorptive.

Index of NACA Technical Publications, July 1956 - June 1957

NASA Technical Reports Server (NTRS)

1957-01-01

This index of NACA Technical Publications covers the NACA research reports issued in the period of July 1956 through June 1957. It is the sixth supplement to the basic 1915-1949 Index. The research reports issued prior to July 1956 which have been declassified since that date have also been included. A list of these reports may be found on pages 243-244. Cards for this list may be discarded as entries for them are included in this Index. Current announcement of newly declassified materials is regularly made in the NACA Research Abstracts and Reclassification Notice. The arrangement of this Index follows: (1) Explanatory chart of NACA publications series designations, (2) outline of subject classification system, (3) chronological list of NACA reports under each subject classification, (4) list of reports declassified from July 1956 through June 1957, (5) alphabetical index to subject categories, and (6) author index. Entries included herein duplicate in part the information of the index cards furnished with the individual research reports. Recipients maintaining card files may wish to discard those index cards on hand for unclassified research reports issued during the July 1956-June 1957 period. Such cards were printed on yellow stock for easy identification in the discard process. Please note that some classified reports issued during the July-December 1956 period are included in the yellow stock area. Therefore care must be taken to avoid destroying such cards. Newly available research reports are currently announced in the NACA Research Abstracts and Reclassification Notice and are normally available for a period of five years after announcement. Most of the older research reports (those issued prior to July 1952) are thus available on a "loan only" basis within the United states.

Nonplanar tertiary amides in rigid chiral tricyclic dilactams. Peptide group distortions and vibrational optical activity.

PubMed

Pazderková, Markéta; Profant, Václav; Hodačová, Jana; Sebestík, Jaroslav; Pazderka, Tomáš; Novotná, Pavlína; Urbanová, Marie; Safařík, Martin; Buděšínský, Miloš; Tichý, Miloš; Bednárová, Lucie; Baumruk, Vladimír; Maloň, Petr

2013-08-22

We investigate amide nonplanarity in vibrational optical activity (VOA) spectra of tricyclic spirodilactams 5,8-diazatricyclo[6,3,0,0(1,5)]undecan-4,9-dione (I) and its 6,6',7,7'-tetradeuterio derivative (II). These rigid molecules constrain amide groups to nonplanar geometries with twisted pyramidal arrangements of bonds to amide nitrogen atoms. We have collected a full range vibrational circular dichroism (VCD) and Raman optical activity (ROA) spectra including signals of C-H and C-D stretching vibrations. We report normal-mode analysis and a comparison of calculated to experimental VCD and ROA. The data provide band-to-band assignment and offer a possibility to evaluate roles of constrained nonplanar tertiary amide groups and rigid chiral skeletons. Nonplanarity shows as single-signed VCD and ROA amide I signals, prevailing the couplets expected to arise from the amide-amide interaction. Amide-amide coupling dominates amide II (mainly C'-N stretching, modified in tertiary amides by the absence of a N-H bond) transitions (strong couplet in VCD, no significant ROA) probably due to the close proximity of amide nitrogen atoms. At lower wavenumbers, ROA spectra exhibit another likely manifestation of amide nonplanarity, showing signals of amide V (δ(oop)(N-C) at ~570 cm(-1)) and amide VI (δ(oop)(C'═O) at ~700 cm(-1) and ~650 cm(-1)) vibrations.

NACA Pilots at the Aircraft Engine Research Laboratory

NASA Image and Video Library

1945-07-21

The Aircraft Engine Research Laboratory’s pilot corps during the final days of World War II: from left to right, Joseph Vensel, Howard Lilly, William Swann, and Joseph Walker. William “Eb” Gough joined the group months after this photograph. These men were responsible for flying the various National Advisory Committee for Aeronautics (NACA) aircraft to test new engine modifications, study ice buildup, and determine fuel performance. Vensel, a veteran pilot from Langley, was the Chief of Flight Operations and a voice of reason at the laboratory. In April 1947 Vensel was transferred to lead the new Muroc Flight Tests Unit in California until 1966. Lilly was a young pilot with recent Navy experience. Lilly also flew in the 1946 National Air Races. He followed Vensel to Muroc in July 1947 where he became the first NACA pilot to penetrate the sound barrier. On May 3, 1948, Lilly became the first NACA pilot to die in the line of duty. Swann was a young civilian pilot when he joined the NACA. He spent his entire career at the Cleveland laboratory, and led the flight operations group from the early 1960s until 1979. Two World War II veterans joined the crew after the war. Walker was a 24-year-old P–38 reconnaissance pilot. He joined the NACA as a physicist in early 1945 but soon worked his way into the cadre of pilots. Walker later gained fame as an X-plane pilot at Muroc and was killed in a June 1966 fatal crash. Gough survived being shot down twice during the war and was decorated for flying rescue missions in occupied areas.

Effects of N-acetylcysteine on noise-induced temporary threshold shift and temporary emission shift

NASA Astrophysics Data System (ADS)

Robinette, Martin

2004-05-01

Animal research has shown that antioxidants can provide significant protection to the cochlea from traumatic noise exposure with some benefit when given after the exposure. Similar results in humans would have a significant impact on both prevention and treatment of noise-induced hearing loss. The current study evaluates the effectiveness of N-acetylcysteine (NAC) on temporary threshold shift (TTS) by using both behavioral and physiological measures. Sixteen healthy, normal-hearing subjects were given NAC or a placebo prior to exposure to a 10-min, 102-dB narrow-band noise, centered at 2 kHz. This exposure was designed to induce a 10-15-dB TTS. Following the noise exposure, pure-tone thresholds (Bekesy) and transient-evoked otoacoustic emissions (TEOAE) were measured for 60 min to monitor the effects of NAC on TTS recovery. Postexposure measures were compared to baseline data. [Work supported by American BioHealth Group.

New regimens for intravenous acetylcysteine, where are we now?

PubMed

Bateman, D Nicholas; Dear, James W; Thomas, Simon H L

2016-01-01

Acetylcysteine has been used as a treatment for paracetamol overdose as a 20.25- or 21-h infusion for nearly 40 years. These regimens give 50% of the dose in the first 15 min or 1 h, and are associated with high rates of adverse reactions. A randomised controlled trial has demonstrated that a shorter (12 h) and simpler (two infusions) acetylcysteine regimen using a slower initial infusion rate produces lower rates of adverse events than the original 20.25-h regimen. However, this study was not sufficiently large to show therapeutic equivalence as a hepatoprotective therapy in paracetamol overdose. Two further studies are now reported, which also suggest lower rates of adverse reactions with lower initial rates of acetylcysteine administration. These modified regimens can now be accepted as better tolerated, but it is unlikely that a randomised study of sufficient size to demonstrate non-inferiority of any novel regimen would ever be funded. Against this background we suggest what can be done to establish the efficacy of these less toxic and potentially shorter alternative acetylcysteine regimens and to establish them into routine clinical use.

N-Acetylcysteine in the treatment of pediatric trichotillomania: a randomized, double-blind, placebo-controlled add-on trial.

PubMed

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

2013-03-01

To examine the efficacy of N-acetylcysteine (NAC) for the treatment of pediatric trichotillomania (TTM) in a double-blind, placebo-controlled, add-on study. 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 outcome was change in severity of hairpulling as measured by the Massachusetts General Hospital-Hairpulling Scale (MGH-HPS). Secondary measures assessed hairpulling severity, automatic versus focused pulling, clinician-rated improvement, and comorbid anxiety and depression. Outcomes were examined using linear mixed models to test the treatment×time interaction in an intention-to-treat population. No significant difference between N-acetylcysteine and placebo was found on any of the primary or secondary outcome measures. On several measures of hairpulling, subjects significantly improved with time regardless of treatment assignment. In the NAC group, 25% of subjects were judged as treatment responders, compared to 21% in the placebo group. We observed no benefit of NAC for the treatment of children with trichotillomania. Our findings stand in contrast to a previous, similarly designed trial in adults with TTM, which demonstrated a very large, statistically significant benefit of NAC. Based on the differing results of NAC in pediatric and adult TTM populations, the assumption that pharmacological interventions demonstrated to be effective in adults with TTM will be as effective in children, may be inaccurate. This trial highlights the importance of referring children with TTM to appropriate behavioral therapy before initiating pharmacological interventions, as behavioral therapy has demonstrated efficacy in both children and adults with trichotillomania. Copyright © 2013 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Catalytic synthesis of amides via aldoximes rearrangement.

PubMed

Crochet, Pascale; Cadierno, Victorio

2015-02-14

Amide bond formation reactions are among the most important transformations in organic chemistry because of the widespread occurrence of amides in pharmaceuticals, natural products and biologically active compounds. The Beckmann rearrangement is a well-known method to generate secondary amides from ketoximes. However, under the acidic conditions commonly employed, aldoximes RHC=NOH rarely rearrange into the corresponding primary amides RC(=O)NH2. In recent years, it was demonstrated that this atom-economical transformation can be carried out efficiently and selectively with the help of metal catalysts. Several homogeneous and heterogenous systems have been described. In addition, protocols offering the option to generate the aldoximes in situ from the corresponding aldehydes and hydroxylamine, or even from alcohols, have also been developed, as well as a series of tandem processes allowing the access to N-substituted amide products. In this Feature article a comprehensive overview of the advances achieved in this particular research area is presented.

Aerodynamic Characteristics of a Two-blade NACA 10-(3)(062)-045 Propeller and of a Two-blade NACA 10-(3)(08)-045 Propeller

NASA Technical Reports Server (NTRS)

Solomon, William

1953-01-01

Characteristics are given for the two-blade NACA 10-(3)(062)-045 propeller and for the two-blade NACA 10-(3)(08)-045 propeller over a range of advance ratio from 0.5 to 3.8, through a blade-angle range from 20 degrees to 55 degrees measured at the 0.75 radius. Maximum efficiencies of the order of 91.5 to 92 percent were obtained for the propellers. The propeller with the thinner airfoil sections over the outboard portion of the blades, the NACA 10-(3)(062)-045 propeller, had lower losses at high tip speeds, the difference amounting to about 5 percent at a helical tip Mach number of 1.10.

Vitamin B5 and N-acetylcysteine in nonalcoholic steatohepatitis: a pre-clinical study in a dietary mouse model

PubMed Central

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

2015-01-01

Background 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. Objectives We aimed to evaluate CoA metabolism and the effects of supplementation with CoA precursors, pantothenate and cysteine, in mouse models of NASH. Methods 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. Results 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. Conclusion 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. PMID:26403427

Alkylsilyl Peroxides as Alkylating Agents in the Copper-Catalyzed Selective Mono-N-Alkylation of Primary Amides and Arylamines.

PubMed

Sakamoto, Ryu; Sakurai, Shunya; Maruoka, Keiji

2017-07-06

The copper-catalyzed selective mono-N-alkylation of primary amides or arylamines using alkylsilyl peroxides as alkylating agents is reported. The reaction proceeds under mild reaction conditions and exhibits a broad substrate scope with respect to the alkylsilyl peroxides, as well as to the primary amides and arylamines. Mechanistic studies suggest that the present reaction should proceed through a free-radical process that includes alkyl radicals generated from the alkylsilyl peroxides. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

New Poly(amide-imide)/Nanocomposites Reinforced Silicate Nanoparticles Based on N-pyromellitimido-L-phenyl Alanine Containing Ether Moieties

NASA Astrophysics Data System (ADS)

Faghihi, Khalil; Shabanian, Meisam; Dadfar, Ehsan

2012-02-01

A series of Poly(amide-imide)/montmorillonite nanocomposites containing N-pyromellitimido-L-phenyl alanine moiety in the main chain were synthesized by a convenient solution intercalation technique. Poly(amide-imide) (PAI) 5 as a source of polymer matrix was synthesized by the direct polycondensation reaction of N-pyromellitimido-L-phenyl alanine 3 with 4,4'-diamino diphenyl ether 4 in the presence of triphenyl phosphite (TPP), CaCl2, pyridine and N-methyl-2-pyrrolidone (NMP). The resulting nanocomposite films were characterized by Fourier transform infrared spectra (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM) and thermogravimetric analysis (TGA). The results showed that organo-modified clay was dispersed homogeneously in PAI matrix. TGA indicated an enhancement of thermal stability of new nanocomposites compared with the pure polymer.

Some NACA Muroc personnel with snowman

NASA Technical Reports Server (NTRS)

1949-01-01

The late 1940s saw increased flight activity, and more women computers were needed at the NACA Muroc Flight Test Unit than the ones who had originally arrived in 1946. A call went out to the NACA Langley, Lewis, and Ames laboratories for more women computers. Pictured in this photograph with the Snowman are some of the women computers who responded to the call for help in 1948 along with Roxanah, Emily, Dorothy, who were already here. Standing left to right: Mary (Tut) Hedgepeth, from Langley; Lilly Ann Bajus, Lewis; Roxanah Yancey, Emily Stephens, Jane Collons (Procurement), Leona Corbett (Personnel), Angel Dunn, Langley. Kneeling left to right: Dorothy (Dottie) Crawford Roth, Lewis; Dorothy Clift Hughes, and Gertrude (Trudy) Wilken Valentine, Lewis. In National Advisory Committee for Aeronautics (NACA) terminology of 1946, computers were employees who performed laborious and time-consuming mathematical calculations and data reduction from long strips of records generated by onboard aircraft instrumentation. Virtually without exception, computers were female; at least part of the rationale seems to have been the notion that the work was long and tedious, and men were not thought to have the patience to do it. Though equipment changed over the years and most computers eventually found themselves programming and operating electronic computers, as well as doing other data processing tasks, being a computer initially meant long hours with a slide rule, hunched over illuminated light boxes measuring line traces from grainy and obscure strips of oscillograph film. Computers suffered terrible eyestrain, and those who didn't begin by wearing glasses did so after a few years. But they were initially essential employees at the Muroc Flight Test Unit and NACA High-Speed Flight Research Station, taking the oscillograph flight records and 'reducing' the data on them to make them useful to research engineers, who analyzed the data.

Massive acetaminophen overdose: effect of hemodialysis on acetaminophen and acetylcysteine kinetics.

PubMed

Ghannoum, Marc; Kazim, Sara; Grunbaum, Ami M; Villeneuve, Eric; Gosselin, Sophie

2016-07-01

Early onset acidosis from mitochondrial toxicity can be observed in massive acetaminophen poisoning prior to the development of hepatotoxicity. In this context, the efficacy of acetylcysteine to reverse mitochondrial toxicity remains unclear and hemodialysis may offer prompt correction of acidosis. Unfortunately, toxicokinetics of acetaminophen and acetylcysteine during extracorporeal treatments hemodialysis have seldom been described. An 18-year-old woman presented to the emergency department 60 minutes after ingestion of 100 g of acetaminophen, and unknown amounts of ibuprofen and ethanol. Initial assessment revealed an agitated patient. Her mental status worsened and she required intubation for airway protection. Investigations showed metabolic acidosis with lactate peaking at 8.6 mmol/L. Liver and coagulation profiles remained normal. Acetaminophen concentration peaked at 981 μg/ml (6496 μmol/L). Pending hemodialysis, the patient received 100 g of activated charcoal and an acetylcysteine infusion at 150 mg/kg over 1 hour, followed by 12.5 mg/kg/h for 4 hours. During hemodialysis, the infusion was maintained at 12.5 mg/kg/h to compensate for expected removal before it was decreased to 6.25 mg/kg for 20 hours after hemodialysis. The patient rapidly improved during hemodialysis and was discharged 48 hours post-admission. The acetaminophen elimination half-life was 5.2 hours prior to hemodialysis, 1.9-hours during hemodialysis and 3.6 hours post hemodialysis. The acetaminophen and acetylcysteine clearances by A-V gradient during hemodialysis were 160.4 ml/min and 190.3 ml/min, respectively. Hemodialysis removed a total of 20.6 g of acetaminophen and 17.9 g of acetylcysteine. This study confirms the high dialyzability of both acetaminophen and acetylcysteine. Hemodialysis appears to be a beneficial therapeutic option in cases of massive acetaminophen ingestion with coma and lactic acidosis. Additionally, these results

Reaction mechanism of the acidic hydrolysis of highly twisted amides: Rate acceleration caused by the twist of the amide bond.

PubMed

Mujika, Jon I; Formoso, Elena; Mercero, Jose M; Lopez, Xabier

2006-08-03

We present an ab initio study of the acid hydrolysis of a highly twisted amide and a planar amide analogue. The aim of these studies is to investigate the effect that the twist of the amide bond has on the reaction barriers and mechanism of acid hydrolysis. Concerted and stepwise mechanisms were investigated using density functional theory and polarizable continuum model calculations. Remarkable differences were observed between the mechanism of twisted and planar amide, due mainly to the preference for N-protonation of the former and O-protonation of the latter. In addition, we were also able to determine that the hydrolytic mechanism of the twisted amide will be pH dependent. Thus, there is a preference for a stepwise mechanism with formation of an intermediate in the acid hydrolysis, whereas the neutral hydrolysis undergoes a concerted-type mechanism. There is a nice agreement between the characterized intermediate and available X-ray data and a good agreement with the kinetically estimated rate acceleration of hydrolysis with respect to analogous undistorted amide compounds. This work, along with previous ab initio calculations, describes a complex and rich chemistry for the hydrolysis of highly twisted amides as a function of pH. The theoretical data provided will allow for a better understanding of the available kinetic data of the rate acceleration of amides upon twisting and the relation of the observed rate acceleration with intrinsic differential reactivity upon loss of amide bond resonance.

A single-arm clinical trial of a 48-hour intravenous N-acetylcysteine protocol for treatment of acetaminophen poisoning.

PubMed

Heard, K; Rumack, B H; Green, J L; Bucher-Bartelson, B; Heard, S; Bronstein, A C; Dart, R C

2014-06-01

Acetylcysteine prevents hepatic injury when administered soon after acetaminophen overdose. The most commonly used treatment protocols are a 72-hour oral and a 21-hour intravenous (IV) protocol. Between 1984 and 1994, 409 patients were enrolled in a study to describe the outcomes of patients who were treated using a 48-hour IV protocol. In 1991, an interim analysis reported the first 223 patients. The objective of this manuscript is to report the rates of hepatotoxicity and adverse events occurring during a 48-hour IV acetylcysteine protocol in the entire 409 patient cohort. This was a multicenter, single-arm, open-label clinical trial enrolling patients who presented with a toxic serum acetaminophen concentration within 24 h of acute acetaminophen ingestion. Patients were treated with 140 mg/kg loading dose followed by 70 mg/kg every 4 h for 12 doses. Serum aminotransferase activities were measured every 8 h during the protocol, and adverse events were recorded. The primary outcome was the percentage of subjects who developed hepatotoxicity defined as a peak serum aminotransferase greater than 1000 IU/L. Four hundred and nine patients were enrolled, and 309 met inclusion for the outcome analysis. The overall percentage of patients developing hepatotoxicity was 18.1%, and 3.4% of patients treated within 10 h developed hepatotoxicity. One acetaminophen-related death occurred in a patient treated at 22 h. Adverse events occurred in 28.9% of enrolled subjects; the most common adverse events were nausea, vomiting, and flushing, and no events were rated as serious by the investigator. Acetaminophen-overdosed patients treated with IV acetylcysteine administered as 140 mg/kg loading dose followed by 70 mg/kg every 4 h for 12 doses had a low rate of hepatotoxicity and few adverse events. This protocol delivers a higher dose of acetylcysteine which may be useful in selected cases involving very large overdoses.

Friedel-Crafts Acylation with Amides

PubMed Central

Raja, Erum K.; DeSchepper, Daniel J.; Nilsson Lill, Sten O.; Klumpp, Douglas A.

2012-01-01

Friedel-Crafts acylation has been known since the 1870s and it is an important organic synthetic reaction leading to aromatic ketone products. Friedel-Crafts acylation is usually done with carboxylic acid chlorides or anhydrides while amides are generally not useful substrates in these reactions. Despite being the least reactive carboxylic acid derivative, we have found a series of amides capable of providing aromatic ketones in good yields (55–96%, 17 examples). We propose a mechanism involving diminished C-N resonance through superelectrophilic activation and subsequent cleavage to acyl cations. PMID:22690740

N-acetylcysteine ameliorates contrast‑induced kidney injury in rats with unilateral hydronephrosis.

PubMed

Xia, Qiang; Liu, Chunxiao; Zheng, Xia

2018-02-01

The aim of the present study was to investigate the protective effects of N‑acetylcysteine (NAC) on contrast‑induced acute kidney injury in rats with unilateral hyronephrosis. Eighty‑two male Sprague Dawley rats were randomized to undergo sham operation (n=14) or unilateral ureteral obstruction (UUO) (n=68). After 3 weeks, the UUO animals were randomized to three groups: NAC gastric perfusion, UUO+iohexol+NAC (n=24); normal saline perfusion, UUO+iohexol (n=24); and controls, UUO (n=20). After 3 days, UUO+iohexol+NAC and UUO+iohexol rats were injected with iohexol. One day after contrast, half of the rats were sacrificed to assess the pathological changes to the kidneys, serum creatinine, serum neutrophil gelatinase‑associated lipocalin (NGAL), renal cell apoptosis rate and expression of apoptosis regulators Bcl‑2/Bax. The remaining rats underwent obstruction relief and were analyzed 3 weeks later. Compared with the controls, serum NGAL levels were high in UUO+iohexol rats 1 day following injection and 3 weeks after obstruction relief, but UUO+iohexol+NAC rats exhibited lower serum NGAL levels compared with UUO+iohexol rats (all P<0.05). Following modeling, UUO+iohexol rats exhibited a significantly higher apoptosis rate of renal tubular cells, higher expression of Bax mRNA, and lower ratio of Bcl‑2/Bax (all P<0.05). Three weeks after obstruction relief, UUO+iohexol+NAC rats exhibited a lower apoptosis rate, lower Bax mRNA expression, higher expression of Bcl‑2 mRNA and higher ratio of Bcl‑2/Bax (all P<0.05) compared with day 1 following drug administration. The prophylactic use of NAC reduced the apoptotic rate of renal tubular cells following contrast exposition, which was accompanied by changes in the expression of Bcl‑2/Bax mRNA.

Analysis of the Na+/Ca2+ Exchanger Gene Family within the Phylum Nematoda

PubMed Central

He, Chao; O'Halloran, Damien M.

2014-01-01

Na+/Ca2+ exchangers are low affinity, high capacity transporters that rapidly transport calcium at the plasma membrane, mitochondrion, endoplasmic (and sarcoplasmic) reticulum, and the nucleus. Na+/Ca2+ exchangers are widely expressed in diverse cell types where they contribute homeostatic balance to calcium levels. In animals, Na+/Ca2+ exchangers are divided into three groups based upon stoichiometry: Na+/Ca2+ exchangers (NCX), Na+/Ca2+/K+ exchangers (NCKX), and Ca2+/Cation exchangers (CCX). In mammals there are three NCX genes, five NCKX genes and one CCX (NCLX) gene. The genome of the nematode Caenorhabditis elegans contains ten Na+/Ca2+ exchanger genes: three NCX; five CCX; and two NCKX genes. Here we set out to characterize structural and taxonomic specializations within the family of Na+/Ca2+ exchangers across the phylum Nematoda. In this analysis we identify Na+/Ca2+ exchanger genes from twelve species of nematodes and reconstruct their phylogenetic and evolutionary relationships. The most notable feature of the resulting phylogenies was the heterogeneous evolution observed within exchanger subtypes. Specifically, in the case of the CCX exchangers we did not detect members of this class in three Clade III nematodes. Within the Caenorhabditis and Pristionchus lineages we identify between three and five CCX representatives, whereas in other Clade V and also Clade IV nematode taxa we only observed a single CCX gene in each species, and in the Clade III nematode taxa that we sampled we identify NCX and NCKX encoding genes but no evidence of CCX representatives using our mining approach. We also provided re-annotation for predicted CCX gene structures from Heterorhabditis bacteriophora and Caenorhabditis japonica by RT-PCR and sequencing. Together, these findings reveal a complex picture of Na+/Ca2+ transporters in nematodes that suggest an incongruent evolutionary history of proteins that provide central control of calcium dynamics. PMID:25397810

Inhibition of development of peripheral neuropathy in streptozotocin-induced diabetic rats with N-acetylcysteine.

PubMed

Sagara, M; Satoh, J; Wada, R; Yagihashi, S; Takahashi, K; Fukuzawa, M; Muto, G; Muto, Y; Toyota, T

1996-03-01

N-acetylcysteine (NAC) is a precursor of glutathione (GSH) synthesis, a free radical scavenger and an inhibitor of tumour necrosis factor alpha (TNF). Because these functions might be beneficial in diabetic complications, in this study we examined whether NAC inhibits peripheral neuropathy. Motor nerve conduction velocity (MNCV) was significantly decreased in streptozotocin-induced-diabetic Wistar rats compared to control rats. Oral administration of NAC reduced the decline of MNCV in diabetic rats. Structural analysis of the sural nerve disclosed significant reduction of fibres undergoing myelin wrinkling and inhibition of myelinated fibre atrophy in NAC-treated diabetic rats. NAC treatment had no effect on blood glucose levels or on the nerve glucose, sorbitol and cAMP contents, whereas it corrected the decreased GSH levels in erythrocytes, the increased lipid peroxide levels in plasma and the increased lipopolysaccharide-induced TNF activity in sera of diabetic rats. Thus, NAC inhibited the development of functional and structural abnormalities of the peripheral nerve in streptozotocin-induced diabetic rats.

Oleoyl serine, an endogenous N-acyl amide, modulates bone remodeling and mass

PubMed Central

Smoum, Reem; Bar, Arik; Tan, Bo; Milman, Garry; Attar-Namdar, Malka; Ofek, Orr; Stuart, Jordyn M.; Bajayo, Alon; Tam, Joseph; Kram, Vardit; O'Dell, David; Walker, Michael J.; Bradshaw, Heather B.; Bab, Itai; Mechoulam, Raphael

2010-01-01

Bone mass is determined by a continuous remodeling process, whereby the mineralized matrix is being removed by osteoclasts and subsequently replaced with newly formed bone tissue produced by osteoblasts. Here we report the presence of endogenous amides of long-chain fatty acids with amino acids or with ethanolamine (N-acyl amides) in mouse bone. Of these compounds, N-oleoyl-l-serine (OS) had the highest activity in an osteoblast proliferation assay. In these cells, OS triggers a Gi-protein-coupled receptor and Erk1/2. It also mitigates osteoclast number by promoting osteoclast apoptosis through the inhibition of Erk1/2 phosphorylation and receptor activator of nuclear-κB ligand (RANKL) expression in bone marrow stromal cells and osteoblasts. In intact mice, OS moderately increases bone volume density mainly by inhibiting bone resorption. However, in a mouse ovariectomy (OVX) model for osteoporosis, OS effectively rescues bone loss by increasing bone formation and markedly restraining bone resorption. The differential effect of exogenous OS in the OVX vs. intact animals is apparently a result of an OVX-induced decrease in skeletal OS levels. These data show that OS is a previously unexplored lipid regulator of bone remodeling. It represents a lead to antiosteoporotic drug discovery, advantageous to currently available therapies, which are essentially either proformative or antiresorptive. PMID:20876113

Structural study of salt forms of amides; paracetamol, benzamide and piperine

NASA Astrophysics Data System (ADS)

Kennedy, Alan R.; King, Nathan L. C.; Oswald, Iain D. H.; Rollo, David G.; Spiteri, Rebecca; Walls, Aiden

2018-02-01

Single crystal x-ray diffraction has been used to investigate the structures of six complexes containing O-atom protonated cations derived from the pharmaceutically relevant amides benzamide (BEN), paracetamol (PAR) and piperine (PIP). The structures of the salt forms [PAR(H)][SO3C6H4Cl], [BEN(H)][O3SC6H4Cl] and [BEN(H)][Br]·H2O are reported along with those of the hemi-halide salt forms [PAR(H)][I3]. PAR, [PIP(H)][I3]·PIP and [PIP(H)][I3]0·5[I]0.5. PIP. The structure of the cocrystal BEN. HOOCCH2Cl is also presented for comparison. The geometry of the amide group is found to systematically change upon protonation, with the Cdbnd O distance increasing and the Csbnd N distance decreasing. The hemi-halide species all feature strongly hydrogen bonded amide(H)/amide pairs. The amide group Cdbnd O and Csbnd N distances for both elements of each such pair are intermediate between those found for simple neutral amide and protonated amide forms. It was found that crystallising paracetamol from aqueous solutions containing Ba2+ ions gave orthorhombic paracetamol.

Antiapoptotic and antigenotoxic effects of N-acetylcysteine in human cells of endothelial origin.

PubMed

Aluigi, M G; De Flora, S; D'Agostini, F; Albini, A; Fassina, G

2000-01-01

N-Acetylcysteine (NAC) is a drug bearing multiple preventive properties that can inhibit genotoxicity and carcinogenicity. NAC also inhibits invasion and metastasis of malignant cells, as well as tumor take. We recently demonstrated the effects of NAC on Kaposi's sarcoma cells supernatant-induced invasion in vitro and angiogenesis in vivo. Many anticancer agents act through cytotoxicity of rapidly proliferating cells and several antineoplastic drugs induce apoptosis of cancer cells. Since endothelial cells are the target for the inhibition of angiogenesis, we wanted to verify that NAC, while inhibiting tumor vascularization and endothelial cell invasion would not induce endothelial cell apoptosis. We tested the ability of NAC to modulate apoptosis and cytogenetic damage in vitro and to promote differentiation on a reconstituted basement membrane (matrigel) in two endothelial cell lines (EAhy926 and HUVE). Treatment with NAC protected endothelial cells from TGF-beta-induced apoptosis and paraquat-induced cytogenetic damage. Therefore, NAC acts as an antiangiogenic agent and, at the same time, appears to prevent apoptosis and oxygen-related genotoxicity in endothelial cells.

Oral Cysteamine bitartrate and N-acetylcysteine combination for patients with infantile neuronal ceroid lipofuscinosis:a pilot study

PubMed Central

Levin, Sondra W.; Baker, Eva H.; Zein, Wadih M.; Zhang, Zhongjian; Quezado, Zenaide M.N.; Miao, Ning; Gropman, Andrea; Griffin, Kurt J.; Bianconi, Simona; Chandra, Goutam; Khan, Omar I.; Caruso, Rafael C.; Liu, Aiyi; Mukherjee, Anil B.

2014-01-01

Summary Background Infantile neuronal ceroid lipofuscinosis (INCL) is a devastating neurodegenerative lysosomal storage disease caused by mutations in the CLN1 gene encoding palmitoyl-protein thioesterase-1 (PPT1). PPT1-deficiency causes lysosomal ceroid accumulation leading to INCL pathogenesis. Previously, we reported that phosphocysteamine and N-acetylcysteine mediated ceroid depletion in cultured cells from INCL patients. We conducted a pilot study to determine whether a combination of cysteamine bitartrate and N-acetylcysteine is beneficial for these patients. Methods Patients (6-month to 3-years old) with any combination of 2 of the 7 most lethal PPT1 mutations were admitted. All patients were recruited from physician referrals and the PPT1 mutations were analyzed prior to admission. Patients were evaluated by electroretinography(ERG), brain MRI and MRS, electroencephalography (EEG), and electron microscopic analyses of leukocytes for granular osmiophilic deposits (GRODs). Patients received oral cysteamine bitartrate (60mg/kg/day) and N-acetylcysteine (60mg/kg/day) and were evaluated every 6 to 12 months until they showed isoelectric EEG attesting to a vegetative state or were too sick to travel. Outcomes were compared with the reported INCL natural history. In two cases, the disease progression was compared with that of a sibling who was above the age limit for inclusion into the protocol. Findings Between March, 2001, and June, 2011, we recruited 10 children with INCL but one was lost to follow-up after the first visit. Thus, a total of 9 patients (5 females and 4 males) were studied. At the first follow-up visit, peripheral leukocytes in all 9 patients showed virtually complete depletion of GRODs and 7 of 9 patients manifested less irritability and/or improved alertness based upon parental and physician observations. Evaluation by Denver scale showed acquisition of no new developmental skills and retinal function assessed by ERG progressively declined

Outcomes after Angiography with Sodium Bicarbonate and Acetylcysteine.

PubMed

Weisbord, Steven D; Gallagher, Martin; Jneid, Hani; Garcia, Santiago; Cass, Alan; Thwin, Soe-Soe; Conner, Todd A; Chertow, Glenn M; Bhatt, Deepak L; Shunk, Kendrick; Parikh, Chirag R; McFalls, Edward O; Brophy, Mary; Ferguson, Ryan; Wu, Hongsheng; Androsenko, Maria; Myles, John; Kaufman, James; Palevsky, Paul M

2018-02-15

Intravenous sodium bicarbonate and oral acetylcysteine are widely used to prevent acute kidney injury and associated adverse outcomes after angiography without definitive evidence of their efficacy. Using a 2-by-2 factorial design, we randomly assigned 5177 patients at high risk for renal complications who were scheduled for angiography to receive intravenous 1.26% sodium bicarbonate or intravenous 0.9% sodium chloride and 5 days of oral acetylcysteine or oral placebo; of these patients, 4993 were included in the modified intention-to-treat analysis. The primary end point was a composite of death, the need for dialysis, or a persistent increase of at least 50% from baseline in the serum creatinine level at 90 days. Contrast-associated acute kidney injury was a secondary end point. The sponsor stopped the trial after a prespecified interim analysis. There was no interaction between sodium bicarbonate and acetylcysteine with respect to the primary end point (P=0.33). The primary end point occurred in 110 of 2511 patients (4.4%) in the sodium bicarbonate group as compared with 116 of 2482 (4.7%) in the sodium chloride group (odds ratio, 0.93; 95% confidence interval [CI], 0.72 to 1.22; P=0.62) and in 114 of 2495 patients (4.6%) in the acetylcysteine group as compared with 112 of 2498 (4.5%) in the placebo group (odds ratio, 1.02; 95% CI, 0.78 to 1.33; P=0.88). There were no significant between-group differences in the rates of contrast-associated acute kidney injury. Among patients at high risk for renal complications who were undergoing angiography, there was no benefit of intravenous sodium bicarbonate over intravenous sodium chloride or of oral acetylcysteine over placebo for the prevention of death, need for dialysis, or persistent decline in kidney function at 90 days or for the prevention of contrast-associated acute kidney injury. (Funded by the U.S. Department of Veterans Affairs Office of Research and Development and the National Health and Medical Research

Bioaccumulation and toxicodynamics of cadmium to freshwater planarian and the protective effect of N-acetylcysteine.

PubMed

Wu, Jui-Pin; Chen, Hon-Cheng; Li, Mei-Hui

2012-08-01

Although toxic responses of freshwater planarians after exposure to environmental toxicants can be observed through external toxicological end points, physiological responses inside the bodies of treated planarians have rarely been investigated. The present study was designed, using cadmium (Cd) as a reference toxicant, to determine its bioaccumulation and toxicodynamics in the freshwater planarian, Dugesia japonica, after acute toxicity was obtained. Accumulated Cd concentrations, metallothionein levels, and the oxidative status in planarians were determined after exposure to Cd. Furthermore, we hypothesized that the acute death of Cd-treated planarians was associated with increased oxidative stress. After Cd-treated planarians were coexposed to antioxidant, N-acetylcysteine (NAC), we found that NAC protected planarians from Cd lethality by maintaining the oxidative status and decreasing the bioaccumulation of Cd. The results of the present study support planarians being used as a practical model for toxicological studies of environmental contaminants in the future.

Na/Ca Ratio in Large Benthic Foraminifera as a Novel Proxy for Past Ocean Calcium

NASA Astrophysics Data System (ADS)

Rosenthal, Y.; Hauzer, H.; Evans, D.; Erez, J.

2017-12-01

Culture experiments with Operculina ammonoides (a large symbiont bearing benthic foraminifer and an extant relative of the Eocene Nummulites) were carried out varying seawater [Ca], temperature and salinity. The main results of these experiments are: 1. Na/Ca in these foraminifera shells varies with the Na/Ca ratio in the seawater 2. Na/Ca shows small, non-systematic variations with temperature (22-28 ºC) that are within our analytical precision. 3. Na/Ca in the shells show very low changes, increasing linearly with salinity. The sensitivity to salinity is very low compared to that caused by changes of Na/Ca in seawater. Over the seawater experimental range of Na/Ca (10-18 mM), a change of 5 ppt salinity induced a slight Na/Ca increase comparable to the analytical error for Na, or that caused by temperature. Initial reconstructions of seawater [Ca], based on these calibrations, generally agree well with previous models and reconstructions confirming that seawater [Ca] concentrations were substantially higher during the early-mid Cenozoic than today.

Synthesis and evaluation of fatty acid amides on the N-oleoylethanolamide-like activation of peroxisome proliferator activated receptor α.

PubMed

Takao, Koichi; Noguchi, Kaori; Hashimoto, Yosuke; Shirahata, Akira; Sugita, Yoshiaki

2015-01-01

A series of fatty acid amides were synthesized and their peroxisome proliferator-activated receptor α (PPAR-α) agonistic activities were evaluated in a normal rat liver cell line, clone 9. The mRNAs of the PPAR-α downstream genes, carnitine-palmitoyltransferase-1 and mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase, were determined by real-time reverse transcription-polymerase chain reaction (RT-PCR) as PPAR-α agonistic activities. We prepared nine oleic acid amides. Their PPAR-α agonistic activities were, in decreasing order, N-oleoylhistamine (OLHA), N-oleoylglycine, Oleamide, N-oleoyltyramine, N-oleoylsertonin, and Olvanil. The highest activity was found with OLHA. We prepared and evaluated nine N-acylhistamines (N-acyl-HAs). Of these, OLHA, C16:0-HA, and C18:1Δ(9)-trans-HA showed similar activity. Activity due to the different chain length of the saturated fatty acid peaked at C16:0-HA. The PPAR-α antagonist, GW6471, inhibited the induction of the PPAR-α downstream genes by OLHA and N-oleoylethanolamide (OEA). These data suggest that N-acyl-HAs could be considered new PPAR-α agonists.

Synthesis and SAR of piperazine amides as novel c-jun N-terminal kinase (JNK) inhibitors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shin, Youseung; Chen, Weiming; Habel, Jeff

2009-09-14

A novel series of c-jun N-terminal kinase (JNK) inhibitors were designed and developed from a high-throughput-screening hit. Through the optimization of the piperazine amide 1, several potent compounds were discovered. The X-ray crystal structure of 4g showed a unique binding mode different from other well known JNK3 inhibitors.

NACA Conference on Aircraft Loads, Flutter, and Structures: A compilation of Papers Presented.

DTIC Science & Technology

1953-03-04

Variation of Atmospheric Turbulence With Altitude and Its Effect on Airplane Gust Loads . . . by Robert L. McDougal, Thomas L. Coleman, and Philip L. Smith ...SKOPINSKI, T. H. NACA - Langley Laboratory xvii CONFIDENTIAL CONFIDENTIAL SMETHERS, Rollo G. Bureau of Aeronautics SMITH , Dana W. NACA Subcommittee on...Aircraft Structural Materials SMITH , Frank C. National Bureau of Standards SMITH , Henry G. Hughes Aircraft Co. SMITH , Howard W. NACA Subcommittee on Aircraft

Thiol redox transitions in cell signaling: a lesson from N-acetylcysteine.

PubMed

Parasassi, Tiziana; Brunelli, Roberto; Costa, Graziella; De Spirito, Marco; Krasnowska, Ewa; Lundeberg, Thomas; Pittaluga, Eugenia; Ursini, Fulvio

2010-06-29

The functional status of cells is under the control of external stimuli affecting the function of critical proteins and eventually gene expression. Signal sensing and transduction by messengers to specific effectors operate by post-translational modification of proteins, among which thiol redox switches play a fundamental role that is just beginning to be understood. The maintenance of the redox status is, indeed, crucial for cellular homeostasis and its dysregulation towards a more oxidized intracellular environment is associated with aberrant proliferation, ultimately related to diseases such as cancer, cardiovascular disease, and diabetes. Redox transitions occur in sensitive cysteine residues of regulatory proteins relevant to signaling, their evolution to metastable disulfides accounting for the functional redox switch. N-acetylcysteine (NAC) is a thiol-containing compound that is able to interfere with redox transitions of thiols and, thus, in principle, able to modulate redox signaling. We here review the redox chemistry of NAC, then screen possible mechanisms to explain the effects observed in NAC-treated normal and cancer cells; such effects involve a modification of global gene expression, thus of functions and morphology, with a leitmotif of a switch from proliferation to terminal differentiation. The regulation of thiol redox transitions in cell signaling is, therefore, proposed as a new tool, holding promise not only for a deeper explanation of mechanisms, but indeed for innovative pharmacological interventions.

N-acetylcysteine inhibits in vivo oxidation of native low-density lipoprotein

PubMed Central

Cui, Yuqi; Narasimhulu, Chandrakala A.; Liu, Lingjuan; Zhang, Qingbin; Liu, Patrick Z.; Li, Xin; Xiao, Yuan; Zhang, Jia; Hao, Hong; Xie, Xiaoyun; He, Guanglong; Cui, Lianqun; Parthasarathy, Sampath; Liu, Zhenguo

2015-01-01

Low-density lipoprotein (LDL) is non-atherogenic, while oxidized LDL (ox-LDL) is critical to atherosclerosis. N-acetylcysteine (NAC) has anti-atherosclerotic effect with largely unknown mechanisms. The present study aimed to determine if NAC could attenuate in vivo LDL oxidation and inhibit atherosclerosis. A single dose of human native LDL was injected intravenously into male C57BL/6 mice with and without NAC treatment. Serum human ox-LDL was detected 30 min after injection, reached the peak in 3 hours, and became undetectable in 12 hours. NAC treatment significantly reduced serum ox-LDL level without detectable serum ox-LDL 6 hours after LDL injection. No difference in ox-LDL clearance was observed in NAC-treated animals. NAC treatment also significantly decreased serum ox-LDL level in patients with coronary artery diseases and hyperlipidemia without effect on LDL level. Intracellular and extracellular reactive oxidative species (ROS) production was significantly increased in the animals treated with native LDL, or ox-LDL and in hyperlipidemic LDL receptor knockout (LDLR−/−) mice that was effectively prevented with NAC treatment. NAC also significantly reduced atherosclerotic plaque formation in hyperlipidemic LDLR−/− mice. NAC attenuated in vivo oxidation of native LDL and ROS formation from ox-LDL associated with decreased atherosclerotic plaque formation in hyperlipidemia. PMID:26536834

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

PubMed

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

2016-02-02

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.

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

PubMed

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.

N-acetylcysteine in contrast-induced acute kidney injury: clinical use against principles of evidence-based clinical medicine!

PubMed

Sadat, Umar

2014-01-01

Contrast-induced acute kidney injury (CI-AKI) is one of the most widely discussed and debated topic in cardiovascular medicine and N-acetylcysteine (NAC) is the most widely used pharmacological agent assessed in clinical trials for offering renal protection against CI-AKI. Results of these clinical trials are though split between those that favor its use and vice versa. In this brief communication we discuss the latest research advances regarding the use of NAC against CI-AKI. Recent clinical evidence and overview of in-depth statistical analyses of relevant clinical trials and their meta-analyses do not support the use of NAC in prophylaxis against CI-AKI. Adequate hydration before and after contrast media exposure, along with avoidance of nephrotoxic drugs, remains the recommended prophylaxis against CI-AKI.

Effect of N-acetylcysteine on endothelial dysfunction in dialysis patients.

PubMed

Sahin, Garip; Yalcin, Ahmet Ugur; Akcar, Nevbahar

2007-01-01

Patients with K/DOQI stage 5 chronic kidney disease (CKD) have higher incidence of cardiovascular events due to the oxidative stress and endothelial dysfunction (ED). The aim of this study is to evaluate the effects of N-acetylcysteine (NAC), which might prevent cardiovascular events by improving oxidative stress on endothelial cells in patients with CKD. Thirty uremic patients (age 40 +/- 12 years, 6 males) on hemodialysis (HD) were evaluated for ED by using high-resolution Doppler ultrasound of brachial artery before and after 6 weeks of oral NAC (2 x 600 mg) medication. Also, 13 healthy controls (35 +/- 9 years, 5 males) were included in the study. Reactive hyperemia following 5 min forearm ischemia was accepted as endothelium-dependent vasodilatation (flow-mediated dilatation; FMD) and compared to endothelium-independent vasodilatation in response to sublingual glyceril trinitrate (GTN). Patients on HD had lower DeltaFMD (0.28 +/- 0.17 vs. 0.41 +/- 0.11, p < 0.05) and FMD% (7.5 +/- 5.05 vs. 11.33 +/- 2.95, p < 0.05) than the controls. Baseline DeltaGTN and GTN% were similar in two groups. NAC treatment significantly increased the DeltaFMD (0.41 +/- 0.11, p < 0.001 vs. baseline) and FMD% (10.59 +/- 3.22, p < 0.01 vs. baseline) of patients on HD, while it had no effect on DeltaGTN and GTN%. These results suggest that NAC treatment could improve the ED by preventing the reduction of FMD in patients on HD. Copyright 2007 S. Karger AG, Basel.

N-acetylcysteine for major mental disorders: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Zheng, W; Zhang, Q-E; Cai, D-B; Yang, X-H; Qiu, Y; Ungvari, G S; Ng, C H; Berk, M; Ning, Y-P; Xiang, Y-T

2018-05-01

This systematic review and meta-analysis of randomized controlled trials (RCTs) examined the efficacy and safety of adjunctive N-acetylcysteine (NAC), an antioxidant drug, in treating major depressive disorder (MDD), bipolar disorder, and schizophrenia. The PubMed, Cochrane Library, PsycINFO, CNKI, CBM, and WanFang databases were independently searched and screened by two researchers. Standardized mean differences (SMDs), risk ratios, and their 95% confidence intervals (CIs) were computed. Six RCTs (n = 701) of NAC for schizophrenia (three RCTs, n = 307), bipolar disorder (two RCTs, n = 125), and MDD (one RCT, n = 269) were identified and analyzed as separate groups. Adjunctive NAC significantly improved total psychopathology (SMD = -0.74, 95% CI: -1.43, -0.06; I 2 = 84%, P = 0.03) in schizophrenia, but it had no significant effect on depressive and manic symptoms as assessed by the Young Mania Rating Scale in bipolar disorder and only a small effect on major depressive symptoms. Adverse drug reactions to NAC and discontinuation rates between the NAC and control groups were similar across the three disorders. Adjunctive NAC appears to be a safe treatment that has efficacy for schizophrenia, but not for bipolar disorder or MDD. Further higher quality RCTs are warranted to determine the role of adjunctive NAC in the treatment of major psychiatric disorders. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Protective effect of N-acetylcysteine against oxygen radical-mediated coronary artery injury.

PubMed

Rodrigues, A J; Evora, P R B; Schaff, H V

2004-08-01

The present study investigated the protective effect of N-acetylcysteine (NAC) against oxygen radical-mediated coronary artery injury. Vascular contraction and relaxation were determined in canine coronary arteries immersed in Kreb's solution (95% O2-5% CO2), incubated or not with NAC (10 mM), and exposed to free radicals (FR) generated by xanthine oxidase (100 mU/ml) plus xanthine (0.1 mM). Rings not exposed to FR or NAC were used as controls. The arteries were contracted with 2.5 microM prostaglandin F2alpha. Subsequently, concentration-response curves for acetylcholine, calcium ionophore and sodium fluoride were obtained in the presence of 20 microM indomethacin. Concentration-response curves for bradykinin, calcium ionophore, sodium nitroprusside, and pinacidil were obtained in the presence of indomethacin plus Nomega-nitro-L-arginine (0.2 mM). The oxidative stress reduced the vascular contraction of arteries not exposed to NAC (3.93 +/- 3.42 g), compared to control (8.56 +/- 3.16 g) and to NAC group (9.07 +/- 4.0 g). Additionally, in arteries not exposed to NAC the endothelium-dependent nitric oxide (NO)-dependent relaxation promoted by acetylcholine (1 nM to 10 microM) was also reduced (maximal relaxation of 52.1 +/- 43.2%), compared to control (100%) and NAC group (97.0 +/- 4.3%), as well as the NO/cyclooxygenase-independent receptor-dependent relaxation provoked by bradykinin (1 nM to 10 microM; maximal relaxation of 20.0 +/- 21.2%), compared to control (100%) and NAC group (70.8 +/- 20.0%). The endothelium-independent relaxation elicited by sodium nitroprusside (1 nM to 1 microM) and pinacidil (1 nM to 10 microM) was not affected. In conclusion, the vascular dysfunction caused by the oxidative stress, expressed as reduction of the endothelium-dependent relaxation and of the vascular smooth muscle contraction, was prevented by NAC.

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

PubMed

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.

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

NASA Astrophysics Data System (ADS)

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.

N-acetylcysteine induces shedding of selectins from liver and intestine during orthotopic liver transplantation

PubMed Central

Taut, F J H; Schmidt, H; Zapletal, C M; Thies, J C; Grube, C; Motsch, J; Klar, E; Martin, E

2001-01-01

In orthotopic liver transplantation (OLT), N-acetylcysteine (NAC) reduces ischaemia/reperfusion (I/R) injury, improves liver synthesis function and prevents primary nonfunction of the graft. To further elucidate the mechanisms of these beneficial effects of NAC, we investigated influence of high-dose NAC therapy on the pattern of adhesion molecule release from liver and intestine during OLT. Nine patients receiving allograft OLT were treated with 150 mg NAC/kg during the first hour after reperfusion; 10 patients received the carrier only. One hour after reperfusion, samples of arterial, portal venous and hepatic venous plasma were taken and blood flow in the hepatic artery and the portal vein was measured. Absolute concentrations of sICAM-1, sVCAM-1, sP-selectin and sE-selectin were not markedly different. However, balance calculations showed release of selectins from NAC-treated livers as opposed to net uptake in controls (P ≤ 0·02 for sP-selectin). This shedding of selectins might be a contributing factor to the decrease in leucocyte adherence and improved haemodynamics found experimentally with NAC-treatment. PMID:11422213

Determination of the radioprotective effects of topical applications of MEA, WR-2721, and N-acetylcysteine on murine skin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Verhey, L.J.; Sedlacek, R.

1983-01-01

Topical applications of MEA (beta-mercaptoethylamine or cysteamine), WR-2721 (S-2-(3-aminopropylamino)-ethylphosphorothioic acid), and N-acetylcysteine (NAC) were tested for their ability to protect the normal skin of the hind legs of mice against acute and late damage from single doses of /sup 137/Cs radiation. No significant protection was observed with either WR-2721 or NAC. MEA was shown to offer significant protection against acute skin damage in both buffered and unbuffered forms, but no significant protection against late contraction. The use of topical MEA on unanesthetized animals breathing carbogen (95% O2, 5% CO2) appears to give an enhanced level of radioprotection over that shownmore » for anesthetized, air-breathing animals.« less

N-acetylcysteine-induced vasodilation involves voltage-gated potassium channels in rat aorta.

PubMed

Han, Wei-Qing; Zhu, Ding-Liang; Wu, Ling-Yun; Chen, Qi-Zhi; Guo, Shu-Jie; Gao, Ping-Jin

2009-05-22

N-acetylcysteine (NAC) has a protective effect against vascular dysfunction by decreasing the level of reactive oxygen species (ROS) in experimental and human hypertension. This study was designed to examine whether NAC would relax vascular rings in vitro via nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway, extracellular Ca2+ and/or K+ channels. Rat aortic arteries were mounted in an organ bath, contracted with 0.1, 0.5 or 1 micromol/L phenylephrine to plateau, and the vasodilatory effect of NAC was examined in the absence or presence of ROS scavengers, inhibitors of NO-cGMP pathway or K+ channels. Vascular smooth muscle cells (VSMCs) were loaded with a calcium sensitive fluorescent dye fluo-3 AM, and [Ca2+](i) was determined with laser-scanning confocal microscopy. NAC (0.1-4 mmol/L) dose-dependently relaxed rat aorta pre-contracted with phenylephrine. Endothelium removal, endothelial nitric oxide synthase inhibitor N(omega)-Nitro-l-arginine (L-NNA) (100 micromol/L) or soluble guanylyl cyclase (sGC) inhibitor (ODQ) (10 micromol/L) did not affect NAC-induced vasodilation. In contrast, NAC-induced vasodilation was blunted after extracellular calcium was removed and calcium imaging showed that 4 mmol/L NAC quickly decreased [Ca2+](i) in fluo-3 AM loaded VSMCs. NAC-induced vasodilation was significantly reduced in the presence of voltage-gated K+ channels (Kv) inhibitor 4-aminopyridine (4-AP). The vasodilatory effect of NAC may be explained at least partly by activation of voltage-gated K+ channels.

Impact of N-acetylcysteine on the hepatic microcirculation after orthotopic liver transplantation.

PubMed

Koeppel, T A; Lehmann, T G; Thies, J C; Gehrcke, R; Gebhard, M M; Herfarth, C; Otto, G; Post, S

1996-05-15

Recent observations showed an improvement of hepatic macro- and microhemodynamics as well as survival rates after warm ischemia of the liver following treatment with N-acetylcysteine (NAC). In this study we assessed the influence of NAC on the hepatic microcirculation after orthotopic liver transplantation (OLT) using intravital fluorescence microscopy. OLT with simultaneous arterialization was performed in 16 male Lewis rats following cold storage in University of Wisconsin solution for 24 hr. Within the experimental group (n = 8) donors received NAC (400 mg/kg) 25 min before hepatectomy. In addition, high-dose treatment of recipients with NAC (400 mg/kg) was started with reperfusion. Control animals (n = 8) received an equivalent amount of Ringer's solution. Intravital fluorescence microscopy was performed 30-90 min after reperfusion assessing acinar and sinusoidal perfusion, leukocyte-endothelium interaction, and phagocytic activity. Treatment with NAC reduced the number of nonperfused sinusoid from 52.4 +/- 0.8% to 15.7 +/- 0.5% (p = 0.0001) (mean +/- SEM). Furthermore, we achieved a significant reduction of leukocytes adhering to sinusoidal endothelium (per mm2 liver surface) from 351.9 +/- 13.0 in controls to 83.6 +/- 4.2 in the experimental group (P = 0.0001). In postsinusoidal venules, treatment with NAC decreased the number of sticking leukocytes (per mm2 endothelium) from 1098.5 +/- 59.6 to 425.9 +/- 37.7 (P = 0.0001). Moreover, bile flow was significantly increased after therapy with NAC (4.3 +/- 1.2 vs. 2.2 +/- 0.7 ml/90 min x 100g liver) (P < 0.05). Phagocytic activity was not influenced by application of NAC. We conclude that high-dose therapy with NAC in OLT attenuates manifestations of microvascular perfusion failure early after reperfusion and should be considered as a means to reduce reperfusion injury.

Nickel-Catalyzed Phosphine Free Direct N-Alkylation of Amides with Alcohols.

PubMed

Das, Jagadish; Banerjee, Debasis

2018-03-16

Herein, we developed an operational simple, practical, and selective Ni-catalyzed synthesis of secondary amides. Application of renewable alcohols, earth-abundant and nonprecious nickel catalyst facilitates the transformations, releasing water as byproduct. The catalytic system is tolerant to a variety of functional groups including nitrile, allylic ether, and alkene and could be extended to the synthesis of bis-amide, antiemetic drug Tigan, and dopamine D2 receptor antagonist Itopride. Preliminary mechanistic studies revealed the participation of a benzylic C-H bond in the rate-determining step.

D-558-1 on ramp with ground crew and NACA pilot Bob Champine

NASA Technical Reports Server (NTRS)

1949-01-01

NACA test pilot Robert Champine is seen in the cockpit of the Douglas D-558-1 Skystreak with the ground crew. Robert A. Champine was a research pilot with the National Advisory Committee for Aeronautics (NACA) and the National Aeronautics and Space Administration (NASA) from December 1947 to 1979, when he retired as Langley Research Center's senior research pilot. He began his career with the NACA at the Langley Memorial Aeronautical Laboratory in Hampton, Virginia (as Langley Research Center was then called). He transferred to the NACA's High-Speed Flight Research Station in the Mojave Desert of California in October 1948, where he flew the X-1 and D-558-1 and -2 research airplanes. On December 2, 1948, Bob became the 6th man and 3rd civilian to break the mysterious sound barrier. He exceeded Mach 1 on NACA flight 23 checking handling qualities and pressure distribution on the XS-1 #2, after having been dropped from the B-29 mother ship, above the Rogers Dry Lake in California. On August 4, 1949, NACA flight 32, he again exceeded Mach 1 performing rolls, pullups, sideslips, and check of stabilizer effectiveness. This was his 13th and last flight in the XS-1. He flew the first NACA research flight of the D-558-1 #3 (Skystreak) on April 22, 1949, and the first NACA research flight of the D-558-2 #2 (Skyrocket) on May 24, 1949, beginning the supersonic research program for these aircraft on June l, 1949. Conceived in 1945, the D558-1 Skystreak was designed by the Douglas Aircraft Company for the U.S. Navy Bureau of Aeronautics, in conjunction with the National Advisory Committee for Aeronautics (NACA). The Skystreaks were turojet powered aircraft that took off from the ground under their own power and had straight wings and tails. All three D-558-1 Skystreaks were powered by Allison J35-A-11 turbojet engines producing 5,000 pounds of thrust. All the Skystreaks were initially painted scarlet, which lead to the nickname 'crimson test tube.' NACA later had the color of

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

PubMed Central

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

Comparison of NACA 6-series and 4-digit airfoils for Darrieus wind turbines

NASA Astrophysics Data System (ADS)

Migliore, P. G.

1983-08-01

The aerodynamic efficiency of Darrieus wind turbines as effected by blade airfoil geometry was investigated. Analysis was limited to curved-bladed machines having rotor solidities of 7-21 percent and operating at a Reynolds number of 3 x 10 to the 6th. Ten different airfoils, having thickness-to-chord ratios of 12, 15, and 18 percent, were studied. Performance estimates were made using a blade element/momentum theory approach. Results indicated that NACA 6-series airfoils yield peak power coefficients as great as NACA 4-digit airfoils and have broader and flatter power coefficient-tip speed ratio curves. Sample calculations for an NACA 63(2)-015 airfoil showed an annual energy output increase of 17-27 percent, depending on rotor solidity, compared to an NACA 0015 airfoil.

N-(4-Trifluoromethylphenyl)amide group of the synthetic histamine receptor agonist inhibits nicotinic acetylcholine receptor-mediated catecholamine secretion.

PubMed

Kim, Dong-Chan; Park, Yong-Soo; Jun, Dong-Jae; Hur, Eun-Mi; Kim, Sun-Hee; Choi, Bo-Hwa; Kim, Kyong-Tai

2006-02-28

The therapeutic targeting of nicotinic receptors requires the identification of drugs that selectively activate or inhibit a limited range of nicotine acetylcholine receptors (nAChRs). In this study, we identified N-(4-trifluoromethylphenyl)amide group of the synthetic histamine receptor ligands, histamine-trifluoromethyltoluide, that act as potent inhibitors of nAChRs in bovine adrenal chromaffin cells. Catecholamine secretion induced by the nAChRs agonist, 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), was significantly inhibited by histamine-trifluoromethyltoluide. Real time carbon-fiber amperometry confirmed the ability of histamine-trifluoromethyltoluide to inhibit DMPP-induced exocytosis in single chromaffin cells. We also found that histamine-trifluoromethyltoluide inhibited DMPP-induced [Ca(2+)](i) and [Na(+)](i) increases, as well as DMPP-induced inward currents in the absence of extracellular calcium. Histamine-trifluoromethyltoluide had no effect on [(3)H]nicotine binding or on calcium increases induced by high K(+), bradykinin, veratridine, histamine, and benzoylbenzoyl ATP. Among the synthetic histamine receptor ligands, clobenpropit exhibited similarity. In addition, 4'-nitroacetanilide also significantly attenuated nAChR-mediated catecholamine secretion. In conclusion, the N-(4-trifluoromethylphenyl)amide group of the histamine-trifluoromethyltoluide might be the critical moiety in the inhibition of nAChR-mediated CA secretion.

Copper(II)-catalyzed amidations of alkynyl bromides as a general synthesis of ynamides and Z-enamides. An intramolecular amidation for the synthesis of macrocyclic ynamides.

PubMed

Zhang, Xuejun; Zhang, Yanshi; Huang, Jian; Hsung, Richard P; Kurtz, Kimberly C M; Oppenheimer, Jossian; Petersen, Matthew E; Sagamanova, Irina K; Shen, Lichun; Tracey, Michael R

2006-05-26

A general and efficient method for the coupling of a wide range of amides with alkynyl bromides is described here. This novel amidation reaction involves a catalytic protocol using copper(II) sulfate-pentahydrate and 1,10-phenanthroline to direct the sp-C-N bond formation, leading to a structurally diverse array of ynamides including macrocyclic ynamides via an intramolecular amidation. Given the surging interest in ynamide chemistry, this atom economical synthesis of ynamides should invoke further attention from the synthetic organic community.

Ultrasound-assisted green bromination of N-cinnamoyl amino acid amides - Structural characterization and antimicrobial evaluation

NASA Astrophysics Data System (ADS)

Stoykova, Boyka; Chochkova, Maya; Ivanova, Galya; Markova, Nadezhda; Enchev, Venelin; Tsvetkova, Iva; Najdenski, Hristo; Štícha, Martin; Milkova, Tsenka

2017-05-01

N-phenylpropenoyl amino acid amides have been brominated using two alternative sonochemically activated green chemistry procedures. The first synthetic procedure has involved an ultrasound assisted bromination in an aqueous medium using ionic liquid as a catalyst of the reaction, whereas in the second one an in situ formation of Br2 via oxidation of HBr by H2O2 has been used. For comparison, the conventional bromination procedure was also used. The newly brominated compounds were characterized by appropriate analytical techniques. A detailed NMR spectroscopic analysis and quantum chemical calculations using Density Functional Theory (DFT) methods have been used to define the stereochemistry of the products. The results confirmed the physicochemical identity and similar yields of the products obtained by the three synthetic procedures employed, and reveal the co-existence of two diastereoisomeric forms of the newly synthesized products. The antibacterial and antifungal activities of the dibrominated amides were evaluated.

NACA Conference on Aircraft Loads, Structures, and Flutter

NASA Technical Reports Server (NTRS)

1957-01-01

This document contains reproductions of technical papers on some of the most recent research results on aircraft loads, flutter, and structures from the NACA laboratories. These papers were presented by members of the staff of the NACA laboratories at the Conference held at the Langley Aeronautical Laboratory March 5, 6, and 7, 1957. The primary purpose of this Conference was to convey to contractors of the military services and others concerned with the design of aircraft these recent research results and to provide those attending an opportunity to discuss the results. The papers in this document are in the same form in which they were presented at the Conference in order to facilitate their prompt distribution. The original presentation and this record are considered as complementary to, rather than as substitutes for, the Committee?s more complete and formal reports. Accordingly, if information from this document is utilized it is requested that this document not be listed as a reference. Individual reports dealing with most of the information presented at the Conference will subsequently be published by NACA and will therefore be suitable as reference material.

A General and Selective Rhodium-Catalyzed Reduction of Amides, N-Acyl Amino Esters, and Dipeptides Using Phenylsilane.

PubMed

Das, Shoubhik; Li, Yuehui; Lu, Liang-Qiu; Junge, Kathrin; Beller, Matthias

2016-05-17

This article describes a selective reduction of functionalized amides, including N-acyl amino esters and dipeptides, to the corresponding amines using simple [Rh(acac)(cod)]. The catalyst shows excellent chemoselectivity in the presence of different sensitive functional moieties. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

N-Acetylcysteine and deferoxamine reduce pulmonary oxidative stress and inflammation in rats after coal dust exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pinho, R.A.; Silveira, P.C.L.; Silva, L.A.

2005-11-01

Coal dust inhalation induces oxidative damage and inflammatory infiltration on lung parenchyma. Thus, the aim of this study was to determine whether N-acetylcysteine (NAC) administered alone or in combination with deferoxamine (DFX), significantly reduced the inflammatory infiltration and oxidative damage in the lungs of rats exposed to coal dust. Forty-two male Wistar rats (200-250 g) were exposed to the coal dust (3 mg/0.5 mL saline, 3 days/week, for 3 weeks) by intratracheal instillation. The animals were randomly divided into three groups: saline 0.9% (n = 8), supplemented with NAC (20 mg/kg of body weight/day, intraperitoneal injection (i.p.)) (n = 8),more » and supplemented with NAC (20 mg/kg of body weight/day, i.p.) plus DFX (20 mg/kg of body weight/week) (n = 8). Control animals received only saline solution (0.5 mL). Lactate dehydrogenase activity and total cell number were determined in the bronchoalveolar lavage fluid. We determined lipid peroxidation and oxidative protein damage parameters and catalase and superoxide dismutase activities in the lungs of animals. Intratracheal instillation of coal dust in the lungs of rats led to an inflammatory response and induced significant oxidative damage. The administration of NAC alone or in association with DFX reduced the inflammatory response and the oxidative stress parameters in rats exposed to coal dust.« less

Earth's magnetic field enabled scalar coupling relaxation of 13C nuclei bound to fast-relaxing quadrupolar 14N in amide groups.

PubMed

Chiavazza, Enrico; Kubala, Eugen; Gringeri, Concetta V; Düwel, Stephan; Durst, Markus; Schulte, Rolf F; Menzel, Marion I

2013-02-01

Scalar coupling relaxation, which is usually only associated with closely resonant nuclei (e.g., (79)Br-(13)C), can be a very effective relaxation mechanism. While working on hyperpolarized [5-(13)C]glutamine, fast liquid-state polarization decay during transfer to the MRI scanner was observed. This behavior could hypothetically be explained by substantial T(1) shortening due to a scalar coupling contribution (type II) to the relaxation caused by the fast-relaxing quadrupolar (14)N adjacent to the (13)C nucleus in the amide group. This contribution is only effective in low magnetic fields (i.e., less than 800 μT) and prevents the use of molecules bearing the (13)C-amide group as hyperpolarized MRS/MRI probes. In the present work, this hypothesis is explored both theoretically and experimentally. The results show that high hyperpolarization levels can be retained using either a (15)N-labeled amide or by applying a magnetic field during transfer of the sample from the polarizer to the MRI scanner. Copyright © 2012 Elsevier Inc. All rights reserved.

A randomized controlled trial of pre-procedure simethicone and N-acetylcysteine to improve mucosal visibility during gastroscopy - NICEVIS.

PubMed

Basford, Peter John; Brown, James; Gadeke, Lisa; Fogg, Carole; Haysom-Newport, Ben; Ogollah, Reuben; Bhattacharyya, Rupam; Longcroft-Wheaton, Gaius; Thursby-Pelham, Fergus; Neale, James R; Bhandari, Pradeep

2016-11-01

Background and study aims: Mucosal views can be impaired by residual bubbles and mucus during gastroscopy. This study aimed to determine whether a pre-gastroscopy drink containing simethicone and N-acetylcysteine improves mucosal visualisation. Patients and methods: We conducted a randomized controlled trial recruiting 126 subjects undergoing routine gastroscopy. Subjects were randomized 1:1:1 to receive: A-pre-procedure drink of water, simethicone and N-acetylcysteine (NAC); B-water alone; or C-no preparation. Study endoscopists were blinded to group allocation. Digital images were taken at 4 locations (lower esophagus/upper gastric body/antrum/fundus), and rated for mucosal visibility (MV) using a 4-point scale (1 = best, 4 = worst) by 4 separate experienced endoscopists. The primary outcome measure was mean mucosal visibility score (MVS). Secondary outcome measures were procedure duration and volume of fluid flush required to achieve adequate mucosal views. Results: Mean MVS for Group A was significantly better than for Group B (1.35 vs 2.11, P  < 0.001) and Group C (1.35 vs 2.21, P  < 0.001). Mean flush volume required to achieve adequate mucosal views was significantly lower in Group A than Group B (2.0 mL vs 31.5 mL, P  = 0.001) and Group C (2.0 mL vs 39.2 mL P  < 0.001). Procedure duration did not differ significantly between any of the 3 groups. MV scores at each of the 4 locations demonstrated significantly better mucosal visibility in Group A compared to Group B and Group C ( P  < 0.0025 for all comparisons). Conclusions: A pre-procedure drink containing simethicone and NAC significantly improves mucosal visibility during gastroscopy and reduces the need for flushes during the procedure. Effectiveness in the lower esophagus demonstrates potential benefit in Barrett's oesophagus surveillance gastroscopy.

[EFFECT OF ACETYLCYSTEINE, CORVITIN AND THEIR COMBINATION ON THE FUNCTIONAL STATE OF LIVER IN RATS WITH PARACETAMOL INDUCED TOXIC HEPATITIS].

PubMed

Ghonghadze, M; Antelava, N; Liluashvili, K; Okujava, M; Pachkoria, K

2017-02-01

Nowadays drug-induced hepatotoxicity is urgent problem worldwide. Currently more than 1000 drugs are hepatotoxic and most often are the reason of acute fulminant hepatitis and hepatocellular failure, the states requiring liver transplantation. The paracetamol induced liver toxicity is related with accumulation of its toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI), which is the free radical and enhances peroxidation of lipids, disturbs the energy status and causes death of hepatocytes. During our research we investigated and assessed the efficacy of acetylcysteine, corvitin and their combination in rat model of paracetamol induced acute toxic hepatitis. The study was performed on mature white male Wistar rates with body mass 150-180 g. 50 rats were randomly divided into 5 groups (10 rats in each group). To get the model of acute toxic hepatitis single intraperitoneal injection of paracetamol solution was used (750 mg/kg). Toxic hepatitis was treated with intrapertoneal administration of 40mg/kg acetylcysteine or 100mg/kg corvitin, as well as with combination of these drugs. Monotherapy with acetylcysteine and corvitin of paracetamol induced toxic hepatitis improved the liver function, decreased relative mass of the liver and animal mortality. The treatment of toxic hepatitis was most effective in the case of simultaneous administration of acetylcysteine and corvitin. The normal value of laboratory tests (ALT, ACT, alkaline phosphatase, total and unconjugated bilirubin) was reached and mortality was not more observed. On the bases of obtained data was concluded that acetylcysteine and corvitin have almost equal hepatoprotective activity. The combination of two drugs actually improves the liver function. The most pronounced hepatoprotective effect may be due to synergic action of acetylcysteine and corvitin and such regime can be recommended for correction of liver function.

Application of novel Ni(II) complex and ZrO2 nanoparticle as mediators for electrocatalytic determination of N-acetylcysteine in drug samples.

PubMed

Karimi-Maleh, Hassan; Salehi, Mehdi; Faghani, Fatemeh

2017-10-01

The electrooxidation of N-acetylcysteine (N-AC) was studied by a novel Ni(II) complex modified ZrO 2 nanoparticle carbon paste electrode [Ni(II)/ZrO 2 /NPs/CPE] using voltammetric methods. The results showed that Ni(II)/ZrO 2 /NPs/CPE had high electrocatalytic activity for the electrooxidation of N-AC in aqueous buffer solution (pH = 7.0). The electrocatalytic oxidation peak currents increase linearly with N-AC concentrations over the concentration ranges of 0.05-600μM using square wave voltammetric methods. The detection limit for N-AC was equal to 0.009μM. The catalytic reaction rate constant, k h , was calculated (7.01 × 10 2  M -1  s -1 ) using the chronoamperometry method. Finally, Ni(II)/ZrO 2 /NPs/CPE was also examined as an ultrasensitive electrochemical sensor for the determination of N-AC in real samples such as tablet and urine. Copyright © 2017. Published by Elsevier B.V.

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

PubMed

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.

Effects of oral N-acetylcysteine on fatigue, critical power, and W' in exercising humans.

PubMed

Corn, Sarah D; Barstow, Thomas J

2011-09-15

The accumulation of reactive oxygen species (ROS) is associated with muscular fatigue. The antioxidant N-acetylcysteine (NAC) can extend time to fatigue (TTF), but the effect appears to be exercise intensity dependent. The purpose of this study was to determine the effects of an acute oral dose of NAC on time to fatigue (TTF), critical power (CP), W' (curvature constant), V(O2) kinetics and muscle EMG during cycling exercise. Male (n=7) subjects performed four tests at power outputs corresponding to 80, 90, 100, and 110% of the peak power output achieved during the incremental test (Pmax) under NAC and placebo (PLA) conditions. TTF was increased only in the 80% Pmax trial (p=0.033). CP was higher with NAC (NAC: 232±28 W versus PLA: 226±31 W; p=0.032), but W' tended to decrease (NAC: 15.5±3.8 kJ versus W': 16.4±4.5 kJ; p=0.10). The change in W' was negatively related to the change in CP (r = -0.96). MdPF and RMS of EMG tended to change less with NAC. There were no significant differences in V(O2) kinetics. These results demonstrate that oral NAC was successful in extending time to fatigue at 80% Pmax but not at higher work rates. Copyright © 2011 Elsevier B.V. All rights reserved.

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

PubMed

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.

Enantioselective Synthesis of α-Oxy Amides via Umpolung Amide Synthesis

PubMed Central

Leighty, Matthew W.; Shen, Bo

2012-01-01

α-Oxy amides are prepared through enantioselective synthesis using a sequence beginning with a Henry addition of bromonitromethane to aldehydes, and finishing with Umpolung Amide Synthesis (UmAS). Key to high enantioselection is the finding that ortho-iodo benzoic acid salts of the chiral copper(II) bis(oxazoline) catalyst deliver both diastereomers of the Henry adduct with high enantiomeric excess, homochiral at the oxygen-bearing carbon. Overall, this approach to α-oxy amides provides an innovative complement to alternatives that focus almost entirely on the enantioselective synthesis of α-oxy carboxylic acids. PMID:22967461

Enantioselective synthesis of α-oxy amides via Umpolung amide synthesis.

PubMed

Leighty, Matthew W; Shen, Bo; Johnston, Jeffrey N

2012-09-19

α-Oxy amides are prepared through enantioselective synthesis using a sequence beginning with a Henry addition of bromonitromethane to aldehydes and finishing with Umpolung Amide Synthesis (UmAS). Key to high enantioselection is the finding that ortho-iodo benzoic acid salts of the chiral copper(II) bis(oxazoline) catalyst deliver both diastereomers of the Henry adduct with high enantiomeric excess, homochiral at the oxygen-bearing carbon. Overall, this approach to α-oxy amides provides an innovative complement to alternatives that focus almost entirely on the enantioselective synthesis of α-oxy carboxylic acids.

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

PubMed

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.

Characterization of Ascentis RP-Amide column: Lipophilicity measurement and linear solvation energy relationships.

PubMed

Benhaim, Deborah; Grushka, Eli

2010-01-01

This study investigates lipophilicity determination by chromatographic measurements using the polar embedded Ascentis RP-Amide stationary phase. As a new generation of amide-functionalized silica stationary phase, the Ascentis RP-Amide column is evaluated as a possible substitution to the n-octanol/water partitioning system for lipophilicity measurements. For this evaluation, extrapolated retention factors, log k'w, of a set of diverse compounds were determined using different methanol contents in the mobile phase. The use of n-octanol enriched mobile phase enhances the relationship between the slope (S) of the extrapolation lines and the extrapolated log k'w (the intercept of the extrapolation),as well as the correlation between log P values and the extrapolated log k'w (1:1 correlation, r2 = 0.966).In addition, the use of isocratic retention factors, at 40% methanol in the mobile phase, provides a rapid tool for lipophilicity determination. The intermolecular interactions that contribute to the retention process in the Ascentis RP-Amide phase are characterized using the solvation parameter model of Abraham.The LSER system constants for the column are very similar to the LSER constants of the n-octanol/water extraction system. Tanaka radar plots are used for quick visual comparison of the system constants of the Ascentis RP-Amide column and the n-octanol/water extraction system. The results all indicate that the Ascentis RP-Amide stationary phase can provide reliable lipophilic data. Copyright 2009 Elsevier B.V. All rights reserved.

Biosynthesis, degradation and pharmacological importance of the fatty acid amides.

PubMed

Farrell, Emma K; Merkler, David J

2008-07-01

The identification of two biologically active fatty acid amides, N-arachidonoylethanolamine (anandamide) and oleamide, has generated a great deal of excitement and stimulated considerable research. However, anandamide and oleamide are merely the best-known and best-understood members of a much larger family of biologically occurring fatty acid amides. In this review, we will outline which fatty acid amides have been isolated from mammalian sources, detail what is known about how these molecules are made and degraded in vivo, and highlight their potential for the development of novel therapeutics.

Biosynthesis, degradation, and pharmacological importance of the fatty acid amides

PubMed Central

Farrell, Emma K.; Merkler, David J.

2008-01-01

The identification of two biologically active fatty acid amides, N-arachidonoylethanolamine (anandamide) and oleamide, has generated a great deal of excitement and stimulated considerable research. However, anandamide and oleamide are merely the best-known and best-understood members of a much larger family of biologically-occurring fatty acid amides. In this review, we will outline which fatty acid amides have been isolated from mammalian sources, detail what is known about how these molecules are made and degraded in vivo, and highlight their potential for the development of novel therapeutics. PMID:18598910

Acetylcysteine for prevention of contrast-induced nephropathy after intravascular angiography: A systematic review and meta-analysis

PubMed Central

Bagshaw, Sean M; Ghali, William A

2004-01-01

Background Contrast-induced nephropathy is an important cause of acute renal failure. We assess the efficacy of acetylcysteine for prevention of contrast-induced nephropathy among patients undergoing intravascular angiography. Methods We conducted a systematic review and meta-analysis of randomized controlled trials comparing prophylactic acetylcysteine plus hydration versus hydration alone in patients undergoing intravascular angiography. Studies were identified by searching MEDLINE, EMBASE, and CENTRAL databases. Our main outcome measures were the risk of contrast-induced nephropathy and the difference in serum creatinine between acetylcysteine and control groups at 48 h. Results Fourteen studies involving 1261 patients were identified and included for analysis, and findings were heterogeneous across studies. Acetylcysteine was associated with a significantly reduced incidence of contrast-induced nephropathy in five studies, and no difference in the other nine (with a trend toward a higher incidence in six of the latter studies). The pooled odds ratio for contrast-induced nephropathy with acetylcysteine relative to control was 0.54 (95% CI, 0.32–0.91, p = 0.02) and the pooled estimate of difference in 48-h serum creatinine for acetylcysteine relative to control was -7.2 μmol/L (95% CI -19.7 to 5.3, p = 0.26). These pooled values need to be interpreted cautiously because of the heterogeneity across studies, and due to evidence of publication bias. Meta-regression suggested that the heterogeneity might be partially explained by whether the angiography was performed electively or as emergency. Conclusion These findings indicate that published studies of acetylcysteine for prevention of contrast-induced nephropathy yield inconsistent results. The efficacy of acetylcysteine will remain uncertain unless a large well-designed multi-center trial is performed. PMID:15500690

Historical perspectives on thermostructural research at the NACA Langley Aeronautical Laboratory from 1948 to 1958

NASA Technical Reports Server (NTRS)

Heldenfels, R. R.

1982-01-01

Some of the early research on structural problems produced by aerodynamic heating, conducted at the Langley Aeronautical Laboratory of the National Advisory Committee for Aeronautics from 1948 to 1958 is described. That was the last decade of the NACA; in 1958 NACA became the nucleus of NASA. The NACA initially contracted for research but was aware that a well-equipped and suitably staffed laboratory was required to fulfill its obligations. Langley was established in 1920; the other listed were added during the NACA expansion in the World War II years. Some specific research activities are described, starting with calculation of the temperature of the structure.

Historical perspectives on thermostructural research at the NACA Langley Aeronautical Laboratory from 1948 to 1958

NASA Astrophysics Data System (ADS)

Heldenfels, R. R.

Some of the early research on structural problems produced by aerodynamic heating, conducted at the Langley Aeronautical Laboratory of the National Advisory Committee for Aeronautics from 1948 to 1958 is described. That was the last decade of the NACA; in 1958 NACA became the nucleus of NASA. The NACA initially contracted for research but was aware that a well-equipped and suitably staffed laboratory was required to fulfill its obligations. Langley was established in 1920; the other listed were added during the NACA expansion in the World War II years. Some specific research activities are described, starting with calculation of the temperature of the structure.

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

PubMed

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.

N-acetylcysteine and acute retinal laser lesions in the colubrid snake eye

NASA Astrophysics Data System (ADS)

Elliott, William R., III; Rentmeister-Bryant, Heike K.; Barsalou, Norman; Beer, Jeremy; Zwick, Harry

2004-07-01

This study examined the role of oxidative stress and the effect of a single dose treatment with N-Acetylcysteine (NAC) on the temporal development of acute laser-induced retinal injury. We used the snake eye/Scanning Laser Ophthalmoscope (SLO) model, an in vivo, non-invasive ocular imaging technique, which has the ability to image cellular retinal detail and allows for studying morphological changes of retinal injury over time. For this study 12 corn-snakes (Elaphe g. guttata) received 5 laser exposures per eye, followed by either a single dose of the antioxidant NAC (150mg/kg, IP in sterile saline) or placebo. Laser exposures were made with a Nd: VO4 DPSS, 532nm laser, coaxially aligned to the SLO. Shuttered pulses were 20msec x 50 mW; 1mJ each. Retinal images were taken using a Rodenstock cSLO and were digitally recorded at 1, 6, 24-hrs, and at 3-wks post-exposure. Lesions were assessed by two raters blind to the conditions of the study yielding measures of damaged area and counts of missing or damaged photoreceptors. Treated eyes showed a significant beneficial effect overall, and these results suggest that oxidative stress plays a role in laser-induced retinal injury. The use of NAC or a similar antioxidant shows promise as a therapeutic tool.

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

PubMed

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.

α-Fluorovinyl Weinreb Amides and α- Fluoroenones from a Common Fluorinated Building Block

PubMed Central

Ghosh, Arun K.; Banerjee, Shaibal; Sinha, Saikat; Kang, Soon Bang; Zajc, Barbara

2009-01-01

Synthesis and reactivity of N-methoxy-N-methyl-(1,3-benzothiazol-2-ylsulfonyl)fluoroacetamide, a building block for Julia olefination, is reported. This reagent undergoes condensation reactions with aldehydes and cyclic ketones, to give α-fluorovinyl Weinreb amides. Olefination reactions proceed under mild, DBU-mediated conditions, or in the presence of NaH. DBU-mediated condensations proceed with either E or Z-selectivity, depending upon reaction conditions, whereas NaH-mediated reactions are ≥98% Z-stereoselective. Conversion of the Weinreb amide moiety in N-methoxy-N-methyl-(1,3-benzothiazol-2-ylsulfanyl)fluoroacetamide to ketones, followed by oxidation, resulted in another set of olefination reagents, namely (1,3-benzothiazol-2-ylsulfonyl)fluoromethyl phenyl and propyl ketones. In the presence of DBU, these compounds react with aldehydes tested to give α-fluoroenones with high Z-selectivity. The use of N-methoxy-N-methyl-(1,3-benzothiazol-2-ylsulfanyl)fluoroacetamide as a common fluorinated intermediate in the synthesis of α-fluorovinyl Weinreb amides and α-fluoroenones has been demonstrated. Application of the Weinreb amide to α-fluoro allyl amine synthesis is also shown. PMID:19361189

NACA: 25 Years of Flight Research

NASA Image and Video Library

2018-05-10

A narrated film documentary of flight tests at the NACA and NASA’s Flight Research Center shows the X-1, D-558-II, X-3, X-4, X-5, and X-15 in flight and on the ground. The story describes what each aircraft contributed to flight’s expansion.

N-acetylcysteine reduces the renal oxidative stress and apoptosis induced by hemorrhagic shock.

PubMed

Moreira, Miriam Aparecida; Irigoyen, Maria Claudia; Saad, Karen Ruggeri; Saad, Paulo Fernandes; Koike, Marcia Kiyomi; Montero, Edna Frasson de Souza; Martins, José Luiz

2016-06-01

Renal ischemia/reperfusion injury induced by hemorrhagic shock (HS) and subsequent fluid resuscitation is a common cause of acute renal failure. The objective of this study was to evaluate the effect of combining N-acetylcysteine (NAC) with fluid resuscitation on renal injury in rats that underwent HS. Two groups of male Wistar rats were induced to controlled HS at 35 mm Hg mean arterial pressure for 60 min. After this period, the HS and fluid resuscitation (HS/R) group was resuscitated with lactate containing 50% of the blood that was withdrawn. The HS/R + NAC group was resuscitated with Ringer's lactate combined with 150 mg/kg of NAC and blood. The sham group animals were catheterized but were not subjected to shock. All animals were kept under anesthesia and euthanized after 120 min of fluid resuscitation or observation. Animals treated with NAC presented attenuation of histologic lesions, reduced oxidative stress, and apoptosis markers when compared with animals from the HS/R group. The serum creatinine was similar in all the groups. NAC is a promising drug for combining with fluid resuscitation to attenuate the kidney injury associated with HS. Copyright © 2016 Elsevier Inc. All rights reserved.

Compatibility and osmolality of inhaled N-acetylcysteine nebulizing solution with fenoterol and ipratropium.

PubMed

Lee, Tzung-Yi; Chen, Chi-Ming; Lee, Chun-Nin; Chiang, Yi-Chun; Chen, Hsiang-Yin

2005-04-15

The compatibility, pH, and osmolality of N-acetylcysteine (NAC) nebulizing solution in the presence of ipratropium bromide or fenoterol hydrobromide were studied. Portions (400 microL) of each mixture were sampled immediately upon mixing and one, two, three, four, five, six, and seven hours after mixing and assayed by high-performance liquid chromatography. Osmolality was measured by sampling 100 microL from the filling cup at a five-minute interval during nebulization and by the freezing-point-depression method. Adding NAC solution to fenoterol solution raised the pH from 3.20 to 7.90 and the osmolality to a mean +/- S.D. of 1400.67 +/- 4.51 mOsm/kg. Fenoterol concentrations decreased to 93.71% and NAC concentrations to 92.54% of initial concentrations after seven hours. Mixing ipratropium with NAC solution raised the pH from 3.74 to 7.95 and the osmolality to a mean +/- S.D. of 1413 +/- 11.79 mOsm/kg. The initial ipratropium concentration declined 7.39% and 10.91% one and two hours after mixing with NAC solution, respectively. NAC and ipratropium were stable in nebulizing solution within one hour of mixing. NAC and fenoterol were compatible for at least seven hours.

Assessment of N-acetylcysteine as a therapy for phosgene-induced acute lung injury.

PubMed

Rendell, Rachel; Fairhall, Sarah; Graham, Stuart; Rutter, Steve; Auton, Philippa; Smith, Adam; Perrott, Rosi; Jugg, Bronwen

2018-06-15

The toxic industrial chemical (TIC 1 ) phosgene remains an important chemical intermediate in many industrial processes. Inhalation of phosgene can cause an acute lung injury (ALI) which, in severe cases may result in death. There are currently no effective pharmacological therapies or evidence-based treatment guidelines for managing exposed individuals. N-acetylcysteine (NAC) is a commercially available drug licensed in the UK and elsewhere for the treatment of paracetamol (acetaminophen) overdose. It has a number of mechanisms of action which may provide therapeutic benefit for the treatment of phosgene-induced ALI. It has previously been shown to provide therapeutic efficacy against the lung damaging effects of sulfur mustard vapour exposure, when given by the inhaled route, in the pig (Jugg et al., 2013). Our research objective was to determine whether inhaled NAC might also be therapeutic for other chemicals, in this case, phosgene. This study has demonstrated that multiple nebulised doses, administered from 30 min after exposure of terminally anaesthetised pigs to phosgene, is not an effective therapy when administered at the times and doses employed in this study. There remains no pharmacological treatment for phosgene-induced lung injury. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

Design, Synthesis, and Biological Evaluation of Peptidomimetic N-Substituted Cbz-4-Hyp-Hpa-Amides as Novel Inhibitors of Plasmodium falciparum.

PubMed

Bacherikov, Valeriy A; Chittiboyina, Amar G; Avery, Mitchell A

2017-08-01

A new series of peptidomimetic N-substituted Cbz-4-Hyp-Hpa-amides were designed, synthesized, and evaluated for inhibition of the Plasmodium falciparum. Substituents on the N-atom of the amide group were selected alkyl-, allyl-, aryl-, 2-hydroxyethyl-, 2-cyanoethyl-, cyanomethyl-, 2-hydroxyethyl-, 2,2-diethoxyethyl-, or 2-ethoxy-2-oxoethylamino groups, and about of 40 new compounds were synthesized and evaluated for antiplasmodial activity in vitro. Antimalarial activity has been investigated as for the final peptide mimetics, and their immediate predecessors, carrying TBDMS or TBDPS protecting groups on 4-hydroxyproline residue and 18 derivatives exhibited toxicity against P. falciparum. Of these agents, compound 23e was shown to have potent antimalarial activity with IC 50 528 ng/ml. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

[The role of N-acetylcysteine against the injury of pulmonary artery induced by LPS].

PubMed

Huang, Xin-li; Ling, Yi-ling; Zhu, Tie-nian

2002-11-01

To investigate the alleviating effect of N-acetylcysteine (NAC) on lung injury induced by lipopolysaccharides (LPS) and its mechanism. The effects of NAC on changes of the pulmonary arterial reactivity and the ultrastructure of pulmonary arterial endothelium induced by LPS were observed with the isolated artery ring technique and scanning electron microscope (SEM). Malondialdehyde (MDA), nitric oxide (NO) contents and superoxide dismutase (SOD) activity of pulmonary artery tissues were detected. The exposure of pulmonary artery to LPS (4 microg/ml, 7 h) led to reduction of endothelium-dependent relaxation response to acetylcholine (ACh), which was reversed by the concomitant exposure to NAC (0.5 mmol/L, 7 h), whereas NAC itself had no effect on the response. Significant structural injury were observed under SEM in LPS group and alleviated the changes in LPS + NAC group. The MDA, NO contents increased but SOD activity decreased in LPS group, which were reversed by the concomitant exposure to NAC. NAC protects pulmonary artery endothelium and enhances endothelium-dependent relaxation response of pulmonary artery by antioxidation effect, which may be one of the mechanisms of its reversing pulmonary artery hypertension and following lung injury induced by LPS.

Orientation and Order of the Amide Group of Sphingomyelin in Bilayers Determined by Solid-State NMR

PubMed Central

Matsumori, Nobuaki; Yamaguchi, Toshiyuki; Maeta, Yoshiko; Murata, Michio

2015-01-01

Sphingomyelin (SM) and cholesterol (Chol) are considered essential for the formation of lipid rafts; however, the types of molecular interactions involved in this process, such as intermolecular hydrogen bonding, are not well understood. Since, unlike other phospholipids, SM is characterized by the presence of an amide group, it is essential to determine the orientation of the amide and its order in the lipid bilayers to understand the nature of the hydrogen bonds in lipid rafts. For this study, 1′-13C-2-15N-labeled and 2′-13C-2-15N-labeled SMs were prepared, and the rotational-axis direction and order parameters of the SM amide in bilayers were determined based on 13C and 15N chemical-shift anisotropies and intramolecular 13C-15N dipole coupling constants. Results revealed that the amide orientation was minimally affected by Chol, whereas the order was enhanced significantly in its presence. Thus, Chol likely promotes the formation of an intermolecular hydrogen-bond network involving the SM amide without significantly changing its orientation, providing a higher order to the SM amide. To our knowledge, this study offers new insight into the significance of the SM amide orientation with regard to molecular recognition in lipid rafts, and therefore provides a deeper understanding of the mechanism of their formation. PMID:26083921

N-acetylcysteine for therapy-resistant tobacco use disorder: a pilot study.

PubMed

Prado, Eduardo; Maes, Michael; Piccoli, Luiz Gustavo; Baracat, Marcela; Barbosa, Décio Sabattini; Franco, Olavo; Dodd, Seetal; Berk, Michael; Vargas Nunes, Sandra Odebrecht

2015-09-01

N-Acetylcysteine (NAC) may have efficacy in treating tobacco use disorder (TUD) by reducing craving and smoking reward. This study examines whether treatment with NAC may have a clinical efficacy in the treatment of TUD. A 12-week double blind randomized controlled trial was conducted to compare the clinical efficacy of NAC 3 g/day versus placebo. We recruited 34 outpatients with therapy resistant TUD concurrently treated with smoking-focused group behavioral therapy. Participants had assessments of daily cigarette use (primary outcome), exhaled carbon monoxide (CO(EXH)) (secondary outcome), and quit rates as defined by CO(EXH) < 6 ppm. Depression was measured with the Hamilton Depression Rating Scale (HDRS). Data were analyzed using conventional and modified intention-to-treat endpoint analyses. NAC treatment significantly reduced the daily number of cigarettes used (Δ mean ± SD = -10.9 ± 7.9 in the NAC-treated versus -3.2 ± 6.1 in the placebo group) and CO(EXH) (Δ mean ± SD = -10.4 ± 8.6 ppm in the NAC-treated versus -1.5 ± 4.5 ppm in the placebo group); 47.1% of those treated with NAC versus 21.4% of placebo-treated patients were able to quit smoking as defined by CO(EXH) < 6 ppm. NAC treatment significantly reduced the HDRS score in patients with tobacco use disorder. These data show that treatment with NAC may have a clinical efficacy in TUD. NAC combined with appropriate psychotherapy appears to be an efficient treatment option for TUD.

N-acetylcysteine Protects Mice from High Fat Diet-induced Metabolic Disorders.

PubMed

Ma, Yongjie; Gao, Mingming; Liu, Dexi

2016-08-01

To study the effects of N-acetylcysteine (NAC, C5H9NO3S) on diet-induced obesity and obesity-related metabolic disorders. Six-week-old male C57BL/6 mice fed a chow or high-fat diet (HFD) were treated with NAC (2 g/L) in drinking water for 11 weeks. Its influences on body weight and food intake were manually measured, and influence on body composition were analyzed by magnetic residence imaging. Glucose meter and ELISA were used to determine serum glucose and insulin levels, as well as lipid content in the liver. The effects of NAC treatment on mRNA levels of genes involved in inflammation, thermogenesis, and lipid metabolism in various tissues were determined by real time PCR. NAC supplementation inhibited the increase of fat mass and the development of obesity when mice were fed an HFD. NAC treatment significantly lowered HFD-induced macrophage infiltration, and enhanced adiponectin gene expression, resulting in reduced hyperglycemia and hyperinsulinemia, and improvement of insulin resistance. NAC oral administration suppressed hepatic lipid accumulation, as evidenced by lower levels of triglyceride and cholesterol in the liver. The beneficial effects are associated with a decrease of hepatic Pparγ and its target gene expression, and an increase in the expression of genes responsible for lipid oxidation and activation of farnesoid X receptor. Furthermore, NAC treatment also stimulates expression of thermogenic genes. These results provide direct proof of the protective potential of NAC against HFD-induced obesity and obesity-associated metabolic disorders.

Effects of N-acetylcysteine on semen parameters and oxidative/antioxidant status.

PubMed

Ciftci, Halil; Verit, Ayhan; Savas, Murat; Yeni, Ercan; Erel, Ozcan

2009-07-01

To examine whether a beneficial effect of N-acetylcysteine (NAC) on semen parameters and oxidative/antioxidant status in idiopathic male infertility exists. The production of reactive oxygen species is a normal physiologic event in various organs. However, overproduction of reactive oxygen species can be detrimental to sperm and has been associated with male infertility. Our study included 120 patients who had attended our clinic and were diagnosed with idiopathic infertility according to medical history and physical and seminal examination findings, as initial evaluations. The patients were divided randomly into 2 groups. Those in the study group (60 men) were given NAC (600 mg/d orally) for 3 months; the control group (60 men) received a placebo. The oxidative status was determined by measuring the total antioxidant capacity, total peroxide and oxidative stress index in plasma samples. The sperm parameters were evaluated after NAC treatment and were compared with those in the control group. NAC had significant improving effects on the volume, motility, and viscosity of semen. After NAC treatment, the serum total antioxidant capacity was greater and the total peroxide and oxidative stress index were lower in the NAC-treated group compared with the control group. These beneficial effects resulted from reduced reactive oxygen species in the serum and reduced viscosity of the semen. No significant differences were found in the number or morphology of the sperm between the 2 groups. We believe that NAC could improve some semen parameters and the oxidative/antioxidant status in patients with male infertility.

Aerodynamic data banks for Clark-Y, NACA 4-digit and NACA 16-series airfoil families

NASA Technical Reports Server (NTRS)

Korkan, K. D.; Camba, J., III; Morris, P. M.

1986-01-01

With the renewed interest in propellers as means of obtaining thrust and fuel efficiency in addition to the increased utilization of the computer, a significant amount of progress was made in the development of theoretical models to predict the performance of propeller systems. Inherent in the majority of the theoretical performance models to date is the need for airfoil data banks which provide lift, drag, and moment coefficient values as a function of Mach number, angle-of-attack, maximum thickness to chord ratio, and Reynolds number. Realizing the need for such data, a study was initiated to provide airfoil data banks for three commonly used airfoil families in propeller design and analysis. The families chosen consisted of the Clark-Y, NACA 16 series, and NACA 4 digit series airfoils. The various component of each computer code, the source of the data used to create the airfoil data bank, the limitations of each data bank, program listing, and a sample case with its associated input-output are described. Each airfoil data bank computer code was written to be used on the Amdahl Computer system, which is IBM compatible and uses Fortran.

Amides in Nature and Biocatalysis.

PubMed

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.

Acute chloroform ingestion successfully treated with intravenously administered N-acetylcysteine.

PubMed

Dell'Aglio, Damon M; Sutter, Mark E; Schwartz, Michael D; Koch, David D; Algren, D A; Morgan, Brent W

2010-06-01

Chloroform, a halogenated hydrocarbon, causes central nervous system depression, cardiac arrhythmias, and hepatotoxicity. We describe a case of chloroform ingestion with a confirmatory serum level and resultant hepatotoxicity successfully treated with intravenously administered N-acetylcysteine (NAC). A 19-year-old man attempting suicide ingested approximately 75 mL of chloroform. He was unresponsive and intubated upon arrival. Intravenously administered NAC was started after initial stabilization was complete. His vital signs were normal. Admission laboratory values revealed normal serum electrolytes, AST, ALT, PT, BUN, creatinine, and bilirubin. Serum ethanol level was 15 mg/dL, and aspirin and acetaminophen were undetectable. The patient was extubated but developed liver function abnormalities with a peak AST of 224 IU/L, ALT of 583 IU/L, and bilirubin level reaching 16.3 mg/dL. NAC was continued through hospital day 6. Serum chloroform level obtained on admission was 91 μg/mL. The patient was discharged to psychiatry without known sequelae and normal liver function tests. The average serum chloroform level in fatal cases of inhalational chloroform poisoning was 64 μg/mL, significantly lower than our patient. The toxicity is believed to be similar in both inhalation and ingestion routes of exposure, with mortality predominantly resulting from anoxia secondary to central nervous system depression. Hepatocellular toxicity is thought to result from free radical-induced oxidative damage. Previous reports describe survival after treatment with orally administered NAC, we report the first use of intravenously administered NAC for chloroform ingestion. Acute oral ingestion of chloroform is extremely rare. Our case illustrates that with appropriate supportive care, patients can recover from chloroform ingestion, and intravenously administered NAC may be of benefit in such cases.

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

PubMed Central

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 < 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). Conclusions Through its immuno-modulatory and cardioprotective properties, NAC has beneficial effect on pulmonary vascular and right heart function in experimental PH. PMID:24929652

A randomized controlled trial of pre-procedure simethicone and N-acetylcysteine to improve mucosal visibility during gastroscopy – NICEVIS

PubMed Central

Basford, Peter John; Brown, James; Gadeke, Lisa; Fogg, Carole; Haysom-Newport, Ben; Ogollah, Reuben; Bhattacharyya, Rupam; Longcroft-Wheaton, Gaius; Thursby-Pelham, Fergus; Neale, James R.; Bhandari, Pradeep

2016-01-01

Background and study aims: Mucosal views can be impaired by residual bubbles and mucus during gastroscopy. This study aimed to determine whether a pre-gastroscopy drink containing simethicone and N-acetylcysteine improves mucosal visualisation. Patients and methods: We conducted a randomized controlled trial recruiting 126 subjects undergoing routine gastroscopy. Subjects were randomized 1:1:1 to receive: A—pre-procedure drink of water, simethicone and N-acetylcysteine (NAC); B—water alone; or C—no preparation. Study endoscopists were blinded to group allocation. Digital images were taken at 4 locations (lower esophagus/upper gastric body/antrum/fundus), and rated for mucosal visibility (MV) using a 4-point scale (1 = best, 4 = worst) by 4 separate experienced endoscopists. The primary outcome measure was mean mucosal visibility score (MVS). Secondary outcome measures were procedure duration and volume of fluid flush required to achieve adequate mucosal views. Results: Mean MVS for Group A was significantly better than for Group B (1.35 vs 2.11, P < 0.001) and Group C (1.35 vs 2.21, P < 0.001). Mean flush volume required to achieve adequate mucosal views was significantly lower in Group A than Group B (2.0 mL vs 31.5 mL, P = 0.001) and Group C (2.0 mL vs 39.2 mL P < 0.001). Procedure duration did not differ significantly between any of the 3 groups. MV scores at each of the 4 locations demonstrated significantly better mucosal visibility in Group A compared to Group B and Group C (P < 0.0025 for all comparisons). Conclusions: A pre-procedure drink containing simethicone and NAC significantly improves mucosal visibility during gastroscopy and reduces the need for flushes during the procedure. Effectiveness in the lower esophagus demonstrates potential benefit in Barrett’s oesophagus surveillance gastroscopy. PMID:27853746

A Multi-center Comparison of the Safety of Oral versus Intravenous Acetylcysteine for Treatment of Acetaminophen Overdose

PubMed Central

2010-01-01

Oral and intravenous (IV) acetylcysteine are used for treatment of acetaminophen poisoning. The objective of this multi-center study was to compare the safety of these two routes of administration. METHODS We conducted a multi-center chart review of all patients treated with acetylcysteine for acetaminophen poisoning. The primary safety outcome was the percentage of patients with of acetylcysteine-related adverse events. RESULTS A total of 503 subjects were included in the safety analysis (306 IV only, 145 oral only and 52 both routes).There were no serious adverse events related to acetylcysteine for either route. Nausea and vomiting were the most common related adverse events and were more common with oral treatment (23% vs 9%). Anaphylactoid reactions were more common with IV administration (6% vs 2%). Conclusions Intravenous and oral acetylcysteine are both associated with minimal side effects and are safe for treatment of acetaminophen toxicity. PMID:20524832

Rocket Propellant Talk at the 1957 NACA Lewis Inspection

NASA Image and Video Library

1957-10-21

A researcher works a demonstration board in the Rocket Engine Test Facility during the 1957 Inspection of the National Advisory Committee for Aeronautics (NACA) Lewis Flight Propulsion Laboratory in Cleveland, Ohio. Representatives from the military, aeronautical industry, universities, and the press were invited to the laboratory to be briefed on the NACA’s latest research efforts and tour the test facilities. Over 1700 people visited the Lewis during the October 7-10, 1957 Inspection. The Soviet Union launched their first Sputnik satellite just days before on October 4. NACA Lewis had been involved in small rockets and propellants research since 1945, but the NACA leadership was wary of involving itself too deeply with the work since ballistics traditionally fell under the military’s purview. The Lewis research was performed by the High Temperature Combustion section in the Fuels and Lubricants Division in a series of small cinderblock test cells. The rocket group was expanded in 1952 and made several test runs in late 1954 using liquid hydrogen as a propellant. A larger test facility, the Rocket Engine Test Facility, was approved and became operational just in time for the Inspection.

Backbone amide 15N chemical shift tensors report on hydrogen bonding interactions in proteins: A magic angle spinning NMR study.

PubMed

Paramasivam, Sivakumar; Gronenborn, Angela M; Polenova, Tatyana

2018-08-01

Chemical shift tensors (CSTs) are an exquisite probe of local geometric and electronic structure. 15 N CST are very sensitive to hydrogen bonding, yet they have been reported for very few proteins to date. Here we present experimental results and statistical analysis of backbone amide 15 N CSTs for 100 residues of four proteins, two E. coli thioredoxin reassemblies (1-73-(U- 13 C, 15 N)/74-108-(U- 15 N) and 1-73-(U- 15 N)/74-108-(U- 13 C, 15 N)), dynein light chain 8 LC8, and CAP-Gly domain of the mammalian dynactin. The 15 N CSTs were measured by a symmetry-based CSA recoupling method, ROCSA. Our results show that the principal component δ 11 is very sensitive to the presence of hydrogen bonding interactions due to its unique orientation in the molecular frame. The downfield chemical shift change of backbone amide nitrogen nuclei with increasing hydrogen bond strength is manifested in the negative correlation of the principal components with hydrogen bond distance for both α-helical and β-sheet secondary structure elements. Our findings highlight the potential for the use of 15 N CSTs in protein structure refinement. Copyright © 2018 Elsevier Inc. All rights reserved.

Improvement of cognitive function in schizophrenia with N-acetylcysteine: A theoretical review.

PubMed

Yolland, Caitlin O B; Phillipou, Andrea; Castle, David J; Neill, Erica; Hughes, Matthew E; Galletly, Cherrie; Smith, Zoe M; Francis, Paul S; Dean, Olivia M; Sarris, Jerome; Siskind, Dan; Harris, Anthony W F; Rossell, Susan L

2018-05-30

Schizophrenia is a debilitating psychiatric illness associated with positive and negative symptoms as well as significant impairments in cognition. Current antipsychotic medications do not alleviate these cognitive deficits, and more effective therapeutic options are required. Increased oxidative stress and altered antioxidant levels, including glutathione (GSH) have been observed both in individuals with cognitive impairment and in people with schizophrenia. A GSH precursor, the antioxidant N-acetylcysteine (NAC) has been investigated as a novel treatment for the cognitive symptoms of schizophrenia, and recent research suggests that NAC may be a promising adjunctive treatment option. However, the current literature lacks integration as to why NAC may effectively improve cognition in schizophrenia. The present theoretical synthesis aimed to address this gap by examining the processes by which NAC may improve cognitive function in schizophrenia. The schizophrenia literature was reviewed in three key domains: cognitive impairment, the relationship between oxidative stress and cognition, and the efficacy of NAC as a novel treatment. This led to a theoretical analysis of the neurobiological processes by which NAC may improve cognition in schizophrenia. This theoretical review concluded that improved cognition may result from a combination of factors, including decreased oxidative stress, neuroprotection of cognitive networks and an increase in glutamatergic modulation of the N-methyl-d-aspartate receptor system. Whilst a number of mechanisms by which NAC may improve cognition and symptoms in schizophrenia have been proposed, there is still limited understanding of the specific metabolic pathways involved and how they interrelate and modify specific symptomology. Exploration of how NAC treatment may act to improve cognitive function could guide clinical trials by investigation of the specific neurotransmitter systems and processes involved, allowing for targeted

Safety and tolerability of acetylcysteine and pirfenidone combination therapy in idiopathic pulmonary fibrosis: a randomised, double-blind, placebo-controlled, phase 2 trial.

PubMed

Behr, Jürgen; Bendstrup, Elisabeth; Crestani, Bruno; Günther, Andreas; Olschewski, Horst; Sköld, C Magnus; Wells, Athol; Wuyts, Wim; Koschel, Dirk; Kreuter, Michael; Wallaert, Benoît; Lin, Chin-Yu; Beck, Jürgen; Albera, Carlo

2016-06-01

Oral acetylcysteine (also known as N-acetylcysteine) is used with pirfenidone to treat idiopathic pulmonary fibrosis (IPF) in Europe. However, no randomised studies have investigated the safety and tolerability of this combination. The PANORAMA study assessed the safety and tolerability of acetylcysteine combined with pirfenidone in patients with IPF. Exploratory efficacy endpoints were also assessed. We did a double-blind randomised trial at 48 sites in eight countries. Patients with IPF aged 40-80 years and established on pirfenidone (at least 1602 mg/day for 8 weeks or longer) were randomly assigned in a 1:1 ratio by interactive voice response system to receive concomitant oral acetylcysteine (600 mg, three times daily) or placebo for 24 weeks. A stratified blocked randomisation scheme was used with a block size of 4. Randomisation was stratified by dose of pirfenidone (2403 mg/day [the maximum dose] or <2403 mg/day). Patients, physicians, study staff and the sponsor were masked to treatment group allocation. The primary endpoint was assessment of adverse events, which were collected at each visit and for 28 days after the last dose of study drug. Exploratory efficacy measurements included forced vital capacity (FVC), carbon monoxide diffusing capacity, and 6 min walk distance. Analyses were done in the modified intention-to-treat population, which included all patients who were randomised and received at least one dose of study medication. This study is registered with the European Clinical Trials Database (EudraCT number 2012-000564-14) and has been completed. 123 patients participated in the study between June 28, 2013, and Feb 24, 2015. 61 were assigned to the acetylcysteine group (60 received study medication and included in analysis) and 62 were assigned to the placebo group (all included in analysis). The occurrence of at least one adverse event (46 [77%] patients receiving acetylcysteine vs 50 [81%] receiving placebo), adverse events related to study

Apoptosis-inducing Factor (AIF) and Its Family Member Protein, AMID, Are Rotenone-sensitive NADH:Ubiquinone Oxidoreductases (NDH-2)*

PubMed Central

Elguindy, Mahmoud M.; Nakamaru-Ogiso, Eiko

2015-01-01

Apoptosis-inducing factor (AIF) and AMID (AIF-homologous mitochondrion-associated inducer of death) are flavoproteins. Although AIF was originally discovered as a caspase-independent cell death effector, bioenergetic roles of AIF, particularly relating to complex I functions, have since emerged. However, the role of AIF in mitochondrial respiration and redox metabolism has remained unknown. Here, we investigated the redox properties of human AIF and AMID by comparing them with yeast Ndi1, a type 2 NADH:ubiquinone oxidoreductase (NDH-2) regarded as alternative complex I. Isolated AIF and AMID containing naturally incorporated FAD displayed no NADH oxidase activities. However, after reconstituting isolated AIF or AMID into bacterial or mitochondrial membranes, N-terminally tagged AIF and AMID displayed substantial NADH:O2 activities and supported NADH-linked proton pumping activities in the host membranes almost as efficiently as Ndi1. NADH:ubiquinone-1 activities in the reconstituted membranes were highly sensitive to 2-n-heptyl-4-hydroxyquinoline-N-oxide (IC50 = ∼1 μm), a quinone-binding inhibitor. Overexpressing N-terminally tagged AIF and AMID enhanced the growth of a double knock-out Escherichia coli strain lacking complex I and NDH-2. In contrast, C-terminally tagged AIF and NADH-binding site mutants of N-terminally tagged AIF and AMID failed to show both NADH:O2 activity and the growth-enhancing effect. The disease mutant AIFΔR201 showed decreased NADH:O2 activity and growth-enhancing effect. Furthermore, we surprisingly found that the redox activities of N-terminally tagged AIF and AMID were sensitive to rotenone, a well known complex I inhibitor. We propose that AIF and AMID are previously unidentified mammalian NDH-2 enzymes, whose bioenergetic function could be supplemental NADH oxidation in cells. PMID:26063804

Apoptosis-inducing Factor (AIF) and Its Family Member Protein, AMID, Are Rotenone-sensitive NADH:Ubiquinone Oxidoreductases (NDH-2).

PubMed

Elguindy, Mahmoud M; Nakamaru-Ogiso, Eiko

2015-08-21

Apoptosis-inducing factor (AIF) and AMID (AIF-homologous mitochondrion-associated inducer of death) are flavoproteins. Although AIF was originally discovered as a caspase-independent cell death effector, bioenergetic roles of AIF, particularly relating to complex I functions, have since emerged. However, the role of AIF in mitochondrial respiration and redox metabolism has remained unknown. Here, we investigated the redox properties of human AIF and AMID by comparing them with yeast Ndi1, a type 2 NADH:ubiquinone oxidoreductase (NDH-2) regarded as alternative complex I. Isolated AIF and AMID containing naturally incorporated FAD displayed no NADH oxidase activities. However, after reconstituting isolated AIF or AMID into bacterial or mitochondrial membranes, N-terminally tagged AIF and AMID displayed substantial NADH:O₂ activities and supported NADH-linked proton pumping activities in the host membranes almost as efficiently as Ndi1. NADH:ubiquinone-1 activities in the reconstituted membranes were highly sensitive to 2-n-heptyl-4-hydroxyquinoline-N-oxide (IC₅₀ = ∼1 μm), a quinone-binding inhibitor. Overexpressing N-terminally tagged AIF and AMID enhanced the growth of a double knock-out Escherichia coli strain lacking complex I and NDH-2. In contrast, C-terminally tagged AIF and NADH-binding site mutants of N-terminally tagged AIF and AMID failed to show both NADH:O₂ activity and the growth-enhancing effect. The disease mutant AIFΔR201 showed decreased NADH:O₂ activity and growth-enhancing effect. Furthermore, we surprisingly found that the redox activities of N-terminally tagged AIF and AMID were sensitive to rotenone, a well known complex I inhibitor. We propose that AIF and AMID are previously unidentified mammalian NDH-2 enzymes, whose bioenergetic function could be supplemental NADH oxidation in cells. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

‘Umpolung’ Reactivity in Semiaqueous Amide and Peptide Synthesis

PubMed Central

Shen, Bo; Makley, Dawn M.; Johnston, Jeffrey N.

2010-01-01

The amide functional group is one of Nature’s key functional and structural elements, most notably within peptides. Amides are also key intermediates in the preparation of a diverse range of therapeutic small molecules. Its construction using available methods focuses principally upon dehydrative approaches, although oxidative and radical-based methods are representative alternatives. During the carbon-nitrogen bond forming step in most every example, the carbon and nitrogen bear electrophilic and nucleophilic character, respectively. Here we show that activation of amines and nitroalkanes with an electrophilic iodine source in wet THF can lead directly to amide products. Preliminary observations support a mechanistic construct in which reactant polarity is reversed (umpolung) during C-N bond formation relative to traditional approaches. The use of nitroalkanes as acyl anion equivalents provides a conceptually innovative approach to amide and peptide synthesis, and one that might ultimately provide for efficient peptide synthesis that is fully reliant on enantioselective methods. PMID:20577205

Enhanced inhibition of bacterial biofilm formation and reduced leukocyte toxicity by chloramphenicol:β-cyclodextrin:N-acetylcysteine complex.

PubMed

Aiassa, Virginia; Zoppi, Ariana; Becerra, M Cecilia; Albesa, Inés; Longhi, Marcela R

2016-11-05

The purpose of this study was to improve the physicochemical and biological properties of chloramphenicol (CP) by multicomponent complexation with β-cyclodextrin (β-CD) and N-acetylcysteine (NAC). The present work describes the ability of solid multicomponent complex (MC) to decrease biomass and cellular activity of Staphylococcus by crystal violet and XTT assay, and leukocyte toxicity, measuring the increase of reactive oxygen species by chemiluminescence, and using 123-dihydrorhodamine. In addition, MC was prepared by the freeze-drying or physical mixture methods, and then characterized by scanning electron microscopy and powder X-ray diffraction. Nuclear magnetic resonance and phase solubility studies provided information at the molecular level on the structure of the MC and its association binding constants, respectively. The results obtained allowed us to conclude that MC formation is an effective pharmaceutical strategy that can reduce CP toxicity against leukocytes, while enhancing its solubility and antibiofilm activity. Copyright © 2016. Published by Elsevier Ltd.

Comparative behavioral toxicity of four sulfhydryl radioprotective compounds in mice: Wr2721, cysteamine, diethyldithiocarbamate, and n-acetylcysteine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Landauer, M.R.; Davis, H.D.; Dominitz, J.A.

1988-01-01

A number of sulfhydryl compounds have been shown to protect against ionizing radiation. One of the most effective radioprotectors is S-2(3-aminopropylamino)ethylphosphorothioic acid, also known aas ethiofos, gammaphos, or WR-2721 (Davidson, 1980; Giambarresi and Jacobs, 1987). This drug is currently under clinical investigation for its potential in protecting normal tissue during radiation treatment and chemotherapy (Blumberg et al., 1982; Glover et al., 1988; Yuhas et al., 1980). B-Mercaptoethylamine (MEA, cysteamine) was for years the standard against which the effectiveness of other radioprotectors was judged, but is more toxic than WR-2721 (Giambarresi and Jacobs, 1987). Diethyldithiocarbamate (DDC) and N-acetylcysteine (NAC) are othermore » compounds shown to have radioprotective properties (Milas et al., 1988; Weiss et al., 1984). Studies in a variety of animal species have shown significant behavioral toxicity after administration of WR-2721 (Bogo et al., 1985; Bogo, 1988; Landauer et al., 1987b, 1988).« less

TROSY of side-chain amides in large proteins

PubMed Central

Liu, Aizhuo; Yao, Lishan; Li, Yue; Yan, Honggao

2012-01-01

By using the mixed solvent of 50% H2O/50% D2O and employing deuterium decoupling, TROSY experiments exclusively detect NMR signals from semideuterated isotopomers of carboxamide groups with high sensitivities for proteins with molecular weights up to 80 kDa. This isotopomer-selective strategy extends TROSY experiments from exclusively detecting backbone to both backbone and side-chain amides, particularly in large proteins. Because of differences in both TROSY effect and dynamics between 15N–HE{DZ} and 15N–HZ{DE} isotopomers of the same carboxamide, the 15N transverse magnetization of the latter relaxes significantly faster than that of the former, which provides a direct and reliable stereospecific distinction between the two configurations. The TROSY effects on the 15N–HE{DZ} isotopomers of side-chain amides are as significant as on backbone amides. PMID:17347000

L-N-Acetylcysteine protects against radiation-induced apoptosis in a cochlear cell line.

PubMed

Low, Wong-Kein; Sun, Li; Tan, Michelle G K; Chua, Alvin W C; Wang, De-Yun

2008-04-01

L-N-Acetylcysteine (L-NAC) significantly reduced reactive oxygen species (ROS) generation and cochlear cell apoptosis after irradiation. The safe and effective use of L-NAC in reducing radiation-induced sensorineural hearing loss (SNHL) should be verified by further in vivo studies. Radiation-induced SNHL is a common complication after radiotherapy of head and neck tumours. There is growing evidence to suggest that ROS play an important role in apoptotic cochlear cell death from ototoxicity, resulting in SNHL. The aim of this study was to evaluate the effectiveness of L-NAC, an antioxidant, on radiation-induced apoptosis in cochlear cells. The OC-k3 cochlear cell line was studied after 0 and 20 Gy of gamma-irradiation. Cell viability assay was performed using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide. Flow cytometry and TUNEL assay were done with and without the addition of 10 mmol/L of L-NAC. Intracellular generation of ROS was detected by 2',7'-dichlorofluorescein diacetate, with comparisons made using fluorescence intensity. L-NAC increased the viability of cells after irradiation. Generation of ROS was demonstrated at 1 h post-irradiation and was significantly reduced by L-NAC (p<0.0001). Flow cytometry and TUNEL assay showed cell apoptosis at 72 h post-irradiation, which was diminished by the addition of L-NAC.

Boundary-Layer Transition on the N.A.C.A. 0012 and 23012 Airfoils in the 8-Foot High-Speed Wind Tunnel, Special Report

NASA Technical Reports Server (NTRS)

Becker, John V.

1940-01-01

Determinations of boundary-layer transition on the NACA 0012 and 2301 airfoils were made in the 8-foot high-speed wind tunnel over a range of Reynolds Numbers from 1,600,000 to 16,800,000. The results are of particular significance as compared with flight tests and tests in wind tunnels of appreciable turbulence because of the extremely low turbulence in the high-speed tunnel. A comparison of the results obtained on NACA 0012 airfoils of 2-foot and 5-foot chord at the same Reynolds Number permitted an evaluation of the effect of compressibility on transition. The local skin friction along the surface of the NACA 0012 airfoil was measured at a Reynolds Number of 10,000,000. For all the lift coefficient at which tests were made, transition occurred in the region of estimated laminar separation at the low Reynolds Numbers and approach the point of minimum static pressure as a forward limit at the high Reynolds Numbers. The effect of compressibility on transition was slight. None of the usual parameters describing the local conditions in the boundary layer near the transition point served as an index for locating the transition point. As a consequence of the lower turbulence in the 8-foot high-speed tunnel, the transition points occurred consistently farther back along the chord than those measured in the NACA full-scale tunnel. An empirical relation for estimating the location of the transition point for conventional airfoils on the basis of static-pressure distribution and Reynolds Number is presented.

Effect of the Reservoir Volume on the Discharge Pressures in the Injection System of the N.A.C.A. Spray Photography Equipment

NASA Technical Reports Server (NTRS)

Rothrock, A M; Lee, D W

1932-01-01

Tests were made to determine the effect of the reservoir volume on the discharge pressures in the injection system of the N.A.C.A. spray photography equipment. The data obtained are applicable to the design of a common rail fuel-injection system. The data show that an injection system of the type described can be designed so that not more than full load fuel quantity can be injected into the engine cylinders, and so that the fuel spray characteristics remain constant over a large range of engine speeds. Formulas are presented for computing the volume of the reservoir and the diameter of the discharge orifice.

N-acetylcysteine modulates glutamatergic dysfunction and depressive behavior in Huntington's disease.

PubMed

Wright, Dean J; Gray, Laura J; Finkelstein, David I; Crouch, Peter J; Pow, David; Pang, Terence Y; Li, Shanshan; Smith, Zoe M; Francis, Paul S; Renoir, Thibault; Hannan, Anthony J

2016-07-15

Glutamatergic dysfunction has been implicated in the pathogenesis of depressive disorders and Huntington's disease (HD), in which depression is the most common psychiatric symptom. Synaptic glutamate homeostasis is regulated by cystine-dependent glutamate transporters, including GLT-1 and system x c - In HD, the enzyme regulating cysteine (and subsequently cystine) production, cystathionine-γ-lygase, has recently been shown to be lowered. The aim of the present study was to establish whether cysteine supplementation, using N-acetylcysteine (NAC) could ameliorate glutamate pathology through the cystine-dependent transporters, system x c - and GLT-1. We demonstrate that the R6/1 transgenic mouse model of HD has lower basal levels of cystine, and showed depressive-like behaviors in the forced-swim test. Administration of NAC reversed these behaviors. This effect was blocked by co-administration of the system x c - and GLT-1 inhibitors CPG and DHK, showing that glutamate transporter activity was required for the antidepressant effects of NAC. NAC was also able to specifically increase glutamate in HD mice, in a glutamate transporter-dependent manner. These in vivo changes reflect changes in glutamate transporter protein in HD mice and human HD post-mortem tissue. Furthermore, NAC was able to rescue changes in key glutamate receptor proteins related to excitotoxicity in HD, including NMDAR2B. Thus, we have shown that baseline reductions in cysteine underlie glutamatergic dysfunction and depressive-like behavior in HD and these changes can be rescued by treatment with NAC. These findings have implications for the development of new therapeutic approaches for depressive disorders. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

PubMed Central

Wilder, Tanganyika; Ryba, David M.; Wieczorek, David F.; Wolska, Beata M.

2015-01-01

S-glutathionylation of cardiac myosin-binding protein C (cMyBP-C) induces Ca2+ 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 Ca2+ 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 Ca2+ 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. PMID:26432840

N-acetylcysteine-induced headache in hospitalized patients with acute acetaminophen overdose.

PubMed

Zyoud, Sa'ed H; Awang, Rahmat; Sulaiman, Syed Azhar Syed; Al-Jabi, Samah W

2011-06-01

Intravenous N-acetylcysteine (IV-NAC) is usually regarded as a safe antidote to acetaminophen overdose. However, during infusion of the loading dose, adverse drug reactions such as a headache may occur. The objectives of this study were to investigate the prevalence of headache in patients presenting to hospital after acetaminophen overdose and to determine which clinical findings are most predictive of headache among these patients. This is a retrospective cohort study of hospital admissions for acute acetaminophen overdose that was conducted over a period of 4 years from January 1, 2005 to December 31, 2008. Demographic data, clinical characteristics, and predictors of headache were analyzed. spss 15 was used for data analysis. Two-hundred and fifty-five patients were studied; their mean age was 23.1 ± 1.6; 83.9% of them were women and 14.9% had a headache during hospitalization. Headache among patients was significantly associated with IV-NAC administration (P = 0.001), intentional ingestion of drug (P = 0.04), acetaminophen concentration above 'possible toxicity' treatment line (P = 0.04), a high acetaminophen concentration (P = 0.04), and a long hospital stay (P = 0.03). Multiple logistic regression showed a significant risk factor for headache in patients administered IV-NAC (P = 0.04). We recorded a high frequency of headache in patients with acute acetaminophen overdose in our geographical area. This study suggests that among those patients, the use of IV-NAC is associated with an increased risk of headache. © 2010 The Authors Fundamental and Clinical Pharmacology © 2010 Société Française de Pharmacologie et de Thérapeutique.

N-acetylcysteine stimulates protein synthesis in enterocytes independently of glutathione synthesis.

PubMed

Yi, Dan; Hou, Yongqing; Wang, Lei; Long, Minhui; Hu, Shengdi; Mei, Huimin; Yan, Liqiong; Hu, Chien-An Andy; Wu, Guoyao

2016-02-01

Dietary supplementation with N-acetylcysteine (NAC) has been reported to improve intestinal health and treat gastrointestinal diseases. However, the underlying mechanisms are not fully understood. According to previous reports, NAC was thought to exert its effect through glutathione synthesis. This study tested the hypothesis that NAC enhances enterocyte growth and protein synthesis independently of cellular glutathione synthesis. Intestinal porcine epithelial cells were cultured for 3 days in Dulbecco's modified Eagle medium containing 0 or 100 μM NAC. To determine a possible role for GSH (the reduced form of glutathione) in mediating the effect of NAC on cell growth and protein synthesis, additional experiments were conducted using culture medium containing 100 μM GSH, 100 μM GSH ethyl ester (GSHee), diethylmaleate (a GSH-depletion agent; 10 μM), or a GSH-synthesis inhibitor (buthionine sulfoximine, BSO; 20 μM). NAC increased cell proliferation, GSH concentration, and protein synthesis, while inhibiting proteolysis. GSHee enhanced cell proliferation and GSH concentration without affecting protein synthesis but inhibited proteolysis. Conversely, BSO or diethylmaleate reduced cell proliferation and GSH concentration without affecting protein synthesis, while promoting protein degradation. At the signaling level, NAC augmented the protein abundance of total mTOR, phosphorylated mTOR, and phosphorylated 70S6 kinase as well as mRNA levels for mTOR and p70S6 kinase in IPEC-1 cells. Collectively, these results indicate that NAC upregulates expression of mTOR signaling proteins to stimulate protein synthesis in enterocytes independently of GSH generation. Our findings provide a hitherto unrecognized biochemical mechanism for beneficial effects of NAC in intestinal cells.

A Complete Tank Test of a Model of Flying-boat Hull - N.A.C.A. Model 16

NASA Technical Reports Server (NTRS)

Shoemaker, James H

1933-01-01

A model of a 2-step flying-boat hull, of the type generally used in England, was tested according to the complete method described in the N.A.C.A. Technical Note No. 464. The lines of this model were taken from offsets given by Mr. William Munro in Flight, May 29, 1931. The data cover the range of loads, speeds, and trim angles that may be of use in applying the hull form to the design of any seaplane. The results are reduced to nondimensional form to aid application to design problems and facilitate comparison with the performance of other hulls. The water characteristics of Model 16 are compared with those of Model 11-A, which is representative of current American practice. The results show that when the two forms are applied to a given seaplane design under optimum conditions for each, the performance of Model 16 will be somewhat inferior to that of Model 11-A.

Proteins regulating the biosynthesis and inactivation of neuromodulatory fatty acid amides.

PubMed

Patricelli, M P; Cravatt, B F

2001-01-01

Fatty acid amides (FAAs) represent a growing family of biologically active lipids implicated in a diverse range of cellular and physiological processes. At present, two general types of fatty acid amides, the N-acylethanolamines (NAEs) and the fatty acid primary amides (FAPAs), have been identified as potential physiological neuromodulators/neurotransmitters in mammals. Representative members of these two subfamilies include the endocannabinoid NAE anandamide and the sleep-inducing FAPA oleamide. In this Chapter, molecular mechanisms proposed for the biosynthesis and inactivation of FAAs are critically evaluated, with an emphasis placed on the biochemical and cell biological properties of proteins thought to mediate these processes.

REACTIONS OF MERCAPTANS. I. FORMATION OF 2-METHYL-2-THIAZOLINE-4- CARBOXYLIC ACID FROM N-ACETYLCYSTEINE. II. A SPECTROPHOTOMETRIC METHOD FOR STUDY OF THE REACTION OF RADIATION-PROTECTIVE MERCAPTANS WITH ARYL DISULFIDES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, H.A. Jr.

1962-08-01

I. Methyl 2-methyl-2-thiazoline-4-carboxylate was synthesized and converted to the corresponding acid. The behavior of the carboxythiazoline in various concentrations of mineral acids was studied spectrophotometrically. The cyclization of N-acetylcysteine to form a thiazoline-ring compound in concentrated mineral acids was also studied by this means. N-Acetylcysteine in concentrated mineral acid solutions yielded 2-methyl-2-thiazoline-4-carboxylic acid, which also was obtained by controlied hydrolysis of the corresponding methyl ester. Hydrolysis of methyl 2-methyl2-thiazoline-4-carboxylate, pK 3.05, in 0.1M sodium hydroxide yielded the corresponding carboxythiazoline in solution, pK 2.20 and 4.95. The carboxythiazoline was hydrolyzed very slowly in 7M hydrochloric acid, but the velocity of reactionmore » increased with decreasing acid concentration to a maximum at about pH 1.7; the products were N- and Sacetylcysteine, as well as cysteine and acetic acid. At acid concentrations below 0.2M, the last two products were formed slowly, and a pseudo-equilibrium could be established between thiazolinium ion, N-, and S-acetylcysteine. Equilibrium constants were determined. II. 4,4'-Dithiobis (benzenesulfonic acid) (I) and 4,4'-dithiobis(1-naphthalenesulfonic acid) (II) were synthesized from sulfanilic and naphthionic acids, respectively. The absorption spectra of I and II and of the corresponding mercaptans were determined. The thiol-disuifide interchange reactions were studied by spectrophotometric means for the reactions of cysteine with I and with II, and the equilibrium constants were determined. The systems had spectra very similar to those of the respective mixed disuifides with cysteine, and it was not possible to determine the concentrations from absorbancy measurements. On the other hand, the mercaptide ions had spectra different from the other species, with maxima at 285 and 348 m mu , respectively, and the concentrations of the corresponding mercaptans could

Antimicrobial activity of alexidine alone and associated with N-acetylcysteine against Enterococcus faecalis biofilm

PubMed Central

Silveira, Luiz Fernando Machado; Baca, Pilar; Arias-Moliz, María Teresa; Rodríguez-Archilla, Alberto; Ferrer-Luque, Carmen María

2013-01-01

The purpose of this study was to assess the efficacy of alexidine (ALX), alone and combined with N-acetylcysteine (NAC), in eradicating two Enterococcus faecalis strain biofilms. The biofilms of E. faecalis ATCC 29212 and the clinical isolate E. faecalis D1 were grown in the MBEC-high-throughput device for 24 h and were exposed to five twofold dilutions of ALX (2%–0.007 8%) alone and combined with 100 mg⋅mL−1 NAC, for 1 and 5 min. Eradication was defined as 100% kill of biofilm bacteria. The Student's t-test was used to compare the efficacy of the associations of the two irrigants. After 1-min contact time, ALX eradicated the biofilms at all concentrations except for 0.007 8% and 0.015 6%–0.007 8% with E. faecalis ATCC 29212 and E. faecalis D1, respectively. Similar results for eradication and concentration were obtained when it was combined with 100 mg⋅mL−1 NAC. After 5 min of contact time, ALX alone and combined with NAC eradicated all enterococci biofilms. ALX showed antimicrobial properties against the two E. faecalis strain biofilms tested at very low concentrations, and its combined use with NAC was not seen to enhance its activity. PMID:23970139

A theoretical and matrix-isolation FT-IR investigation of the conformational landscape of N-acetylcysteine

NASA Astrophysics Data System (ADS)

Boeckx, Bram; Ramaekers, Riet; Maes, Guido

2010-06-01

The conformational landscape of N-acetylcysteine (NAC) has been investigated by a combined experimental matrix-isolation FT-IR and theoretical methodology. This combination is a powerful tool to study the conformational behavior of relatively small molecules. Geometry optimizations at the HF/3-21 level resulted in 438 different geometries with an energy difference smaller than 22 kJ mol -1. Among these, six conformations were detected with a relative energy difference smaller than 10 kJ mol -1 at the DFT(B3LYP)/6-31++G∗∗ level of theory. These were finally subjected to MP2/6-31++G∗∗ optimizations which resulted in five minima. The vibrational and thermodynamical properties of these conformations were calculated at both the DFT and MP2 methodologies. Experimentally NAC was isolated in an argon matrix at 16 K after being sublimated at 323 K. The most stable MP2 form appeared to be dominant in the experimental spectra but the presence of three other conformations with Δ EMP2 < 10 kJ mol -1 was also demonstrated. The experimentally observed abundance of the H-bond containing conformations appeared to be in good accordance with the predicted MP2 value.

Preliminary Flight Tests of the N.A.C.A. Roots Type Aircraft Engine Supercharger

NASA Technical Reports Server (NTRS)

Gardiner, Arthur W; Reid, Elliott G

1928-01-01

An investigation of the suitability of the N.A.C.A. Roots type aircraft engine supercharger to flight-operating conditions, as determined the effects of the use of the supercharger upon engine operation and airplane performance, is described in this report. Attention was concentrated on the operation of the engine-supercharger unit and on the improvement of climbing ability; some information concerning high speeds at altitude was obtained. The supercharger was found to be satisfactory under flight-operating conditions. Although two failures occurred during the tests, the causes of both were minor and have been eliminated. Careful examination of the engines revealed no detrimental effects which could be attributed to supercharging. Marked improvements in climbing ability and high speeds at altitude were effected. It was also found that the load which could be carried to a given moderate or high altitude in a fixed time was considerably augmented. A slight sacrifice of low-altitude performance was necessitated, however, by the use of a fixed-pitch propeller. From a consideration of the very satisfactory flight performance of the Roots supercharger and of its inherent advantages, it is concluded that this type is particularly attractive for use in certain classes of commercial airplanes and in a number of military types.

Investigation of the NACA 4-(5)(08)-03 and NACA 4-(10)(08)-03 Two-Blade Propellers at Forward Mach Numbers to 0.725 to Determine the Effects of Camber and Compressibility on Performance

NASA Technical Reports Server (NTRS)

Delano, James B

1951-01-01

As part of a general investigation of propellers at high forward speeds, tests of two-blade propellers having the NACA 4-(5)(08)-03 and NACA 4-(10)(08)-03 blade designs were made in the Langley 8-foot high-speed tunnel through a range of blade angle from 20 degrees to 60 degrees for forward Mach numbers from 0.165 to 0.70 to determine the effect of camber and compressibility on propeller characteristics. Results previously reported for similar tests of a two-blade propeller having the NACA 4-(3)(08)-03 blade design are included for comparison.

Vultee YA–31C Vengeance at the NACA

NASA Image and Video Library

1945-03-21

A Bell P-39 Airacobra in the NACA Aircraft Engine Research Laboratory’s Icing Research Tunnel for a propeller deicing study. The tunnel, which began operation in June 1944, was built to study the formation of ice on aircraft surfaces and methods of preventing or eradicating that ice. Ice buildup adds extra weight to aircraft, effects aerodynamics, and sometimes blocks airflow through engines. NACA design engineers added the Icing Research Tunnel to the new AERL’s original layout to take advantage of the massive refrigeration system being constructed for the Altitude Wind Tunnel. The Icing Research Tunnel is a closed-loop atmospheric wind tunnel with a 6- by 9-foot test section. The tunnel can produce speeds up to 300 miles per hour and temperatures from about 30 to -45⁰ F. During World War II AERL researchers analyzed different ice protection systems for propeller, engine inlets, antennae, and wings in the icing tunnel. The P-39 was a vital low-altitude pursuit aircraft of the US during the war. NACA investigators investigated several methods of preventing ice buildup on the P-39’s propeller, including the use of internal and external electrical heaters, alcohol, and hot gases. They found that continual heating of the blades expended more energy than the aircraft could supply, so studies focused on intermittent heating. The results of the wind tunnel investigations were then compared to actual flight tests on aircraft.

Ramjet Testing in the NACA's Altitude Wind Tunnel

NASA Image and Video Library

1946-02-21

A 20-inch diameter ramjet installed in the Altitude Wind Tunnel at the National Advisory Committee for Aeronautics (NACA) Lewis Flight Propulsion Laboratory. The Altitude Wind Tunnel was used in the 1940s to study early ramjet configurations. Ramjets provide a very simple source of propulsion. They are basically a tube which takes in high-velocity air, ignites it, and then expels the expanded airflow at a significantly higher velocity for thrust. Ramjets are extremely efficient and powerful but can only operate at high speeds. Therefore a turbojet or rocket was needed to launch the vehicle. This NACA-designed 20-inch diameter ramjet was installed in the Altitude Wind Tunnel in May 1945. The ramjet was mounted under a section of wing in the 20-foot diameter test section with conditioned airflow ducted directly to the engine. The mechanic in this photograph was installing instrumentation devices that led to the control room. NACA researchers investigated the ramjet’s overall performance at simulated altitudes up to 47,000 feet. Thrust measurements from these runs were studied in conjunction with drag data obtained during small-scale studies in the laboratory’s small supersonic tunnels. An afterburner was attached to the ramjet during the portions of the test program. The researchers found that an increase in altitude caused a reduction in the engine’s horsepower. They also determined the optimal configurations for the flameholders, which provided the engine’s ignition source.

Effect of N-acetylcysteine administration on the expression and activities of antioxidant enzymes and the malondialdehyde level in the blood of lead-exposed workers.

PubMed

Kasperczyk, Sławomir; Dobrakowski, Michał; Kasperczyk, Aleksandra; Machnik, Grzegorz; Birkner, Ewa

2014-03-01

We investigated whether treatment with N-acetylcysteine (NAC) reduces oxidative stress intensity and restores the expression and activities of superoxide dismutase (Sod1, SOD), catalase (Cat, CAT) and glutathione peroxidase (Gpx1, GPx) in lead-exposed workers. The exposed population was divided randomly into two groups. Workers in the first group (reference group, n=49) were not administered any drugs, while workers in the second group (n=122) were treated with NAC at three doses for 12 weeks (200 mg, 400 mg, 800 mg/day). NAC administered orally to lead-exposed workers normalized antioxidant enzyme activities in blood cells. Oxidative stress intensity measured as malondialdehyde (MDA) levels in serum, leukocytes and erythrocytes significantly decreased after NAC administration. NAC may be an alternative therapy for chronic lead intoxication. Copyright © 2014 Elsevier B.V. All rights reserved.

Amides are novel protein modifications formed by physiological sugars.

PubMed

Glomb, M A; Pfahler, C

2001-11-09

The Maillard reaction, or nonenzymatic browning, proceeds in vivo, and the resulting protein modifications (advanced glycation end products) have been associated with various pathologies. Despite intensive research only very few structures have been established in vivo. We report here for the first time N(6)-[2-[(5-amino-5-carboxypentyl)amino]-2-oxoethyl]lysine (GOLA) and N(6)-glycoloyllysine (GALA) as prototypes for novel amide protein modifications produced by reducing sugars. Their identity was confirmed by independent synthesis and coupled liquid chromatography/mass spectrometry. Model reactions with N(alpha)-t-butoxycarbonyl-lysine showed that glyoxal and glycolaldehyde are immediate precursors, and reaction pathways are directly linked to N(epsilon)-carboxymethyllysine via glyoxal-imine structures. GOLA, the amide cross-link, and 1,3-bis(5-amino-5-carboxypentyl)imidazolium salt (GOLD), the imidazolium cross-link, share a common intermediate. The ratio of GOLA to GOLD is greater when glyoxal levels are low at constant lysine concentrations. GOLA and GALA formation from the Amadori product of glucose and lysine depends directly upon oxidation. With the advanced glycation end product inhibitors aminoguanidine and pyridoxamine we were able to dissect oxidative fragmentation of the Amadori product as a second mechanism of GOLA formation exactly coinciding with N(epsilon)-carboxymethyllysine synthesis. In contrast, the formation of GALA appears to depend solely upon glyoxal-imines. After enzymatic hydrolysis GOLA was found at 66 pmol/mg of brunescent lens protein. This suggests amide protein modifications as important markers of pathophysiological processes.

An assessment of the variation in the concentration of acetylcysteine in infusions for the treatment of paracetamol overdose.

PubMed

Bailey, George P; Wood, David M; Archer, John R H; Rab, Edmund; Flanagan, Robert J; Dargan, Paul I

2017-02-01

Intravenous acetylcysteine is the treatment of choice for paracetamol poisoning. A previous UK study in 2001 found that 39% of measured acetylcysteine infusion concentrations differed by >20% from anticipated concentrations. In 2012, the UK Commission on Human Medicines made recommendations for the management of paracetamol overdose, including provision of weight-based acetylcysteine dosing tables. The aim of this study was to assess variation in acetylcysteine concentrations in administered infusions following the introduction of this guidance. A 6-month single-centre prospective study was undertaken at a UK teaching hospital. After preparation, 5-ml samples were taken from the first, second and third/any subsequent acetylcysteine infusions. Acetylcysteine was measured in diluted (1:50) samples by high-performance liquid chromatography. Comparisons between measured and expected concentrations based on prescribed weight-based dose and volume were made for each infusion. Ninety samples were collected. There was a variation of ≤10% in measured compared to expected concentration for 45 (50%) infusions, of 10-20% for 27 (30%) infusions, 20.1-50% for 14 (16%) infusions and >50% for four (4%) infusions. There was a median (interquartile range) variation in measured compared to expected concentration of -3.6 mg ml -1 (-6.7 to -2.3) for the first infusion, +0.2 mg ml -1 (-0.9 to +0.4) for the second infusion and -0.3 mg ml -1 (-0.6 to +0.2) for third and fourth infusions. There has been a moderate improvement in the variation in acetylcysteine dose administered by infusion. Further work is required to understand the continuing variation and consideration should be given to simplification of acetylcysteine regimes to decrease the risk of administration errors. © 2016 The British Pharmacological Society.

An assessment of the variation in the concentration of acetylcysteine in infusions for the treatment of paracetamol overdose

PubMed Central

Bailey, George P.; Wood, David M.; Archer, John R. H.; Rab, Edmund; Flanagan, Robert J.

2016-01-01

Background Intravenous acetylcysteine is the treatment of choice for paracetamol poisoning. A previous UK study in 2001 found that 39% of measured acetylcysteine infusion concentrations differed by >20% from anticipated concentrations. In 2012, the UK Commission on Human Medicines made recommendations for the management of paracetamol overdose, including provision of weight‐based acetylcysteine dosing tables. The aim of this study was to assess variation in acetylcysteine concentrations in administered infusions following the introduction of this guidance. Methods A 6‐month single‐centre prospective study was undertaken at a UK teaching hospital. After preparation, 5‐ml samples were taken from the first, second and third/any subsequent acetylcysteine infusions. Acetylcysteine was measured in diluted (1:50) samples by high‐performance liquid chromatography. Comparisons between measured and expected concentrations based on prescribed weight‐based dose and volume were made for each infusion. Results Ninety samples were collected. There was a variation of ≤10% in measured compared to expected concentration for 45 (50%) infusions, of 10–20% for 27 (30%) infusions, 20.1–50% for 14 (16%) infusions and >50% for four (4%) infusions. There was a median (interquartile range) variation in measured compared to expected concentration of −3.6 mg ml−1 (−6.7 to −2.3) for the first infusion, +0.2 mg ml−1 (−0.9 to +0.4) for the second infusion and −0.3 mg ml−1 (−0.6 to +0.2) for third and fourth infusions. Conclusion There has been a moderate improvement in the variation in acetylcysteine dose administered by infusion. Further work is required to understand the continuing variation and consideration should be given to simplification of acetylcysteine regimes to decrease the risk of administration errors. PMID:27558662

An experimental low Reynolds number comparison of a Wortmann FX67-K170 airfoil, a NACA 0012 airfoil and a NACA 64-210 airfoil in simulated heavy rain

NASA Technical Reports Server (NTRS)

Craig, Anthony P.; Hansman, R. John

1987-01-01

Wind tunnel experiments were conducted on Wortmann FX67-K170, NACA 0012, and NACA 64-210 airfoils at rain rates of 1000 mm/hr and Reynolds numbers of 310,000 to compare the aerodynamic performance degradation of the airfoils and to attempt to identify the various mechanisms which affect performance in heavy rain conditions. Lift and drag were measured in dry and wet conditions, a variety of flow visualization techniques were employed, and a computational code which predicted airfoil boundary layer behavior was used. At low angles of attack, the lift degradation in wet conditions varied significantly between the airfoils. The Wortmann section had the greatest overall lift degradation and the NACA 64-210 airfoil had the smallest. At high angles of attack, the NACA 64-210 and 0012 airfoils had improved aerodynamic performance in rain conditions due to an apparent reduction of the boundry layer separation. Performance degradation in heavy rain for all three airfoils at low angles of attack could be emulated by forced boundary layer transition near the leading edge. The secondary effect occurs at time scales consistent with top surface water runback times. The runback layer is thought to effectively alter the airfoil geometry. The severity of the performance degradation for the airfoils varied. The relative differences appeared to be related to the susceptibility of each airfoil to premature boundary layer transition.

MS/MS Digital Readout: Analysis of Binary Information Encoded in the Monomer Sequences of Poly(triazole amide)s.

PubMed

Amalian, Jean-Arthur; Trinh, Thanh Tam; Lutz, Jean-François; Charles, Laurence

2016-04-05

Tandem mass spectrometry was evaluated as a reliable sequencing methodology to read codes encrypted in monodisperse sequence-coded oligo(triazole amide)s. The studied oligomers were composed of monomers containing a triazole ring, a short ethylene oxide segment, and an amide group as well as a short alkyl chain (propyl or isobutyl) which defined the 0/1 molecular binary code. Using electrospray ionization, oligo(triazole amide)s were best ionized as protonated molecules and were observed to adopt a single charge state, suggesting that adducted protons were located on every other monomer unit. Upon collisional activation, cleavages of the amide bond and of one ether bond were observed to proceed in each monomer, yielding two sets of complementary product ions. Distribution of protons over the precursor structure was found to remain unchanged upon activation, allowing charge state to be anticipated for product ions in the four series and hence facilitating their assignment for a straightforward characterization of any encoded oligo(triazole amide)s.

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

PubMed

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.

Synthesis of chlorophyll-a derivatives possessing various amides as potential sensitizers for photovoltaic cells

NASA Astrophysics Data System (ADS)

Cui, Yuxiao; Ogasawara, Shin; Tamiaki, Hitoshi

32-Carboxy-pyropheophorbides-a possessing a variety of N-substituted carbamoyl groups at the 172-position were prepared by modifying naturally occurring chlorophyll-a. 32-Methoxycarbonyl-pyropheophorbide-a was obtained via the protection of the 172-carboxy group with an allyl group, and amidated with various primary and secondary amines at the free 17-propionate residue, followed by the acidic hydrolysis of the methyl ester in the 3-substituent to give the desired pyropheophorbide-a secondary and tertiary amides, respectively, bearing the trans-32-COOH. The synthetic pigments potentially usable for dye-sensitized solar cells gave almost the same optical properties in a solution. 32-Carboxy-pyropheophorbide-a N-monosubstituted or N,N-disubstituted amides were prepared from chemical modification of chlorophyll-a, which are potentially promising as available and environmentally friendly pigments for dye-sensitized solar cells.

Na/Ca Intermixing around Silicate and Phosphate Groups in Bioactive Phosphosilicate Glasses Revealed by Heteronuclear Solid-State NMR and Molecular Dynamics Simulations.

PubMed

Mathew, Renny; Stevensson, Baltzar; Edén, Mattias

2015-04-30

We characterize the intermixing of network-modifying Na(+)/Ca(2+) ions around the silicate (QSi(n)) and phosphate (QP(n)) tetrahedra in a series of 16 Na2O–CaO–SiO2–P2O5 glasses, whose P content and silicate network connectivity were varied independently. The set includes both bioactive and bioinactive compositions and also encompasses two soda-lime-silicate members devoid of P, as well as two CaO–SiO2 glasses and one Na2O–SiO2–P2O5 glass. The various Si/P↔Na/Ca contacts were probed by molecular dynamics (MD) simulations together with heteronuclear magic-angle-spinning (MAS) nuclear magnetic resonance (NMR) experimentation utilizing (23)Na{(31)P} and (23)Na{(29)Si} REDOR, as well as (31)P{ (23)Na} and (29)Si{(23)Na} REAPDOR. We introduce an approach for quantifying the extent of Na(+)/Ca(2+) ordering around a given QP(n) or QSi(n) group, encoded by the preference factor 0⩽ PM ⩽ 1 conveying the relative weights of a random cation intermixing (PM = 0) and complete preference/ordering (PM = 1) for one of the species M, which represents either Na(+) or Ca(2+). The MD-derived preference factors reveal phosphate and silicate species surrounded by Na(+)/Ca(2+) ions intermixed nearly randomly (PM ≲ 0.15), except for the QSi(4) and QSi(1) groups, which manifest more significant cation ordering with preference for Na+ and Ca2+, respectively. The overall weak preferences are essentially independent of the Si and P contents of the glass, whereas PM primarily correlates with the total amount of network modifiers: as the latter is increased, the Na/Ca distribution around the {QP(0), QSi(1), QSi(2)} groups with preference for Ca2(+ )tend to randomize (i.e., PCa decreases), while the PNa-values grow slightly for the {QP(1), QSi(3), QSi(4)} species already preferring coordination of Na. The set of experimental preference factors {PCa} for the orthophosphate (QP(0)) groups extracted from (31)P{(23)Na} REAPDOR NMR-derived M2(P–Na) dipolar second moments agrees

Nebulized heparin and N-acetylcysteine for smoke inhalational injury: A case report.

PubMed

Ashraf, Umair; Bajantri, Bharat; Roa-Gomez, Gabriella; Venkatram, Sindhaghatta; Cantin, Amanda; Diaz-Fuentes, Gilda

2018-05-01

Every year, ∼40,000 people suffer burn-related injuries in the United States. Despite recent advances, the odds of dying from exposure to fire, flames, or smoke are one in ∼1500. Smoke inhalation causes injury to the airways via a complex physiological process, and the treatment is mainly supportive. Many recent interventions aim to decrease the formation of fibrin casts, the main cause of airway damage in these patients. Among these, treatment with a combination of nebulized heparin and N-acetylcysteine (NAC) has shown benefit. We describe the case of a 58-year-old man who presented after smoke inhalation during a fire. Soot was found in the nostrils when he was admitted to our hospital, and after he began coughing up carbonaceous material, he was electively intubated and placed on volume assist control ventilation. Bronchoscopy on the first day of intensive care confirmed the injury from smoke inhalation and revealed mucosal edema and soot involving the tracheobronchial tree. Inhaled unfractionated heparin of 10,000 IU in 3 mL of 0.9% normal saline alternating every 2 hours with 3 mL of 20% NAC was started 48 hours after admission and continued for 7 days. Bronchoscopy on the fifth day of intensive care showed significant improvement in airway edema and a resolution of soot. On the basis of our experience with this case and limited literature, we posit that nebulized heparin and NAC may be of benefit in patients with inhalational smoke-induced lung injury and mild-to-severe lung injury scores.

Potential Role of N-Acetylcysteine in the Management of Substance Use Disorders

PubMed Central

Gipson, Cassandra D.; Malcolm, Robert J.; Kalivas, Peter W.; Gray, Kevin M.

2014-01-01

There is a clear and pressing need to expand pharmacotherapy options for substance use disorders (SUDs) in order to improve sustained abstinence outcomes. Preclinical literature has demonstrated the role of glutamate in addiction, suggesting that new targets for pharmacotherapy should focus on the restoration of glutamatergic function. Glutamatergic agents for SUDs may span multiple addictive behaviors and help demonstrate potentially overlapping mechanisms in addiction. The current review will focus specifically on N-acetylcysteine (NAC), a safe and well-tolerated glutamatergic agent, as a promising potential pharmacotherapy for the treatment of SUDs across several substances of abuse. Building on recently published reviews of the clinical efficacy of NAC across a broad range of conditions, this review will more specifically discuss NAC as a pharmacotherapy for SUDs, devoting particular attention to the safety and tolerability profile of NAC, the wealth of preclinical evidence that has demonstrated the role of glutamate dysregulation in addiction, and the limited but growing clinical literature that has assessed the efficacy of NAC across multiple substances of abuse. Preliminary clinical studies show the promise of NAC in terms of safety, tolerability, and potential efficacy for promoting abstinence from cocaine, nicotine, and cannabis. Results from randomized clinical trials have been mixed, but several mechanistic and methodological factors are discussed to refine the use of NAC in promoting abstinence and relapse prevention across several substances of abuse. Further preclinical and clinical investigation into the use of NAC for SUDs will be vital in addressing current deficits in the treatment of SUDs. PMID:24442756

Oxidative Stress and Respiratory System: Pharmacological and Clinical Reappraisal of N-Acetylcysteine

PubMed Central

Santus, Pierachille; Corsico, Angelo; Solidoro, Paolo; Braido, Fulvio; Di Marco, Fabiano

2014-01-01

The large surface area for gas exchange makes the respiratory system particularly susceptible to oxidative stress-mediated injury. Both endogenous and exogenous pro-oxidants (e.g. cigarette smoke) trigger activation of leukocytes and host defenses. These mechanisms interact in a “multilevel cycle” responsible for the control of the oxidant/antioxidant homeostasis. Several studies have demonstrated the presence of increased oxidative stress and decreased antioxidants (e.g. reduced glutathione [GSH]) in subjects with chronic obstructive pulmonary disease (COPD), but the contribution of oxidative stress to the pathophysiology of COPD is generally only minimally discussed. The aim of this review was to provide a comprehensive overview of the role of oxidative stress in the pathogenesis of respiratory diseases, particularly COPD, and to examine the available clinical and experimental evidence on the use of the antioxidant N-acetylcysteine (NAC), a precursor of GSH, as an adjunct to standard therapy for the treatment of COPD. The proposed concept of “multilevel cycle” helps understand the relationship between respiratory diseases and oxidative stress, thus clarifying the rationale for using NAC in COPD. Until recently, antioxidant drugs such as NAC have been regarded only as mucolytic agents. Nevertheless, several clinical trials indicate that NAC may reduce the rate of COPD exacerbations and improve small airways function. The most plausible explanation for the beneficial effects observed in patients with COPD treated with NAC lies in the mucolytic and antioxidant effects of this drug. Modulation of bronchial inflammation by NAC may further account for these favorable clinical results. PMID:24787454

Role of Na+/Ca2+ Exchangers in Therapy Resistance of Medulloblastoma Cells.

PubMed

Pelzl, Lisann; Hosseinzadeh, Zohreh; Al-Maghout, Tamer; Singh, Yogesh; Sahu, Itishri; Bissinger, Rosi; Schmidt, Sebastian; Alkahtani, Saad; Stournaras, Christos; Toulany, Mahmoud; Lang, Florian

2017-01-01

Alterations of cytosolic Ca2+-activity ([Ca2+]i) are decisive in the regulation of tumor cell proliferation, migration and survival. Transport processes participating in the regulation of [Ca2+]i include Ca2+ extrusion through K+-independent (NCX) and/or K+-dependent (NCKX) Na+/Ca2+-exchangers. The present study thus explored whether medulloblastoma cells express Na+/Ca2+-exchangers, whether expression differs between therapy sensitive D283 and therapy resistant UW228-3 medulloblastoma cells, and whether Na+/Ca2+-exchangers participate in the regulation of cell survival. In therapy sensitive D283 and therapy resistant UW228-3 medulloblastoma cells transcript levels were estimated by RT-PCR, protein abundance by Western blotting, cytosolic Ca2+-activity ([Ca2+]i) from Fura-2-fluorescence, Na+/ Ca2+-exchanger activity from the increase of [Ca2+]i (Δ[Ca2+]i) and from whole cell current (Ica) following abrupt replacement of Na+ containing (130 mM) and Ca2+ free by Na+ free and Ca2+ containing (2 mM) extracellular perfusate as well as cell death from PI -staining and annexin-V binding in flow cytometry. The transcript levels of NCX3, NCKX2, and NCKX5, protein abundance of NCX3, slope and peak of Δ[Ca2+]i as well as Ica were significantly lower in therapy sensitive D283 than in therapy resistant UW228-3 medulloblastoma cells. The Na+/Ca2+-exchanger inhibitor KB-R7943 (10 µM) significantly blunted Δ[Ca2+]i, and augmented the ionizing radiation-induced apoptosis but did not significantly modify clonogenicity of medulloblastoma cells. Apoptosis was further enhanced by NCX3 silencing. Na+/Ca2+-exchanger activity significantly counteracts apoptosis but does not significantly affect clonogenicity after radiation of medulloblastoma cells. © 2017 The Author(s). Published by S. Karger AG, Basel.

Rhodium(III)-Catalyzed Amidation of Unactivated C(sp(3) )-H Bonds.

PubMed

Wang, He; Tang, Guodong; Li, Xingwei

2015-10-26

Nitrogenation by direct functionalization of C-H bonds represents an important strategy for constructing C-N bonds. Rhodium(III)-catalyzed direct amidation of unactivated C(sp(3) )-H bonds is rare, especially under mild reaction conditions. Herein, a broad scope of C(sp(3) )-H bonds are amidated under rhodium catalysis in high efficiency using 3-substituted 1,4,2-dioxazol-5-ones as the amide source. The protocol broadens the scope of rhodium(III)-catalyzed C(sp(3) )-H activation chemistry, and is applicable to the late-stage functionalization of natural products. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Gas-Phase Amidation of Carboxylic Acids with Woodward’s Reagent K Ions

PubMed Central

Peng, Zhou; Pilo, Alice L.; Luongo, Carl A.; McLuckey, Scott A.

2015-01-01

Gas-phase amidation of carboxylic acids in multiply-charged peptides is demonstrated via ion/ion reactions with Woodward’s reagent K (wrk) in both positive and negative mode. Woodward’s reagent K, N-ethyl-3-phenylisoxazolium-3′-sulfonate, is a commonly used reagent that activates carboxylates to form amide bonds with amines in solution. Here, we demonstrate that the analogous gas-phase chemistry occurs upon reaction of the wrk ions and doubly protonated (or doubly deprotonated) peptide ions containing the carboxylic acid functionality. The reaction involves the formation of the enol ester intermediate in the electrostatic complex. Upon collisional activation, the ethyl amine on the reagent is transferred to the activated carbonyl carbon on the peptide, resulting in the formation of an ethyl amide (addition of 27 Da to the peptide) with loss of a neutral ketene derivative. Further collision-induced dissociation (CID) of the products and comparison with solution-phase amidation product confirms the structure of the ethyl amide. PMID:26122523

Optimization of Aryl Amides that Extend Survival in Prion-Infected Mice

PubMed Central

Giles, Kurt; Berry, David B.; Condello, Carlo; Dugger, Brittany N.; Li, Zhe; Oehler, Abby; Bhardwaj, Sumita; Elepano, Manuel; Guan, Shenheng; Silber, B. Michael; Olson, Steven H.

2016-01-01

Developing therapeutics for neurodegenerative diseases (NDs) prevalent in the aging population remains a daunting challenge. With the growing understanding that many NDs progress by conformational self-templating of specific proteins, the prototypical prion diseases offer a platform for ND drug discovery. We evaluated high-throughput screening hits with the aryl amide scaffold and explored the structure–activity relationships around three series differing in their N-aryl core: benzoxazole, benzothiazole, and cyano. Potent anti-prion compounds were advanced to pharmacokinetic studies, and the resulting brain-penetrant leads from each series, together with a related N-aryl piperazine lead, were escalated to long-term dosing and efficacy studies. Compounds from each of the four series doubled the survival of mice infected with a mouse-passaged prion strain. Treatment with aryl amides altered prion strain properties, as evidenced by the distinct patterns of neuropathological deposition of prion protein and associated astrocytic gliosis in the brain; however, none of the aryl amide compounds resulted in drug-resistant prion strains, in contrast to previous studies on compounds with the 2-aminothiazole (2-AMT) scaffold. As seen with 2-AMTs and other effective anti-prion compounds reported to date, the novel aryl amides reported here were ineffective in prolonging the survival of transgenic mice infected with human prions. Most encouraging is our discovery that aryl amides show that the development of drug resistance is not an inevitable consequence of efficacious anti-prion therapeutics. PMID:27317802

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

PubMed Central

Wang, Gangduo; Wang, Jianling; Ma, Huaxian; Ansari, G.A.S.; Khan, M. Firoze

2017-01-01

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. PMID:23993974

Oxidative stress in hemodialysis patients receiving intravenous iron therapy and the role of N-acetylcysteine in preventing oxidative stress.

PubMed

Swarnalatha, G; Ram, R; Neela, Prasad; Naidu, M U R; Dakshina Murty, K V

2010-09-01

To determine the contribution of injectable iron administered to hemodialysis (HD) patients in causing oxidative stress and the beneficial effect of N-acetylcysteine (NAC) in reducing it, we studied in a prospective, double blinded, randomized controlled, cross over trial 14 adult HD patients who were randomized into two groups; one group received NAC in a dose of 600 mgs twice daily for 10 days prior to intravenous iron therapy and the other group received placebo. Both the groups were subjected to intravenous iron therapy, 100 mg of iron sucrose in 100 mL of normal saline given over a period of one hour. Blood samples for the markers of oxidative stress were taken before and after iron therapy. After the allowance of a week of wash out period for the effect of N-acetylcysteine we crossed over the patients to the opposite regimen. We measured the lipid peroxidation marker, malondiaaldehyde (MDA), to evaluate the oxidative stress and total anti-oxidant capacity (TAC) for the antioxidant level in addition to the highly sensitive C-reactive protein (HsCRP). Non-invasive assessment of endothelial dysfunction was measured by digital plethysmography before and after intravenous iron therapy. There was an increase of MDA (21.97 + 3.65% vs 7.06 + 3.65%) and highly sensitive C-reactive protein (HsCRP) (11.19 + 24.63% vs 13.19 + 7.7%) after iron administration both in the placebo and the NAC groups. NAC reduced the baseline acute systemic generation of oxidative stress when compared to placebo, which was statistically significant with MDA (12.76 + 4.4% vs 9.37 + 4.40%: P = 0.032) but not with HsCRP though there was a declining trend (2.85 + 22.75 % vs 8.93 + 5.19%: P = 0.112). Pre-treatment with NAC reduced the endothelial dysfunction when compared to placebo, but it was not statistically significant, except for reflection index (RI). We conclude that in our HD patients NAC reduced the oxidative stress before and after the administration of intravenous iron therapy in

Effects of N-acetylcysteine and terbutaline treatment on hemodynamics and regional albumin extravasation in porcine septic shock

DOE Office of Scientific and Technical Information (OSTI.GOV)

Groeneveld, A.B.; den Hollander, W.; Straub, J.

We studied the therapeutic effects of continuously infused N-acetylcysteine, an O2 radical scavenger (N, n = 6), and terbutaline, a beta 2-agonist (T, n = 6), versus dextrose (controls C, N = 6) on hemodynamics and regional albumin extravasation in porcine septic shock. After instrumentation, injection of 99mTc-labeled red blood cells, and baseline measurements, pigs received a 90 min infusion of 11 +/- 9 X 10(8).kg-1 live Escherichia coli bacteria. Thereafter, therapy was started, and 131I human serum albumin was injected. Images were obtained hourly using a gamma camera and a computer until 5 hours after baseline. Regions of interestmore » were drawn in the 99mTc images, yielding regional 131I/99mTc radioactivity ratios, with blood samples as reference. From these ratios, an albumin leak index, a rate constant of transvascular albumin transport, was calculated. Control pigs developed pulmonary hypertension, arterial hypotension, hemoconcentration, and lactic acidemia. In spite of tachycardia and unchanged filling pressures, cardiac output fell. In arterial blood, white cell count, PO2, albumin level, and colloid osmotic pressure fell. The albumin leak index (X10(-3).min-1) measured 1.56 +/- 0.59 over the lungs and 2.87 +/- 1.19 over the abdomen in C, confirming previously found increased albumin flux in both lung and abdomen, the latter exceeding the former. Neither N nor T significantly affected hemodynamic and biochemical changes. The drugs neither decreased the regional albumin leak index nor attenuated the formation of albumin-rich ascites found at autopsy. However, the lung albumin index obtained at autopsy was significantly reduced with N (P less than .01 vs. C), at similar gravimetrically determined extravascular lung water (EVLW). EVLW positively correlated with pulmonary albumin extravasation in C and T but not in N.« less

Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure.

PubMed

Lee, William M; Hynan, Linda S; Rossaro, Lorenzo; Fontana, Robert J; Stravitz, R Todd; Larson, Anne M; Davern, Timothy J; Murray, Natalie G; McCashland, Timothy; Reisch, Joan S; Robuck, Patricia R

2009-09-01

N-acetylcysteine (NAC), an antidote for acetaminophen poisoning, might benefit patients with non-acetaminophen-related acute liver failure. In a prospective, double-blind trial, acute liver failure patients without clinical or historical evidence of acetaminophen overdose were stratified by site and coma grade and assigned randomly to groups that were given NAC or placebo (dextrose) infusion for 72 hours. The primary outcome was overall survival at 3 weeks. Secondary outcomes included transplant-free survival and rate of transplantation. A total of 173 patients received NAC (n = 81) or placebo (n = 92). Overall survival at 3 weeks was 70% for patients given NAC and 66% for patients given placebo (1-sided P = .283). Transplant-free survival was significantly better for NAC patients (40%) than for those given placebo (27%; 1-sided P = .043). The benefits of transplant-free survival were confined to the 114 patients with coma grades I-II who received NAC (52% compared with 30% for placebo; 1-sided P = .010); transplant-free survival for the 59 patients with coma grades III-IV was 9% in those given NAC and 22% in those given placebo (1-sided P = .912). The transplantation rate was lower in the NAC group but was not significantly different between groups (32% vs 45%; P = .093). Intravenous NAC generally was well tolerated; only nausea and vomiting occurred significantly more frequently in the NAC group (14% vs 4%; P = .031). Intravenous NAC improves transplant-free survival in patients with early stage non-acetaminophen-related acute liver failure. Patients with advanced coma grades do not benefit from NAC and typically require emergency liver transplantation.

Rationale, design, and baseline characteristics of the Acetylcystein for Contrast-Induced nephropaThy (ACT) Trial: a pragmatic randomized controlled trial to evaluate the efficacy of acetylcysteine for the prevention of contrast-induced nephropathy

PubMed Central

2009-01-01

Background Aceltylcysteine has been evaluated in several small trials as a means of reducing the risk of contrast-induced nephropathy (CIN), however systematic reviews of these studies do not provide conclusive answers. Therefore, a large randomized controlled trial (RCT) is needed to provide a reliable answer as to whether acetylcysteine is effective in decreasing the risk of CIN in high-risk patients undergoing angiographic procedures. Methods ACT is a RCT of acetylcysteine versus placebo in 2,300 patients at-risk for CIN undergoing an intravascular angiographic procedure. The randomization list will be concealed. Participants, health care staff, investigators and outcome assessors will be blinded to whether patients receive acetylcysteine or placebo. All analysis will follow the intention-to-treat principle. The study drugs (acetylcysteine 1200 mg or placebo) will be administered orally twice daily for two doses before and two doses after the procedure. The primary outcome is the occurrence of CIN, defined as a 25% elevation of serum creatinine above baseline between 48 and 96 hours after angiography. Discussion The first patient entered the trial on September, 2008. Up to April 7, 2009, 810 patients had been included in 35 centers. The mean age was 69 (Standard deviation: 10), 18% had a baseline serum creatinine >1.5 mg/dL, 57% were diabetics and 13% had a history of heart failure. The ongoing ACT Trial is the largest multicentre RCT that will determine whether acetylcysteine is effective in decreasing the risk of CIN in patients at risk undergoing angiography. Trial registration Clinicaltrials.gov NCT00736866 PMID:19497091

Effect of N-acetylcysteine treatment on oxidative stress and inflammation after severe burn.

PubMed

Csontos, C; Rezman, B; Foldi, V; Bogar, L; Drenkovics, L; Röth, E; Weber, G; Lantos, J

2012-05-01

Oxidative stress and inflammation generate edema in burns. The aim of our study was to assess effect of N-acetylcysteine (NAC) on oxidative stress, inflammation, fluid requirement, multiple organ dysfunction (MOD) score and vasoactive drug requirement. In this study 15 patients were on standard therapy, whereas for other 15 patients NAC was supplemented. Blood samples were taken on admission and on the next five consecutive mornings. Levels of malondialdehyde, protein sulfhydril (PSH) groups, reduced gluthation (GSH), activity of myeloperoxidase, catalase and superoxide dismutase enzymes and induced free radical generating capacity were measured as well as concentrations of TNF-α, IL-6, IL-8, and IL-10. MOD score, use of vasopressor agents and fluid utilisation were recorded daily. NAC treatment increased GSH level on days 4-5 (p<0.05) and PSH level on days 2-6 (p<0.05) compared to controls. Plasma IL-6 was lower on days 4-5 (p<0.05), IL-8 on days 4-6 (p<0.05) and IL-10 on days 4-6 (p<0.05) in NAC group. NAC group received less catecholamines than controls (p<0.01) from day 4 without significant differences in MOD score. NAC treatment is associated with a diminished oxidative stress reflected in preserved antioxidant levels, lower inflammation mirrored in lower interleukin levels and less vasopressor requirement. Copyright © 2011 Elsevier Ltd and ISBI. All rights reserved.

NACA Researcher Sets up a Test of a New Seat Design

NASA Image and Video Library

1954-05-21

A researcher at the National Advisory Committee for Aeronautics (NACA) Lewis Flight Propulsion Laboratory prepares for a test of an NACA-designed aircraft seat. The laboratory had undertaken a multi-year investigation into the causes and prevention of fires on low altitude aircraft crashes. The program was expanded in the mid-1950s to include the study of impact on passengers, types of seat restraints, and seat design. The crash impact portion of the program began by purposely wrecking surplus Fairchild C-82 Packet and Piper Cub aircraft into barricades at the end of a test runway at the Ravenna Arsenal, located approximately 40 miles south of the Lewis lab in Cleveland. Instrumented dummies and cameras were installed in the pilot and passenger areas. After determining the different loads and their effects on the passengers, the NACA researchers began designing new types of seats and restraints. The result was an elastic seat that flexed upon impact, absorbing 75 percent of the loads before it slowly recoiled. This photograph shows the seats mounted on a pendulum with a large spring behind the platform to provide the jolt that mimicked the forces of a crash. The seat was constructed without any potentially damaging metal parts and included rubber-like material, an inflated back and arms, and a seat cushion. After the pendulum tests, the researchers compared the flexible seats to the rigid seats during a crash of a transport aircraft. They found the passengers in the rigid seats received 66 percent higher g-forces than the NACA-designed seats.

Index of NACA Technical Publications: 1915-1949

NASA Technical Reports Server (NTRS)

1949-01-01

The Index of NACA Technical Publications covers reports issued from the date of origin of the Committee in 1915 until approximately September 1949. Because omissions were noted after publication of the Index issued in 1947, and since many new reports have been released since that time, it was decided to issue a new volume to supersede completely the 1947 Index, with supplements to be issued regularly in the future. Commencing with all publications issued after September 1, 1949, subject classifications were revised, the most important change involving the transfer of aircraft loads reports from the Aerodynamics classification to Structures. For those maintaining a file of NACA index cards, it is recommended that cards issued for reports dated prior to September 1, 1949 be removed from the file. This volume includes the same index information. Supplements covering periods following September 1, 1949, will be arranged according to the revised subject classifications. On the pages immediately following, the subject classifications are indexed in order of breakdown. There is included in the back of this volume an alphabetical arrangement of the subject classifications.

N-Acetylcysteine Selectively Antagonizes the Activity of Imipenem in Pseudomonas aeruginosa by an OprD-Mediated Mechanism

PubMed Central

Rodríguez-Beltrán, Jerónimo; Cabot, Gabriel; Valencia, Estela Ynés; Costas, Coloma; Bou, German; Oliver, Antonio

2015-01-01

The modulating effect of N-acetylcysteine (NAC) on the activity of different antibiotics has been studied in Pseudomonas aeruginosa. Our results demonstrate that, in contrast to previous reports, only the activity of imipenem is clearly affected by NAC. MIC and checkerboard determinations indicate that the NAC-based modulation of imipenem activity is dependent mainly on OprD. SDS-PAGE of outer membrane proteins (OMPs) after NAC treatments demonstrates that NAC does not modify the expression of OprD, suggesting that NAC competitively inhibits the uptake of imipenem through OprD. Similar effects on imipenem activity were obtained with P. aeruginosa clinical isolates. Our results indicate that imipenem-susceptible P. aeruginosa strains become resistant upon simultaneous treatment with NAC and imipenem. Moreover, the generality of the observed effects of NAC on antibiotic activity was assessed with two additional bacterial species, Escherichia coli and Acinetobacter baumannii. Caution should be taken during treatments, as the activity of imipenem may be modified by physiologically attainable concentrations of NAC, particularly during intravenous and nebulized regimes. PMID:25801561

N-acetylcysteine selectively antagonizes the activity of imipenem in Pseudomonas aeruginosa by an OprD-mediated mechanism.

PubMed

Rodríguez-Beltrán, Jerónimo; Cabot, Gabriel; Valencia, Estela Ynés; Costas, Coloma; Bou, German; Oliver, Antonio; Blázquez, Jesús

2015-01-01

The modulating effect of N-acetylcysteine (NAC) on the activity of different antibiotics has been studied in Pseudomonas aeruginosa. Our results demonstrate that, in contrast to previous reports, only the activity of imipenem is clearly affected by NAC. MIC and checkerboard determinations indicate that the NAC-based modulation of imipenem activity is dependent mainly on OprD. SDS-PAGE of outer membrane proteins (OMPs) after NAC treatments demonstrates that NAC does not modify the expression of OprD, suggesting that NAC competitively inhibits the uptake of imipenem through OprD. Similar effects on imipenem activity were obtained with P. aeruginosa clinical isolates. Our results indicate that imipenem-susceptible P. aeruginosa strains become resistant upon simultaneous treatment with NAC and imipenem. Moreover, the generality of the observed effects of NAC on antibiotic activity was assessed with two additional bacterial species, Escherichia coli and Acinetobacter baumannii. Caution should be taken during treatments, as the activity of imipenem may be modified by physiologically attainable concentrations of NAC, particularly during intravenous and nebulized regimes. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

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

PubMed

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.

A new acylamidase from Rhodococcus erythropolis TA37 can hydrolyze N-substituted amides.

PubMed

Lavrov, K V; Zalunin, I A; Kotlova, E K; Yanenko, A S

2010-08-01

A new acylamidase was isolated from Rhodococcus erythropolis TA37 and characterized. N-Substituted acrylamides (isopropyl acrylamide, N,N-dimethyl-aminopropyl acrylamide, and methylene-bis-acrylamide), acid para-nitroanilides (4'-nitroacetanilide, Gly-pNA, Ala-pNA, Leu-pNA), and N-acetyl derivatives of glycine, alanine, and leucine are good substrates for this enzyme. Aliphatic amides (acetamide, acrylamide, isobutyramide, n-butyramide, and valeramide) are also used as substrates but with less efficiency. The enzyme subunit mass by SDS-PAGE is 55 kDa. Maximal activity is exhibited at pH 7-8 and 55°C. The enzyme is stable for 15 h at 22°C and for 0.5 h at 45°C. The Michaelis constant (K(m)) is 0.25 mM with Gly-pNA and 0.55 mM with Ala-pNA. The acylamidase activity is suppressed by inhibitors of serine proteases (phenylmethylsulfonyl fluoride and diisopropyl fluorophosphate) but is not suppressed by inhibitors of aliphatic amidases (acetaldehyde and nitrophenyl disulfides). The N-terminal amino acid sequence of the acylamidase is highly homologous to those of two putative amidases detected from sequenced R. erythropolis genomes. It is suggested that the acylamidase together with the detected homologs forms a new class within the amidase signature family.

Halogenated fatty amides - A brand new class of disinfection by-products.

PubMed

Kosyakov, Dmitry S; Ul'yanovskii, Nikolay V; Popov, Mark S; Latkin, Tomas B; Lebedev, Albert T

2017-12-15

An array of similar halogenated nitrogen-containing compounds with elemental composition C n H 2n NO 2 X, C n H 2n-2 NO 2 X and C n H 2n-1 NOX 2 (X = Cl, Br; n = 16, 18, 22) was detected in drinking water with high performance liquid chromatography - high resolution mass spectrometry (HPLC-HRMS) method. Compounds of this type were never mentioned among disinfection by-products. Tandem mass spectrometry allowed referring them to halohydrines or dihalogenated fatty amides, the products of conjugated electrophilic addition of halogens to the double bonds of unsaturated fatty amides. The proposed structures were confirmed by conducting aqueous chlorination with standard solution of oleamide. These compounds may be considered as a brand new class of disinfection by products, while their toxicities require special study. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mechanisms for an effect of acetylcysteine on renal function after exposure to radio-graphic contrast material: study protocol

PubMed Central

2012-01-01

Background Contrast-induced nephropathy is a common complication of contrast administration in patients with chronic kidney disease and diabetes. Its pathophysiology is not well understood; similarly the role of intravenous or oral acetylcysteine is unclear. Randomized controlled trials to date have been conducted without detailed knowledge of the effect of acetylcysteine on renal function. We are conducting a detailed mechanistic study of acetylcysteine on normal and impaired kidneys, both with and without contrast. This information would guide the choice of dose, route, and appropriate outcome measure for future clinical trials in patients with chronic kidney disease. Methods/Design We designed a 4-part study. We have set up randomised controlled cross-over studies to assess the effect of intravenous (50 mg/kg/hr for 2 hrs before contrast exposure, then 20 mg/kg/hr for 5 hrs) or oral acetylcysteine (1200 mg twice daily for 2 days, starting the day before contrast exposure) on renal function in normal and diseased kidneys, and normal kidneys exposed to contrast. We have also set up a parallel-group randomized controlled trial to assess the effect of intravenous or oral acetylcysteine on patients with chronic kidney disease stage III undergoing elective coronary angiography. The primary outcome is change in renal blood flow; secondary outcomes include change in glomerular filtration rate, tubular function, urinary proteins, and oxidative balance. Discussion Contrast-induced nephropathy represents a significant source of hospital morbidity and mortality. Over the last ten years, acetylcysteine has been administered prior to contrast to reduce the risk of contrast-induced nephropathy. Randomized controlled trials, however, have not reliably demonstrated renoprotection; a recent large randomized controlled trial assessing a dose of oral acetylcysteine selected without mechanistic insight did not reduce the incidence of contrast-induced nephropathy. Our study should

Mechanisms for an effect of acetylcysteine on renal function after exposure to radio-graphic contrast material: study protocol.

PubMed

Sandilands, Euan A; Cameron, Sharon; Paterson, Frances; Donaldson, Sam; Briody, Lesley; Crowe, Jane; Donnelly, Julie; Thompson, Adrian; Johnston, Neil R; Mackenzie, Ivor; Uren, Neal; Goddard, Jane; Webb, David J; Megson, Ian L; Bateman, Nicholas; Eddleston, Michael

2012-02-03

Contrast-induced nephropathy is a common complication of contrast administration in patients with chronic kidney disease and diabetes. Its pathophysiology is not well understood; similarly the role of intravenous or oral acetylcysteine is unclear. Randomized controlled trials to date have been conducted without detailed knowledge of the effect of acetylcysteine on renal function. We are conducting a detailed mechanistic study of acetylcysteine on normal and impaired kidneys, both with and without contrast. This information would guide the choice of dose, route, and appropriate outcome measure for future clinical trials in patients with chronic kidney disease. We designed a 4-part study. We have set up randomised controlled cross-over studies to assess the effect of intravenous (50 mg/kg/hr for 2 hrs before contrast exposure, then 20 mg/kg/hr for 5 hrs) or oral acetylcysteine (1200 mg twice daily for 2 days, starting the day before contrast exposure) on renal function in normal and diseased kidneys, and normal kidneys exposed to contrast. We have also set up a parallel-group randomized controlled trial to assess the effect of intravenous or oral acetylcysteine on patients with chronic kidney disease stage III undergoing elective coronary angiography. The primary outcome is change in renal blood flow; secondary outcomes include change in glomerular filtration rate, tubular function, urinary proteins, and oxidative balance. Contrast-induced nephropathy represents a significant source of hospital morbidity and mortality. Over the last ten years, acetylcysteine has been administered prior to contrast to reduce the risk of contrast-induced nephropathy. Randomized controlled trials, however, have not reliably demonstrated renoprotection; a recent large randomized controlled trial assessing a dose of oral acetylcysteine selected without mechanistic insight did not reduce the incidence of contrast-induced nephropathy. Our study should reveal the mechanism of effect of

Direct amidation of esters with nitroarenes

NASA Astrophysics Data System (ADS)

Cheung, Chi Wai; Ploeger, Marten Leendert; Hu, Xile

2017-03-01

Esters are one of the most common functional groups in natural and synthetic products, and the one-step conversion of the ester group into other functional groups is an attractive strategy in organic synthesis. Direct amidation of esters is particularly appealing due to the omnipresence of the amide moiety in biomolecules, fine chemicals, and drug candidates. However, efficient methods for direct amidation of unactivated esters are still lacking. Here we report nickel-catalysed reductive coupling of unactivated esters with nitroarenes to furnish in one step a wide range of amides bearing functional groups relevant to the development of drugs and agrochemicals. The method has been used to expedite the syntheses of bio-active molecules and natural products, as well as their post-synthetic modifications. Preliminary mechanistic study indicates a reaction pathway distinct from conventional amidation methods using anilines as nitrogen sources. The work provides a novel and efficient method for amide synthesis.

DNA-Catalyzed Amide Hydrolysis.

PubMed

Zhou, Cong; Avins, Joshua L; Klauser, Paul C; Brandsen, Benjamin M; Lee, Yujeong; Silverman, Scott K

2016-02-24

DNA catalysts (deoxyribozymes) for a variety of reactions have been identified by in vitro selection. However, for certain reactions this identification has not been achieved. One important example is DNA-catalyzed amide hydrolysis, for which a previous selection experiment instead led to DNA-catalyzed DNA phosphodiester hydrolysis. Subsequent efforts in which the selection strategy deliberately avoided phosphodiester hydrolysis led to DNA-catalyzed ester and aromatic amide hydrolysis, but aliphatic amide hydrolysis has been elusive. In the present study, we show that including modified nucleotides that bear protein-like functional groups (any one of primary amino, carboxyl, or primary hydroxyl) enables identification of amide-hydrolyzing deoxyribozymes. In one case, the same deoxyribozyme sequence without the modifications still retains substantial catalytic activity. Overall, these findings establish the utility of introducing protein-like functional groups into deoxyribozymes for identifying new catalytic function. The results also suggest the longer-term feasibility of deoxyribozymes as artificial proteases.

Reduction of adverse effects from intravenous acetylcysteine treatment for paracetamol poisoning: a randomised controlled trial.

PubMed

Bateman, D Nicholas; Dear, James W; Thanacoody, H K Ruben; Thomas, Simon H L; Eddleston, Michael; Sandilands, Euan A; Coyle, Judy; Cooper, Jamie G; Rodriguez, Aryelly; Butcher, Isabella; Lewis, Steff C; Vliegenthart, A D Bastiaan; Veiraiah, Aravindan; Webb, David J; Gray, Alasdair

2014-02-22

Paracetamol poisoning is common worldwide. It is treated with intravenous acetylcysteine, but the standard regimen is complex and associated with frequent adverse effects related to concentration, which can cause treatment interruption. We aimed to ascertain whether adverse effects could be reduced with either a shorter modified acetylcysteine schedule, antiemetic pretreatment, or both. We undertook a double-blind, randomised factorial study at three UK hospitals, between Sept 6, 2010, and Dec 31, 2012. We randomly allocated patients with acute paracetamol overdose to either the standard intravenous acetylcysteine regimen (duration 20·25 h) or a shorter (12 h) modified protocol, with or without intravenous ondansetron pretreatment (4 mg). Masking was achieved by infusion of 5% dextrose (during acetylcysteine delivery) or saline (for antiemetic pretreatment). Randomisation was done via the internet and included a minimisation procedure by prognostic factors. The primary outcome was absence of vomiting, retching, or need for rescue antiemetic treatment at 2 h. Prespecified secondary outcomes included a greater than 50% increase in alanine aminotransferase activity over the admission value. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov (identifier NCT01050270). Of 222 patients who underwent randomisation, 217 were assessable 2 h after the start of acetylcysteine treatment. Vomiting, retching, or need for rescue antiemetic treatment at 2 h was reported in 39 of 108 patients assigned to the shorter modified protocol compared with 71 of 109 allocated to the standard acetylcysteine regimen (adjusted odds ratio 0·26, 97·5% CI 0·13-0·52; p<0·0001), and in 45 of 109 patients who received ondansetron compared with 65 of 108 allocated placebo (0·41, 0·20-0·80; p=0·003). Severe anaphylactoid reactions were recorded in five patients assigned to the shorter modified acetylcysteine regimen versus 31 who were allocated to the

Phenolic Amides Are Potent Inhibitors of De Novo Nucleotide Biosynthesis.

PubMed

Pisithkul, Tippapha; Jacobson, Tyler B; O'Brien, Thomas J; Stevenson, David M; Amador-Noguez, Daniel

2015-09-01

An outstanding challenge toward efficient production of biofuels and value-added chemicals from plant biomass is the impact that lignocellulose-derived inhibitors have on microbial fermentations. Elucidating the mechanisms that underlie their toxicity is critical for developing strategies to overcome them. Here, using Escherichia coli as a model system, we investigated the metabolic effects and toxicity mechanisms of feruloyl amide and coumaroyl amide, the predominant phenolic compounds in ammonia-pretreated biomass hydrolysates. Using metabolomics, isotope tracers, and biochemical assays, we showed that these two phenolic amides act as potent and fast-acting inhibitors of purine and pyrimidine biosynthetic pathways. Feruloyl or coumaroyl amide exposure leads to (i) a rapid buildup of 5-phosphoribosyl-1-pyrophosphate (PRPP), a key precursor in nucleotide biosynthesis, (ii) a rapid decrease in the levels of pyrimidine biosynthetic intermediates, and (iii) a long-term generalized decrease in nucleotide and deoxynucleotide levels. Tracer experiments using (13)C-labeled sugars and [(15)N]ammonia demonstrated that carbon and nitrogen fluxes into nucleotides and deoxynucleotides are inhibited by these phenolic amides. We found that these effects are mediated via direct inhibition of glutamine amidotransferases that participate in nucleotide biosynthetic pathways. In particular, feruloyl amide is a competitive inhibitor of glutamine PRPP amidotransferase (PurF), which catalyzes the first committed step in de novo purine biosynthesis. Finally, external nucleoside supplementation prevents phenolic amide-mediated growth inhibition by allowing nucleotide biosynthesis via salvage pathways. The results presented here will help in the development of strategies to overcome toxicity of phenolic compounds and facilitate engineering of more efficient microbial producers of biofuels and chemicals. Copyright © 2015, Pisithkul et al.

Phenolic Amides Are Potent Inhibitors of De Novo Nucleotide Biosynthesis

PubMed Central

Pisithkul, Tippapha; Jacobson, Tyler B.; O'Brien, Thomas J.; Stevenson, David M.

2015-01-01

An outstanding challenge toward efficient production of biofuels and value-added chemicals from plant biomass is the impact that lignocellulose-derived inhibitors have on microbial fermentations. Elucidating the mechanisms that underlie their toxicity is critical for developing strategies to overcome them. Here, using Escherichia coli as a model system, we investigated the metabolic effects and toxicity mechanisms of feruloyl amide and coumaroyl amide, the predominant phenolic compounds in ammonia-pretreated biomass hydrolysates. Using metabolomics, isotope tracers, and biochemical assays, we showed that these two phenolic amides act as potent and fast-acting inhibitors of purine and pyrimidine biosynthetic pathways. Feruloyl or coumaroyl amide exposure leads to (i) a rapid buildup of 5-phosphoribosyl-1-pyrophosphate (PRPP), a key precursor in nucleotide biosynthesis, (ii) a rapid decrease in the levels of pyrimidine biosynthetic intermediates, and (iii) a long-term generalized decrease in nucleotide and deoxynucleotide levels. Tracer experiments using 13C-labeled sugars and [15N]ammonia demonstrated that carbon and nitrogen fluxes into nucleotides and deoxynucleotides are inhibited by these phenolic amides. We found that these effects are mediated via direct inhibition of glutamine amidotransferases that participate in nucleotide biosynthetic pathways. In particular, feruloyl amide is a competitive inhibitor of glutamine PRPP amidotransferase (PurF), which catalyzes the first committed step in de novo purine biosynthesis. Finally, external nucleoside supplementation prevents phenolic amide-mediated growth inhibition by allowing nucleotide biosynthesis via salvage pathways. The results presented here will help in the development of strategies to overcome toxicity of phenolic compounds and facilitate engineering of more efficient microbial producers of biofuels and chemicals. PMID:26070680

Phenolic amides are potent inhibitors of De Novo nucleotide biosynthesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pisithkul, Tippapha; Jacobson, Tyler B.; O'Brien, Thomas J.

An outstanding challenge toward efficient production of biofuels and value-added chemicals from plant biomass is the impact that lignocellulose-derived inhibitors have on microbial fermentations. Elucidating the mechanisms that underlie their toxicity is critical for developing strategies to overcome them. Here, using Escherichia coli as a model system, we investigated the metabolic effects and toxicity mechanisms of feruloyl amide and coumaroyl amide, the predominant phenolic compounds in ammonia-pretreated biomass hydrolysates. Using metabolomics, isotope tracers, and biochemical assays, we showed that these two phenolic amides act as potent and fast-acting inhibitors of purine and pyrimidine biosynthetic pathways. Feruloyl or coumaroyl amide exposuremore » leads to (i) a rapid buildup of 5-phosphoribosyl-1-pyrophosphate (PRPP), a key precursor in nucleotide biosynthesis, (ii) a rapid decrease in the levels of pyrimidine biosynthetic intermediates, and (iii) a long-term generalized decrease in nucleotide and deoxynucleotide levels. Tracer experiments using 13C-labeled sugars and [ 15N]ammonia demonstrated that carbon and nitrogen fluxes into nucleotides and deoxynucleotides are inhibited by these phenolic amides. We found that these effects are mediated via direct inhibition of glutamine amidotransferases that participate in nucleotide biosynthetic pathways. In particular, feruloyl amide is a competitive inhibitor of glutamine PRPP amidotransferase (PurF), which catalyzes the first committed step in de novo purine biosynthesis. Finally, external nucleoside supplementation prevents phenolic amide-mediated growth inhibition by allowing nucleotide biosynthesis via salvage pathways. Furthermore, the results presented here will help in the development of strategies to overcome toxicity of phenolic compounds and facilitate engineering of more efficient microbial producers of biofuels and chemicals.« less

Phenolic amides are potent inhibitors of De Novo nucleotide biosynthesis

DOE PAGES

Pisithkul, Tippapha; Jacobson, Tyler B.; O'Brien, Thomas J.; ...

2015-06-12

An outstanding challenge toward efficient production of biofuels and value-added chemicals from plant biomass is the impact that lignocellulose-derived inhibitors have on microbial fermentations. Elucidating the mechanisms that underlie their toxicity is critical for developing strategies to overcome them. Here, using Escherichia coli as a model system, we investigated the metabolic effects and toxicity mechanisms of feruloyl amide and coumaroyl amide, the predominant phenolic compounds in ammonia-pretreated biomass hydrolysates. Using metabolomics, isotope tracers, and biochemical assays, we showed that these two phenolic amides act as potent and fast-acting inhibitors of purine and pyrimidine biosynthetic pathways. Feruloyl or coumaroyl amide exposuremore » leads to (i) a rapid buildup of 5-phosphoribosyl-1-pyrophosphate (PRPP), a key precursor in nucleotide biosynthesis, (ii) a rapid decrease in the levels of pyrimidine biosynthetic intermediates, and (iii) a long-term generalized decrease in nucleotide and deoxynucleotide levels. Tracer experiments using 13C-labeled sugars and [ 15N]ammonia demonstrated that carbon and nitrogen fluxes into nucleotides and deoxynucleotides are inhibited by these phenolic amides. We found that these effects are mediated via direct inhibition of glutamine amidotransferases that participate in nucleotide biosynthetic pathways. In particular, feruloyl amide is a competitive inhibitor of glutamine PRPP amidotransferase (PurF), which catalyzes the first committed step in de novo purine biosynthesis. Finally, external nucleoside supplementation prevents phenolic amide-mediated growth inhibition by allowing nucleotide biosynthesis via salvage pathways. Furthermore, the results presented here will help in the development of strategies to overcome toxicity of phenolic compounds and facilitate engineering of more efficient microbial producers of biofuels and chemicals.« less

Linear Strength Vortex Panel Method for NACA 4412 Airfoil

NASA Astrophysics Data System (ADS)

Liu, Han

2018-03-01

The objective of this article is to formulate numerical models for two-dimensional potential flow over the NACA 4412 Airfoil using linear vortex panel methods. By satisfying the no penetration boundary condition and Kutta condition, the circulation density on each boundary points (end point of every panel) are obtained and according to which, surface pressure distribution and lift coefficients of the airfoil are predicted and validated by Xfoil, an interactive program for the design and analysis of airfoil. The sensitivity of results to the number of panels is also investigated in the end, which shows that the results are sensitive to the number of panels when panel number ranges from 10 to 160. With the increasing panel number (N>160), the results become relatively insensitive to it.

N-acetylcysteine attenuates reactive-oxygen-species-mediated endoplasmic reticulum stress during liver ischemia-reperfusion injury

PubMed Central

Sun, Yong; Pu, Li-Yong; Lu, Ling; Wang, Xue-Hao; Zhang, Feng; Rao, Jian-Hua

2014-01-01

AIM: To investigate the effects of N-acetylcysteine (NAC) on endoplasmic reticulum (ER) stress and tissue injury during liver ischemia reperfusion injury (IRI). METHODS: Mice were injected with NAC (300 mg/kg) intraperitoneally 2 h before ischemia. Real-time polymerase chain reaction and western blotting determined ER stress molecules (GRP78, ATF4 and CHOP). To analyze the role of NAC in reactive oxygen species (ROS)-mediated ER stress and apoptosis, lactate dehydrogenase (LDH) was examined in cultured hepatocytes treated by H2O2 or thapsigargin (TG). RESULTS: NAC treatment significantly reduced the level of ROS and attenuated ROS-induced liver injury after IRI, based on glutathione, malondialdehyde, serum alanine aminotransferase levels, and histopathology. ROS-mediated ER stress was significantly inhibited in NAC-treated mice. In addition, NAC treatment significantly reduced caspase-3 activity and apoptosis after reperfusion, which correlated with the protein expression of Bcl-2 and Bcl-xl. Similarly, NAC treatment significantly inhibited LDH release from hepatocytes treated by H2O2 or TG. CONCLUSION: This study provides new evidence for the protective effects of NAC treatment on hepatocytes during IRI. Through inhibition of ROS-mediated ER stress, NAC may be critical to inhibit the ER-stress-related apoptosis pathway. PMID:25386077

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Critchley, J.A.J.H.; Beeley, J.M.; Clark, R.J.

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). Themore » 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.« less

Separating the from the Imagined: Flight Research at the NACA and NASA, 1915-1998

NASA Technical Reports Server (NTRS)

Gorn, Michael H.

2000-01-01

One of the most important, but under-appreciated, aspects of the NACA/NASA mission is its aeronautical R&D efforts. Within a short time of the first flight of the Wright brothers in 1903, the United States government recognized the importance of fostering development in the new and critical field of aeronautics. NASA's predecessor, the National Advisory Committee for Aeronautics (NACA), was chartered by Congress in 1915 specifically "to supervise and direct the scientific study of the problems of flight, with a view to their practical solution. " This became an enormously important government research and development activity for the next half century, materially enhancing the development of aeronautics 'in America. The results of the NACA's research appeared in more than 16,000 research reports of one type or another, distributed widely for the benefit of all. Many of the reports documenting R&D conducted under NACA auspices are still being used today. Since the creation of NASA in 1958, the critical R&D function has continued but is not well known. This work documents the historical R&D program of the agency by focusing on flight research.

Occurrence of N-phenylpropenoyl-L-amino acid amides in different herbal drugs and their influence on human keratinocytes, on human liver cells and on adhesion of Helicobacter pylori to the human stomach.

PubMed

Hensel, A; Deters, A M; Müller, G; Stark, T; Wittschier, N; Hofmann, T

2007-02-01

Thirty commonly used medicinal plants were screened by a selective and specific LC-MS/MS method for the occurrence of N-phenylpropenoyl- L-amino acid amides, a new homologous class of secondary products. In 15 plants, one or more of the respective derivatives (1 to 12) were found and quantitated. Especially roots from Angelica archangelica, fruits of Cassia angustifolia, C. senna, Coriandrum sativum, leaves from Hedera helix, flowers from Lavandula spec. and from Sambucus nigra contained high amounts (1 to 11 microg/g) of mixtures of the different amides 1 to 12. For functional investigations on potential activity in cellular physiology, two amides with an aliphatic (8) and an aromatic amino acid residue (5) were used. N-(E)-Caffeic acid L-aspartic acid amide (8) and N-(E)-caffeic acid L-tryptophan amide (5) stimulated mitochondrial activity as well as the proliferation rate of human liver cells (HepG2) at 10 microg/mL significantly. When monitoring the influence of selected phase I and II metabolizing enzymes, both compounds did not influence CYP3A4 gene expression, but stimulated CYP1A2 gene expression and inhibited GST expression. Also, the proliferation of human keratinocytes (NHK) was increased up to 150% by both amides 5 and 8; this stimulation was also detectable on the level of gene expression by an up-regulation of the transcription factor STAT6. The aliphatic aspartic compound 8 showed strong antiadhesive properties on the adhesion of Helicobacter pylori to human stomach tissue.

Optimization of Aryl Amides that Extend Survival in Prion-Infected Mice.

PubMed

Giles, Kurt; Berry, David B; Condello, Carlo; Dugger, Brittany N; Li, Zhe; Oehler, Abby; Bhardwaj, Sumita; Elepano, Manuel; Guan, Shenheng; Silber, B Michael; Olson, Steven H; Prusiner, Stanley B

2016-09-01

Developing therapeutics for neurodegenerative diseases (NDs) prevalent in the aging population remains a daunting challenge. With the growing understanding that many NDs progress by conformational self-templating of specific proteins, the prototypical prion diseases offer a platform for ND drug discovery. We evaluated high-throughput screening hits with the aryl amide scaffold and explored the structure-activity relationships around three series differing in their N-aryl core: benzoxazole, benzothiazole, and cyano. Potent anti-prion compounds were advanced to pharmacokinetic studies, and the resulting brain-penetrant leads from each series, together with a related N-aryl piperazine lead, were escalated to long-term dosing and efficacy studies. Compounds from each of the four series doubled the survival of mice infected with a mouse-passaged prion strain. Treatment with aryl amides altered prion strain properties, as evidenced by the distinct patterns of neuropathological deposition of prion protein and associated astrocytic gliosis in the brain; however, none of the aryl amide compounds resulted in drug-resistant prion strains, in contrast to previous studies on compounds with the 2-aminothiazole (2-AMT) scaffold. As seen with 2-AMTs and other effective anti-prion compounds reported to date, the novel aryl amides reported here were ineffective in prolonging the survival of transgenic mice infected with human prions. Most encouraging is our discovery that aryl amides show that the development of drug resistance is not an inevitable consequence of efficacious anti-prion therapeutics. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

N-acetylcysteine enhances endothelium-dependent vasorelaxation in the isolated rat mesenteric artery.

PubMed

Lopez, B L; Snyder, J W; Birenbaum, D S; Ma, X I

1998-10-01

Previous studies have suggested that N-acetylcysteine (NAC) may confer additional protection in acetaminophen (APAP) overdose by improving hepatic microcirculation. We hypothesize that NAC enhances release of nitric oxide (NO) from the vasculature. Sprague-Dawley rat superior mesenteric artery rings were suspended in oxygenated Krebs-Henseleit tissue baths and contracted with U-46619 (a thromboxane A2-mimetic). In part 1, the effect of NAC on endothelial cell (EC) release of NO was assessed by measurement of vasorelaxation induced by acetylcholine (ACh, an EC-dependent vasorelaxor) in the presence and absence of NAC. In part 2, the effect of glutathione (a major component of NAC hepatoprotection) was examined by measuring ACh-induced vasorelaxation in rings from rats treated with L-buthionine sulfoxamine (BSO, a glutathione synthesis inhibitor). Data were analyzed by repeated-measures ANOVA. Addition of 15 to 30 mmol/L NAC after ring contraction had no direct vasodilatory effect. By contrast, pretreatment of rings with NAC (15 mmol/L) enhanced vasorelaxation induced by ACh (95.0% +/- 7.9% versus 62.3% +/- 7.6% for control; ACh dose, 1 mumol/L; P < .001) or by A23187, a receptor-independent, NO-mediated vasodilator (91.6% +/- 9.6% versus 68.3% +/- 12.1% for control; A23187 dose, 1 mumol/L; P < .001). In rings from BSO-treated rats, NAC also enhanced vasorelaxation (76.5% +/- 7.1%; P < .001 versus control), but to a lesser degree than in nontreated rats. NAC enhances endothelium-dependent vasodilation in an isolated rat mesenteric artery ring preparation. In addition to its antioxidant effects, NAC may decrease APAP hepatotoxicity by stimulating NO production and improving microvascular circulation.

Raman spectra of crystalline secondary amides

NASA Astrophysics Data System (ADS)

Kolesov, Boris A.

2017-05-01

We present a Raman-spectroscopic study of secondary amides (acetanilide, methacetin, phenacetine, orthorhombic and monoclinic polymorphs of paracetamol) as well as simple amides formanilide and benzanilide. The study was carried out on single crystals and in the temperature range of 5-300 K. The series of compounds with the same molecular fragment - acetamide group - can serve as a model system to study the interrelation between this group and the properties of the intermolecular "peptide-type" NH ⋯ Odbnd C hydrogen bonds. For all of the "acetamide family" of the compounds, similar changes in the Raman spectra were observed upon cooling of the samples: emergence of new Amide I(-) and Amide I(+) bands, which are red and blue shifted, respectively, from the conventional Amide-I band by around of 5-10 cm- 1. Corresponding changes in the same temperature range were observed for the Nsbnd H out-of-plane bending (Amide V) and Nsbnd H stretching vibrations of the Nsbnd H ⋯ Odbnd C hydrogen bond. All of the spectral changes observed upon cooling of the samples can be presumed to result from a delocalization of the Amide-I and Nsbnd H modes and appearance of dynamical (Davydov's) splitting at low temperature.

40 CFR 721.3720 - Fatty amide.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Fatty amide. 721.3720 Section 721.3720... Fatty amide. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as a fatty amide (PMN P-91-87) is subject to reporting under this section...

40 CFR 721.2120 - Cyclic amide.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Cyclic amide. 721.2120 Section 721... Cyclic amide. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as a cyclic amide (PMN P-92-131) is subject to reporting under this section for the...

Condensation Reactions and Formation of Amides, Esters, and Nitriles Under Hydrothermal Conditions

NASA Astrophysics Data System (ADS)

Rushdi, Ahmed I.; Simoneit, Bernd R. T.

2004-06-01

Hydrothermal pyrolysis experiments were performed to assess condensation (dehydration) reactions to amide, ester, and nitrile functionalities from lipid precursors. Beside product formation, organic compound alteration and stability were also evaluated. Mixtures of nonadecanoic acid, hexadecanedioic acid, or hexadecanamide with water, ammonium bicarbonate, and oxalic acid were heated at 300°C for 72 h. In addition, mixtures of ammonium bicarbonate and oxalic acid solutions were used to test the abiotic formation of organic nitrogen compounds at the same temperature. The resulting products were condensation compounds such as amides, nitriles, and minor quantities of N-methylalkyl amides, alkanols, and esters. Mixtures of alkyl amide in water or oxalic acid yielded mainly hydrolysis and dehydration products, and with ammonium bicarbonate and oxalic acid the yield of condensation products was enhanced. The synthesis experiments with oxalic acid and ammonium bicarbonate solutions yielded homologous series of alkyl amides, alkyl amines, alkanes, and alkanoic acids, all with no carbon number predominances. These organic nitrogen compounds are stable and survive under the elevated temperatures of hydrothermal fluids.

Orders of Magnitude. A History of the NACA and NASA, 1915-1990. The NASA History Series.

ERIC Educational Resources Information Center

Bilstein, Roger E.

This is a history of the National Advisory Committee for Aeronautics (NACA) and its successor agency the National Aeronautics and Space Administration (NASA). Main chapters included are: (1) "NACA Origins (1915-1930)"; (2) "New Facilities, New Designs (1930-1945)"; (3) "Going Supersonic (1945-1958)"; (4) "On the…

Discovery of competing anaerobic and aerobic pathways in umpolung amide synthesis allows for site-selective amide 18O-labeling

PubMed Central

Shackleford, Jessica P.; Shen, Bo; Johnston, Jeffrey N.

2012-01-01

The mechanism of umpolung amide synthesis was probed by interrogating potential sources for the oxygen of the product amide carbonyl that emanates from the α-bromo nitroalkane substrate. Using a series of 18O-labeled substrates and reagents, evidence is gathered to advance two pathways from the putative tetrahedral intermediate. Under anaerobic conditions, a nitro-nitrite isomerization delivers the amide oxygen from nitro oxygen. The same homolytic nitro-carbon fragmentation can be diverted by capture of the carbon radical intermediate with oxygen gas (O2) to deliver the amide oxygen from O2. This understanding was used to develop a straightforward protocol for the preparation of 18O-labeled amides in peptides by simply performing the umpolung amide synthesis reaction under an atmosphere of . PMID:22184227

N-Acetylcysteine treatment of dystrophic mdx mice results in protein thiol modifications and inhibition of exercise induced myofibre necrosis.

PubMed

Terrill, Jessica R; Radley-Crabb, Hannah G; Grounds, Miranda D; Arthur, Peter G

2012-05-01

Oxidative stress is implicated as a factor that increases necrosis of skeletal muscles in Duchenne Muscular Dystrophy (DMD) and the dystrophic mdx mouse. Consequently, drugs that minimize oxidative stress are potential treatments for muscular dystrophy. This study examined the in vivo benefits to mdx mice of an antioxidant treatment with the cysteine precursor N-acetylcysteine (NAC), administered in drinking water. NAC was completely effective in preventing treadmill exercise-induced myofibre necrosis (assessed histologically) and the increased blood creatine kinase levels (a measure of sarcolemma leakiness) following exercise were significantly lower in the NAC treated mice. While NAC had no effect on malondialdehyde level or protein carbonylation (two indicators of irreversible oxidative damage), treatment with NAC for one week significantly decreased the oxidation of glutathione and protein thiols, and enhanced muscle protein thiol content. These data provide in vivo evidence for protective benefits of NAC treatment on dystropathology, potentially via protein thiol modifications. Copyright © 2011 Elsevier B.V. All rights reserved.

Synthesis and bio-physicochemical properties of amide-functionalized N-methylpiperazinium surfactants.

PubMed

Chauhan, Vinay; Singh, Sukhprit; Mishra, Rachana; Kaur, Gurcharan

2014-12-15

Four new amide functionalized N-methylpiperazinium amphiphiles having tetradecyl, hexadecyl alkyl chain lengths and counterions; chloride or bromide have been synthesized and characterized by various spectroscopic techniques. These new surfactants have been investigated in detail for their self-assembling behavior by surface tension, conductivity and fluorescence measurements. The thermodynamic parameters of these surfactants indicate that micellization is exothermic and entropy-driven. The dynamic light scattering (DLS) and transmission electron microscopy (TEM) experiments have been performed to insight the aggregate size of these cationics. Thermal degradation of these new surfactants has also been evaluated by thermal gravimetric analysis (TGA). These new surfactants form stable complexes with DNA as acknowledged by agarose gel electrophoresis, ethidium bromide exclusion and zeta potential measurements. They have also been found to have low cytotoxicity by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay on the C6 glioma cell line. Copyright © 2014 Elsevier Inc. All rights reserved.

The effects of NACA 0012 airfoil modification on aerodynamic performance improvement and obtaining high lift coefficient and post-stall airfoil

NASA Astrophysics Data System (ADS)

Sogukpinar, Haci

2018-02-01

In this study, aerodynamic performances of NACA 0012 airfoils with distinct modification are numerically investigated to obtain high lift coefficient and post-stall airfoils. NACA 0012 airfoil is divided into two part thought chord line then suction sides kept fixed and by changing the thickness of the pressure side new types of airfoil are created. Numerical experiments are then conducted by varying thickness of NACA 0012 from lower surface and different relative thicknesses asymmetrical airfoils are modified and NACA 0012-10, 0012-08, 0012-07, 0012-06, 0012-04, 0012-03, 0012-02, 0012-01 are created and simulated by using COMSOL software.

Phases and phase transition in insoluble and adsorbed monolayers of amide amphiphiles: Specific characteristics of the condensed phases.

PubMed

Vollhardt, D

2015-08-01

For understanding the role of amide containing amphiphiles in inherently complex biological processes, monolayers at the air-water interface are used as simple biomimetic model systems. The specific characteristics of the condensed phases and phase transition in insoluble and adsorbed monolayers of amide amphiphiles are surveyed to highlight the effect of the chemical structure of the amide amphiphiles on the interfacial interactions in model monolayers. The mesoscopic topography and/or two-dimensional lattice structures of selected amino acid amphiphiles, amphiphilic N-alkylaldonamide, amide amphiphiles with specific tailored headgroups, such as amide amphiphiles based on derivatized ethanolamine, e.g. acylethanolamines (NAEs) and N-,O-diacylethanolamines (DAEs) are presented. Special attention is devoted the dominance of N,O-diacylated ethanolamine in mixed amphiphilic acid amide monolayers. The evidence that a first order phase transition can occur in adsorption layers and that condensed phase domains of mesoscopic scale can be formed in adsorption layers was first obtained on the basis of the experimental characteristics of a tailored amide amphiphile. New thermodynamic and kinetic concepts for the theoretical description of the characteristics of amide amphiphile's monolayers were developed. In particular, the equation of state for Langmuir monolayers generalized for the case that one, two or more phase transitions occur, and the new theory for phase transition in adsorbed monolayers are experimentally confirmed at first by amide amphiphile monolayers. Despite the significant progress made towards the understanding the model systems, these model studies are still limited to transfer the gained knowledge to biological systems where the fundamental physical principles are operative in the same way. The study of biomimetic systems, as described in this review, is only a first step in this direction. Copyright © 2014 Elsevier B.V. All rights reserved.

Amides and Hydrazides from Amine and Hydrazine Hydrochlorides.

ERIC Educational Resources Information Center

Shama, Sami A.; Tran, Thuan L.

1978-01-01

This safe and efficient procedure for the synthesis of N-substituted amides and hydrazides is a modification of the Schotten-Bausmann procedure in which the amine or hydrazide is replaced by the corresponding hydrochloride salt, and the use of alkali is eliminated. (Author/BB)

A Randomized Controlled Pilot Trial of Oral N-Acetylcysteine in Children with Autism

PubMed Central

Hardan, Antonio Y.; Fung, Lawrence K.; Libove, Robin A.; Obukhanych, Tetyana V.; Nair, Surekha; Herzenberg, Leonore A.; Frazier, Thomas W.; Tirouvanziam, Rabindra

2016-01-01

Background An imbalance in the excitatory/inhibitory systems with abnormalities in the glutamatergic pathways has been implicated in the pathophysiology of autism. Furthermore, chronic redox imbalance was also recently linked to this disorder. The goal of this pilot study was to assess the feasibility of using oral N-acetylcysteine (NAC), a glutamatergic modulator and an antioxidant in the treatment of behavioral disturbance in children with autism. Methods This is a 12-week, double-blind, randomized, placebo-controlled study of NAC in children with autistic disorder. Subjects randomized to NAC were initiated at 900 mg daily for 4 weeks, then 900 mg twice-daily for 4 weeks and 900 mg three-times-daily for 4 weeks. The primary behavioral measure (Aberrant Behavior Checklist – Irritability subscale) and safety measures were performed at baseline, 4, 8, and 12 weeks. Secondary measures included the ABC-Stereotypy subscale, Repetitive Behavior Scale – Revised (RBS-R), and Social Responsiveness Scale (SRS). Results Thirty-three subjects (31 males, 2 females; aged 3.2–10.7 years) were randomized in the study. Follow-up data was available on fourteen subjects in the NAC group and fifteen in the placebo group. Oral NAC was well-tolerated with limited side effects. Compared to placebo, NAC resulted in significant improvements on ABC-Irritability subscale (F=6.80; p<.001; d=.96). Conclusions Data from this pilot investigation support the potential usefulness of NAC for treating irritability in children with autistic disorder. Large randomized controlled investigations are warranted. ClinicalTrials.gov Identifier NCT00627705 PMID:22342106

1H NMR spectra. Part 30(+): 1H chemical shifts in amides and the magnetic anisotropy, electric field and steric effects of the amide group.

PubMed

Abraham, Raymond J; Griffiths, Lee; Perez, Manuel

2013-03-01

The (1)H spectra of 37 amides in CDCl(3) solvent were analysed and the chemical shifts obtained. The molecular geometries and conformational analysis of these amides were considered in detail. The NMR spectral assignments are of interest, e.g. the assignments of the formamide NH(2) protons reverse in going from CDCl(3) to more polar solvents. The substituent chemical shifts of the amide group in both aliphatic and aromatic amides were analysed using an approach based on neural network data for near (≤3 bonds removed) protons and the electric field, magnetic anisotropy, steric and for aromatic systems π effects of the amide group for more distant protons. The electric field is calculated from the partial atomic charges on the N.C═O atoms of the amide group. The magnetic anisotropy of the carbonyl group was reproduced with the asymmetric magnetic anisotropy acting at the midpoint of the carbonyl bond. The values of the anisotropies Δχ(parl) and Δχ(perp) were for the aliphatic amides 10.53 and -23.67 (×10(-6) Å(3)/molecule) and for the aromatic amides 2.12 and -10.43 (×10(-6) Å(3)/molecule). The nitrogen anisotropy was 7.62 (×10(-6) Å(3)/molecule). These values are compared with previous literature values. The (1)H chemical shifts were calculated from the semi-empirical approach and also by gauge-independent atomic orbital calculations with the density functional theory method and B3LYP/6-31G(++) (d,p) basis set. The semi-empirical approach gave good agreement with root mean square error of 0.081 ppm for the data set of 280 entries. The gauge-independent atomic orbital approach was generally acceptable, but significant errors (ca. 1 ppm) were found for the NH and CHO protons and also for some other protons. Copyright © 2013 John Wiley & Sons, Ltd.

NACA collections: A directory of significant collections of the documents of the National Advisory Committee for Aeronautics

NASA Technical Reports Server (NTRS)

Smith, Ruth S.

1994-01-01

An alphabetical listing is given of 42 centers that hold National Advisory Committee for Aeronautics (NACA) documents. Information is given on the number of NACA holdings in paper copy, bound volumes, and microfiche. Additional information is given on the bibliographic records and availability.

Selective hydrogenation of amides to alcohols in water solvent over a heterogeneous CeO2-supported Ru catalyst.

PubMed

Tamura, Masazumi; Ishikawa, Susumu; Betchaku, Mii; Nakagawa, Yoshinao; Tomishige, Keiichi

2018-06-20

CeO2-supported Ru (Ru/CeO2) worked as an effective and reusable heterogeneous catalyst for the selective dissociation of the C-N bond in amides, particularly primary amides, with H2 in water solvent at low reaction temperature of 333 K, and high yields of the corresponding alcohols were obtained from primary amides.

Wind-tunnel investigation of an NACA 23012 airfoil with 30 percent-chord venetian-blind flaps

NASA Technical Reports Server (NTRS)

Rogallo, F M; Spano, Bartholomew S

1942-01-01

Report presents the results of an investigation made in the NACA 7 by 10-foot wind tunnel of a NACA 23012 airfoil with 30-percent-chord venetian-blind flaps having one, two, three, and four slats of Clark y section. The three-slat arrangements was aerodynamically the best of those tested but showed practically no improvement over the comparable arrangement used in the preliminary tests published in NACA Technical Report No. 689. The multiple-slat flaps gave slightly higher lift coefficients than the one-slat (Fowler) flap but gave considerably greater pitching-moment coefficients. An analysis of test data indicates that substitution of a thicker and more cambered section for the Clark y slats should improve the aerodynamic and the structural characteristics of the venetian-blind flap.

Storing red blood cells with vitamin C and N-acetylcysteine prevents oxidative stress-related lesions: a metabolomics overview.

PubMed

Pallotta, Valeria; Gevi, Federica; D'alessandro, Angelo; Zolla, Lello

2014-07-01

Recent advances in red blood cell metabolomics have paved the way for further improvements of storage solutions. In the present study, we exploited a validated high performance liquid chromatography-mass spectrometry analytical workflow to determine the effects of vitamin C and N-acetylcysteine supplementation (anti-oxidants) on the metabolome of erythrocytes stored in citrate-phosphate-dextrose saline-adenine-glucose-mannitol medium under blood bank conditions. We observed decreased energy metabolism fluxes (glycolysis and pentose phosphate pathway). A tentative explanation of this phenomenon could be related to the observed depression of the uptake of glucose, since glucose and ascorbate are known to compete for the same transporter. Anti-oxidant supplementation was effective in modulating the redox poise, through the promotion of glutathione homeostasis, which resulted in decreased haemolysis and less accumulation of malondialdehyde and oxidation by-products (including oxidized glutathione and prostaglandins). Anti-oxidants improved storage quality by coping with oxidative stress at the expense of glycolytic metabolism, although reservoirs of high energy phosphate compounds were preserved by reduced cyclic AMP-mediated release of ATP.

Storing red blood cells with vitamin C and N-acetylcysteine prevents oxidative stress-related lesions: a metabolomics overview

PubMed Central

Pallotta, Valeria; Gevi, Federica; D’Alessandro, Angelo; Zolla, Lello

2014-01-01

Background Recent advances in red blood cell metabolomics have paved the way for further improvements of storage solutions. Materials and methods In the present study, we exploited a validated high performance liquid chromatography-mass spectrometry analytical workflow to determine the effects of vitamin C and N-acetylcysteine supplementation (anti-oxidants) on the metabolome of erythrocytes stored in citrate-phosphate-dextrose saline-adenine-glucose-mannitol medium under blood bank conditions. Results We observed decreased energy metabolism fluxes (glycolysis and pentose phosphate pathway). A tentative explanation of this phenomenon could be related to the observed depression of the uptake of glucose, since glucose and ascorbate are known to compete for the same transporter. Anti-oxidant supplementation was effective in modulating the redox poise, through the promotion of glutathione homeostasis, which resulted in decreased haemolysis and less accumulation of malondialdehyde and oxidation by-products (including oxidized glutathione and prostaglandins). Discussion Anti-oxidants improved storage quality by coping with oxidative stress at the expense of glycolytic metabolism, although reservoirs of high energy phosphate compounds were preserved by reduced cyclic AMP-mediated release of ATP. PMID:25074788

Oral N-acetylcysteine reduces plasma homocysteine concentrations regardless of lipid or smoking status.

PubMed

Hildebrandt, Wulf; Sauer, Roland; Bonaterra, Gabriel; Dugi, Klaus A; Edler, Lutz; Kinscherf, Ralf

2015-11-01

Elevated total plasma homocysteine (tHcy) is considered to be an independent cardiovascular disease risk factor, although tHcy lowering by B-vitamins improves only certain clinical endpoints. N-acetylcysteine (NAC), a thiol-containing antioxidant, acutely lowers tHcy and possibly also blood pressure. However, to our knowledge, at present no conclusive long-term evaluation exists that controls for factors such as hyperlipidemia, smoking, medication, and disease stage, all of which affect the thiol redox state, including tHcy. We reanalyzed 2 double-blind, placebo-controlled trials in unmedicated middle-aged men, one in a hyperlipidemic group (HYL group; n = 40) and one in a normolipidemic group (NOL group; n = 42), each stratified for smokers and nonsmokers. We evaluated the effect of 4 wk of oral NAC (1.8 g/d) on tHcy (primary endpoint), plasma thiol (cysteine), and intracellular glutathione concentrations as well as on blood pressure. The HYL group had total cholesterol >220 mg/dL or triglycerides >150 mg/dL. NAC treatment significantly (P = 0.001, multivariate analysis of variance for repeated measures) lowered postabsorptive plasma concentrations of tHcy by -11.7% ± 3.0% (placebo: 4.1% ± 3.6%) while increasing those of cysteine by 28.1% ± 5.7% (placebo: 4.0% ± 3.4%) with no significant impact of hyperlipidemia or smoking. Moreover, NAC significantly decreased systolic (P = 0.003) and diastolic (P = 0.017) blood pressure within all subjects with a significant reduction in diastolic pressure in the HYL group (P = 0.008) but not in the NOL group. An explorative stepwise multiple regression analysis identified 1) post-treatment cysteine as well as 2) pretreatment tHcy and 3) albumin plasma concentrations as being significant contributors to tHcy reduction. Four weeks of oral NAC treatment significantly decreased plasma tHcy concentrations, irrespective of lipid or smoking status, and lowered systolic blood pressure in both normolipidemic and hyperlipidemic men

N-Acetylcysteine Reverses Anxiety and Oxidative Damage Induced by Unpredictable Chronic Stress in Zebrafish.

PubMed

Mocelin, Ricieri; Marcon, Matheus; D'ambros, Simone; Mattos, Juliane; Sachett, Adrieli; Siebel, Anna M; Herrmann, Ana P; Piato, Angelo

2018-06-06

There is accumulating evidence on the use of N-acetylcysteine (NAC) in the treatment of patients with neuropsychiatric disorders. As a multi-target drug and a glutathione precursor, NAC is a promising molecule in the management of stress-related disorders, for which there is an expanding field of research investigating novel therapies targeting oxidative pathways. The deleterious effects of chronic stress in the central nervous system are a result of glutamatergic hyperactivation, glutathione (GSH) depletion, oxidative stress, and increased inflammatory response, among others. The aim of this study was to investigate the effects of NAC in zebrafish submitted to unpredictable chronic stress (UCS). Animals were initially stressed or not for 7 days, followed by treatment with NAC (1 mg/L, 10 min) or vehicle for 7 days. UCS decreased the number of entries and time spent in the top area in the novel tank test, which indicate increased anxiety levels. It also increased reactive oxygen species (ROS) levels and lipid peroxidation (TBARS) while decreased non-protein thiols (NPSH) and superoxide dismutase (SOD) activity. NAC reversed the anxiety-like behavior and oxidative damage observed in stressed animals. Additional studies are needed to investigate the effects of this agent on glutamatergic modulation and inflammatory markers related to stress. Nevertheless, our study adds to the existing body of evidence supporting the clinical evaluation of NAC in mood disorders, anxiety, post-traumatic stress disorder, and other conditions associated with stress.

Effect of acetylcysteine on adaptation of intestinal smooth muscle after small bowel bypass

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weisbrodt, N.W.; Belloso, R.M.; Biskin, L.C.

1986-03-05

The authors have postulated that the adaptive changes in function and structure of bypassed segments of small bowel are due in part to the change in intestinal contents following operation. The purpose of these experiments was to determine if a mucolytic agent could alter the adaptation. Rats were anesthetized and a 70% jejunoileal bypass was performed. The bypassed segments then were perfused with either saline or acetylcysteine for 3-12 days. Then, either intestinal transit was determined using Cr-51, or segments were taken for morphometric analysis. Transit, as assessed by the geometric center, was increased 32% by acetylcysteine treatment. Treatment alsomore » caused a decrease in hypertrophy of the muscularis. Muscle wet weight, muscle cross-sectional area, and muscle layer thickness all were significantly less in those animals infused with acetyl-cysteine. No decreases in hypertrophy were seen in the in-continuity segments. These data indicate that alterations in intestinal content can affect the course of adaptation of intestinal muscle in response to small bowel bypass.« less

Drive Fan of the NACA's Icing Research Tunnel

NASA Image and Video Library

1956-10-21

A researcher examines the drive fan inside the Icing Research Tunnel at the National Advisory Committee for Aeronautics (NACA) Flight Propulsion Research Laboratory in Cleveland, Ohio. The facility was built in the mid-1940s to simulate the atmospheric conditions that caused ice to build up on aircraft. Carrier Corporation refrigeration equipment reduced the internal air temperature to -45⁰ F, and a spray bar system injected water droplets into the air stream. The 24-foot diameter drive fan, seen in this photograph, created air flow velocities up to 400 miles per hour. The 1950s were prime years for the Icing Research Tunnel. NACA engineers had spent the 1940s trying to resolve the complexities of the spray bar system. The final system put into operation in 1950 included six horizontal spray bars with 80 nozzles that produced a 4- by 4-foot cloud in the test section. The icing tunnel was used for extensive testing of civilian and military aircraft components in the 1950s. The NACA also launched a major investigation of the various methods of heating leading edge surfaces. The hot-air anti-icing technology used on today’s commercial transports was largely developed in the facility during this period. Lewis researchers also made significant breakthroughs with icing on radomes and jet engines. Although the Icing Research Tunnel yielded major breakthroughs in the 1950s, the Lewis icing research program began tapering off as interest in the space program grew. The icing tunnel’s use declined in 1956 and 1957. The launch of Sputnik in October 1957 signaled the end of the facility’s operation. The icing staff was transferred to other research projects and the icing tunnel was temporarily mothballed.

N-acetylcysteine with apocynin prevents hyperoxaluria-induced mitochondrial protein perturbations in nephrolithiasis.

PubMed

Sharma, Minu; Sud, Amit; Kaur, Tanzeer; Tandon, Chanderdeep; Singla, S K

2016-09-01

Diminished mitochondrial activities were deemed to play an imperative role in surged oxidative damage perceived in hyperoxaluric renal tissue. Proteomics is particularly valuable to delineate the damaging effects of oxidative stress on mitochondrial proteins. The present study was designed to apply large-scale proteomics to describe systematically how mitochondrial proteins/pathways govern the renal damage and calcium oxalate crystal adhesion in hyperoxaluria. Furthermore, the potential beneficial effects of combinatorial therapy with N-acetylcysteine (NAC) and apocynin were studied to establish its credibility in the modulation of hyperoxaluria-induced alterations in mitochondrial proteins. In an experimental setup with male Wistar rats, five groups were designed for 9 d. At the end of the experiment, 24-h urine was collected and rats were euthanized. Urinary samples were analyzed for kidney injury marker and creatinine clearance. Transmission electron microscopy revealed distorted renal mitochondria in hyperoxaluria but combinatorial therapy restored the normal mitochondrial architecture. Mitochondria were isolated from renal tissue of experimental rats, and mitochondrial membrane potential was analyzed. The two-dimensional electrophoresis (2-DE) based comparative proteomic analysis was performed on proteins isolated from renal mitochondria. The results revealed eight differentially expressed mitochondrial proteins in hyperoxaluric rats, which were identified by Matrix-assisted laser desorption/ionization time of flight/time of flight (MALDI-TOF/TOF) analysis. Identified proteins including those involved in important mitochondrial processes, e.g. antioxidant defense, energy metabolism, and electron transport chain. Therapeutic administration of NAC with apocynin significantly expunged hyperoxaluria-induced discrepancy in the renal mitochondrial proteins, bringing them closer to the controls. The results provide insights to further understand the underlying

Desktop Access to Full-Text NACA and NASA Reports: Systems Developed by NASA Langley Technical Library

NASA Technical Reports Server (NTRS)

Ambur, Manjula Y.; Adams, David L.; Trinidad, P. Paul

1997-01-01

NASA Langley Technical Library has been involved in developing systems for full-text information delivery of NACA/NASA technical reports since 1991. This paper will describe the two prototypes it has developed and the present production system configuration. The prototype systems are a NACA CD-ROM of thirty-three classic paper NACA reports and a network-based Full-text Electronic Reports Documents System (FEDS) constructed from both paper and electronic formats of NACA and NASA reports. The production system is the DigiDoc System (DIGItal Documents) presently being developed based on the experiences gained from the two prototypes. DigiDoc configuration integrates the on-line catalog database World Wide Web interface and PDF technology to provide a powerful and flexible search and retrieval system. It describes in detail significant achievements and lessons learned in terms of data conversion, storage technologies, full-text searching and retrieval, and image databases. The conclusions from the experiences of digitization and full- text access and future plans for DigiDoc system implementation are discussed.

Preliminary Tests in the NACA Free-Spinning Wind Tunnel

NASA Technical Reports Server (NTRS)

Zimmerman, C H

1937-01-01

Typical models and the testing technique used in the NACA free-spinning wind tunnel are described in detail. The results of tests on two models afford a comparison between the spinning characteristics of scale models in the tunnel and of the airplanes that they represent.

Efficacy of N-acetylcysteine, D-mannose and Morinda citrifolia to Treat Recurrent Cystitis in Breast Cancer Survivals

PubMed Central

MARCHIORI, DEBORA; PAOLO ZANELLO, PIER

2017-01-01

Background/Aim: Breast cancer survivors in adjuvant therapy, frequently experience the estrogen deficiency with genitourinary symptoms mostly represented by recurrent bacterial cystitis. The objective of the present study was to evaluate the effectiveness of N-acetylcysteine, D-mannose and Morinda citrifolia fruit extract (NDM), when associated to antibiotic therapy, in reducing the persistence of recurrent cystitis in this risk population. Patients and Methods: Sixty breast cancer survived women with recurrent cystitis were retrospectively examined. Group 1, comprised of 40 patients treated with antibiotic therapy associated with NDM lasting for six months, Group 2 comprised of 20 patients treated with antibiotics alone. Results: The use of NDM in combination with antibiotic therapy showed a significant reduction in positive urine cultures, compared to antibiotics alone. Subjects of Group 1 rather than those of Group 2, showed improvement in symptoms score of urgency, frequency, urge incontinence, recurrent cystitis, bladder and urethral pain. Conclusion: In breast cancer survived women affected by genitourinary discomfort, the combination of NDM and antibiotic therapy showed a greater efficacy in reducing urinary tract infections and urinary discomfort with respect to antibiotic use only. PMID:28882961

Efficacy of N-acetylcysteine, D-mannose and Morinda citrifolia to Treat Recurrent Cystitis in Breast Cancer Survivals.

PubMed

Marchiori, Debora; Zanello, Pier Paolo

2017-01-01

Breast cancer survivors in adjuvant therapy, frequently experience the estrogen deficiency with genitourinary symptoms mostly represented by recurrent bacterial cystitis. The objective of the present study was to evaluate the effectiveness of N-acetylcysteine, D-mannose and Morinda citrifolia fruit extract (NDM), when associated to antibiotic therapy, in reducing the persistence of recurrent cystitis in this risk population. Sixty breast cancer survived women with recurrent cystitis were retrospectively examined. Group 1, comprised of 40 patients treated with antibiotic therapy associated with NDM lasting for six months, Group 2 comprised of 20 patients treated with antibiotics alone. The use of NDM in combination with antibiotic therapy showed a significant reduction in positive urine cultures, compared to antibiotics alone. Subjects of Group 1 rather than those of Group 2, showed improvement in symptoms score of urgency, frequency, urge incontinence, recurrent cystitis, bladder and urethral pain. In breast cancer survived women affected by genitourinary discomfort, the combination of NDM and antibiotic therapy showed a greater efficacy in reducing urinary tract infections and urinary discomfort with respect to antibiotic use only. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Adjunctive N-acetylcysteine in depression: exploration of interleukin-6, C-reactive protein and brain-derived neurotrophic factor.

PubMed

Hasebe, Kyoko; Gray, Laura; Bortolasci, Chiara; Panizzutti, Bruna; Mohebbi, Mohammadreza; Kidnapillai, Srisaiyini; Spolding, Briana; Walder, Ken; Berk, Michael; Malhi, Gin; Dodd, Seetal; Dean, Olivia M

2017-12-01

This study aimed to explore effects of adjunctive N-acetylcysteine (NAC) treatment on inflammatory and neurogenesis markers in unipolar depression. We embarked on a 12-week clinical trial of NAC (2000 mg/day compared with placebo) as an adjunctive treatment for unipolar depression. A follow-up visit was conducted 4 weeks following the completion of treatment. We collected serum samples at baseline and the end of the treatment phase (week 12) to determine changes in interleukin-6 (IL6), C-reactive protein (CRP) and brain-derived neurotrophic factor (BDNF) following NAC treatment. NAC treatment significantly improved depressive symptoms on the Montgomery-Asberg Depression Rating Scale (MADRS) over 16 weeks of the trial. Serum levels of IL6 were associated with reductions of MADRS scores independent of treatment response. However, we found no significant changes in IL6, CRP and BDNF levels following NAC treatment. Overall, this suggests that our results failed to support the hypothesis that IL6, CRP and BDNF are directly involved in the therapeutic mechanism of NAC in depression. IL6 may be a useful marker for future exploration of treatment response.

The retinal rod Na(+)/Ca(2+),K(+) exchanger contains a noncleaved signal sequence required for translocation of the N terminus.

PubMed

McKiernan, C J; Friedlander, M

1999-12-31

The retinal rod Na(+)/Ca(2+),K(+) exchanger (RodX) is a polytopic membrane protein found in photoreceptor outer segments where it is the principal extruder of Ca(2+) ions during light adaptation. We have examined the role of the N-terminal 65 amino acids in targeting, translocation, and integration of the RodX using an in vitro translation/translocation system. cDNAs encoding human RodX and bovine RodX through the first transmembrane domain were correctly targeted and integrated into microsomal membranes; deletion of the N-terminal 65 amino acids (aa) resulted in a translation product that was not targeted or integrated. Deletion of the first 65 aa had no effect on membrane targeting of full-length RodX, but the N-terminal hydrophilic domain no longer translocated. Chimeric constructs encoding the first 65 aa of bovine RodX fused to globin were translocated across microsomal membranes, demonstrating that the sequence could function heterologously. Studies of fresh bovine retinal extracts demonstrated that the first 65 aa are present in the native protein. These data demonstrate that the first 65 aa of RodX constitute an uncleaved signal sequence required for the efficient membrane targeting and proper membrane integration of RodX.

The role of the thiol N-acetylcysteine in the prevention of tumor invasion and angiogenesis.

PubMed

Morini, M; Cai, T; Aluigi, M G; Noonan, D M; Masiello, L; De Flora, S; D'Agostini, F; Albini, A; Fassina, G

1999-01-01

We have extensively studied the effects of N-acetylcysteine (NAC), a cytoprotective drug that can prevent in vivo carcinogenesis. Here we review our findings NAC completely inhibits gelatinolytic activity of metalloproteases and chemotactic and invasive activities of tumor cells. In addition, NAC reduces the number of lung metastases when malignant murine melanoma cells are injected into nude mice. NAC treatment decreases the weight of primary tumors and produces a dose-related increase in tumor latency. Moreover, oral administration of NAC reduces the formation of spontaneous metastases. In experimental metastasis assays, we have found a synergistic reduction in the number of lung metastases after treatment with doxorubicin (DOX) and NAC in nude mice. In tumorigenicity and spontaneous metastasis assays, the combined administration of DOX and oral NAC again has shown synergistic effects on the frequency and weight of primary tumors and local recurrences and completely prevented the formation of lung metastases. The addition of NAC to endothelial cells strongly reduces their invasive activity in response to angiogenic stimuli. NAC inhibited the degradation and release of radiolabeled type IV collagen by activated endothelial cells, indicating that NAC blocks gelatinase activity. Oral administration of NAC reduces the angiogenic response induced by KS tumor cell products, confirming the ability of NAC to inhibit the invasive activity of endothelial cells in vivo and thereby blocking angiogenesis.

Sex-specific effects of N-acetylcysteine in neonatal rats treated with hypothermia after severe hypoxia-ischemia.

PubMed

Nie, Xingju; Lowe, Danielle W; Rollins, Laura Grace; Bentzley, Jessica; Fraser, Jamie L; Martin, Renee; Singh, Inderjit; Jenkins, Dorothea

2016-07-01

Approximately half of moderate to severely hypoxic-ischemic (HI) newborns do not respond to hypothermia, the only proven neuroprotective treatment. N-acetylcysteine (NAC), an antioxidant and glutathione precursor, shows promise for neuroprotection in combination with hypothermia, mitigating post-HI neuroinflammation due to oxidative stress. As mechanisms of HI injury and cell death differ in males and females, sex differences must be considered in translational research of neuroprotection. We assessed the potential toxicity and efficacy of NAC in combination with hypothermia, in male and female neonatal rats after severe HI injury. NAC 50mg/kg/d administered 1h after initiation of hypothermia significantly decreased iNOS expression and caspase 3 activation in the injured hemisphere versus hypothermia alone. However, only females treated with hypothermia +NAC 50mg/kg showed improvement in short-term infarct volumes compared with saline treated animals. Hypothermia alone had no effect in this severe model. When NAC was continued for 6 weeks, significant improvement in long-term neuromotor outcomes over hypothermia treatment alone was observed, controlling for sex. Antioxidants may provide insufficient neuroprotection after HI for neonatal males in the short term, while long-term therapy may benefit both sexes. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

(E)-α,β-unsaturated amides from tertiary amines, olefins and CO via Pd/Cu-catalyzed aerobic oxidative N-dealkylation.

PubMed

Shi, Renyi; Zhang, Hua; Lu, Lijun; Gan, Pei; Sha, Yuchen; Zhang, Heng; Liu, Qiang; Beller, Matthias; Lei, Aiwen

2015-02-21

A novel Pd/Cu-catalyzed chemoselective aerobic oxidative N-dealkylation/carbonylation reaction has been developed. Tertiary amines are utilized as a "reservoir" of "active" secondary amines in this transformation, which inhibits the formation of undesired by-products and the deactivation of the catalysts. This protocol allows for an efficient and straightforward construction of synthetically useful and bioactive (E)-α,β-unsaturated amide derivatives from easily available tertiary amines, olefins and CO.

Formation of the thioester, N,S-diacetylcysteine, from acetaldehyde and N,N'-diacetylcystine in aqueous solution with ultraviolet light

NASA Technical Reports Server (NTRS)

Weber, A. L.

1981-01-01

The thioester, N,S-diacetylcysteine, is formed during the illumination of phosphate buffered (pH 7.0) aqueous solutions of acetaldehyde and N,N'-diacetylcystine with ultraviolet light. The yield of N,S-diacetylcysteine relative to N-acetylcysteine and unidentified products progressively increases as ultraviolet light below 239 nm, 253 nm and 281 nm is cut off with optical filters. When ultraviolet light below 320 nm is removed with an optical filter, there is no detectable reaction. Illumination of 0.025 M N,N'-diacetylcystine with 0.5 M and 1.0 M acetaldehyde with filtered ultraviolet light gives, respectively, 20% and 80% yields of N,S-diacetylcysteine. In the reaction with 1.0 M acetaldehyde, N-acetylcysteine forms early in the reaction and later decreases with its conversion to N,S-diacetylcysteine. The prebiotic significance of these reactions is discussed.

Facile solvolysis of a surprisingly twisted tertiary amide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bloomfield, Aaron J.; Chaudhuri, Subhajyoti; Mercado, Brandon Q.

2016-01-05

In this study, a bicyclo[2.2.2]octane derivative containing both a tertiary amide and a methyl ester was shown crystallographically to adopt a conformation in which the amide is in the cis configuration, which is sterically disfavored, but electronically favored. The steric strain induces a significant torsion (15.9°) of the amide, thereby greatly increasing the solvolytic lability of the amide to the extent that we see competitive amide solvolysis in the presence of the normally more labile methyl ester also present in the molecule.

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

PubMed

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

Insecticidal, repellent and fungicidal properties of novel trifluoromethylphenyl amides

USDA-ARS?s Scientific Manuscript database

Twenty trifluoromethylphenyl amides were synthesized and evaluated as fungicides and as mosquito toxicants and repellents. Against Aedes aegypti larvae, (trifluoromethyl)phenyl)-3,5-dinitrobenzamide (1e) was the most toxic compound (24 h LC50 1940 nM), while against adults (trifluoromethyl)phenyl)-...

Direct Reaction of Amides with Nitric Oxide To Form Diazeniumdiolates

PubMed Central

2015-01-01

We report the apparently unprecedented direct reaction of nitric oxide (NO) with amides to generate ions of structure R(C=O)NH–N(O)=NO–, with examples including R = Me (1a) or 3-pyridyl (1b). The sodium salts of both released NO in pH 7.4 buffer, with 37 °C half-lives of 1–3 min. As NO-releasing drug candidates, diazeniumdiolated amides would have the advantage of generating only 1 equiv of base on hydrolyzing exhaustively to NO, in contrast to their amine counterparts, which generate 2 equiv of base. PMID:25210948

Rhodium-catalyzed asymmetric hydroboration of γ,δ-unsaturated amide derivatives: δ-borylated amides.

PubMed

Hoang, G L; Zhang, S; Takacs, J M

2018-05-08

γ,δ-Unsaturated amides in which the alkene moiety bears an aryl or heteroaryl substituent undergo regioselective rhodium-catalyzed δ-borylation by pinacolborane to afford chiral secondary benzylic boronic esters. The results contrast the γ-borylation of γ,δ-unsaturated amides in which the disubstituted alkene moiety bears only alkyl substituents; the reversal in regiochemistry is coupled with a reversal in the sense of π-facial selectivity.

Precision synthesis of colloidal inorganic nanocrystals using metal and metalloid amides

NASA Astrophysics Data System (ADS)

Yarema, Maksym; Caputo, Riccarda; Kovalenko, Maksym V.

2013-08-01

Rational selection of molecular precursors is the key consideration in the synthesis of inorganic nanocrystals and nanoparticles. This review highlights the state-of-the-art and future potential of metal amides as precursors in the solution-phase synthesis of monodisperse colloidal nanocrystals of metals and metal alloys, as well as metal oxides and chalcogenides. We exclusively focus on homoleptic metal and metalloid alkylamides M(NR2)n and silylamides M[N(SiMe3)2]n as predominant choice of element-nitrogen bonded precursors, which are often advantageous to commonly used metal-oxygen and metal-carbon bonded counterparts. In particular, these amides are highly reactive in oxidation, reduction and metathesis reactions; they are oxygen-free, easy-to-make and/or commercially available. A comprehensive literature review is complemented by our theoretical studies on the thermal stability of metal silylamides using molecular dynamics simulations.

N-acetylcysteine protects against cadmium-induced germ cell apoptosis by inhibiting endoplasmic reticulum stress in testes.

PubMed

Ji, Yan-Li; Wang, Hua; Zhang, Cheng; Zhang, Ying; Zhao, Mei; Chen, Yuan-Hua; Xu, De-Xiang

2013-03-01

Cadmium (Cd) is a reproductive toxicant that induces germ cell apoptosis in the testes. Previous studies have demonstrated that endoplasmic reticulum (ER) stress is involved in Cd-induced germ cell apoptosis. The aim of the present study was to investigate the effects of N-acetylcysteine (NAC), an antioxidant, on Cd-induced ER stress and germ cell apoptosis in the testes. Male CD-1 mice were intraperitoneally injected with CdCl2 (2.0 mg kg(-1)). As expected, acute Cd exposure induced germ cell apoptosis in the testes, as determined by terminal dUTP nick-end labelling (TUNEL). However, the administration of NAC alleviated Cd-induced germ cell apoptosis in the testes. Further analysis showed that NAC attenuated the Cd-induced upregulation of testicular glucose-regulated protein 78 (GRP78), an important ER molecular chaperone. Moreover, NAC inhibited the Cd-induced phosphorylation of testicular eukaryotic translation initiation factor 2α (eIF2α), a downstream target of the double-stranded RNA-activated kinase-like ER kinase (PERK) pathway. In addition, NAC blocked the Cd-induced activation of testicular X binding protein (XBP)-1, indicating that NAC attenuates the Cd-induced ER stress and the unfolded protein response (UPR). Interestingly, NAC almost completely prevented the Cd-induced elevation of C/EBP homologous protein (CHOP) and phosphorylation of c-Jun N-terminal kinase (JNK), two components of the ER stress-mediated apoptotic pathway. In conclusion, NAC protects against Cd-induced germ cell apoptosis by inhibiting endoplasmic reticulum stress in the testes.