Sample records for zytokinfreisetzung unter n-acetylcystein

  1. N-acetylcysteine: multiple clinical applications.

    Millea, Paul J


    N-acetylcysteine is the acetylated variant of the amino acid L-cysteine and is widely used as the specific antidote for acetaminophen overdose. Other applications for N-acetylcysteine supplementation supported by scientific evidence include prevention of chronic obstructive pulmonary disease exacerbation, prevention of contrast-induced kidney damage during imaging procedures, attenuation of illness from the influenza virus when started before infection, treatment of pulmonary fibrosis, and treatment of infertility in patients with clomiphene-resistant polycystic ovary syndrome. Preliminary studies suggest that N-acetylcysteine may also have a role as a cancer chemopreventive, an adjunct in the eradication of Helicobacter pylori, and prophylaxis of gentamicin-induced hearing loss in patients on renal dialysis.

  2. N-acetylcysteine increased rice yield



    N-acetylcysteine (NAC) biosynthesized reduced glutathione (GSH), which maintains redox homeostasis in plants under normal and stressful conditions. To justify the effects of NAC on rice production, we measured yield parameters, chlorophyll (Chl) content, minimum Chl fluorescence (Fo), maximum Chl fluorescence (Fm), quantum yield (Fv/Fm), net photosynthesis rate (Pn), photosynthetically active radiation (PAR), and relative water content (RWC). Four treatments, N1G0 (nitrogen (N) with no NAC), ...

  3. Damage induced by paracetamol compared with N-acetylcysteine

    Abdullah Kisaoglu


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

  4. N-acetylcysteine in acute pancreatitis

    Laura; Ramudo; Manuel; A; Manso


    Premature trypsinogen activation and production of oxygen free radicals (OFR) are early pathogenic events which occur within acinar cells and trigger acute pancreatitis (AP). OFR exert their harmful effects on various cell components causing lipid peroxidation, disturbances in calcium homeostasis and DNA damage, which lead to increased cell injury and eventually cell death. This review presents the most recent data concerning the effects of N-Acetylcysteine (NAC), in the treatment of AP. NAC is an antioxidant capable of restoring the levels of Glutathione, the most important cellular antioxidant. Studies show the benef icial effects of NAC treatment in preventing OFR production and therefore attenuating oxidative damage. Additionally, NAC treatment has been shown to prevent the increase in cytosolic Ca2+ concentration and reduce the accumulation of enzymes in acinar cells during AP. The prevention, by NAC, of these pathological events occurring within acinar would contribute to reducing the severity of AP. NAC is also capable of reducing the activation of transcription factors especially sensitive to the cellular redox state, such as Nuclear factor-κB, signal transducer and activator of transcription-3 and mitogenactivated protein kinase. This leads to a down-regulation of cytokines, adhesion molecules and chemokine expression in various cell types during AP. These f indingspoint to NAC as a powerful therapeutic treatment, attenuating oxidative-stress-induced cell injury and other pathological events at early stages of AP, and potentially contributing to reducion in the severity of disease.

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

    Ahmad Ghanizadeh


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

  6. N-Acetylcysteine in the prevention of ototoxicity

    Tepel, Martin


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

  7. Effect of oral N-acetylcysteine on mucus clearance.

    Millar, A B; Pavia, D; Agnew, J E; Lopez-Vidriero, M T; Lauque, D; Clarke, S W


    Oral N-acetylcysteine has been advocated as a mucolytic agent for use in chronic bronchitis. We have investigated the effects of regular use of this drug at a dose of 200 mg thrice daily for 4 weeks in nine patients with chronic bronchitis on lung function, lung mucociliary clearance and sputum viscosity in a controlled, double-blind, crossover study. No significant differences were found in lung function, mucociliary clearance curves or sputum viscosity following treatment with N-acetylcysteine compared to control or placebo measurements.

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

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


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

  9. Systematic review of N-acetylcysteine in cystic fibrosis

    Duijvestijn, YCM; Brand, PLP


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

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

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


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

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

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

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

  12. Systematic review of N-acetylcysteine in cystic fibrosis

    Duijvestijn, YCM; Brand, PLP


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

  13. Systematic review of N-acetylcysteine in cystic fibrosis

    Duijvestijn, YCM; Brand, PLP

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

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

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


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

  15. Treatment of a Gastric Lactobezoar with N-Acetylcysteine

    Brandon Sparks


    Full Text Available Lactobezoars are a rare finding with potentially serious sequelae in pediatric patients with feeding intolerance. Aggressive treatment may be preferred to traditional treatments to avoid complications in medically complex patients. In our patient, N-acetylcysteine lavage was a safe and effective alternative that resulted in rapid resolution of his feeding intolerance.

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

    Mlejnek, Petr; Dolezel, Petr


    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.

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

    Iversen, Helle Klingenberg


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

  18. Effects of N-acetylcysteine on asthma exacerbation.

    Aliyali, Masoud; Poorhasan Amiri, Ali; Sharifpoor, Ali; Zalli, Fatemeh


    Airway mucus hypersecretion and increased oxidative stress are clinical and pathophysiological features of asthma exacerbation. We studied effects of N-acetylcysteine (NAC) as a mucolytic and antioxidant agent in asthma exacerbation. In this randomized, single-blinded, placebo-controlled study 50 patients ( 17 male, 33 female, mean age 48.94+/-13.68) with asthma exacerbation were randomized to receive either oral 600 mg b.d. N-acetylcysteine or placebo in addition to standard treatment during 5 days hospitalization. Daily measurements of wheezing, dyspnea, cough, sputum, expectoration, night sleep scores and morning PEFR were performed. There was no significant difference in wheezing score between patients assigned NAC and those assigned placebo in day 5(0.84[SD 0.94] VS 0.87[SD 0.79]) and also in cough score (0.72[SD 0.84] VS 0.79[SD 0.97]), dyspnea score (0.84[SD 1.06] VS 0.91[SD 1.01]), sputum score(0.79[SD 0.83] VS 0.62[SD 0.71]), expectoration score(0.79[SD 0.97] VS 0.83[SD 1.09]), night sleep score(1[SD 1.17] VS 0.67[SD 0.98] and morning PEFR (256[SD 96.36] VS 282[SD 98.86]). We concluded that addition of N-acetylcysteine to usual asthma medication has no significant effect in treatment of asthma exacerbation.

  19. Evaluation of N-acetylcysteine for the prevention of contrast-induced nephropathy

    Sara K. Richter


    Full Text Available Background: Contrast-induced nephropathy (CIN remains a leading cause of acute renal failure in hospitalized patients. N-Acetylcysteine has been studied previously for the prevention of CIN, resulting in mixed findings. Objective: The objective of this study was to determine the impact of N-acetylcysteine on the development of CIN in order to guide its use at community, teaching hospitals. Methods: Patients admitted between January 1 and December 31, 2011, receiving intravenous radiocontrast dye were included if they were compliant with two or more of the following conditions: baseline serum creatinine >1.2 mg/dL or estimated creatinine clearance <50 mL/min, age ≥75 years, diabetes mellitus, heart failure, or hypertension. The primary outcome was the difference in the proportion of patients in each group (N-acetylcysteine or no N-acetylcysteine who developed CIN, which was defined as a ≥0.5 mg/dL increase in serum creatinine or a ≥25% increase in serum creatinine within 12–96 hours post-exposure to contrast. Results: A total of 302 patients were included, 151 who received N-acetylcysteine and 151 who did not receive N-acetylcysteine. Patients who received N-acetylcysteine had significantly worse renal function at baseline than those who did not receive N-acetylcysteine (mean pre-contrast serum creatinine, 1.41 vs. 0.95 mg/dL, p<0.0001. A lower proportion of patients developing CIN was observed between those who received N-acetylcysteine and those who did not receive N-acetylcysteine (10.2% vs. 21.8%, p=0.0428. Conclusions: The use of N-acetylcysteine was likely associated with a reduced incidence of CIN in patients at risk for CIN development. Based on these results, hospitals may benefit from the development of a protocol to guide the appropriate use of N-acetylcysteine.

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

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


    1. The combined antidote effect of N-acetylcysteine and ethanol on the toxicity of acetaminophen was investigated. 2. Fed male mice were given acetaminophen i.p. (600 mg kg-1) and after 5 min in addition ethanol i.p. (0.2 ml, 19% v/v), N-acetylcysteine i.p. (1.2 g kg-1, 0.2 ml), N-acetylcysteine ...

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

    Sisombath, Natalie S.; Jalilehvand, Farideh


    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...

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

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


    Oxidative stress is of importance in the pathophysiology of sickle cell disease (SCD). In this open label randomized pilot study the effects of oral N-acetylcysteine (NAC) on phosphatidylserine (PS) expression as marker of cellular oxidative damage (primary end point), and markers of hemolysis, coagulation and endothelial activation and NAC tolerability (secondary end points) were studied. Eleven consecutive patients (ten homozygous [HbSS] sickle cell patients, one HbSβ(0)-thalassemia patient) were randomly assigned to treatment with either 1,200 or 2,400 mg NAC daily during 6 weeks. The data indicate an increment in whole blood glutathione levels and a decrease in erythrocyte outer membrane phosphatidylserine exposure, plasma levels of advanced glycation end-products (AGEs) and cell-free hemoglobin after 6 weeks of NAC treatment in both dose groups. One patient did not tolerate the 2,400 mg dose and continued with the 1,200 mg dose. During the study period, none of the patients experienced painful crises or other significant SCD or NAC related complications. These data indicate that N-acetylcysteine treatment of sickle cell patients may reduce SCD related oxidative stress.

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

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


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

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

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


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

  5. N-Acetylcysteine in the Treatment of Excoriation Disorder

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


    -3000 mg/d) or placebo was administered for 12 weeks. Main Outcomes and Measures 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......Importance Excoriation (skin-picking) disorder (SPD) is a disabling, underrecognized condition in which individuals repeatedly pick at their skin, leading to noticeable tissue damage. To date, there has been no clearly effective pharmacologic or psychological treatment for SPD. Objective...... To determine whether N-acetylcysteine, an amino acid that appears to restore extracellular glutamate concentration in the nucleus accumbens, will be more effective than placebo in reducing compulsive picking behavior. Design, Setting, and Participants A randomized, double-blind trial was conducted...

  6. N-acetylcysteine amide, a promising antidote for acetaminophen toxicity.

    Khayyat, Ahdab; Tobwala, Shakila; Hart, Marcia; Ercal, Nuran


    Acetaminophen (N-acetyl-p-aminophenol, APAP) is one of the most widely used over the counter antipyretic and analgesic medications. It is safe at therapeutic doses, but its overdose can result in severe hepatotoxicity, a leading cause of drug-induced acute liver failure in the USA. Depletion of glutathione (GSH) is one of the initiating steps in APAP-induced hepatotoxicity; therefore, one strategy for restricting organ damage is to restore GSH levels by using GSH prodrugs. N-acetylcysteine (NAC), a GSH precursor, is the only currently approved antidote for an acetaminophen overdose. Unfortunately, fairly high doses and longer treatment times are required due to its poor bioavailability. In addition, oral and I.V. administration of NAC in a hospital setting are laborious and costly. Therefore, we studied the protective effects of N-acetylcysteine amide (NACA), a novel antioxidant with higher bioavailability, and compared it with NAC in APAP-induced hepatotoxicity in C57BL/6 mice. Our results showed that NACA is better than NAC at a low dose (106mg/kg) in preventing oxidative stress and protecting against APAP-induced damage. NACA significantly increased GSH levels and the GSH/GSSG ratio in the liver to 66.5% and 60.5% of the control, respectively; and it reduced the level of ALT by 30%. However, at the dose used, NAC was not effective in combating the oxidative stress induced by APAP. Thus, NACA appears to be better than NAC in reducing the oxidative stress induced by APAP. It would be of great value in the health care field to develop drugs like NACA as more effective and safer options for the prevention and therapeutic intervention in APAP-induced toxicity.

  7. Spectral characterization of fluorescent 5-iodoacetamidotetramethylrhodamine and its N-acetylcysteine derivative

    Zandvoort, van M.A.M.J.; Vossen, D.L.J.; Ginkel, van G.; Torre, R.; Bartolini, P.; Ricci, M.; Thomas-Oates, J.; Zuilhof, H.


    This study describes a spectroscopic characterization of the fluorescent probe 5-iodoacetamidotetramethylrhodamine and its N-acetylcysteine derivative in various solvents. The monomeric character and the purity of the two compounds was established in ethanol, ethanol-water, water, dimethylformamide,

  8. Neuron differentiation and neuritogenesis stimulated by N-acetylcysteine(NAC)

    Hao-ran QIAN; Yi YANG


    Aim:To investigate the effect of N-acetylcysteine (NAC),a potent antioxidant,on neuron differentiation of cultured mouse embryonic stem cells (ESCs) induced by retinoic acid (RA) in vitro.Superior cervical ganglion (SCG) neurons were used to study the effect of NAC on neuritogenesis.Methods:Immunoblotting was performed to detect the expression of microtubule-associated protein 2 (MAP2).MTT assays were used to determine cell viability.Cell death was estimated with trypan blue exclusion and Hoechst 33342 staining.Immunocytochemical analysis was carried out to identify neurons.Results:We obtained a high percentage of MAP2-positive neurons derived from embryoid bodies (EBs) induced by RA by administering 1 mmol/L NAC at differentiation day O.On differentiation day 8,the expression of MAP2 protein was strongly upregulated in the presence of NAC.NAC promoted neuron differentiation of ES cells in a dose- and time-dependent manner.Notably,NAC suppressed cell death caused/Jy RA during neuron differentiation.In addition,neurite extension of SCG neurons was greatly stimulated in the presence of NAC.Conclusion:These results show that NAC enhanced both neuron differentiation and neuritogenesis,suggesting that it may be used in the development of novel therapeutic approaches targeting neuron loss and neurite dystrophy in neurodegenerative diseases.

  9. N-acetylcysteine Prevents Alcohol Related Neuroinflammation in Rats.

    Schneider, Ricardo; Bandiera, Solange; Souza, Débora Guerini; Bellaver, Bruna; Caletti, Greice; Quincozes-Santos, André; Elisabetsky, Elaine; Gomez, Rosane


    Alcoholism has been characterized as a systemic pro-inflammatory condition and alcohol withdrawal has been linked to various changes in the brain homeostasis, including oxidative stress and glutamate hyperactivity. N-acetylcysteine (NAC) is an anti-inflammatory and antioxidant multi-target drug with promising results in psychiatry, including drug addiction. We assessed the effects of NAC on the serum and brain inflammatory cytokines after cessation of chronic alcohol treatment in rats. Male Wistar rats received 2 g/kg alcohol or vehicle twice a day by oral gavage for 30 days. Rats were treated, from day 31 to 34, with NAC (60 or 90 mg/kg) or saline, intraperitoneally, once daily. Rats were sacrificed at day 35, trunk blood was collected and the frontal cortex and hippocampus dissected for assessment of TNF-α, IL-1β, IL-6, IL-18, IL-10. NAC prevented the increase of pro-inflammatory cytokines and the decrease of anti-inflammatory cytokine in the frontal cortex and hippocampus. No changes were observed on serum cytokines. We conclude that NAC protects against inflammation induced by chronic (30 days) alcohol ingestion followed by 5 days cessation in two rat brain areas. Because inflammation has been documented and associated with craving and relapse in alcoholics, the data revealed by this study points to the validity of NAC clinical evaluation in the context of alcohol detoxification and withdrawal.

  10. N-acetylcysteine, a novel treatment for Helicobacter pylori infection.

    Huynh, Hien Quoc; Couper, Richard T L; Tran, Cuong D; Moore, Lynette; Kelso, Richard; Butler, Ross N


    N-Acetylcysteine (NAC), being both a mucolytic agent and a thiol-containing antioxidant, may affect the establishment and maintenance of H. pylori infection within the gastric mucus layer and mucosa. Agar and broth dilution susceptibility tests determined the MIC of H. pylori strain SSI to NAC. H. pylori load in SSI strain-infected C57BL mice was determined as colony forming units per gram of gastric tissue. Gastritis assessment was scored and gastric surface hydrophobicity was determined by contact angle measurement. MICs of NAC were 5 to 10 and 10 to 15 mg/ml using the agar dilution and broth dilution methods, respectively. NAC (120 mg per day for 14 days) reduced the H. pylori load in mice by almost 1 log compared with sham treatment. Pretreatment with NAC (40 mg/day) also significantly reduced the H. pylori load but did not prevent H. pylori colonization. Both H. pylori infection and NAC reduced the surface hydrophobicity of murine gastric mucosa. No significant differences were observed in the gastritis scores of H. felis- or H. pylori-infected mice receiving either NAC or sham treatments. This study demonstrates that NAC inhibits the growth of H. pylori in both agar and broth susceptibility tests and in H. pylori-infected mice. NAC did not alter the severity of H. pylori- or H. felis-induced gastritis.

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

    Miyake, Nobumi; Miyamoto, Seiya


    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.

  12. N-Acetylcysteine and mucociliary activity in mammalian airways.

    Iravani, J; Melville, G N; Horstmann, G


    The effect of N-acetylcysteine on mucus trasnport velocity (MV), ciliary beat frequency (CBF), mucus production (MP), mucus lysis and on the micro-morphology of the secretory cells was studied in mammalian airways. The results showed that: 1. MV increased in healthy rats and rabbits, as well as in bronchitic rats, after concentrations as low as 10(-14) g/ml. Depression of MV occurred first at 10(-6) and 10(-5) g/ml in healthy and bronchitic animals, respectively. 2. CBF was stimulated at concentrations between 10(-12) and 10(-10) g/ml and decreased at concentrations above 10(-8) g/ml. 3. MP increased by approximately 100% over control values. 4. Lysis of stagnant mucus was evident first at a concentration of 10(-11) g/ml after 15 min incubation. 5. TEM confirmed the increased activity of the mucus secreting cells and showed that no pathological changes occurred within the cell following incubation at 10(-7) g/ml for up to 150 min. The importance of these findings on the overall mucociliary function is discussed.

  13. Effect of N-acetylcysteine on vasospasm in subarachnoid hemorrhage

    Nelson de Azambuja Pereira Filho


    Full Text Available Vasospasm remains an extremely serious complication that affects patients presenting with subarachnoid hemorrhage (SAH due to ruptured intracranial aneurysms. The current therapeutic armamentarium is still insufficient in many cases, and the search for new therapies is necessary. In this study, we evaluated the effect of N-acetylcysteine (NAC on cerebral arterial vasospasm using an experimental model. Twenty-four wistar rats were divided into 4 groups: [1] Control, [2] SAH, [3] SAH+NAC and [4] SAH+Placebo. The experimental model employed double subarachnoid injections of autologous blood. The proposed dose of NAC was 250 mg/kg intraperitoneally per day. We analyzed the inner area of the basilar artery to assess the action of NAC. The experimental model proved to be very adequate, with a mortality rate of 4%. The inner area of the basilar artery in the SAH group showed significant difference to the control group (p=0.009. The use of NAC significantly reduced vasospasm as compared to the untreated group (p=0.048 and established no significant difference to the control group (p=0.098. There was no significant improvement with the administration of placebo (p=0.97. The model of the dual hemorrhage proved to be very useful for vasospasm simulation, with overall low mortality. The administration of NAC significantly reduced vasospasm resulting from SAH, and may represent a new therapeutic alternative.

  14. Improvement in endothelial dysfunction in patients with systemic lupus erythematosus with N-acetylcysteine and atorvastatin

    Jyothsna Kudaravalli


    Conclusion: The presence of arterial stiffness indicated endothelial dysfunction. There was reduction in RI and SI with treatment of N-acetylcysteine and atorvastatin suggesting improvement in endothelial dysfunction. There was decrease in CRP (a marker of inflammation and MDA after treatment with N-acetylcysteine suggesting improvement in endothelial dysfunction. There was reduction in CRP after treatment with atorvastatin, suggesting improvement in endothelial function. Improvement in endothelial dysfunction is associated with decreased incidence of cardiovascular and cerebrovascular accidents.

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

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


    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). The efficacy of N-acetylcysteine in wound healing is comparable to dexpanthenol, and both substances can be used to improve wound healing. PMID:25583306

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

    Scholze, Alexandra


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

  17. Does N-acetylcysteine modulate posttranslational modifications of transthyretin in hemodialysis patients?

    Henze, Andrea; Raila, Jens; Scholze, Alexandra;


    ) in plasma of hemodialysis patients in a randomized, placebo-controlled study. TTR was selected due to its low molecular weight and the free cysteine residue in the polypeptide chain, which is known to be extensively modified by formation of mixed disulfides. The intravenous application of N......-acetylcysteine during a hemodialysis session resulted in a substantial increase of native TTR from median 15% (range 8.8-30%) to median 40% (37-50) and reduction of S-cysteinylated TTR [51% (44-60) vs. 6.6% (2.4-10)]. Additionally the pronounced formation of a TTR-N-acetylcysteine adduct was detected. However, all...

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

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


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

  19. Evaluation of topical n-acetylcysteine in diversion colitis

    Marcos Gonçalves de Almeida


    Full Text Available INTRODUCTION: Diversion colitis (DC is a benign condition characterized by the appearance of inflammation in the mucosa of the colon or rectum devoid of fecal stream. Oxidative stress has been associated with the etiopathogenesis of the disease. N-acetylcysteine (NAC is a substance with antioxidant properties, used in different treatments of inflammatory diseases. The purpose of this study was to evaluate the effects of topical applications of NAC in an experimental model of DC. METHODS: Thirty-six Wistar rats were submitted to deviation of fecal stream by proximal colostomy and a distal mucosal fistula. They were distributed into 3 experimental groups of 12 animals according to the daily application of enemas containing 0.9% saline or 2 doses of NAC, 25 mg/kg and 100 mg/kg, respectively. In each group, half of the animals were sacrificed after two weeks of irrigation and half after four weeks of irrigation. The diagnosis of colitis was assessed by histopathological analysis and the grade of inflammation by inflammatory grading scale. The results were evaluated with the Mann-Whitney test, adopting significance level of 5% (pINTRODUÇÃO: Colite de exclusão (CE é uma condição benigna caracterizada pelo desenvolvimento de inflamação na mucosa do cólon desprovida de trânsito fecal. O estresse oxidativo tem sido implicado na patogênese da doença. A n-acetilcisteína (NAC é uma substância com efeitos antioxidantes, sendo utilizada no tratamento de várias doenças inflamatórias. OBJETIVO: Avaliar os efeitos da aplicação tópica de NAC em modelo de CE. MÉTODO: Trinta e seis ratos Wistar foram submetidos ao desvio do trânsito por meio de colostomia proximal e fístula mucosa distal. Os animais foram distribuídos em três grupos experimentais de igual tamanho segundo a aplicação de enemas diários contendo soro fisiológico 0,9% ou NAC nas concentrações de 25 mg/kg ou 100 mg/kg. Em cada grupo, metade dos animais foi sacrificada ap

  20. Effects of oral N-acetylcysteine on plasma homocysteine and whole blood glutathione levels in healthy, non-pregnant women.

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


    Oral N-acetylcysteine supplementation in nine young healthy females induced a quick and highly significant decrease in plasma homocysteine levels and an increase in whole blood concentration of the antioxidant glutathione. N-acetylcysteine impresses as an efficient drug in lowering homocysteine concentration and might be beneficial for individuals with hyperhomocysteinemia who are at increased risk of cardiovascular disease.

  1. The mechanism of N-acetylcysteine photoprotection is not related to dipyrimidine photoproducts

    Nijmeijer, B.A.; Steenvoorden, D.P.T.; Beijersbergen Van Henegouwen, G.M.J.; Roza, L.; Vink, A.A.


    Topical application of N-acetylcysteine prior to UVB irradiation of BALB/c mice has previously been shown to inhibit systemic suppression of the contact hypersensitivity response. Formation of cis-urocanic acid, however, is not affected. Besides urocanic acid, UV-induced DNA damage has been held res

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

    Rybolt, Thomas R.; And Others


    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)

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

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


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

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


    NAC is a potent antioxidant that is used clin- ically to treat acetaminophen overdose and as amucolytic to treat cystic fibrosis (Ramon Diaz-Arrastia...effect of N-acetylcysteine in the nucleus accumbens on neurotransmission and relapse to cocaine . Biol. Psychiatry 71 (11), 978–986 (http

  5. The mechanism of N-acetylcysteine photoprotection is not related to dipyrimidine photoproducts

    Nijmeijer, B.A.; Steenvoorden, D.P.T.; Beijersbergen Van Henegouwen, G.M.J.; Roza, L.; Vink, A.A.


    Topical application of N-acetylcysteine prior to UVB irradiation of BALB/c mice has previously been shown to inhibit systemic suppression of the contact hypersensitivity response. Formation of cis-urocanic acid, however, is not affected. Besides urocanic acid, UV-induced DNA damage has been held res

  6. The mechanism of N-acetylcysteine photoprotection is not related to dipyrimidine photoproducts

    Nijmeijer, B.A.; Steenvoorden, D.P.T.; Beijersbergen Van Henegouwen, G.M.J.; Roza, L.; Vink, A.A.


    Topical application of N-acetylcysteine prior to UVB irradiation of BALB/c mice has previously been shown to inhibit systemic suppression of the contact hypersensitivity response. Formation of cis-urocanic acid, however, is not affected. Besides urocanic acid, UV-induced DNA damage has been held

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

    Jepsen, S; Herlevsen, P; Knudsen, P


    OBJECTIVE: To examine whether the antioxidant N-acetylcysteine could ameliorate the course of the adult respiratory distress syndrome (ARDS) in man. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Medical and surgical ICU in a regional hospital. PATIENTS: Sixty-six ICU patients...

  8. N-acetylcysteine attenuates progression of liver pathology in a rat model of nonalcoholic steatohepatitis

    A "two-hit" model for non-alcoholic steatohepatitis (NASH) has been proposed in which steatosis constitutes the "first hit" and sensitizes the liver to potential "second hits" resulting in NASH. Oxidative stress is considered a candidate for the second hit. N-acetylcysteine (NAC), an antioxidant, ...

  9. Effect of ciprofloxacin and N-acetylcysteine on bacterial adherence and biofilm formation on ureteral stent surfaces.

    El-Feky, Mohamed A; El-Rehewy, Mostafa S; Hassan, Mona A; Abolella, Hassan A; Abd El-Baky, Rehab M; Gad, Gamal F


    The aim of this study was to evaluate the effect of ciprofloxacin (CIP), N-acetylcysteine (NAC) alone and in combination on biofilm production and pre-formed mature biofilms on ureteral stent surfaces. Two strains each of Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebseilla pneumoniae, Pseudomonas aeruginosa and Proteus vulgaris, recently isolated from patients undergoing ureteral stent removal and shown to be capable of biofilm production, were used in this study. The inhibitory effects of ciprofloxacin, N-acetylcysteine and ciprofloxacin/N-acetylcysteine combination were determined by static adherence assay. Ciprofloxacin (MIC and 2 MIC) and N-acetylcysteine (2 and 4 mg/ml) inhibited biofilm production by > or = 60% in all tested microorganisms. Disruption of pre-formed biofilms of all tested microorganisms was found to be > or = 78% in the presence of ciprofloxacin (MIC and 2 MIC) and > or = 62% in the presence of N-acetylcysteine (2 and 4 mg/ml), compared to controls. Ciprofloxacin/N-acetylcysteine showed the highest inhibitory effect on biofilm production (94-100%) and the highest disruptive effect on the pre-formed biofilms (86-100%) in comparison to controls. N-acetylcysteine was found to increase the therapeutic efficacy of ciprofloxacin by degrading the extracellular polysaccharide matrix of biofilms. These data are statistically significant. The inhibitory effects of ciprofloxacin and N-acetylcysteine on biofilm production were also verified by scanning electron microscope (SEM). In conclusion, Ciprofloxacin/N-acetylcysteine combinations have the highest inhibitory effect on biofilm production and the highest ability to eradicate pre-formed mature biofilms.

  10. Inhibitory effects of N-acetylcysteine on superoxide anion generation in human polymorphonuclear leukocytes.

    Villagrasa, V; Cortijo, J; Martí-Cabrera, M; Ortiz, J L; Berto, L; Esteras, A; Bruseghini, L; Morcillo, E J


    It has been suggested that reactive oxygen species released by activated polymorphonuclear leukocytes (PMN) in man is one mechanism of tissue injury. Therapeutic action aimed at increasing antioxidant defence mechanisms is still a clinical challenge. This study examines the activity of N-acetylcysteine, a known antioxidant, in the protection of PMN exposed in-vitro to the chemoattractant peptide fMet-Leu-Phe (FMLP), the protein kinase C activator phorbol myristate acetate or the lipid peroxidation promoter t-butyl hydroperoxide. FMLP (3-300 nM) and phorbol myristate acetate (160 pm-160 nM) induced concentration-related superoxide anion generation. Pre-treatment with N-acetylcysteine (33-333 microM) resulted in concentration-related inhibition of superoxide production induced by FMLP (30 nM) or phorbol myristate acetate (16 nM);-log IC50 values were 3.97 +/- 0.07 and 3.91 +/- 0.10, respectively. Changes in intracellular calcium ion concentration ([Ca2+]i) induced by FMLP (30 nM) were studied in fura-2-loaded human PMN. FMLP produced a transient calcium response, i.e. a peak followed by decay to a residual value above baseline. N-Acetylcysteine (333 microM) did not affect either basal [Ca2+]i values or changes in [Ca2+]i values after treatment with FMLP. Activation by phorbol myristate acetate caused a reduction in glutathione levels from 5.94 +/- 0.86 (control) to 1.84 +/- 0.51 nmol/3 x 10(6) cells (P 0.05 compared with control). Exposure to t-butyl hydroperoxide (0.5 mM, 30 min) markedly increased malondialdehyde levels (from 0.03 +/- 0.02 to 0.73 +/- 0.07 nmol/10(6) cells), and index of lipid peroxidation. Malondialdehyde levels were significantly reduced in PMN treated with N-acetylcysteine (333 microM; 0.55 +/- 0.04 nmol/10(6) cells; P < 0.05 compared with untreated cells exposed to t-butyl hydroperoxide). In conclusion, N-acetylcysteine reduces superoxide generation in response to FMLP and phorbol myristate acetate and partially protects against lipid

  11. Effect of ciprofloxacin and N-acetylcysteine on bacterial adherence and biofilm formation on ureteral stent surfaces

    El-Feky, Mohamed A; El-Rehewy, Mostafa S; Hassan, Mona A; Abolella, Hassan A; Abd El-Baky, Rehab M; Gad, Gamal F


    The aim of this study was to evaluate the effect of ciprofloxacin (CIP), N-acetylcysteine (NAC) alone and in combination on biofilm production and pre-formed mature biofilms on ureteral stent surfaces...

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

    Dan Bagger-Sjöbäck

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

  13. Effect of N-acetylcysteine in hearts of rats submitted to controlled hemorrhagic shock

    Luiz Dantas de Oliveira Filho


    Full Text Available AbstractIntroduction:Pharmacological therapy is a strategy for the prevention of complications associated with ischemia and reperfusion injury that occurs after volume replacement in the treatment of hemorrhagic shock.Objective:The aim of this study was to evaluate the effect of N-acetylcysteine associated with fluid resuscitation in cardiac injury in a rat hemorrhagic shock model.Methods:Mice Wister male rats were randomly and subjected to controlled hemorrhagic shock for 60 min. and then, subjected to resuscitation with Ringer lactate. In a group of six animals, 150mg/kg of N-acetylcysteine were added to fluid volume replacement. The animals were observed for 120 min and after this period, were euthanized and cardiac tissue was collected for histopathological analysis and measurement of thiobarbituric acid reactive substances and pro-and anti-inflammatory interleukin.Results:Cardiac tissue of the group treated with N-acetylcysteine showed lower concentrations of thiobarbituric acid reactive substances (0.20±0.05 vs. 0.27±0.05, P=0.014 and reduced histopathological damage and edema when compared to the group whose volume replacement occurred only with Ringer lactate. There was no difference in the expression of cytokines interleukin 6 (2,138.29±316.89 vs. 1,870.16±303.68, P=0.091 and interleukin 10 (1.019,83±262,50 vs. 848.60±106.5, P=0.169 between the treated groups.Conclusion:The association of N-acetylcysteine on volume replacement attenuates oxidative stress in the heart, as well myocardial damage and edema, but does not modify the expression of inflammatory cytokines.

  14. Combined treatment with oral metronidazole and N-acetylcysteine is effective in ethylmalonic encephalopathy.

    Viscomi, Carlo; Burlina, Alberto B; Dweikat, Imad; Savoiardo, Mario; Lamperti, Costanza; Hildebrandt, Tatjana; Tiranti, Valeria; Zeviani, Massimo


    Ethylmalonic encephalopathy is caused by mutations in ETHE1, a mitochondrial matrix sulfur dioxygenase, leading to failure to detoxify sulfide, a product of intestinal anaerobes and, in trace amounts, tissues. Metronidazole, a bactericide, or N-acetylcysteine, a precursor of sulfide-buffering glutathione, substantially prolonged the lifespan of Ethe1-deficient mice, with the combined treatment being additive. The same dual treatment caused marked clinical improvement in five affected children, with hardly any adverse or side effects.

  15. Cephazolin-Induced Toxic Epidermal Necrolysis Treated with Intravenous Immunoglobulin and N-Acetylcysteine

    Carlos Saavedra


    Full Text Available Toxic epidermal necrolysis is the most severe form of drug-induced skin reaction and includes denudation of >30% of total body surface area. The mechanism of disease is not completely understood, but immunologic mechanisms, cytotoxic reactions, and delayed hypersensitivity seem to be involved. We report a case of cephazolin-induced toxic epidermal necrolysis treated with intravenous immunoglobulin and N-acetylcysteine with excellent response.

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

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


    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 capil lary endothelial injury mediated by oxygen-derived freeradicals. 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 (10patients 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.

  17. Effects of histidine and N-acetylcysteine on doxorubicin-induced cardiomyopathy in rats.

    Farshid, Amir Abbas; Tamaddonfard, Esmaeal; Simaee, Naeime; Mansouri, Sanam; Najafi, Sima; Asri-Rezaee, Siamak; Alavi, Hossein


    The amino acids histidine and n-acetylcysteine have many biological activities such as antioxidant effect. The present study investigated the effects of histidine and n-acetylcysteine on the heart lesions induced by doxorubicin (DOX) in rats. Forty-eight male Wistar rats were divided into two major groups treated intraperitoneally (i.p.) with normal saline and 4 mg/kg of DOX, respectively. Each group was further divided into four subgroups that were treated with separate and combined i.p. injections of histidine and n-acetylcysteine (NAC) at a same dose of 40 mg/kg. Electrocardiography (ECG) was recorded using lead II. The heart lesions were evaluated by light microscopy. Serum levels of creatine phosphokinase and lactate dehydrogenase and heart tissue malondialdehyde levels were measured. Histidine and especially NAC at a same dose of 40 mg/kg recovered ECG changes, improved heart lesions and prevented biochemical changes induced by DOX. Co-administration of histidine and NAC showed better responses when compared with them used alone. The results of the present study showed protective effects for histidine and NAC on the heart. Reduction in free radical-induced toxic effects may be involved in cardioprotective properties of histidine and NAC.

  18. Inhibition by oral N-acetylcysteine of cigarette smoke-induced "bronchitis" in the rat.

    Rogers, D F; Jeffery, P K


    Specific pathogen-free rats were exposed to the cigarette smoke (CS) of 25 cigarettes daily for 14 days and concurrently given N-acetylcysteine (Nac) as 1% of their drinking water (average daily dose 973 mg/kg). The thickness of the epithelium was measured at four airway levels and the numbers of mucus-containing secretory cells, stained for neutral or acidic glycoprotein (NGP or AGP respectively), were counted in surface epithelium at eight airway levels. Cigarette smoke increased the thickness of the epithelium at three of the airway levels studied by between 37 and 72%. The number of secretory cells was increased at all airway levels distal to the upper trachea by between 102 and 421%. Secretory cells containing NGP were reduced in number but this was more than offset by a large increase in the number of secretory cells containing AGP at all airway levels. N-acetylcysteine inhibited CS-induced epithelial thickening. Nac also inhibited the CS-induced increase in the number of secretory cells with AGP, but had little effect on the CS-induced reduction in the number of cells with NGP. Thus, prophylactic oral N-acetylcysteine led to an overall inhibition of CS-induced mucous cell hyperplasia and epithelial hypertrophy. The results suggest a novel anti-inflammatory action for a drug with known mucolytic effects.

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

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


    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.

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

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


    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.

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

    Akram Pourbakht


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

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

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


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

  3. 7-N-Acetylcysteine-pyrrole conjugate—A potent DNA reactive metabolite of pyrrolizidine alkaloids

    Xiaobo He


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

  4. Attenuation by oral N-acetylcysteine of bleomycin-induced lung injury in rats.

    Cortijo, J; Cerdá-Nicolás, M; Serrano, A; Bioque, G; Estrela, J M; Santangelo, F; Esteras, A; Llombart-Bosch, A; Morcillo, E J


    Antioxidant therapy may be useful in diseases with impaired oxidant-antioxidant balance such as pulmonary fibrosis. This study examines the effect of N-acetylcysteine (NAC) on bleomycin-induced lung fibrosis in rats. NAC (3 mmol x kg(-1); oral) was given daily from 1 week prior to a single intratracheal instillation of bleomycin (2.5 U x kg(-1)) or saline, until 14 days postinstillation. NAC partially decreased the augmented collagen deposition in bleomycin-exposed rats (hydroxyproline content was 4,354+/-386 and 3,416+/-326 microg x lung(-1) in vehicle-treated and NAC-treated rats, respectively; p < 0.05). The histological assessment using a semiquantitative score showed less collagen deposition and inflammatory cells in NAC-treated rats compared to those receiving bleomycin alone. NAC failed to inhibit the bleomycin-induced increases in lung wet weight and in cell counts and protein levels of bronchoalveolar lavage fluid, but significantly increased total glutathione and taurine levels in bronchoalveolar lavage fluid. These results indicate that oral N-acetylcysteine improves the pulmonary antioxidant protection and may be useful in reducing lung damage produced by bleomycin.

  5. A comparison of a new mucolytic N-acetylcysteine L-lysinate with N-acetylcysteine: airway epithelial function and mucus changes in dog.

    Tomkiewicz, R P; App, E M; De Sanctis, G T; Coffiner, M; Maes, P; Rubin, B K; King, M


    A newly synthesized mucolytic agent, N-acetylcysteine L-lysinate (Nacystelyn) was studied. Tracheal mucus velocity (TMV), transepithelial potential difference (PD), rheological properties, and ion content of collected airway secretions were evaluated in six healthy mongrel dogs after placebo, Nacystelyn (NAL) and acetylcysteine (NAC) metered dose inhaler (MDI) aerosols. Although TMV was increased and viscoelasticity decreased after both treatments, the treatment effect with NAL was significantly greater. Furthermore, NAL increased the negative PD and CI- content of secretions in the trachea, an effect not observed after NAC. Both compounds increased ciliary beat frequency (CBF) on the frog palate at a concentration range similar to that approximated in dog airways. The increased mucociliary clearance could be partially explained by favourable rheological changes combined with stimulation of CBF. Since both compounds break disulfide bonds in mucus polymers, the greater change in mucus rheology and clearance rate after NAL, without change in water content, could be explained by the increase in CI- content. Nacystelyn appears to combine different modes of action which synergistically cause an increase in the clearance rate of airway secretions.

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

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


    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 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.

  7. Effect of N-acetylcysteine on the oxidative burst induced by phagocytosis of bacteria in human leukocytes.

    Colomé, J A; Jordá, J; Espinós, D; Bruseghini, L; Esteras, A


    The basal peroxide production and the oxidative burst induced by phagocytosis of opsonized E. coli was studied by flow cytometry using dihydrorhodamine 123. The human leukocytes were incubated in the absence and presence of N-acetylcysteine. The oxidative response to the phagocytosis of bacteria differed among cell populations. Thus, 90% of granulocytes and 50% of monocytes showed an oxidative burst in response to opsonized bacteria while less than 1% of lymphocytes showed a fluorescence signal. N-Acetylcysteine (4.7, 9.5, 19, 38 or 76 mM) produced a dose-dependent inhibition of the oxidative response to phagocytosis in the three cellular populations reaching almost complete inhibition for 76 mM. This protective effect of N-acetylcysteine against oxidative stress in leukocytes was obtained without cytotoxicity (assessed by flow cytometry with staining with propidium iodide) or changes in the pH of the medium. These results give further support to the antioxidant effect of N-acetylcysteine in human peripheral blood cells.

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

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

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

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

    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...

  10. N-acetylcysteine: an old drug with variable Anti-influenza properties

    Tomas Casanova


    Full Text Available N-acetylcysteine (NAC is a mucolytic drug commonly used as an adjuvant therapy in patients with respiratory conditions associated with excessive mucus production. NAC also has antioxidant activities which proved useful in the management of oxidative stress. These antioxidant capacities of NAC are mostly indirect, via a pro-glutathione effect where NAC provides L-cysteine residues required for glutathione synthesis. This activity is thought to be the basis of the protective effect of NAC administration in influenza patients and in mouse models of the disease. NAC was shown to limit lung inflammation, damage associated with the virus, and limit viral growth, at least in vitro. However, the antiviral activity was highly variable depending on the influenza A strain. The reasons for these inter-strain variations are still unknown but might be related to the level of NF-κB activation required for the virus to achieve its infectious cycle.

  11. Short communication: N-Acetylcysteine-mediated modulation of antibiotic susceptibility of bovine mastitis pathogens.

    Yang, F; Liu, L H; Li, X P; Luo, J Y; Zhang, Z; Yan, Z T; Zhang, S D; Li, H S


    The aim of this study was to investigate the effects of N-acetylcysteine (NAC) on antibiotic susceptibility of bovine mastitis pathogens including Staphylococcus aureus, Streptococcus dysgalactiae, Escherichia coli, and Streptococcus agalactiae. Minimum inhibitory concentrations (MIC) were tested by the agar-based E-test method. The presence of 10mM NAC reduced the MIC of penicillin and ampicillin but enhanced the MIC of erythromycin and ciprofloxacin for all of the strains. In addition, NAC-mediated modulation of MIC of kanamycin, tetracycline, and vancomycin was diverse, depending on the target bacterial pathogen and antibiotic being used. The results suggest that NAC is an important modulator of antibiotic activity against the major bovine mastitis pathogens. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  12. Protective Effects of N-Acetylcysteine in Concanavalin A-Induced Hepatitis in Mice

    Chengfen Wang


    Full Text Available This study was designed to study the protective effects and mechanisms of N-acetylcysteine (NAC in concanavalin A-induced hepatitis in mice. In this study, pretreatment with NAC ameliorated the histopathological changes and suppressed inflammatory cytokines in ConA-induced hepatitis. The expression of IL-2, IL-6, TNF-α, and IFN-γ was significantly reduced in the NAC-treated groups. NAC activated PI3K/Akt pathway and inhibited the activation of NF-κB. Additionally, NAC reduced autophagosome formation, as assessed by detecting the expression of LC3 and Beclin 1. Our results demonstrate that NAC can alleviate ConA-induced hepatitis by regulating the PI3K/Akt pathway and reducing the late stages of autophagy. Our results described a new pharmaceutical to provide more effective therapies for immune hepatitis.

  13. Effect of N-acetylcysteine in subjects with slow pulmonary mucociliary clearance.

    Todisco, T; Polidori, R; Rossi, F; Iannacci, L; Bruni, B; Fedeli, L; Palumbo, R


    There is significant evidence that in the general population there are subjects either with fast or slow pulmonary mucociliary clearance rates. At the moment we do not know the physiological importance of such finding. Slow clearers should be regarded as a subpopulation at risk for bronchopulmonary diseases. Therefore, it would be of considerable interest if their mucociliary function could be stimulated by drugs for preventive purposes. Twelve apparently healthy subjects with slow mucociliary clearance rate, selected in an epidemiologic survey in a non-smokers population were given 0.6 g oral N-acetylcysteine/day/60 days in a double-blind cross-over randomized study. After treatment their mucociliary clearance rates increased by about 35% as compared with baseline values, and returned to pre-treatment values after the washout period. Subjects were unresponsive to placebo treatment. It would seem that slow clearers are protected against lung aggressions by prevention and/or mucus-active drugs.

  14. Electroanalysis of dopamine at a gold electrode modified with N-acetylcysteine self-assembled monolayer.

    Liu, Ting; Li, Meixian; Li, Qianyuan


    Voltammetric behavior of dopamine (DA) on a gold electrode modified with the self-assembled monolayer (SAM) of N-acetylcysteine has been investigated, and one pair of well-defined redox peaks of dopamine is obtained at the SAM modified gold electrode. The oxidation peak current increases linearly with the concentration of dopamine in the range of 1.0x10 (-6)to 2.0x10 (-4)moll(-1). The detection limit is 8.0x10(-7)moll(-1). This method will be applicable to the determination of dopamine in injection of dopamine hydrochloride, and the good recovery of dopamine is obtained. Furthermore, The SAM modified gold electrode can resolve well the voltammetric responses of dopamine and ascorbic acid (AA), so it can also be applied to the determination of dopamine in the presence of ascorbic acid.

  15. Redispersible liposomal-N-acetylcysteine powder for pulmonary administration: development, in vitro characterization and antioxidant activity.

    Ourique, Aline Ferreira; Chaves, Paula Dos Santos; Souto, Gabriele Dadalt; Pohlmann, Adriana Raffin; Guterres, Silvia Stanisçuaski; Beck, Ruy Carlos Ruver


    Liposomal dry powders of N-acetylcysteine (SD-NAC-Lip) were developed for pulmonary administration. Liposomes were prepared by reverse phase evaporation and spray dried using lactose (10%, w/w) as drying adjuvant. The powders were characterized according to process yield, drug content, residual water content, particle size distribution, morphology and redispersion behavior. In vitro aerosol performance was evaluated using an eight-stage Andersen Cascade Impactor. Moreover, in vitro antioxidant activity was determined by measuring thiobarbituric acid reactive species (TBARS) present in the lungs of healthy Wistar rats after induction of oxidation by iron/EDTA. The spray-drying process had a high yield (71%±2), drug content (mg/g) according to the expected value, moisture content below 9%, geometric mean diameter under 3μm with span value lower than 1. Spherical particles were observed by scanning electron microscopy. Liposomal dry-powders were able to recover the nanometric size of the original dispersion after their redispersion in aqueous medium, as shown by laser diffraction and transmission electron microscopy. Furthermore, the powders presented aerodynamic diameter of about 7μm and respirable fraction above 30%, indicating suitable properties for pulmonary use. The encapsulation of N-acetylcysteine in liposomes was essential to maintain its in vitro antioxidant activity after the drying process. In addition, the powder containing the encapsulated drug had better in vitro antioxidant activity than the liquid and solid formulations containing the non-encapsulated drug, which makes it a good candidate for the treatment of pulmonary diseases associated with oxidative stress.

  16. N-acetylcysteine improves renal hemodynamics in rats with cisplatin-induced nephrotoxicity.

    Abdelrahman, Aly M; Al Salam, Suhail; AlMahruqi, Ahmed S; Al husseni, Ishaq S; Mansour, Mohamed A; Ali, Badreldin H


    This work investigated the effect of N-acetylcysteine (NAC), on renal hemodynamics in cisplatin (CP)-induced nephrotoxicity in Wistar-Kyoto (WKY) rats. The animals were divided into four groups (n = 5 or 6). The first and second groups received normal saline (control) and intraperitoneal (i.p.) N-acetylcysteine (500 mg kg(-1) per day for 9 days), respectively. The third and fourth groups were given a single intraperitoneal (i.p.) injection of CP (5 mg kg(-1)) and an i.p. injection of CP (5 mg kg(-1)) together with i.p. NAC (500 mg kg(-1) per day for 9 days), respectively. At the end of the experiment, rats were anesthetized and blood pressure and renal blood flow were monitored, followed by intravenous (i.v.) injection of norepinephrine (NE) for measurement of renal vasoconstrictor responses. CP caused a significant reduction in renal blood flow but did not affect NE-induced renal vasoconstriction. In addition, CP significantly increased plasma concentrations of urea and creatinine and urinary N-acetyl-beta-D-glucosaminidase (NAG) activity and kidney relative weight. CP decreased body weight and creatinine clearance. Histopathologically, CP caused remarkable renal damage compared with control. NAC alone did not produce any significant change in any of the variables measured. However, NAC significantly ameliorated CP-induced hemodynamic, biochemical and histopathological changes. The concentration of platinum in the kidneys of CP ? NAC treated rats was less than in CP-treated rats by 37%. The results show that administration of i.p. NAC (500 mg kg(-1) per day for 9 days) reversed the renal hemodynamic changes as well as the biochemical and histopathological indices of CP-induced nephrotoxicity in WKY rats.

  17. Ultrastructural evaluation of the effect of N-acetylcysteine on methotrexate nephrotoxicity in rats.

    Çağlar, Yildiz; Özgür, Hülya; Matur, Irem; Yenilmez, Ebru Dündar; Tuli, Abdullah; Gönlüşen, Gülfiliz; Polat, Sait


    The aim of this study is to investigate the possible protective effect of N-Acetylcysteine (NAC) against the likely methotrexate (MTX) toxicity on the kidney using ultrastructural together with biochemical data. Moreover, the immunohistochemical detection of Ki67 nuclear antigen is to be evaluated. Fifteen male Wistar albino rats, weighing 240-290 g, were divided into three equal groups: Rats receiving MTX alone, rats receiving MTX plus NAC treatment, and rats comprising the control group. MTX (18 mg/kg/day, body weight) in dissolved physiologic saline was administered intraperitoneally to rats during 3 days. For the MTX plus NAC group, N-Acetylcysteine (300 mg/kg/day, body weight) was administered together with MTX. At the end of the third day, all the rats were killed with cervical dislocation to obtain blood and tissue samples. Application of MTX principally induced prominent large vacuolization in the proximal convoluted tubule cells, and focal thickening in the glomerular basal lamina of some glomeruli. A decrease in tissue SOD (superoxide dismutase) and GSH-Px (glutathione peroxidase), and an increase in serum urea nitrogen and creatinine and in tissue MDA (malondialdehyde) levels were also seen in the MTX group. These changes were significantly reversed in the MTX-plus-NAC-treated group. Most of the vacuoles in the proximal convoluted tubule cells disappeared. Furthermore, an increase in antioxidant enzyme activities, a decrease in serum urea nitrogen and creatinine, and tissue MDA levels were all significant. Additionally, an increase in the number of Ki67 positive-stained cells in proximal tubules was also noted. In conclusion, NAC may be a promising substance against MTX-induced renal damage. It might be useful to use NAC supplementally to minimize MTX-induced nephrotoxicity.

  18. Contraction of human airways by oxidative stress protection by N-acetylcysteine.

    Cortijo, J; Martí-Cabrera, M; de la Asuncíon, J G; Pallardó, F V; Esteras, A; Bruseghini, L; Viña, J; Morcillo, E J


    We examined the in vitro effects of tert-butylhydroperoxide (tBu-OOH) in human bronchial muscle. tert-Butylhydroperoxide produced concentration-dependent contractions of bronchial rings (maximum effect was 56.5 +/- 9.6% of contraction by 1 mM acetylcholine; effective concentration 50% was approximately 100 microM). tert-Butylhydroperoxide (0.5 mM)-induced contraction was enhanced by epithelial removal but abolished by indomethacin (cyclooxygenase inhibitor) and zileuton (lipoxygenase inhibitor). tert-Butylhydroperoxide produced a transient rise in intracellular calcium in human cultured airway smooth muscle cells (HCASMC). The bronchial reactivity to acetylcholine and histamine was not altered by tBu-OOH. In HCASMC, tBu-OOH (0.5 mM, 30 min) increased malondialdehyde levels (MDA; from 7.80 +/- 0.83 to 26.82 +/- 1.49 nmol mg(-1) protein), accompanied by a decrease of reduced glutathione (GSH; from 16.7 +/- 2.6 to 6.9 +/- 1.9 nmol mg(-1) protein) and an increase of oxidized glutathione (from 0.09 +/- 0.03 to 0.18 +/- 0.03 nmol mg(-1) protein). N-acetylcysteine (0.3 mM) inhibited by approximately 60% the bronchial contraction resulting from tBu-OOH (0.5 mM) and protected cultured cells exposed to tBu-OOH (MDA was lowered to 19.51 +/- 1.19 nmol mg(-1) protein, and GSH content was replenished). In summary, tBu-OOH caused contraction of human bronchial muscle mediated by release of cyclo-oxygenase and lipoxygenase products without producing airways hyperreactivity. N-acetylcysteine decreases tBu-OOH-induced contraction and protects human cultured airway smooth muscle cells exposed to tBu-OOH.

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

    Mazo DF


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

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

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


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

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

    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


    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.

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

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


    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.

  3. Effect of N-acetylcysteine in COPD patients with different microsomal epoxide hydrolase genotypes

    Zhang JQ


    Full Text Available Jian-Qing Zhang,1 Jia-Qiang Zhang,1 Hua Liu,2 Zhi-Huan Zhao,1 Li-Zhou Fang,1 Ling Liu,1 Wei-Ping Fu,1 Jing-Kui Shu,1 Jia-Gang Feng,1 Lu-Ming Dai1 1Department of Respiratory Critical Care Medicine, 2Department of Clinical Laboratory, First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China Background: The role of the antioxidant N-acetylcysteine (NAC in the treatment of chronic obstructive pulmonary disease (COPD has not been clarified as yet. In early studies, we found that the proportion of smokers with COPD having extremely slow/slow microsomal epoxide hydrolase (EPHX1 enzyme activity is significantly higher than that in healthy smokers. The purpose of this study was to evaluate whether different EPHX1 enzyme activity is related to differential therapeutic effects of treatment with NAC in COPD.Methods: A total of 219 patients with COPD were randomly allocated to an extremely slow/slow EPHX1 enzyme activity group (n=157 or a fast/normal EPHX1 enzyme activity group (n=62 according to their EPHX1 enzyme activity. Both groups were treated with NAC 600 mg twice daily for one year. The main study parameters, including forced expiratory volume in one second (FEV1, St George’s Respiratory Questionnaire (SGRQ, and yearly exacerbation rate, were measured at baseline and at 6-month intervals for one year.Results: Both FEV1 and SGRQ symptom scores were improved after treatment with NAC in the slow activity group when compared with the fast activity group. Further, changes in FEV1 and SGRQ symptom score in patients with mild-to-moderate COPD were more significant than those in patients with severe-to-very severe COPD. The yearly exacerbation rates were reduced in both groups, but the reduction in the slow activity group was significantly lower than in the fast activity group.Conclusion: NAC treatment in COPD patients with extremely slow/slow EPHX1 enzyme activity improves FEV1 and the SGRQ symptom score, especially

  4. The influence of N-acetylcysteine on the measurement of prothrombin time and activated partial thromboplastin time in healthy subjects

    Jepsen, S; Hansen, A B


    The purpose of the study was to evaluate whether the infusion of N-acetylcysteine decreased the measurement of prothrombin time and activated partial thromboplastin time (APTT) in healthy persons. N-acetylcysteine was administered intraveneously 10 mg kg-1 as a loading dose and then at a rate of 10...... mg kg-1 h-1 for 32 h in six male subjects. The intrinsic, extrinsic and common pathway of coagulation were monitored with activated partial thromboplastin time (APTT), and prothrombin time, respectively. In addition, the extrinsic coagulation pathway was monitored with the clotting activity of single...... factors II, VII, and X. No effect on the intrinsic coagulation pathway was observed. There was a significant and rapid decrease in prothrombin time. Coagulation factors II, VII and X, the three components of prothrombin time, decreased significantly to different degrees. We conclude that infusion of N...

  5. Effects of N-acetylcysteine, oral glutathione (GSH) and a novel sublingual form of GSH on oxidative stress markers: A comparative crossover study

    Schmitt, Bernard; Vicenzi, Morgane; Garrel, Catherine; Denis, Frédéric M


    .... The purpose of this study was to compare the bioavailability, the effect on oxidative stress markers and the safety of a new sublingual form of GSH with two commonly used dietary supplements, N-acetylcysteine (NAC) and oral GSH...

  6. Effects of N-acetylcysteine on matrix metalloproteinase-9 secretion and cell migration of human corneal epithelial cells

    Ramaesh, T; Ramaesh, K; Riley, S C; West, J.D.; Dhillon, B


    Matrix metalloproteinase-9 (MMP-9) secreted by corneal epithelial cells has a role in the remodelling of extracellular matrix and migration of epithelial cells. Elevated levels of MMP-9 activity in the ocular surface may be involved in the pathogenesis of corneal diseases. N-acetylcysteine (NAC) has been used to treat corneal diseases, including recurrent epithelial erosions. In this study, its effects on the MMP-9 secretion and human corneal epithelial (HCE) cell migration were evaluated in ...

  7. Comparison of the effects of erdosteine and N-acetylcysteine on apoptosis regulation in endotoxin-induced acute lung injury.

    Demiralay, Rezan; Gürsan, Nesrin; Ozbilim, Gülay; Erdogan, Gülgün; Demirci, Elif


    This study was carried out to investigate comparatively the frequency of apoptosis in lung epithelial cells after intratracheal instillation of endotoxin [lipopolysaccharide (LPS)] in rats and the role of tumor necrosis factor alpha (TNF-alpha) on apoptosis, and the effects of erdosteine and N-acetylcysteine on the regulation of apoptosis. Female Wistar rats were given oral erdosteine (10-500 mg kg(-1)) or N-acetylcysteine (10-500 mg kg(-1)) once a day for 3 consecutive days. Then the rats were intratracheally instilled with LPS (5 mg kg(-1)) to induce acute lung injury. The rats were killed at 24 h after LPS administration. Lung tissue samples were stained with hematoxylin-eosin for histopathological assessments. The apoptosis level in the lung bronchial and bronchiolar epithelium was determined using the TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick endlabelling) method. Cytoplasmic TNF-alpha was evaluated by immunohistochemistry. Pretreatment with erdosteine and pretreatment with N-acetylcysteine at a dose of 10 mg kg(-1) had no protective effect on LPS-induced lung injury. When the doses of drugs increased, the severity of the lung damage caused by LPS decreased. It was found that as the pretreatment dose of erdosteine was increased, the rate of apoptosis induced by LPS in lung epithelial cells decreased and this decrease was statistically significant in doses of 300 mg kg(-1) and 500 mg kg(-1). Pretreatment with N-acetylcysteine up to a dose of 500 mg kg(-1) did not show any significant effect on apoptosis regulation. It was noticed that both antioxidants had no significant effect on the local production level of TNF-alpha. These findings suggest that erdosteine could be a possible therapeutic agent for acute lethal lung injury and its mortality.

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

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


    Ischemia–reperfusion (I/R) injury has a complex pathophysiology resulting from a number of contributing factors. Therefore, it is difficult to achieve effective treatment or protection by individually targeting the mediators or mechanisms. Our aim was to analyze the individual and combined effects of N-acetylcysteine (NAC) and the prostaglandin E1 (PGE1) analog alprostadil on hepatic I/R injury in rats. Thirty male Sprague-Dawley rats were randomly divided into five groups (six rats per group...

  9. The Metabolic Responses of Aspergillus flavus to N-Acetylcysteine, Ascorbate, and H2O2


    Aflatoxin, the secondary metabolite of Aspergillus flavus and A. Parasiticus, is the most toxic product in nature. In this study, N-acetylcysteine (NAC), ascorbate, and H2O2 were used to ascertain their effects on fungal metabolic esponse of A. Flavus. The results demonstrated that NAC did not affect fungal growth, but inhibited the aflatoxin B1 production, with the concomitant sporulation reduction. NAC increased the ratio of reduced glutathione (GSH) and oxidized glutathione (GSSG), hut decreased the activity of glutathione reductase (GR). Ascorbate had similar effect on fungal growth, sporulation,and GR activity, but GSH/GSSG and total glutathione (tGSH, including GSH and GSSG) were significantly increased. H2O2 at high concentration (5 mM) inhibited fungal growth, but the aflatoxin production was increased. At the same time, it reduced GR activity and enhanced tGSH. Though reductive agents had different effects on GSH metabolism, reductive conditions inhibited aflatoxin production and sporulation without any effect on fungal growth. The results in this report confirmed that the relationship between oxidative stress and aflatoxin production is theoretically important in controlling aflatoxin contamination.

  10. N-Acetylcysteine Attenuates Diabetic Myocardial Ischemia Reperfusion Injury through Inhibiting Excessive Autophagy

    Wang, Sheng; Yan, Fuxia; Wang, Tingting; He, Yi


    Background. Excessive autophagy is a major mechanism of myocardial ischemia reperfusion injury (I/RI) in diabetes with enhanced oxidative stress. Antioxidant N-acetylcysteine (NAC) reduces myocardial I/RI. It is unknown if inhibition of autophagy may represent a mechanism whereby NAC confers cardioprotection in diabetes. Methods and Results. Diabetes was induced in Sprague-Dawley rats with streptozotocin and they were treated without or with NAC (1.5 g/kg/day) for four weeks before being subjected to 30-minute coronary occlusion and 2-hour reperfusion. The results showed that cardiac levels of 15-F2t-Isoprostane were increased and that autophagy was evidenced as increases in ratio of LC3 II/I and protein P62 and AMPK and mTOR expressions were significantly increased in diabetic compared to nondiabetic rats, concomitant with increased postischemic myocardial infarct size and CK-MB release but decreased Akt and eNOS activation. Diabetes was also associated with increased postischemic apoptotic cell death manifested as increases in TUNEL positive cells, cleaved-caspase-3, and ratio of Bax/Bcl-2 protein expression. NAC significantly attenuated I/RI-induced increases in oxidative stress and cardiac apoptosis, prevented postischemic autophagy formation in diabetes, and reduced postischemic myocardial infarction (all p < 0.05). Conclusions. NAC confers cardioprotection against diabetic heart I/RI primarily through inhibiting excessive autophagy which might be a major mechanism why diabetic hearts are less tolerant to I/RI. PMID:28265179

  11. [Prooxidant and cytotoxic action of N-acetylcysteine and glutathione combined with vitamin Bl2b].

    Solov'eva, M E; Solov'ev, V V; Faskhutdinova, A A; Kudriavtsev, A A; Akatov, V S


    We studied the prooxidant and cytotoxic action of thiols N-acetylcystein (NAC) and glutathione (GSH) combined with vitamin Bl2b. The synergism of action of the thiols and Bl2b resulted in human carcinoma cell damage was found. It was shown that GSH and NAC in physiological doses combined with Bl2b caused the initiation of apoptosis. It was established that prooxidant action of the thiols combined with vitamin Bl2b, i. e. generation and accumulation of hydrogen peroxide in culture medium, led to intracellular oxidative stress and injury of cell redox system. These effects were completely abolished by nonthiol antioxidants catalase and pyruvate. The chelators of iron phenanthroline and deferoxamine did not suppress the H2O2 accumulation in culture medium but significantly inhibited the cell death induced by the thiols combined with Bl2b. Therefore, the thiols GSH and NAC widely used as antioxidants, in combination with vitamin Bl2b show prooxidant characteristics and induce, with the participation of intracellular iron, apoptotic HEp-2 cell death.

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

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


    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.

  13. Antimicrobial activity of alexidine alone and associated with N-acetylcysteine against Enterococcus faecalis biofilm

    Luiz Fernando Machado Silveira; Pilar Baca; Mara Teresa Arias-Moliz; Alberto Rodrguez-Archilla; Carmen Mara Ferrer-Luque


    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?mL21 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?mL21 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.

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

    Elson Asevedo


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

  15. The effect of N-acetylcysteine (NAC) on human cognition - A systematic review.

    Skvarc, David R; Dean, Olivia M; Byrne, Linda K; Gray, Laura; Lane, Stephen; Lewis, Matthew; Fernandes, Brisa S; Berk, Michael; Marriott, Andrew


    Oxidative stress, neuroinflammation and neurogenesis are commonly implicated as cognitive modulators across a range of disorders. N-acetylcysteine (NAC) is a glutathione precursor with potent antioxidant, pro-neurogenesis and anti-inflammatory properties and a favourable safety profile. A systematic review of the literature specifically examining the effect of NAC administration on human cognition revealed twelve suitable articles for inclusion: four examining Alzheimer's disease; three examining healthy participants; two examining physical trauma; one examining bipolar disorder, one examining schizophrenia, and one examining ketamine-induced psychosis. Heterogeneity of studies, insufficiently powered studies, infrequency of cognition as a primary outcome, heterogeneous methodologies, formulations, co-administered treatments, administration regimes, and assessment confounded the drawing of firm conclusions. The available data suggested statistically significant cognitive improvements following NAC treatment, though the paucity of NAC-specific research makes it difficult to determine if this effect is meaningful. While NAC may have a positive cognitive effect in a variety of contexts; larger, targeted studies are warranted, specifically evaluating its role in other clinical disorders with cognitive sequelae resulting from oxidative stress and neuroinflammation. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  16. Protective effects of alpha lipoic acid versus N-acetylcysteine on ifosfamide-induced nephrotoxicity.

    El-Sisi, Alaa El-Din E; El-Syaad, Magda E; El-Desoky, Karima I; Moussa, Ethar A


    Ifosfamide (IFO) is a highly effective chemotherapeutic agent for treating a variety of pediatric solid tumors. However, its use is limited due to its serious side effect on kidneys. The side-chain oxidation of IFO in renal tubular cells produces a reactive toxic metabolite that is believed to be responsible for its nephrotoxic effect. Therefore, this study was carried out to investigate the possible underlying mechanisms that may be involved in IFO-induced nephrotoxicity, including free radical generation and the possible role of alpha lipoic acid (ALA) versus N-acetylcysteine (NAC) in protection against this toxicity. Male albino rats were injected intraperitoneally with saline, IFO (50 mg/kg daily for 5 days), IFO + ALA (100 mg/kg daily for 8 days) and IFO + NAC (200 mg/kg daily for 8 days). Kidney malondialdehyde, nitric oxide and glutathione contents and serum biochemical parameters and histopathological analysis were determined. Both ALA and NAC markedly reduced the severity of renal dysfunction induced by IFO. NAC was more nephroprotective than ALA. This study suggests that oxidative stress is possibly involved in the IFO-induced nephrotoxicity in rats. The study also suggests the potential therapeutic role for ALA and NAC against IFO-induced nephrotoxicity.


    Laishram Elizabeth


    Full Text Available BACKGROUND Gentamicin exerts a unique pharmacokinetic effect on renal physiology and its use at high dose or prolonged treatment requires monitoring of kidney function test. Antioxidants has been claimed to have nephroprotective potential and hence antioxidant compound, N-acetylcysteine (NAC has been used in renal impairment; however, its efficacy is not very well documented. Therefore, the present study has been undertaken to evaluate the role of antioxidant (NAC in impaired kidney function due to high dose Gentamicin in rat models. Gentamicin at the dose of 80 mg/kg b.w. intramuscularly was given in 18 adult healthy albino rats for 10 days and varying doses of antioxidant NAC (20 and 40 mg/kg were given orally for 3 wks. starting from day 5 of the experiment. Blood urea and creatinine levels were measured on day 5, 10 and after completion of treatment of NAC and histopathology examination conducted. Intramuscular injection of high dose of Gentamicin significantly produced biochemical signs of nephrotoxicity. Serum creatinine levels were significantly lowered in NAC treated group compared to the control group. The group treated with NAC 40 mg/kg for 3 wks. had significantly lowered renal biochemical parameters and histopathological features compared to control.

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

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


    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.

  19. N-Acetylcysteine mucolysis in the management of chronic obstructive pulmonary disease.

    Sadowska, Anna M


    To develop an efficient therapy for chronic obstructive pulmonary disease (COPD), N-acetylcysteine (NAC) has been tested as a medication that can suppress various pathogenic processes in this disease. NAC is a thiol compound, which provides sulfhydryl groups. NAC can act as a precursor of reduced glutathione and as a direct reactive oxygen species scavenger, hence regulating the redox status in the cells. In this way NAC can interfere with several signaling pathways that play a role in regulating apoptosis, angiogenesis, cell growth and inflammatory response. Mucus hypersecretion has been reported in COPD and in other respiratory conditions. Two pathological processes have been described to play an important role in COPD, namely oxidative stress and inflammation. Both of these processes can induce mucin gene expression leading to mucin production. NAC, therefore, may influence mucin expression by acting on oxidative stress and inflammation, and play a role as a mucolytic agent. In this review we focus on the mucolysis of NAC in the management of COPD.

  20. N-acetylcysteine impairs survival of luteal cells through mitochondrial dysfunction.

    Löhrke, Berthold; Xu, Jinxian; Weitzel, Joachim M; Krüger, Burkhard; Goldammer, Tom; Viergutz, Torsten


    N-acetylcysteine (NAC) is known as an antioxidant and used for mucus viscosity reduction. However, this drug prevents or induces cell death depending on the cell type. The response of steroidogenic luteal cells to NAC is unknown. Our data shows that NAC can behave as an antioxidant or prooxidant in dependency on the concentration and mitochondrial energization. NAC elevated the flowcytometric-measured portion of hypodiploid (dying) cells. This rise was completely abolished by aurintricarboxylic acid, an inhibitor of topoisomerase II. NAC increased the secretion of nitric oxide and cellular nitrotyrosine. An image analysis indicated that cells pretreated with NAC and loaded with DHR showed a fluorescent structure probably elicited by the oxidative product of DHR, rhodamine 123 that sequesters mitochondrially. Pretreating luteal cells with NAC or adding NAC directly to mitochondrial fractions followed by assessing the mitochondrial transmembrane potential difference (Deltapsi) by the JC-1 technique demonstrated a marked decrease in Deltapsi. A protonophore restored Deltapsi and rotenone (an inhibitor of respiratory chain complex I) inhibited mitochondrial recovering. Thus, in steroidogenic luteal cells from healthy mature corpus luteum, NAC impairs cellular survival by interfering with mitochondrial metabolism. The protonophore-induced recovering of NAC-provoked decrease in Deltapsi indicates that an ATP synthase-favored route of H(+) re-entry to the matrix is essentially switched off by NAC while other respiratory chain complexes remain intact. These data may be important for therapeutic timing of treatments with NAC. (c) 2010 International Society for Advancement of Cytometry.

  1. The effect of N-acetylcysteine on chloride efflux from airway epithelial cells.

    Varelogianni, Georgia; Oliynyk, Igor; Roomans, Godfried M; Johannesson, Marie


    Defective chloride transport in epithelial cells increases mucus viscosity and leads to recurrent infections with high oxidative stress in patients with CF (cystic fibrosis). NAC (N-acetylcysteine) is a well known mucolytic and antioxidant drug, and an indirect precursor of glutathione. Since GSNO (S-nitrosoglutathione) previously has been shown to be able to promote Cl- efflux from CF airway epithelial cells, it was investigated whether NAC also could stimulate Cl- efflux from CF and non-CF epithelial cells and through which mechanisms. CFBE (CF bronchial epithelial cells) and normal bronchial epithelial cells (16HBE) were treated with 1 mM, 5 mM, 10 mM or 15 mM NAC for 4 h at 37 degrees C. The effect of NAC on Cl- transport was measured by Cl- efflux measurements and by X-ray microanalysis. Cl- efflux from CFBE cells was stimulated by NAC in a dose-dependent manner, with 10 mM NAC causing a significant increase in Cl- efflux with nearly 80% in CFBE cells. The intracellular Cl- concentration in CFBE cells was significantly decreased up to 60% after 4 h treatment with 10 mM NAC. Moreover immunocytochemistry and Western blot experiments revealed expression of CFTR channel on CFBE cells after treatment with 10 mM NAC. The stimulation of Cl- efflux by NAC in CF airway epithelial cells may improve hydration of the mucus and thereby be beneficial for CF patients.

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

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


    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.

  3. Effects of N-acetylcysteine in ozone-induced chronic obstructive pulmonary disease model.

    Feng Li

    Full Text Available INTRODUCTION: Chronic exposure to high levels of ozone induces emphysema and chronic inflammation in mice. We determined the recovery from ozone-induced injury and whether an antioxidant, N-acetylcysteine (NAC, could prevent or reverse the lung damage. METHODS: Mice were exposed to ozone (2.5 ppm, 3 hours/12 exposures, over 6 weeks and studied 24 hours (24h or 6 weeks (6W later. Nac (100 mg/kg, intraperitoneally was administered either before each exposure (preventive or after completion of exposure (therapeutic for 6 weeks. RESULTS: After ozone exposure, there was an increase in functional residual capacity, total lung volume, and lung compliance, and a reduction in the ratio of forced expiratory volume at 25 and 50 milliseconds to forced vital capacity (FEV25/FVC, FEV50/FVC. Mean linear intercept (Lm and airway hyperresponsiveness (AHR to acetylcholine increased, and remained unchanged at 6W after cessation of exposure. Preventive NAC reduced the number of BAL macrophages and airway smooth muscle (ASM mass. Therapeutic NAC reversed AHR, and reduced ASM mass and apoptotic cells. CONCLUSION: Emphysema and lung function changes were irreversible up to 6W after cessation of ozone exposure, and were not reversed by NAC. The beneficial effects of therapeutic NAC may be restricted to the ASM.

  4. N-acetylcysteine in patients with COPD exacerbations associated with increased sputum.

    Ayfer Aytemur, Zeynep; Baysak, Aysegul; Ozdemir, Ozer; Köse, Timur; Sayiner, Abdullah


    N-acetylcysteine (NAC) has been shown not to alter the clinical outcome in chronic obstructive pulmonary disease (COPD) exacerbations. However, NAC may improve symptoms through its mucolytic effect in the subgroup of patients with increased sputum production. The aims of this study were to determine whether NAC improves symptoms and pulmonary function in patients with COPD exacerbation and increased sputum production. This was a placebo-controlled study, where patients with severe COPD and increased sputum production, who were hospitalized for an exacerbation, were included. They were randomized to receive either NAC 200 mg tid or placebo in addition to the usual treatment. Forty-two patients were included and were equally distributed to NAC and placebo groups. The symptoms, namely, ease of sputum production and dyspnea at rest and on exertion significantly improved in both groups; but there was no difference in improvement between NAC and placebo groups (p = 0.96, 0.62, 0.31, respectively). Similarly, forced expiratory volume-one second (FEV1) and PaO2 levels improved significantly in NAC (964 ± 599-1239 ± 543 ml, p NAC does not have any beneficial effect on clinical outcomes in patients with severe COPD exacerbation associated with increased and/or viscous mucus production.

  5. Endotracheal nebulization of N-acetylcysteine increases airway resistance in cats with experimental asthma.

    Reinero, Carol R; Lee-Fowler, Tekla M; Dodam, John R; Cohn, Leah A; DeClue, Amy E; Guntur, Vamsi P


    N-acetylcysteine (NAC), a mucolytic and antioxidant, is speculated to cause bronchoconstriction in cats when delivered via aerosol. We hypothesized that in cats with experimental asthma, aerosol delivery of NAC (400mg cumulative dose) via an endotracheal tube would increase airflow limitation as measured by ventilator-acquired mechanics. After endotracheal drug delivery, airway resistance and inspiratory plateau pressure (Pplat) measurements were obtained in six mechanically ventilated asthmatic cats. Results demonstrated significantly increased airway resistance (P=0.0007) compared with aerosolized saline control; Pplats were not significantly different (P=0.059). All cats exhibited at least one adverse effect: excessive airway secretions (n=3), spontaneous cough (n=2), unilateral strabismus (n=1) and post-anesthetic death (n=1). No adverse reactions were noted with saline aerosol; cough was noted in one cat with methacholine challenge. In conclusion, airway resistance and adverse reactions were documented in all cats after NAC aerosol delivery. Further studies must be performed to evaluate if it is an effective mucolytic and/or antioxidant in cats and to determine if bronchodilator pre-treatment will negate NAC-induced bronchoconstriction.

  6. N-acetylcysteine chemoprotection without decreased cisplatin antitumor efficacy in pediatric tumor models.

    Muldoon, Leslie L; Wu, Y Jeffrey; Pagel, Michael A; Neuwelt, Edward A


    Decreasing oxidative damage with the antioxidant agent N-acetylcysteine (NAC) can block the side effects of chemotherapy, but may diminish anti-tumor efficacy. We tested the potential for interactions of high dose NAC against a minimally effective cisplatin chemotherapy regimen in rat models of human pediatric cancers. Athymic rats received subcutaneous implantation of human SK-N-AS neuroblastoma cells or intra-cerebellar implantation of human D283-MED medulloblastoma cells. Rats were untreated or treated with cisplatin (3 or 4 mg/kg IV) with or without NAC (1,000 mg/kg IV) 30 min before or 4 h after cisplatin treatment. Blood urea nitrogen (BUN) and tumor volumes were measured. Cisplatin decreased the growth of SK-N-AS neuroblastoma subcutaneous tumors from 17.7 ± 4.9 to 6.4 ± 2.5 fold over baseline 2 weeks after treatment (P cisplatin efficacy, while 4 h delayed NAC did not significantly affect cisplatin anti-tumor effects (relative tumor volume 6.8 ± 2.0 fold baseline, P cisplatin efficacy (tumor volume 6.8 ± 8.1 mm(3), P = 0.014 versus control). Cisplatin was minimally nephrotoxic in these models. NAC decreased cisplatin-induced elevations in BUN (P < 0.02). NAC chemoprotection did not alter cisplatin therapy, if delayed until 4 h after chemotherapy. These data support a Phase I/II clinical trial of delayed NAC to reduce ototoxicity in children with localized pediatric cancers.

  7. Thiol Redox Transitions in Cell Signaling: a Lesson from N-Acetylcysteine

    Tiziana Parasassi


    Full Text Available 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.

  8. Effect of N-acetylcysteine on neutrophil functions during experimental acute pancreatitis.

    Atayoğlu, Kemal; Gürleyik, Günay; Demirel, Gülderen; Özkara, Selvinaz


    Systemic inflammatory responses and extrapancreatic vital organ impairment are mediated by activated neutrophil functions and products, such as oxygen-derived free radicals, in patients with acute pancreatitis (AP). The present study is an examination of effects of an antioxidant, N-acetylcysteine (NAC), on local and systemic histopathological changes and neutrophil functions during AP. This experimental study was performed on 24 Wistar albino rats equally divided into 3 groups: Group 1 comprised sham laparotomy, Group 2 had AP induced with taurocholate infusion, and Group 3 consisted of AP with NAC treatment. Histopathological features in pancreas, kidney, and lung tissues were examined for local and systemic changes during AP. Neutrophil functions were evaluated using flow cytometry. Serum levels of pancreatic enzymes were elevated, and histopathological parameters showed acinar cell damage and pancreatic tissue necrosis in the 2 groups with AP. Severe histopathological changes were found in pulmonary and renal tissues, and flow cytometry results indicated defective neutrophil functions in the group with AP alone. NAC treatment significantly ameliorated phagocytosis, chemotaxis, and opsonization of neutrophils (pfunctions could provoke severe systemic inflammatory responses. In addition to local inflammation and necrosis, severe systemic responses and histopathological changes in extrapancreatic vital organs occur during AP. Treatment with antioxidant NAC significantly reverses detrimental systemic responses in extrapancreatic vital organs by significantly ameliorating neutrophil functions despite ongoing AP.

  9. Effects of Repeated Cocaine Exposure on Habit Learning and Reversal by N-Acetylcysteine

    Corbit, Laura H; Chieng, Billy C; Balleine, Bernard W


    Exposure to drugs of abuse can result in a loss of control over both drug- and nondrug-related actions by accelerating the transition from goal-directed to habitual control, an effect argued to reflect changes in glutamate homeostasis. Here we examined whether exposure to cocaine accelerates habit learning and used in vitro electrophysiology to investigate its effects on measures of synaptic plasticity in the dorsomedial (DMS) and dorsolateral (DLS) striatum, areas critical for actions and habits, respectively. We then administered N-acetylcysteine (NAC) in an attempt to normalize glutamate homeostasis and hence reverse the cellular and behavioral effects of cocaine exposure. Rats received daily injections of cocaine (30 mg/kg) for 6 days and were then trained to lever press for a food reward. We used outcome devaluation and whole-cell patch-clamp electrophysiology to assess the behavioral and cellular effects of cocaine exposure. We then examined the ability of NAC to reverse the effects of cocaine exposure on these measures. Cocaine treatment produced a deficit in goal-directed action, as assessed by outcome devaluation, and increased the frequency of spontaneous and miniature excitatory postsynaptic currents (EPSCs) in the DMS but not in the DLS. Importantly, NAC treatment both normalized EPSC frequency and promoted goal-directed control in cocaine-treated rats. The promotion of goal-directed control has the potential to improve treatment outcomes in human cocaine addicts. PMID:24531561

  10. Role of N-acetylcysteine in rifampicin-induced hepatic injury of young rats

    SV Rana; S Attri; K Vaiphei; R Pal; A Attri; K Singh


    AIM: To study the role of N-acetylcysteine (NAC) as a protective agent in rifampicin (RMP)-induced oxidative hepatic injury of young rats.METHODS: Hepatic injury was produced by giving 50mg/kg body weight/day of RMP for 3 wk. A dose of NAC (100mg/kg body weight/day) was given in combination with RMP intraperitoneally. Analysis of lipid peroxidation, thiol levels, cytochrome P450, superoxide dismutase (SOD), catalase, glutathione peroxidase, reductase and transferase were estimated in liver along with the body weight, liver weight and histological observations.RESULTS: RMP exposure resulted in no change in body and liver weight while antioxidative enzymes were altered but the non protein thiol (GSH) status was well preserved. Cytochrome P4s0 system and peroxidation of lipids were induced by RMP exposure. Partial protection was observed with NAC against RMP-induced changes in liver, which was evidenced from the prevention of increase in lipid peroxidation and the reduction in SOD and catalase enzyme levels.CONCLUSION: NAC protects young rats against RMP-induced oxidative hepatic injury.

  11. Effect of N-acetylcysteine on inflammation biomarkers in pediatric acute pyelonephritis: a randomized controlled trial.

    Allameh, Zahra; Karimi, Abdollah; Rafiei Tabatabaei, Seddigheh; Sharifian, Mostafa; Salamzadeh, Jamshid


    This study was designed to investigate the effect of N-acetylcysteine (NAC), as a potent and safe antioxidant, on inflammatory biomarkers of acute pyelonephritis in pediatric patients. Children (pyelonephritis were recruited in a randomized placebo-controlled trial. They were randomly allocated to 2 groups and recieved placebo or NAC effervescent tablets with daily dose based on their weight, for 5 days. The children were evaluated for serum procalcitonin level, leukocyte count, C-reactive protein (CRP), serum creatinine, and clinical symptoms on the 1st and the 5th days. Seventy patients, 35 in each group, with a mean age of 5.54 ± 3.10 years completed the study. There was no significant difference between the two groups in the amount of changes in procalcitonin levels after 5 days (P = .90). Within-group analysis confirmed CRP reduction in both groups (P < .001); however, between-group analysis did not show significant difference in CRP reductions, either (P = .65). No significant differences were found between the two groups in the day of resolving pyuria (P = .46), day of resolving bacteriuria (P = .81), or reductions in leukocyte count (P = .64) and neutrophil count (P = .49). A short period of NAC administration with the recommended doses could not lead to a significant decrease in inflammation biomarkers. Studies on higher doses and longer duration of NAC administration along with evaluation of the long-term effects of the intervention by tools such as renal scntigraphy are suggested.

  12. Effect of N-acetylcysteine, allopurinol and vitamin E on jaundice-induced brain oxidative stress in rats.

    Karageorgos, Nikolaos; Patsoukis, Nikolaos; Chroni, Elisabeth; Konstantinou, Dimitris; Assimakopoulos, Stelios F; Georgiou, Christos


    We examined the possible protective effect of certain antioxidants (N-acetylcysteine, allopurinol and vitamin E) against the oxidative stress of brain tissue induced by experimental obstructive jaundice in rats. Thirty-six male Wistar rats were randomly divided into six groups; group I control, group II sham operated, group III bile duct ligated and groups IV, V, and VI in which the rats, after bile duct ligation, were given every day an intraperitoneal injection with N-acetylcysteine, allopurinol and Vit-E respectively. All rats were sacrificed on the tenth day by exsanguination and the oxidative state in samples from cortex, midbrain and cerebellum was assessed by measuring the thiol redox state and lipid peroxidation quantified by MDA measurements. The main finding was that all three antioxidants decrease lipid peroxidation in the three brain areas. Cysteine levels increased and protein thiol levels were reserved only in the group treated with N-acetylcysteine, whereas oxidized glutathione increased dramatically in the group treated with allopurinol, suggesting that each antioxidant agent had a certain influence profile on the different antioxidant defense systems. The observed effects of the antioxidants in this experimental model could also provide insight into some aspects of jaundice-induced hepatic encephalopathy in humans.

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

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


    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

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

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


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

  15. N-acetylcysteine attenuates ischemia/reperfusion-induced cardiocyte apoptosis in diabetic rats

    Li Ma; Shanglong Yao; Kezhong Li


    Objective: To study the effects of N-acetylcysteine (NAC) on iscbemia/ reperfusion (I/R)-induced myocyte apoptosis in diabetic rats. Methods:The I/R heart model was made by ligation of the left anterior descending coronary artery (LAD) close to its origin. The LAD was occluded for 30 min followed by removal of ligation to allow subsequent reperfusion for 3 h. 72 rats were randomly divided into two groups: non-diabetic group (C, n = 36) and diabetic group (D, n = 36).The animals in C group were randomly reassigned into sham-ope rated group (CS, n = 12) , I/R group (C I/R, n = 12) and treated with NAC group (CN, n = 12). The rats in D group were also reassigned to sham-operated group (DS, n = 12) , I/R group (DI/R, n = 12) and treated with NAC group (DN, n = 12). Malondialdehyde (MDA) and creatine kinase isoenzyme-MB (CK-MB) were measured. Infarct size(IS/AAR%), the apoptosis index(AI) by TUNEL staining, the number of the cells positive for Caspase-3 and positive expression index (PEI) were calculated. Results:After I/R, the IS/AAR%, CK-MB, MDA, AI and Caspase-3 PEI were higher in diabetic group than those in non-diabetic group. Treatment with NAC decreased the above parameters in both non-diabetic and diabetic rats, but the parameters in diabetic rats were higher than those in non-diabetic rats. Conclusion:Diabetic rat hearts are more susceptible to I/R-induced myocardial necrosis and myocyte apoptosis. NAC can decrease the infarct size and attenuate cardiomyocyte apoptosis in both non-diabetic and diabetic rats, but the therapeutic effects are less effective in diabetic rats than those in non-diabetic rats.

  16. N-acetylcysteine Ameliorates Prostatitis via miR-141 Regulating Keap1/Nrf2 Signaling.

    Wang, Liang-Liang; Huang, Yu-Hua; Yan, Chun-Yin; Wei, Xue-Dong; Hou, Jian-Quan; Pu, Jin-Xian; Lv, Jin-Xing


    Chronic prostatitis was the most common type of prostatitis and oxidative stress was reported to be highly elevated in prostatitis patients. In this study, we determined the effect of N-acetylcysteine (NAC) on prostatitis and the molecular mechanism involved in it. Male Sprague-Dawley rats were divided into three groups: control group (group A, n = 20), carrageenan-induced chronic nonbacterial prostatitis (CNP) model group (group B, n = 20), and carrageenan-induced CNP model group with NAC injection (group C, n = 20). Eye score, locomotion score, inflammatory cell count, cyclooxygenase 2 (COX2) expression, and Evans blue were compared in these three groups. The expression of miR-141 was determined by quantitative real-time PCR (qRT-PCR). Moreover, protein expressions of Kelch-like ECH-associated protein-1 (Keap1) and nuclear factor erythroid-2 related factor 2 (Nrf2) and its target genes were examined by Western blot. Luciferase reporter assay was performed in RWPE-1 cells transfected miR-141 mimic or inhibitor and the plasmid carrying 3'-UTR of Keap1. The value of eye score, locomotion score, inflammatory cell count, and Evans blue were significantly decreased in group C, as well as the expression of COX2, when comparing to that of group B. These results indicated that NAC relieved the carrageenan-induced CNP. Further, we found that NAC increased the expression of miR-141 and activated the Keap1/Nrf2 signaling. Luciferase reporter assay revealed that miR-141 mimic could suppress the activity of Keap1 and stimulate the downstream target genes of Nrf2. In addition, miR-141 inhibitor could reduce the effect of NAC on prostatitis. NAC ameliorates the carrageenan-induced prostatitis and prostate inflammation pain through miR-141 regulating Keap1/Nrf2 signaling.

  17. Investigations on the endometrial response to intrauterine administration of N-acetylcysteine in oestrous mares.

    Melkus, E; Witte, T; Walter, I; Heuwieser, W; Aurich, C


    In mares, mating-induced persistent endometritis contributes to low fertility. The condition is in part related to delayed clearance of mucus accumulated within the uterine lumen. The objective of this study was to investigate the endometrial response of healthy mares to intrauterine (i.u.) treatment with N-acetylcysteine (NAC). Oestrous mares (n = 12) were randomly assigned to a treatment (TM) or control (C) group and received an i.u. infusion of 5% NAC and saline (total volume 140 ml), respectively. Endometrial biopsies were collected in five of the mares 24 h after treatment, in the remaining seven mares 72 h after treatment. Endometrial biopsies were evaluated for integrity of the luminal epithelium, number of polymorphonuclear neutrophils (PMN), staining for cyclooxygenase 2 (COX2), staining with Kiel 67 antigen (Ki-67), lectins and periodic acid-Schiff (PAS). The integrity of endometrial epithelial cells was not affected by treatment (no statistical differences between groups or times). At 24 h after treatment, the mean number of PMN in endometrial biopsies from NAC- and C-mares did not differ, but at 72 h after treatment, number of PMN was significantly higher (p NAC-treated mares (2.3 ± 0.2 PMN/field). At 72 h after treatment, the intensity of staining for COX2 was significantly higher after saline than after NAC treatment (p NAC-treated mares than in C-mares 72 h after treatment (p mucus in deep uterine glands differed significantly between groups at 24 h after treatment (p NAC does not adversely affect the endometrial function. Moreover, an anti-inflammatory effect on the equine endometrium was observed.

  18. N-acetylcysteine inhibits Na+ absorption across human nasal epithelial cells.

    Rochat, Thierry; Lacroix, Jean-Silvain; Jornot, Lan


    N-acetylcysteine (NAC) is a widely used mucolytic drug in patients with a variety of respiratory disorders. The mechanism of action is based on rupture of the disulfide bridges of the high molecular glycoproteins present in the mucus, resulting in smaller subunits of the glycoproteins and reduced viscosity of the mucus. Because Na(+) absorption regulates airway surface liquid volume and thus the efficiency of mucociliary clearance, we asked whether NAC affects the bioelectric properties of human nasal epithelial cells. A 24-h basolateral treatment with 10 mM of NAC decreased the transepithelial potential difference and short-circuit current (I(SC)) by 40%, and reduced the amiloride-sensitive current by 50%, without affecting the transepithelial resistance. After permeabilization of the basolateral membranes of cells with amphotericin B in the presence of a mucosal-to-serosal Na(+) gradient (135:25 mM), NAC inhibited 45% of the amiloride-sensitive current. The Na(+)-K(+)-ATPase pump activity and the basolateral K(+) conductance were not affected by NAC treatment. NAC did not alter total cell mRNA and protein levels of alpha-epithelial Na(+) channel (EnaC) subunit, but reduced abundance of alpha-ENaC subunits in the apical cell membrane as quantified by biotinylation. This effect can be ascribed to the sulphydryl (SH) group of NAC, since N-acetylserine and S-carboxymethyl-l-cysteine were ineffective. Given the importance of epithelial Na(+) channels in controlling the thin layer of fluid that covers the surface of the airways, the increase in the fluidity of the airway mucus following NAC treatment in vivo might be in part related to downregulation of Na(+) absorption and consequently water transport.

  19. [Omeprazole/amoxicillin: improved eradication of Helicobacter pylori in smokers because of N-acetylcysteine].

    Zala, G; Flury, R; Wüst, J; Meyenberger, C; Ammann, R; Wirth, H P


    Colonization of Helicobacter pylori (HP) beneath the protective film of gastric mucus enables the organism to survive in the hostile environment of the gastric mucosa. N-acetylcysteine (NAC), a sulfhydryl compound with potent mucolytic activity, induces a reduction of gastric barrier mucus thickness of about 75% and reduces mucus viscoelasticity. We therefore tested the hypothesis whether better eradication results could be achieved by addition of NAC to omeprazole/amoxicillin (OME/AMOX). 34 HP positive outpatients with endoscopically documented recurrent duodenal ulcer were included in an ongoing, prospective, randomized trial. Exclusion criteria were: alcoholism, previous gastric surgery, or intake of antibiotics, OME, bismuth salts, corticosteroids or NSAIDs within 4 weeks before study entry. Patients currently smoking > 10 cigarettes/day were classified as smokers. HP infection was confirmed by histology (3 biopsy specimens from gastric antrum and 2 from gastric body; H&E, Giemsa) and at least positive rapid urease test or culture. All 34 patients underwent ulcer therapy with OME (20 mg per day) for 20 days (d 1-20). Group A: in 17 patients (5 females, 12 males, mean age 46 [29-74] years; 8 smokers, 9 nonsmokers) the subsequent eradication therapy, consisting of oral OME (40 mg bid) and AMOX solute (750 mg tid) for 10 days, was combined with NAC solute (2 x 600 mg bid (d 21-30). Group B: 17 patients (2 females, 15 males, mean age 39 [19-70] years; 11 smokers, 6 nonsmokers) underwent eradication therapy without NAC (d 21-30). Control endoscopy was done after a minimal interval of 30 days from the end of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. The effect of N-acetylcysteine on the microscopic fluid dynamics of rat tears.

    Tragoulias, Sophia T; Anderton, Philip J


    BACKGROUND: The classical view of the tear film is of a 10-micron film of aqueous tears, sandwiched between thin layers of lipid and mucus. This has been challenged recently by the revelation that the tear film may be considerably thicker than 10 microns and that dissolved mucus and protein may play a much more important role than simply promoting tear adherence. In particular, the primary role of mucus may be to form a structured aqueous gel that adheres closely to the corneal surface and evens out its irregularities, thus providing a high-quality optical surface. METHODS: We have used the robust tear film of the rat eye as an animal model to investigate the contribution of mucus and low-molecular-weight (LMW) proteins to tear film structure. The ocular surface was first exposed to saline, which washed away the tear film. Single drops of a tear/saline mixture, treated with various concentrations of the thiol-reducing agent N-acetylcysteine (NAC), were placed on the ocular surface and the resulting fluid behaviour was recorded with video-microscopy. RESULTS: At five per cent concentration, NAC appeared to degrade the gap-filling and anti-evaporative qualities of the tears, features that give the rat tear film its robust characteristics. Lower concentrations had no significant effect. DISCUSSION: In a previous publication, we showed that five per cent NAC alters the profile of LMW proteins in rat tears. The present observations suggest that the robust wetting properties of rat tears depend critically on their mucus and/or LMW protein content and possibly are related to the formation of an aqueous/mucous gel.

  1. N-acetylcysteine stimulates protein synthesis in enterocytes independently of glutathione synthesis.

    Yi, Dan; Hou, Yongqing; Wang, Lei; Long, Minhui; Hu, Shengdi; Mei, Huimin; Yan, Liqiong; Hu, Chien-An Andy; Wu, Guoyao


    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.

  2. Effects of budesonide and N-acetylcysteine on acute lung hyperinflation, inflammation and injury in rats.

    Jansson, Anne-Helene; Eriksson, Christina; Wang, Xiangdong


    Leukocyte activation and production of inflammatory mediators and reactive oxygen species are important in the pathogenesis of lipopolysaccharide (LPS)-induced acute lung injury. The present study investigated acute lung hyperinflation, edema, and lung inflammation 4 h after an intratracheal instillation of LPS (0.5, 2.5, 5, 10, 50, 100, 500, 1000, and 5000 microg/ml/kg). Effects of budesonide, an inhaled anti-inflammatory corticosteroids, and N-acetylcysteine (NAC), an antioxidant, were evaluated in Wistar rats receiving either low (2.5 microg/ml/kg) or high (50 microg/ml/kg) concentrations of LPS. This study demonstrates that LPS in a concentration-dependent pattern induces acute lung hyperinflation measured by excised lung gas volume (25-45% above control), lung injury indicated by increased lung weight (10-60%), and lung inflammation characterized by the infiltration of leukocytes (40-14000%) and neutrophils (80-17000%) and the production of cytokines (up to 2700%) and chemokines (up to 350%) in bronchoalveolar lavage fluid (BALF). Pretreatment with NAC partially prevented tumor necrosis factor alpha (TNFalpha) production induced by the low concentration of LPS, while pretreatment with budesonide totally prevented the increased production of TNFalpha, interleukin (IL)-1beta, IL-6, and monocyte chemoattractive protein (MCP)-1 after LPS challenge at both low and high concentrations. Budesonide failed to prevent BALF levels of macrophage inflammatory protein (MIP)-2 and cytokine-induced neutrophil chemoattractant 1 (GRO/CINC-1) as well as lung hyperinflation induced by both low and high concentrations of LPS. Pretreatment with budesonide totally prevented the formation of lung edema at the low concentration of LPS and had partial effects on acute lung injury and leukocyte influx at the high concentrations. Thus, our data indicate that therapeutic effects of budesonide and NAC are dependent upon the severity of the disease.

  3. Glutamate transporter GLT-1 mediates N-acetylcysteine inhibition of cocaine reinstatement.

    Reissner, Kathryn J; Gipson, Cassandra D; Tran, Phuong K; Knackstedt, Lori A; Scofield, Michael D; Kalivas, Peter W


    Both pre-clinical and clinical studies indicate that N-acetylcysteine (NAC) may be useful in treating relapse to addictive drug use. Cocaine self-administration in rats reduces both cystine-glutamate exchange and glutamate transport via GLT-1 in the nucleus accumbens, and NAC treatment normalizes these two glial processes critical for maintaining glutamate homeostasis. However, it is not known if one or both of these actions by NAC is needed to inhibit relapse to cocaine seeking. To determine whether the restoration of GLT-1 and/or cystine-glutamate exchange is required for NAC to inhibit cue-induced reinstatement of cocaine seeking, we utilized the rat self-administration/extinction/reinstatement model of cocaine relapse. Rats were pre-treated in the nucleus accumbens with vivo-morpholino antisense oligomers targeting either GLT-1 or xCT (catalytic subunit of the cystine-glutamate exchanger) overlapping with daily NAC administration during extinction (100 mg/kg, i.p. for the last 5 days). Rats then underwent cue-induced reinstatement of active lever pressing in the absence of NAC, to determine if preventing NAC-induced restoration of one or the other protein was sufficient to block the capacity of chronic NAC to inhibit reinstatement. The vivo-morpholino suppression of xCT reduced cystine-glutamate exchange but did not affect NAC-induced reduction of reinstated cocaine seeking. In contrast, suppressing NAC-induced restoration of GLT-1 not only prevented NAC from inhibiting reinstatement, but augmented the capacity of cues to reinstate cocaine seeking. We hypothesized that the increased reinstatement after inhibiting NAC induction of GLT-1 resulted from increased extracellular glutamate, and show that augmented reinstatement is prevented by blocking mGluR5. Restoring GLT-1, not cystine-glutamate exchange, is a key mechanism whereby daily NAC reduces cue-induced cocaine reinstatement.

  4. Novel Thioester Prodrug of N-acetylcysteine for Odor Masking and Bioavailability Enhancement.

    Bhilare, Neha V; Dhaneshwar, Suneela S; Sinha, Akanksha J; Kandhare, Amit D; Bodhankar, Subhash L


    The mucolytic N-acetylcysteine (NAC) is used to control the excessive mucus secretion if mucus is the underlying cause of broncho-constriction. Its major drawbacks are poor bioavailability due to extensive first pass effect, poor lipophilicity, high protein binding and offensive odor. For minimizing above shortcomings of NAC, in present study thioester (A1) prodrug of NAC was synthesized by conventional as well as microwave-assisted methods. Release studies of A-1 were carried out using HPLC and pharmacological evaluation was performed in ovalbumin-induced model of pulmonary inflammation in Sprague dawley rats. A-1 was found to be stable in HCl buffer, phosphate buffer, stomach homogenates but furnished 30% NAC in 6h and 1.7% of NAC in 4h when incubated with small intestinal and liver homogenates respectively. Upon oral administration of A-1 to rats, 4.85% NAC was detected in blood at 8h. Urine samples pooled over a period of 24h exhibited 0.75% NAC while negligible concentration was found in 24 h pooled samples of feces. The findings of this preliminary investigation demonstrated significant effects of thioester prodrug A-1 as compared to NAC through reduction of lung inflammation, airway eosinophilia and reversal of lung function parameters in ovalbumin- challenged rats at half the equimolar dose of NAC. Interestingly masking thiol group through thioester formation resulted in odorless prodrug. We propose that thioester prodrug using palmitic acid as a carrier is a promising strategy to enhance bioavailability of NAC by increasing its lipophilicity/ absorption and minimizing its first pass metabolism.

  5. N-acetylcysteine reverses immunotoxic effects of methyl mercury and augments murine lymphocyte proliferation in vitro

    Omara, F.; Fournier, M.; Bernier, J. [Univ. du Quebec, Montreal, Quebec (Canada); Blakley, B.


    N-Acetylcysteine (NAC) is a thiol antioxidant used clinically to treat chronic inflammatory lung disorders and acetaminophen poisoning in humans. The authors evaluated in vitro the effect of NAC on mitogen-induced blastogenesis in C57BI/6 mouse splenocytes by {sup 3}H-thymidine uptake, and its ability to protect against the immunotoxic effects of methyl mercury on lymphocyte proliferation. Lymphocyte proliferation stimulated by optimal and suboptimal concentrations of concanavalin A (Con A), lipopolysaccharide (LPS), or a combination of calcium ionophore A23187 and phorbol-12-myristate-13-acetate (PMA) were markedly enhanced by NAC. NAC itself was a weak mitogen. The kinetics of the NAC effect on splenocyte proliferation were mitogen dependent. NAC enhanced Con A-induced splenocyte proliferation in a dose-dependent and linear manner but enhanced the LPS-induced response at 50--400 {micro}g/ml of NAC followed by a decline in response to control value at higher concentrations. In splenocytes stimulated with PMA plus A23187, NAC increased proliferation at 50--200 pg/ml followed by a constant response at 200--1,000 {micro}g/ml NAC. When splenocytes were stimulated with higher concentrations of Con A (10 {micro}g/ml) or LPS (150 {micro}g/ml) which markedly suppress splenocyte proliferation, NAC significantly enhanced the Con A-induced response and reversed the inhibitory effect of high concentrations of LPS. NAC also protected lymphocytes against mitogen activation-induced cell death. Methyl mercury at 5 {times} 10{sup {minus}7}--1 {times} 10{sup {minus}6} suppressed Con A- and LPS-induced splenocyte proliferation by over 80%. However, NAC completely reversed the immunotoxic effects of methyl mercury on the mitogen-induced splenocyte proliferation even when the cells were pre-incubated with methyl mercury for 6 or 24 hr before stimulation with the mitogens.

  6. S-nitroso-N-acetylcysteine ameliorates ischemia-reperfusion injury in the steatotic liver

    Wellington Andraus


    Full Text Available BACKGROUND: Steatosis is currently the most common chronic liver disease and it can aggravate ischemia-reperfusion (IR lesions. We hypothesized that S-nitroso-N-acetylcysteine (SNAC, an NO donor component, can ameliorate cell damage from IR injury. In this paper, we report the effect of SNAC on liver IR in rats with normal livers compared to those with steatotic livers. METHODS: Thirty-four rats were divided into five groups: I (n=8, IR in normal liver; II (n=8, IR in normal liver with SNAC; III (n=9, IR in steatotic liver; IV (n=9, IR in steatotic liver with SNAC; and V (n=10, SHAN. Liver steatosis was achieved by administration of a protein-free diet. A SNAC solution was infused intraperitoneally for one hour, beginning 30 min. after partial (70% liver ischemia. The volume of solution infused was 1 ml/100 g body weight. The animals were sacrificed four hours after reperfusion, and the liver and lung were removed for analysis. We assessed hepatic histology, mitochondrial respiration, oxidative stress (MDA, and pulmonary myeloperoxidase. RESULTS: All groups showed significant alterations compared with the group that received SHAN. The results from the steatotic SNAC group revealed a significant improvement in liver mitochondrial respiration and oxidative stress compared to the steatotic group without SNAC. No difference in myeloperoxidase was observed. Histological analysis revealed no difference between the non-steatotic groups. However, the SNAC groups showed less intraparenchymal hemorrhage than groups without SNAC (p=0.02. CONCLUSION: This study suggests that SNAC effectively protects against IR injury in the steatotic liver but not in the normal liver.

  7. N-acetylcysteine attenuates oxidative stress and liver pathology in rats with non-alcoholic steatohepatitis


    AIM: To evaluate attenuating properties of N-acetylcysteine (NAC) on oxidative stress and liver pathology in rats with non-alcoholic steatohepatitis (NASH).METHODS: Male Sprague-Dawley rats were randomly divided into three groups. Group 1 (control, n = 8) was free accessed to regular dry rat chow (RC) for 6 wk.Group 2 (NASH, n = 8) was fed with 100% fat diet for 6 wk. Group 3 (NASH+ NAC20, n = 9) was fed with 100% fat diet plus 20 mg/kg per day of NAC orally for 6 wk. All rats were sacrificed to collect blood and liver samples at the end of the study.RESULTS: The levels of total glutathione (GSH)and hepatic malondialdehyde (MDA) were increased significantly in the NASH group as compared with the control group (GSH; 2066.7 ± 93.2 vs 1337.5 ± 31.5 μmol/L and MDA; 209.9± 43.9 vs 3.8 ±1.7 μmol/g protein, respectively, P < 0.05). Liver histopathology from group 2 showed moderate to severe macrovesicular steatosis, hepatocyte ballooning, and necroinflammation.NAC treatment improved the level of GSH (1394.8 ± 81.2 μmol/L, P < 0.05), it did not affect MDA (150.1 ± 27.0 μmol/g protein), but led to a decrease in fat deposition and necroinflammation.CONCLUSION: NAC treatment could attenuate oxidative stress and improve liver histology in rats with NASH.

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

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


    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.

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

    S.G. Suke


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

  10. The Effect of N-acetylcysteine on Biomarkers for Radiation-Induced Oxidative Damage in a Rat Model

    Tamer, Lülüfer; GÜRGÜL, Serkan; Erdal,Nurten; Demirel, Can; Kilciksiz, Sevil; Ayaz, Lokman; Örs, Yasemin


    Our study aimed to investigate the potential radioprotective effects of N-acetylcysteine (NAC) by comparing its biochemical effects with those of WR-2721, as a representative of clinically used radioprotectors, in preventing oxidative damage caused by gamma irradiation (single dose, 6Gy) in normal rat tissue. The rats (n=40) were divided randomly and equally into 4 groups:Control (C), Radiation (R), R+NAC (received irradiation and 1,000mg/kg NAC) and R+WR-2721 (received irradiation and...

  11. N-acetylcysteine and contrast-induced nephropathy: a meta-analysis of 13 randomized trials.

    Zagler, Axel; Azadpour, Maziar; Mercado, Carlos; Hennekens, Charles H


    Contrast-induced nephropathy (CIN) following coronary angiography increases morbidity and mortality. Randomized trials of small sample size have evaluated whether N-acetylcysteine (NAC) prevents CIN in patients with renal dysfunction. To conduct a meta-analysis of the randomized trials the following databases were searched: MEDLINE (1966-2003), Cochrane Controlled Trials Register, ACP Journal Club online, published abstracts presented at the major cardiology and nephrology meetings, references from reviews. Two authors independently evaluated all relevant randomized trials. Eligibility criteria were (1) randomized placebo controlled trials of NAC, (2) patients with impaired renal function (creatinine >1.2 mg/dL) undergoing coronary angiography, (3) patients receiving intravenous fluids and low-osmolarity nonionic contrast media, (4) the primary outcome was CIN (increases in creatinine of either at least 0.5 mg/dL or 25% from baseline to 48 hours). Of 589 trials reviewed 3 disagreements were easily resolved by mutual discussion and 13 were selected. Data extraction included patient characteristics, intravenous fluid regimen, type and dose of contrast media, dosing regimen, creatinine at baseline and 48 hours and CIN requiring dialysis. Four of the 13 trials reported statistically significant results. In meta-analysis of the 13 trials, which included 1892 patients, the RR was 0.68 (95%CI, 0.46-1.01). The addition of the trial of patients undergoing computerized tomography, which had formulated the hypothesis, yielded a statistically significant reduction (RR 0.64 [95%CI 0.42-0.96]) as did an earlier meta-analysis of 7 trials. Our meta-analysis of the most currently available randomized data concerning NAC before coronary angiography to prevent CIN in patients with impaired renal function is neither conclusive nor provides proof beyond a reasonable doubt to influence clinical practice and public policy. The intervention has minimal toxicity but the width of the 95% CI

  12. Effects of N-acetylcysteine on Clara cells in rats with cigarette smoke exposure

    LIAO Ji-ping; CHI Chun-hua; LI Hai-chao; TANG Xiu-ying


    Background The number of Clare cells and the Clara cell 16-kDa protein (CC16) levels of the lung decrease in patients with chronic obstructive pulmonary disease (COPD). N-acetylcysteine (NAC) is a powerful antioxidant and can reduce the frequency of acute exacerbations of COPD. But the exact mechanism is unclear. The present study was designed to investigate the effects of NAC on Clara cells in rats with cigarette smoke exposure.Methods Eighteen adult male Wistar rats were randomly divided into 3 groups, 12 exposed to cigarette smoke (CS) thrice a day, 10 cigarettes for 30 minutes each time for 1 week, without (CS group) or with (CS+NAC group) oral intake of NAC 80 mg·kg~(-1)·d~(-1), and another 6 rats exposed to fresh air (control group). Clara cells were observed by an electron microscope. The Mrna expression of CC16 and CC16 protein in lungs were determined by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry respectively. The glutathion (GSH) level in plasma and lung tissue were tested by fluorimetry assay.Results Compared with the controls, the pathologic score of small airways significantly increased in the CS exposed rats (20.3±14.7 vs. 53.7±11.5, P 0.05). No significant difference was found in the expression of CC16 Mrna among the three groups. Correlation analysis indicated that the percentage of CC16-positive cells in bronchioles negatively correlated with the pathologic score of small airways (r=-0.592, P<0.05), but not with GSH level.Conclusions One-week CS exposure decreased the number of Clara cells and the expression of CC16 in bronchioles in rats. NAC might provide protection of the Clara cells from oxidative damage and possibly through the elevation of the synthesis and secretion of CC16. These data indicate that NAC decreases airway inflammation induced by CS via induction of CC16.

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

    Serbülent Gökhan Beyaz


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

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

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


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

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

    Leonardo Victor Barbosa Pereira

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

  16. Examination of the Ability of N-acetylcysteine Administration during Anesthesia to Prevent Perioperative Deterioration of Pulmonary Function in Patients Undergoing Nephrectomy.

    Um, Dea Ja; Hong, Seok-Joo; Park, Jong Taek


    Postoperative pulmonary complications are associated with significant morbidity and mortality in patients undergoing major surgeries. Acetylcysteine is a known antioxidant and is also used as a mucolytic agent to reduce hypersecretion and the viscosity of mucus secretions by the lung. Several studies have revealed that high doses of N-acetylcysteine can significantly prevent pulmonary complications. However, it has not yet been established whether low doses of N-acetylcysteine are also of clinical benefit. Here, we investigated the efficacy of a low dose of N-acetylcysteine, which was administered intravenously to patients under general anesthesia, in preventing perioperative deterioration of pulmonary function. A total of 52 patients who were scheduled for nephrectomy were randomly assigned to receive either 600 mg of intravenous N-acetylcysteine or the same volume of normal saline. Patient hemodynamic and pulmonary parameters and the incidence of pulmonary complications were recorded and compared between the groups. No significant pulmonary complications occurred in either group. Moreover, no significant differences were observed regarding either patient characteristics or hemodynamic parameters between the two groups. Contrary to our expectations, the pulmonary parameters were also not significantly different between the two groups. A low dose of N-acetylcysteine appears to have only limited value in preventing perioperative pulmonary complications.

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

    Danuta Plewka


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

  18. N-acetylcysteine infusion reduces the resistance index of renal artery in the early stage of systemic sclerosis

    Edoardo ROSATO; Rosario CIANCI; Biagio BARBANO; Ginevra MENGHI; Antonietta GIGANTE; Carmelina ROSSI; Enrico M ZARDI; Antonio AMOROSO; Simonetta PISARRI; Felice SALSANO


    Aim: To evaluate resistance index (RI) changes in renal artery after N-acetylcysteine infusion in patients with systemic sclerosis. Methods: In an open-label study 40 patients with systemic sclerosis (SSc) were treated with N-acetylcysteine (NAC) iv infusion over 5 consecutive hours, at a dose of 0.015g·kg~(-1)·h~(-1).Renal haemodynamic effects were evaluated by color Doppler examination before and after NAC infusion. Results: NAC infusion significantly reduced RI in a group of sclerodermic patients with early/active capillaroscopic pattern, modified Rodnan Total Skin Score (mRTSS)14 and severe-end stage score to the vascular domain of DSS. In patients with reduction of RI after NAC infusion, diffusion capacity for carbon monoxide mean value was significantly higher than in those patients with an increase of RI. No significant differences in renal blood flow were found between patients with different subsets of SSc. Conclusion: In patients with low disease severity NAC ameliorates vascular renal function.

  19. An open-label pilot study of N-acetylcysteine for skin-picking in Prader-Willi syndrome.

    Miller, Jennifer L; Angulo, Moris


    Prader-Willi syndrome (PWS) is a complex neurodevelopmental disorder caused by an abnormality on the long arm of chromosome 15 (q11-q13) that results in a host of behavioral characteristics including excessive interest in food, skin picking, difficulty with a change in routine, and obsessive and compulsive behaviors. Skin-picking can result in serious and potentially life-threatening infections. Recent evidence suggests that the excitatory neurotransmitter glutamate is dysregulated in obsessive-compulsive behaviors, and modulation of the glutaminergic pathway may decrease compulsive behaviors, such as recurrent hair pulling or skin-picking behaviors. N-acetylcysteine (NAC), a derivative of the amino acid cysteine, is thought to act either via modulation of NMDA glutamate receptors or by increasing glutathione in pilot studies. Thirty-five individuals with confirmed PWS (ages 5-39 years, 23 females/12 males) and skin-picking behavior for more than 1 year were treated with N-acetylcysteine (Pharma-NAC®) at a dose of 450-1,200 mg/day. Skin-picking symptoms and open lesions were assessed after 12 weeks of treatment by counting and measuring lesions before and after the medication. All 35 individuals had improvement in skin-picking behaviors. Ten (29%) individuals (six males and four females) did not have complete resolution of skin-picking behavior, but had significant reduction in the number of active lesions. Longer-term, placebo-controlled trials are needed to further assess the potential benefit of this treatment.

  20. The protective effect of N-acetylcysteine against acrylamide toxicity in liver and small and large intestine tissues.

    Altinoz, E; Turkoz, Y; Vardi, N


    The aim of this study was to investigate the protective effects of N-acetylcysteine against acrylamide toxicity in liver and small and large intestine tissues in rats.The rats were divided into four groups. Acrylamide administration increased MDA levels in all tissues significantly (p acrylamide+NAC administration decreased MDA levels significantly as compared to the acrylamide group, and lowered it to a level close to the control group values (p acrylamide group (p acrylamide+NAC administration increased GSH levels significantly in all tissues. Whereas GST activity decreased significantly in the acrylamide group in liver and small intestine tissues as compared to the other groups (p acrylamide+NAC group in all tissues as compared to the acrylamide group (p acrylamide group. Small intestine histopathology showed that the intestinal villous epithelial cells were damaged significantly in the acrylamide group.Our results indicate that a high level of acrylamide causes oxidative damage in liver and small and large intestine tissues, while N-acetylcysteine administration in a pharmacological dose shows to have an antioxidant effect in preventing this damage (Tab. 2, Fig. 2, Ref. 66).

  1. Oral N-acetylcysteine reduces bleomycin-induced lung damage and mucin Muc5ac expression in rats.

    Mata, M; Ruíz, A; Cerdá, M; Martinez-Losa, M; Cortijo, J; Santangelo, F; Serrano-Mollar, A; Llombart-Bosch, A; Morcillo, E J


    Oxidative stress is involved in the pathogenesis of pulmonary fibrosis, therefore antioxidants may be of therapeutic value. Clinical work indicates that N-acetylcysteine (NAC) may be beneficial in this disease. The activity of this antioxidant was examined on bleomycin-induced lung damage, mucus secretory cells hyperplasia and mucin Muc5ac gene expression in rats. NAC (3 mmol x kg(-1) x day(-1)) or saline was given orally to Sprague-Dawley rats for 1 week prior to a single intratracheal instillation of bleomycin (2.5 U x kg(-1)) and for 14 days postinstillation. NAC decreased collagen deposition in bleomycin-exposed rats (hydroxyproline content was 4,257+/-323 and 3,200+/-192 microg x lung(-1) in vehicle- and NAC-treated rats, respectively) and lessened the fibrotic area assessed by morphometric analysis. The bleomycin-induced increases in lung tumour necrosis factor-alpha and myeloperoxidase activity were reduced by NAC treatment. The numbers of mucus secretory cells in airway epithelium, and the Muc5ac messenger ribonucleic acid and protein expression, were markedly augmented in rats exposed to bleomycin. These changes were significantly reduced in NAC-treated rats. These results indicate that bleomycin increases the number of airway secretory cells and their mucin production, and that oral N-acetylcysteine improved pulmonary lesions and reduced the mucus hypersecretion in the bleomycin rat model.

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

    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


    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 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.

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

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


    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…

  4. Effects of N-acetylcysteine on outcomes in chronic obstructive pulmonary disease (Bronchitis Randomized on NAC Cost-Utility Study, BRONCUS): a randomised placebo-controlled trial.

    Decramer, M.; Rutten-van Molken, M.P.; Dekhuijzen, P.N.R.; Troosters, T.; Herwaarden, C.L.A. van; Pellegrino, R.; Schayck, C.P. van; Olivieri, D.; Donno, M. Del; Backer, W. de; Lankhorst, I.L.M.; Ardia, A.


    BACKGROUND: Increased oxidative stress is important in the pathogenesis of chronic obstructive pulmonary disease (COPD). We postulated that treatment with the antioxidant N-acetylcysteine would reduce the rate of lung-function decline, reduce yearly exacerbation rate, and improve outcomes. METHODS:

  5. Effects of N-acetylcysteine on outcomes in chronic obstructive pulmonary disease (Bronchitis Randomized on NAC Cost-Utility Study, BRONCUS): a randomised placebo-controlled trial.

    Decramer, M.; Rutten-van Molken, M.P.; Dekhuijzen, P.N.R.; Troosters, T.; Herwaarden, C.L.A. van; Pellegrino, R.; Schayck, C.P. van; Olivieri, D.; Donno, M. Del; Backer, W. de; Lankhorst, I.L.M.; Ardia, A.


    BACKGROUND: Increased oxidative stress is important in the pathogenesis of chronic obstructive pulmonary disease (COPD). We postulated that treatment with the antioxidant N-acetylcysteine would reduce the rate of lung-function decline, reduce yearly exacerbation rate, and improve outcomes. METHODS:


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


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

  7. A double-blind placebo controlled trial with oral ambroxol and N-acetylcysteine for mucolytic treatment in cystic fibrosis.

    Ratjen, F; Wönne, R; Posselt, H G; Stöver, B; Hofmann, D; Bender, S W


    The therapeutic efficacy of oral N-acetylcysteine (NAC) and ambroxol as compared with the effect of placebos was studied in 36 cystic fibrosis (CF) patients with mild to moderate pulmonary disease. The patients were randomly assigned to one of three regimens, matched on the basis of age and Chrispin-Norman scores. The trial was conducted over a period of 12 weeks. Patients were assessed clinically and by extensive pulmonary function techniques (body-plethysmography, maximal expiratory flow-volume curves, trapped air determination). Although no clinical differences could be observed between the three groups, significant impairment in the placebo group was found for trapped air and FEV1 when compared to the active groups, suggesting a therapeutic effect of ambroxol and NAC in CF.

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

    Tse HN


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

  9. Acute and Chronic Effects of N-acetylcysteine on Pentylenetetrazole-induced Seizure and Neuromuscular Coordination in Mice

    Sasan Zaeri


    Full Text Available Background: N-acetylcysteine (NAC has been indicated against experimental seizures, but with relatively inconclusive results. This study was undertaken to evaluate whether NAC exerts a dose-dependent anticonvulsant effect and to determine NAC safe therapeutic dose range and its muscle-relaxant activity in both acute and chronic uses. Methods: Following intraperitoneal (i.p. administration of N-acetylcysteine acutely (50-300 mg/kg or chronically for 8 days (25-300 mg/kg, mice were injected with PTZ (90 mg/kg, i.p. and latency times to the onset of myoclonic and clonic seizures and protection against death were recorded. Changes in body weight and mortality rate were considered as parameters for drug safety. The muscle-relaxant activity of NAC was assessed by rotarod test. Results: Acute and chronic treatment with NAC delayed latency times to myoclonic and clonic seizures in a dose-dependent manner, but with no significant prevention against PTZ-induced death. Chronic administration of 300 mg/kg NAC was fully lethal while lower doses (100 and 150 mg/kg resulted in a significant weight loss and decreased stay time on rotarod. Acute treatment with NAC had no significant effect on stay time on rotarod at all studied doses. Conclusion: NAC exerts a dose-dependent anticonvulsant effect in acute and chronic uses, with no muscle relaxant activity. NAC has higher efficacy in preventing seizure in chronic than acute treatment, but its chronic use at higher doses of 75 mg/kg may be associated with side effects and/or toxicity. These findings suggest that low doses of NAC may have a potential use as a prophylactic treatment for absence seizure in human.

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

    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


    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

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

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


    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.

  12. Disruption of steroidogenesis after dimethoate exposure and efficacy of N-acetylcysteine in rats: an old drug with new approaches.

    Jallouli, Manel; El Bini Dhouib, Ines; Dhouib, Hanène; Lasram, Montassar; Gharbi, Najoua; El Fazaa, Saloua


    Organophosphates (OPs) like dimethoate (DMT), are pesticides used worldwide, which can affect both animals and human. Whereas their toxicity is due to acetylcholinesterase inhibition, their secondary toxic effects have been related to free oxygen radical biosynthesis. The present study was designed to investigate the reprotoxic effects of DMT and the protective role of N-acetylcysteine (NAC) in male rat. DMT (20 mg/ kg/body weight) was administered daily to rats via gavage in corn oil and NAC (2 g/l) was added to drinking water for 30 days. Rats were sacrificed on the 30th day, 2 h after the last administration. Markers of testis injury (steroidogenesis impairment) and oxidative stress (lipid peroxidation, reduced glutathione, and antioxidant status) were assessed. In DMT-exposed rats, the serum level of testosterone was decreased. Further, a significant increase in lipid peroxidation level and a significant decrease in the activities of antioxidant enzymes were observed in the testis of rats during DMT intoxication. Real-time PCR (RT-PCR) analysis demonstrated a decrease in messenger RNA (mRNA) levels for testicular steroidogenic acute regulatory StAR protein, cytochrome P450scc, 3β-hydroxysteroid dehydrogenase (3β-HSD), and 17β hydroxysteroid dehydrogenase (17β-HSD) in the testis after DMT exposure. No significant changes in the oxidative stress status and selected reproductive variables were observed on CTN group, whereas NAC restored the oxidative stress and the steroidogenesis on NAC group. Dimethoate induces reprotoxicity and oxidative stress. N-acetylcysteine showed therapeutic recovery effects against dimethoate toxicity.

  13. Efficacy of N-Acetylcysteine Augmentation on Obsessive Compulsive Disorder: A Multicenter Randomized Double Blind Placebo Controlled Clinical Trial

    Ahmad Ghanizadeh


    Full Text Available Objective: Glutamate is considered a target for treating obsessive-compulsive disorder (OCD. The efficacy and safety of the nutritional supplement of N-Acetylcysteine (NAC as an adjuvant to serotonin reuptake inhibitor (SSRI for treating children and adolescents with OCD has never been examined.Methods: This was a 10-week randomized double-blind placebo-controlled clinical trial with 34 OCD outpatients. The patients received citalopram plus NAC or placebo. Yale-Brown Obsessive-Compulsive Scale (YBOCS and Pediatric Quality of Life Inventory (PedsQL™ were used. Adverse effects were monitored.Results: YBOCS score was not different between the two groups at baseline, but the score was different between the two groups at the end of this trial (P<0.02. The YBOCS score of NAC group significantly decreased from 21.0(8.2 to 11.3(5.7 during this study. However, no statistically significant decrease of YBOCS was found in the placebo group. The Cohen’s d effect size was 0.83.The mean change of score of resistance/control to obsessions in the NAC and placebo groups was 1.8(2.3 and 0.8(2.1, respectively (P = 0.2. However, the mean score of change for resistance/control to compulsion in the NAC and placebo groups was 2.3(1.8 and 0.9(2.3, respectively. Cohen’s d effect size was 0.42.The score of three domains of quality of life significantly decreased in N-Acetylcysteine group during this trial. However, no statistically significant decrease was detected in the placebo group. No serious adverse effect was found in the two groups.Conclusion: This trial suggests that NAC adds to the effect of citalopram in improving resistance/control to compulsions in OCD children and adolescents. In addition, it is well tolerated.

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

    Tommaso Cai


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

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

    Cai, Tommaso; Gallelli, Luca; Meacci, Francesca; Brugnolli, Anna; Prosperi, Letizia; Roberta, Stefani; Eccher, Cristina; Mazzoli, Sandra; Lanzafame, Paolo; Caciagli, Patrizio; Malossini, Gianni; Bartoletti, Riccardo


    We evaluated, in a preliminary study, the efficacy of umbelliferone, arbutin, and N-acetylcysteine to inhibit biofilm formation on urinary catheter. We used 20 urinary catheters: 5 catheters were incubated with Enterococcus faecalis (control group); 5 catheters were incubated with E. faecalis in presence of umbelliferone (150 mg), arbutin (60 mg), and N-acetylcysteine (150 mg) (group 1); 5 catheters were incubated with E. faecalis in presence of umbelliferone (150 mg), arbutin (60 mg), and N-acetylcysteine (400 mg) (group 2); and 5 catheters were incubated with E. faecalis in presence of umbelliferone (300 mg), arbutin (60 mg), and N-acetylcysteine (150 mg) (group 3). After 72 hours, planktonic microbial growth and microorganisms on catheter surface were assessed. In the control group, we found a planktonic load of ≥10(5) CFU/mL in the inoculation medium and retrieved 3.69 × 10(6) CFU/cm from the sessile cells adherent to the catheter surface. A significantly lower amount in planktonic (p < 0.001) and sessile (p = 0.004) bacterial load was found in group 3, showing <100 CFU/mL and 0.12 × 10(6) CFU/cm in the incubation medium and on the catheter surface, respectively. In groups 1 and 2, 1.67 × 10(6) CFU/cm and 1.77 × 10(6) CFU/cm were found on catheter surface. Our results document that umbelliferone, arbutin, and N-acetylcysteine are able to reduce E. faecalis biofilm development on the surface of urinary catheters.

  16. Oral administration of S-nitroso-N-acetylcysteine prevents the onset of non alcoholic fatty liver disease in rats

    Claudia PMS de Oliveira; Marcelo G de Oliveira; Fernanda I Simplicio; Vicência MR de Lima; Katia Yuahasi; Fabio P Lopasso; Ven(a)ncio AF Alves; Dulcinéia SP Abdalla; Flair J Carrilho; Francisco RM Laurindo


    AIM: To evaluate the potential of S-nitroso-N-acetylcysteine (SNAC) in inhibition of lipid peroxidation and the effect of oral SNAC administration in the prevention of nonalcoholic fatty liver disease (NAFLD) in an animal model.METHODS: NAFLD was induced in Wistar male rats by choline-deficient diet for 4 wk. SNAC-treated animals (n=6) (1.4 mg/kg/day of SNAC, orally) were compared to 2 control groups: one (n=6) received PBS solution and the other (n=6) received NAC solution (7 mg/kg/d).Histological variables were semiquantitated with respect to macro and microvacuolar fat changes, its zonal distribution, foci of necrosis, portal and perivenular fibrosis, and inflammatory infiltrate with zonal distribution.LOOHs from samples of liver homogenates were quantified by HPLC. Nitrate levels in plasma of portal vein were assessed by chemiluminescence. Aqueous low-density lipoprotein (LDL) suspensions (200 μg protein/mL) were incubated with CuCl2 (300 μmol/L) in the absence and presence of SNAC (300 μmol/L) for 15 h at 37 ℃. Extent of LDL oxidation was assessed by fluorimetry. Linoleic acid (LA) (18.8 μmol/L) oxidation was induced by soybean lipoxygenase (SLO) (0.056 μmol/L) at 37 ℃ in the presence and absence of N-acetylcysteine (NAC) and SNAC (56 and 560 μmol/L) and monitored at 234 nm.RESULTS: Animals in the control group developed moderate macro and microvesicular fatty changes in periportal area. SNAC-treated animals displayed only discrete histological alterations with absence of fatty changes and did not develop liver steatosis. The absence of NAFLD in the SNAC-treated group was positively correlated with a decrease in the concentration of LOOH in liver homogenate, compared to the control group (0.7±0.2 nmol/mg vs 3.2±0.4 nmol/mg protein, respectively, P<0.05), while serum levels of aminotransferases were unaltered. The ability of SNAC in preventing lipid peroxidation was confirmed in in vitro experiments using LA and LDL as model substrates

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

    Adelson M Rodrigues

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

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

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


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

  19. Inhibition of brain creatine kinase activity after renal ischemia is attenuated by N-acetylcysteine and deferoxamine administration.

    Di-Pietro, Priscila B; Dias, Márcia L; Scaini, Giselli; Burigo, Márcio; Constantino, Larissa; Machado, Roberta A; Dal-Pizzol, Felipe; Streck, Emilio L


    Encephalopathy may accompany acute or chronic renal failure, and the mechanisms responsible for neurological complications in patients with renal failure are poorly known. Considering that creatine kinase (CK) is important for brain energy homeostasis and is inhibited by free radicals, and that oxidative stress is probably involved in the pathogenesis of uremic encephalopathy, we measured CK activity (hippocampus, striatum, cerebellum, cerebral cortex and prefrontal cortex) in brain if rats submitted to renal ischemia and the effect of administration of antioxidants (N-acetylcysteine, NAC and deferoxamine, DFX) on this enzyme. We verified that CK activity was not altered in cerebellum and striatum of rats. CK activity was inhibited in prefrontal cortex and hippocampus of rats 12h after renal ischemia. The treatment with antioxidants prevented such effect. Cerebral cortex was also affected, but in this area CK activity was inhibited 6 and 12h after renal ischemia. Moreover, only NAC or NAC plus DFX were able to prevent the inhibition on the enzyme. Although it is difficult to extrapolate our findings to the human condition, the inhibition of brain CK activity after renal failure may be associated to neuronal loss and may be involved in the pathogenesis of uremic encephalopathy.

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

    Schmidt, L E; Dalhoff, K


    AIMS: To identify risk factors in the development of side-effects to N-acetylcysteine (NAC) in patients with paracetamol poisoning. METHODS: A retrospective study was carried out based upon the hospital charts of 529 consecutive patients admitted with paracetamol poisoning, all treated with NAC......, at the Department of Hepatology, Copenhagen University Hospital (the tertiary care centre of liver disease in Denmark). RESULTS: Forty-five patients (8.5%; 95% confidence intervals (CI) 6.4, 11%) developed side-effects to NAC and 18 patients (3.4%; 95% CI 2.1, 5.4%) developed systemic side-effects. Asthmatics were...... 2.9 times (95% CI 2.1, 4.7) more likely to develop side-effects (Chi-square: P = 0.004). Side-effects were of similar severity in asthmatics and nonasthmatics. A history of medical allergy was not a risk factor. Serum paracetamol was lower in patients with side-effects than in those without (Mann...

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

    Nai-Chia Fan


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

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

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


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

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

    Ausama Ayoob Jaccob


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

  4. Effect of N-acetylcysteine on gas exchange after methacholine challenge and isoprenaline inhalation in the dog.

    Ueno, O; Lee, L N; Wagner, P D


    N-acetylcysteine (NAC) has antioxidant and possibly mucolytic properties. To determine whether NAC could be of benefit in acute bronchoconstriction induced by methacholine, 12 of 24 anaesthetized dogs (group 1) received NAC i.v. (loading dose 150, then 20 The other 12 (group 2) received diluent. Nebulized methacholine (1%) was then inhaled until arterial oxygen tension (PaO2) fell to a mean of 5.5 kPa, after which isoprenaline 0.5% was inhaled in six dogs of each group to reverse bronchoconstriction. Over the next 3 h we measured total lung resistance, functional residual capacity (FRC), haemodynamic variables, and pulmonary gas exchange for respiratory and inert gases. After methacholine challenge, lung resistance increased and then fell similarly for both groups, but PaO2 was higher in the NAC group (by 0.6-1.9 kPa) throughout the observation period. The ventilation-perfusion distribution measured by inert gas elimination also showed less abnormality in the NAC treated dogs over this time. Mucus was visible during post-mortem in the large airways in about half of the dogs in both groups, with no significant differences between them. These results show that NAC produces a measurable improvement in gas exchange following methacholine challenge (both with and without subsequent isoprenaline therapy) by mechanisms that remain to be determined.

  5. N-acetylcysteine Enhances Cystic Fibrosis Sputum Penetration and Airway Gene Transfer by Highly Compacted DNA Nanoparticles.

    Suk, Jung Soo; Boylan, Nicholas J; Trehan, Kanika; Tang, Benjamin C; Schneider, Craig S; Lin, Jung-Ming G; Boyle, Michael P; Zeitlin, Pamela L; Lai, Samuel K; Cooper, Mark J; Hanes, Justin


    For effective airway gene therapy of cystic fibrosis (CF), inhaled gene carriers must first penetrate the hyperviscoelastic sputum covering the epithelium. Whether clinically studied gene carriers can penetrate CF sputum remains unknown. Here, we measured the diffusion of a clinically tested nonviral gene carrier, composed of poly-l-lysine conjugated with a 10 kDa polyethylene glycol segment (CK30PEG10k). We found that CK30PEG10k/DNA nanoparticles were trapped in CF sputum. To improve gene carrier diffusion across sputum, we tested adjuvant regimens consisting of N-acetylcysteine (NAC), recombinant human DNase (rhDNase) or NAC together with rhDNase. While rhDNase alone did not enhance gene carrier diffusion, NAC and NAC + rhDNase increased average effective diffusivities by 6-fold and 13-fold, respectively, leading to markedly greater fractions of gene carriers that may penetrate sputum layers. We further tested the adjuvant effects of NAC in the airways of mice with Pseudomonas aeruginosa lipopolysaccharide (LPS)-induced mucus hypersecretion. Intranasal dosing of NAC prior to CK30PEG10k/DNA nanoparticles enhanced gene expression by up to ~12-fold compared to saline control, reaching levels observed in the lungs of mice without LPS challenge. Our findings suggest that a promising synthetic nanoparticle gene carrier may transfer genes substantially more effectively to lungs of CF patients if administered following adjuvant mucolytic therapy with NAC or NAC + rhDNase.

  6. Suppression of prolactin signaling by pyrrolidine dithiocarbamate is alleviated by N-acetylcysteine in mammary epithelial cells.

    Wang, Jen-Hsing; Du, Jyun-Yi; Wu, Yi-Ying; Chen, Meng-Chi; Huang, Chun-Hao; Shen, Hsin-Ju; Lee, Chin-Feng; Lin, Ting-Hui; Lee, Yi-Ju


    Prolactin is the key hormone to stimulate milk synthesis in mammary epithelial cells. It signals through the Jak2-Stat5 pathway to induce the expression of β-casein, a milk protein which is often used as a marker for mammary differentiation. Here we examined the effect of pyrrolidine dithiocarbamate (PDTC) on prolactin signaling. Our results show that PDTC downregulates prolactin receptor levels, and inhibits prolactin-induced Stat5 tyrosine phosphorylation and β-casein expression. This is not due to its inhibitory action on NF-κB since application of another NF-κB inhibitor, BAY 11-7082, and overexpression of I-κBα super-repressor do not lead to the same results. Instead, the pro-oxidant activity of PDTC is involved as inclusion of the antioxidant N-acetylcysteine restores prolactin signaling. PDTC triggers great extents of activation of ERK and JNK in mammary epithelial cells. These do not cause suppression of prolactin signaling but confer serine phosphorylation of insulin receptor substrate-1, thereby perturbing insulin signal propagation. As insulin facilitates optimal β-casein expression, blocking insulin signaling by PDTC might pose additional impediment to β-casein expression. Our results thus imply that lactation will be compromised when the cellular redox balance is dysregulated, such as during mastitis.

  7. Development and optimization of N-Acetylcysteine-loaded poly (lactic-co-glycolic acid) nanoparticles by electrospray.

    Karimi Zarchi, Ali Akbar; Abbasi, Shayan; Faramarzi, Mohammad Ali; Gilani, Kambiz; Ghazi-Khansari, Mahmoud; Amani, Amir


    N-Acetylcysteine (NAC) loaded PLGA nanoparticles were prepared by electrospray method. The influence of independent parameters such as concentration, flow rate and nozzle to collector distance was studied on particle size and size distribution of generated nanoparticles using a Box-Behnken experimental design. Smallest size was found to be obtained at minimum value for both flow rate and concentration of polymer, regardless of collecting distance value in the ranges studied. Additionally, the minimum value of size distribution was observed at lowest values of both concentration of polymer and collecting distance, regardless of flow rate value. In total, a sample with minimum size and polydispersity was predicted to have flow rate, polymer concentration and collecting distance values of 0.06(ml/h), 0.5(%w/w) and 9.28(cm), respectively. The experimentally prepared nanoparticles with lowest size and size distribution values, had a size of 122(nm) and size distribution of 24. Zeta potential, drug loading and encapsulation efficiency of optimized nanoparticles were -6.58, 5% and 54.5%, respectively.

  8. Effects of verapamil, carbenoxolone and N-acetylcysteine on gastric wall mucus and ulceration in stressed rats.

    Koo, M W; Ogle, C W; Cho, C H


    The effects of verapamil on gastric wall mucus and ulceration were studied in rats which were restrained and exposed to 4 degrees C (stress). Stress for 2 h significantly depleted stomach wall mucus and produced marked gastric glandular ulcers. Verapamil pretreatment (2, 4, 8 or 16 mg/kg), injected intraperitoneally 30 min before experimentation, significantly prevented stress-induced mucus depletion and gastric ulceration; however, it did not itself influence stomach wall mucus levels in nonstressed animals. Intragastric administration of carbenoxolone (100 or 200 mg/kg), also given 30 min before stress, exhibited similar actions as verapamil. A 15% solution of N-acetylcysteine (10 ml/kg), given orally, strongly decreased the mucus content in both nonstress and stress conditions; it induced ulcers in nonstressed rats, and worsened stress ulceration. These effects were not reversed by verapamil pretreatment. The influence of multiple-dose pretreatment with verapamil or carbenoxolone on mucus content and ulceration in the gastric glandular mucosa during stress is also discussed. It is concluded that gastric wall mucus depletion is likely to play an important role in stress ulcer formation; the antiulcer action of verapamil could partly be due to the preservation of mucus.

  9. High-dose N-acetylcysteine in the prevention of COPD exacerbations: rationale and design of the PANTHEON Study.

    Zheng, Jin-Ping; Wen, Fu-Qiang; Bai, Chun-Xue; Wan, Huan-Ying; Kang, Jian; Chen, Ping; Yao, Wan-Zhen; Ma, Li-Jun; Xia, Qi-Kui; Gao, Yi; Zhong, Nan-Shan


    Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation; from a pathophysiological point of view it involves many components, including mucus hypersecretion, oxidative stress and inflammation. N-acetylcysteine (NAC) is a mucolytic agent with antioxidant and anti-inflammatory properties. Long-term efficacy of NAC 600mg/d in COPD is controversial; a dose-effect relationship has been demonstrated, but at present it is not known whether a higher dose provides clinical benefits. The PANTHEON Study is a prospective, ICS stratified, randomized, double-blind, placebo-controlled, parallel-group, multi-center trial designed to assess the efficacy and safety of high-dose (1200 mg/daily) NAC treatment for one year in moderate-to-severe COPD patients. The primary endpoint is the annual exacerbation rate. Secondary endpoints include recurrent exacerbations hazard ratio, time to first exacerbation, as well as quality of life and pulmonary function. The hypothesis, design and methodology are described and baseline characteristics of recruited patients are presented. 1006 COPD patients (444 treated with maintenance ICS, 562 ICS naive, aged 66.27±8.76 yrs, average post-bronchodilator FEV1 48.95±11.80 of predicted) have been randomized at 34 hospitals in China. Final results of this study will provide objective data on the effects of high-dose (1200 mg/daily) long-term NAC treatment in the prevention of COPD exacerbations and other outcome variables.

  10. N-acetylcysteine enhances cystic fibrosis sputum penetration and airway gene transfer by highly compacted DNA nanoparticles.

    Suk, Jung Soo; Boylan, Nicholas J; Trehan, Kanika; Tang, Benjamin C; Schneider, Craig S; Lin, Jung-Ming G; Boyle, Michael P; Zeitlin, Pamela L; Lai, Samuel K; Cooper, Mark J; Hanes, Justin


    For effective airway gene therapy of cystic fibrosis (CF), inhaled gene carriers must first penetrate the hyperviscoelastic sputum covering the epithelium. Whether clinically studied gene carriers can penetrate CF sputum remains unknown. Here, we measured the diffusion of a clinically tested nonviral gene carrier, composed of poly-l-lysine conjugated with a 10 kDa polyethylene glycol segment (CK(30)PEG(10k)). We found that CK(30)PEG(10k)/DNA nanoparticles were trapped in CF sputum. To improve gene carrier diffusion across sputum, we tested adjuvant regimens consisting of N-acetylcysteine (NAC), recombinant human DNase (rhDNase) or NAC together with rhDNase. While rhDNase alone did not enhance gene carrier diffusion, NAC and NAC + rhDNase increased average effective diffusivities by 6-fold and 13-fold, respectively, leading to markedly greater fractions of gene carriers that may penetrate sputum layers. We further tested the adjuvant effects of NAC in the airways of mice with Pseudomonas aeruginosa lipopolysaccharide (LPS)-induced mucus hypersecretion. Intranasal dosing of NAC prior to CK(30)PEG(10k)/DNA nanoparticles enhanced gene expression by up to ~12-fold compared to saline control, reaching levels observed in the lungs of mice without LPS challenge. Our findings suggest that a promising synthetic nanoparticle gene carrier may transfer genes substantially more effectively to lungs of CF patients if administered following adjuvant mucolytic therapy with NAC or NAC + rhDNase.

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

    Maria Grazia Porpora


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

  12. Evaluation of prophylactic and therapeutic effects of silymarin and N-acetylcysteine in acetaminophen-induced hepatotoxicity in cats.

    Avizeh, R; Najafzadeh, H; Razijalali, M; Shirali, S


    Cats most commonly receive toxic amounts of acetaminophen (APAP) because owners medicate them without consulting a veterinarian. The aim of this study was to compare the hepatoprotective action of silymarin and N-acetylcysteine (NAC) against APAP poisoning. Twenty healthy cats were randomly allotted to five equal groups. Animals in group A were given APAP (single dose 150 mg/kg, p.o.); groups B and C consisted of cats that received NAC (100 mg/kg, p.o.) or silymarin (30 mg/kg, p.o.) concurrent with APAP administration respectively; groups D and E were treated like groups B and C, respectively, but 4 h after APAP administration. The serum concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), methemoglobin, and total and direct bilirubin were measured before APAP administration and 4, 24, and 72 h later. A single oral administration of APAP significantly elevated serum concentrations of ALT, AST, ALP, LDH, methemoglobin, and total and direct bilirubin. In both the groups receiving APAP plus NAC or silymarin, levels of serum enzyme activities, methemoglobin, and total and direct bilirubin remained within the normal values. It was concluded that silymarin as well as NAC can protect liver tissue against oxidative stress in cats with an APAP intoxication.

  13. Protective effect of N-acetylcysteine against ethanol-induced gastric ulcer: A pharmacological assessment in mice.

    Jaccob, Ausama Ayoob


    Since there is an increasing need for gastric ulcer therapies with optimum benefit-risk profile. This study was conducted to investigate gastro-protective effects of N-acetylcysteine (NAC) against ethanol-induced gastric ulcer models in mice. A total of 41 mice were allocated into six groups consisted of 7 mice each. Groups 1 (normal control) and 2 (ulcer control) received distilled water at a dose of 10 ml/kg, groups 3, 4 and 5 were given NAC at doses 100, 300 and 500 mg/kg, respectively, and the 6(th) group received ranitidine (50 mg/kg). All drugs administered orally once daily for 7 days, on the 8(th) day absolute ethanol (7 ml/kg) was administrated orally to all mice to induce the acute ulcer except normal control group. Then 3 h after, all animals were sacrificed then consequently the stomachs were excised for examination. NAC administration at the tested doses showed a dose-related potent gastro-protective effect with significant increase in curative ratio, PH of gastric juice and mucus content viscosity seen with the highest dose of NAC and it is comparable with that observed in ranitidine group. The present findings demonstrate that, oral NAC shows significant gastro-protective effects comparable to ranitidine confirmed by anti-secretory, cytoprotective, histological and biochemical data, but the molecular mechanisms behind such protection are complex.

  14. Attenuation of bleomycin-induced lung fibrosis by oral sulfhydryl containing antioxidants in rats: erdosteine and N-acetylcysteine.

    Yildirim, Zeki; Kotuk, Mahir; Iraz, Mustafa; Kuku, Irfan; Ulu, Ramazan; Armutcu, Ferah; Ozen, Suleyman


    Antioxidant therapy may be useful in diseases with impaired oxidant antioxidant balance such as lung fibrosis. The effects of sulfhydryl-containing antioxidant agents N-acetylcysteine (NAC) and erdosteine on the bleomycin-induced lung fibrosis were compared in rats. The animals were divided into four groups: Vehicle + vehicle, vehicle + bleomycin (2.5 U/kg), bleomycin + (10 mg/kg), and bleomycin + NAC (3 mmol/kg). Bleomycin administration resulted in prominent lung fibrosis as measured by lung hydroxyproline content and lung histology which is almost completely prevented by erdosteine and NAC. Hydroxyproline content was 18.7 +/- 3.5 and 11.2 +/- 0.6 mg/g dried tissue in bleomycin and saline treated rats, respectively (P erdosteine and NAC pretreated, respectively. Erdosteine and NAC significantly reduced depletion of glutathione peroxidase, and prevented increases in myeloperoxidase activities, nitric oxide, and malondialdehyde levels in lung tissue produced by bleomycin. Data presented here indicate that erdosteine and NAC similarly prevented bleomycin-induced lung fibrosis and their antioxidant effects were also similar in this experiment.

  15. Protein oxidation and lipid peroxidation after renal ischemia-reperfusion injury: protective effects of erdosteine and N-acetylcysteine.

    Erdogan, Hasan; Fadillioglu, Ersin; Yagmurca, Murat; Uçar, Muharrem; Irmak, M Kemal


    Oxygen radicals have roles in the renal ischemia-reperfusion (IR) injury usually encountered in several conditions such as renal transplantation. The aim of this study was to investigate the effects of erdosteine and N-acetylcysteine (NAC) on the oxidant/antioxidant status and microscopy of renal tissues after IR injury. Male Sprague-Dawley rats were randomly assigned to four groups: control untreated rats, IR (30 min ischemia and 120 min reperfusion), IR + NAC (i.p.; 180 mg/kg) and IR + erdosteine (oral; 50 mg/kg/day for 2 days before experiments) groups. After unilateral renal IR, the right kidney was rapidly excised and sectioned vertically into two pieces for microscopic examination and biochemical analysis. Erdosteine and NAC treatment did not cause any significant change in the activity of superoxide dismutase (SOD) in comparison with the IR group, even if the SOD activity increased in IR groups than in the control group. Catalase (CAT) activity was decreased in the IR group in comparison with control and IR + erdosteine groups (Perdosteine group than in the IR + NAC group (PErdosteine or NAC treatments ameliorated these increased TBARS and PC contents in comparison with the IR group (PErdosteine but not NAC apparently reduced the renal tissue damage. The pathological damage score after IR was significantly reduced after erdosteine treatment (PErdosteine and NAC treatments improved the biochemical results of IR injury. However, on microscopic evaluations, animals receiving erdosteine showed a great reduction in renal damage when compared with the NAC group.

  16. The effects of erdosteine, N-acetylcysteine, and vitamin E on nicotine-induced apoptosis of hippocampal neural cells.

    Demiralay, Rezan; Gürsan, Nesrin; Erdem, Havva


    This study investigated the frequency of apoptosis in rat hippocampal neural cells after intraperitoneal nicotine injection, examining the roles of the inflammatory markers myeloperoxidase (MPO) and tumor necrosis factor alpha (TNF-alpha) in nicotine-induced brain damage and the protective effects of three known antioxidant agents, N-acetylcysteine (NAC), erdosteine, and vitamin E. Female Wistar rats were divided into seven groups, each composed of nine rats: 2 negative control groups, 2 positive control groups, one erdosteine-treated group (500 mg/kg), one NAC-treated group (500 mg/kg), and one vitamin E-treated group (500 mg/kg). Nicotine was intraperitoneally injected at a dosage of 0.6 mg/kg for 21 days. Following nicotine injection, the antioxidants were administered orally; treatment was continued until the rats were killed. Apoptosis level in hippocampal neural cells was determined by using TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick endlabeling) method. Staining of cytoplasmic TNF-alpha in hippocampal neural cells and hippocampus MPO activity were evaluated by immunohistochemistry. Nicotine administration had no effect on local TNF-alpha production, or hippocampal MPO activity. The treatments with erdosteine, NAC and vitamin E significantly reduced the rate of nicotine-induced hippocampal neural cell apoptosis. This findings suggest that erdosteine and NAC can be as effective as vitamin E in protecting against nicotine-induced hippocampal neural cell apoptosis.

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

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


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

  18. Protective effect of N-acetylcysteine against nicardipine hydrochloride-induced autophagic cell death of human vascular endothelial cells.

    Ochi, Masanori; Tanaka, Yoshiyuki; Toyoda, Hiromu


    Nicardipine hydrochloride (NIC) injection has been widely used for emergency treatment of abnormally high blood pressure. However, NIC injection often causes severe peripheral vascular injury. The purpose of the present study was to reduce the NIC-induced cell injury in human vascular endothelial cells by use of clinical agents. The mechanism of NIC-induced cell injury was evaluated by time-lapse microscopic imaging, autophagosome staining with monodansylcadaverine, immunostaining of light chain 3 isoform B (LC-3B) and assessment of cell viability after exposure to NIC with or without an inhibitor of autophagosome formation (3-methyladenine, 3-MA). Results from autophagosome labeling and immunostaining of LC-3B revealed an increase of autophagosomes and LC-3B in NIC-treated cells. NIC-mediated reduction of cell viability was inhibited by 3-methyladenine. Moreover, we found that N-acetylcysteine (NAC) reduced NIC-induced cell injury in human vascular endothelial cells. These findings suggest that NIC causes severe peripheral venous irritation via induction of autophagic cell death and that inhibition of autophagy with NAC could contribute to the reduction of NIC-induced vascular injury.

  19. Protective effect of salidroside on contrast-induced nephropathy in comparison with N-acetylcysteine and its underlying mechanism.

    Xing, Yue; Wei, Ri-bao; Tang, Lu; Yang, Yue; Zheng, Xiao-yong; Wang, Zi-cheng; Gao, Yu-wei


    To study the prevention effect of salidroside on contrast-induced-nephropathy (CIN) and its underlying mechanism. A total of 24 Wistar rats were randomly divided into 4 groups with 6 in each group. Rats were firstly administrated with normal saline (control and model groups), N-acetylcysteine (NAC, NAC group) and salidroside (salidroside group) for 7 days before model establishment in each group, respectively. Histopathological analysis was performed by periodic acid-Schiff (PAS) staining. Oxidative stress related parameters including superoxide dismutase (SOD) and methane dicarboxylic aldehyde (MDA), nitric oxide (NO), angiotensin II (Ang II), 8-hydroxy-2'-deoxyguanosine (8-OHdG), mRNA and protein levels of endothelial nitric oxide synthase (eNOS), and nitric oxide synthase (NOS) activity were measured. Compared with the control group, the levels of MDA, Ang II and 8-OHdG were all significantly increased and levels of SOD, NO, and eNOS mRNA and protein were decreased significantly in the model group (Psalidroside groups and no significant different was found between these two groups (P>0.05). Salidroside can be the potential substitute of NAC to prevent CIN. The underlying mechanism may be associated with oxidative stress damage caused by contrast agents.

  20. Protective Effect of N-Acetylcysteine Against Toxicity on the Rat Blood After Chronic Exposure to Carbosulfan

    Ines El-Bini Dhouib


    Full Text Available The present study investigated the protective effects of N-acetylcysteine (NAC, is widely known as an antidote to acetaminophen overdose, on carbosulfan (CB-induced hematotoxicity and oxidative stress in male rats. CB was administered at a dose of 25 mg/kg or simultaneously administered with NAC (2 g/l for 30 days. Results of hematological examination showed that red blood cells, hematocrite, hemoglobin, and reticulocytes levels were significantly lower in CB-exposed rats compared with those in the control. Administration of CB caused a significant increase in the superoxide dismutase and catalase activities. However, the glutathione (GSH and thiols group (TSH levels were significantly increased as well as GSH S-transferase activity and levels of glutathione peroxidase on erythrocytes of males rats compared with those in the control. Also, CB-treated rats showed significant elevation in lipid peroxidation (LPO and acetylcholinesterase (AChE on erythrocytes in comparison with the control. Co-administration with NAC exhibited chemoprotective effects against CB-mediated hematotoxicity, augmented erythrocyte antioxidant status, and prevented the induction of anemia.

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

    Panjehpour, M; Alaie, S H


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

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

    Gang Chen


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

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

    Divyesh Thakker


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

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

    Erica Hoffer


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

  5. Effect of N-acetylcysteine on blood and tissue lipid peroxidation in lipopolysaccharide-induced obstructive jaundice.

    Caglikulekci, Mehmet; Dirlik, Musa; Pata, Cengiz; Plasse, Marylene; Tamer, Lulufer; Ogetman, Zekai; Ercan, Bahadir


    In obstructive jaundice, free radical production is increased and antioxidative activity is reduced. N-Acetylcysteine (NAC) has a beneficial effect with anti-inflammatory and antioxidant activity, acting as a free radical scavenger. NAC inhibits inducible nitric oxide synthase, suppresses cytokine expression/release, and inhibits adhesion molecule expression and nuclear factor kappa B. The aim of this study was to investigate the effects of NAC on liver/renal tissue and serum lipid peroxidation in lipopolysaccharide (LPS)-induced obstructive jaundice. We randomized 60 rats into 6 groups: group 1, Sham; group 2, obstructive jaundice (OJ) induced after bile-duct ligation; group 3, OJ + NAC (100 mg kg- 1 subcutaneously); group 4, OJ + LPS (10 mg kg-1); group 5, OJ + NAC + LPS; and group 6, OJ + LPS + NAC. For each group, the biochemical markers of lipid peroxidation and the antioxidant products were measured in serum and liver/renal tissue after sacrifice. Almost all lipid peroxidation products levels were increased and antioxidant products levels were decreased in groups who received LPS (groups 4, 5, and 6), but the effect was less remarkable when NAC was administered before LPS (group 5). The same trend was seen for groups with OJ +/- LPS who did not received NAC or received it after induced toxemia (groups 2, 4, and 6) as compared to groups 1 and 3. Moreover, in the case of OJ + LPS, rats treated with NAC before LPS (group 5) had lower lipid peroxidation products levels and higher antioxidant products levels as compared to those who did not received NAC (group 4). This phenomenon was not reproducible with NAC administered after LPS (group 6). Thus, results of this study showed that NAC prevents the deleterious effects of LPS in obstructive jaundice by reducing lipid peroxidation in serum and liver/renal tissue if administered before LPS. Nonetheless, NAC failed to prevent the lipid peroxidation in the case of established endotoxemia in obstructive jaundice.

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

    Seyed Masoom Masoompour


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

  7. Redox regulation of MMP-3/TIMP-1 ratio in intestinal myofibroblasts: effect of N-acetylcysteine and curcumin.

    Fontani, Filippo; Marcucci, Tommaso; Picariello, Lucia; Tonelli, Francesco; Vincenzini, Maria Teresa; Iantomasi, Teresa


    Matrix metalloproteinases (MMPs) play a critical role in inflammation and ulcerations in gut of Crohn׳s disease (CD) patients. Intestinal subepithelial myofibroblasts (ISEMFs) secrete MMPs in response to inflammatory stimuli. Previous data showed in CD-ISEMFs increased oxidative status. The aim of this study was to investigate the role of ISEMFs in modulating the production of MMP-3 and TIMP-1, an inhibitor of MMPs activity. A relationship among oxidative stress, activity of antioxidants and MMP-3/TIMP-1 was also studied. ISEMFs isolated from CD patient colon and human colonic cell line of myofibroblasts (18Co) were used. Oxidative state was modulated by buthionine sulfoximine, an inhibitor of glutathione (GSH) synthesis, and N-acetylcysteine (NAC), GSH precursor. An up-regulation of MMP-3 due to increased oxidative state was found in CD-ISEMFs. Stimulation by tumor necrosis factor (TNF)α increased further MMP-3 levels. On the contrary, no change in TIMP-1 production was determined. NAC treatment decreased MMP-3 production in CD-ISMEFs and removed the enhancement due to TNFα. Similar effects were observed in 18Co cells treated with curcumin, antioxidant with anti-inflammatory properties. The involvement of MAPKs on MMP-3 redox regulation was also shown. This study demonstrates the involvement of ISEMFs and high oxidative state in the increased MMP-3 production found in intestinal mucosa of CD patients. NAC and curcumin normalize MMP-3 levels mainly in TNFα stimulated cells. A modulation of MMP-3 production by NAC and curcumin due to their direct action on transcriptional factors has been also suggested. Therefore, they could have a therapeutic use for the prevention and treatment of fistulaes in CD.

  8. Effects of N-acetylcysteine and terbutaline treatment on hemodynamics and regional albumin extravasation in porcine septic shock

    Groeneveld, A.B.; den Hollander, W.; Straub, J.; Nauta, J.J.; Thijs, L.G. (Free Univ. Hospital, Amsterdam (Netherlands))


    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 interest 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.

  9. Role of N-acetylcysteine treatment in non-acetaminophen-induced acute liver failure: A prospective study

    Nabi, Tauseef; Nabi, Sumaiya; Rafiq, Nadeema; Shah, Altaf


    Background/Aims: Acute liver failure (ALF) is a rare but severe medical emergency. To date, there is no established treatment for non-acetaminophen-induced acute liver failure (NAI-ALF) other than liver transplantation, and little is known about the use of N-acetylcysteine (NAC) in NAI-ALF. A randomized case control study was conducted with the aim to determine the effect of NAC on the mortality of NAI-ALF patients, as well as to evaluate the safety and efficacy of NAC use. Patients and Methods: A total of 80 patients diagnosed with NAI-ALF were included in the study. Forty patients received NAC infusion for 72 h whereas the control group received placebo. The variables evaluated were demographic characteristics, signs and symptoms, biochemical parameters, and clinical course during hospitalization. Results: The two groups (NAC and control) were comparable for various baseline characteristics (such as etiology of ALF, INR, alanine aminotransferase, creatinine, albumin, and grade of encephalopathy), except for age. Although majority of patients had undetermined etiology (32.5% in NAC group and 42.5% in control group), the second main cause was acute hepatitis E and drug or toxin-induced ALF. The mortality decreased to 28% with the use of NAC versus 53% in the control group (P = 0.023). The use of NAC was associated with shorter length of hospital stay in survived patients (P = 0.002). Moreover, the survival of patients was improved by NAC (P = 0.025). Also, drug-induced ALF showed improved outcome compared to other etiologies. Conclusion: The findings of the study recommend the use of NAC along with conventional treatments in patients with NAI-ALF in non-transplant centers while awaiting referrals and conclude the use of NAC as safe. PMID:28611340

  10. Protective effect of N-acetylcysteine on lung dendritic cells against damage in multiple organ dysfunction syndrome model

    Hong-wei WANG


    Full Text Available Objective To explore the protective effect of N-acetylcysteine (NAC on lung dendritic cells (DCs from damage in multiple organ dysfunction syndrome (MODS mouse model. Methods Animal model of MODS was established by injecting zymosan into the peritoneal cavity of BALB/c mice, and the mice were thereafter randomly divided into zymosan group, zymosan + NAC group and control group, 20 for each. MPO activity in lung tissue was measured by biochemical analysis 48 hours after modeling. Pathological changes of the lung were observed under light microscope. Lung DCs were separated by density gradient centrifugation and CD11c+ immunomagnetic beads. DCs' phenotypes of MHC-Ⅱ/ⅠAd and CD86 were analyzed by flow cytometry. Apoptosis of DCs was detected by flow cytometry with double labeling of Annexin V and 7-AAD. Results Compared with control group, the MPO activity in lung tissue remarkably increased in zymosan group (P lt; 0.05. Infiltration by a large number of neutrophilic granulocytes was found in lungs, suggesting serious injuries in lung. The expressions of MHC-Ⅱ/Ⅰ-Ad and CD86 on DC surface and the percentage of DC apoptosis increased dramatically (P lt; 0.05. Compared with zymosan group, the MPO activity remarkably declined and the lung injury was mitigatory (P lt; 0.05; the number of infiltrating neutrophilic granulocytes decreased greatly, and the expressions of MHC-Ⅱ/Ⅰ-Ad and CD86 on the DC surface and the percentage of DC apoptosis decreased dramatically (P lt; 0.05 in zymosan + NAC group. Conclusion NAC in vivo could inhibit DC activation-induced apoptosis and relieve lung injury, thus being of protective effect on lung DCs against damage in MODS model.

  11. Mucolytic treatment with N-acetylcysteine L-lysinate metered dose inhaler in dogs: airway epithelial function changes.

    Tomkiewicz, R P; App, E M; Coffiner, M; Fossion, J; Maes, P; King, M


    N-acetylcysteine L-lysinate Nacystelyn (L-NAC) is a newly synthesized mucolytic agent, of which the action in vivo has not been well defined. In six healthy mongrel dogs, the rheological properties of mucus, its mucociliary and cough clearability, and the transepithelial potential difference (PD) of the tracheobronchial epithelium were evaluated after placebo and L-NAC metered dose inhaler (MDI) aerosols. The principal index of mucus rigidity, log G*, decreased at all airway sites with L-NAC administration, i.e. the mucus became less rigid and more deformable (the overall change in G* was 0.29 log units, i.e. ca. twofold decrease). The viscoelasticity-derived mucus transportability parameters, mucociliary (MCI) and cough (CCI) clearability indices, increased with L-NAC MDI, particularly CCI, which predicts the effect of mucus rheology on cough clearability. PD increased significantly with L-NAC administration at all measurement sites, which appears to be a novel effect for a direct acting mucolytic agent. Tracheal mucus linear velocity (TMV) increased after L-NAC compared with placebo, as did the normalized frog palate transport rate (NFPTR). The increase in NFPTR was greater than that predicted from the mucus rheological properties alone, suggesting that L-NAC still resident in the collected mucus stimulated the frog palate cilia. The index of mucus flux, the collection rate in mg.min-1, was higher with L-NAC compared with placebo. From our results, we conclude that L-NAC shows potential benefit in terms of improving mucus rheological properties and clearability. It may act, in part, by stimulating the fresh secretion of mucus of lower viscoelasticity. The stimulation of mucociliary clearance could be related to ion flux changes, as indicated by the increase in PD.

  12. Relationships between intrauterine infusion of N-acetylcysteine, equine endometrial pathology, neutrophil function, post-breeding therapy, and reproductive performance.

    Gores-Lindholm, Alicia R; LeBlanc, Michelle M; Causey, Robert; Hitchborn, Anna; Fayrer-Hosken, Richard A; Kruger, Marius; Vandenplas, Michel L; Flores, Paty; Ahlschwede, Scott


    Persistent endometritis in the mare is associated with hypersecretion of mucus by endometrial epithelium and migration of neutrophils into the uterine lumen. This study examines the relationships between N-acetylcysteine (NAC), a mucolytic agent with anti-inflammatory properties, and endometrial architecture, serum neutrophil function, post-breeding therapy, and reproductive performance of NAC-treated mares in a clinical setting. In study 1, endometrial biopsies from mares receiving intrauterine saline (fertile-control, n = 6) or 3.3% NAC (fertile-treatment, n = 6; barren-treatment, n = 10) were evaluated by histology and image analysis. In study 2, phagocytic activity of serum-derived neutrophils was measured after adding 0.5% or 3% NAC. In study 3, pregnancy rates of repeat breeders (n = 44) receiving an intrauterine infusion of 3.3% NAC 24-36 hours before mating (group 1) was recorded, as was first cycle of the season pregnancy rates of reproductively normal mares (group 2, n = 85), and mares treated for bacterial endometritis the cycle before mating (group 3, n = 25). Intrauterine NAC did not adversely affect endometrial histology. Extracellular mucus thickness and staining intensity were reduced in fertile-treatment mares (P NAC solution, but not by 0.5% NAC (P NAC was not irritating and inhibited the oxidative burst of neutrophils. Repeat breeder mares, with evidence of mucus hypersecretion, but no uterine pathogens, when treated with NAC followed by post-mating uterine lavage and oxytocin (and in some cases intrauterine antibiotics), achieved a pregnancy rate of 77%.

  13. Respiratory syncytial virus inhibits ciliagenesis in differentiated normal human bronchial epithelial cells: effectiveness of N-acetylcysteine.

    Mata, Manuel; Sarrion, Irene; Armengot, Miguel; Carda, Carmen; Martinez, Isidoro; Melero, Jose A; Cortijo, Julio


    Persistent respiratory syncytial virus (RSV) infections have been associated with the exacerbation of chronic inflammatory diseases, including chronic obstructive pulmonary disease (COPD). This virus infects the respiratory epithelium, leading to chronic inflammation, and induces the release of mucins and the loss of cilia activity, two factors that determine mucus clearance and the increase in sputum volume. These alterations involve reactive oxygen species-dependent mechanisms. The antioxidant N-acetylcysteine (NAC) has proven useful in the management of COPD, reducing symptoms, exacerbations, and accelerated lung function decline. NAC inhibits RSV infection and mucin release in human A549 cells. The main objective of this study was to analyze the effects of NAC in modulating ciliary activity, ciliagenesis, and metaplasia in primary normal human bronchial epithelial cell (NHBEC) cultures infected with RSV. Our results indicated that RSV induced ultrastructural abnormalities in axonemal basal bodies and decreased the expression of β-tubulin as well as two genes involved in ciliagenesis, FOXJ1 and DNAI2. These alterations led to a decrease in ciliary activity. Furthermore, RSV induced metaplastic changes to the epithelium and increased the number of goblet cells and the expression of MUC5AC and GOB5. NAC restored the normal functions of the epithelium, inhibiting ICAM1 expression, subsequent RSV infection through mechanisms involving nuclear receptor factor 2, and the expression of heme oxygenase 1, which correlated with the restoration of the antioxidant capacity, the intracellular H(2)O(2) levels and glutathione content of NHBECs. The results presented in this study support the therapeutic use of NAC for the management of chronic respiratory diseases, including COPD.

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

    Avinash Agarwal


    Full Text Available Introduction: The primary objective of this study was to determine the serum level of antioxidant enzymes and to correlate them with outcome in patients of aluminum phosphide (ALP poisoning and, secondly, to evaluate the effect of N-acetylcysteine (NAC given along with supportive treatment of ALP poisoning. Design: We conducted a cohort study in patients of ALP poisoning hospitalized at a tertiary care center of North India. The treatment group and control group were enrolled during the study period of 1 year from May 2011 to April 2012. Interventions: Oxidative stress was evaluated in each subject by estimating the serum levels of the enzymes, viz. catalase, superoxide dismutase (SOD and glutathione reductase (GR. The treatment group comprised of patients who were given NAC in addition to supportive treatment (magnesium sulfate and vasopressors, if required, while in the control group, only supportive treatment was instituted. The primary endpoint of the study was the survival of the patients. Measurements and Results: The baseline catalase (P = 0.008 and SOD (P < 0.01 levels were higher among survivors than non-survivors. Of the total patients in the study, 31 (67.4% expired and 15 (32.6% survived. Among those who expired, the mean duration of survival was 2.92 ± 0.40 days in the test group and 1.82 ± 0.33 days in the control group (P = 0.043. Conclusions: This study suggests that the baseline level of catalase and SOD have reduced in ALP poisoning, but baseline GR level has not suppressed but is rather increasing with due time, and more so in the treatment group. NAC along with supportive treatment may have improved survival in ALP poisoning.

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

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


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

  16. N-acetylcysteine an allium plant compound improves high-sucrose diet-induced obesity and related effects.

    Souza, Gisele A; Ebaid, Geovana X; Seiva, Fábio R F; Rocha, Katiucha H R; Galhardi, Cristiano Machado; Mani, Fernanda; Novelli, Ethel L B


    This study was designed to determine whether N-acetylcysteine (NAC, C(5)H(9)-NO(3)S), a compound from Allium species may be used as a complementary therapeutic agent, to inhibit high-sucrose induced-obesity and its effects on glucose tolerance, in vivo low-density lipoprotein (LDL)-oxidation and serum oxidative stress in rats. Initially, 24 male Wistar rats were divided into two groups: controls receiving standard chow (C, n = 6) and those receiving high-sucrose diet (HS, n = 18). After 22 days, (HS) group was divided into three groups (n = 6/group); (HS-HS) continued to eat high-sucrose diet and water; (HS-N) continued to eat high-sucrose diet and received 2 mg l(-1)-NAC in its drinking water; (HS-CN) changing high-sucrose to standard chow and receiving 2 mg l(-1)-NAC in its drinking water. After 22 days of the HS-group division (44 days of experimental period) body weight, body mass index and surface area were enhanced in HS-HS rats (P obesity markers, feed efficiency, LH and ox-LDL, as well normalized glucose response, TG and VLDL (P diet-induced obesity and its effects on glucose tolerance, lipid profile, in vivo LDL-oxidation and serum oxidative stress, enhancing antioxidant defences. The application of this agent may be feasible and beneficial for high-sucrose diet-induced obesity, which certainly would bring new insights on obesity-related adverse effects control.

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

    Jiang-Qin Liu

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

  18. Effects of N-acetylcysteine and imipramine in a model of acute rhythm disruption in BALB/c mice.

    Pilz, Luísa K; Trojan, Yasmine; Quiles, Caroline L; Benvenutti, Radharani; Melo, Gabriela; Levandovski, Rosa; Hidalgo, Maria Paz L; Elisabetsky, Elaine


    Circadian rhythm disturbances are among the risk factors for depression, but specific animal models are lacking. This study aimed to characterize the effects of acute rhythm disruption in mice and investigate the effects of imipramine and N-acetylcysteine (NAC) on rhythm disruption-induced changes. Mice were exposed to 12:12-hour followed by 10:10-hour light:dark cycles (LD); under the latter, mice were treated with saline, imipramine or NAC. Rhythms of rest/activity and temperature were assessed with actigraphs and iButtons, respectively. Hole-board and social preference tests were performed at the beginning of the experiment and again at the 8th 10:10 LD, when plasma corticosterone and IL-6 levels were also assessed. Actograms showed that the 10:10 LD schedule prevents the entrainment of temperature and activity rhythms for at least 13 cycles. Subsequent light regimen change activity and temperature amplitudes showed similar patterns of decline followed by recovery attempts. During the 10:10 LD schedule, activity and temperature amplitudes were significantly decreased (paired t test), an effect exacerbated by imipramine (ANOVA/SNK). The 10:10 LD schedule increased anxiety (paired t test), an effect prevented by NAC (30 mg/kg). This study identified mild but significant behavioral changes at specific time points after light regimen change. We suggest that if repeated overtime, these subtle changes may contribute to lasting behavioral disturbancess relevant to anxiety and mood disorders. Data suggest that imipramine may contribute to sustained rhythm disturbances, while NAC appears to prevent rhythm disruption-induced anxiety. Associations between sleep/circadian disturbances and the recurrence of depressive episodes underscore the relevance of potential drug-induced maintenance of disturbed rhythms.

  19. Randomised, controlled trial of N-acetylcysteine for treatment of acute exacerbations of chronic obstructive pulmonary disease [ISRCTN21676344

    Poole Phillippa J


    Full Text Available Abstract Background Prophylactic treatment with N-acetylcysteine (NAC for 3 months or more is associated with a reduction in the frequency of exacerbations of chronic obstructive pulmonary disease (COPD. This raises the question of whether treatment with NAC during an acute exacerbation will hasten recovery from the exacerbation. Methods We have examined this in a randomised, double-blind, placebo controlled trial. Subjects, admitted to hospital with an acute exacerbation of COPD, were randomised within 24 h of admission to treatment with NAC 600 mg b.d. (n = 25 or matching placebo (n = 25. Treatment continued for 7 days or until discharge (whichever occurred first. To be eligible subjects had to be ≥ 50 years, have an FEV1 ≤ 60% predicted, FEV1/VC ≤ 70% and ≥ 10 pack year smoking history. Subjects with asthma, heart failure, pneumonia and other respiratory diseases were excluded. All subjects received concurrent treatment with prednisone 40 mg/day, nebulised salbutamol 5 mg q.i.d and where appropriate antibiotics. FEV1, VC, SaO2 and breathlessness were measured 2 hours after a dose of nebulised salbutamol, at the same time each day. Breathlessness was measured on a seven point Likert scale. Results At baseline FEV1 (% predicted was 22% in the NAC group and 24% in the control group. There was no difference between the groups in the rate of change of FEV1, VC, SaO2 or breathlessness. Nor did the groups differ in the median length of stay in hospital (6 days for both groups. Conclusions Addition of NAC to treatment with corticosteroids and bronchodilators does not modify the outcome in acute exacerbations of COPD.

  20. The effects of erdosteine, N-acetylcysteine and vitamin E on nicotine-induced apoptosis of cardiac cells.

    Demiralay, Rezan; Gürsan, Nesrin; Erdem, Havva


    This study was conducted to investigate the frequency of apoptosis in rat cardiomyocytes after intratraperitoneal nicotine injection, in order to examine the roles of inflammatory markers [myeloperoxidase (MPO) and tumor necrosis factor alpha (TNF-alpha)] in nicotine-induced cardiac damage and to determine the protective effects of three known antioxidant agents (N-acetylcysteine (NAC), erdosteine and vitamin E) on nicotine toxicity in the heart. Female Wistar rats were divided into seven groups, each composed of nine rats: two negative control groups, two positive control groups, one erdosteine-treated group (500 mg kg(-1)), one NAC-treated group (500 mg kg(-1)) and one vitamin E-treated group (500 mg kg(-1)). Nicotine was intraperitoneally injected at a dosage of 0.6 mg kg(-1) for 21 days. Following nicotine injection, the antioxidants were administered orally; treatment was continued until the rats were killed. Heart tissue samples were stained with hematoxylin-eosin for histopathological assessments. Apoptosis level in cardiomyocytes was determined by using TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick endlabelling) method. Staining of cytoplasmic TNF-alpha in cardiomyocytes and heart MPO activity were evaluated by immunohistochemistry. The treatments with erdosteine, NAC and vitamin E significantly reduced the rate of nicotine-induced cardiomyocyte apoptosis. The effect of vitamin E on apoptosis regulation was weaker than the effects of erdosteine and NAC. Erdosteine, NAC and vitamin E significantly reduced the increases in the local production of TNF-alpha and heart MPO activity. This findings suggest that the effects of erdosteine and NAC on apoptosis regulation are stronger than that of vitamin E.

  1. Indocyanine green clearance varies as a function of N-acetylcysteine treatment in a murine model of acetaminophen toxicity.

    Milesi-Hallé, Alessandra; Abdel-Rahman, Susan M; Brown, Aliza; McCullough, Sandra S; Letzig, Lynda; Hinson, Jack A; James, Laura P


    Standard assays to assess acetaminophen (APAP) toxicity in animal models include determination of ALT (alanine aminotransferase) levels and examination of histopathology of liver sections. However, these assays do not reflect the functional capacity of the injured liver. To examine a functional marker of liver injury, the pharmacokinetics of indocyanine green (ICG) were examined in mice treated with APAP, saline, or APAP followed by N-acetylcysteine (NAC) treatment.Male B6C3F1 mice were administered APAP (200 mg/kg IP) or saline. Two additional groups of mice received APAP followed by NAC at 1 or 4 h after APAP. At 24 h, mice were injected with ICG (10 mg/kg IV) and serial blood samples (0, 2, 10, 30, 50 and 75 min) were obtained for determination of serum ICG concentrations and ALT. Mouse livers were removed for measurement of APAP protein adducts and examination of histopathology. Toxicity (ALT values and histology) was significantly increased above saline treated mice in the APAP and APAP/NAC 4 h mice. Mice treated with APAP/NAC 1 h had complete protection from toxicity. APAP protein adducts were increased in all APAP treated groups and were highest in the APAP/NAC 1 h group. Pharmacokinetic analysis of ICG demonstrated that the total body clearance (Cl(T)) of ICG was significantly decreased and the mean residence time (MRT) was significantly increased in the APAP mice compared to the saline mice. Mice treated with NAC at 1 h had Cl(T) and MRT values similar to those of saline treated mice. Conversely, mice that received NAC at 4 h had a similar ICG pharmacokinetic profile to that of the APAP only mice. Prompt treatment with NAC prevented loss of functional activity while late treatment with NAC offered no improvement in ICG clearance at 24 h. ICG clearance in mice with APAP toxicity can be utilized in future studies testing the effects of novel treatments for APAP toxicity.

  2. N-acetylcysteine possesses antidepressant-like activity through reduction of oxidative stress: behavioral and biochemical analyses in rats.

    Smaga, Irena; Pomierny, Bartosz; Krzyżanowska, Weronika; Pomierny-Chamioło, Lucyna; Miszkiel, Joanna; Niedzielska, Ewa; Ogórka, Agata; Filip, Małgorzata


    The growing body of evidence implicates the significance of oxidative stress in the pathophysiology of depression. The aim of this paper was to examine N-acetylcysteine (NAC) - a putative precursor of the most important tissue antioxidant glutathione - in an animal model of depression and in ex vivo assays to detect oxidative stress parameters. Imipramine (IMI), a classical and clinically-approved antidepressant drug was also under investigation. Male Wistar rats which underwent either bulbectomy (BULB; removal of the olfactory bulbs) or sham surgery (SHAM; olfactory bulbs were left undestroyed) were treated acutely or repeatedly with NAC (50-100mg/kg, ip) or IMI (10mg/kg, ip). Following 10-daily injections with NAC or IMI or their solvents, or 9-daily injections with a corresponding solvent plus acute NAC or acute IMI forced swimming test on day 10, and locomotor activity were performed; immediately after behavioral tests animals were decapitated. Biochemical tests (the total antioxidant capacity - TAC and the superoxide dismutase activity - SOD) were performed on homogenates in several brain structures. In behavioral studies, chronic (but not acute) administration of NAC resulted in a dose-dependent reduction in the immobility time seen only in BULB rats while chronic IMI produced a significant decrease in this parameter in both SHAM and BULB animals. On the other hand, chronic administration of NAC and IMI resulted in a significant increase in cellular antioxidant mechanisms (SOD activity) that reversed the effects of BULB in the frontal cortex, hippocampus and striatum. Our study further supports the antidepressant-like activity of NAC and links its effect as well as IMI actions with the enhancement of brain SOD activity.

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

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


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

  4. Comparative antilipidemic effect of N-acetylcysteine and sesame oil administration in diet-induced hypercholesterolemic mice

    Karatzas Theodoros


    Full Text Available Abstract Background There is an increasing number of novel antilipidemic therapies under consideration. The putative hypolipidemic effect of N-acetylcysteine (NAC and sesame oil was studied in a mouse model of dietary-induced hypercholesterolemia. Methods Male C57bl/6 mice were assigned to the following groups: (NC control group, (HC group receiving test diet supplemented with 2% cholesterol and 0.5% cholic acid for 8 weeks, (HCN group receiving the test diet with NAC supplementation (230 mg/kg p.o. and (HCS group fed the test diet enriched with 10% sesame oil. Total serum cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides were assayed at the beginning and at the end of the experiment. Total peroxides and nitric oxide (NO levels were measured in the serum at the end of the experiment. Hepatic and aortic lesions were evaluated by haematoxylin-eosin staining. Results Higher serum levels of total and LDL-cholesterol were recorded in all groups fed the high cholesterol diet. The HCN group presented reduced lipid levels compared to HC and HCS groups. No differences were observed between HCS and HC groups. Peroxide content in serum was markedly increased in mice consuming high cholesterol diet. NAC and sesame oil administration led to a significant decrease of serum lipid peroxidation in the levels of control group, whereas only NAC restored NO bioavailability. In terms of liver histology, the lesions observed in HCN group were less severe than those seen in the other high cholesterol groups. Conclusion Co-administration of NAC, but not sesame oil, restored the disturbed lipid profile and improved hepatic steatosis in the studied diet-induced hypercholesterolemic mice. Both agents appear to ameliorate serum antioxidant defense.

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

    Fernanda S Rodrigues

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

  6. N-Acetylcysteine Prevents Spatial Memory Impairment Induced by Chronic Early Postnatal Glutaric Acid and Lipopolysaccharide in Rat Pups

    Rodrigues, Fernanda S.; Souza, Mauren A.; Magni, Danieli V.; Ferreira, Ana Paula O.; Mota, Bibiana C.; Cardoso, Andreia M.; Paim, Mariana; Xavier, Léder L.; Ferreira, Juliano; Schetinger, Maria Rosa C.; Da Costa, Jaderson C.; Royes, Luiz Fernando F.; Fighera, Michele R.


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

  7. Efficacy and safety of N-acetylcysteine in prevention of noise induced hearing loss: a randomized clinical trial.

    Kopke, Richard; Slade, Martin D; Jackson, Ronald; Hammill, Tanisha; Fausti, Stephen; Lonsbury-Martin, Brenda; Sanderson, Alicia; Dreisbach, Laura; Rabinowitz, Peter; Torre, Peter; Balough, Ben


    Despite a robust hearing conservation program, military personnel continue to be at high risk for noise induced hearing loss (NIHL). For more than a decade, a number of laboratories have investigated the use of antioxidants as a safe and effective adjunct to hearing conservation programs. Of the antioxidants that have been investigated, N-acetylcysteine (NAC) has consistently reduced permanent NIHL in the laboratory, but its clinical efficacy is still controversial. This study provides a prospective, randomized, double-blinded, placebo-controlled clinical trial investigating the safety profile and the efficacy of NAC to prevent hearing loss in a military population after weapons training. Of the 566 total study subjects, 277 received NAC while 289 were given placebo. The null hypothesis for the rate of STS was not rejected based on the measured results. While no significant differences were found for the primary outcome, rate of threshold shifts, the right ear threshold shift rate difference did approach significance (p = 0.0562). No significant difference was found in the second primary outcome, percentage of subjects experiencing an adverse event between placebo and NAC groups (26.7% and 27.4%, respectively, p = 0.4465). Results for the secondary outcome, STS rate in the trigger hand ear, did show a significant difference (34.98% for placebo-treated, 27.14% for NAC-treated, p-value = 0.0288). Additionally, post-hoc analysis showed significant differences in threshold shift rates when handedness was taken into account. While the secondary outcomes and post-hoc analysis suggest that NAC treatment is superior to the placebo, the present study design failed to confirm this. The lack of significant differences in overall hearing loss between the treatment and placebo groups may be due to a number of factors, including suboptimal dosing, premature post-exposure audiograms, or differences in risk between ears or subjects. Based on secondary outcomes and post hoc

  8. Acute supplementation of N-acetylcysteine does not affect muscle blood flow and oxygenation characteristics during handgrip exercise.

    Smith, Joshua R; Broxterman, Ryan M; Ade, Carl J; Evans, Kara K; Kurti, Stephanie P; Hammer, Shane M; Barstow, Thomas J; Harms, Craig A


    N-acetylcysteine (NAC; antioxidant and thiol donor) supplementation has improved exercise performance and delayed fatigue, but the underlying mechanisms are unknown. One possibility isNACsupplementation increases limb blood flow during severe-intensity exercise. The purpose was to determine ifNACsupplementation affected exercising arm blood flow and muscle oxygenation characteristics. We hypothesized thatNACwould lead to higher limb blood flow and lower muscle deoxygenation characteristics during severe-intensity exercise. Eight healthy nonendurance trained men (21.8 ± 1.2 years) were recruited and completed two constant power handgrip exercise tests at 80% peak power until exhaustion. Subjects orally consumed either placebo (PLA) orNAC(70 mg/kg) 60 min prior to handgrip exercise. Immediately prior to exercise, venous blood samples were collected for determination of plasma redox balance. Brachial artery blood flow (BABF) was measured via Doppler ultrasound and flexor digitorum superficialis oxygenation characteristics were measured via near-infrared spectroscopy. FollowingNACsupplementaiton, plasma cysteine (NAC: 47.2 ± 20.3 μmol/L vs.PLA: 9.6 ± 1.2 μmol/L;P = 0.001) and total cysteine (NAC: 156.2 ± 33.9 μmol/L vs.PLA: 132.2 ± 16.3 μmol/L;P = 0.048) increased. Time to exhaustion was not significantly different (P = 0.55) betweenNAC(473.0 ± 62.1 sec) andPLA(438.7 ± 58.1 sec). RestingBABFwas not different (P = 0.79) withNAC(99.3 ± 31.1 mL/min) andPLA(108.3 ± 46.0 mL/min).BABFwas not different (P = 0.42) during exercise or at end-exercise (NAC: 413 ± 109 mL/min;PLA: 445 ± 147 mL/min). Deoxy-[hemoglobin+myoglobin] and total-[hemoglobin+myoglobin] were not significantly different (P = 0.73 andP = 0.54, respectively) at rest or during exercise between conditions. We conclude that acuteNACsupplementation does not alter oxygen delivery during exercise in men.

  9. N-acetylcysteine and allopurinol synergistically enhance cardiac adiponectin content and reduce myocardial reperfusion injury in diabetic rats.

    Tingting Wang

    Full Text Available BACKGROUND: Hyperglycemia-induced oxidative stress plays a central role in the development of diabetic myocardial complications. Adiponectin (APN, an adipokine with anti-diabetic and anti-ischemic effects, is decreased in diabetes. It is unknown whether or not antioxidant treatment with N-acetylcysteine (NAC and/or allopurinol (ALP can attenuate APN deficiency and myocardial ischemia reperfusion (MI/R injury in the early stage of diabetes. METHODOLOGY/PRINCIPAL FINDINGS: Control or streptozotocin (STZ-induced diabetic rats were either untreated (C, D or treated with NAC (1.5 g/kg/day or ALP (100 mg/kg/day or their combination for four weeks starting one week after STZ injection. Plasma and cardiac biochemical parameters were measured after the completion of treatment, and the rats were subjected to MI/R by occluding the left anterior descending artery for 30 min followed by 2 h reperfusion. Plasma and cardiac APN levels were decreased in diabetic rats accompanied by decreased cardiac APN receptor 2 (AdipoR2, reduced phosphorylation of Akt, signal transducer and activator of transcription 3 (STAT3 and endothelial nitric oxide synthase (eNOS but increased IL-6 and TNF-α (all P<0.05 vs. C. NAC but not ALP increased cardiac APN concentrations and AdipoR2 expression in diabetic rats. ALP enhanced the effects of NAC in restoring cardiac AdipoR2 and phosphorylation of Akt, STAT3 and eNOS in diabetic rats. Further, NAC and ALP, respectively, decreased postischemic myocardial infarct size and creatinine kinase-MB (CK-MB release in diabetic rats, while their combination conferred synergistic protective effects. In addition, exposure of cultured rat cardiomyocytes to high glucose resulted in significant reduction of cardiomyocyte APN concentration and AdipoR2 protein expression. APN supplementation restored high glucose induced AdipoR2 reduction in cardiomyocytes. CONCLUSIONS/SIGNIFICANCE: NAC and ALP synergistically restore myocardial APN and AdipoR2

  10. Effects of oral treatment with N-acetylcysteine on the viscosity of intrauterine mucus and endometrial function in estrous mares.

    Witte, T S; Melkus, E; Walter, I; Senge, B; Schwab, S; Aurich, C; Heuwieser, W


    Persistent breeding-induced endometritis is ranked as the third most common medical problem in the adult mare and leads to enormous economic loss in horse breeding. In mares suffering from persistent breeding-induced endometritis, increased amounts of intrauterine (i.u.) fluid or viscous mucus in estrus or after breeding may act as a barrier for sperm and can contribute to low fertility. Current therapies of these mares aim to eliminate i.u. fluid and mucus by uterine lavage and/or administration of ecbolic drugs. Recently, i.u. administration of N-acetylcysteine (NAC) has been shown to support therapy in mares with endometritis. It was the objective of the present study to investigate effects of an oral administration of NAC on the viscosity of i.u. fluid in estrous mares. It was hypothesized that oral treatment with NAC reduces the viscosity of i.u. fluid and has a positive effect on the inflammatory response of the endometrium. Mares (n = 12) were included in the study as soon as estrus was detected (ovarian follicle >3.0 cm and endometrial edema), which was defined as Day 1. They were randomly assigned to a treatment (10 mg/kg NAC on Days 1-4) or a control group (no treatment). On days 1 and 5 i.u. mucus was collected and its rheologic properties were accessed. On Day 5, endometrial biopsies were obtained and evaluated for integrity of the luminal epithelium, number of polymorphonuclear neutrophils (PMN), staining for cyclooxygenase 2 (COX2), staining with Kiel 67 antigen (Ki-67), lectins and periodic acid Schiff (PAS). In the treatment group, viscosity of i.u. mucus increased significantly between Days 1 and 5 (P NAC treatment the mean number of PMN in endometrial biopsies was significantly lower compared to mares of the control group (1.9 ± 0.3 vs. 4.8 ± 0.4; P NAC treatment compared to control mares (P mucus in deep uterine glands differed significantly between groups (both P NAC treatment does not reduce viscosity of uterine mucus but has an

  11. Dietary antioxidants (selenium and N-acetylcysteine) modulate paraoxonase 1 (PON1) in PCB 126-exposed rats.

    Shen, Hua; Li, Miao; Wang, Bingxuan; Lai, Ian K; Robertson, Larry W; Ludewig, Gabriele


    Environmental pollutants polychlorinated biphenyls (PCBs), especially dioxin-like PCBs, cause oxidative stress and associated toxic effects, including cancer and possibly atherosclerosis. We previously reported that PCB 126, the most potent dioxin-like PCB congener, not only decreases antioxidants such as hepatic selenium (Se), Se-dependent glutathione peroxidase, and glutathione (GSH) but also increases levels of the antiatherosclerosis enzyme paraoxonase 1 (PON1) in liver and serum. To probe the interconnection of these three antioxidant systems, Se, GSH, and PON1, we examined the influence of varying levels of dietary Se and N-acetylcysteine (NAC), a scavenger of reactive oxygen species (ROS) and precursor for GSH synthesis, on PON1 in the absence and presence of PCB 126 exposure. Male Sprague-Dawley rats, fed diets with differing Se levels (0.02, 0.2, or 2 ppm) or NAC (1%), were treated with a single intraperitoneal injection of corn oil or various doses of PCB 126 and euthanized 2 weeks later. PCB 126 significantly increased liver PON1 mRNA, protein level and activity, and serum PON1 activity in all dietary groups but did not consistently increase thiobarbituric acid levels (thiobarbituric acid reactive substances, TBARS), an indicator of lipid oxidation and oxidative stress, in liver or serum. Inadequate (high or low) dietary Se decreased baseline and PCB 126-induced aryl hydrocarbon receptor (AhR) expression but further increased PCB 126-induced cytochrome P450 1A1 (CYP1A1) expression, the enzyme believed to be the cause for PCB 126-induced oxidative stress. In addition, a significant inverse relationship was observed not only between dietary Se levels and PON1 mRNA and PON1 activity but also with TBARS levels in the liver, suggesting significant antioxidant protection from dietary Se. NAC lowered serum baseline TBARS levels in controls and increased serum PON1 activity but lowered liver PON1 activities in animals treated with 1 μmol/kg PCB 126, suggesting

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

    Gisele A. Souza


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

  13. The effects of erdosteine, N-acetylcysteine, and vitamin E on nicotine-induced apoptosis of pulmonary cells.

    Demiralay, Rezan; Gürsan, Nesrin; Erdem, Havva


    This study was conducted to investigate the frequency of apoptosis in the pulmonary epithelial cells of rats after intratraperitoneal nicotine injection, in order to examine the role of inflammatory markers [myeloperoxidase (MPO) and tumor necrosis factor-alpha (TNF-alpha)] in nicotine-induced lung damage, and to determine the protective effects of three known antioxidant agents [N-acetylcysteine (NAC), erdosteine, and vitamin E] on the lung toxicity of nicotine in the lungs. Female Wistar rats were divided into seven groups, each composed of nine rats: two negative control groups, two positive control groups, one erdosteine-treated group (500 mg/kg), one NAC-treated group (500 mg/kg), and one vitamin E-treated group (500 mg/kg). Nicotine was injected intraperitoneally at a dosage of 0.6 mg/kg for 21 days. Following nicotine injection, the antioxidants were administered orally, treatment was continued until the rats were killed. Lung tissue samples were stained with hematoxylin-eosin (H&E) for histopathological assessments. The apoptosis level in the lung bronchiolar and alveolar epithelium was determined by using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) method. Cytoplasmic TNF-alpha in the bronchiolar and alveolar epithelial cells and the lung MPO activity were evaluated immunohistochemically. The protective effect of vitamin E on lung histology was stronger than that of erdosteine or NAC. Treatment with erdosteine, NAC, and vitamin E significantly reduced the rate of nicotine-induced pulmonary epithelial cell apoptosis, and there were no significant differences in apoptosis among the three antioxidants groups. Erdosteine, NAC, and vitamin E significantly reduced the increases in TNF-alpha staining and lung MPO activity. The effects of erdosteine on the increases in the local TNF-alpha level and lung MPO activity were weaker than that of NAC or vitamin E. This findings suggest that erdosteine and NAC can be as effective as

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

    Costa Nicola


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

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

    Karolline S. da Silva


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

  16. Pathogenesis of cigarette smoke-induced chronic obstructive pulmonary disease and therapeutic effects of glucocorticoids and N-acetylcysteine in rats

    徐凌; 蔡柏蔷; 朱元珏


    Background T lymphocytes and matrix metalloproteinase (MMP) play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the details of the mechanisms involved are unclear. The aims of this study were to investigate the changes in interferon-γ (IFN-γ), interleukin-4 (IL-4), MMP-9, MMP-12 and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels in a smoke-induced COPD rat model and the therapeutic effects of glucocorticoids and N-acetylcysteine.Methods Male Wistar rats were exposed to cigarette smoke for 3.5 months. Budesonide or N-acetylcysteine was given in the last month. Lung function was measured at the end of the study. IL-4 and IFN-γ levels were then determined in bronchoalveolar lavage fluid and lung tissue samples by enzyme-linked immunosorbent assay. The expression of MMP-9, MMP-12 and TIMP-1 mRNA in lung tissue was determined by RT-PCR. Results In comparison with the control group, rats exposed to smoke had a significant increase in IL-4 and MMP-12 levels and a significant decrease in IFN-γ levels. In addition, the IL-4/ IFN-γ ratio and MMP-12/TIMP-1 ratio were both higher. At the same time, the ratio of forced expiratory volume in 0.3 second to forced vital capacity (FEV0.3/FVC) and dynamic compliance (Cdyn) decreased and expiratory resistance (Re) increased. By measuring pulmonary mean linear intercept and mean alveolar numbers, obvious emphysematous changes were observed in the smoke exposed group. After treatment with budesonide, IL-4 and MMP-12 decreased and IFN-γ increased. The IL-4/IFN-γ ratio returned to normal, though the MMP-12/TIMP-1 ratio remained unchanged. FEV0.3/FVC was significantly higher and Re was significantly lower than that in untreated smoke exposed rats. No significant differences were found in pulmonary mean linear intercept and mean alveolar numbers. After treatment with N-acetylcysteine, IFN-γ increased and the IL-4/IFN-γ ratio decreased. The MMP-12/TIMP-1 ratio remained

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

    Andrzej Plewka


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

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

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


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

  19. Prolonged N-acetylcysteine therapy in late acetaminophen poisoning associated with acute liver failure--a need to be more cautious?

    Athuraliya, T Nimmi C; Jones, Alison L


    Since the 1970s, N-acetylcysteine (NAC) has shown proven efficacy as an antidote for acetaminophen (APAP) poisoning and APAP-induced liver failure for early presenters. The current evidence of benefits of NAC for late presenters is controversial because of the poor understanding of the mechanism of late toxicity. In the previous issue of Critical Care, Yang and colleagues use a mouse model to demonstrate that NAC in doses similar to those used therapeutically to treat APAP poisoning in humans impairs liver regenerative capacity and that the effect is more pronounced when administered for a longer duration. Studies based on cell cultures support this evidence. Cytokine and growth factor signalling pathways are recognised to be involved in the process of liver regeneration and apoptosis. This research paper generates several issues related to the future management of APAP-induced liver failure and research into the mechanism of toxicity, especially of late toxicity.

  20. The effect of N-acetylcysteine supplementation upon viral load, CD4, CD8, total lymphocyte count and hematocrit in individuals undergoing antiretroviral treatment.

    Spada, Celso; Treitinger, Arício; Reis, Marcellus; Masokawa, Ivete Y; Verdi, Júlio C; Luiz, Magali C; Silveira, Mariete V S; Michelon, Cleonice M; Avila-Junior, Silvio; Gil, lone D O; Ostrowskyl, Stephanie


    Individuals infected with the human immunodeficiency virus (HIV-1) present with decreased CD4, a progressive increase in viral load, compromised cell immune defense, and hematologic alterations. The aim of this study was to assess the serum viral load, CD4, CD8, lymphocyte count and hematocrit at the beginning of antiretroviral therapy in individuals who were supplemented with N-acetylcysteine (NAC). Twenty volunteers participated in this double-blind, placebo-controlled 180-day study. Ten participants received 600 mg of NAC per day (NAC group) and the other ten serving as a control group received placebo. The above mentioned parameters were determined before treatment, and after 60, 120 and 180 days. In NAC-treated patients hematocrit remained stable and an increase in CD4 cell count took place earlier than that in the control group.

  1. Resolution of norfloxacin-induced acute liver failure after N-acetylcysteine therapy: further support for the use of NAC in drug-induced ALF?

    Elliott, Timothy Ross; Symes, Tiffany; Kannourakis, George; Angus, Peter


    Liver injury due to idiosyncratic drug reactions can be difficult to diagnose and may lead to acute liver failure (ALF), which has a high mortality rate. N-acetylcysteine (NAC) is effective treatment for paracetamol toxicity, but its role in non-paracetamol drug-induced ALF is controversial. We report on the use of a validated bedside tool to establish causality for drug-induced liver injury (DILI) and describe the first case of resolution of norfloxacin-induced ALF after NAC therapy. NAC is easy to administer and generally has a good safety profile. We discuss the evidence to support the use of NAC in ALF secondary to DILI and possibilities for further clinical research in this field. 2016 BMJ Publishing Group Ltd.

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

    Jonathan ePoels


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

  3. Veränderungen kognitiver Funktionen unter LH-RH-Therapie bzw. unter Bicalutamid-Monotherapie

    Brössner C


    Full Text Available Einleitung: Androgendeprivationstherapie mit LH-RH-Agonisten bzw. Androgenrezeptorblockade mit Bicalutamid wurde zur Standardtherapie beim fortgeschrittenen Prostatakarzinom. Der Großteil der existierenden Literatur beschreibt unter LH-RH-Gabe und damit verbundener Senkung des Testosteronspiegels eine Verschlechterung bestimmter kognitiver Gedächtnisleistungen. Ziel unserer prospektiven, konsekutiven Studie ist es, kognitive und emotionale Funktionen sowie die Lebensqualität bei Männern unter LH-RH bzw. unter Bicalutamid-Monotherapie zu untersuchen. Methoden: In Gruppe A wurden 15 Männer (mean 70,5 a; 57–81 inkludiert, die ein LH-RHAnalogon für 1 Jahr erhielten. In Gruppe B wurden 12 Männer (mean 69,3 a; 56–80 unter Bicalutamid-Monotherapie (150 mg/d für 1 Jahr inkludiert. Zum Zeitpunkt der kognitiven Testung waren alle Patienten frei von klinischer Metastasierung und die PSA-Werte waren 0,5 ng/ml. Für die Untersuchung der kognitiven Leistungen wurde eine umfangreiche neuropsychologische alters-, geschlechts- und bildungskorrigierte Testbatterie eingesetzt: Tests für Aufmerksamkeit (ZVT, Stroop-Test, Gedächtnis (NAI, WMS-R, Demenz (MMSE, Lebensqualität (WHOQOL-BREF, Wahrnehmung (Mosaik-Test, Sprache (LPS 50 Depression (BDI sowie für Angst (STAI wurden durchgeführt. Ergebnisse: In Gruppe A (unter LH-RH fanden wir signifikante Defizite im topografischen (T = 39,3 und visuellen Langzeitgedächtnis (T = 35,6. Das visuelle und verbale Arbeitsgedächtnis zeigte in dieser Gruppe grenzwertige Defizite (T = 40,67 und T = 41,67. In Gruppe B (Bicalutamid konnten wir dagegen bei keinem der Patienten ein kognitives Defizit feststellen. Schlussfolgerung: Unsere Daten suggerieren einen signifikanten negativen Einfluss der LH-RHLangzeittherapie auf bestimmte kognitive Funktionen. Im Gegensatz dazu fanden wir keine Veränderungen unter Bicalutamid-Monotherapie.

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

    Abu El-Saad AM


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

  5. N-Acetylcysteine in Combination with IGF-1 Enhances Neuroprotection against Proteasome Dysfunction-Induced Neurotoxicity in SH-SY5Y Cells

    Anand, Pinki; Kuang, Anxiu; Akhtar, Feroz; Scofield, Virginia L.


    Ubiquitin proteasome system (UPS) dysfunction has been implicated in the development of many neuronal disorders, including Parkinson's disease (PD). Previous studies focused on individual neuroprotective agents and their respective abilities to prevent neurotoxicity following a variety of toxic insults. However, the effects of the antioxidant N-acetylcysteine (NAC) on proteasome impairment-induced apoptosis have not been well characterized in human neuronal cells. The aim of this study was to determine whether cotreatment of NAC and insulin-like growth factor-1 (IGF-1) efficiently protected against proteasome inhibitor-induced cytotoxicity in SH-SY5Y cells. Our results demonstrate that the proteasome inhibitor, MG132, initiates poly(ADP-ribose) polymerase (PARP) cleavage, caspase 3 activation, and nuclear condensation and fragmentation. In addition, MG132 treatment leads to endoplasmic reticulum (ER) stress and autophagy-mediated cell death. All of these events can be attenuated without obvious reduction of MG132 induced protein ubiquitination by first treating the cells with NAC and IGF-1 separately or simultaneously prior to exposure to MG132. Moreover, our data demonstrated that the combination of the two proved to be significantly more effective for neuronal protection. Therefore, we conclude that the simultaneous use of growth/neurotrophic factors and a free radical scavenger may increase overall protection against UPS dysfunction-mediated cytotoxicity and neurodegeneration. PMID:27774335

  6. N-Acetylcysteine counteracts oxidative stress and protects alveolar epithelial cells from lung contusion-induced apoptosis in rats with blunt chest trauma.

    Topcu-Tarladacalisir, Yeter; Tarladacalisir, Taner; Sapmaz-Metin, Melike; Karamustafaoglu, Altemur; Uz, Yesim Hulya; Akpolat, Meryem; Cerkezkayabekir, Aysegul; Turan, Fatma Nesrin


    The aim of this study was to investigate the protective effects of N-acetylcysteine (NAC) on peroxidative and apoptotic changes in the contused lungs of rats following blunt chest trauma. The rats were randomly divided into three groups: control, contusion, and contusion + NAC. All the rats, apart from those in the control group, performed moderate lung contusion. A daily intramuscular NAC injection (150 mg/kg) was given immediately following the blunt chest trauma and was continued for two additional days following cessation of the trauma. Samples of lung tissue were taken in order to evaluate the tissue malondialdehyde (MDA) level, histopathology, and epithelial cell apoptosis using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and active caspase-3 immunostaining. In addition, we immunohistochemically evaluated the expression of surfactant protein D (SP-D) in the lung tissue. The blunt chest trauma-induced lung contusion resulted in severe histopathological injury, as well as an increase in the MDA level and in the number of cells identified on TUNEL assay together with active caspase-3 positive epithelial cells, but a decrease in the number of SP-D positive alveolar type 2 (AT-2) cells. NAC treatment effectively attenuated histopathologic, peroxidative, and apoptotic changes, as well as reducing alterations in SP-D expression in the lung tissue. These findings indicate that the beneficial effects of NAC administrated following blunt chest trauma is related to the regulation of oxidative stress and apoptosis.

  7. Colonic and Hepatic Modulation by Lipoic Acid and/or N-Acetylcysteine Supplementation in Mild Ulcerative Colitis Induced by Dextran Sodium Sulfate in Rats

    Fabiana Andréa Moura


    Full Text Available Lipoic acid (LA and N-acetylcysteine (NAC are antioxidant and anti-inflammatory agents that have not yet been tested on mild ulcerative colitis (UC. This study aims to evaluate the action of LA and/or NAC, on oxidative stress and inflammation markers in colonic and hepatic rat tissues with mild UC, induced by dextran sodium sulfate (DSS (2% w/v. LA and/or NAC (100 mg·kg·day−1, each were given, once a day, in the diet, in a pretreatment phase (7 days and during UC induction (5 days. Colitis induction was confirmed by histological and biochemical analyses (high performance liquid chromatography, spectrophotometry, and Multiplex®. A redox imbalance occurred before an immunological disruption in the colon. NAC led to a decrease in hydrogen peroxide (H2O2, malondialdehyde (MDA levels, and myeloperoxidase activity. In the liver, DSS did not cause damage but treatments with both antioxidants were potentially harmful, with LA increasing MDA and LA + NAC increasing H2O2, tumor necrosis factor alpha, interferon gamma, and transaminases. In summary, NAC exhibited the highest colonic antioxidant and anti-inflammatory activity, while LA + NAC caused hepatic damage.

  8. Amelioration of social isolation-triggered onset of early Alzheimer's disease-related cognitive deficit by N-acetylcysteine in a transgenic mouse model.

    Hsiao, Ya-Hsin; Kuo, Jinn-Rung; Chen, Shun-Hua; Gean, Po-Wu


    Epidemiological study reveals that socially isolated persons have increased risk of developing Alzheimer's disease (AD). Whether this risk arises from an oxidative stress is unclear. Here we show that N-acetylcysteine (NAC), an anti-oxidant, is capable of preventing social isolation-induced accelerated impairment of contextual fear memory and rundown of hippocampal LTP in 3-month old APP/PS1 mice. Increased hippocampal levels of γ-secretase activity, Aβ-40 and Aβ-42 seen in the isolated APP/PS1 mice were reduced by chronic treatment of NAC. In addition, social isolation-induced increase in calpain activity and p25/p35 ratio concomitant with decrease in membrane-associated p35 and p35/Cdk5 activity was normalized by NAC. NAC pretreatment also reversed isolation-induced decrease in GluR1 Ser831 phosphorylation, surface expression of AMPARs and p35-GluR1-CaMKII interactions. These results suggest that NAC decreases γ-secretase activity resulting in the attenuation of Aβ production, calpain activity and conversion of p35 to p25 which stabilized p35-GluR1-CaMKII interactions and restored GluR1 and GluR2 surface expression. Our results indicate that NAC is effective in mouse models of AD and has translation potential for the human disorder. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. The antioxidant N-acetylcysteine prevents HIF-1 stabilization under hypoxia in vitro but does not affect tumorigenesis in multiple breast cancer models in vivo.

    Jaclyn Sceneay

    Full Text Available Intratumoral hypoxia is a poor prognostic factor associated with reduced disease-free survival in many cancer types, including breast cancer. Hypoxia encourages tumor cell proliferation, stimulates angiogenesis and lymphangiogenesis, and promotes epithelial-mesenchymal transition and metastasis. Tumor cells respond to a hypoxic state by stabilizing the Hif-1α subunit of the Hypoxia-Inducible Factor (HIF transcription factor to promote expression of various tumor- and metastasis-promoting hypoxic response genes. The antioxidant N-acetylcysteine (NAC was recently shown to prevent Hif-1α stabilization under hypoxia, and has been identified as a potential alternative method to target the hypoxic response in tumors. We utilized three orthotopic syngeneic murine models of breast cancer, the PyMT, EO771 and 4T1.2 models, to investigate the ability of NAC to modulate the hypoxic response in vitro and in vivo. While NAC prevented Hif-1α stabilization under hypoxia in vitro and increased levels of glutathione in the blood of mice in vivo, this did not translate to a difference in tumor growth or the hypoxic state of the tumor compared to untreated control mice. In addition, NAC treatment actually increased metastatic burden in an experimental metastasis model. This work raises questions regarding the validity of NAC as an anti-tumorigenic agent in breast cancer, and highlights the need to further investigate its properties in vivo in different cancer models.

  10. Pseudoporfiria induzida pela diálise tratada com N-acetilcisteína oral Pseudoporphyria induced by dialysis treated with oral N-acetylcysteine

    Marcelo Massaki Guiotoku


    Full Text Available Pseudoporfiria é dermatose bolhosa rara, semelhante clínica e histopatologicamente à porfiria cutânea tardia. Acomete, principalmente, pacientes renais crônicos em diálise peritoneal ou hemodiálise. Medicamentos também podem ser envolvidos na etiologia. O diagnóstico e o manejo desta entidade é um desafio para os dermatologistas. Os autores demonstram um caso de pseudoporfiria, relacionada à diálise, com evolução favorável após o uso de N-acetilcisteína oral.Pseudoporphyria is a rare bullous dermatosis that clinically and histopathologically is similar to porphyria cutanea tarda. It mainly affects patients with chronic renal failure on peritoneal dialysis or hemodialysis. Medications can also be involved in the etiology. Diagnosis and management of this condition is a challenge for dermatologists. The authors report a case of pseudoporphyria related to dialysis with favorable outcome after the use of oral N-acetylcysteine.

  11. The Effect of Iloprost and N-Acetylcysteine on Skeletal Muscle Injury in an Acute Aortic Ischemia-Reperfusion Model: An Experimental Study

    Osman Tiryakioglu


    Full Text Available Objective. The objective of this study was to examine the effects of iloprost and N-acetylcysteine (NAC on ischemia-reperfusion (IR injuries to the gastrocnemius muscle, following the occlusion-reperfusion period in the abdominal aorta of rats. Materials and Methods. Forty male Sprague-Dawley rats were randomly divided into four equal groups. Group 1: control group. Group 2 (IR: aorta was occluded. The clamp was removed after 1 hour of ischemia. Blood samples and muscle tissue specimens were collected following a 2-hour reperfusion period. Group 3 (IR + iloprost: during a 1-hour ischemia period, iloprost infusion was initiated from the jugular catheter. During a 2-hour reperfusion period, the iloprost infusion continued. Group 4 (IR + NAC: similar to the iloprost group. Findings. The mean total oxidant status, CK, and LDH levels were highest in Group 2 and lowest in Group 1. The levels of these parameters in Group 3 and Group 4 were lower compared to Group 2 and higher compared to Group 1 (P<0.05. The histopathological examination showed that Group 3 and Group 4, compared to Group 2, had preserved appearance with respect to hemorrhage, necrosis, loss of nuclei, infiltration, and similar parameters. Conclusion. Iloprost and NAC are effective against ischemia-reperfusion injury and decrease ischemia-related tissue injury.

  12. The effect of iloprost and N-acetylcysteine on skeletal muscle injury in an acute aortic ischemia-reperfusion model: an experimental study.

    Tiryakioglu, Osman; Erkoc, Kamuran; Tunerir, Bulent; Uysal, Onur; Altin, H Firat; Gunes, Tevfik; Aydin, Selim


    The objective of this study was to examine the effects of iloprost and N-acetylcysteine (NAC) on ischemia-reperfusion (IR) injuries to the gastrocnemius muscle, following the occlusion-reperfusion period in the abdominal aorta of rats. Forty male Sprague-Dawley rats were randomly divided into four equal groups. Group 1: control group. Group 2 (IR): aorta was occluded. The clamp was removed after 1 hour of ischemia. Blood samples and muscle tissue specimens were collected following a 2-hour reperfusion period. Group 3 (IR + iloprost): during a 1-hour ischemia period, iloprost infusion was initiated from the jugular catheter. During a 2-hour reperfusion period, the iloprost infusion continued. Group 4 (IR + NAC): similar to the iloprost group. The mean total oxidant status, CK, and LDH levels were highest in Group 2 and lowest in Group 1. The levels of these parameters in Group 3 and Group 4 were lower compared to Group 2 and higher compared to Group 1 (P Iloprost and NAC are effective against ischemia-reperfusion injury and decrease ischemia-related tissue injury.

  13. Effects of guaifenesin, N-acetylcysteine, and ambroxol on MUC5AC and mucociliary transport in primary differentiated human tracheal-bronchial cells

    Seagrave JeanClare


    Full Text Available Abstract Background Therapeutic intervention in the pathophysiology of airway mucus hypersecretion is clinically important. Several types of drugs are available with different possible modes of action. We examined the effects of guaifenesin (GGE, N-acetylcysteine (NAC and ambroxol (Amb on differentiated human airway epithelial cells stimulated with IL-13 to produce additional MUC5AC. Methods After IL-13 pre-treatment (3 days, the cultures were treated with GGE, NAC or Amb (10–300 μM in the continued presence of IL-13. Cellular and secreted MUC5AC, mucociliary transport rates (MTR, mucus rheology at several time points, and the antioxidant capacity of the drugs were assessed. Results IL-13 increased MUC5AC content (~25% and secretion (~2-fold and decreased MTR, but only slightly affected the G’ (elastic or G” (viscous moduli of the secretions. GGE significantly inhibited MUC5AC secretion and content in the IL-13-treated cells in a concentration-dependent manner (IC50s at 24 hr ~100 and 150 μM, respectively. NAC or Amb were less effective. All drugs increased MTR and decreased G’ and G” relative to IL-13 alone. Cell viability was not affected and only NAC exhibited antioxidant capacity. Conclusions Thus, GGE effectively reduces cellular content and secretion of MUC5AC, increases MTR, and alters mucus rheology, and may therefore be useful in treating airway mucus hypersecretion and mucostasis in airway diseases.

  14. Effect of vitamin E and N-acetylcysteine on phosphatidylserine externalization and induction of coagulation by high-glucose-treated human erythrocytes.

    Jain, S K; Palmer, M; Chen, Y


    This study examines the effect of high glucose levels on the markers of oxidative stress, phosphatidylserine (PS) externalization, and induction of coagulation by high-glucose-treated red blood cells (RBCs). Washed normal RBCs were suspended to 15% hematocrit in phosphate-buffered saline and incubated with different concentrations of glucose for 24 hours in a shaking water bath at 37 degrees C. This treatment caused depletion of vitamin E and accumulation of vitamin E-quinone and malondialdehyde ([MDA] an end product of lipid peroxidation), externalization of PS in the membrane bilayer, and induction of coagulation by RBCs. Pretreatment of RBCs with N-acetylcysteine (NAC) and vitamin E reduced membrane lipid peroxidation, PS externalization, and the tendency of high-glucose-treated RBCs to clot plasma. This study provides further evidence for the increased oxidative stress in RBCs exposed to high glucose levels. In addition, it suggests a role for membrane lipid peroxidation in the PS externalization in the membrane bilayer and in the induction of clotting by RBCs exposed to hyperglycemia. It also suggests that certain antioxidants can decrease cellular damage and restore certain cellular functions in diabetes.

  15. Targeting glia with N-Acetylcysteine modulates brain glutamate and behaviours relevant to neurodevelopmental disorders in C57BL/6J mice

    Alice Marie Sybille Durieux


    Full Text Available An imbalance between excitatory (E glutamate and inhibitory (I GABA transmission may underlie neurodevelopmental conditions such as Autism Spectrum Disorder (ASD and schizophrenia. This may be direct, through alterations in synaptic genes, but there is increasing evidence for the importance of indirect modulation of E/I balance through glial mechanisms. Here we used C57BL/6J mice to test the hypothesis that striatal glutamate levels can be shifted by N-acetylcysteine (NAC, which acts at the cystine-glutamate antiporter of glial cells. Striatal glutamate was quantified in-vivo using proton magnetic resonance spectroscopy. The effect of NAC on behaviours relevant to ASD was examined in a separate cohort. NAC induced a time-dependent decrease in striatal glutamate, which recapitulated findings of lower striatal glutamate reported in ASD. NAC-treated animals were significantly less active and more anxious in the open field test; and NAC-treated females had significantly impaired prepulse inhibition of startle response. This at least partly mimics greater anxiety and impaired sensorimotor gating reported in neurodevelopmental disorders. Thus glial mechanisms regulate glutamate acutely and have functional consequences even in adulthood. Glial cells may be a potential drug target for the development of new therapies for neurodevelopmental disorders across the life-span.

  16. Oral N-acetylcysteine or S-carboxymethylcysteine inhibit cigarette smoke-induced hypersecretion of mucus in rat larynx and trachea in situ.

    Rogers, D F; Turner, N C; Marriott, C; Jeffery, P K


    Two weeks exposure of rats to cigarette smoke (CS) significantly (p less than 0.05) increased the secretion of fucose-containing glycoconjugates above normal in an in situ preparation of larynx and trachea. After equilibration mean basal secretion in CS-exposed rats was 24 micrograms (per 30 min collection) which was 8 times higher than that of unexposed animals (p less than 0.01). N-acetylcysteine (NAC) or S-carboxymethylcysteine (SCMC) given as 1% of the drinking water, before and after daily exposure to CS, significantly inhibited the development of the CS-induced increase in fucose secretion reducing the mean for basal secretion in each group to 7 and 5 micrograms, respectively (p less than 0.05). Neither NAC nor SCMC had significant effects on baseline glycoconjugate secretion in control animals. Albumin was inconsistently present in the secretions of both control and CS-exposed animals, whereas in those exposed to CS and also given one of the two cysteine derivatives there was a consistent increase in albumin transudation.

  17. A novel thiol compound, N-acetylcysteine amide, attenuates allergic airway disease by regulating activation of NF-kappaB and hypoxia-inducible factor-1alpha.

    Lee, Kyung Sun; Kim, So Ri; Park, Hee Sun; Park, Seoung Ju; Min, Kyung Hoon; Lee, Ka Young; Choe, Yeong Hun; Hong, Sang Hyun; Han, Hyo Jin; Lee, Young Rae; Kim, Jong Suk; Atlas, Daphne; Lee, Yong Chul


    Reactive oxygen species (ROS) play an important role in the pathogenesis of airway inflammation and hyperresponsiveness. Recent studies have demonstrated that antioxidants are able to reduce airway inflammation and hyperreactivity in animal models of allergic airway disease. A newly developed antioxidant, small molecular weight thiol compound, N-acetylcysteine amide (AD4) has been shown to increase cellular levels of glutathione and to attenuate oxidative stress related disorders such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. However, the effects of AD4 on allergic airway disease such as asthma are unknown. We used ovalbumin (OVA)-inhaled mice to evaluate the role of AD4 in allergic airway disease. In this study with OVA-inhaled mice, the increased ROS generation, the increased levels of Th2 cytokines and VEGF, the increased vascular permeability, the increased mucus production, and the increased airway resistance in the lungs were significantly reduced by the administration of AD4. We also found that the administration of AD4 decreased the increases of the NF-kappaB and hypoxia-inducible factor-1alpha (HIF-1alpha) levels in nuclear protein extracts of lung tissues after OVA inhalation. These results suggest that AD4 attenuates airway inflammation and hyperresponsiveness by regulating activation of NF-kappaB and HIF-1alpha as well as reducing ROS generation in allergic airway disease.

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

    Donrawee Leelarungrayub


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

  19. Gastrin-releasing peptide receptor antagonist or N-acetylcysteine combined with omeprazol protect against mitochondrial complex II inhibition in a rat model of gastritis.

    Rezin, Gislaine T; Petronilho, Fabricia C; Araújo, João H; Gonçalves, Cinara L; Daufenbach, Juliana F; Cardoso, Mariane R; Roesler, Rafael; Schwartsmann, Gilberto; Dal-Pizzol, Felipe; Streck, Emilio L


    The pathophysiology of gastritis involves an imbalance between gastric acid attack and mucosal defence. In addition, the gastric mucosal injury results in adenosine triphosphate (ATP) depletion leading to mitochondrial dysfunction. Several studies have shown the association of mitochondrial disorders with gastrointestinal dysfunction. In the present study, we investigated the activity of mitochondrial respiratory chain complexes activity in the stomach of rats with gastritis induced by indomethacin (IDM) and treated with omeprazole (OM), N-acetylcysteine (NAC) and the gastrin-releasing peptide receptor (GRPR) antagonist RC-3095. Adult male Wistar rats were pre-treated for 7 days with OM, NAC, RC-3095, combination of OM plus RC-3095, OM plus NAC and water (control). The animals were then submitted to fasting for 24 hr; IDM was administered. The rats were killed 6 hr later, and the stomachs were used for evaluation of macroscopic damage and respiratory chain activity. Our results showed that complex I and IV activities were not affected by administration of IDM. On the other hand, complex II and III activities were inhibited. In addition, OM plus RC-3095 and OM plus NAC did not reverse complex II activity inhibition. However, the complex III activity inhibition was reversed only with the combined use of OM plus RC-3095 and OM plus NAC. Our results are in agreement with previous studies indicating mitochondrial dysfunction in the pathophysiology of gastrointestinal tract disease and we suggest that GRPR antagonism might be a novel therapeutic strategy in gastritis.

  20. Colonic and Hepatic Modulation by Lipoic Acid and/or N-Acetylcysteine Supplementation in Mild Ulcerative Colitis Induced by Dextran Sodium Sulfate in Rats

    Moura, Fabiana Andréa; de Andrade, Kívia Queiroz; de Araújo, Orlando Roberto Pimentel; Santos, Juliana Célia de Farias


    Lipoic acid (LA) and N-acetylcysteine (NAC) are antioxidant and anti-inflammatory agents that have not yet been tested on mild ulcerative colitis (UC). This study aims to evaluate the action of LA and/or NAC, on oxidative stress and inflammation markers in colonic and hepatic rat tissues with mild UC, induced by dextran sodium sulfate (DSS) (2% w/v). LA and/or NAC (100 mg·kg·day−1, each) were given, once a day, in the diet, in a pretreatment phase (7 days) and during UC induction (5 days). Colitis induction was confirmed by histological and biochemical analyses (high performance liquid chromatography, spectrophotometry, and Multiplex®). A redox imbalance occurred before an immunological disruption in the colon. NAC led to a decrease in hydrogen peroxide (H2O2), malondialdehyde (MDA) levels, and myeloperoxidase activity. In the liver, DSS did not cause damage but treatments with both antioxidants were potentially harmful, with LA increasing MDA and LA + NAC increasing H2O2, tumor necrosis factor alpha, interferon gamma, and transaminases. In summary, NAC exhibited the highest colonic antioxidant and anti-inflammatory activity, while LA + NAC caused hepatic damage. PMID:27957238

  1. Effects of guaifenesin, N-acetylcysteine, and ambroxol on MUC5AC and mucociliary transport in primary differentiated human tracheal-bronchial cells.

    Seagrave, Jeanclare; Albrecht, Helmut H; Hill, David B; Rogers, Duncan F; Solomon, Gail


    Therapeutic intervention in the pathophysiology of airway mucus hypersecretion is clinically important. Several types of drugs are available with different possible modes of action. We examined the effects of guaifenesin (GGE), N-acetylcysteine (NAC) and ambroxol (Amb) on differentiated human airway epithelial cells stimulated with IL-13 to produce additional MUC5AC. After IL-13 pre-treatment (3 days), the cultures were treated with GGE, NAC or Amb (10-300 μM) in the continued presence of IL-13. Cellular and secreted MUC5AC, mucociliary transport rates (MTR), mucus rheology at several time points, and the antioxidant capacity of the drugs were assessed. IL-13 increased MUC5AC content (~25%) and secretion (~2-fold) and decreased MTR, but only slightly affected the G' (elastic) or G" (viscous) moduli of the secretions. GGE significantly inhibited MUC5AC secretion and content in the IL-13-treated cells in a concentration-dependent manner (IC50s at 24 hr ~100 and 150 μM, respectively). NAC or Amb were less effective. All drugs increased MTR and decreased G' and G" relative to IL-13 alone. Cell viability was not affected and only NAC exhibited antioxidant capacity. Thus, GGE effectively reduces cellular content and secretion of MUC5AC, increases MTR, and alters mucus rheology, and may therefore be useful in treating airway mucus hypersecretion and mucostasis in airway diseases.

  2. Potentiometric and UV Spectral Studies of Binary and Ternary Complexes of Some Metal Ions with N-Acetylcysteine and Amino Acids

    Shaesta Quyoom


    Full Text Available The formation constants of the binary 1:1 and 1:2 complexes of Cu(II, Zn(II, Cd(II, Hg(II, and Pb(II with N-acetylcysteine (NAC and 1:1:1 ternary complexes of the said metal ions with NAC as a primary ligand and some biologically important amino acids as secondary ligands have been determined potentiometrically in aqueous medium. Acid dissociation constants of the ligands used and the formation constants of the binary and the ternary complexes were determined at 25 °C and in ionic strength I=0.1 mol dm-3 (KNO3.The formation constants of the 1:1 complexes were found to be higher than 1:2 complexes and the metal ions follow the order Hg(II >Cu(II >Cd(II >Zn(II. In addition UV-spectral studies of the NAC-Metal (II complexes have also been conducted at appropriate pH values to give further information about the structural nature of NAC- Metal (II complexes in aqueous medium.

  3. Protective effect of N-acetylcysteine supplementation on mitochondrial oxidative stress and mitochondrial enzymes in cerebral cortex of streptozotocin-treated diabetic rats.

    Kamboj, Sukhdev S; Sandhir, Rajat


    Diabetic encephalopathy, characterized by cognitive deficits involves hyperglycemia-induced oxidative stress. Impaired mitochondrial functions might play an important role in accelerated oxidative damage observed in diabetic brain. The aim of the present study was to examine the role of mitochondrial oxidative stress and dysfunctions in the development of diabetic encephalopathy along with the neuroprotective potential of N-acetylcysteine (NAC). Chronic hyperglycemia accentuated mitochondrial oxidative stress in terms of increased ROS production and lipid peroxidation. Significant decrease in Mn-SOD activity along with protein and non-protein thiols was observed in the mitochondria from diabetic brain. The activities of mitochondrial enzymes; NADH dehydrogenase, succinate dehydrogenase and cytochrome oxidase were decreased in the diabetic brain. Increased mitochondrial oxidative stress and dysfunctions were associated with increased cytochrome c and active caspase-3 levels in cytosol. Electron microscopy revealed mitochondrial swelling and chromatin condensation in neurons of diabetic animals. NAC administration, on the other hand was found to significantly improve diabetes-induced biochemical and morphological changes, bringing them closer to the controls. The results from the study provide evidence for the role of mitochondrial oxidative stress and dysfunctions in the development of diabetic encephalopathy and point towards the clinical potential of NAC as an adjuvant therapy to conventional anti-hyperglycemic regimens for the prevention and/or delaying the progression of CNS complications. Copyright © 2010 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

  4. N-acetylcysteine downregulates phosphorylated p-38 expression but does not reverse the increased superoxide anion levels in the spinal cord of rats with neuropathic pain.

    Horst, A; de Souza, J A; Santos, M C Q; Riffel, A P K; Kolberg, C; Ribeiro, M F M; de Fraga, L S; Partata, W A


    We determined the effect of N-acetylcysteine (NAC) on the expression of the phosphorylated p38 (p-p38) protein and superoxide anion generation (SAG), two important players in the processing of neuropathic pain, in the lumbosacral spinal cord of rats with chronic constriction injury (CCI)-induced neuropathic pain. The sciatic functional index (SFI) was also measured to assess the functional recovery post-nerve lesion. Thirty-six male Wistar rats were divided equally into the following groups: Naive (rats did not undergo surgical manipulation); Sham (rats in which all surgical procedures involved in CCI were used except the ligature), and CCI (rats in which four ligatures were tied loosely around the right common sciatic nerve), which received 2, 4, or 8 intraperitoneal injections of NAC (150 mg·kg-1·day-1) or saline beginning 4 h after CCI. Rats were sacrificed 1, 3, and 7 days after CCI. The SFI was measured on these days and the lumbosacral spinal cord was used for analysis of p-p38 expression and SAG. CCI induced a decrease in SFI as well as an increase in p-p38 expression and SAG in the spinal cord. The SFI showed a partial recovery at day 7 in saline-treated CCI rats, but recovery was improved in NAC-treated CCI rats. NAC induced a downregulation in p-p38 expression at all time-points evaluated, but did not reverse the increased SAG induced by CCI. Since p-p38 is a mediator in neuropathic pain and/or nerve regeneration, modulation of this protein may play a role in NAC-induced effects in CCI rats.

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

    Abu El-Saad, Ahmed M; Al-Kahtani, Mohammed A; Abdel-Moneim, Ashraf M


    Environmental exposure to arsenic represents a serious challenge to humans and other animals. The aim of the present study was to test the protective effect of antioxidant N-acetylcysteine (NAC) either individually or in combination with a chelating agent, meso-2,3-dimercaptosuccinic acid (DMSA), against sodium arsenite oral toxicity in male rats. Five groups were used: control; arsenic group (orally administrated in a concentration of 2 mg/kg body weight [b.w.]); the other three groups were orally administrated sodium arsenite in a concentration of 2 mg/kg b.w. followed by either NAC (10 mg/kg b.w., intraperitoneally [i.p.]), DMSA (50 mg/kg b.w., i.p.) or NAC plus DMSA. Arsenic toxicity caused significant rise in serum aspartate aminotransferase, alanine aminotransferase and total bilirubin, and a significant decrease in total protein (TP) and albumin levels after 3 weeks of experimental period. In addition, arsenic-treated rats showed significantly higher arsenic content in liver and significant rise in hepatic malondialdehyde level. By contrast, sharp decreases in glutathione content and catalase and glutathione reductase activities were discernible. NAC and/or DMSA counteracted most of these physiologic and biochemical defects. NAC monotherapy was more effective than DMSA in increasing TP, while DMSA was more effective in decreasing alanine aminotransferase. The combined treatment was superior over monotherapies in recovery of TP and glutathione. Biochemical data were well supported by histopathological and ultrastructural findings. In conclusion, the combination therapy of NAC and DMSA may be an ideal choice against oxidative insult induced by arsenic poisoning.

  6. N-acetylcysteine for the prevention of stricture after circumferential endoscopic submucosal dissection of the esophagus: a randomized trial in a porcine model

    Barret Maximilien


    Full Text Available Abstract Background Circumferential endoscopic submucosal dissection (CESD of the esophagus would allow for both the eradication of Barrett’s esophagus and its related complications, such as advanced neoplasia. However, such procedures generally induce inflammatory repair resulting in a fibrotic stricture. N-acetylcysteine (NAC is an antioxidant that has shown some efficacy against pulmonary and hepatic fibrosis. The aim of our study was to evaluate the benefit of NAC in the prevention of esophageal cicatricial stricture after CESD in a swine model. Animals and methods Two groups of six pigs each were subjected to general anesthesia and CESD: after randomization, a first group received an oral NAC treatment regimen of 100 mg/kg/day, initiated one week before the procedure, whereas a second group was followed without any prophylactic treatment. Follow-up endoscopies took place seven, fourteen, twenty-one, and twenty-eight days after CESD. Necropsy, histological assessment of esophageal inflammation, and fibrosis were performed on day 28. Results The median esophageal lumen diameter on day 21 (main judgment criterion was 4 mm (range 2 to 5 in group 1 and 3 mm (range 1 to 7 in group 2 (P = 0.95. No significant difference was observed between the two groups regarding clinical evaluation (time before onset of clinically significant esophageal obstruction, number of dilations, esophageal inflammation and fibrosis, or oxidative stress damage on immunohistochemistry. Conclusions Despite its antioxidant effect, systemic administration of NAC did not show significant benefit on esophageal fibrosis in our animal model of esophageal wound healing within the experimental conditions of this study. Since the administered doses were relatively high, it seems unlikely that NAC might be a valuable option for the prevention of post-endoscopic esophageal stricture.

  7. Chlorambucil (nitrogen mustard) induced impairment of early vascular endothelial cell migration - effects of α-linolenic acid and N-acetylcysteine.

    Steinritz, Dirk; Schmidt, Annette; Simons, Thilo; Ibrahim, Marwa; Morguet, Christian; Balszuweit, Frank; Thiermann, Horst; Kehe, Kai; Bloch, Wilhelm; Bölck, Birgit


    Alkylating agents (e.g. sulfur and nitrogen mustards) cause a variety of cell and tissue damage including wound healing disorder. Migration of endothelial cells is of utmost importance for effective wound healing. In this study we investigated the effects of chlorambucil (a nitrogen mustard) on early endothelial cells (EEC) with special focus on cell migration. Chlorambucil significantly inhibited migration of EEC in Boyden chamber and wound healing experiments. Cell migration is linked to cytoskeletal organization. We therefore investigated the distribution pattern of the Golgi apparatus as a marker of cell polarity. Cells are polarized under control conditions, whereas chlorambucil caused an encircling perinuclear position of the Golgi apparatus, indicating non-polarized cells. ROS are discussed to be involved in the pathophysiology of alkylating substances and are linked to cell migration and cell polarity. Therefore we investigated the influence of ROS-scavengers (α-linolenic acid (ALA) and N-acetylcysteine (NAC)) on the impaired EEC migration. Both substances, in particular ALA, improved EEC migration. Notably ALA restored cell polarity. Remarkably, investigations of ROS and RNS biomarkers (8-isoprostane and nitrotyrosine) did not reveal a significant increase after chlorambucil exposure when assessed 24h post exposure. A distinct breakdown of mitochondrial membrane potential (measured by TMRM) that recovered under ALA treatment was observed. In conclusion our results provide compelling evidence that the alkylating agent chlorambucil dramatically impairs directed cellular migration, which is accompanied by perturbations of cell polarity and mitochondrial membrane potential. ALA treatment was able to reconstitute cell polarity and to stabilize mitochondrial potential resulting in improved cell migration. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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

    Ehsani Maryam


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

  9. Protective role of L-ascorbic acid, N-acetylcysteine and apocynin on neomycin-induced hair cell loss in zebrafish.

    Wu, Chia-Yen; Lee, Han-Jung; Liu, Chi-Fang; Korivi, Mallikarjuna; Chen, Hwei-Hsien; Chan, Ming-Huan


    Hair cells are highly sensitive to environmental insults and other therapeutic drugs. The adverse effects of drugs such as aminoglycosides can cause hair cell death and lead to hearing loss and imbalance. The objective of the present study was to evaluate the protective activity of L-ascorbic acid, N-acetylcysteine (NAC) and apocynin on neomycin-induced hair cell damage in zebrafish (Danio rerio) larvae at 5 days post fertilization (dpf). Results showed that the loss of hair cells within the neuromasts of the lateral lines after neomycin exposure was evidenced by a significantly lower number of neuromasts labeled with fluorescent dye FM1-43FX observed under a microscope. Co-administration with L-ascorbic acid, NAC and apocynin protected neomycin-induced hair cell loss within the neuromasts. Moreover, these three compounds reduced the production of reactive oxygen species (ROS) in neuromasts exposed to neomycin, indicating that their antioxidant action is involved. In contrast, the neuromasts were labeled with specific fluorescent dye Texas-red conjugated with neomycin to detect neomycin uptake. Interestingly, the uptake of neomycin into hair cells was not influenced by these three antioxidant compounds. These data imply that prevention of hair cell damage against neomycin by L-ascorbic acid, NAC and apocynin might be associated with inhibition of excessive ROS production, but not related to modulating neomycin uptake. Our findings conclude that L-ascorbic acid, NAC and apocynin could be used as therapeutic drugs to protect aminoglycoside-induced listening impairment after further confirmatory studies.

  10. Effects of laxative and N-acetylcysteine on mucus accumulation, bacterial load, transit, and inflammation in the cystic fibrosis mouse small intestine.

    De Lisle, Robert C; Roach, Eileen; Jansson, Kyle


    The accumulation of mucus in affected organs is characteristic of cystic fibrosis (CF). The CF mouse small intestine has dramatic mucus accumulation and exhibits slower interdigestive intestinal transit. These factors are proposed to play cooperative roles that foster small intestinal bacterial overgrowth (SIBO) and contribute to the innate immune response of the CF intestine. It was hypothesized that decreasing the mucus accumulation would reduce SIBO and might improve other aspects of the CF intestinal phenotype. To test this, solid chow-fed CF mice were treated with an osmotic laxative to improve gut hydration or liquid-fed mice were treated orally with N-acetylcysteine (NAC) to break mucin disulfide bonds. Treatment with laxative or NAC reduced mucus accumulation by 43% and 50%, respectively, as measured histologically as dilation of the intestinal crypts. Laxative and NAC also reduced bacterial overgrowth in the CF intestine by 92% and 63%, respectively. Treatment with laxative normalized small intestinal transit in CF mice, whereas NAC did not. The expression of innate immune response-related genes was significantly reduced in laxative-treated CF mice, whereas there was no significant effect in NAC-treated CF mice. In summary, laxative and NAC treatments of CF mice reduced mucus accumulation to a similar extent, but laxative was more effective than NAC at reducing bacterial load. Eradication of bacterial overgrowth by laxative treatment was associated with normalized intestinal transit and a reduction in the innate immune response. These results suggest that both mucus accumulation and slowed interdigestive small intestinal transit contribute to SIBO in the CF intestine.

  11. The effects of phenethyl isothiocyanate, N-acetylcysteine and green tea on tobacco smoke-induced lung tumors in strain A/J mice.

    Witschi, H; Espiritu, I; Yu, M; Willits, N H


    Male and female strain A/J mice were exposed to a mixture of cigarette sidestream and mainstream smoke at a chamber concentration of total suspended particulates of 82.5 mg/m3. Exposure time was 6 h/day, 5 days/week for 5 months. The animals were allowed to recover for another 4 months in filtered air before sacrifice and lung tumor count. Male animals were fed either 0.2% N-acetylcysteine (NAC) or 0.05% phenethyl isothiocyanate (PEITC) in diet AIN-76A with 5% corn oil added. Female animals received normal laboratory chow and were given a 1.25% extract of green tea in the drinking water. Corresponding control groups were fed diets without NAC or PEITC or given plain tap water. Exposure to tobacco smoke increased lung tumor multiplicity to 1.1-1.6 tumors/lung, significantly higher than control values (0.5-1.0 tumors/lung). None of the putative chemopreventive agents (NAC, PEITC or green tea extract) had a protective effect. In positive control experiments, PEITC significantly reduced both lung tumor multiplicity and incidence in mice treated with the tobacco smoke-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). In mice treated with three different doses of urethan and fed NAC in the diet, a significant reduction in lung tumor multiplicity was found only at one dose level. Green tea extract did not reduce lung tumor multiplicity in animals treated with a single dose of NNK. It was concluded that successful chemoprevention of tobacco smoke-induced lung tumorigenesis might require administration of several chemopreventive agents rather than just a single one.

  12. Accelerated urinary excretion of methylmercury following administration of its antidote N-acetylcysteine requires Mrp2/Abcc2, the apical multidrug resistance-associated protein.

    Madejczyk, Michael S; Aremu, David A; Simmons-Willis, Tracey A; Clarkson, Thomas W; Ballatori, Nazzareno


    N-Acetylcysteine (NAC) is a sulfhydryl-containing compound that produces a dramatic acceleration of urinary methylmercury (MeHg) excretion in poisoned mice, but the molecular mechanism for this effect is poorly defined. MeHg readily binds to NAC to form the MeHg-NAC complex, and recent studies indicate that this complex is an excellent substrate for the basolateral organic anion transporter (Oat)-1, Oat1/Slc22a6, thus potentially explaining the uptake from blood into the renal tubular cells. The present study tested the hypothesis that intracellular MeHg is subsequently transported across the apical membrane of the cells into the tubular fluid as a MeHg-NAC complex using the multidrug resistance-associated protein-2 (Mrp2/Abcc2). NAC markedly stimulated urinary [(14)C]MeHg excretion in wild-type Wistar rats, and a second dose of NAC was as effective as the first dose in stimulating MeHg excretion. In contrast with the normal Wistar rats, NAC was much less effective at stimulating urinary MeHg excretion in the Mrp2-deficient (TR-) Wistar rats. The TR- rats excreted only approximately 30% of the MeHg excreted by the wild-type animals. To directly test whether MeHg-NAC is a substrate for Mrp2, studies were carried out in plasma membrane vesicles isolated from livers of TR- and control Wistar rats. Transport of MeHg-NAC was lower in vesicles prepared from TR- rats, whereas transport of MeHg-cysteine was similar in control and TR- rats. These results indicate that Mrp2 is involved in urinary MeHg excretion after NAC administration and suggest that the transported molecule is most likely the MeHg-NAC complex.

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

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


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

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

    Luczak, Michal W; Zhitkovich, Anatoly


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

  15. Co-administration of metformin and N-acetylcysteine with dietary control improves the biochemical and histological manifestations in rats with non-alcoholic fatty liver

    Naglaa Mohamed El-Lakkany


    Full Text Available Non-alcoholic fatty liver disease (NAFLD is a burgeoning health problem that affects 1/3 of the adult population and an increasing number of children in developed countries. Oxidative stress and insulin resistance are the mechanisms that seem to be mostly involved in its pathogenesis. This study was conceived in a NAFLD rat model to evaluate the efficacy of both metformin (MTF and N-acetylcysteine (NAC with dietary control on biochemical and histologic liver manifestations. Rats were classified into nine groups; normal (I, NAFLD-induced by feeding high-fat diet (HFD; II for 12 weeks, NAFLD switched to regular diet (RD; III, NAFLD-HFD or -RD treated with MTF in a dose of 150 mg/kg (IV, V, NAC in a dose of 500 mg/kg (VI, VII or MTF+NAC (VIII, IX respectively for 8 weeks. After 20 weeks, the rats in group II showed notable steatosis, lobular inflammation, fibrosis accompanied with elevated (P < 0.05 serum alanine transaminase (ALT, aspartate aminotransferase (AST, alkaline phosphatase (ALP, gamma glutamyl transferase (g-GT, cholesterol, triglycerides, LDL, VLDL, leptin, tumor necrosis factor (TNF-α, transforming growth factor (TGF-β1 and hepatic malondialdehyde (MDA compared with group I. Meanwhile, hepatic superoxide dismutase (SOD, glutathione GSH with serum HDL, adiponectin were significantly decreased (P < 0.05. These changes were to a less extent in group III. MTF or NAC individually resulted in improvement of most of these biochemical and histological parameters. These improvements were more pronounced in the combined groups VIII and IX versus each drug alone. NAC supplementation concomitant with MTF could be beneficial for the treatment of NAFLD and prevention of nonalcoholic steatohepatitis (NASH.

  16. Co-administration of metformin and N-acetylcysteine with dietary control improves the biochemical and histological manifestations in rats with non-alcoholic fatty liver.

    El-Lakkany, Naglaa Mohamed; Seif El-Din, Sayed Hassan; Sabra, Abdel-Nasser Abdel-Aal; Hammam, Olfat Ali; Ebeid, Fatma Abdel-Latif


    Non-alcoholic fatty liver disease (NAFLD) is a burgeoning health problem that affects 1/3 of the adult population and an increasing number of children in developed countries. Oxidative stress and insulin resistance are the mechanisms that seem to be mostly involved in its pathogenesis. This study was conceived in a NAFLD rat model to evaluate the efficacy of both metformin (MTF) and N-acetylcysteine (NAC) with dietary control on biochemical and histologic liver manifestations. Rats were classified into nine groups; normal (I), NAFLD-induced by feeding high-fat diet (HFD; II) for 12 weeks, NAFLD switched to regular diet (RD; III), NAFLD-HFD or -RD treated with MTF in a dose of 150 mg/kg (IV, V), NAC in a dose of 500 mg/kg (VI, VII) or MTF+NAC (VIII, IX) respectively for 8 weeks. After 20 weeks, the rats in group II showed notable steatosis, lobular inflammation, fibrosis accompanied with elevated (P < 0.05) serum alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (γ-GT), cholesterol, triglycerides, LDL, VLDL, leptin, tumor necrosis factor (TNF-α), transforming growth factor (TGF-β1) and hepatic malondialdehyde (MDA) compared with group I. Meanwhile, hepatic superoxide dismutase (SOD), glutathione GSH with serum HDL, adiponectin were significantly decreased (P < 0.05). These changes were to a less extent in group III. MTF or NAC individually resulted in improvement of most of these biochemical and histological parameters. These improvements were more pronounced in the combined groups VIII and IX versus each drug alone. NAC supplementation concomitant with MTF could be beneficial for the treatment of NAFLD and prevention of nonalcoholic steatohepatitis (NASH).

  17. Therapeutic efficacy of Wuzhi tablet (Schisandra sphenanthera Extract) on acetaminophen-induced hepatotoxicity through a mechanism distinct from N-acetylcysteine.

    Fan, Xiaomei; Chen, Pan; Jiang, Yiming; Wang, Ying; Tan, Huasen; Zeng, Hang; Wang, Yongtao; Qu, Aijuan; Gonzalez, Frank J; Huang, Min; Bi, Huichang


    Acetaminophen (APAP) hepatotoxicity is the most common cause of drug-induced liver injury and N-acetylcysteine (NAC) is the primary antidote of APAP poisoning. Wuzhi tablet (WZ), the active constituents well identified and quantified, is a preparation of an ethanol extract of Schisandra sphenanthera and exerts a protective effect toward APAP-induced hepatotoxicity in mice. However, the clinical use of WZ to rescue APAP-induced acute liver injury and the mechanisms involved in the therapeutic effect of WZ remain unclear. Therefore, the effect of WZ on APAP hepatotoxicity was compared with NAC in mice, and molecular pathways contributing to its therapeutic action were investigated. Administration of WZ 4 hours after APAP treatment significantly attenuated APAP hepatotoxicity and exerted much better therapeutic effect than NAC, as revealed by morphologic, histologic, and biochemical assessments. Both WZ and NAC prevented APAP-induced c-Jun N-terminal protein kinase activation and mitochondrial glutathione depletion in livers. The protein expression of nuclear factor erythroid 2-related factor 2 target genes including Gclc, Gclm, Ho-1, and Nqo1 was increased by WZ administration. Furthermore, p53 and p21 levels were upregulated upon APAP exposure, which were completely reversed by postdosing of WZ 4 hours after APAP treatment over 48 hours. In comparison with NAC, WZ significantly increased the expression of cyclin D1, cyclin D-dependent kinase 4, proliferating cell nuclear antigen, and augmenter of liver regeneration in APAP-injured livers. This study demonstrated that WZ possessed a therapeutic efficacy against APAP-induced liver injury by inhibiting oxidative stress and stimulating a regenerative response after liver injury. Thus WZ may represent a new therapy for APAP-induced acute liver injury.

  18. Effect of high/low dose N-acetylcysteine on chronic obstructive pulmonary disease: a systematic review and meta-analysis.

    Shen, Yanfei; Cai, Wanru; Lei, Shu; Zhang, Zhongheng


    Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality and morbidity worldwide, characterised by persistent airflow limitation, mucus hypersecretion, oxidative stress and airway inflammation. N-acetylcysteine (NAC) have anti-oxidant and anti-inflammatory properties, which have been shown an uncertain benefit in COPD patients. Systematic searches were conducted in Cochrane, Medline and Embase electronic databases. A meta-analysis was performed to evaluate the different effect between high and low-dose NAC treatment on COPD exacerbation. This review yielded 11 studies. The methodological quality of included studies were scored using the Jadad score, with a scale of 1 to 5 (score of 5 being the highest). Data showed high-dose NAC can reduce both the total number of exacerbations (RR = 0.59, 0.47 to 0.74, 95%CI, p 3 showed no significant decrease (RR = 0.98, 0.90 to 1.06, 95%CI, p = 0.59). And low-dose NAC showed no benefit in the total number of exacerbations (RR = 0.97, 0.68 to 1.37, 95%CI, p = 0.85). Neither high nor low-dose NAC treatment showed benefit in forced expiratory volume in one second(FEV1)(WMD = 1.08, -9.97 to 12.13, 95%CI, p = 0.85). Long-term high-dose NAC treatment may lead to a lower rate of exacerbations. But the effect of low-dose NAC treatment remains uncertain. Further researches are needed to confirm this outcome and to clarify its mechanisms.

  19. Ex Vivo and in Vivo Evaluation of the Effect of Coating a Coumarin-6-Labeled Nanostructured Lipid Carrier with Chitosan-N-acetylcysteine on Rabbit Ocular Distribution.

    Liu, Dandan; Li, Jinyu; Cheng, Bingchao; Wu, Qingyin; Pan, Hao


    This study is focused on further understanding the characteristics of chitosan-N-acetylcysteine surface-modified nanostructured lipid carriers (CS-NAC-NLCs) in their interaction with ocular mucosa. Coumarin-6 (C6)-labeled NLCs, including uncoated NLCs, chitosan hydrochloride (CH)-, and CS-NAC-coated NLCs, were developed using a melt-emulsification technique and subsequently decorated with different types or portions of chitosan derivatives. Mucoadhesion was evaluated ex vivo using a flow-through process with fluorescence detection. The results demonstrated that the presence of CS-NAC on the C6-NLC surface provided the most obvious enhancement in adhesion due to the formation of both noncovalent (ionic) and covalent (disulfide bridges) interactions with mucus chains. Meanwhile, the concentration of CS-NAC in the formulation positively influenced the viscosity of the nanoparticles and hence prolonged their retention in the ocular tissue. Transcorneal penetration studies revealed that CS-NAC-NLC particles were able to penetrate through the entire corneal epithelium primarily via a transcellular route. The transport depth and velocity strongly relied on the modification material and the particle size. Ex vivo fluorescence imaging and in vivo ocular distribution investigations showed that C6 was broadly distributed in rabbit eye tissues and absorbed by aqueous humor after CS-NAC-NLC instillation. In relation to C6 eye drops, CS-NAC-NLCs achieved considerably higher Cmax (4.01-fold), MRT0-∞ (1.87-fold), and AUC0-∞ (16.29-fold) in the aqueous humor. Moreover, the increase in drug absorption was greater in the cornea than in the conjunctiva. Thereby, it is possible to draw a conclusion that CS-NAC-NLCs presented great potential for drug application to the front portion of the eye.

  20. The Protective Effects of N-Acetylcysteine on Exogenous Hydrogen Peroxide and Endogenous Superoxide Anion induced DNA Strand Breakage in Human Spermatozoa%`

    徐德祥; 沈汉民; 王俊南


    Objective To explore the protective effects of N-Acetylcysteine (NAC) on exogenous hydrogen peroxide and endogenous superoxide anion-induced DNA strand breakage in human spermatozoa by using the single-cell gel electropherosis (SCGE)Methods Sperm cells were exposed to 0. 5 mmol/L of H2O2 or 5. 0 mmol/L of β -NADPH with or without 0. 1, 0. 5, 1. 0 mmol/L of NAC. The percentage of sperm comet cells and the comet tail lengths were measured in the treated sperm cells by using SCGE.Results Both percentage of comet sperm nuclei and mean tail length in sperm cells exposed to 0. 5 mmol/L hydrogen peroxide with different concentrations of NAC decrease significantly in a dose-dependent manner as compared with sperm cells exposed to H2O2 without NAC or catalase. Although mean tail length in sperm cells exposed to 5. 0 mmol/L of β-NADPH with different concentrations of NAC decreases significantly compared with sperm cells exposed to β-NADPH without NAC or SOD,there were no significant differences on the percentage of sperm comet cells between sperm cells exposed to 5. 0 mmol/L of β-NADPH with different concentrations of NAC and sperm cells exposed to 5. 0 mmol/L of β-NADPH without NAC.Conclusion NAC has a protective effect on exogenous hydrogen peroxide-induced DNA damage, while protective effect of NAC against O2- induced DNA strand break age is significant but very weak.

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

    Lígia S Muranaka

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

  2. N-acetylcysteine attenuates hexavalent chromium-induced hypersensitivity through inhibition of cell death, ROS-related signaling and cytokine expression.

    Yu-Hsuan Lee

    Full Text Available Chromium hypersensitivity (chromium-induced allergic contact dermatitis is an important issue in occupational skin disease. Hexavalent chromium (Cr (VI can activate the Akt, Nuclear factor κB (NF-κB, and Mitogen-activated protein kinase (MAPK pathways and induce cell death, via the effects of reactive oxygen species (ROS. Recently, cell death stimuli have been proposed to regulate the release of inflammatory cytokines, such as tumor necrosis factor-α (TNF-α and interleukin-1 (IL-1. However, the exact effects of ROS on the signaling molecules and cytotoxicity involved in Cr(VI-induced hypersensitivity have not yet been fully demonstrated. N-acetylcysteine (NAC could increase glutathione levels in the skin and act as an antioxidant. In this study, we investigated the effects of NAC on attenuating the Cr(VI-triggered ROS signaling in both normal keratinocyte cells (HaCaT cells and a guinea pig (GP model. The results showed the induction of apoptosis, autophagy and ROS were observed after different concentrations of Cr(VI treatment. HaCaT cells pretreated with NAC exhibited a decrease in apoptosis and autophagy, which could affect cell viability. In addition, Cr (VI activated the Akt, NF-κB and MAPK pathways thereby increasing IL-1α and TNF-α production. However, all of these stimulation phenomena could be inhibited by NAC in both of in vitro and in vivo studies. These novel findings indicate that NAC may prevent the development of chromium hypersensitivity by inhibiting of ROS-induced cell death and cytokine expression.

  3. Qualitative methods in early-phase drug trials: broadening the scope of data and methods from an RCT of N-acetylcysteine in schizophrenia.

    Berk, Michael; Munib, Ahmed; Dean, Olivia; Malhi, Gin S; Kohlmann, Kristy; Schapkaitz, Ian; Jeavons, Sue; Katz, Fiona; Anderson-Hunt, Murray; Conus, Philippe; Hanna, Barbara; Otmar, Renée; Ng, Felicity; Copolov, David L; Bush, Ashley I


    The pharmacokinetic profile of a drug often gives little indication of its potential therapeutic application, with many therapeutic uses of drugs being discovered serendipitously while being studied for different indications. As hypothesis-driven, quantitative research methodology is exclusively used in early-phase trials, unexpected but important phenomena may escape detection. In this context, this study aimed to examine the potential for integrating qualitative research methods with quantitative methods in early-phase drug trials. To our knowledge, this mixed methodology has not previously been applied to blinded psychopharmacologic trials. We undertook qualitative data analysis of clinical observations on the dataset of a randomized, double-blind, placebo-controlled trial of N-acetylcysteine (NAC) in patients with DSM-IV-TR-diagnosed schizophrenia (N = 140). Textual data on all participants, deliberately collected for this purpose, were coded using NVivo 2, and emergent themes were analyzed in a blinded manner in the NAC and placebo groups. The trial was conducted from November 2002 to July 2005. The principal findings of the published trial could be replicated using a qualitative methodology. In addition, significant differences between NAC- and placebo-treated participants emerged for positive and affective symptoms, which had not been captured by the rating scales utilized in the quantitative trial. Qualitative data in this study subsequently led to a positive trial of NAC in bipolar disorder. The use of qualitative methods may yield broader data and has the potential to complement traditional quantitative methods and detect unexpected efficacy and safety signals, thereby maximizing the findings of early-phase clinical trial research. Identifier: ACTRN12605000363684. © Copyright 2011 Physicians Postgraduate Press, Inc.

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

    Ritesh Kumar Srivastava

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

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

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


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

  6. Randomized, Double-Blind, Placebo-Controlled Trial of N-Acetylcysteine Augmentation for Treatment-Resistant Obsessive-Compulsive Disorder.

    Costa, Daniel L C; Diniz, Juliana B; Requena, Guaraci; Joaquim, Marinês A; Pittenger, Christopher; Bloch, Michael H; Miguel, Euripedes C; Shavitt, Roseli G


    To evaluate the efficacy of serotonin reuptake inhibitor (SRI) augmentation with N-acetylcysteine (NAC), a glutamate modulator and antioxidant medication, for treatment-resistant obsessive-compulsive disorder (OCD). We conducted a randomized, double-blind, placebo-controlled, 16-week trial of NAC (3,000 mg daily) in adults (aged 18-65 years) with treatment-resistant OCD, established according to DSM-IV criteria. Forty subjects were recruited at an OCD-specialized outpatient clinic at a tertiary hospital (May 2012-October 2014). The primary outcome measure was the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores. To evaluate the variables group, time, and interaction effects for Y-BOCS scores at all time points, we used nonparametric analysis of variance with repeated measures. Secondary outcomes were the severity scores for anxiety, depression, specific OCD symptom dimensions, and insight. Both groups showed a significant reduction of baseline Y-BOCS scores at week 16: the NAC group had a reduction of 4.3 points (25.6 to 21.3), compared with 3.0 points (24.8 to 21.8) for the placebo group. However, there were no significant differences between groups (P = .92). Adding NAC was superior to placebo in reducing anxiety symptoms (P = .02), but not depression severity or specific OCD symptom dimensions. In general, NAC was well tolerated, despite abdominal pain being more frequently reported in the NAC group (n [%]: NAC = 9 [60.0], placebo = 2 [13.3]; P < .01). Our trial did not demonstrate a significant benefit of NAC in reducing OCD severity in treatment-resistant OCD adults. Secondary analysis suggested that NAC might have some benefit in reducing anxiety symptoms in treatment-resistant OCD patients. identifier: NCT01555970.

  7. N-acetylcysteine attenuates ischemia-reperfusion-induced apoptosis and autophagy in mouse liver via regulation of the ROS/JNK/Bcl-2 pathway.

    Chengfen Wang

    Full Text Available BACKGROUND: Hepatic ischemia-reperfusion injury (HIRI remains a pivotal clinical problem after hemorrhagic shock, transplantation, and some types of toxic hepatic injury. Apoptosis and autophagy play important roles in cell death during HIRI. It is also known that N-acetylcysteine (NAC has significant pharmacologic effects on HIRI including elimination of reactive oxygen species (ROS and attenuation of hepatic apoptosis. However, the effects of NAC on HIRI-induced autophagy have not been reported. In this study, we evaluated the effects of NAC on autophagy and apoptosis in HIRI, and explored the possible mechanism involved. METHODS: A mouse model of segmental (70% hepatic warm ischemia was adopted to determine hepatic injury. NAC (150 mg/kg, a hepatoprotection agent, was administered before surgery. We hypothesized that the mechanism of NAC may involve the ROS/JNK/Bcl-2 pathway. We evaluated the expression of JNK, P-JNK, Bcl-2, Beclin 1 and LC3 by western blotting and immunohistochemical staining. Autophagosomes were evaluated by transmission electron microscopy (TEM. RESULTS: We found that ALT, AST and pathological changes were significantly improved in the NAC group. Western blotting analysis showed that the expression levels of Beclin 1 and LC3 were significantly decreased in NAC-treated mice. In addition, JNK, p-JNK, Bax, TNF-α, NF-κB, IL2, IL6 and levels were also decreased in NAC-treated mice. CONCLUSION: NAC can prevent HIRI-induced autophagy and apoptosis by influencing the JNK signal pathway. The mechanism is likely to involve attenuation of JNK and p-JNK via scavenged ROS, an indirect increase in Bcl-2 level, and finally an alteration in the balance of Beclin 1 and Bcl-2.

  8. [The application of n-acetylcysteine as an antioxidant and mucolytic in mechanical ventilation in intensive care patients. A prospective, randomized, placebo-controlled, double-blind study].

    Konrad, F; Schoenberg, M H; Wiedmann, H; Kilian, J; Georgieff, M


    Oxygen radicals and oxygen radial mediators are thought to be important components in the development of acute lung injury, sepsis, and multiple organ failure. Injured patients, patients with pulmonary diseases, and multiple trauma patients also showed an elevated lipid peroxidation, indicating increased oxidant stress. N-Acetylcysteine (NAC) has been used as an antioxidant in a wide variety of experiments. NAC has been suggested to act by raising concentrations of cysteine, and hence glutathione, and by scavenging of oxidant species [1, 11, 17, 29]. The present study was designed to investigate whether the application of NAC in intubated patients has an effect on concentrations of reduced glutathione in plasma and bronchoalveolar lavage fluid (BAL) and on the lipid peroxidation products malondialdehyde and conjugated dienes. Because NAC has been widely used as a mucolytic drug for the treatment of lung diseases, the influence on tracheobronchial mucus was studied, too. METHODS. In a randomized, double-blind, placebo-controlled study, a total of 38 long-term ventilated patients of a surgical intensive care unit were investigated. Patients were treated for 5 days with either 3 g NAC/day or placebo. The plasma concentration of reduced glutathione, malondialdehyde, and conjugated dienes were measured on admission and on the 3rd and 5th days of treatment [8, 34, 48]. Additionally, the numbers of tracheobronchial suctionings were registered and chest radiographs were evaluated. A fibre-bronchoscopy was performed on admission and on the 3rd day of treatment. The amount and viscidity of tracheobronchial secretions were examined semiquantitatively, and glutathione levels were measured in the unconcentrated BAL. The study was approved by the ethics committee of the University of Ulm. RESULTS. The two groups were comparable with respect to age, sex, APACHE II score and diagnosis (Table 1). We found no significant differences in reduced glutathione levels in the plasma or in

  9. N-acetylcysteine instead of theophylline in patients with COPD who are candidates for elective off-pump CABG surgery: Is it possible in cardiovascular surgery unit?

    Seyed Jalil Mirhosseini


    Full Text Available Background: Forced expiratory volume in one second (FEV1 is a good predictor of chronic obstructive pulmonary disease (COPD. COPD is characterized by a chronic limitation of airflow. This study was designed to compare the effects and complications of theophylline alone, N-acetylcysteine (NAC alone, and a combination of the two drugs on the rates of FEV1 in patients with COPD who were candidates for off-pump coronary artery bypass graft (CABG surgery. Methods: This clinical trial was performed on 100 patients who had a smoking history of 27 pack years with a range of 20 to 40 pack years but were not heavy smokers and were candidates for elective off-pump CABG surgery in Afshar Cardiovascular Hospital, Yazd, Iran. The patients with a history of asthma and bronchospasm and non-COPD respiratory disorders were excluded. There were three groups, that is, the theophylline group (n=33 that received theophylline 10 mg/kg TDS after consumption of food, NAC group (n=33 who received NAC 10-15 mg/kg BD after consumption of food, and the combined group (n=32 who received theophylline and NAC together. Data were analyzed by analysis of variance (ANOVA, Chi-square, and exact test for quantitative and qualitative variables. Results: One hundred patients with COPD enrolled in this study as possible candidates for CABG surgery. Average age of the patients was 60.36±10.21 years. Of the participants, 83 (83.3% were male and 17 (17% were female. Rate of postoperative FEV1 to basal FEV1 was 0.76±0.32, 0.66±0.22, and 0.69±0.24 in the treatments with theophylline, NAC, and the combination, respectively. Theophylline, NAC, and a combination of these drugs can decrease the rate of postoperative FEV1 compared to basal FEV1 significantly. (P=0.0001 Conclusion: Theophylline alone, NAC alone, and a combination of these drugs improve pulmonary function, and there are no significant differences between these protocols. Stomach discomfort and cardiac complications in

  10. Identification of a mechanism by which the methylmercury antidotes N-acetylcysteine and dimercaptopropanesulfonate enhance urinary metal excretion: transport by the renal organic anion transporter-1.

    Koh, Albert S; Simmons-Willis, Tracey A; Pritchard, John B; Grassl, Steven M; Ballatori, Nazzareno


    N-Acetylcysteine (NAC) and dimercaptopropanesulfonate (DMPS) are sulfhydryl-containing compounds that produce a dramatic acceleration of urinary methylmercury (MeHg) excretion in poisoned animals, but the molecular mechanism for this effect is unknown. NAC and DMPS are themselves excreted in urine in high concentrations. The present study tested the hypothesis that the complexes formed between MeHg and these anionic chelating agents are transported from blood into proximal tubule cells by the basolateral membrane organic anion transporters (Oat) 1 and Oat3. Xenopus laevis oocytes expressing rat Oat1 showed increased uptake of [(14)C]MeHg when complexed with either NAC or DMPS but not when complexed with L-cysteine, glutathione, dimercaptosuccinate, penicillamine, or gamma-glutamylcysteine. In contrast, none of these MeHg complexes were transported by Oat3-expressing oocytes. The apparent K(m) values for Oat1-mediated transport were 31 +/- 2 microM for MeHg-NAC and 9 +/- 2 microM for MeHg-DMPS, indicating that these are relatively high-affinity substrates. Oat1-mediated uptake of [(14)C]MeHg-NAC and [(14)C]MeHg-DMPS was inhibited by prototypical substrates for Oat1, including p-aminohippurate (PAH), and was trans-stimulated when oocytes were preloaded with 2 mM glutarate but not glutamate. Conversely, efflux of [(3)H]PAH from Oat1-expressing oocytes was trans-stimulated by glutarate, PAH, NAC, DMPS, MeHg-NAC, MeHg-DMPS, and a mercapturic acid, indicating that these are transported solutes. [(3)H]PAH uptake was competitively inhibited by NAC (K(i) of 2.0 +/- 0.3 mM) and DMPS (K(i) of 0.10 +/- 0.02 mM), providing further evidence that these chelating agents are substrates for Oat1. These results indicate that the MeHg antidotes NAC and DMPS and their mercaptide complexes are transported by Oat1 but are comparatively poor substrates for Oat3. This is the first molecular identification of a transport mechanism by which these antidotes may enhance urinary excretion of

  11. N-acetylcysteine increases the frequency of bone marrow pro-B/pre-B cells, but does not reverse cigarette smoking-induced loss of this subset.

    Victoria L Palmer

    Full Text Available BACKGROUND: We previously showed that mice exposed to cigarette smoke for three weeks exhibit loss of bone marrow B cells at the Pro-B-to-pre-B cell transition, but the reason for this is unclear. The antioxidant N-acetylcysteine (NAC, a glutathione precursor, has been used as a chemopreventive agent to reduce adverse effects of cigarette smoke exposure on lung function. Here we determined whether smoke exposure impairs B cell development by inducing cell cycle arrest or apoptosis, and whether NAC treatment prevents smoking-induced loss of developing B cells. METHODOLOGY/PRINCIPAL FINDINGS: Groups of normal mice were either exposed to filtered room air or cigarette smoke with or without concomitant NAC treatment for 5 days/week for three weeks. Bone marrow B cell developmental subsets were enumerated, and sorted pro-B (B220(+CD43(+ and pre-B (B220(+CD43(- cell fractions were analyzed for cell cycle status and the percentage of apoptotic cells. We find that, compared to sham controls, smoke-exposed mice have ∼60% fewer pro-B/pre-B cells, regardless of NAC treatment. Interestingly, NAC-treated mice show a 21-38% increase in total bone marrow cellularity and lymphocyte frequency and about a 2-fold increase in the pro-B/pre-B cell subset, compared to sham-treated controls. No significant smoking- or NAC-dependent differences were detected in frequency of apoptotic cells or the percentage cells in the G1, S, or G2 phases of the cycle. CONCLUSIONS/SIGNIFICANCE: The failure of NAC treatment to prevent smoking-induced loss of bone marrow pre-B cells suggests that oxidative stress is not directly responsible for this loss. The unexpected expansion of the pro-B/pre-B cell subset in response to NAC treatment suggests oxidative stress normally contributes to cell loss at this developmental stage, and also reveals a potential side effect of therapeutic administration of NAC to prevent smoking-induced loss of lung function.

  12. Organic Anion Transporter 5 (Oat5) Urinary Excretion Is a Specific Biomarker of Kidney Injury: Evaluation of Urinary Excretion of Exosomal Oat5 after N-Acetylcysteine Prevention of Cisplatin Induced Nephrotoxicity.

    Bulacio, Romina Paula; Anzai, Naohiko; Ouchi, Motoshi; Torres, Adriana Mónica


    Cisplatin is a commonly used chemotherapeutic agent. Its main side-effect is nephrotoxicity. It was reported that the organic anion transporter 5 (Oat5) urinary excretion is elevated, implying renal perturbation, when no modifications of traditional markers of renal damage are still observed in cisplatin-induced acute kidney injury (AKI). It was also demonstrated that Oat5 is excreted in urine by the exosomal pathway. This study was designated to demonstrate the specific response of the urinary excretion of exosomal Oat5 to kidney injury independently of other cisplatin toxic effects, in order to strengthen Oat5 urinary levels as a specific biomarker of AKI. To accomplish that aim, we evaluated if urinary excretion of exosomal Oat5 returns to its basal levels when cisplatin renal damage is prevented by the coadministration of the renoprotective compound N-acetylcysteine. Four days after cisplatin administration, AKI was induced in cisplatin-treated male Wistar rats (Cis group), as it was corroborated by increased urea and creatinine plasma levels. Tubular damage was also observed. In cotreated animals (Cis + NAC group), plasma urea and creatinine concentrations tended to return to their basal values, and tubular damage was improved. Urinary excretion of exosomal Oat5 was notably increased in the Cis group, but when renal injury was ameliorated by N-acetylcysteine coadministration, that increase was undetected. So, in this work we observed that urinary excretion of exosomal Oat5 was only increased if renal insult is produced, demonstrating its specificity as a renal injury biomarker.

  13. Effect of N-Acetylcysteine on Mortality and Liver Transplantation Rate in Non-Acetaminophen-Induced Acute Liver Failure: A Multicenter Study.

    Darweesh, Samar K; Ibrahim, Mona F; El-Tahawy, Mahmoud A


    Previous studies and systematic reviews have not provided conclusive evidence on the effect of N-acetylcysteine (NAC) in non-acetaminophen-induced acute liver failure (NAI-ALF). We aimed to study the value of intravenous NAC in reducing liver transplantation and mortality in NAI-ALF. In a prospective, multicenter, observational study, acute liver failure patients without clinical or historical evidence of acetaminophen overdose were enrolled. NAC infusion (in empirical dose) was given as 150 mg/kg in 100 ml dextrose 5% over half an hour, then 70 mg/kg in 500 ml dextrose 5% over 4 h, then 70 mg/kg in 500 ml dextrose 5% over 16 h. Thereafter continuous infusion was administered over 24 h of 150 mg/kg in 500 ml dextrose 5% until up to two consecutive normal international normalized ratios (INRs) were obtained. Our endpoints were recovery, transplantation, or death. The primary outcome of the study was to assess reduction in mortality or liver transplantation. The secondary outcome was the evaluation of other clinical outcomes (length of ICU and hospital stays, organ system failure, and hepatic encephalopathy). The study included a total of 155 adults; the NAC group (n = 85) were given NAC between January 2011 to December 2013 and the control group (n = 70) were not given NAC and were included from files dating between 2010 and 2011. Both groups (before NAC) were comparable with regard to etiology, age, sex, smoking, presence of co-morbidities, encephalopathy, liver profile, and INR. The success rate (transplant-free survival) in the NAC group was 96.4%. While in the control group, 17 patients (23.3%) recovered and 53 (76.6%) did not recover, of these 37 (53.3%) had liver transplantation and 16 (23.3%) died (p < 0.01). The NAC group had significantly shorter hospital stays (p < 0.001), less encephalopathy (p = 0.02), and less bleeding (p < 0.01) than the control group. The control group reported a higher ICU admission (p = 0.01) rate and

  14. Chelating capacity and the adverse effects of two treatments (N-acetylcysteine and D-penicillamine in patients with mercury poisoning in Segovia, a municipality at the northeastern part of Antioquia, Colombia

    Fanny Cuesta González


    Full Text Available

    OBJECTIVE: to compare the chelating capacity and the adverse effects of treatments with either Nacetylcysteine or D-penicillamine in patients with mercury poisoning in Segovia, a municipality at the northeastern part of Antioquia, Colombia.

    METHODS: 50 patients with toxic levels of mercury were enrolled in a 10 days open label, randomized comparison of either D-penicillamine (750 mg/day or Nacetilcysteine (1.8 g/day. Patients were followed on a daily basis to assess the elimination of mercury in urine and the frequency of adverse effects of each treatment.

    RESULTS: 32 patients completed 10 days of drug treatment. Averages of mercury elimination in 24 hours urine, before and after treatment with D-penicillamine and N-acetylcysteine, were not different (211.96 mcg ± 190 and 262.15 mcg ± 305 and 232.85 mcg ± 248 and 218.65 mcg ± 240, respectively, P > 0.05 for all comparisons. Evaluation of the frequency of adverse effects showed a significant difference between the two groups: D-penicillamine (50% and N-acetylcysteine (11% p = 0.0079.

    CONCLUSION: this study

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

    Faintuch, B L


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

  16. Role of N-acetylcysteine on fibrosis and oxidative stress in cirrhotic rats Papel da N-acetilcisteína na fibrose e estresse oxidativo em ratos cirróticos

    Gustavo Pereira-Filho


    Full Text Available BACKGROUND: 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. AIM: 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. METHODS: The animals were randomly in three experimentals 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. RESULTS: 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. CONCLUSION: N-acetylcysteine seams to offer protection against hepatic fibrosis and oxidative stress in cirrhotic rat livers.RACIONAL: A cirrose é o estágio final da disfunção hepática, sendo caracterizada por fibrose difusa, que compõe a resposta principal do organismo ao dano hepático. O tetracloreto de carbono inalatório é um modelo experimental efetivo, que desencadeia a cirrose e permite obter modificações histológicas e fisiológicas similares às vistas em humanos. OBJETIVO: Investigar os efeitos da N-acetilcisteina (NAC sobre a fibrose e o estresse oxidativo no fígado de ratos cirróticos, analisando as provas hepáticas, a lipoperoxidação, a atividade da enzima

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

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


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

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

    Cristiane Kayser


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

  19. Effect of N-acetylcysteine on pulmonary cell death in a controlled hemorrhagic shock model in rats Efeito da N-acetilcisteína na morte celular pulmonar em um modelo de choque hemorrágico controlado em ratos

    Paulo Fernandes Saad


    Full Text Available PURPOSE: To evaluate the effect of N-acetylcysteine (NAC combined with fluid resuscitation on pulmonary cell death in rats induced with controlled hemorrhagic shock (HS. METHODS: Two arteries (MAP calculation and exsanguination and one vein (treatments were catheterized in 22 anesthetized rats. Two groups of male albino rats were induced with controlled HS at 35mmHg MAP for 60 min. After this period, the RL group was resuscitated with Ringer's lactate and the RL+NAC group was resuscitated with Ringer's lactate combined with 150mg/Kg NAC. The control group animals were cannulated only. The animals were euthanized after 120 min of fluid resuscitation. Lung tissue samples were collected to evaluate the following: histopathology, TUNEL and imunohistochemical expression of caspase 3. RESULTS: RL showed a greater number of cells stained by TUNEL than RL + NAC, but there was no change in caspase 3 expression in any group. CONCLUSION: N-acetylcysteine associate to fluid resuscitation, after hemorrhagic shock, decreased cell death attenuating lung injury.OBJETIVO: Avaliar o efeito da N-acetilcisteína (NAC combinada ao fluido de reposição volêmica na morte celular pulmonar de ratos submetidos ao choque hemorrágico (CH controlado. MÉTODOS: Duas artérias (cálculo da PAM e exsanguinação e uma veia (tratamentos foram cateterizadas em 22 ratos anestesiados. Dois grupos de ratos machos albinos foram induzidos ao CH controlado com PAM de 35mmHg por 60 min. Após este período, o grupo RL foi ressuscitado com Ringer lactato e o grupo RL+NAC foi ressuscitado com Ringer lactato associado com 150mg/Kg de NAC. O grupo controle sofreu somente o procedimento cirúrgico de cateterização. Os animais sofreram eutanásia após 120 min. da ressuscitação. Amostras de tecido pulmonar foram coletadas para histopatologia, TUNEL e a imuno-expressão da caspase 3. RESULTADOS: RL apresentou maior número de células marcadas pelo TUNEL do que RL+NAC, porém sem

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

    Natália Valadares de Moraes


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

  1. Nephroprotective Effects of N-Acetylcysteine Amide against Contrast-Induced Nephropathy through Upregulating Thioredoxin-1, Inhibiting ASK1/p38MAPK Pathway, and Suppressing Oxidative Stress and Apoptosis in Rats

    Duan, Yiru; Zheng, Junli; Wang, Yiquan; Wang, Guohua; Norgren, Svante; Hei, Tom K.


    Contrast-induced nephropathy (CIN) is a leading cause of hospital-acquired acute kidney injury (AKI) due to apoptosis induced in renal tubular cells. Our previous study demonstrated the novel N-acetylcysteine amide (NACA); the amide form of N-acetyl cysteine (NAC) prevented renal tubular cells from contrast-induced apoptosis through inhibiting p38 MAPK pathway in vitro. In the present study, we aimed to compare the efficacies of NACA and NAC in preventing CIN in a well-established rat model and investigate whether thioredoxin-1 (Trx1) and apoptosis signal-regulating kinase 1 (ASK1) act as the potential activator for p38 MAPK. NACA significantly attenuated elevations of serum creatinine, blood urea nitrogen, and biomarkers of AKI. At equimolar concentration, NACA was more effective than NAC in reducing histological changes of renal tubular injuries. NACA attenuated activation of p38 MAPK signal, reduced oxidative stress, and diminished apoptosis. Furthermore, we demonstrated that contrast exposure resulted in Trx1 downregulation and increased ASK1/p38 MAPK phosphorylation, which could be reversed by NACA and NAC. To our knowledge, this is the first report that Trx1 and ASK1 are involved in CIN. Our study highlights a renal protective role of NACA against CIN through modulating Trx1 and ASK1/p38 MAPK pathway to result in the inhibition of apoptosis among renal cells. PMID:28105252

  2. Meta-analysis of N-acetylcysteine on prevention of contrast-induced nephropathy%乙酰半胱氨酸预防造影剂肾病疗效的荟萃分析

    龚颖倩; 徐石张; 黄天伦; 徐高四


    Objective To investigate the efficacy of N-acetylcysteine on prevention of contrast -induced nephropathy (CIN).Methods According to the regulation of evidence-based medicine,the selection criteria,elimination criteria and search strategy were defined.PubMed,Cochrane Library,Wiley Online Library and Google Scholar were searched.The literature limited range was from January 2000 to December 2011.Two investigators extracted the data independently from all the studies that accorded with selection criteria using a suitable form.All the statistical analyses were performed with RevMan version 5.1.Results A total of 151 potential literatures were screened and 16 remained literatures (including 4588 patients) were identified to accord with the criteria in this meta-analysis.In 14 literatures,the Jadad score was 3 at least.The meta-analysis of 16 trials showed N-acetylcysteine could prevent CIN from happening [odds ratio (OR)=0.65,95% CI 0.46-0.92,P=0.01].In the groups of average Scr baseline < 132.6 μmol/L,result displayed the OR of incidence associated with Nacetylcysteine for prevention of CIN was 0.93 (95% CI 0.75-1.15,P=0.49).In the groups of average Scr baseline ≥ 132.6 μmol/L,the OR for N-acetylcysteine associated with incidence of CIN was 0.52 (95% CI 0.30-0.93,P=0.03).Conclusion There is specific effect that N-acetylcysteine prevents CIN from happening in the groups of average Scr baseline ≥ 132.6 μmol/L.%目的 系统评价乙酰半胱氨酸(NAC)对造影剂肾病的预防疗效.方法 按循证医学的要求,制定相应的纳入标准、排除标准及检索策略,检索PubMed、Cochrane Library、Wiley Online Library、Google Scholar电子数据库,检索时限为2000年至2011年,获得NAC预防造影剂肾病的相关文献.由2位研究者根据纳入和排除标准独立选择符合标准的随机对照试验(RCT)并提取相关数据.采用RevMan 5.1软件进行荟萃分析.结果 初步检索出151篇相关文献,有16

  3. Nephroprotective Effects of N-Acetylcysteine Amide against Contrast-Induced Nephropathy through Upregulating Thioredoxin-1, Inhibiting ASK1/p38MAPK Pathway, and Suppressing Oxidative Stress and Apoptosis in Rats

    Xuezhong Gong


    Full Text Available Contrast-induced nephropathy (CIN is a leading cause of hospital-acquired acute kidney injury (AKI due to apoptosis induced in renal tubular cells. Our previous study demonstrated the novel N-acetylcysteine amide (NACA; the amide form of N-acetyl cysteine (NAC prevented renal tubular cells from contrast-induced apoptosis through inhibiting p38 MAPK pathway in vitro. In the present study, we aimed to compare the efficacies of NACA and NAC in preventing CIN in a well-established rat model and investigate whether thioredoxin-1 (Trx1 and apoptosis signal-regulating kinase 1 (ASK1 act as the potential activator for p38 MAPK. NACA significantly attenuated elevations of serum creatinine, blood urea nitrogen, and biomarkers of AKI. At equimolar concentration, NACA was more effective than NAC in reducing histological changes of renal tubular injuries. NACA attenuated activation of p38 MAPK signal, reduced oxidative stress, and diminished apoptosis. Furthermore, we demonstrated that contrast exposure resulted in Trx1 downregulation and increased ASK1/p38 MAPK phosphorylation, which could be reversed by NACA and NAC. To our knowledge, this is the first report that Trx1 and ASK1 are involved in CIN. Our study highlights a renal protective role of NACA against CIN through modulating Trx1 and ASK1/p38 MAPK pathway to result in the inhibition of apoptosis among renal cells.

  4. The add-on N-acetylcysteine is more effective than dimethicone alone to eliminate mucus during narrow-band imaging endoscopy: a double-blind, randomized controlled trial.

    Chen, Ming-Jen; Wang, Horng-Yuan; Chang, Chen-Wang; Hu, Kuang-Chun; Hung, Chien-Yuan; Chen, Chih-Jen; Shih, Shou-Chuan


    Recent studies have shown that pronase can improve mucosal visibility, but this agent is not uniformly available for human use worldwide. This study aimed to assess the efficacy of N-acetylcysteine (NAC), a mucolytic agent, in improving mucus elimination as measured by decreased endoscopic water flushes during narrow-band imaging (NBI) endoscopy. A consecutive series of patients scheduled for upper gastrointestinal endoscopy at outpatient clinics were enrolled in this double-blind, randomized controlled trial. The control group drank a preparation of 100 mg dimethicone (5 ml at 20 mg/ml) plus water up to 100 ml, and the NAC group drank 300 mg NAC plus 100 mg dimethicone and water up to 100 ml. During the endoscopy, the endoscopist used as many flushes of water as deemed necessary to produce a satisfactory NBI view of the entire gastric mucosa. In all, 177 patients with a mean age of 51 years were evaluated in this study. Significantly lesser water was used for flushing during NBI endoscopy for the NAC group than the control group; 40 ml (30-70, 0-120) versus 50 ml (30-100, 0-150) (median (interquartile range, range), p = 0.0095). Considering the safety profile of NAC, decreasing the number of water flushes for optimal vision and unavailability of pronase in some areas, the authors suggest the use of add-on NAC to eliminate mucus during NBI endoscopy.

  5. A simple method for measuring thickness of the mucus gel layer adherent to rat, frog and human gastric mucosa: influence of feeding, prostaglandin, N-acetylcysteine and other agents.

    Kerss, S; Allen, A; Garner, A


    1. A technique has been developed for measuring thickness of the gastric surface mucus gel layer. Mucosal sections (1.6 mm) were cut from frog and rat stomach and human antrum, mounted transversely and viewed by an inverse microscope (x 200 magnification) under dark field illumination or phase contrast. The mucus layer was readily distinguishable and its dimensions could be recorded by means of an eyepiece graticule. 2. Mean mucus gel thickness in rat, frog was 73, 76, 55 and 192 micrometer respectively. However, there was variation in the average thickness of the gel layer between individual mucosae from the same species (up to twofold). Mucus thickness between adjacent regions of the same mucosal section also varied markedly (up to tenfold). 3. Topical administration of 16,16-dimethylprostaglandin E2 by oral intubation caused a significant increase in thickness in both rat and frog at doses of 5 microgram/ml and 0.5 microgram/ml respectively. Feeding and exposure of the mucosa to N-acetylcysteine (10-20%, w/v) produced variable effects whereas pepsin (1 mg/ml) caused a marked reduction in thickness of the surface gel layer in both rat and frog. 4. The technique provides a rapid and simple method for determining gastrointestinal mucus thickness in relation to mucosal morphology. It is ideally suited for studying the control of mucus secretion and effect of drugs.

  6. The effect of N-acetylcysteine (NAC) on liver and renal tissue inducible nitric oxide synthase (iNOS) and tissue lipid peroxidation in obstructive jaundice stimulated by lipopolysaccharide (LPS).

    Cağlikülekci, Mehmet; Pata, Cengiz; Apa, Duygu Dusmez; Dirlik, Musa; Tamer, Lulufer; Yaylak, Faik; Kanik, Arzu; Aydin, Suha


    Morbidity and mortality rates are very high in obstructive jaundice when it is associated with sepsis and multiple organ failure. Nitric oxide (NO) formation and increased expression of inducible nitric oxide synthase (iNOS) also take place in obstructive jaundice (OJ). N-Acetylcysteine (NAC) has a beneficial effect by demonstrating anti-inflammatory activity such as inhibits cytokine expression/release, inhibiting the adhesion molecule expression and inhibiting nuclear factor kappa B (NFkappaB). The aim of this study was to investigate the effects of NAC on liver and renal tissue iNOS, and liver tissue lipid peroxidation in lipopolysaccharide (LPS) induced obstructive jaundice. We randomized 48 rats into six groups. Group A: Sham group; group B: OJ group; group C: OJ+NAC; group D: OJ+LPS (Escherichia coli LPS serotype L-2630, 100mg, Sigma) group E: OJ+NAC+LPS; group F: OJ+LPS+NAC. NAC was started subcutaneously 100mg/kg. LPS was injected intraperitoneally and then at the tenth day we sacrificed the rats. Liver malondialdehyde (MDA) increased and liver ATPase decreased in groups B-D when compared to group A. After the administration of NAC (groups C-E), liver MDA levels decreased, tissue ATPase levels increased as compared to other groups. The liver and renal tissue iNOS expression was increased in groups B, D, and F. After the administration of NAC (groups C-E) the liver and renal tissue iNOS expression were decreased. Our results indicated that NAC prevented the deleterious effects of LPS in OJ by reducing iNOS expression via lipid peroxidation in liver and renal tissue; if it was administrated before LPS. But NAC failed to prevent the iNOS expression and lipid peroxidation if there was established endotoxemia in OJ.

  7. A systematic review and meta-analysis of the efficacy and safety of N-acetylcysteine in preventing aminoglycoside-induced ototoxicity: implications for the treatment of multidrug-resistant TB.

    Kranzer, Katharina; Elamin, Wael F; Cox, Helen; Seddon, James A; Ford, Nathan; Drobniewski, Francis


    Ototoxicity is a severe side effect of aminoglycoside antibiotics. Aminoglycosides are recommended for the treatment of multidrug-resistant TB (MDR-TB). N-Acetylcysteine (NAC) appears to protect against drug- and noise-induced hearing loss. This review aimed to determine if coadministering NAC with aminoglycoside affected ototoxicity development, and to assess the safety and tolerability of prolonged NAC administration. Eligible studies reported on the efficacy of concomitant NAC and aminoglycoside administration for ototoxicity prevention or long-term (≥ 6 weeks) administration of NAC regardless of indication. Pooled estimates were calculated using a fixed-effects model. Heterogeneity was assessed using the I(2) statistic. Three studies reported that NAC reduced ototoxicity in 146 patients with end-stage renal failure receiving aminoglycosides. Pooled relative risk for otoprotection at 4-6 weeks was 0.14 (95% CI 0.05 to 0.45), and the risk difference was -33.3% (95% CI 45.5% to 21.2%). Eighty-three studies (N=9988) described the administration of NAC for >6 weeks. Abdominal pain, nausea and vomiting, diarrhoea and arthralgia were increased 1.4-2.2 times. This review provides evidence for the safety and otoprotective effect of NAC when coadministered with aminoglycoside. It represents a strong justification for a clinical trial to investigate the effect of concomitant NAC treatment in patients receiving aminoglycosides as part of MDR-TB treatment. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to

  8. N-acetylcysteine inhibits activation of toll-like receptor 2 and 4 gene expression in the liver and lung after partial hepatic ischemia-reper fusion injur y in mice

    Xin Jin; Lin Wang; He-Shui Wu; Lei Zhang; Chun-You Wang; Yuan Tian; Jing-Hui Zhang


    BACKGROUND: Toll-like receptor 2 and 4 (TLR2/4) may play important roles in ischemia-reperfusion (I/R) injury, and N-acetylcysteine (NAC) can prevent the generation of reactive oxygen species (ROS) induced by I/R injury. This study aimed to investigate the changes in TLR2/4 gene expression in the liver and lung after I/R injury with or without NAC pretreatment. METHODS:BALB/c mice were used in a model of partial hepatic I/R injury and randomly assigned to a sham-operated control group (SH), a hepatic ischemia/reperfusion group (I/R) or a NAC pretreated, hepatic I/R group (I/R-NAC). The levels of TNF-α in the portal vein and plasma alanine aminotransferase (ALT) were measured at 1 and 3 hours after reperfusion. The lung wet-to-dry ratio was measured, and the expression of TLR2/4 mRNA and protein in the liver and lung were assessed with RT-PCR and Western blotting at the same time points. RESULTS: Compared with the I/R group, the expression of TLR2/4 mRNA and protein in the liver and lung in the I/R-NAC group was decreased at the same time point (P CONCLUSIONS:TLR2/4 was activated in the liver and lung in the process of partial hepatic I/R injury. NAC inhibited the activation of TLR2/4 and the induction of TNF-αresulting from I/R injury via modulating the redox state, thus it may mitigate liver and lung injury following partial hepatic I/R in mice.

  9. The combination effects of acetaminophen and N-acetylcysteine on cytokines production and NF-κB activation of lipopolysaccharide-challenged piglet mononuclear phagocytes in vitro and in vivo.

    Qiu, Yinsheng; Zhang, Jiawei; Liu, Yu; Ma, Hongwei; Cao, Fangyuan; Xu, Jun; Hou, Yongqing; Xu, Lingyun


    Lipopolysaccharide (LPS) is a known activator of mononuclear phagocytes. LPS activates the pro-inflammatory gene expression and induces the release of mediators/cytokines by TLR4-NF-κB signaling pathway. The purpose of this study was to investigate the effects of acetaminophen (AAP) and N-acetylcysteine (NAC), individually as well as in combination on LPS-induced cytokines production and NF-κB activation in piglets. AAP (0.125-1.0mM) and NAC (0.0625-1.0mM) down-regulate the expression of cytokines and inhibit NF-κB p65 protein transfer from the cytoplasm to the nucleus in vitro. NAC enhances the inhibition action of AAP on cytokines expression in vitro. IL-6 in piglet plasma of the AAP group (mixed feed concentration of 600 mg/kg) was significantly reduced (Ppiglet plasma of the NAC group (mixed feeding concentration of 1200 mg/kg) were significantly lower at 3h after LPS stimulation (Ppiglet plasma of AAP (mixed feed concentration of 600 mg/kg) plus NAC (mixed feeding concentration of 1200 mg/kg) group were significantly lower (P<0.05) at 3h after LPS activation. The level of IL-10 in the group with AAP plus NAC was significantly lower (P<0.05) at 24h after LPS stimulation, while the rest of the inflammatory cytokines were returned to the original levels. The NF-κB p65 concentration ratio had significantly reduced (P<0.05) when AAP and NAC were used in combination. In summary, NAC could enhance the anti-inflammatory effects of AAP both in vitro and in vivo.

  10. The effect of N-acetylcysteine on the airway inflammation and remodeling of obese asthma mice%乙酰半胱氨酸对肥胖哮喘小鼠气道炎症和重建的作用

    韩伟; 李双保; 唐华平; 陈凯; 苏毅


    Objectives To evaluate the effect of N-Acetylcysteine on the airway inflammation and remodeling of obese asthma mice with high-fat diets. Methods Forty female C57BL/6J mice were randomly divided into 4 groups, asthma group (A), obese asthma group (B), treatment group (C) and normal control group (D). Group A were sensitized and challenged by ovalbum (OVA) and normal diets. Group B were sensitized and challenged as group A but fed with high-fat diets, while group C were sensitized, challenged and fed as group B, but administrated N-Acetylcysteine 200 mg/kg. d from the third week after challenge. The cells in BALF were counted and classified after staining, IL-6 and 8-iso-PGF2α(8-iso-PGF2α) in lung tissues were detected by ELISA. WAt, WAm, Pbm, as the remodeling indices, measured in lung pathological section. All parameters were compared among 4 groups. Results In comparison with group D, the leukocytes and EOS in BALF, WAt/Pbm, WAm/Pbm in lung section were increased as well as IL-6 and 8-iso-PGF2α in lung tissue elevated in group A and group B, while the maximum changes were observed in group B (P <0. 05). After NAC treatment, the IL-6, 8-iso-PGF2α and WAt/ Pbm were decreased significantly (P <0. 05). Pearson correlation analysis showed that WAt/Pbm and IL-6 were in positive correlation with 8-iso-PGF2α (r =0. 817, 0. 737, P <0. 01). Conclusions N-Acetylcysteine can alleviate the airway inflammation and remodel reaction of asthma by a substantial inhibition of the oxidative stress reaction in lung.%目的 探讨乙酰半胱氨酸对哮喘气道炎症和重建的影响.方法 60只雌性C57/6J小鼠按随机数字表法分为哮喘组(A组),肥胖哮喘组(B组),治疗组(C组),对照组(D组),每组15只.经腹腔注射与雾化吸入卵蛋白(OVA)制作慢性哮喘模型,高脂饮食制造肥胖模型.计数支气管肺泡灌洗液(BALF)中细胞总数及分类,ELISA法测定肺组织匀浆中IL-6和8-异前列腺素F2α(8-iso-PGF2α)水平,肺组织切

  11. Die Cerebrale Toxoplasmose bei AIDS : Untersuchungen zur Pharmakokinetik von Sulfadiazin unter Urinalkalisierung

    Väth, Thomas


    Die cerebrale Toxoplasmose stellt eine wichtige opportunistische Infektion im Verlauf einer HIV-Infektion dar. Unter der Standardtherapie mit Sulfadiazin kommt es häufig zu nephrotoxischen Nebenwirkungen aufgrund einer Kristallisation des Sulfadiazin und seines Metaboliten N4-Acetylsulfadiazin im Harntrakt. Die Therapie dieser Nebenwirkung erfordert unter Anderem die Alkalisierung des Harns. In der vorliegenden Arbeit wurde der Einfluss einer Urinalkalisierung auf die Pharmakokinetik beider S...

  12. Nächtliche diastolische Hypotonie unter antihypertensiver Therapie im Alter

    Dzien A


    Full Text Available Der positive Einfluß der Behandlung der arteriellen Hypertonie zur Senkung des kardiovaskulären Risikos ist bekannt, insbesondere bei älteren Patienten über 65 Jahre erlebten die anzustrebenden Zielwerte eine ständige Herabsetzung. Zuletzt wurden auch kritische Stimmen laut, die bei zu schneller und tiefgehender Senkung - vor allem des diastolischen Blutdruckes - eine Erhöhung des Risikos für kardiovaskuläre Erkrankungen erkennen lassen. Der Grund unserer Untersuchung war, die Sicherheit der Praxismessung als Kontrollmethode bei Patienten über 65 Jahre unter antihypertensiver Therapie zu überprüfen. Zu diesem Zwecke wurden bei 117 Patienten mit einer gesicherten kombinierten arteriellen Hypertonie sowohl eine Praxisblutdruckmessung als auch eine 24 h-Blutdruckmessung durchgeführt. Aus unserer Untersuchung geht hervor, daß vor allem bei über 65 Jahre alten Patienten die routinemäßig durchgeführte Praxismessung keine ausreichende Sicherheit über die tatsächliche medikamentöse Blutdruckbeeinflussung gibt.

  13. Activation of mGluR2/3 underlies the effects of N-acetylcystein on amygdala-associated autism-like phenotypes in a valproate-induced rat model of autism

    Yu-Wen eChen


    Full Text Available Autism-like phenotypes in male valproate (VPA-exposed offspring have been linked to high glutamatergic neurotransmission in the thalamic-amygdala pathway. Glial cystine/glutamate exchange (system Xc-, which exchanges extracellular cystine for intracellular glutamate, plays a significant role in the maintenance of extracellular glutamate. N-acetylcysteine (NAC is a cystine prodrug that restores extracellular glutamate by stimulating system Xc-. In this study, we examined the effects of NAC on autism-like phenotypes and neurotransmission in the thalamic–amygdala synapses, as well as the involvement of metabotropic glutamate receptors 2/3 (mGluR2/3. Valproate-treated rats received a single intraperitoneal injection of 500 mg/kg NaVPA on E12.5. On postnatal day 21 (P21, NAC or saline was administered once daily for 10 days. From day 8 to 10, NAC was given 1/2 hour prior to behavioral testing. Chronic administration of NAC restored the duration and frequency of social interaction and ameliorated anxiety-like behaviors in VPA-exposed offspring. In amygdala slices, NAC treatment normalized the increased frequency of mEPSCs and decreased the paired pulse facilitation (PPF induced by VPA exposure. The effects of NAC on social interaction and anxiety-like behavior in the VPA-exposed offspring were blocked after intra-amygdala infusion of mGluR2/3 antagonist LY341495. The expressions of mGluR2/3 protein and mGluR2 mRNA were significantly lower in the VPA-exposed offspring. In contrast, the mGluR3 mRNA level did not differ between the saline- and VPA-exposed offspring. These results provide the first evidence that the disruption of social interaction and enhanced presynaptic excitatory transmission in VPA-exposed offspring could be rescued by NAC, which depends on the activation of mGluR2/3.

  14. N-acetylcysteine protects H9c2 cells against injuries induced by methyl-glyoxal%N-乙酰半胱氨酸对抗丙酮醛引起的心肌细胞损伤

    董小变; 吴娟; 庄晓东; 黄泽娜; 胡洵; 廖新学


    目的:观察N-乙酰半胱氨酸(N-acetylcysteine, NAC)对抗丙酮醛诱导的H9c2心肌细胞损伤及相关机制。方法:实验分为正常对照组、丙酮醛损伤组(不同浓度丙酮醛处理)、NAC+丙酮醛组( NAC与丙酮醛共处理)、SP600125预处理+丙酮醛组、NAC组和SP600125组。 H9c2心肌细胞常规消化种板,经相应处理24 h后:应用CCK-8法检测心肌细胞的存活率;Western blot法检测H9c2心肌细胞内磷酸化和总的c-Jun氨基端激酶(p-JNK、t-JNK)表达水平;双氯荧光素(DCFH-DA)染色法检测心肌细胞内活性氧(ROS)水平;罗丹明123(Rh123)染色法检测细胞线粒体膜电位( MMP);Hoechst 33258染色法观察H9c2心肌细胞凋亡形态学变化。结果:与对照组相比,不同浓度的丙酮醛均能够降低H9c2心肌细胞存活率,且呈剂量依赖性(P<0.01), NAC在一定浓度范围内(500~1500μmol/L)可对抗丙酮醛引起心肌细胞损伤(P<0.01),抑制丙酮醛引起细胞内ROS水平升高,对抗丙酮醛引起细胞内MMP降低,抑制丙酮醛诱导细胞内JNK蛋白的磷酸化(P<0.01)。与NAC的细胞保护作用类似,选择性JNK抑制剂SP600125也可抑制丙酮醛诱导的细胞损伤,包括减轻氧化应激、改善线粒体膜电位及抑制细胞凋亡。结论:N-乙酰半胱氨酸能够保护H9 c2心肌细胞对抗丙酮醛引起的损伤,其机制可能与其降低细胞内ROS水平、改善MMP、抑制JNK磷酸化和抗凋亡有关。%AIM:To investigate the protective effect of N-acetylcysteine (NAC) on H9c2 cells from injuries induced by methylglyoxal (MG) and the potential mechanism.METHODS:H9c2 cells were divided into control group, MG treatment group, NAC +MG treatment group, SP600125 pretreatment +MG group, NAC group and SP600125 group.The viability of the H9c2 cells was measured by CCK-8 assay.The protein levels of p-JNK and t-JNK were tested by Western blot

  15. N-乙酰半胱氨酸治疗重症肝病的临床疗效研究%Therapeutic efficacy of N-acetylcysteine in treatment of patients with severe liver diseases

    朱婷; 聂青和; 李谨革; 曹义战; 赵保民; 高禄化; 王媛媛; 李汨


    目的:探讨作为转化医学“华丽转身”的典范---N-乙酰半胱氨酸(N-acetylcysteine, NAC)治疗重症肝病的临床疗效及安全性。方法选取HBV感染引起的重症肝病266例,随机分为治疗组136例(其中肝硬化失代偿期87例,肝衰竭49例)和对照组130例(其中肝硬化失代偿期85例,肝衰竭45例)。对266例采取维护肝细胞膜稳定性及肝细胞膜修复(保肝)、抗病毒、合理应用抗生素、营养支持及输注新鲜血浆、全血或人血白蛋白等综合治疗措施,均未使用谷胱甘肽制剂。治疗组加用NAC(8 g,1次/d),治疗45 d为1个疗程。45 d后观察患者的肝功能、终末期肝病模型(model for end-stage liver disease, MELD)评分、Child-Pugh评分及药物不良反应。结果2组症状均有所改善,治疗组治疗45 d后肝功能(部分或全部)等均明显改善,MELD及Child-Pugh评分均明显下降,且改善幅度明显优于对照组(P<0.05)。治疗期间无NAC严重药物不良反应事件。结论 NAC可明显改善重症肝病患者的各项肝功能指标,且无严重不良反应,可在临床上推广应用。%Objective To investigate the therapeutic efficacy and safety of N-acetylcysteine (NAC), which is regarded as the model of “gorgeous turn”of translational medicine, in treatment of patients with severe liver diseases. Methods A total of 266 patients with severe liver diseases due to HBV infection were enrolled in the study, and randomized into a treatment group (n=136, 87 with decompensated liver cirrhosis, and 49 with liver failure) and a control group (n=130, 85 with decompensated liver cirrhosis, and 45 with liver failure). All of the 266 patients were given the comprehensive treatment measures, such as maintaining hepatocyte membrane stable and hepatocyte membrane repair, antiviral therapy, rational use of antibiotics, nutritional support and the trans-fusion of fresh plasma, whole blood

  16. Nefropatia induzida por contraste: avaliação da proteção pela n-acetilcisteína e alopurinol em ratos uninefrectomizados Contrast-induced nephropathy: evaluation of n-acetylcysteine and allopunirol protective effect in uninephrectomized rats

    José Carlos Carraro Eduardo


    Full Text Available OBJETIVO: A nefropatia por contraste é a terceira causa de insuficiência renal aguda em pacientes hospitalizados. O objetivo deste estudo foi avaliar a ação da n-acetilcisteína e do alopurinol na proteção renal em ratos de ambos os sexos que receberam diatrizoato. MATERIAIS E MÉTODOS: Ratos Wistar adultos jovens, uninefrectomizados e submetidos a restrição hídrica, receberam solução salina (grupo 1: machos; grupo 2: fêmeas, diatrizoato (grupo 3: machos; grupo 4: fêmeas, diatrizoato e n-acetilcisteína (grupo 5: machos, diatrizoato e alopurinol (grupo 6: machos e diatrizoato e n-acetilcisteína + alopurinol (grupo 7: machos. A filtração glomerular foi avaliada pela creatinina. O teste t de Student e o teste do sinal foram utilizados para análises estatísticas. RESULTADOS: Ratos que receberam diatrizoato apresentaram elevação estatisticamente significante da creatinina sérica, quando comparados aos controles, porém não houve diferença entre os sexos. Os animais que receberam alopurinol não mostraram aumento significante da creatinina, enquanto a administração de n-acetilcisteína não impediu a elevação da creatinina. CONCLUSÃO: O alopurinol mostrou-se mais efetivo que a n-acetilcisteína na proteção funcional renal ao dano induzido pelo diatrizoato de sódio. Não houve diferença entre os sexos na intensidade do dano renal pelo diatrizoato de sódio.OBJECTIVE: Contrast medium-induced nephropathy is the third most frequent cause of iatrogenic acute renal failure involving inpatients. The present study was aimed at evaluating the protective effect of n-acetylcysteine and allopurinol in both male and female rats receiving diatrizoate. MATERIALS AND METHODS: Thirty-five young adult Wistar rats submitted to hydric restriction were divided into groups as follows: groups 1 and 2 (respectively male and female rats receiving saline solution; groups 3 and 4 (respectively male and female rats receiving diatrizoate; group 5

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

    Ricardo Obalski de Mello


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

  18. N-乙酰半胱氨酸对慢性饮酒大鼠肺纤维化的干预作用%The Intervention of N-Acetylcysteine on the Pulmonary Fibrosis of Chronic Ethanol Ingestion in Rats

    王静宜; 于洪志; 武俊萍; 杜钟珍; 吴琦


    Objective: To explore the influence of N -acetylcysteine (NAC) on the pulmonary fibrosis induced by chronic ethanol ingestion in rats, and observe the changes of pathogenesis of pulmonary fibrosis with detecting the content of superoxide dismutase (SOD) and malondialdehyde (MDA) of lung tissue. Methods: Thirty healthy male Sprague-Dawley rats were randomly divided into alcohol group (n=10), alcohol+NAC group (n=10), and control group (n=10). Ethanol liquid diet was given to rats in alcohol group and alcohol+NAC group. NAC 300 mg/(kg·d) was given to rats of alcohol+NAC group. The pathological changes of lung tissue were observed after 8-week treatment. The activity of SOD and content of MDA of lung tissue were detected. Results: there were varying degree of alveolar and alveolar septal infiltration of inflammatory cells, and more deposition of collagen fibers at intervals of alveolar in alcohol group. The similar pathological changes were found in alcohol+NAC group, but the degree was lower than that of alcohol group. The degree of alveolitis and the degree of pulmonary fibrosis were lower in alcohol+NAC group than those in alcohol group (P < 0.05 or P < 0.01, respectively). The SOD activity of lung tissue was higher in alcohol+NAC group than that of alcohol group. The MDA content of lung tissue was lower in alcohol+NAC group than that of alcohol group (P < 0.05). Conclusion: NAC can increase the SOD activity and decrease the content of MDA of lung tissue, and restrain the oxidative stress induced by alcohol, decrease the degree of pulmonary fibrosis induced by chronic ethanol ingestion in rats.%目的:探讨N-乙酰半胱氨酸(NAC)对慢性饮酒大鼠肺组织的病理形态及肺组织超氧化物歧化酶(SOD)、丙二醛(MDA)含量的影响.方法:30只健康雄性大鼠随机分成乙醇组、NAC组、对照组各10只,乙醇组和NAC组每日给予乙醇液体饲料,NAC组给予NAC 300 mg/(kg·d).8周后处死,观察肺组织病理改变,检测肺组织

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

    Denoel Marcelino de Oliveira


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

  20. Neurologisches Outcome nach CPR bei schockresistentem Kammerflimmern unter Gabe von Sedacoron(R

    Müller R


    Full Text Available Bei einer protrahierten CPR mit schockresistentem Kammerflimmern kann unter Gabe von Sedacoron(R ein zufriedenstellender internistischer Zustand erreicht werden. Neurologisch bleiben nach 6 Wochen geringe Defizite des Kurzzeitgedächtnisses. Der Autor regt mit dieser Kasuistik eine Fortsetzung der ARREST- und der ALIVE-Studie an, wobei das neurologische Outcome Beachtung finden sollte.

  1. Protective effect of N-acetylcysteine on kidney as a remote organ after skeletal muscle ischemia-reperfusion Efeito protetor da N-acetilcisteína no rim como um órgão remoto músculo esquelético após isquemia-reperfusão

    Mohammad Ashrafzadeh Takhtfooladi


    Full Text Available PURPOSE: To investigate whether N-acetylcysteine has a protective effect against renal injury as a remote organ after skeletal muscle ischemia-reperfusion in rats. METHODS: Twenty Wistar male rats were divided randomly into two experimental groups: group ischemia-reperfusion (group I and group ischemia-reperfusion + N-acetylcysteine (group II. After ketamine and xylazine anesthesia, femoral artery was exposed. All animals were undergone 2h of ischemia by occlusion femoral artery and 24h of reperfusion. Rats that were treated with N-acetylcysteine given IV at a dose of 150 mg/kg-¹, immediately before reperfusion. After 24h of reperfusion, the blood samples were collected and submitted for evaluation of plasmatic urea, creatinine values and then rats were euthanized and left kidney harvested for histopathological analysis under light microscopy. RESULTS: The urea (35±7.84 mg.dL-1, creatinine (1.46±0.47 mg.dL-1 values were significantly lower in group II (P=0.000. Renal histopathologic study in group I showed extensive distal and proximal tubular cells necrosis and sloughing of epithelial cells into the tubular lumen, cast formation in tubule and glomerul, glomerul fibrosis and hemorrhage. Histopathologically, there was a significant difference (p=0.037 between two groups. CONCLUSION: The N-acetylcysteine was able to decrease renal injury induced by skeletal muscle ischemia reperfusion in rats.OBJETIVO: Investigar se a N-acetilcisteína tem um efeito protetor contra a lesão renal como um órgão remoto músculo esquelético após isquemia-reperfusão em ratos. MÉTODOS: Vinte ratos Wistar machos foram distribuídos aleatoriamente em dois grupos experimentais: grupo isquemia-reperfusão (grupo I e grupo isquemia-reperfusão N-acetilcisteína (grupo II. Após a anestesia de ketamina e xilazina, a artéria femoral foi exposta. Todos os animais foram submetidos a 2h de isquemia pela oclusão da artéria femoral e 24h de reperfusão. Os ratos que

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

    Faintuch, Bluma Linkowski


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

  3. N-乙酰半胱氨酸对模拟失重大鼠肺损伤的防护作用研究%Protective Effect of N-acetylcysteine on Pulmonary Injury under Simulated Weightless Condition in Rats

    李月越; 王萍; 朱敏立; 赵雅辉; 王小辉; 崔彦


    Objective To observe the effect of N-acetylcysteine (NAC) on pulmonary injury under simulated weightlessness in rats. Methods Tail-suspension method was used to establish the models of weightless simulation in rats. A total of 24 clean Wistar rats were randomly divided into group A, B and C ( n=8 for each group) . Group B was treated with NAC (300 mg/kg) by intragastric administration every day from the first day, while group A and C were treated with same volume of sterile water via intragastric injection. The models of weightless simulation were established in group A and B by tail-suspension method after the rats had been administrated for 2 d, while the rats in group C were free-running in the cage. The rats were killed at the end of the 7th d. The levels of superficial CD11b/c of neutrophilic granu-locyte, reactive oxygen species (ROS) concentration of neutrophilic granulocyte, contents of IL (interleukin)-10, IL-6 and TNF ( tumor necrosis factor)-αin the blood samples were detected. The superior lobe tissues of right lung were given hematoxylin and eosin stain ( HE stain) , and the pathological changes of lung tissues in slices were observed. Results In group A, under microscope, the sizes of alveoli were discrepant, the alveolar septum became wide with edema, and blood vessels were dilated and congested, and neutrophils and infiltrated lymphocytes were found in the interstitial. Simi-lar changes of group A were found in group B, but the degrees were less than those in group A, while there were no obvi-ously similar changes in group C. There were statistically significant differences in CD11b/c, ROS concentration, TNF-α, IL-10 and IL-6 (P<0. 05, P<0. 01). Conclusion NAC can alleviate inflammation and lung damages of rats under simulated weightlessness, and the antioxidation effect of NAC may play a role in protection of lung injury under weightless condition.%目的 观察N-乙酰半胱氨酸( NAC)对模拟失重状态下大鼠肺损伤的影响. 方法

  4. Laktoseintoleranz bei Morbus Crohn und Colitis ulcerosa unter Berücksichtigung der ethnischen Herkunft

    Demirci, Ilknur


    Die Frage der Inzidenz einer Laktosemalabsorption bei Morbus Crohn und Colitis ulcerosa wurde retrospektiv unter Berücksichtigung der ethnischen Herkunft untersucht. Bei 243 Patienten wurden zur Diagnose einer Laktosemalabsorption der Laktosetoleranztest und der H2-Atemtest durchgeführt. Dabei fand sich bei 23 (14,3%) von 161 Morbus Crohn Patienten eine Laktosemalabsorption. Nach ethnischer Differenzierung, zeigte sich in der mitteleuropäischen Population eine Häufigkeit von 13,2%...

  5. 柱前衍生-高效液相色谱荧光法测定人血浆中乙酰半胱氨酸及其生物等效性研究%Determination of N-acetylcysteine in human plasma by precolumn derivatization and HPLC-FLD method and study on its bioequivalence

    张乐; 胡岚岚; 周世文; 汤建林


    To establish an HPLC and fluorescent detection method with N-( 1-Pyrenyl) maleimide (NPM) as a pre-column derivatization reagent to determine N-acetylcysteine (NAC) in human plasma and study on its bioequivalence in Chinese healthy volunteers. The analytes were separated on a Diamonsil C18 column (5 μm×l50mm×4.6mm) using 10 mmol ·L-1 NaH2PO4 aqueous solution including 10 mmol·L+1 TMA and acetonitrile (50:50) as a mobile phase at a flow rate The plasma concentration was determined by the method mentioned above. As a result the calibration curve was found to be linear over a range of 0.1-6.58 μg·mL-1, and the limit of the quantitation was 0.1 μg·mL+1. The recovery of the method ranged from 85.3%—103.3%. The coefficients of variation for inter-day and intra-day precisions were both<15%. As an accurate, rapid and sensitive method, this assay has been successfully applied in the therapeutic drug monitoring, and the study of pharmacokinetic and bioavailability of NAC. The test preparation and the reference preparation are bioequivalence.%建立一种快速、准确测定人血浆中乙酰半胱氨酸(N-acetylcysteine,NAC)含量的柱前衍生-高效液相色谱荧光法,并使用该方法对NAC不同剂型间的人体生物等效性进行研究.以NAC与N-(1-芘)马来酰亚胺(N-(1-Pyrenyl)maleimide,NPM)进行衍生化反应后进样测定;采用Diamonsil C18色谱柱(5μm×150 mmx4.6 mm)分离,流动相组成为:乙腈-10mmol·L-1 NaH2PO4(含TMA 10mmol·L-1,H3PO4调pH至3.4)为50:50.采用上述方法测定人血浆中NAC浓度,计算药物动力学参数并进行生物等效性评价.NAC 0.1~6.58μg·mL-1的浓度范围内呈良好线性,血浆中NAC定量下线为0.1 μg·mL-1,方法回收率在85.3%~103.3%之间,日内、日间RSD均小于15%.该方法准确、快速、灵敏,可用于NAC的治疗药物监测、人体内药代动力学及生物等效性研究,两种制剂生物等效.

  6. Protective effect of N-acetylcysteine on cisplatin-induced acute Kidney injury related to p38MAPK pathway in rats%N-乙酰半胱氨酸影响p38有丝分裂原活化蛋白激酶对顺铂诱导急性肾损伤的保护作用

    罗景慧; 杨迎暴; 安田日出夫; 菱田明


    目的 研究N-乙酰半胱氨酸(N-acetylcysteine,NAC)对顺铂(cisplatin,CDDP)诱导大鼠急性肾损伤(acute kidney injury,AKI)后组织细胞凋亡的影响和与p38有丝分裂原活化蛋白激酶(p38 mitogen activated protein kinase,p38MAPK)的关系.方法 静脉注射CDDP制备大鼠AKI模型.大鼠随机分为正常对照组、AKI模型对照组、NAC低剂量组(50 mg·kg-1)、NAC中剂量组(100 mg·kg-1)、NAC高剂量组(200 mg·kg-1)、特异性p38MAPK抑制剂SB203580组(10 mg·kg-1).大鼠预先连续给药3 d,给予CDDP,再继续给药5 d.TUNEL法进行细胞凋亡检查.试剂盒测定肾脏组织caspase-3.Western blot测定caspase-3、Bax、Bcl-2、磷酸化p38MAPK(phosphorylated p38MAPK,p-p38MAPK)表达.结果 与正常对照组相比,CDDP诱导AKI模型组肾组织凋亡细胞增加,caspase-3、Bax、p-p38MAPK表达升高,Bcl-2表达降低(P<0.01 ).与AKI模型组相比,NAC与SB203580减少凋亡细胞、降低肾脏组织caspase-3、Bax、p-p38MAPK表达和增加Bcl-2表达(P<0.01).结论 NAC可有效防治CDDP诱导大鼠AKI,并与p38MAPK相关.%Aim To investigate the effects of N-acetylcysteine( NAC ) on cisplatin ( CDDP )-induced acute kidney injury( AKI ) and its relationship with p38 mitogen activated protein kinase( p38 MAPK ) pathway.Methods The rat was injected CDDP intravenously to make AKI model.The rats were randomly divided into 6 groups,including the normal control group, AKI model group, NAC 50 mg · kg-1 group, NAC 100 mg·kg-1 group,NAC 200 mg · kg-1 group and p38MAPK specific inhibitor SB203580 10 mg· kg-1 group.NAC and SB203580 were administered once a day for three days before CDDP was given.And then NAC and SB203580 were continuously given o.d.for five days.The apoptosis of kidney was monitored by TUNEL.The content of caspase-3 in kidney was determined by the commercial kit.The expression of caspase-3 , Bax , Bcl2 , phosphorylated p38MAPK( p-p38MAPK )were measured by Western blot.Results Compared with the normal

  7. Investigation of LPP combustors under elevated pressure conditions; Untersuchungen zu LPP-Flugtriebwerksbrennkammern unter erhoehtem Druck

    Fink, R.


    The development of new combustor concepts for aero engines to meet future emissions regulations in based on a detailed knowledge of the combustion process and the velocity field. In the presented thesis, non intrusive measurements were performed in a model combustion chamber under almost realistic pressure and temperature conditions. The species OH, NO, unburned hydrocarbons and fuel droplets were detected in 2 dimensions with the Laser Induced Fluorescence (LIF). The velocity field was measured with the Particle Image Velocimetry technique (PIV). [German] Die Weiterentwicklung neuer Brennkammerkonzepte zur Erfuellung zukuenftiger Schadstoffemissionsrichtlinien erfordert genaue Kenntnisse der ablaufenden Verbrennungs- und Stroemungsvorgaenge in der Brennkammer. Bei den in der Arbeit vorgestellten Untersuchungen wurden in einer LPP-Modellbrennkammer unter annaehernd realistischen Eintrittsbedingungen die Spezies OH, NO, unverbrannte Kohlenwasserstoffe sowie noch fluessiger Brennstoff zweidimensional anhand der Laserinduzierten Fluoreszenz (LIF) nachgewiesen. Das Stroemungsfeld wurde mit Hilfe der Particle Image Velocimetry (PIV) gemessen.

  8. Metabolische Veränderungen bei antiretroviraler Therapie unter besonderer Berücksichtigung der mitochondrialen Toxizität

    Froese, Kirstin Antje


    Die symptomatische Hyperlaktatämie oder Laktatazidose ist eine seltene lebensbedrohliche Nebenwirkung, die unter Einnahme von Nukleosidanaloga, insbesondere Thymidinanaloga, im Rahmen der antiretroviralen Therapie (ART) bei HIV-Infektion auftreten kann. Circa 15–35% der mit Nukleosidanaloga behandelten Patienten zeigen zudem regelmäßig einen leicht erhöhten Serum-Laktatspiegel, ohne dabei klinische Symptome einer Hyperlaktatämie zu entwickeln. Der dafür zumindest teilweis...

  9. Johannes Sobotta (1869-1945) - Leben und Wirken unter besonderer Berücksichtigung seiner Würzburger Zeit

    Kayßer, Katharina


    Professor Johannes Sobotta (1869 - 1945) forschte und lehrte als Anatom in Berlin, Würzburg, Königsberg und Bonn. Sein 1904 erstmalig erschienener "Atlas der deskriptiven Anatomie des Menschen" wurde in 14 Sprachen übersetzt und gehört auch in der 21.Auflage noch immer zur Standard-Literatur der medizinischen Ausbildung. Die vorliegende Dissertation gibt einen umfassenden Einblick in Sobottas Lebenswerk unter besonderer Berücksichtigung seiner Würzburger Zeit.

  10. Johannes Sobotta (1869-1945) - Leben und Wirken unter besonderer Berücksichtigung seiner Würzburger Zeit

    Kayßer, Katharina


    Professor Johannes Sobotta (1869 - 1945) forschte und lehrte als Anatom in Berlin, Würzburg, Königsberg und Bonn. Sein 1904 erstmalig erschienener "Atlas der deskriptiven Anatomie des Menschen" wurde in 14 Sprachen übersetzt und gehört auch in der 21.Auflage noch immer zur Standard-Literatur der medizinischen Ausbildung. Die vorliegende Dissertation gibt einen umfassenden Einblick in Sobottas Lebenswerk unter besonderer Berücksichtigung seiner Würzburger Zeit.

  11. Die Business Community als CRM-Instrument unter besonderer Berücksichtigung von Business Intelligence Technologien

    Schober, Andrea


    Das Management von Kundenbeziehungen hat sich in der klassischen Ökonomie unter dem Begriff »Customer Relationship Management« (kurz: CRM) etabliert und sich in den letzten Jahren als erfolgreicher Ansatz erwiesen. In der grundlegenden Zielsetzung, wertvolle, d.h. profitable und kreditwürdige Kunden an ein Unternehmen zu binden, kommen Business-Intelligence Technologien zur Generierung von Kundenwissen aus kundenbezogenen Daten zum Einsatz. Als technologische Plattform der Kommunikatio...

  12. Machbarkeit und Akzeptanz eines Notfall-Management-Systems unter Etablierung der "First Responder Defibrillation" : Ergebnisse eines 2 Jahres Zeitraums

    Robert, Nils


    Problem: Die Letalität nach innerklinischen Reanimationen ist hoch. Daher wurde nach Einführung eines Notfall- Managementsystems unter Etablierung der "First Responder" Defibrillation das Überleben retrospektiv untersucht und die Meinung der Mitarbeiter erfragt. Methode: Aus 2 Jahren wurden 41 Reanimationen untersucht. Eine Mitarbeiterumfrage zum Wissen und der Meinung zum Notfall-Management wurde durchgeführt. Ergebnis: Das Outcome nach Reanimation betrug 30%. 89-100% der Mita...

  13. Asymptomatische zerebrale Mikroembolien nach Lungenvenenablation unter therapeutischer Antikoagulation bei Patienten mit Vorhofflimmern

    Sigmund E


    Full Text Available Einleitung: Patienten nach Pulmonalvenenisolation (PVI bei Vorhofflimmern (VHF zeigen eine erhöhte Inzidenz für asymptomatische zerebrale Mikroembolien. Ziel unserer Untersuchung war es, erstmals unter laufender therapeutischer oraler Antikoagulation die Häufigkeit dieser Läsionen aufzuzeigen. Zur Veranschaulichung dieser Ereignisse wurde jeweils vor und nach linksatrialer Ablationsbehandlung eine diffusionsgewichtete zerebrale Magnetresonanztomographie (DW-MRT durchgeführt und zudem relevante klinische und prozedurale Parameter dokumentiert. Methodik: Insgesamt wurden 80 konsekutive Patienten mit paroxysmalem (n = 52; 65,0 % oder persistierendem VHF (n = 28; 35,0 % im Rahmen dieser Pilotstudie einer linksatrialen Radiofrequenzablation unterzogen. Bei Patienten mit persistierendem VHF erfolgten zusätzlich zur PVI lineare Ablationen (Dachlinie, mitrale Isthmuslinie und/oder CFAE-Ablation („complex fractionated atrial electrograms“ mit einem 3,5 mm offen gekühlten Ablationskatheter. Präund postinterventionell wurde bei allen Patienten ein zerebrales MRT durchgeführt. Ergebnisse: Nach PVI konnten bei 13 von 80 Patienten (16,3 % neu aufgetretene mikroembolische zerebrale Läsionen nachgewiesen werden. Alle Patienten waren neurologisch völlig asymptomatisch. Einziger signifikanter klinischer Parameter in der univarianten Analyse, welcher eine Korrelation dieser Läsionen zeigte, war die Art des VHF (5/52 paroxysmal – 9,6 % vs. 8/28 persistierend – 28,6 %; p = 0,033. Signifikante periprozedurale Parameter waren die Durchführung einer elektrischen Kardioversion im Rahmen der Ablationsbehandlung (p = 0,009 sowie die CFAE-Ablation (p = 0,05. In der multivarianten Analyse zeigte lediglich die Elektrokardioversion einen Trend zur Signifikanz mit 3,98-fachem Risiko (95 %-CI: 0,83–19; p = 0,08. Schlussfolgerung: Auch unter kontinuierlicher therapeutischer Antikoagulation konnte die Inzidenz zerebraler Mikroembolien nach Lungenvenenablation im

  14. Determination the concentration of the N-acetylcysteine conjugate of phenethyl isothiocyanate in healthy human urine by HPLC%高效液相色谱法测定健康人尿液中苯乙基异硫氰酸酯乙酸半胱氨酸缀合物的浓度

    许译升; 郑枫; 刘红霞


    目的 建立高效液相色谱法测定健康人尿液中苯乙基异硫氰酸酯乙酰半胱氨酸缀合物的浓度.方法 色谱柱为Sepax Amethyst-C18柱,流动相为0.2%磷酸水溶液-甲醇(35:65),流量:1 mL ·min-1,紫外检测波长250 nm;氯雷他定为内标.结果 尿液中代谢物在0.8~64.0μg · mL-1内线性关系良好,回归方程为γ =0.08χ-1.28×10-3(n=8,γ=0.9982),提取回收率大于80%,批内和批间精密度RSD < 10%.结论 该方法可用于测定人尿液中苯乙基异硫氰酸酯乙酰半胱氨酸缀合物的浓度.%Objective To establish a HPLC method for the determination the concentration of N - acetylcysteine conjugate of phenethyl isothio-cyanate (PEITC - NAC) in healthy human urine. Methods Separation was carried on a Sepax Amethyst - C18 and the mobile phase was consisted of 0. 2% phosphoric acid - methanol (35: 65) with the flow rate of 1 mL ? Min"1. The detection wavelength was 250 nm. Results A good linearity was demonstrated between 0. 8 - 64. 0 u,g ? mL"1 by linear e-quation y =0. 08* - 1. 28 x 10"3 (n = 8, y = 0. 9982 ) . The within -batch and between - batch deviation was showed by RSD < 10%. Conclusion The method can be applied for the determination the concentration of PEITC - NAC in human urine.

  15. Research on N-acetylcysteine prolonging survival duration of donor heart after heart transplantation in rats%N-乙酰半胱氨酸提高大鼠心脏移植的供心存活时间研究

    陆学荣; 杨学慧; 李占清; 伊雪; 崔翔宇; 王帅; 王耕银; 邬鹏宇


    目的 观察N-乙酰半胱氨酸(N-acetylcysteine,NAC)预处理对心脏移植缺血再灌注损伤(ischemiareperfusion injury,IRI)的保护作用.方法 健康雄性Lewis大鼠80只和BN大鼠20只,按数字表法随机分为3组.对照组:摘取供体心脏前30 min或移植前30 min经下腔静脉注射0.9%氯化钠溶液2 mL;供体预处理组:摘取供心前30 min经下腔静脉注射NAC 300 mg/kg,受体不处理;受体预处理组:受体于移植前30 min经下腔静脉注射NAC 300 mg/kg,供体不处理.供心冷藏于4℃HTK(histidine-tryptophan-ketoglutarate)液18h后建立大鼠腹腔异位心脏移植模型(Lewis→ewis).使用Kaplan-Meier分析其生存率(BN→Lewis);分别于移植后24h取移植物检测过氧化脂质(lactoperoxidase,LPO)和超氧化物歧化酶(superoxide dismutase,SOD)活性.结果 NAC预处理组大鼠生存率明显高于对照组,差异有统计学意义(P<0.05).移植后24 h供心心肌组织中SOD浓度较对照组高,差异有统计学意义[(4.71±1.09) U/mLvs.(2.38±0.39) U/mL,P<0.05];两组LPO浓度比较,差异无统计学意义(P>0.05).供体预处理组与受体预处理心肌组织中LPO、SOD浓度比较,差异无统计学意义(P>0.05).结论 在大鼠心脏移植中NAC通过直接抗氧化及提高氧化酶活性减轻了供心IRI,提高了供心的存活率.

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

    Schmidt, L E; Dalhoff, K P


    the full course of NAC. In all cases the recommended treatment with antihistamine or steroids against adverse effects was administered. We conclude that treatment with NAC is safe. Accordingly we find no reason to change the recommendation for treatment of paracetamol intoxication in Denmark....

  17. N-acetylcysteine as a single therapy for sudden deafness.

    Chen, Chao-Hsien; Young, Yi-Ho


    Like NAC ameliorates hearing loss from acoustic trauma in the inner ear, NAC may also rescue hearing loss from sudden deafness confined to the inner ear. This study assesses the effect of N-acetyl-L-cysteine (NAC) as a single therapy for sudden deafness. Thirty-five sudden deafness patients with neither systemic disorders nor central signs in electronystagmography were treated with NAC alone and assigned to Group A. For comparison, another 35 sudden deafness patients treated by corticosteroids and plasma expander were assigned to Group B. There were no significant differences between the two groups in terms of age, sex, laterality, and pre-treatment mean hearing level. All patients underwent an inner ear test battery comprising audiometry, and ocular vestibular-evoked myogenic potential (oVEMP), cervical VEMP (cVEMP), and caloric tests. Groups A and B did not significantly differ in the pre-treatment mean hearing level, and percentages of abnormal oVEMP, cVEMP, and caloric tests, indicating that the involvement severity of sudden deafness between the two groups was similar. However, Group A (43 ± 27 dB) showed significantly greater mean hearing gain than Group B (21 ± 28 dB), and Group A (91%) revealed better improved rate of hearing than Group B (57%).

  18. Tierexperimentelle Untersuchung zur Effektivitat dertransarteriellen Chemoembolisation unter Einsatz von Poly-Laktide-co-Glykolide -Mikrospharen


    Zusammenfassung: Evaluierung der Effektivitat von Poly-Laktide-co-Glykolide ( PLCG )-Mikrospharen als Embolisationsmaterial in der transarteriellen Chemoembolisation (TACE) imtierexperimentellen Modell. Bei mannlichen ACI-Ratten (n = 11) erfolgte die Implantation einessoliden Morris Hepatomas (1 mm3) subkapsular in den linken Leberlappen. 13 Tage nach Implan-tation wurden die Tumorvolumina kernspintomographisch bestimmt. Die Tiere wurden in Thera-piegruppe (n= 4) und Kontrollgruppe (n = 7) geteilt. Nach Laparotomie und retrograder Ka-theterisierung der Arteria gastroduodenalis wurden 40 mg PLCG-Mikrospharen und 0,05 mg Mit-omyein in Therapiegruppe, 1, 5 mi 0, 9 % Kochsalzlosung in Kontrollgruppe zum Vergleichangewendet. Zur Effektivitatsbeurteilung der beiden Methoden erfolgte 14 Tage nach Katheter-isierung eine erneute kernspintomographische Volumenbestimmung der Tumoren. Eine deutlicheTumorvolumenzunahme von 27,12fache in Kontrollgruppe wurde im Beobachtungszeitraum gese-hen. Im Vergleich zur Kontrollgruppe zeigte die Therapiegruppe eine sehr geringere Tumorvolu-menzunahme von 2,87fache im Beobachtungszeitraum. Die Tumorvolumenzunahme zwischen derbeiden Gruppen zeigten beim T-Test einen signifikanten Unterschied (P<0,05). Das Wachstumdes Lebertumors wurde unter Einsatz von PLCG-Mikrospharen in der TACE im tierexperi-mentellen Modell deutlich gehemmt.

  19. Tierexperimentelle Untersuchungen zur Effektivit(a)t der transarteriellen Chemoembolisation (TACE) unter Einsatz von Bletilla striata

    QIAN Jun; Vossoughi Daryusch; Maataoui Adel; Oppermann Elsiez; Bechstein Wolf; Vogl Thomas Josef


    Evaluierung der Effektivit(a)t von Bletilla striata bei transerteriellenChemoembo lisation (TACE) im Kleintiermodell. Nach subkapsul(a)rer Implantation (Tag 0) eines soliden Morris Hepatoms (2 mm3) bei ACI-Ratten (n = 30) wurden am 13. Tag die Tumorvolumina (V1) magnettomographisch bestimmt. Im Anschlu erfolgten nach Laparatomie die retrograde Katheterisierung der Arteria gastroduodenalis und die Anwendung folgender Therapieprotokolle: (A) TACE (0,1 mg MitomycinC + 0,1 mL Lipiodol) + Bletilla striata (1,0 mg) (n=10); (B) TACE (Bletilla striata (1,0 mg) + Ligatur (n=10); (C) TACE allein (Kontrollgruppe, n=10). Zur Effektivit(a)tsbeurteilung der unterschiedlichen Therapieprotokolle erfolgte am 28. Tag eine erneute magnettomographische Bestimmung der Tumorvolumina (V2). Das durchschnittliche Tumorvolumen der Gruppen A, Bund C vor und nach interventioneller Therapie betrug 0,0355 cm3 und 0,2248 cm3 , 0,0374 cm3 und 0,0573 cm3 sowie 0,0380 cm3 und 0,3674 cm3. Das errechnete durchschnittliche Verh(a)ltnis (V2/V1) betrug 6,28, 1,53 sowie 9,14. Im Vergleich zur Kontrollgruppe C Beobachtungszeitraum ermittelt werden, wahrend zwischen Gruppe A und Gruppe C keine statistisch signifikanten (P>0,05) Unterschiede im Tumorwachstum festgestellt werden konnten. Das Wachstum der induzierten Lebertumoren konnte unter Behandlung mittels TACE + Bletilla striata + Ligatur im Tiermodell statistisch signifikant im Vergleich zur Kontrollgruppe gehemmt werden.

  20. Therapeutic effect of N-acetylcysteine and montelukast sodium in patients with idiopathic pulmonary fibrosis%N-乙酰半胱氨酸联合孟鲁司特钠治疗特发性肺纤维化临床疗效观察

    王传海; 李承红


    Objective To investigate the effect of N-acetylcysteine (NAC) and montelukast sodium in pa-tients with idiopathic pulmonary fibrosis (IPF). Methods A total of 64 patients with IPF confirmed by clinical data and imaging examination from January 2008 to June 2014 were selected in our hospital. According to random number table, the patients were randomly divided into the observation group and the control group with 32 patients in each group. The control group applied conventional glucocorticoids treatment, while the observation group used NAC and montelukast sodium based on glucocorticoids treatment. All patients were treated for 3 months. The therapeutic effect, vital capacity (VC), diffusion capacity for carbon monoxide (DLco), pH value, oxygen partial pressure (PaO2), oxygen saturation (SaO2), partial pressure of carbon dioxide (PaCO2) and medication safety were compared between the two groups. Results In the observation group, the total effective rate was 81.25%, which was significantly higher than 57.60%in the control group (P0.05). After treatment, the differences in VC, DLco between the two groups were statistical-ly significant (P0.05). After treatment, the dif-ferences in PaO2, SaO2 between the two groups were statistically significant (P0.05). No serious adverse reaction was found in the two groups. Conclusion The conventional glucocorticoids therapy added with NAC and montelukast sodium in the treatment of IPF can effectively improve the symptoms of patients, and slow down the decrease of VC, DLco, PaO2, SaO2.%目的 探讨N-乙酰半胱氨酸(NAC)联合孟鲁司特钠治疗特发性肺纤维化(IPF)的临床疗效.方法 选择我院2008年1月至2014年6月经临床-影像证实的IPF患者64例,按随机数字表法分为观察组和对照组,每组32例,观察组在口服常规激素治疗基础上加用NAC联合孟鲁司特钠,对照组口服常规糖皮质激素治疗,疗程3个月.比较两组患者的临床疗效、肺活量(VC)、一氧化碳弥

  1. Effect of N-acetylcysteine on lung and heart injury of rats with a fast floating escape induced decompression sickness%N-乙酰半胱氨酸对快速上浮脱险致减压病大鼠心肺组织的影响

    王芳芳; 方以群; 攸璞; 包晓辰; 马骏; 张师


    Objective To investigate the effect of N-acetylcysteine ( NAC) on lung and heart injury of rats with a fast floating escape induced decompression sickness .Methods Eighty male Sprague-Dawley rats were randomly and evenly divided into four groups:control group and three NAC prevention groups .The NAC groups were treated with different doses of NAC(250, 500 or 1000 mg/kg)by intraperitoneal injection 1 h before entrance.In the control group, rats were given an equal volume of saline1h before entrance.The air was pressurized at the 2t/7 exponential rate to 1.5 MPa which was maintained for 4 min and then uniformly decompressed to atmospheric pressure .The extravehicular survival and pathological changes in the lung and heart tissue were detected 0.5 h after rat egress.Results The survival rate of rats treated with NAC 500 mg/kg(90%) was significantly higher than that of those treated with saline (65%)alone (P<0.05).There was large break and fusion in the structure of pulmonary alveolus of control group besides obvious erythrocyte exudation , cardiac muscle fibers edema ,and obvious denaturation and break .Conclusion NAC can play a protective role in rats with a fast floating escape induced decompression sickness by mitigating the injury to and inflammation of lung and heart tissue .%目的:研究N-乙酰半胱氨酸( NAC)对快速上浮脱险致减压病大鼠心肺组织的影响。方法雄性SD大鼠80只,随机分为4组,每组20只。实验组于进舱前1 h通过腹腔注射NAC溶液(注射剂量分别为250、500和1000 mg/kg),对照组于进舱前1 h腹腔注射相同体积生理盐水。压缩空气以指数速率2t/7加压至1.5 MPa,停留4 min后匀速减压至常压出舱。出舱后即观察大鼠行为学表现并统计存活率,出舱后0.5 h活杀大鼠,取心、肺组织,观察其病理变化。结果 NAC 500 mg/kg组大鼠存活率(90%)显著高于对照组(65%)(P<0.05);对照组大鼠肺泡结

  2. N-乙酰半胱氨酸对支气管哮喘小鼠模型肺脏树突状细胞功能的影响%Effects of N-acetylcysteine on the function of lung endritie cells in asthma mouse models

    朱蓉; 洪永青; 白冲


    Objective To investigate the effects of N-acetylcysteine(NAC) on the function of lung dendritic cells (DC) in asthma mouse models. Methods The murine asthmatic models were established by sensitizing and challenging BALB/C mice with ovalbumin(OVA). Forty-eight mice were divided into three groups of A (interfered with NAC), B( interfered with dexamethason) and C (without drug as the control) with 16 mice each. Serum immunoglobulin E (IgE), interleukin-13 (IL-13) and interferon-γ (IFN-γ) in bronchoalveolar lavage fluid (BLAF) and in vitro co-cultured supernatant of DCs and DO11. 10 spleen T lymphocytes were detected by ELISA. The expressions of MHCⅡ. CD80 and CD86 were detected with flow cytometry. Results Serum IgE was lower in groups of A and B than that in group C (P<0. 01). IL-13 in BALF was lower,but IFN-γ was higher in groups of A and B than that in group C (P<0. 01). The expressions of CD80,CD86 and MHC Ⅱ in groups of A and B were down regulated In the supernatant, IL-13 was lower,but IFN-γ was higher in groups of A and B than that in group C (P<0. 01). Conclusion NAC can reverse Th2-deviated immune response and its therapeutic action in asthma may be through the DC of the lungs.%目的 观察N-乙酰半胱氨酸(NAC)干预支气管哮喘模型后,其肺脏树突状细胞(DC)表面分子表达的变化及其对T淋巴细胞分化的影响.方法 卵蛋白(OVA)致敏、激发裸鼠(BALB/C)哮喘模型后随机分成对照(C)组、地塞米松干预(B)组和NAC干预(A)组,每组16只.ELISA法进行检测血清总IgE、肺泡灌洗液(BLAF)和肺脏DC和DO11.10(OVA特异性转基因小鼠)脾脏T淋巴细胞共培养液上清中白细胞介素(IL)13和γ干扰素(IFN-γ)水平.结果 A、B组血清IgE水平低于C组(P<0.01).A、B组BALF中IL-13低于c组,而IFN-γ水平升高于C组(P<0.01).A、B组肺脏DC表面分子CD80、CD86、MHC Ⅱ下调.与C组比较,小鼠肺脏DC和T淋巴细胞共培养后,A、B组上清IL-13水平明显降

  3. Theaterpädagogische Prozesse in Biographieverläufen unter dem Aspekt der ästhetischen Bildung

    Reinwand, Vanessa-Isabelle


    Im Zentrum der vorliegenden Arbeit steht die Frage, wie ästhetische Prozesse im Theaterspiel von den Akteuren wahrgenommen werden und sich diese ästhetischen Erfahrungen in Biographien niederschlagen. Unter einem primär pädagogischen Blickwinkel soll darauf aufbauend untersucht werden, wie ästhetische Bildungsprozesse verlaufen. Wie und in welchem Ausmaß künstlerische Tätigkeiten, z.B. das Theaterspiel, bildend wirken, stellt in der Pädagogik empirisch ein noch weitgehend unerforschtes Feld d...

  4. Wirkungen eines Krafttrainings unter verminderter Blutzufuhr bei Männern im Alter von 40 bis 60 Jahren

    Hasler, Kathrin Doris


    Verschiedene Studien konnten bereits einen positiven Effekt eines Krafttrainings unter verminderter Blutzufuhr feststellen. Dabei konnte oft eine Verbesserung der Maximalkraft nachgewiesen werden. Die Probanden waren zumeist junge Männer. In dieser Studie wurden dagegen Männer im mittleren Lebensalter getestet. Neben Maximalkraftwerten wurden auch Kraftausdauerwerte erhoben. Das Probandenkollektiv bestand aus 17 Männern im Alter von 50,7 ± 6,8 Jahren mit einer Körpergröße von 177,5 ± 6,2 c...

  5. Schattenwirtschaft unter Palmen: Der touristisch informelle Sektor im Urlaubsparadies Patong, Thailand

    Bianca Gantner


    Full Text Available Seit den 1960er-Jahren spielt der Tourismussektor innerhalb der thailändischen Wirtschaft eine wichtige Rolle und ist durch ein stetiges Wachstum gekennzeichnet. Für über 50 Prozent der Personen, die in Thailand ihren Lebensunterhalt durch informelle Beschäftigung (Schattenwirtschaft sichern, stellt dieser boomende Sektor eine bedeutende Verdienstquelle dar. Unter Verwendung qualitativer Methoden (Interviews und teilnehmende Beobachtung untersucht dieser Artikel den touristisch informellen Sektor des Ortes Patong auf der Insel Phuket und stellt sowohl die Entstehung und den Verlauf als auch die Akteurs- und Angebotsstruktur dieses Sektors dar. Die aktuelle Entwicklung wird dabei verglichen mit dem Modell Vorlaufers, das die Entwicklung einer staatlich geförderten Tourismusdestination beschreibt. Entgegen der Annahme dieses Modells, mit einem Wachstum des Tourismussektors würde der Anteil an formeller gegenüber der informellen Beschäftigung steigen, zeigt sich, dass kein Rückgang des touristisch informellen Sektors zu erkennen ist, dieser weiterhin ein integraler Bestandteil der Tourismuswirtschaft Patongs geblieben ist und eine wichtige Verdienstquelle für MigrantInnen und die lokale Bevölkerung darstellt. --- Since the 1960s, tourism has become a vital part of the Thai economy and has been characterised by a steady growth. For more than 50 percent of all Thais working in the informal sector (shadow economy, the booming tourism industry represents an important source of income. In this article Patong on Phuket serves as a case study for examining the network of actors, the touristic supply structure as well as its evolution and developments over the years by using qualitative methods (interviews and participant observation. The empirical data will then be compared to Vorlaufer’s scheme on the development of a state-sponsored tourist destination. In contrast to the scheme’s assumption of a decline of the informal and a rise of the

  6. Erwachsenenbildung unter genderkritischer Perspektive Adult Education from a Gender-Critical Perspective

    Jürgen Budde


    Full Text Available Im Bereich der Erwachsenen- und Ausbildungsforschung werden Genderdimensionen bislang nur wenig in den Blick genommen. 2006 sind jedoch gleich zwei Arbeiten erschienen, die sich mit der Erwachsenenbildung unter Genderperspektive beschäftigen. Sabine Liedtkes Studie analysiert das bislang wenig bearbeitete Feld des beruflichen Ausbildungssystems. Anhand der Rekonstruktion der Kategorien „Beruf“ und „Arbeit“ dokumentiert sie ein dichotomes Geschlechtermodell im dualen System, welches an tradierte Geschlechterbilder angelehnt ist. Ihr Fazit ist, dass die Berufspädagogik die dichotome Struktur von Geschlecht fördert, da sie sich auf den gewerblich-technischen und industriellen Bereich konzentriert und so zu einer Reproduktion von hierarchischen Geschlechtermodellen beiträgt. Angela Venth richtet dagegen mit der allgemeinen Erwachsenenbildung den Fokus auf den zweiten großen Sektor und ergänzt so die Genderanalyse. Sie arbeitet anhand von Programmanalysen, Tagungsauswertungen und Fortbildungsdokumentationen heraus, dass auch in der allgemeinen Erwachsenenbildung ein geschlechterdichotomes Bild mit einem normativen männlichen Maßstab zugrunde gelegt wird. Die dichotome Struktur von allgemeiner und beruflicher Bildung sowie die Missachtung alltagsbezogener Bildung versperren, so Venth, die Möglichkeit der Veränderung von Geschlechterverhältnissen.Until now, gender dimensions have rarely been at the center of research on adult education and training. In 2006, however, two works appeared simultaneously that dealt with adult education from the perspective of gender. Sabine Liedtkes study analyses a field that research rarely attends to, the occupational training system. Utilizing the reconstruction of the categories “profession” and “work,” she documents the dichotomous gender model in the German dual system of traineeship, which is founded on traditional gendered images. She concludes that occupational pedagogy promotes the

  7. Rigiscan®-Monitoring der Erektion unter audiovisueller sexueller Stimulation ohne/mit Viagra™ bei Patienten mit erektiler Dysfunktion

    Perabo FGE


    Full Text Available Die orale Medikation mit Sildenafil (Viagra™ hat sich zur Therapie der erektilen Dysfunktion etabliert und relativiert die Differentialdiagnose zwischen psychogener und organischer Dysfunktion mit den entsprechenden therapeutischen Konsequenzen. Diesem Problem widmet sich diese Studie zur Prüfung der erektilen Antwort unter RigiScan®-Monitoring ohne/mit 50 mg Viagra™. 64 Patienten (mittleres Alter 48 Jahre mit einer erektilen Dysfunktion arteriogener (n = 10, venöser (n = 7, gemischt neurogen/vaskulärer (n = 15 und psychogener (n = 32 Genese von mehr als 6 Monaten Dauer wurden in die Studie aufgenommen. Alle Patienten wurden eingehend diagnostisch abgeklärt, inklusive Hormonlabor, dynamischer Pharmako-Duplexsonographie und, falls indiziert, mit einer Cavernosometrie/ -graphie. Zur Testung der penilen Rigidität und zur Objektivierung der Erektion wurde das "real-time" RigiScan® verwendet. In zwei konsekutiven Messungen wurden sowohl die direkte erektile Antwort auf visuelle Stimulation als auch die nächtlichen Erektionen abgeleitet und die Meßergebnisse mit den Begleiterkrankungen, "lifestyle"-Faktoren und dem Ergebnis der Pharmako-Duplexsonographie korreliert. Es fand sich keine Korrelation zwischen der Ätiologie der erektilen Dysfunktion in bezug auf organische oder psychogene Genese und dem Alter der Patienten, der Dauer der Erektionsstörung, dem Nikotinabusus, den Blutfetten, den Testosteronwerten, dem klinischen Ergebnis der Pharmakotestung (Erektionsgrad und dem duplexsonographisch gemessenen Fluß der penilen Arterien. Hingegen zeigte sich eine positive Korrelation zwischen Genese der erektilen Dysfunktion (organisch bzw. psychogen und dem RigiScan®-Meßergebnis (r = 0,29. Patienten mit psychogen bedingter Erektionsstörung profitierten am meisten von Viagra™, während Patienten mit vaskulärer Genese oder gemischt neurogener/vaskulärer Genese deutlich schlechter auf Viagra™ ansprachen. Es bestand keine Korrelation

  8. N-乙酰半胱氨酸对甲基乙二醛诱导的大鼠海马神经元毒性损伤的保护作用%Effects of N-acetylcysteine upon methylglyoxal-induced damage in hippocampal neuronal cells

    周红; 郑秀琴; 张志珺; 滕皋军


    Objective To explore the effects of N-acetylcysteine (NAC) upon the methylglyoxal (MG)-induced injury of hippocampal neuronal cells.Methods Primary cultures of 1-day-old SD rat hippocampal neuron were exposed to MG and/or NAC for 24 h respectively.Apoptosis was quantified by flow cytometer using annexin V-FITC and propidium iodide (PI) staining.The level of intracellular reactive oxygen species (ROS) was measured by an oxidant-sensitive dye 2,7-dichorofluoresin diacetate (DCFH).The protein and mRNA levels of BDNF and TrkB were assayed with Western blot and real-time reversetranscription polymerase chain reaction (RT-PCR) respectively.Results After a 24 h cell incubation with 100 μmol/L MG,the ratio of apoptotic cells in MG group (8.80±0.31)% significantly increased versus the control group (1.60±0.15)% and MG + NAC group (4.83±0.31)% respectively.The level of intracellular oxidation of MG group (10 229±946) also significantly increased versus the NAC group (2118±320),control group (4265±82),MG + NAC group (3886±415) and pretreated NAC + MG group (2997±606).MG increased the cellular levels of BDNF but decreased the TrkB mRNA and protein expression significantly.However,NAC significantly decreased the BDNF and increased the TrkB mRNA and protein expression in rat hippocampal neuron after MG induction.All these differences were considered statistically significant.Conclusion MG-induced neurotoxicity in hippocampal neurons is mediated by oxidative stress and it can impair the BDNF/TrkB signal pathway.Antioxidant NAC has protective effect upon MG-induced neurotoxicity through its antiapoptotic action and its antioxidant effect on ROS level.And it works partly by activating the BDNF/TrkB signal pathway.%目的 探讨N-乙酰半胱氨酸(NAC)对甲基乙二醛(MG)诱导的海马神经元损伤的保护作用及可能机制.方法 取新生24 h SD大鼠的海马神经元原代培养至第7天,予MG和(或)NAC干预24 h,异硫氰酸荧光

  9. Calcium phosphate cement incorporated with N-acetylcysteine-loaded silk fibroin microspheres:preparation and characterization%N-乙酰半胱氨酸丝素微球复合磷酸钙骨水泥的制备及表征

    姜磊; 皮斌; 冯焘; 李斌; 陆英杰; 杨惠林; 朱雪松


    BACKGROUND:Calcium phosphate bone cement has been applied to clinical surgery because of its good biocompatibility and osteoconduction. However poor mechanical properties and lack of osteoinductivity limit its wide application. OBJECTIVE:To develop calcium phosphate cement incorporated with N-acetylcysteine (NAC) loaded silk fibroin microspheres (SFM), which is a kind of new injectable bone graft material with slow-release function, and evaluate its physical and chemical properties and cel compatibility. METHODS: Empty SFMs were prepared with emulsion solvent evaporation to absorb NAC solution of different concentrations by NAC-SFM and the concentration of NAC at the maximum drug loading ratio was determined. Then, NAC-SFM was loaded into calcium phosphate bone cement to test the drug release propertiesin vitro. MC3T3-E1 osteoblasts were cultured on the surface of NAC-SFM calcium phosphate bone cement and cel attachment and growth were observed by scanning electron microscope. Additionaly, MC3T3-E1 cels were cultured with three kinds of bone cement extracts (calcium phosphate cement, SFM-calcium phosphate cement, NAC-SFM-calcium phosphate cement, as wel as cultured in theα-minimum essential medium containing a volume fraction of 10% fetal bovine serum and 1% penicilin-streptomycin double antibody as the control. MTS assay was used to evaluate cel proliferation. RESULTS AND CONCLUSION:Microspheres in the composite bone cement presented with smooth surface, same size, diffused distribution and no obvious destroy. Thus, the SFM could remain stable in the reaction process of the composite bone cement. The double slow release system which contained silk fibroin microspheres and calcium phosphate bone cement showed a significant decrease in the cumulative release percentage of NAC within the first 24 hours compared with the control group (P   目的:制备复合N-乙酰半胱氨酸丝素微球的注射性磷酸钙骨水泥,构建一种具有药物缓释功能

  10. N-乙酰半胱氨酸对重症急性胰腺炎大鼠肠道屏障功能障碍与二次打击的保护作用%N-acetylcysteine prevents intestine barrier functional disturbance and"second attack"following sodiuln taurocholate-induced severe acute pancreatitis in rats

    邹忠东; 张再重; 王瑜; 陈少全; 涂小煌; 王烈


    Objective To evaluate the protective effect of N-acetylcysteine(NAC)on the small intestinal mucosal barrier and other organs in severe acute pancreatitis(SAP)rats.Methods Fifty-four Wistar male rats were divided into sham operation group(n=6),SAP group(n=24),and SAP+NAC group(300 mg/kg body wt)(n=24).Sham operation group underwent laparotomy only.SAP model was established by retrograde injection of 5%sodium taurocholate into the bile-pancreatic duct in Wistar rats.The rats in SAP+NAC group were administered with NAC 300 mg/kg body wt intaperitoneally 2 h before SAP model establishment.Rats were killed at 3,6,12 and 24 h after operation.The terminal ileum was collected for examination under light microscopy.The samples of the pancreas,the lung and the liver were collected for measuring the levels of myeloperoxidase(MPO).The blood levels of diamine oxidase(DAO).tumor necrosis factor Mpha(TNF-α)and interleukin-6(IL-6)were also measured.Results The contents of TNF-α,IL-6 and DAO in SAP group were increased significantly at all the 4 time points as compared with those in sham operation group(P<0.01).The levels of MPO in the pancreas.the lung and liver of SAP group were increased significantly at 6,12 and 24 h as compared with those in sham operation group(P<0.05 or P<0.01).As compared with SAP group,the contents of TNF-α and IL-6 were signifieanfly decreased in SAP+NAC group at all the 4 time points(P<0.05 or P<0.01),while the level of DAO significantly decreased in SAP+NAC group except for the 3-h time point(P<0.05 or P<0.01).The contents of MPO in the pancreas,the lung and the liver were significantly decreased in SAP+NAC group at 12 and 24 h after operation(P<0.05 or P<0.01).Conclusion NAC may protect the small intestine mucosal barrier and other organs by reducing the polymorphonuclear leucocyte detaining,which might be relate to the reduction of neutrophil aggregation by decreasing the release of TNF-α and IL-6.%目的 观察N-乙酰半胱氨

  11. Multiquadratic methods, collocation and kriging - comparison with geostatistical model assumptions; Multiquadratische Methode, Kollokation und Kriging - Vergleich unter geostatistischen Modellannahmen

    Menz, J. [Technische Univ. Freiburg (Germany). Inst. fuer Markscheidewesen und Geodaesie; Bian Shaofeng [Technical Univ. of Surveying and Mapping, Wuhan (China)


    The contribution shows that Hardy`s multisquare method leads to results that are similar in their structure to the predictions by collocation. On the basis of geostatistical model assumptions, equations for calculating the prediction error are presented, and the multisquare method is compared with the collocation method on this basis. Equivalences between collocation and kriging are gone into, and information is presented on how predictions can be improved in the Bayesian sense. [Deutsch] In der folgenden Arbeit soll zuerst gezeigt werden, dass die Multiquadratische Methode nach HARDY zu Vorhersagen fuehrt, die in ihrer Struktur den Vorhersagen durch Kollokation entsprechen. Unter geostatistischen Modellannahmen werden nach dem Fehlerfortpflanzungsgesetz Formeln fuer die Berechnung der Vorhersagefehler angegeben. Auf der Grundlage dieser Formeln wird die Multiquadratische Methode mit der Kollokation verglichen. Es wird auf die Aequivalenzen zwischen Kollokation und Kriging verwiesen und angegeben, wie sich die Vorhersagen im BAYESschen Sinne verbessern lassen. (orig./MSK)

  12. Nährig, Dietrich & Karl Hermann Harms, unter Mitarbeit von Josef Kiechle, Hanspeter Rausch, Wolfgang Schawaller & Jörg Spelda (2003: Rote Listen und Checklisten der Spinnentiere (Arachnida Baden-Württembergs

    Blick, Theo


    Full Text Available book review: Nährig Dietrich & Karl Hermann Harms, unter Mitarbeit von Josef Kiechle, Hanspeter Rausch, Wolfgang Schawaller & Jörg Spelda (2003: Rote Listen und Checklisten der Spinnentiere (Arachnida Baden-Württembergs.

  13. Messung der Vorwärts-Rückwärts-Ladungsassymetrie von b-Quarks bei Energien nahe der Z0-Resonanz. Untersuchung von Ereignissen mit initialem b-Quark unter Verwendung der Jetladungstechnik mit dem DELPHI Detektor

    Schwering, Britta

    Messung der Vorwärts-Rückwärts-Ladungsassymetrie von b-Quarks bei Energien nahe der Z0-Resonanz. Untersuchung von Ereignissen mit initialem b-Quark unter Verwendung der Jetladungstechnik mit dem DELPHI Detektor

  14. Entwurf, Entwicklung und Inbetriebnahme eines verteilten Rechnerkontrollsystems für die Elektronen-Stretcher-Anlage ELSA, unter besonderer Berücksichtigung der Extraktion im Nachbeschleunigungsbetrieb bis 3.5 GeV

    Picard, M


    Entwurf, Entwicklung und Inbetriebnahme eines verteilten Rechnerkontrollsystems für die Elektronen-Stretcher-Anlage ELSA, unter besonderer Berücksichtigung der Extraktion im Nachbeschleunigungsbetrieb bis 3.5 GeV

  15. Entwicklung und Inbetriebnahme eines verteilten Rechnerkontrollsystems zur Steuerung der Elektronen-Stretcher-Anlage ELSA, unter besonderer Berücksichtigung der Anforderungen des Nachbeschleunigungsbetriebs bis 3.5 GeV

    Götz, T


    Entwicklung und Inbetriebnahme eines verteilten Rechnerkontrollsystems zur Steuerung der Elektronen-Stretcher-Anlage ELSA, unter besonderer Berücksichtigung der Anforderungen des Nachbeschleunigungsbetriebs bis 3.5 GeV

  16. Online-Dienstleistung als Herausforderung für AnbieterInnen unter besonderer Berücksichtigung der Situation in Österreich

    Birgit Kollek


    Full Text Available Online-Beratung findet zunehmend auch im Dienstleistungssektor statt und damit nicht mehr nur im psychosozialen Beratungskontext. Gerade die Interaktivität des Mediums Internet macht dabei den Reiz für AnbieterInnen aus, die Dienstleistungsangebote auch im virtuellen Raum den KundInnen anzubieten. Der Artikel beleuchtet die notwendigen Schritte und Sichtweisen für eine professionelle Projektplanung solcher Angebote im Internet unter besonderer Berücksichtigung der Situation in Österreich.

  17. Mechanical-biological waste treatment with thermal processing of partial fractions; Mechanisch-biologische Restabfallbehandlung unter Einbindung thermischer Verfahren fuer Teilfraktionen



    Technologies for mechanical-biological treatment of waste in the Land of Hessen were compared including thermal processes like combustion and gasification. The new and more rigid limiting values specified in the Technical Guide for Municipal Waste Treatment (Technische Anleitung Siedlungsabfall - TASI) get a special mention. [Deutsch] Verschiedene Technologien der mechanisch-biologischen Restabfallbehandlung im Raum Hessen wurden unter Einbezug thermischer Verfahren (Verbrennung, Vergasung) miteinander verglichen. Dabei wurden besonders auf die verschaerften Grenzwerte der Technischen Anleitung Siedlungsabfall (TASI) eingegangen. (ABI)

  18. Hazard assessment investigations in connection with the formation of a lake on the tongue of Unterer Grindelwaldgletscher, Bernese Alps, Switzerland

    M. A. Werder


    Full Text Available The surface of Unterer Grindelwaldgletscher glacier tongue has subsided by more than 200 m over the last 150 years. The surface lowering is not uniform over the glacier tongue but depends on the thickness of the uneven debris cover, which led to the formation of a depression on the tongue. A lake can form in this basin, which occurred for the first time in 2005. Such a glacier lake can drain rapidly leading to a so-called outburst flood. The lake basin has been increasing in size at an alarming rate and in 2008, it reached a volume which poses a significant flooding threat to the communities downstream, as was exemplified by an outburst of the lake in May 2008. The future evolution of the lake basin was extrapolated based on surface lowering rates between 2004–2008. An outburst flood model was tuned with the measured hydrograph from 2008 and then was run with the extrapolated lake bathymetries to simulate future lake outbursts and estimate their flood hydrographs. We discuss the rapidly increasing risk for Grindelwald and other communities, as well as the installation of an early warning system and possible prevention measures.

  19. Medienpädagogik unter der differenztheoretischen Lupe. Eine Identitätssuche zwischen Disziplin und Profession

    Franziska Linke


    Full Text Available Der Beitrag diskutiert die dem Themenheft zugrundeliegende Fragestellung nach der Konstitution der Medienpädagogik aus einer systemtheoretischen Perspektive. Dabei wird im Anschluss an Stichweh (2013 Ansatz der funktionalen Differenzierung ein Untersuchungsrahmen aufgezeigt, der es ermöglicht, die Medienpädagogik sowohl aus wissenschaftssoziologischer als auch professionssoziologischer Perspektive zu betrachten. Gerade die zentrale Rolle der (digitalen Medien für Lern- und Bildungsprozesse sowie für den Arbeitsmarkt (u. a. KMK 2016 verlangt eine stetige Reflexion professioneller Handlungssysteme der Medienpädagogik, die nicht losgelöst von der Frage nach dem Selbstverständnis der Medienpädagogik als Wissenschaftsdisziplin gelingen kann (u. a. Hugger 2001. Divergierende theoretische Positionierungen der Akteurinnen und Akteure sowie verschiedene Zielvorstellungen zur Medienpädagogik selbst und zu dem, was sie praktisch leisten kann, erschweren ein solches Vorhaben. Die Autorinnen des Beitrags begeben sich daher, unter Berücksichtigung der Differenzierung zwischen Disziplin und Profession, auf die Suche nach möglichen Antworten. Vorgeschlagen wird eine erweiterte Betrachtungsweise, welche die Medienpädagogik als wissenschaftliche Produktionsgemeinschaft beschreibt und dadurch Potenziale eröffnet theoretische und empirische Erkenntnisse von Akteurinnen und Akteuren unterschiedlicher wissenschaftlicher Disziplinen mit Medienzusammenhang zu berücksichtigen. Ferner wird dargelegt, dass ein solcher Beschreibungsansatz neue Forschungsperspektiven auf die professionstheoretische Einordnung praktischer Handlungssysteme der Medienpädagogik eröffnen kann.

  20. Kontrastmittelverstärkte Magnet-Resonanz-Urographie unter forcierter Diurese - Stellenwert in der Differentialdiagnostik bei Obstruktionen des oberen Harntraktes

    Jung P


    Full Text Available Die Magnet-Resonanz-Urographie (MRU ist ein relativ neues Verfahren in der Diagnostik des oberen Harntraktes. Das Ziel dieser Studie war der Vergleich der Aussagefähigkeit der MRU unter Gabe von Gadolinium und Furosemid und dem konventionellen Urogramm (IVU in der Diagnostik der Ursache von Obstruktionen im Bereich des Harnleiters. 82 Patienten mit im IVU nachgewiesener Obstruktion des oberen Harntraktes oder urographisch stummer Niere bei sonographisch nachgewiesener Dilatation wurden der MRU zugeführt. Die Bilder beider Untersuchungsmethoden wurden von voneinander unabhängigen Untersuchern befundet. Zwei Urologen befundeten die IVU-Bilder, zwei Radiologen die MRU-Bilder, die Radiologen kannten die IVU-Diagnose nicht. Bei unklarer Diagnose wurden weitere Untersuchungen wie Computertomographie, retrograde Pyelographie oder Ureteroskopie durchgeführt. Die Diagnosen waren: Harnleitersteine bei 72 Patienten, Harnleitertumore bei 8 Patienten und extraureterale Tumore bei 2 Patienten. Eine richtige Diagnose bei den Steinpatienten wurde durch IVU bei 49 von 72 Patienten und durch MRU bei 64 von 72 Patienten gestellt. In dieser Patientengruppe wurden durch die MRU zwei falsche Diagnosen gestellt. Fehlende Kontrastmittelausscheidung war der Hauptgrund für Versagen der IVU. 3 der 8 Patienten mit Harnleitertumoren wurden durch die IVU richtig dignostiziert, bei dreien wurde eine falsche Diagnose gestellt. Durch die MRU konnten in dieser Gruppe 7 von 8 Patienten korrekt diagnostiziert werden, es wurde keine falsche Diagnose erhoben. IVU wird zunächst die Standarduntersuchungstechnik zur Darstellung des oberen Harntraktes bleiben, aber durch diese Studie konnte die Möglichkeit gezeigt werden, die in der MRU in Kombination mit Gadolinium und Furosemid liegt. Die größte Bedeutung dieser Untersuchung liegt in der urographisch stummen Niere, bei Untersuchungen in der Schwangerschaft, bei Kindern und bei Patienten mit Kontrastmittelunverträglichkeit.

  1. Sustained energy supply under globalisation and liberalisation conditions; Nachhaltige Energieversorgung unter den Bedingungen der Globalisierung und Liberalisierung

    Hempelmann, Rolf [Enquete-Kommission des Deutschen Bundestags, Berlin (Germany)


    The major challenge at the threshold of this century is to structure the energy supply in the sense of sustained development. The Committee of Enquiry of the Federal German Parliament 'Sustained energy supply under globalisation and liberalisation conditions' is developing medium to long-term concepts in this respect. Analysis of the boundary conditions of future energy policy shows that the consequences of future enrichment of climatic gases in the atmosphere and no longer the availability and productiveness of the energy deposits could become the limiting factor. Following the analysis of the technological and non-technological future potentials for sustained energy supply the Committee of Enquiry is currently working on the formulation of strategies for the energy industry transformation process. (orig.) [German] An der Schwelle dieses Jahrhunderts stellt sich die grosse Herausforderung, die Energieversorgung im Sinne einer nachhaltigen Entwicklung zu strukturieren. Die Enquete-Kommission des Deutschen Bundestags 'Nachhaltige Energieversorgung unter den Bedingungen der Globalisierung und Liberalisierung' entwickelt hierzu mittel- bis laengerfristige Konzepte. Die Analyse der Rahmenbedingungen kuenftiger Energiepolitik zeigt, dass die Folgen einer weiteren Anreicherung von Klimagasen in der Atmosphaere und nicht mehr die Verfuegbarkeit und Ergiebigkeit der Energielagerstaetten zum limitierenden Faktor werden koennten. Nach der Analyse der technologischen und nicht-technologischen Zukunftspotentiale fuer eine nachhaltige Energieversorgung arbeitet die Enquete-Kommission derzeit an der Formulierung von Strategien fuer den energiewirtschaftlichen Transformationsprozess. Vortrag gehalten auf der GVSt-Konferenz 'Kohle - Energie fuer die Zukunft' anlaesslich der E-World of Energy am 14. Februar 2002. (orig.)

  2. Rectal cancer - local staging and imaging under neoadjuvant therapy; Rektumkarzinom - Lokales Staging und Bildgebung unter neoadjuvanter Therapie

    Karpitschka, M. [Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Campus Grosshadern, Institut fuer Klinische Radiologie, Muenchen (Germany)


    Rectal cancer restaging after neoadjuvant therapy is based on two principles: an anatomic definition of the tumor allowing surgical planning and prognostic stage grouping. Emerging data suggest that reassessment using a combination of different imaging modalities may help to provide valuable prognostic information before definitive surgery. Perfusion computed tomography (CT) may provide special information regarding tumor vascularity. Evaluation of therapy response, especially of the circumferential resection margin (CRM) is necessary for surgical planning. For local staging high-resolution and diffusion-weighted magnetic resonance imaging has proven to be of high diagnostic accuracy. The M status should be assessed using multidetector computed tomography (MDCT) according to response evaluation criteria in solid tumors (RECIST) while lymph node evaluation requires either magnetic resonance imaging or positron emission tomography/computed tomography scanning. (orig.) [German] Beim Rektumkarzinom ist das Restaging nach neoadjuvanter Therapie von zentraler Bedeutung. Einerseits kann anhand der aktuellen Tumorausdehnung das weitere chirurgische Vorgehen geplant, andererseits durch die radiologische Evaluation des Therapieansprechens eine prognostische Einschaetzung getroffen werden. Als bildgebende Modalitaeten stehen die Endosonographie, die CT bzw. PET/CT und die MRT zur Verfuegung. Die Perfusions-CT koennte in Zukunft wertvolle Informationen bzgl. des Therapieansprechens liefern, da hierdurch die Tumorvaskularitaet und ihre Veraenderungen unter Therapie dargestellt werden koennen. Die Evaluation des Therapieansprechens, insbesondere die Beurteilung des zirkumferenziellen Resektionsrandes (CRM) ist zur operativen Planung erforderlich. Die Bildgebung nach neoadjuvanter Therapie ist praeoperativer Standard in der Rektumchirurgie. Fuer die Beurteilung des lokalen Therapieansprechens (T-Status) hat sich die hochaufloesende Duennschicht-MRT bewaehrt, wohingegen der M

  3. Investigations of coal ignition in a short-range flame burner using optical measuring systems; Untersuchungen zur Kohlezuendung am Flachflammenbrenner unter Verwendung optischer Messtechnik

    Hackert, G.; Kremer, H.; Wirtz, S. [Bochum Univ. (Germany). Lehrstuhl fuer Energieanlagentechnik


    The short-range flame burner and the KOALA reactor of DMT are experimental facilities for realistic simulation of coal conversion processes at high temperatures and pressures in atmospheric conditions. The TOSCA system enable measurements of temperatures, sizes, shapes and velocities of the fuel particles, which serve as a basis for a three-dimensional simulation model of coal combustion. In the future, further parameter studies will deepen the present knowledge of coal dust combustion under pressure and enable optimisation of the numerical models for simulation of industrial-scale systems for coal dust combustion under pressure. [Deutsch] Mit dem Flachflammenbrenner und dem KOALA-Reaktor der DMT stehen Versuchsapparaturen zur Verfuegung, mit deren Hilfe die Kohleumwandlungsprozesse bei hohen Temperaturen unter Druck und unter atmosphaerischen Bedingungen realistisch wiedergegeben werden. Das TOSCA-System erlaubt dabei die Bestimmung von Temperaturen, Groessen, Formen und Geschwindigkeiten der Brennstoffpartikel. Diese Daten liefern die Grundlage fuer die Erstellung eines dreidimensionalen Simulationsmodells zur Modellierung der Kohleverbrennung. In Zukunft werden weitere Parameterstudien das Verstaendnis der Kohlenstaubdruckverbrennung vertiefen und ein Optimierung der numerischen Modelle ermoeglichen, so dass die Simulation grosstechnischer Kohlenstaubdruckverbrennungsanlagen realisiert werden kann. (orig.)

  4. Damage characterisation of silicon carbides for applications in gas turbines in complex load conditions; Charakterisierung des Schaedigungsverhaltens von Siliciumcarbiden fuer den Einsatz in Gasturbinen unter komplexen Beanspruchungsbedingungen

    Nestle, E.


    A tensile test facility for simultaneous thermal, mechanical and corrosive loading was developed and constructed for the purpose of characterizing the damage characteristics of ceramic high-temperature materials. Apart from tensile tests for up to 830 h, tests were also carried out on four-point bending test pieces and disk-shaped oxidation test pieces. The experiments were made at 1450 - 1550 C in dry or moist air. The materials investigated were one hot-pressed silicon carbide and two sintered silicon carbides. [German] Um keramische Hochtemperaturwerkstoffe bezueglich ihres Schaedigungsverhaltens charakterisieren zu koennen, wurde im Rahmen der vorliegenden Arbeit eine Zugpruefanlage zur gleichzeitigen Beanspruchung unter thermischen, mechanischen und korrosiven Bedingungen entwickelt und aufgebaut. Neben den in dieser Anlage durchgefuehrten Zugpruefungen mit Versuchszeiten bis zu 830 h wurden begleitende Untersuchungen an Vierpunkt-Biegeproben und scheibenfoermigen Oxidationsproben durchgefuehrt. Die Versuche konzentrierten sich auf den Temperaturbereich 1450-1550 unter trockenen und feuchten Luftatmosphaeren. Bei den untersuchten Werkstoffen handelte es sich um eine heissgepresste und zwei gesinterte Siliciumcarbid-Qualitaeten. (orig.)

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

    Spencer C. Greene, MD, FACEP, FACMT


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

  6. Visusminderung unter Silikon

    Dornonville de la Cour, Morten; Lux, Anja; Heegaard, Steffen


    Silicone oil is used as intravitreal tamponading agent in surgery for rhegmatogenous retinal detachment (RRD) cases complicated with proliferative vitreoretinopathy (PVR). Recently, a number of case series have appeared where profound central visual loss has been found in eyes after uncomplicated...

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

    Aricio Treitinger


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

  8. Multislice spiral CT of the paranasal sinuses; Mehrschicht-Spiral-CT der Nasennebenhoehlen: Erste Erfahrungen unter besonderer Beruecksichtigung der Strahlenexposition

    Dammann, F.; Bode, A.; Heuschmid, M.; Kopp, A.; Georg, C.; Pereira, P.L.; Claussen, C.D. [Tuebingen Univ. (Germany). Radiologische Universitaetsklinik


    Purpose: To evaluate the potential of multislice CT in the diagnosis of the paranasal sinuses. Methods: Dose measurements were performed exposing an Alderson Rando phantom in a four-slice spiral CT (MS-CT) while applying a variety of scan parameters. Additionally, 30 consecutive patients underwent a transversal examination by the MS-CT using 1/1/3.5/0.5 mm spiral parameters and an additional transversal or coronal scan on a conventional single slice spiral CT (SS-CT) with 2/3/1 mm. Coronal reformations of the MS-CT were compared with the primary coronal SS-CT, or coronal reformations of the transversal SS-CT, respectively, with regard to image quality and depiction of relevant anatomical details of the region. Results: Superficial exposure values at the level of the eye lenses as well as for the thyroid gland were superior for MS-CT (3.62 mGy, and 0.12 mGy, resp.) as compared to SS-CT (2.96 mGy, and 0.07 mGy). Image quality was equal or superior for MS-CT as compared to SS-CT in all but one case. Drawbacks of SS-CT, such as dental amalgam artifacts, stair step artifacts or partial volume artifacts did not notably affect the coronal reformations of MS-CT. Conclusions: MS-CT seems to have the potential to replace primary coronal CT of the paranasal sinuses without any loss of image quality, but may even improve the overall diagnostic value. Radiation doses may still have to be reduced. (orig.) [German] Ziel: Erprobung eines Multislice-CT (MS-CT) zur Diagnostik der Nasennebenhoehlen (NNH). Methode: An einem Alderson Rando Phantom wurden Dosismessungen bei der Spiral-CT der NNH mit einem Mehrschicht-CT (MS-CT) unter Verwendung unterschiedlicher Scanparameter durchgefuehrt. Anschliessend wurden 30 konsekutive Patienten an dem MS-CT mit den Spiralparametern 1/1/3,5/0,5 mm und einem konventionellen Einzeilen Spiral-CT (SS-CT; 2/3/1 mm) untersucht. Die koronaren Rekonstruktionen der transversalen MS-CT wurden mit den koronaren Rekonstruktionen bzw. den primaeren koronaren

  9. Corrosion behaviour of gas turbine alloys under high velocity burnt fuels; Korrosionsverhalten von Gasturbinenwerkstoffen unter stroemenden Heissgasbedingungen

    Haubold, T.I.; Brill, U. [Krupp VDM GmbH, Altena (Germany); Abel, H.J. [Fachhochschule Dortmund (Germany). Fachbereich 5/Maschinenbau, Laborgruppe Werkstofftechnik; Klauke, P. [Fachhochschule Gelsenkirchen (Germany). Fachbereich Chemie und Materialtechnik


    1200 C with a corrosion rate of less than 0.1 mm/a. The aluminium content of app. 3 wt.-% which is remarkably high for a wrought alloy leads to the formation of a thin dense and adherent alumina scale. Alloy C-263 is a chromia former which is not suitable for temperatures higher than 1000 C. (orig.) [German] Die Neuentwicklung von Nickelbasissuperlegierungen fuer die fliegende und stationaere Gasturbine verfolgt das Ziel einer deutlichen Verbesserung der mechanischen Eigenschaften bei hohen Temperaturen, um die Metalltemperature erhoehen zu koennen und damit den Wirkungsgrad anzuheben, die Emissionen zu vermindern und den Treibstoffverbrauch zu reduzieren. Bei einer solchen Werkstoffentwicklung darf jedoch die Weiterentwicklung der Hochtemperaturkorrosionsbestaendigkeit nicht vernachlaessigt werden. Zusaetzlich zu den heute bereits ueblichen zyklischen und isothermen Korrosionsversuchen, die in Laboroefen durchgefuehrt wurden, sind die zwei Gasturbinenwerkstoffe Nicrotan trademark 6325 hAlC (alloy 2100 GT) und Nicrofer 5120 CoTi (alloy C-263) auf einem burner-rig-Pruefstand unter stroemenden Heissgasbedingungen untersucht worden. Bei diesem Pruefstand trifft ein Heissgasstrom aus verbranntem Erdgas mit Gasgeschwindigkeiten zwischen 60 m/s and 150 m/s auf die Probe. Die hierdurch erreichten Materialtemperaturen liegen zwischen 900 C und 1200 C. Die Proben wurden in den hier vorgestellten Versuchen bei einer Temperatur von 1000 C dem Heissgasstrom fuer 1 h bzw. 10 h ausgesetzt. Die Gasgeschwindigkeiten betrugen 60 m/s, 100 m/s bzw. 140 m/s. Bei einer Stunde Versuchsdauer nahmen beide Werkstoffe noch an Masse zu, wobei Nicrofer 5120 CoTi bei allen Gasgeschwindigkeiten einen deutlich hoeheren Massenzuwachs zeigte. Bei 10 h Versuchsdauer stiegen die Masserverluste bei Nicrofer 5120 CoTi mit steigender Gasgeschwindigkeit an. Bei Nicrotan trademark 6325 hAlC laesst sich ein Massenverlust erst bei der hoechsten Gasgeschwindigkeit verzeichnen. In der metallographischen und

  10. [Dimitri Steinke: Die Zivilrechtsordnungen des Baltikums unter dem Einfluss ausländischer, insbesondere deutscher Rechtsquellen. (Osnabrücker Schriften zur Rechtsgeschichte, Bd. 16.) V&R unipress. Göttingen 2009. 243 S. ISBN 978-3-89971-573-6] / M

    Luts-Sootak, Marju, 1966-


    Arvustus: Dimitri Steinke. Die Zivilrechtsordnungen des Baltikums unter dem Einfluss ausländischer, insbesondere deutscher Rechtsquellen. (Osnabrücker Schriften zur Rechtsgeschichte ; 16). Göttingen, 2009

  11. [Dimitri Steinke: Die Zivilrechtsordnungen des Baltikums unter dem Einfluss ausländischer, insbesondere deutscher Rechtsquellen. (Osnabrücker Schriften zur Rechtsgeschichte, Bd. 16.) V&R unipress. Göttingen 2009. 243 S. ISBN 978-3-89971-573-6] / M

    Luts-Sootak, Marju, 1966-


    Arvustus: Dimitri Steinke. Die Zivilrechtsordnungen des Baltikums unter dem Einfluss ausländischer, insbesondere deutscher Rechtsquellen. (Osnabrücker Schriften zur Rechtsgeschichte ; 16). Göttingen, 2009

  12. N-acetylcysteine and hemodialysis treatment of a severe case of methyl ethyl ketone peroxide intoxication

    van Enckevort, C C G; Touw, D J; Vleming, L-J


    The plastic hardener methyl ethyl ketone peroxide (MEKP) is an unstable peroxide that releases free oxygen radicals. Ingestion of this compound induces widespread liver necrosis that is often fatal, extensive ulceration with subsequent scarring, and stenosis of the proximal digestive tract in surviv

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

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


    and vegetable shortening, at two different concentrations (100 and 400 mg/kg), with the appropriate controls and shams, under controlled laboratory settings. We found that NAC failed to elicit an increase in GSH over three time periods and concluded that NAC is not an effective method to enhance GSH levels...... in teleost fish using the concentrations and vehicles tested here. We emphasize the importance of validation studies across all new species/taxa when possible and suggest that more investigation is required with regard toNAC manipulation in fish if this approach is to be used...

  14. S-nitroso-N-acetylcysteine attenuates liver fibrosis in experimental nonalcoholic steatohepatitis [Corrigendum

    Mazo DF


    Full Text Available Mazo DF, de Oliveira MG, Pereira IV, Cogliati B, Stefano JT, de Souza GF, Rabelo F, Lima FR, Ferreira Alves VA, Carrilho FJ, de Oliveira CP. Drug Des Devel Ther. 2013:7:553–563. On page 554, the sentence "Therefore, we chose SNAC as a potential antifibrinogenic NO donor drug for treating fibrosis..." contains an error. The term "antifibrinogenic" should be replaced by "antifibrogenic". On page 558, Figure 3 (D, the intermediate block corresponding to SNAC is missing. View original paper by Mazo et al

  15. N-acetylcysteine (NAC) decreases binge eating in a rodent model

    Hurley, Matthew M.; Resch, Jon M.; Maunze, Brian; Frenkel, Mogen M.; Baker, David A.; Choi, SuJean


    Binge eating behavior involves rapid consumption of highly palatable foods leading to increased weight gain. Feeding in binge disorders resembles other compulsive behaviors, many of which are responsive to N-acetyl cysteine (NAC), which is a cysteine prodrug often used to promote non-vesicular glutamate release by a cystine-glutamate antiporter. To examine the potential for NAC to alter a form of compulsive eating, we examined the impact of NAC on binge eating in a rodent model. Specifically,...

  16. Oxidative Stress and Inflammation in Hepatic Diseases: Therapeutic Possibilities of N-Acetylcysteine

    Kívia Queiroz de Andrade


    Full Text Available Liver disease is highly prevalent in the world. Oxidative stress (OS and inflammation are the most important pathogenetic events in liver diseases, regardless the different etiology and natural course. N-acetyl-l-cysteine (the active form (NAC is being studied in diseases characterized by increased OS or decreased glutathione (GSH level. NAC acts mainly on the supply of cysteine for GSH synthesis. The objective of this review is to examine experimental and clinical studies that evaluate the antioxidant and anti-inflammatory roles of NAC in attenuating markers of inflammation and OS in hepatic damage. The results related to the supplementation of NAC in any form of administration and type of study are satisfactory in 85.5% (n = 59 of the cases evaluated (n = 69, 100%. Within this percentage, the dosage of NAC utilized in studies in vivo varied from 0.204 up to 2 g/kg/day. A standard experimental design of protection and treatment as well as the choice of the route of administration, with a broader evaluation of OS and inflammation markers in the serum or other biological matrixes, in animal models, are necessary. Clinical studies are urgently required, to have a clear view, so that, the professionals can be sure about the effectiveness and safety of NAC prescription.

  17. N-acetylcysteine improves arterial vascular reactivity in patients with chronic kidney disease

    Wittstock, Antje; Burkert, Magdalena; Zidek, Walter;


    Patients with stage 5 chronic kidney disease show increased cardiovascular morbidity and mortality that are partly related to impaired arterial vascular reactivity. We investigated whether intravenous administration of the antioxidant acetylcysteine improves arterial vascular reactivity in these ......Patients with stage 5 chronic kidney disease show increased cardiovascular morbidity and mortality that are partly related to impaired arterial vascular reactivity. We investigated whether intravenous administration of the antioxidant acetylcysteine improves arterial vascular reactivity...

  18. Observing reducing effect of N-acetylcysteine in the metabolism of yeast

    Sebastián Chapela


    Full Text Available The research focuses on the design of experimental teaching using readily available materials and simple methods to implement. It arises as an example for learning, using baker's yeast Saccharomyces cerevisiae, because it has many of the metabolic pathways existing in mammalian cells. In this paper it was developed an essay that allow students to observe macroscopically the capacity of N- Acetyl cysteine (NAC to stimulate the reducing power of yeast using indicator Methylene Blue (MB color change.

  19. Protective effects of N-acetylcysteine on brain-dead rat liver

    Shui-Jun Zhang; Ting-Wu Ma; Xiu-Xian Ma; Jian-Jun Gou; Ji-Hua Shi; Wen-Zhi Guo


    BACKGROUND: Brain-dead donors have been the main sources in organ transplantation. But many studies show that brain-death affects the organ's function after transplantation. This study was undertaken to investigate liver injury after brain-death in rats and the protective effects of N-acetyleysteine (NAC) on liver injury. METHODS: A total of 30 Wistar rats were randomized into 3 groups: normal control group (C), brain-dead group (B), and NAC pretreatment group (N). At 4 hours after the establishment of a brain-dead model, serum was collected to determine the levels of ALT, AST, TNF-α and hyaluronic acid (HA). Hepatic tissue was obtained for electron microscopic examination. RESULTS:At 4 hours, the levels of ALT, AST, TNF-α, and HA in group N were signiifcantly higher than those in group C, but these parameters were signiifcantly lower than those in group B. Electron microscopy showed activated Kupffer cells, denuded sinusoidal endothelial cells (SECs), and widened fenestration in group B, but eliminated activation of Kupffer cells and intact SECs in group N. CONCLUSION: Brain death can cause liver injury, and N-acetyleysteine can protect the liver from the injury.

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

    Youssef Al-Tonbary


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

  1. Antioxidant properties of N-acetylcysteine: their relevance in relation to chronic obstructive pulmonary disease.

    Dekhuijzen, P.N.R.


    Oxidative stress has been implicated in the pathogenesis and progression of chronic obstructive pulmonary disease. Both reactive oxidant species from inhaled cigarette smoke and those endogenously formed by inflammatory cells constitute an increased intrapulmonary oxidant burden. Structural changes

  2. Antioxidant properties of N-acetylcysteine: their relevance in relation to chronic obstructive pulmonary disease.

    Dekhuijzen, P.N.R.


    Oxidative stress has been implicated in the pathogenesis and progression of chronic obstructive pulmonary disease. Both reactive oxidant species from inhaled cigarette smoke and those endogenously formed by inflammatory cells constitute an increased intrapulmonary oxidant burden. Structural changes

  3. N-acetylcysteine and hemodialysis treatment of a severe case of methyl ethyl ketone peroxide intoxication

    van Enckevort, C C G; Touw, D J; Vleming, L-J


    The plastic hardener methyl ethyl ketone peroxide (MEKP) is an unstable peroxide that releases free oxygen radicals. Ingestion of this compound induces widespread liver necrosis that is often fatal, extensive ulceration with subsequent scarring, and stenosis of the proximal digestive tract in surviv

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

    Avni Kılıç


    Full Text Available Objective: The aim of this study is evaluating the protective activity of N-acetyl cysteine and resveratrol treatment against ischemia - reperfusion damage created experimentally in rat ovaries. Methods: 42 female Wistar rats were used in our study. Rats were separated randomly into six groups consisting of seven rats as sham, torsion, torsion- detorsion, torsion-detorsion+saline, torsion-detorsion+resveretrol (20 mg/kg and torsion- detorsion+N-acetyl cysteine (150 mg/kg. Except Sham, ovarian torsion procedure was implemented to all other groups for 2 hours. Detorsion procedure was implemented to other groups for 2 hours, except the torsion group. Medications were given through intraperitoneal way half an hour before the detorsion procedure in saline (two milliliter, resveratrol (20 mg/kg and N-acetyl cysteine (150 mg/kg groups. Then, 2 ml of blood samples were drawn for markers of oxidative stress and tumour necrosis factor-alpha (TNF-α work and the ovaries, which were torsioned for the histologic examination, were ex­tracted from all rats. Edema, congestion, hemorrhage, leuko­cyte infiltration and degeneration of follicles were evaluated by histopathological examination. Results: According to histopathologic damage scores, the least damage was seen in sham group and the most damage was seen T-DT group (1.00±0.81 vs. 11.00±1.15, respectively; p<0.001. It was seen that resveratrol and N-acetyl cysteine treatments were effective in decreasing tissue damage (total damage score average 83.85±0.89 vs. 3.85±0.89, respec­tively; p<0.001, and on the other hand there was not any dif­ference between resveratrol and N-acetyl cysteine treatments (p=0.966. Besides, it was determined that oxidative stress levels were higher in torsion - detorsion group and the resve­ratrol and N-acetyl cysteine treatment caused a significant de­crease in oxidative stress levels. In additionally, the reductions of TNF-α levels were found to be equally effective in both drugs (8.68±1.88 vs. 7.85±2.08, P=0.968. Conclusion: Presented study showed that resveratrol and N-acetyl cysteine treatment can be effective in preventing tissue damage and oxidative stress, which is induced by ischemia-reperfusion that is created in rat ovaries. On the other hand, no difference was found between the resveratrol and N-acetyl cysteine with regards to protective activity.

  5. Oral N-acetylcysteine administration does not stabilise the process of established severe preeclampsia.

    Roes, E.M.; Raijmakers, M.; Boo, T.M. de; Zusterzeel, P.L.M.; Merkus, H.M.; Peters, W.H.M.; Steegers, E.A.P.


    OBJECTIVE: To stabilise the disease process in women with early onset severe preeclampsia and/or HELLP syndrome by enhancing maternal antioxidants effects of glutathione. STUDY DESIGN: In a randomised, double-blind, placebo-controlled trial, women with severe preeclampsia and/or HELLP syndrome

  6. N-acetylcysteine attenuates nicotine-induced kindling in female periadolescent rats.

    Okamura, Adriana Mary Nunes Costa; Gomes, Patrícia Xavier L; de Oliveira, Gersilene V; de Araújo, Fernanda Yvelize R; Tomaz, Viviane S; Chaves Filho, Adriano José Maia; de Sousa, Francisca Cléa F; Vasconcelos, Silvânia Maria Mendes; de Lucena, David Freitas; Macêdo, Danielle


    Kindling is a form of behavioral sensitization that is related to the progression of several neuropsychiatric disorders such as bipolar disorder. We recently demonstrated that female periadolescent rats are more vulnerable to nicotine (NIC)-induced kindling than their male counterparts. Furthermore, we evidenced that decreases in brain antioxidative defenses may contribute to this gender difference. Here we aimed to determine the preventive effects of the antioxidant N-acetyl cysteine (NAC) against NIC-kindling in female periadolescent rats. To do this female Wistar rats at postnatal day 30 received repeated injections of NIC 2mg/kg, i.p. every weekday for up to 19 days. NAC90, 180 or 270 mg/kg, i.p. was administered 30 min before NIC. The levels of glutathione (GSH), superoxide dismutase (SOD) activity, lipid peroxidation (LP) and nitrite were determined in the prefrontal cortex (PFC), hippocampus (HC) and striatum (ST). The development of kindling occurred at a median time of 16.5 days with 87.5% of NIC animals presenting stage 5 seizures in the last day of drug administration. NAC270 prevented the occurrence of kindling. NIC-kindled animals presented decreased levels of GSH and increased LP in the PFC, HC and ST, while SOD activity was decreased in the ST. NAC180 or 270 prevented the alterations in GSH induced by NIC, but only NAC270 prevented the alterations in LP. Nitrite levels increased in the ST of NAC270 pretreated NIC-kindled animals. Taken together we demonstrated that NAC presents anti-kindling effects in female animals partially through the restoration of oxidative alterations.

  7. Semiquinone formation and DNA base damage by toxic quinones and inhibition by N-acetylcysteine (NAC)

    Lewis, D.C.; Shibamoto, T.


    Toxic, mutagenic, carcinogenic, and teratogenic effects have been reported for some quinones as well as compounds metabolized to quinones. Semiquinone radical formation, thymidine degradation, and protection by NAC were studied in a hypoxanthine/xanthine oxidase (HX/XO) system. Quinone, benzo(a)pyrene-3,6-quinone, danthron, doxorubicin, emodin, juglone, menadione, and moniliformin were tested. Diethylstilbestrolquinone, N-acetylquinoneimine, and benzoquinonediimine, hypothesized toxic metabolites of diethylstilbestrol, acetaminophen and p-phenylenediamine, respectively, were synthesized and studied. Semiquinone radical formation was assessed in a HX/XO system monitoring cytochrome C reduction. Large differences in rates of semiquinone radical formation were noted for different quinones, with V/Vo values ranging from 1.2 to 10.6. DNA base degradation, thymine or thymidine glycol formation, and thiobarbituric acid reactive substance (TBARS) production were measured in a similar system containing thymine, thymidine, calf thymus DNA, or deoxyribose. TBARS formation was observed with deoxyribose, but thymidine degradation without TBARS formation was noted with thymidine. NAC (0.5 to 10 mM) caused dose-dependent inhibition of quinone-induced cytochrome C reduction.

  8. Co-administration of N-Acetylcysteine and Acetaminophen Efficiently Blocks Acetaminophen Toxicity.

    Owumi, Solomon E; Andrus, James P; Herzenberg, Leonard A; Herzenberg, Leonore A


    Preclinical Research Although acetaminophen (APAP) is an effective analgesic and anti-pyretic, APAP overdose is the most frequent cause of serious, often lethal, drug-induced hepatotoxicity. Administration of N-acetyl cysteine (NAC) within 8 hours of APAP overdose effectively mitigates APAP-induced hepatotoxicity. Thus, preventing APAP toxicity before it occurs by formulating APAP with NAC is logical and, as we show here in a mouse model, is effective in preventing APAP toxicity. Thus, toxic oral APAP doses sufficient to cause severe widespread liver damage do not cause significant damage when administered concurrently with equal amounts of NAC, that is, in the NAC-APAP treated animals, hepatic transaminases increase only marginally and liver architecture remains fully intact. Thus, we conclude that concomitant oral dosing with APAP and NAC can provide a convenient and effective way of preventing toxicity associated with large dosage of APAP. From a public health perspective, these findings support the concept that a co-formulation of APAP plus NAC is a viable over-the-counter (OTC) alternative to the current practice of providing APAP OTC and treating APAP toxicity if/when it occurs. In essence, our findings indicate that replacing the current OTC APAP with a safe and functional APAP/NAC formulation could prevent the accidental and intentional APAP toxicity that occurs today.

  9. Is N-acetylcysteine effective in the treatment of pulmonary fibrosis?

    Jeldres Pulgar, Alejandro; Labarca, Gonzalo


    La fibrosis pulmonar idiopática es una enfermedad respiratoria crónica y progresiva, que en etapas finales conlleva una alta mortalidad. Se han planteado múltiples opciones terapéuticas, entre ellas la N-acetilcisteína, pero su rol no está claramente establecido. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 30 bases de datos, identificamos ocho revisiones sistemáticas que en conjunto incluyen 16 estudios aleatorizados. Realizamos un metanálisis y tablas de resumen de los resultados utilizando el método GRADE. Concluimos que N-acetilcisteína probablemente aumenta el riesgo de hospitalización y exacerbaciones. Si bien no está claro si esto conlleva un aumento de mortalidad porque la certeza de la evidencia es muy baja, en general existe consenso en que no debiera utilizarse, a no ser que sea en el contexto de un nuevo estudio clínico.

  10. Influence of the N-acetylcysteine in the muscular degenaration process in dystrophic mice

    Rafael de Senzi Moraes Pinto


    Estudos recentes demonstram o envolvimento do estresse oxidativo nas distrofinopatias. Neste trabalho, verificamos se o uso do antioxidante N-acetilcisteína (NAC) no período que antecede a mionecrose diminui a degeneração muscular em camundongos mdx, modelo experimental da distrofia muscular de Duchenne. Quinze camundongos mdx com 14 dias de vida receberam por via intraperitoneal 150mg/kg de NAC diluído em salina por 14 dias. Quinze camundongos mdx receberam salina pela mesma via e período. O...

  11. Hydrogen diffusion into fatigue cracks of aluminium alloy 6013 in a corrosive environment; Wasserstoffeinlagerung an Ermuedungsrissen der Aluminiumlegierung 6013 unter korrosiver Umgebung

    Lenk, Christian Alexander


    The author attempted a time-resolved detection of raised hydrogen concentrations in the plastic deformation region of fatigue cracks in an aluminium test piece deformed by cyclic stress in a corrosive environment. Mechanical material parameters like the crack propagation velocity under cyclic stress change dramatically in a corrosive environment. This is assumed to be caused by hydrogen diffusion, but so far there is no method that reliably measures additional hydrogen from the corrosive environment. For this reason, a special analytical configuration was set up which makes use of the thermal desorption method. First, chips with a thickness of about 20 micrometers are sawed out of the test specimen in high-vacuum conditions. The chips fall into a hot melting vessel in a UHV chamber, where the hydrogen contained in the chips is released. The resulting pressure increase is recorded by a mass spectrometer. A hydrogen profile of the test specimen is obtained by assigning the chip position to the signal. For the corrosive medium in which the test specimen is immersed during crack initiation, i.e. NaCl solution, heavy water was used. This makes it possible to distinguish between the hydrogen contained in a piece of technical aluminium alloy (AA6013) and the deuterium diffusing in from the corrosive fluid. The deuterium is found exclusively in the test piece volume in the strongly plastically deformed region surrounding the fatigue crack. (orig.) [German] Das Ziel der vorliegenden Arbeit besteht im ortsaufgeloesten Nachweis einer erhoehten Wasserstoffkonzentration im plastisch deformierten Bereich von Ermuedungsrissen einer unter korrosiver Umgebung zyklisch verformten Aluminiumprobe. Mechanische Materialparameter wie z.B. die Rissausbreitungsgeschwindigkeit unter zyklischer Belastung aendern sich drastisch in korrosiver Umgebung. Als Ursache fuer dieses Verhalten wird eine Eindiffusion von Wasserstoff vermutet, jedoch gibt es bisher keine Messung die den zusaetzlichen

  12. Einfluss der Kaliumdüngung auf das Wachstum und die Wassernutzungseffizienz von Ackerbohne (Vicia faba), Sommerweizen (Triticum aestivum) und Tomate (Solanum lycopersicum) unter Kontroll-, Trockenstress- bzw. Salinitätsbedingungen

    Reeb, verh. Gerwers, Dominik


    Ziel dieser Arbeit war es, den speziellen Einfluss einer Kalium-(K)-Düngung auf das Pflanzenwachstum herauszustellen. Es wurde untersucht, ob der Wasserhaushalt der Pflanzen durch Kalium verbessert und inwiefern die Wassernutzungseffizienz (WUE) verändert wird. Dabei wurde auch nach speziellen Wirkungen von K auf die Verbesserung der WUE unter Trockenstress- und Salinitätsbedingungen geforscht. Die Verbesserung der WUE könnte auf eine Verringerung des Wasserverbrauches und /...

  13. Presentation of the Well Tractor Concept and practical experience in extreme conditions; Vorstellung des Well Tractor Konzepts mit Erfahrungen bei Einsaetzen unter Extrembedingungen

    Kater, H.; Preiss, F. [Preussag Wireline- und Messservice, Edemissen (Germany)


    So-called extended reach boreholes with horizontal sections of more than 2000 m, short radius drilling, multilaterals and other variations are common enough. Problems occur when this type of borehole needs to be surveyed or modified. The contribution describes the newly developed ``Well Tracotor{sup circledR}`` technology and outlines its potential. (orig.) [Deutsch] Sogenannte Extended Reach Bohrungen mit Horizontalsektionen von mehr als 2.000 Meter Laenge, Short Radius Drilling, Multilaterals und andere Variationen sind bohrtechnisch einwandfrei durchfuehrbar und gehoeren zum gaengigen Repertoire der Bohrfirmen. Grosse Probleme entstehen jedoch wenn dieser Bohrungstyp vermessen, komplettiert oder aufgewaeltigt werden soll. Insbesondere Bohrlochmessfirmen haben es in den letzten ca. 20 Jahren versaeumt Innovationen zwecks oekonomischen Einsatzes ihrer Technologie in diesen Bohrungen bereitzustellen. Die Durchfuehrung von Perforationen und Bohrlochmessungen, das Setzen von Stopfen, Schneiden von Rohren und auch einfachste Slickline-Operationen sind bei einer Bohrlochneigung beginnend bei ca. 60 bis 80 nur unter Anwendung von kosten- und zeitintensiven Verfahren moeglich. Eine guenstige Alternative zu diesen Verfahren bietet der Well Tractor. Diese Technologie ermoeglicht das Einfahren von Geraeten, die ueblicherweise am Kabel oder Draht eingesetzt werden, in Horizontalbohrungen. Im Folgenden werden das technische Konzept, ein Vergleich mit alternativen Verfahren, und verschiedene Referenzen des Well Tracotors {sup trademark} dargestellt. Weiterhin wird auf die Modifikationen eingegangen, die noetig waren, um dieses Geraet den Gegebenheiten in tiefen, heissen Gasbohrungen anzupassen. Abschliessend soll durch einen Ausblick auf zum Teil schon im Feldtest befindliche Weiterentwicklungen das weitere Potential dieser Technologie aufgezeichnet werden. (orig.)

  14. MR-imaging of finger osteoarthritis: Morphology and cartrilage signal intensity before and after treatment with ademetionin; Magnetresonanztomographie der Fingerpolyarthrose: Morphologie und Knorpelsignalverhalten unter Ademetonintherapie

    Koenig, H. [Radiologische Klinik, Abt. fuer Roentgendiagnostik und Nuklearmedizin, Univ.-Klinikum Steglitz, FU Berlin (Germany); Stahl, H. [Radiologische Klinik, Univ.-Klinikum Rudolf-Virchow, FU Berlin (Germany); Sieper, J. [Medizinische Klinik und Poliklinik, Univ.-Klinikum Steglitz, FU Berlin (Germany); Wolf, K.J. [Radiologische Klinik, Abt. fuer Roentgendiagnostik und Nuklearmedizin, Univ.-Klinikum Steglitz, FU Berlin (Germany)


    This report deals with a prospective study of 21 patients with finger osteoarthritis treated over a period of three months with either Ademetionin (therapy group: 14/21) or without (control group: 7/21). MR-Imaging was carried out before and after treatment using spin-echo and 3D-Flash sequences. Morphological parameters and signal intensity changes of the hyaline cartilage were evaluated. The increase of the cartilage signal intensity was significant in the therapy group, this can be interpreted as an structural improvement. Also a decrease of the cartilage signal intensity with age was found. The morphological parameters showed no significant changes in the therapy and control groups. (orig.) [Deutsch] Im Rahmen einer prospektiven Studie wurden magnetresonanztomographische Untersuchungen bei Patientinnen mit Fingerpolyarthrose vor und nach Ademetionintherapie durchgefuehrt. Es erfolgten zwei Messungen an einer Kontrollgruppe (n=7, keine Ademetionintherapie) und an der Therapiegruppe (n=14) im Abstand von drei Monaten. Zur Anwendung kamen eine Doppel-Spin-Echo-Sequenz sowie eine 3D-Flash-Sequenz. Ausgewertet wurden neben morphologischen Parametern auch der Signalintensitaetsverlauf im Bereich des hyalinen Gelenkknorpels der Interphalangealgelenke. Signifikant war der Knorpelsignalzuwachs unter Ademetionintherapie, dies kann als Zeichen einer strukturellen Befundbesserung interpretiert werden. Ebenfalls signifikant zeigte sich die Abnahme der Knorpelsignalintensitaet mit zunehmendem Lebensalter der Patientinnen. Bei den morphologischen Befundaenderungen konnte kein signifikanter Therapieeffekt festgestellt werden. (orig.)

  15. Materials used for thermal insulation under special consideration of the use of ceramic fibres; Werkstoffe zur Waermedaemmung unter Beruecksichtigung des Einsatzes von Keramikfasern

    Sonnenschein, G. [Verwaltungsgemeinschaft Maschinenbau- und Metall-Berufsgenossenschaft und Huetten- und Walzwerks-Berufsgenossenschaft, Duesseldorf (Germany)


    In the field of industrial thermal insulation, a range of construction materials is available. Aside from the classic refractory blocks and castables, fibre products are also often used for high-temperature applications today. Builders and planners must also assess whether the insulating materials can be used that pose the least possible risk to people and the environment alongside the considerations that have to be made about the technical, economic, and ecological conditions. TRGS (the technical rules for hazardous substances) 619 ''Substitute materials for ceramic fibres in the construction of kilns and furnaces'' (Ersatzstoffe fuer Keramikfasern im Ofen- und Feuerfestbau) helps planners make the appropriate choices for high-temperature thermal insulation under consideration of all conditions. (orig.) [German] Im Bereich der industriellen Waermedaemmung stehen den Anwendern eine Reihe von Baustoffen zur Verfuegung. Neben den klassischen Feuerfeststeinen und Stampfmassen werden heute auch Faserprodukte fuer die Hochtemperaturanwendung eingesetzt. Der Anwender hat neben den technischen, oekonomischen und oekologischen Bedingungen auch zu pruefen, ob Isolierstoffe mit einem moeglichst geringen Risiko fuer Mensch und Umwelt eingesetzt werden koennen. Die TRGS 619 ''Ersatzstoffe fuer Keramikfasern im Ofen- und Feuerfestbau'' ermoeglicht eine Entscheidungsfindung zur Hochtemperatur-Waermedaemmung unter Beachtung aller Bedingungen. (orig.)

  16. Mixture formation and pre-reaction in an injection jet in Diesel engine boundary conditions; Gemischbildung und Vorreaktionen in einem Einspritzstrahl unter dieselmotorischen Randbedingungen

    Eisele, G.; Koss, H.J.; Knoche, K.F.


    To examine the mixture formation and combustion, fuel is injected in Diesel engine boundary conditions in a pressure chamber. Spectroscopic methods permit the noncontact investigation with high spatial and temporal resolution of the physical and chemical processes. The jet of an excimer laser is focussed in the injection jet for this purpose. The local mixture compostion is determined from the Raman spectra, and fluorescence spectra permit one to obtain qualitative information on the appearance and distribution of the OH and NH radicals in the injection jet. For example, it was found that with a chamber temperature of 500 C, the first clear OH fluorescence occurs about 1.8 ms after the start of injection at the edge of the jet in the area of lean mixture. (orig.) [Deutsch] Zur Untersuchung der Gemischbildung und Verbrennung wird Kraftstoff unter dieselmotorischen Randbedingungen in einer Druckkammer eingespritzt. Spektroskopische Methoden erlauben die beruehrungslose und zudem oertlich und zeitlich hochaufgeloeste Untersuchung der physikalischen und chemischen Vorgaenge. Dazu wird der Strahl eines Excimerlasers in den Einspritzstrahl fokussiert. Aus Ramanspektren laesst sich die lokale Gemischzusammensetzung bestimmen, Fluoreszenzspektren erlauben qualitative Aussagen ueber Auftreten und Verteilung der OH- und NH-Radikale im Einspritzstrahl. So zeigt sich zum Beispiel, dass bei einer Kammertemperatur von 500 C die ersten deutlichen OH-Fluoreszenzen ca. 1,8 ms nach Einspritzbeginn am Strahlrand im Bereich mageren Gemisches auftreten (orig.)

  17. Clinical relevance of computed tomography under emergency conditions. Diagnostic accuracy, therapeutical consequences; Klinische Relevanz der Computertomographie unter Notdienstbedingungen. Diagnostische Treffsicherheit, therapeutische Konsequenzen

    Weber, C.; Jensen, F.; Wedegaertner, U.; Adam, G. [Universitaetskrankenhaus Eppendorf, Hamburg (Germany). Radiologisches Zentrum, Klinik und Poliklinik fuer Diagnostische und Interventionelle Radiologie


    Purpose: To evaluate the diagnostic accuracy and therapeutic consequences of computed tomography performed on an emergency basis in a primary care hospital. Material and Methods: In 418 patients, 463 computed tomographies (thorax, abdomen, pelvis, spine, aorta, neck and extremities) were performed within 12 months, providing 999 diagnoses. The computed tomography diagnoses were retrospectively evaluated and correlated to surgery and discharge diagnoses. Therapeutical consequence were analyzed and allocated to a time period < 36 h (urgent) and {>=} 36-72 h (elective). Average age was 49 (1-94) years (41% female and 59% male). Discharge diagnosis was defined as gold standard, provided that it was supported by clinical, blood chemical, diagnostic and possible surgical data. Results: In 176 of 999 diagnoses (18%), the diagnoses were classified as ''noncorrelatable''. Of the 823 correlated diagnoses, 431 were true positive, 14 false positive, 66 false negative and 312 true negative. Sensitivity, specificity and diagnostic accuracy of computed tomography was 87,96 and 90%. Computed tomography had therapeutic consequences (surgery, drainage, puncture, reposition, thrombolytic therapy, chemotherapy, bronchoscopy, endoscopy, percutaneous transluminal angioplasty, coiling etc.) in 57% and no direct therapeutic interventions in 43%. Computed tomography excluded the suspected diagnosis in 36% and resulted in a conservative therapeutic regiment in 7%. Surgery was performed on 134 of the 418 patients (32%) who underwent computed tomography, with the surgery urgent in 71 (17%) and elective in 63 (15%) of the 418 patient. (orig.) [German] Ziel: Bewertung der diagnostischen Treffsicherheit und therapeutischen Konsequenzen der Computertomographie unter Notdienstbedingungen in einem Krankenhaus der Maximalversorgung. Material und Methoden: Innerhalb des definierten Studienzeitraums (12 Monate) wurden bei 418 Patienten 463 Computertomographien (Thorax, Abdomen

  18. The thermo-valve: a device for expanding compressed liquids and simultaneously gaining heat; Die Thermodrossel: Eine Anlage zur Entspannung komprimierter Fluessigkeiten unter Waermeabgabe

    Keller, J.U. [Siegen Univ. (Gesamthochschule) (Germany). Inst. fuer Fluid- und Thermodynamik; Goebel, M.U. [Siegen Univ. (Gesamthochschule) (Germany). Inst. fuer Fluid- und Thermodynamik


    The coefficient of performance (COP) of compression refrigeration cycles and heat pumps can be increased by substituting the expansion valve (throttle) by a so-called thermo-valve of heating vortex tube. This is a device in which compressed liquid working fluid coming in at ambient temperature is partly expanded. The saturated steam generated is superheated by liquid working fluid coming in subsequently. Then the steam is sent to a Ranque-Hilsch vortex tube to be expanded to evaporator`s pressure level. The hot end flow of gas leaving the vortex tube is cooled down in another heat exchanger and after this either recombined with the cold end flow leaving the tube and the fully expanded liquid stream or directly sent back to the compressor of the cycle. Due to the cooling of the hot end flow, the liquid portion in the liquid-gas mixture of the working fluid entering the evaporator of the cycle is increased, and so is the cooling capacity of the fluid and hence the cycle`s COP. For refrigeration cycles and heat pumps using R 22 or R 134a this increase can be about 5% and 10% respectively. However, if CO{sub 2} is used as working fluid the increase may be about 15% for refrigerators and 25% for room heating only heat pumps. In this paper the basic principles of the thermo-valve will be presented. Also several of its modifications will be discussed. A simple thermodynamic model to calculate the heat released is given. The design of and experiments with a prototype, using R 22 as working fluid will be discussed, the measurements performed so far verifying the figures given above. (orig.) [Deutsch] Die Entspannung komprimierter fluessiger Arbeitsstoffe der Energie- und Verfahrenstechnik erfolgt normalerweise in einer sog. Drossel isenthalp und stark irreversible, d.h. mit Exergieverlusten. Zur Nutzung der Exergie stehen grundsaetzlich zwei Wege offen, naemlich der Einsatz von Entspannungsmaschinen oder Thermodrosseln. Erstere koennen unter besonderen Umstaenden

  19. Die psychosomatische Dimension der funktionellen gastrointestinalen Störungen - Erfolg der Psychotherapie unter besonderer Berücksichtigung der Hypnotherapie

    Moser G


    Full Text Available Funktionelle gastrointestinale Störungen (FGIS stellen die häufigsten Erkrankungen in den ärztlichen Ordinationen dar. Die FGIS sind mit häufiger Arbeitsunfähigkeit, Verminderung der Lebensqualität und hohen medizinischen Kosten verbunden. Die meisten Patienten leiden unter psychosozialen Problemen. Deshalb ist es wichtig, die Beschwerden der Betroffenen in bezug auf ihre bio-psycho-soziale Situation zu beurteilen und ihr Zustandsbild nicht allein als biomedizinische Krankheit zu definieren. Betreuende Ärzte und Ärztinnen sollten die Relevanz der psychosozialen Aspekte erkennen, damit sie die Betroffenen für eine Überweisung zu Spezialisten (Psychosomatiker/innen, Psychotherapeut/inn/en vorbereiten und dafür interessieren bzw. motivieren können, beteiligte psychologische Faktoren weiter explorieren zu lassen. Die meisten Forschungsergebnisse zu Psychotherapie bei FGIS fokussieren auf das Reizdarmsyndrom, wobei verschiedenen Therapiemethoden (z. B. Verhaltenstherapie, Psychodynamische Therapie, Hypnotherapie oder Entspannungstechniken untersucht wurden. Randomisierte kontrollierte Psychotherapie-Studien mit Nachuntersuchung zeigen eine deutliche Überlegenheit der Psychotherapien gegenüber den konventionell medikamentösen Therapien. Enorm erfolgreich scheint die "gut-directed" Hypnose zu sein. Positives Ansprechen auf Psychotherapie allgemein ist wahrscheinlich, wenn (1 Stress die Symptome verstärkt oder auslöst, (2 milde Angst und Depression vorhanden ist, (3 das vorherrschende Symptom Schmerz und Durchfall und nicht Verstopfung ist, (4 der Schmerz sich mit Nahrungsaufnahme, Defäkation oder Stress verändert und nicht konstant vorhanden ist, und (5 das Beschwerdebild noch relativ kurz andauert. Psychotherapie ist zu Beginn relativ teuer, denn sie bedarf mehrerer längerer Sitzungen. Ihr Erfolg bleibt aber bestehen oder verstärkt sich langfristig sogar, da die Arztbesuche und medizinischen Kosten auf Dauer reduziert und dadurch

  20. Deformation behavior and load limits of asphaltic concrete under the conditions of cores in embankment dams; Deformationsverhalten und Belastungsgrenzen des Asphaltbetons unter den Bedingungen von Staudammkerndichtungen

    Mueller, U.


    Based on the analysis of existing dams with asphaltic diaphragm and investigations in the three-phase-system of asphaltic concrete a recipe for the composition of asphaltic cores is recommended. For the construction, rest and operating period of an embankment dam the load and the reaction of the asphaltic concrete cores as well as the appearing stress and deformations are described. Extensive material testings have been performed and at 41 asphaltic concrete specimens triaxial stress controlled pressure and creeping tests have been carried out. The evaluation of the triaxial tests led to proportions of the main stress and deformation limits as criteria of breaking. Under application of the standard equation for nonlinear viscoelastic element-laws a rheonom element formulation was developed from the experiment data and transformed into its differential form. With this approach the stress and deformation behavior of watertight asphaltic diaphragm can be precalculated for a period up to 10 years. The applicability of this approach, which can be also used within FE-calculations as well, is illustrated in four examples. (orig.) [Deutsch] Nach der Analyse bestehender Staudaemme mit Asphaltbetonkerndichtung und Untersuchungen zum Dreiphasensystem Asphaltbeton wird eine Rezepturempfehlung fuer den Asphaltkerndichtungsbau aufgestellt. Fuer die Bau-, Ruhe- und Betriebsphase eines Staudammes werden die Beanspruchungen und Reaktionen der Asphaltbetonkerndichtung sowie die auftretenden Spannungen und Verformungen beschrieben. Nach umfangreichen Materialpruefungen sind an 41 Asphaltbetonpruefkoerpern triaxiale spannungsgesteuerte Druck-Kriechversuche durchgefuehrt worden. Die Auswertung der Triaxialversuche ergab ein Grenzhauptspannungsverhaeltnis und Deformationsgrenzen als Bruchkriterien. Unter Verwendung der Standarformulierung fuer nichtlineare viskoelastische Stoffgesetze wurde aus den Versuchsdaten ein rheonomer Stoffansatz entwickelt und in seine differentielle Form

  1. Municipal climate protection as a measure for sustainable energy supply under the conditions of globalization and liberalization? An empirical investigation considering the municipal actors and public utility companies; Kommunaler Klimaschutz als Instrument einer nachhaltigen Energieversorgung unter den Bedingungen von Globalisierung und Liberalisierung? Eine empirische Untersuchung unter besonderer Beruecksichtigung der Akteure Kommune und Stadtwerke

    Bielitza-Mimjaehner, Ralf


    With the background of the threatening global warming that requires a reduction of greenhouse gas emission by 20 % until 2010 und by 80% until 2050 in Germany, t is reasonable to consider local or municipal climate protection activities. A climate protection politics ''from the bottom'' is not only contributing to a real greenhouse gas reduction, but also triggering the stagnant international climate politics and enhances the sustainable development on a local level. Due to this fact amongst others the Enquete commission of the German Bundestag ''sustainable energy supply under the conditions of globalization and liberalization'' identifies the municipal climate protection activities as important part within the mix of measures that will allow the initiation of an alteration of the actual energy system toward a sustainable energy supply in the long-run. The consequences of globalization and liberalization on the municipal level have not yet been discussed or considered by the Enquete commission. This thesis analyses the conditions induced by the globalization and liberalization on the municipal climate protection activities as constituent of a sustainable energy supply. The project is focusing on the municipal actors and the public utility companies as central point of the considerations. [German] Vor dem Hintergrund einer drohenden globalen Erwaermung, die eine Reduktion der klimawirksamen Treibhausgase bundesweit um 20 % bis 2010 und um 80 % bis 2050 noetig macht, sind Klimaschutzaktivitaeten auf einer lokalen oder kommunalen Ebene in mehreren Dimensionen sinnvoll. Den tatsaechlichen, bezifferbaren Reduktionen von CO2, die hier geleistet werden, gesellt sich ein ''vorbildhafter'' Druck auf eine stockende internationale Klimapolitik hinzu, ebenso leistet die ''Klimaschutzpolitik von unten'' einer nachhaltigen Entwicklung der lokalen Ebene durch Lerneffekte Vorschub. Unter anderem aus

  2. Sustainable power supply in conditions of globalisation and deregulation. Selected bibliography (as of 4 June 2000); Nachhaltige Energieversorgung unter den Bedingungen der Globalisierung und der Liberalisierung. Auswahlbibliographie (Redaktionsschluss: 04. Juni 2000)



    The bibliography was produced on behalf of the Enquiry Commission for Sustainable Power Supply in Conditions of Globalisation and Deregulation. It comprises publications on the following subjects: Air pollution abatement, energy markets, power industry, sustainable power supply, renewable energy sources, new energy engineering, environment-friendly mobility. [German] Die vorliegende Bibliographie wurde auf Anregung der Enquete-Kommission Nachhaltige Energieversorgung unter den Bedingungen der Globalisierung und der Liberalisierung erstellt. Die Gliederung der Bibliographie orientiert sich an den im Einsetzungsbeschlu paragraph aufgefuehrten thematischen Schwerpunkten: Klimaschutz, Energiemaerkte, Energiewirtschaft, nachhaltige Energieversorgung, erneuerbare Energie, neue Energietechnik, umweltfreundliche Mobilitaet. (orig.)

  3. Alkali release and sorption during combustion and gasification of coal under pressure; Freisetzung und Einbindung von Alkalien bei der Verbrennung und Vergasung von Kohle unter Druck

    Steffin, C.R.; Wanzl, W.; Heek, K.H. van [DMT-Gesellschaft fuer Forschung und Pruefung mbH, Essen (Germany). Geschaeftsbereich FuelTec - Kokerei- und Brennstofftechnik


    Investigations and model calculations have shown that water-soluble alkaline substances (in German coal, mostly NaCl) are released by a desorption process rather than a purely physical evaporation process. Sorption takes place in the presence of reactive oxygen species (H{sub 2}O or O{sub 2}), but only the reaction with water vapour is applicable to technical processes. Soorption is preferred to desorption at low temperatures both kinetically and thermodynamically. Metakaolin has a high alkali sorption capacity and potential depending significantly on the chemical properties of the clay mineral. With increasing basicity, the sorption potential decreases drastically, which has a significant effect in terms of fuel selection and mode of operation of the process of coal dust combustion under pressure. A fuel with low alkali emissions would be a coal grade with a small fraction of water-soluble alkalis and a high fraction of acid clay minerals. Intensive scrubbing in a wet chemical treatment stage may serve to reduce the water-soluble alkalis. [Deutsch] Die Untersuchungen und Modellrechnungen haben gezeigt, dass die Freisetzung der wasserloeslichen Alkalien, was in deutschen Steinkohlen hauptsaechlich NaCl ist, ein Desorptionsmechanismus zugrunde liegt und die Vorstellung eines rein physikalischen Verdampfungsprozesses verworfen werden muss. Die Einbindung der Alkalien findet unter Teilnahme reaktiver Sauerstoffspezies (H{sub 2}O oder O{sub 2}) statt, wobei aber nur die Reaktion mit Wasserdampf auch auf technische Prozesse uebertragbar ist. Die Einbindung ist gegenueber der Desorption bei niedrigen Temperaturen kinetisch und thermodynamisch bevorzugt. Metakaolin besitzt eine hohe Kapazitaet und ein hohes Potential zur Einbindung von Alkalien, wobei die Faehigkeit zur Einbindung ganz entscheidend von den chemischen Eigenschaften des Tonminerals abhaengig ist. Mit steigender Basizitaet nimmt das Einbindungspotential der Mineralsubstanz drastisch ab. Das hat auch

  4. Blasting in gravity dams with full stowage drivage method, approval and supervision of construction; Sprengen in Gewichtsstaumauern unter Vollstau - Vortriebsverfahren, Genehmigung und Bauueberwachung

    Aberle, B. [DMT GmbH, Essen/Dortmund (Germany). Abt. Fels- und Tunnelbau; Hellmann, J. [DMT GmbH, Essen/Dortmund (Germany). Abt. Explosionsschutz


    Sanierungsmassnahmen an Talsperren realisiert. Dazu mussten viele Mauern nachtraeglich mit einem Kontrollgang in Laengsrichtung ausgeruestet werden. Diese Gaenge dienen als Erkundungsstollen fuer den Zustand der Gruendungsfuge, als Draenagefassung fuer den erhoehten Sohlwasserdruck und fuer die Aufnahme von Messeinrichtungen in der Talsperre. Fuer die Auffahrung dieser Kontrollgaenge wurden verschiedene Verfahren angewendet. Der haendische Vortrieb einer Tunnelbohrmaschine und der Sprengvortrieb kamen dabei zum Einsatz. Das Sprengen in einer Staumauer, insbesondere unter Staubedingungen, erfordert besondere Massnahmen zum Schutz des Bauwerks. In diesem Beitrag werden die Ursachen fuer eine Sanierung, das Genehmigungsverfahren und die Ueberwachung eines Sprengvortriebs in einer Staumauer beschrieben. (orig.)

  5. New approaches for the reliability-oriented structural optimization considering time-variant aspects; Neue Ansaetze fuer die zuverlaessigkeitsorientierte Strukturoptimierung unter Beachtung zeitvarianter Aspekte

    Kuschel, N.


    The optimization of structures with respect to cost, weight or performance is a well-known application of the nonlinear optimization. However reliability-based structural optimization has been subject of only very few studies. The approaches suggested up to now have been unsatisfactory regarding general possibility of application or easy handling by user. The objective of this thesis is the development of general approaches to solve both optimization problems, the minimization of cost with respect to constraint reliabilty and the maximization of reliability under cost constraint. The extented approach of an one-level-method will be introduced in detail for the time-invariant problems. Here, the reliability of the sturcture will be analysed in the framework of the First-Order-Reliability-Method (FORM). The use of time-variant reliability analysis is necessary for a realistic modelling of many practical problems. Therefore several generalizations of the new approaches will be derived for the time-variant reliability-based structural optimization. Some important properties of the optimization problems are proved. In addition some interesting extensions of the one-level-method, for example the cost optimization of structural series systems and the cost optimization in the frame of the Second-Order-Reliabiity-Method (SORM), are presented in the thesis. (orig.) [German] Die Optimierung von Tragwerken im Hinblick auf die Kosten, das Gewicht oder die Gestalt ist eine sehr bekannte Anwendung der nichtlinearen Optimierung. Die zuverlaessigkeitsorientierte Strukturoptimierung wurde dagegen weit seltener untersucht. Die bisher vorgeschlagenen Ansaetze koennen bezueglich ihrer allgemeinen Verwendbarkeit oder ihrer nutzerfreundlichen Handhabung nicht befriedigen. Das Ziel der vorliegenden Arbeit ist nun die Entwicklung allgemeiner Ansaetze zur Loesung der beiden Optimierungsprobleme, einer Kostenminimierung unter Zuverlaessigkeitsrestriktionen und einer

  6. Investigations on practical risk assessment of pit fires, taking into account the time course of fires. Final report; Risikobeurteilung von Grubenbraenden. Untersuchungen zur praxisnahen Risikobeurteilung von Grubenbraenden unter Beruecksichtigung des zeitlichen Brandablaufs. Schlussbericht

    Foit, W.; Michelis, J.


    The data and knowledge of pit fires in the initial or early stage and their further development in experimental conditions are only available to a small extent so far. The aim of this investigation project to which the Land North Rhine-Westphalia made a financial contribution, was practical experiments on the semi-technical or natural scale on the question of how pit fires can occur and with what time dependence a small, locally limited fire develops into a large open pit fire. In addition, it should determine whether early recognition of fires occurring can be improved by new commercially available fire alarm systems. (orig./MSK) [Deutsch] Daten und Kenntnisse von Grubenbraenden im Entstehungs- oder Fruehstadium und deren weitere Entwicklung unter versuchstechnischen Bedingungen liegen bisher nur in geringem Umfang vor. Ziel des vorliegenden Untersuchungsvorhabens, das vom Land NRW bezuschusst wurde, waren praxisgerechte Versuche im halbtechnischen oder im natuerlichen Massstab zu der Fragestellung, wie Grubenbraende entstehen koennen und unter welcher zeitlichen Abhaengigkeit sich ein kleiner, oertlich begrenzter Entstehungsbrand zu einem grossen, offenen Grubenbrand ausbildet. Zusaetzlich sollte ermittelt werden, ob die Brandfrueherkennung von Entstehungsbraenden durch neue kommerziell erhaeltliche Brandmeldesysteme verbessert werden kann. (orig./MSK)

  7. Characterisation of different vegetable motor fuels with regard to their suitability as diesel substitutes and with special consideration to their chemical and physical properties; Charakterisierung verschiedener Pflanzenoelkraftstoffe hinsichtlich ihrer Eignung als Dieselkraftstoffsubstitute unter besonderer Beruecksichtigung ihrer chemischen und physikalischen Eigenschaften

    Klee, P.H.


    The author presents a characterisation of vegetable motor fuels on the basis of their chemical and physical properties. Apart from commercial diesel fuel, he investigated a rapeseed oil mixed fuel and four vegetable oil methyl esters. Exhaust emissions of aldehydes, ketones and PAH, both with and without legal limit values, were measured and compared with emissions using an oxidation catalytic converter. Different types of modifications were made in the fuel injection system of the engine in order to reduce nitric oxide emissions. The investigations show that vegetable fuels have an advantage in terms of emissions. Vegetable fuel structure and emission characteristics were shown to correlate. [Deutsch] In der vorliegenden Arbeit erfolgt eine umfassende Charakterisierung der motorischen Verwendung von verschiedenen Pflanzenkraftstoffen auf der Basis ihrer chemischen und physikalischen Eigenschaften. Neben handelsueblichem Dieselkraftstoff werden ein Rapsoelmischkraftstoff und vier Pflanzenoelmethylester untersucht. Es werden sowohl die gesetzlich limitierten, als auch die gesetzlich nicht limitierten Abgasemissionen an Aldehyden, Ketonen und polyzyklischen aromatischen Kohlenwasserstoffen untersucht. Die Rohemissionen werden mit den Emissionen unter Verwendung eines Oxidationskatalysators verglichen. Zur Absenkung der Stickoxidemissionen unter Verwendung von Pflanzenkraftstoffen werden verschiedene Modifikationen am Einspritzsystem des Motors vorgenommen. Die durchgefuehrten Untersuchungen zeigen weitreichende Emissionsvorteile von Pflanzenkraftstoffen auf. Der systematische Zusammenhang zwischen Pflanzenkraftstoffstruktur und Emissionsverhalten wird nachgewiesen. (orig.)

  8. Receptor imaging of schizophrenic patients under treatment with typical and atypical neuroleptics; Nuklearmedizinische Rezeptordiagnostik bei schizophrenen Patienten unter Therapie mit typischen und atypischen Neuroleptika

    Dresel, S.; Tatsch, K. [Klinik und Poliklinik fuer Nuklearmedizin der Ludwig-Maximilians-Univ. Muenchen (Germany); Meisenzahl, E. [Psychiatrische Klinik der Ludwig-Maximilians-Univ. Muenchen (Germany); Scherer, J. [Bezirkskrankenhaus Haar (Germany)


    -motorische Nebenwirkungen hervorzurufen. Die Besetzung postsynaptischer Dopamin-D2-Rezeptoren wird als ein wesentlicher Aspekt der antipsychotischen Wirksamkeit der Neuroleptika angesehen. Diese koennen nuklearmedizinisch durch [I-123]IBZM-SPECT dargestellt werden. Fuer das typische Neuroleptikum Haloperidol wurde eine dosisabhaengige, exponentielle Besetzung der Dopamin-D2-Rezeptoren nachgewiesen. Ab einem Schwellenwert des spezifischen Bindungsindex von 0,4 (Norm: >0,95) zeigten mit einer Ausnahme alle untersuchten Patienten extrapyramidal-motorische Nebenwirkungen. Auch unter Therapie mit dem atypischen Neuroleptikum Clozapin ergab sich eine exponentielle Dosis-Wirkungsbeziehung mit jedoch einem deutlich flacheren Kurvenverlauf im Vergleich zu Haloperidol. Extrapyramidalmotorische Nebenwirkungen traten bei diesen Patienten nicht auf. Neuere, als atypisch eingestufte Neuroleptika wie Risperidon und Olanzapin zeigten ebenfalls eine exponenzielle Dosis-Wirkungsbeziehung, wobei deren Kurvenverlaeufe zwischen denen von Haloperidol und Clozapin lagen. Extrapyramidal-motorische Nebenwirkungen traten bei den letzteren Neuroleptika seltener als bei Haloperidol, bei Olanzapin nur bei einem Patienten in unserem eigenen Patientengut auf. Das pharmakologische Profil atypischer Neuroleptika zeichnet sich neben der Bindung an die postsynaptischen Dopamin-D2-Rezeptoren auch durch Bindung an Rezeptoren diverser anderer Neurotransmittersysteme, insbesondere des serotonergen Systems, aus. Somit ist wahrscheinlich, dass die niedrigere Inzidenz fuer extrapyramidal-motorische Nebenwirkungen bei atypischen Neuroleptika durch (orig.)

  9. MRI-based N-staging in esophageal cancer; N-Staging des Oesophaguskarzinoms mittels MRT unter Verwendung von artefaktreduzierenden LOTA-Sequenzen

    Krupski, G.; Lorenzen, J.; Nicolas, V.; Adam, G. [Universitaetsklinikum Hamburg-Eppendorf, Hamburg (Germany). Abt. fuer Diagnostische und Interventionelle Radiologie; Gawad, K.; Izbicki, J.R. [Universitaetsklinikum Hamburg-Eppendorf, Hamburg (Germany). Abt. fuer Allgemeinchirurgie


    artefaktreduzierenden Sequenzen in LOTA (Long Term Averaging)-Technik gestattet eine deutlich artefaktgeminderte, praezise Untersuchung insbesondere des hinteren Mediastinums. In einer prospektiven Untersuchung soll die Wertigkeit der MRT unter Verwendung der LOTA-Technik (Siemens AG, Erlangen) fuer das N-Staging des Oesophagus-Karzinoms untersucht werden. Material und Methoden: Bei 15 Patienten (10 Plattenepithel-Karzinome und 5 distale Adeno-Karzinome) wurde maximal 4 Wochen vor Oesophagektomie eine standardisierte MRT des Oesophagus an einem 1,5 T Kernspintomographen (Magnetom Symphony, Siemens AG, Erlangen) durchgefuehrt. Die Qualitaet der erzeugten Bilder wurde anhand der Abgrenzbarkeit des Oesophagus zur Umgebung sowie der mehrschichtigen Darstellung der Aortenwand, respektive Pars membranacea der Trachea, beurteilt. Als Kriterien fuer eine metastatische Infiltration eines Lymphknotens wurde ein Groesse von mehr als 15 mm oder eine rundliche Darstellung verbunden mit einer Gd-DTPA-Aufnahme gewertet. Die Auswertung erfolgte unabhaengig durch zwei erfahrene Radiologen. Die erhobenen Daten wruden mit denen der histopathologischen Aufarbeitung des Operationspraeparates verglichen. Ergebnisse: Es zeigt sich bei 14 von 15 Patienten eine gute bis sehr gute Bildqualitaet. Hinsichtlich des N-Stagings ergab sich eine Sensitivitaet von 100% bei einer Spezifitaet von 78% fuer einen metastatischen Lymphknotenbefall. Bei fehlender Darstellbarkeit des Truncus coeliacus wurde eine Lymphknotenmetastase in einem nicht vergroesserten Lymphknoten am Truncus coeliacus (M1) nicht beschrieben. Schlussfolgerung: Mit der MRT gelingt es beim Oesophagus-Karzinom durch Verwendung von EKG-Gating und LOTA-Sequenzen, das N-Stadium in annaehernd gleicher Qualitaet wie mit dem Goldstandard Endosonographie zu beurteilen. Die Kernspintomographie sollte daher in verstaerktem Masse insbesondere bei Patienten eingesetzt werden, bei denen die Endosonographie nicht moeglich ist. (orig.)

  10. Percolation experiments to determine fluid-matrix interaction (with particular regard to pretreatment of the drill core); Kerndurchstroemungsversuche zur Ermittlung von Fluid-Matrix-Wechselwirkungen (unter besonderer Beruecksichtigung der Kernvorbehandlung)

    Martin, M.; Seibt, A. [TU Bergakademie Freiberg (Germany). Inst. fuer Bohrtechnik und Fluidbergbau; Hoth, P. [GeoForschungsZentrum Potsdam (Germany)


    The injection of fluids into sandstone reservoirs leads to interactions between these waters, the reservoir rocks, and the formation fluids. Estimations about possible permeability reducing processes caused by these interactions are therefore of great importance for the exploitation of sandstone aquifers as geothermal reservoirs. Percolation experiments under in situ conditions with core samples from North German geothermal boreholes were done in order to investigate these fluid-rock interactions. (orig./AKF) [Deutsch] Die Injektion von Fluiden in Aquiferspeicher fuehrt zu Wechselwirkungen zwischen dem Speichergestein, den Formationsfluiden und den injizierten Loesungen. Fuer die Bewirtschaftung der Speicher sind insbesondere Kenntnisse ueber moegliche Permeabilitaetsreduzierungen durch diese Wechselwirkungen von Bedeutung. Mit Hilfe von Kern-Durchstroemungsexperimenten, durchgefuehrt unter lagerstaettenaehnlichen Bedingungen mit Original- bzw. modifizierten Fluiden, wurde daher das Durchstroemungsverhalten von unterschiedlich ausgebildeten Reservoirsandsteinen aus norddeutschen Geothermiebohrungen untersucht. (orig./AKF)

  11. Alternative natural gas supply agreements under TPA?. A concept for short-term contracts in a competitive market; Alternative Vertragsformen der Erdgasbranche unter TPA?. Ansatz zur Gestaltung kurzfristiger Vertraege in einem wettbewerblich organisierten Markt

    Ruegge, P.


    The most recent version of EC Commission proposals are looking towards unbundling and the introduction of third party access to liberalise the monopolistic transportation area of the natural gas market. The main problems facing the natural gas industry, according to the transit directive, are in contracting (i.e. investment security, risk allocation) and price-fixing for supply as well as an alleged full-capacity problem. Competition in their area signifies a stark contrast to the present `Take or pay`` system. This study examines the prospects of altering the existing contrast systems from the TPA point of view. In this system, that would indicate short-term delivery contracts to increase flexibility of the long-distance cuble system and so release extra capacity. Concentration is given in this study on how to implement such short-term contracts and also on how investment can be seewed. (UA) [Deutsch] Die Vorschlaege der EG-Kommission sehen in ihrer letzten Version das sogenannte ``Unbundling`` und die Einfuehrung von Third Party Access vor, um den auf der Transportstufe monopolistisch organisierten Erdgasmarkt zu liberalisieren. Die Hauptprobleme, vor die sich die europaeische Erdgasindustrie hinsichtlich der Transitrichtlinie gestellt sieht, sind in den Bereichen der Vertragsgestaltung (sprich Investitionsabsicherung bzw. Risikoallokation) sowie der Preisbildung fuer Durchleitungen und in einem angeblich ausgelastetem Kapazitaetsproblem zu sehen. Wettbewerb auf dieser Marktstufe bedeutet einen krassen Gegensatz gegenueber dem derzeitigen System von Take or Pay-Verpflichtungen. Diese Arbeit befasst sich mit der grundsaetzlichen Moeglichkeit einer Veraenderung des bestehenden Vertragssystems unter TPA-Gesichtspunkten. Das bedeutet, dass in diesem System kurzfristige Liefervertraege abgeschlossen werden muessen, damit die notwendige Flexibilitaet des Fernleitungssystems hergestellt werden kann, um freie Kapazitaeten zu schaffen. Es wird sich jedoch auf das Problem

  12. Clarithromycin and N-acetylcysteine co-spray-dried powders for pulmonary drug delivery: A focus on drug solubility.

    Manniello, Michele Dario; Del Gaudio, Pasquale; Aquino, Rita P; Russo, Paola


    Cystic fibrosis (CF) lungs are usually susceptible to Pseudomonas aeruginosa colonization and this bacterium is resistant to immune system clearance and drug control. Particularly, the biofilm mode of growth protects several microorganisms from host defenses and antibacterial drugs, mainly due to a delayed penetration of the drug through the biofilm matrix. Biofilm, together with lung mucus viscosity and tenacity, reduces, therefore, the effectiveness of conventional antibiotic therapy in CF. The aim of this research was to design and develop a stable, portable, easy to use dry powder inhaler (DPI) for CF patients, able to release directly to the lung an association of macrolide antibiotics (clarithromycin) and a mucolytic agent (N-Acetyl-Cysteine). Its effectiveness is based on the counteracting of the characteristics of P. aeruginosa infections in CF (lung bacterial adhesion to lung epithelium, biofilm formation and mucus viscosity) and the ability to let the antimicrobial drug exert their pharmacological action. A solution of these two drugs, without any excipients, was spray-dried to obtain respirable microparticles, characterized by aerodynamic diameters suitable for inhalation (acetylcysteine which can interact with clarithromycin dimethyl-amino group, a consistent enhancement of drug solubility was obtained, compared to raw material and to the drug sprayed alone. The mucolytic agent added in the DPI may improve the macrolide diffusion into the mucus, enabling its action.

  13. Existing and potential therapeutic uses for N-acetylcysteine: the need for conversion to intracellular glutathione for antioxidant benefits.

    Rushworth, Gordon F; Megson, Ian L


    N-acetyl-l-cysteine (NAC) has long been used therapeutically for the treatment of acetaminophen (paracetamol) overdose, acting as a precursor for the substrate (l-cysteine) in synthesis of hepatic glutathione (GSH) depleted through drug conjugation. Other therapeutic uses of NAC have also emerged, including the alleviation of clinical symptoms of cystic fibrosis through cysteine-mediated disruption of disulfide cross-bridges in the glycoprotein matrix in mucus. More recently, however, a wide range of clinical studies have reported on the use of NAC as an antioxidant, most notably in the protection against contrast-induced nephropathy and thrombosis. The results from these studies are conflicting and a consensus is yet to be reached regarding the merits or otherwise of NAC in the antioxidant setting. This review seeks to re-evaluate the mechanism of action of NAC as a precursor for GSH synthesis in the context of its activity as an "antioxidant". Results from recent studies are examined to establish whether the pre-requisites for effective NAC-induced antioxidant activity (i.e. GSH depletion and the presence of functional metabolic pathways for conversion of NAC to GSH) have received adequate consideration in the interpretation of the data. A key conclusion is a reinforcement of the concept that NAC should not be considered to be a powerful antioxidant in its own right: its strength is the targeted replenishment of GSH in deficient cells and it is likely to be ineffective in cells replete in GSH.

  14. Recurrent acute rhinosinusitis: a single blind clinical study of N-acetylcysteine vs ambroxol associated to corticosteroid therapy.

    Macchi, A; Terranova, P; Castelnuovo, P


    The aim of rhinosinusitis treatment is to restore sinusal eutrophism and to normalize ventilation and mucociliary transport. Frequently the improvement of sinusal physiological conditions is associated with a reduction of infections and pulmonary symptoms. The treatment of these diseases often requires the combination of medical and surgical strategies. In particular, the aim of the medical therapy is multiple: to treat the infection (with antibiotics), to reduce the mucosal swelling (with corticosteroids) and to improve mucus drainage (with mucolytics or muco-regulators). The use of atomized nasal douche, as a washing of the nasal fossas, is chosen because of its local action minimizing systemic adverse effects. The surgical treatment is secondary to medical failure, and it is focused on clearing the sinusal ostia in the sphenoethmoidal recess and the osteomeatal complex. In case of recurrent sinonasal diseases the importance of the surgical operation is represented by the fact that the medical treatment better reaches the target in the sinusal space. This study is focused on the primary medical treatment of acute recurrent rhinosinusitis. The patients who immediately needed surgical treatment were excluded from the study (because of the presence of an anatomical obstruction of the osteomeatal complex and/or the sphenoethmoidal recess, hence non-susceptible to improvement by medical therapy alone), and these patients were immediately addressed to undergo a CT scan examination in order to be involved in a future surgical programme. The medical treatment for those forms which do not require antibiotics (i.e. when infections are not involved), is based on the use of topical corticosteroids. While there are controversies on the real efficacy of adding mucolytic agents to the steroids, they are commonly prescribed in clinical practice, with the rationale of reducing viscosity and improving clearance of mucus in order to help the restoration of the physiological sinus conditions. The primary aim of the medical treatment is to reduce the number of acute episodes and thus to increase the time between the exacerbations, allowing a good quality of life without necessitating surgical procedure.

  15. N-acetylcysteine modifies the acute effects of isosorbide-5-mononitrate in angina pectoris patients evaluated by exercise testing

    Svendsen, Jesper Hastrup; Klarlund, K; Aldershvile, J


    , given together with a single oral dose of the long-acting nitrate, isosorbide-5-mononitrate (5-ISMN, 60 mg), would modify the nitrate effect evaluated by exercise testing before and after additional sublingual doses of nitroglycerin (NTG). Ten patients with angina pectoris and angiographically proven...... significant coronary artery disease were included. All patients received a baseline therapy with beta blockers. None of the patients had developed nitrate tolerance at inclusion. NAC/5-ISMN treatment significantly prolonged the total exercise time as compared with placebo/5-ISMN (7.7 +/- 2.1 min vs. 6.8 +/- 1...

  16. Cytoprotective effects of amifostine, ascorbic acid and N-acetylcysteine against methotrexate-induced hepatotoxicity in rats

    Akbulut, Sami; Elbe, Hulya; Eris, Cengiz; Dogan, Zumrut; Toprak, Gulten; Otan, Emrah; Erdemli, Erman; Turkoz, Yusuf


    AIM: To investigate the potential role of oxidative stress and the possible therapeutic effects of N-acetyl cysteine (NAC), amifostine (AMF) and ascorbic acid (ASC) in methotrexate (MTX)-induced hepatotoxicity.

  17. MR-imaging of the breast at 0.5 Tesla: menstrual-cycle dependency of parenchymal contrast enhancement in healthy volunteers with oral contraceptive use?; MR-Mammographie bei 0,5 Tesla: Menstruationszyklusabhaengigkeit der Kontrastmittelanreicherung unter hormoneller Kontrazeption?

    Lorenzen, J.; Welger, J.; Krupski, G.; Adam, G. [Klinik und Poliklinik fuer Diagnostische und Interventionelle Radiologie, Universitaetsklinikum Hamburg-Eppendorf (Germany); Lisboa, B.W. [Klinik und Poliklinik fuer Frauenheilkunde und Geburtshilfe, Universitaetsklinikum Hamburg-Eppendorf (Germany)


    Introduction: To evaluate changes of contrast medium enhancement of the breast parenchyma due to menstrual cycle in healthy volunteers with oral contraceptive use in MR-imaging of the breast. Material and Methods: 15 healthy volunteers (age: 22 - 36, mean 28,2) without breast disease were examined two times during one menstrual cycle (days 7 - 14 and days 21 - 2). Two volunteers were examined only in the second part of the cycle (days 21 - 2). All volunteers used oral contraceptives for more than 6 month continuously. Examinations were performed with a 0,5 T magnet (dynamic 3D-gradient echo protocol with subtraction postprocessing). We evaluated the number of enhancing foci and the parenchymal contrast medium enhancement during the different phases of the cycle by region of interest. Results: Only a total of two enhancing foci were found in 2 of 17 volunteers. Time/signal intensity diagrams in these both cases were not suspicious (< 80% initial signal increase after of contrast medium injection, no wash-out phenomenon) and sonography of the breast in these two cases was inconspicuous. Contrast medium enhancement of breast parenchyma in cycle days 7 - 14 (mean enhancement: 0.12 - 0.26, minutes 1 - 9 p.i.) was not significantly different (p = 0.2209; Wilcoxon signed rank test) from cycle days 21 - 2 (mean: 0.13 - 0.32). Conclusion: Menstrual cycle dependency of parenchymal contrast medium enhancement seems to be of minor relevance for premenopausal women with use of oral contraceptives. (orig.) [German] Fragestellung: Untersuchung der Kontrastmittelaufnahme des Brustparenchyms in Abhaengigkeit vom Menstruationszyklus bei gesunden Probandinnen unter oraler Kontrazeption. Material und Methode: Bei 15 gesunden Probandinnen ohne Brusterkrankung in der Anamnese wurde eine MR-Mammographie zweimal waehrend eines Menstruationszyklus durchgefuehrt (Zyklustag: 7 - 14 und 21 - 2). Bei zwei weiteren Probandinnen erfolgte die MR-Mammographie nur in der zweiten Zyklushaelfte

  18. The value of magnetic resonance imaging (MRI) in the treatment planning of vertebral metastasis considering economic aspects. A cost benefit-analysis; Die Wertigkeit der Magnetresonanztomographie (MRT) unter oekonomischen Aspekten bei der Bestrahlungsplanung von Wirbelkoerpermetastasen. Eine Kosten-Nutzen-Analyse

    Prott, F.J.; Schlehuber, E.; Scharding, B.J.; Rinast, E. [Strahlentherapie Wiesbaden, St.-Josefs-Hospital (Germany); Micke, O. [Klinik und Poliklinik fuer Strahlentherapie - Radioonkologie, Universitaetsklinikum Muenster (Germany)


    Is magnetic resonance imaging (MRI) based target volume definition for treatment planning of vertebral metastasis effective under economic considerations.From 1994 to 1999, a total of 137 patients with bone metastases affecting the vertebral column underwent MRI of the cercival, thoracic, or lumbar spine for the treatment planning of palliative radiation therapy. The following radiation treatment consisted in a irradiation of the affected vertebral region up to a total dose of 30-40 Gy.The cost calculation for radiotherapy and magnetic resonance tomography was done using the common tariff model (EBM) of the German Health Insurances.In 73% of patients (101 patients), magnetic resonance imaging resulted in marked corrections of the irradiation fields which would have resulted in the necessity of treatment for recurrence in the case of treatment planning without MRI.Consequently, the higher cost of MRI of 345.00 DEM (176,40 EUR) lead to a saving of 497.00 DEM (254,11 EUR) compared to a recurrence treatment of 10 fractions and of 1,428.00 DEM (730,12 EUR) compared to 20 fractions. The transport expenses for the second treatment could be saved as well.Even under economic considerations MRI is effective. (orig.) [German] Ist eine MRT-gestuetzte Zielvolumendefinition bei der Strahlentherapie von Knochenmetastasen ein sinnvolles Vorgehen unter oekonomischen Gesichtspunkten?1994-1999 wurde bei 137 Patienten mit einem ossaer metastasierenden Tumor und Befall der Wirbelsaeule eine Magnetresonanztomographie (MRT) zur Planung einer palliativen Radiatio durchgefuehrt. Die nachfolgende Strahlentherapie bestand aus einer Radiatio des betroffenen Wirbelkoerperabschnitts bis zu einer Gesamtherddosis von 30-40 Gy. Fuer die Berechnung der Kosten wurde der einheitliche Bewertungsmassstab der Deutschen Krankenkassen zugrunde gelegt.Aufgrund der MRT-Untersuchungen wurde bei 73% der Patienten eine Veraenderung des Bestrahlungsfeldes vorgenommen, die im Falle einer nicht MRT

  19. Description of a disposition line on the stress corrosion cracking behaviour of ferritic reactor pressure vessel steels under BWR-conditions; Beschreibung einer einhuellenden Risswachstumskurve zum Spannungsrisskorrosionsverhalten von ferritischen Reaktordruckbehaelter (RDB)-Staehlen unter Siedewasserreaktor (SWR)-Bedingungen

    Bruemmer, G. [HEW, Hamburg (Germany); Hoffmann, H. [VGB-GS, Essen (Germany); Ilg, U. [EnBW Kraftwerke AG, Philippsburg (Germany); Wachter, O. [E.ON-Kernkraft, Hannover (Germany); Widera, M. [RWE Power, Essen (Germany); Roth, A. [Framatome ANP GmbH, Erlangen (Germany)


    The inner surface of the reactor pressure vessel of BWR reactors is lined with a welded, corrosion-resistant steel liner. In an assumed case of liner rupture down to the low-alloy ferritic base material, an integrity assessment of the pressure vesssel in consideration of the effects of reactor coolant is of utmost importance, and research in this field has been going on for more than ten years now. An analysis of the available data shows that it is now possible to describe a disposition line on the stress corrosion cracking behaviour of ferritic reactor pressure vessel steels in BWR conditions. Crack growth rates of a stress intensity factor corresponding to a T/4 wall defect (i.e. 25 percent of the wall thickness) are technically not relevant. This scientific finding is supported by measurements of about 450 reactor operation years of all German LWR reactor plants, none of which showed crack initiation in the reactor pressure vessel. [German] Die mediumberuehrte Innenoberflaeche des Reaktordruckbehaelters (RDB) von Siedewasserreaktoren (SWR) ist mit einer korrosionsbestaendigen austenitischen Schweissplattierung versehen. Fuer den unterstellten Fall einer bis auf den niedriglegierten, ferritischen Grundwerkstoff durchgerissenen Pattierung ist fuer die Beurteilung der Integritaet des RDB unter Beruecksichtigung der Einwirkung des Reaktorkuehlmittels die Klaerung der Frage eines korrosionsgestuetzten Risswachstums von grosser Bedeutung. Dieses Thema ist daher bereits seit mehr als 10 Jahren Gegenstand umfangreicher Forschungsaktivitaeten. Ende der 80er- und Anfang der 90er-Jahre wurden fuer ferritische RDB-Staehle von SWR-Anlagen Risswachstumsgeschwindigkeiten veroeffentlicht, die binnen weniger als einem Jahr zum Durchriss der drucktragenden Wand eines RDB gefuehrt haetten. Daraufhin wurden internationale Forschungsaktivitaeten zur Ermittlung zuverlaessiger und reproduzierbarer Risswachstumsdaten initiiert, deren Ergebnisse zusammenfassend dargestellt werden. Die

  20. Permeability to brine of crushed salt rock for waste isolation, considering long-term pressure variation of overlying strata and dissolution processes. Final report; Durchlaessigkeitsverhalten von Steinsalzversatz gegenueber Laugen unter Beruecksichtigung von zeitlich veraenderlichen Ueberlagerungsdruecken und Loesungsvorgaengen. Abschlussbericht

    Froehlich, H. [Battelle Ingenieurtechnik GmbH, Eschborn (Germany); Conen, O. [Technische Univ. Darmstadt (Germany); Haefner, F.; Bruck, J. v. der [Technische Univ. Bergakademie Freiberg (Germany)


    It cannot be excluded that there will be ingress of brines to underground isolation plants for nuclear and chemical toxic wastes. The transport mechanisms in the waste repository are much determined by the perviousness of the backfilling and the sealing material used after waste emplacement in salt rock mine shafts. The critical quantity is the permeability, both for inflow of brine into the bedded waste areas, and for contaminated brine squeeze-out mechanisms. The project research work was to establish the mass transfer parameters for calculating the transport mechanisms in backfilled and sealed shafts. Using near-reality simulation of conditions, the time-dependent influence of pressure variations of overlying strata, humidity and salt/brine interactions on the permeability was examined and quantified. (orig./CB) [German] In Endlagern fuer nukleare und chemotoxische Abfaelle im Salinar kann der Zutritt von Laugen nicht prinzipiell ausgeschlossen werden. Die Transportvorgaenge innerhalb des Endlagers werden wesentlich von der Durchlaessigkeit der Versatzmaterialien und der Verschluesse bestimmt. Die bestimmende Groesse, sowohl fuer den Laugenzufluss in die Einlagerungsbereiche als auch fuer das Auspressen kontaminierter Lauge aus dem Endlager, ist dabei die Permeabilitaet. Ziel der hier vorgestellten Arbeiten war es, Stofftransportparameter fuer die Berechnung von Ausbreitungsvorgaengen in den verfuellten Bereichen eines salinaren Endlagers bereitzustellen. Unter Simulation realitaetsnaher Bedingungen wurde der Einfluss von zeitabhaengigem Ueberlagerungsdruck (Gebirgsdruck), Feuchte und die Wechselwirkung von Salz/Lauge auf das Durchlaessigkeitsverhalten untersucht und quantifiziert. (orig.)

  1. Comparison calculation/experiment on the load case ``shutdown of TH high pressure pumps under consideration of fluid structure interaction``; Vergleich Rechnung/Messung zum Lastfall ``Abschaltung der TH-Hochdruckpumpen unter Beruecksichtigung der Fluid-Struktur-Wechselwirkung``

    Erath, W.; Nowotny, B.; Maetz, J. [KED, Rodenbach (Germany)


    Measurements of an experiment in a pipe system with pump shutdown and valve closing have been performed in the nuclear power plant KRB II. Comparative calculations of fluid and structure including interaction show an excellent agreement with the measured results. Theory and implementation of the fluid/structure interaction and the results of the comparison are described. It turns out that the consideration of the fluid/structure interaction is mostly a significant increase of the effective structural damping. (orig.) [Deutsch] Es wurden Messungen am nuklearen Nachkuehlsystem des Kernkraftwerks Gundremmingen (KRB II) bei einem Versuche mit Pumpenabschalten und Ventilschliessen durchgefuehrt. Vergleichsrechnungen der Fluid-Strukturdynamik unter echter Beruecksichtigung der Wechselwirkung ergaben eine ausgezeichnete Uebereinstimmung der Rechnung mit den Messungen. Es werden Theorie und Implementierung der Koppelung der Fluid- und Struktur-Berechnungen sowie die Vergleiche von Messung und Rechnung beschrieben. Es ergibt sich, dass die Beruecksichtigung der Wechselwirkung notwendig ist zur genaueren Berechnung von `weichen` Rohrleitungsystemen. Eine wichtige Folge der Wechselwirkung ist meist eine deutliche Erhoehung der effektiven Strukturdaempfung. (orig.)

  2. Case report: massive lower intestinal bleeding from ileal varices. Treatment with transjugular intrahepatic portosystemic shunt (TIPSS); Fallbericht: Massive untere gastrointestinale Blutung aus ilealen Varizen. Behandlung mittels transjugulaerem intrahepatischem portosystemischem Shunt (TIPSS)

    Lopez-Benitez, R. [Universitaetsklinikum Heidelberg (Germany). Abteilung fuer Diagnostische und Iinterventionelle Radiologie; Universitaetsklinikum, Abteilung fuer Diagnostische und Interventionelle Radiologie, Heidelberg (Germany); Seidensticker, P.; Richter, G.M.; Stampfl, U.; Hallscheidt, P. [Universitaetsklinikum Heidelberg (Germany). Abteilung fuer Diagnostische und Iinterventionelle Radiologie


    Acute gastrointestinal bleeding in patients with liver cirrhosis is associated with a high mortality. Ileal varices and collaterals from ectopic vessels are extremely rare, encountered in less than 5% of the cirrhotic patients. The diagnosis is frequently delayed because the regular diagnostic methods such as gastroscopy or colonoscopy are unsuccessful in accurate the source of bleeding in the majority of the cases. We report an unusual case of massive and uncontrollable lower intestinal bleeding from ileal varices with right ovarian vein anastomosis in a 56 year-old female patient with liver cirrhosis and previous history of abdominal and pelvic surgery. The accurate angiographic and computed tomography diagnosis allowed fast decompression of the portal venous system using a transjugular intrahepatic portosystemic shunt. (orig.) [German] Akute gastrointestinale Blutungen sind bei Leberzirrhosepatienten mit einer hohen Mortalitaet verbunden. Ileale Varizen und Kollateralen aus anderen ektopen Gefaessen des Darms sind extrem selten und treten bei weniger als 5% aller Zirrhosepatienten auf. Die Diagnosestellung erfolgt oft verspaetet, da die ueblichen diagnostischen Untersuchungsmethoden wie Gastroskopie oder Koloskopie in den meisten Faellen die Blutungsquelle nicht ausreichend darstellen. Wir berichten ueber einen ungewoehnlichen Fall von massiver und unkontrollierbarer unterer gastroinstestinaler (GI-)Blutung aus ilealen Varizen mit Verbindung zur rechten V. ovarica einer 56-jaehrigen Frau, bei der anamnestisch eine Leberzirrhose und abdominelle Operationen sowie Operationen im Bereich des Beckens bekannt waren. Die genaue angiographische und computertomographische Diagnose erlaubte eine rasche Dekompression des Portalvenensystems mittels eines transjugulaeren portosystemischen Shunts. (orig.)

  3. Materials model for describing the austenite-martensite phase transformation considering transformation-induced plasticity; Ein Materialmodell zur Beschreibung der Austenit-Martensit Phasentransformation unter Beruecksichtigung der transformationsinduzierten Plastizitaet

    Oberste-Brandenburg, C.


    In this thesis, a model to describe the austenite martensite transformation was developed. The transformation induced plasticity (TRIP) was taken into consideration. The model can be used to design complex structures. A local examination of the energy and entropy balance at the phase boundary serves as the starting point for the identification of the thermodynamical driving force and the thermodynamic flow. For both, a tensorial description is necessary for a general nonhydrostatically stressed solid. In the second part, a material law for the description of TRIP-Steels was developed based on the values derived in the first part. The different mechanical behavior of the phases, especially the differing yield stresses, was taken into account. The model developed was implemented into the finite element program MARC. Simulations of the material and the structural behavior were performed. The experimentally observed strong dependence of the transformation kinetics on the yield stress of the austenite and the dependence of the orientation of the martensite inclusion on the stress state could be verified. (orig.) [German] Im Rahmen dieser Arbeit wurde ein Materialmodell zur Beschreibung der Austenit-Martensit Phasenumwandlung unter Beruecksichtigung der transformationsinduzierten Plastizitaet (TRIP) entwickelt. Das Modell ist zur Berechnung ausgedehnter Strukturen einsetzbar. Eine lokale Betrachtung der Energie- und Entropiebilanz an der Phasengrenze bildet den Ausgangspunkt zur Identifikation der thermodynamischen Kraft und des thermodynamischen Flusses bei Beschreibung der Transformationskinetik. Fuer beide Groessen muss fuer den allgemein nichthydrostatischen Spannungszustand eine tensorielle Beschreibung verwendet werden. Im zweiten Teil der Arbeit bilden diese Groessen die Basis zur Entwicklung eines Stoffgesetzes zur Beschreibung des TRIP-Phaenomens. Es wird das unterschiedliche mechanische Verhalten der Phasen, insbesondere die stark unterschiedlichen

  4. Pressurized fluidized-bed power stations. Combined cycle power plants with fluidized-bed combustion, with particular regard to emissions; Druckwirbelschicht-Kraftwerke. Kombikraftwerke mit Druckwirbelschichtfeuerung - Entwicklung fuer Braunkohle unter besonderer Beruecksichtigung des Emissionsverhaltens

    Chalupnik, R.W.


    Investigations were carried out to find whether this technology is suited for lignite. The state of the art of the pressurized fluidized bed technology for coal is presented. The planning of the experimental programme is explained, including unresolved problems of thermal calculation, raw lignite transport characteristics, and emissions. Emissions of atmospheric and pressurized fluidized bed combustion of coal and lignite are compared, and the results of a theoretical investigation of the potential performance are presented. Recommendations are made for further studies, and an outlook is given to future 'second generation' concepts with higher efficiencies resulting from higher gas turbine inlet temperatures. [German] Die vorliegende Arbeit berichtet ueber die Entwicklung der Kombikraftwerkstechnik mit Druckwirbelschichttechnik. Nachdem die bisherigen Aktivitaeten weltweit fast ausschliesslich fuer den Einsatz von Steinkohle betrieben wurden, bestand die Aufgabenstellung in der Erarbeitung von ersten grundlegenden Ergebnissen, aufgrund derer zu beurteilen war, ob die Druckwirbelschichttechnik fuer den Einsatz von Braunkohle geeignet ist. Kapitel 2 stellt den Stand der Technik der Druckwirbelschichtverbrennung fuer Steinkohle dar. In Kapitel 3 wird die Planung des Versuchsprogramms erlaeutert, die sich an den offenen Fragestellungen zu den waermetechnischen Rechnungen, zum Foerderverhalten von Rohbraunkohle und zum Emissionsverhalten orientierte. In der Diskussion der Ergebnisse in Kapitel 4 erfolgt eine Einordnung und Bewertung der ermittelten Emissionswerte im Vergleich zur Wirbelschichtverbrennung unter atmosphaerischen und druckaufgeladenen Bedingungen von Stein- und Braunkohle. In Kapitel 5 schliesslich werden die Ergebnisse einer durchgefuehrten theoretischen Untersuchung zur Ermittlung des Wirkungsgradpotentials dargestellt. Ferner werden Empfehlungen fuer ergaenzende, weiterfuehrende Untersuchungen gegeben. Fuer die langfristige potentielle

  5. Micro- and macromechanical simulation of the deformation of steels under consideration of transformation and diffusion processes; Mikro- und makromechanische Simulation des Deformationsverhaltens von Staehlen unter Beruecksichtigung von Umwandlungs- und Diffusionsvorgaengen

    Daves, W.


    The goal of the present work was to develop a continuum mechanical description of the deformation behaviour of steels and cast iron, which makes it possible to calculate the residual stresses during and after heat treatment. The formation of microresidual stresses at transformation processes is discussed. In a survey, analytical and numerical models existing and developed by the author are presented for the transformation and the dispersion plasticity. The further calculation of the residual stresses in composite rollers is done using the preset transformation plasticity models. For the simulation of nitriding, a continuum mechanical concept is developed, which considers the diffusion of nitrogen into the material, the kinetics of nitride formation, the volume change in the nitride layer in consequence of the interstitial nitrogen and of the nitrides, the plastifying, the creep and a hardness increase of the material during nitriding. The results agree very well in their quality with the measurements. The material model used for the calculations is described in detail. (orig.) [Deutsch] Das Ziel der vorliegenden Arbeit ist es, eine kontinuumsmechanische Beschreibung des Deformationsverhaltens von Staehlen und Gusseisen zu entwickeln, welche es ermoeglicht, die Eigenspannungen waehrend und nach einer Waermebehandlung zu berechnen. Zu Beginn wird die Entstehung von Mikroeigenspannungen bei Umwandlungsvorgaengen behandelt. In einer Uebersicht werden bestehende und vom Verfasser entwickelte analytische und numerische und numerische Modelle fuer die Umwandlungs- und Ausscheidungsplastizitaet vorgestellt. Weiteres erfolgt die Berechnung der Eigenspannungen in Verbundwalzen unter Anwendung der vorgestellten Umwandlungsplastizitaetsmodelle. Fuer die Simulation des Nitrierens wird ein kontinuumsmechanisches Konzept entwickelt, welches die Diffuson des Stickstoffes in das Material, die Kinetik der Nitridbildung, die Volumsaenderung in der Nitridschicht zufolge des

  6. A laser-based study of kerosine evaporation and -mixing for lean prevaporized combustion at elevated pressure; Lasermesstechnische Untersuchung der Kerosinverdampfung und -mischung fuer die magere Vormischverbrennung unter erhoehtem Druck

    Brandt, M.


    The evaporation and mixing of a kerosine spray in the turbulent airstream of a prevaporizer is investigated at conditions prevailing in the combustion chamber of gas turbines. An experiment is described that allows to study an evaporating fuel spray downstream a prefilming airblast atomizer with Phase-Doppler anemometry, laser-induced fluorescence and an infrared light absorption technique. At an air pressure of 9 bars, an air temperature of 750 K, a mean air velocity of 120 m/s and a fuel flow rate of 1 g/s the kerosine spray evaporates completely without autoignition. At this operating condition the parameters air pressure, air temperature and air turbulence are varied. The influence of these parametric variations on the dropsize distribution, the evaporation rate and the concentration profiles of liquid and evaporated fuel is presented and discussed. (orig.) [German] Die Verdampfung und Vermischung eines Kerosinsprays in der turbulenten Luftstroemung eines Vorverdampfers wird unter Bedingungen untersucht, die in Brennkammern fuer Gasturbinen vorherrschen. Ein Experiment wird vorgestellt, welches es erlaubt, ein verdampfendes Kraftstoffspray stromab eines ebenen Luftstromzerstaeubers mit Filmleger mittels der Phasen-Doppler-Anemometrie, Laser-induzierter Fluoreszenz und einer Infrarotabsorptionsmesstechnik zu untersuchen. Bei einem Luftdruck von 9 bar, einer Vorwaermetemperatur der Luft von 750 K, einer mittleren Luftgeschwindigkeit von 120 m/s und einem Kraftstoffmassenstrom von 1 g/s verdampft das Kerosinspray vollstaendig, ohne die Selbstzuendungszeit zu erreichen. Bei dieser Betriebsbedingung werden die Parameter Luftdruck, Lufttemperatur und Turbulenzgrad variiert. Der Einfluss dieser Parameter auf das Tropfengroessenspektrum, den Verdampfungsgrad und die Konzentrationsprofile des fluessigen sowie des verdampften Kraftstoffs wird dargestellt und diskutiert. (orig.)

  7. A survey of anticoagulation practice among German speaking microsurgeons – Perioperative management of anticoagulant therapy in free flap surgery [Erhebung über die antikoagulatorische Praxis unter deutschsprachigen Mikrochirurgen – Perioperatives Management der antikoagulatorischen Therapie bei freien Lappentransplantaten

    Jokuszies, Andreas


    Full Text Available [english] Background: Anticoagulation is a crucial element in microsurgery. Although various clinical studies and international surveys have revealed that anticoagulation strategies can vary and result in similar outcomes, anticoagulative regimen are far away from standardization. In Germany and german speaking countries standardized anticoagulation protocols concerning free flap surgery do not exist so far. Methods: To evaluate the current practice of clinics in Germany, Austria and Switzerland with specialization in microsurgery we performed a questionnaire surveying the perioperative regimen of anticoagulant and antiplatelet therapy in free flap surgery. The microsurgeons were interrogated on several anticoagulant, rheologic and antiplatelet medications, their dosage and perioperative frequency of application pre-, intra- and postoperative.Results: The questionnaire revealed that the used antithrombotic and perioperative regimens varied from department to department presumably based on the personal experience of the surgeon. Multiple approaches are used with a wide range of anticoagulants used either alone or in combination, with different intervals of application and different dosages. Conclusion: Therefore consensus meetings should be held in future leading to conduct prospective multicenter studies with formulation of standardized anticoagulative and perioperative protocols in microsurgery reducing flap failure to other than pharmacologic reasons.[german] Hintergrund: Die Antikoagulation stellt ein zentrales Element in der Mikrochirurgie dar. Zahlreiche klinische Studien und internationale Erhebungen zu antikoagulatorischen Strategien weisen eine grosse Varianz bei vergleichbaren Resultaten nach, entbehren jedoch einer Standardisierung. Auch in Deutschland und deutschsprachigen Ländern fehlen bislang standardisierte Regime zur Antikoagulation in der Mikrochirurgie.Methodik: Zur Erhebung der antikoagulatorischen Praxis unter

  8. Dynamic MRI of the lumbar spine for the evaluation of microcirculation during anti-angiogenetic therapy in patients with myelodysplastics syndromes; Dynamische MRT der Lendenwirbelsaeule zur Beurteilung der Mikrozirkulation unter anti-angiogenetischer Therapie bei Patienten mit myelodysplastischen Syndromen

    Scherer, A.; Wittsack [Institut fuer Diagnostische Radiologie, Duesseldorf (Germany); Strupp, C. [Klinik fuer Haematologie, Onkologie und klinische Immunologie, Duesseldorf (Germany); Engelbrecht, V. [Institut fuer Diagnostische Radiologie, Duesseldorf (DE)] (and others)


    (Normalpersonen: 0,124{+-}0,042, MDS: 0,136{+-}0,036) gemessen. Bei 7 der 9 MDS-Patienten konnte unter Thalidomidtherapie eine Reduktion der Amplitude und Austauschratenkonstante in den d-MRT-Verlaufsuntersuchungen nachgewiesen werden. Klinisch zeigten diese Patienten ein Therapieansprechen mit kompletter oder partieller Krankheitsremission. (orig.)

  9. The implementation of cogeneration plants in new and older buildings for power generation under technical and economic aspects; Der Einsatz von Blockheizkraftwerken im Neubau und Gebaeudebestand zur Waerme-, Kaelte- sowie Elektrizitaetserzeugung unter techni-schen und betriebswirtschaftlichen Gesichtspunkten

    Mauersberger, Frank; Lipski, Thomas [heima-welte Haustechnik GmbH und Co.KG, Balingen (Germany); Cibis, Dominik [Europaeische Studienakademie Kaelte-Klima-Lueftung, Maintal (Germany)


    Cogeneration plants have become a key element of modern space HVAC systems. Serial production resulted in higher quality and lower production cost, which made them interesting also for private buildings. However, cogeneration plants must compete with other systems, e.g. high-efficiency boilers and heat pumps. An accurate economic assessment requires not only acquisition and processing of building-specific data but also adherence to the restrictive specifications of the Energy Conservation Ordinance (EnEV) and Renewables Act (EEWaermeG) discussed in more detail. The EEWaermeG 2011 specifies not just heating systems but also refrigeration systems. Here, a cogeneration plant combined with a sorption refrigerator will have higher economic efficiency and will fully meet the specifications of the EEWaermeG. Of course, this is a challenge for planners, architects and constructors. The contribution outlines the various options of combined heat, cold, and power generation and presents efficiency calculations for an economic assessment. [German] Blockheizkraftwerke zur Waerme- und Elektrizitaetserzeugung nehmen heute einen immer groesseren Stellenwert in der modernen Gebaeudetechnik ein. Die industrielle Serienproduktion verhalf dem BHWK zu einer deutlich gesteigerten Qualitaet und ermoeglichte durch gesunkene Produktionskosten den Einsatz im privaten Wohnraum. Im Neubau sowie im Gebaeudebestand steht das BHKW jedoch in direkter Konkurrenz mit anderen Waermeerzeugern wie Brennwertgeraeten und Waermepumpen. Um eine exakte Wirtschaftlichkeitsbetrachtung der jeweiligen Waermeerzeuger erstellen zu koennen, muessen nicht nur gebaeudespezifische Daten erfasst und berechnet werden, sondern es muss auch auf die restriktiven Vorgaben der Energieeinsparverordnung (EnEV) und des Erneuerbare-Energien-Waerme-Gesetzes (EEWaermeG) genauer eingegangen werden. Im EEWaermeG 2011 wird unter anderem erstmalig neben der Waerme- auch auf die erneuerbare Kaelteerzeugung eingegangen. Hier kann

  10. Inelastic analysis of the deformation behaviour of internally cooled IN 738 LC turbine blades using the microstructural dependent constitutive equations; Inelastische Analyse des Verformungsverhaltens einer innengekuehlten Gasturbinenschaufel aus dem Werkstoff IN 738 LC unter Verwendung des strukturabhaengigen Werkstoffmodells

    Beckmoeller, S.; Schubert, F.; Penkalla, H.J.; Nickel, H.; Breitbach, G.


    Werkstoffmodells, das im IWE der KFA entwickelt wurde, fuer strukturmechanische Untersuchungen von innengekuehlten, stationaeren Gasturbinenschaufel diskutiert. Die mehraxiale Ueberpruefung des Modells geschah zum einen mit Hilfe von Torsionshohlproben aus dem Werkstoff IN 738 LC und zum anderen mit Experimenten an feingegossenen Modellturbinenschaufeln derselben Legierung. Die Belastung der Modellschaufel bestand aus einer Zuglast zur Simulation der Fliehkraefte, sowie aus Temperaturzyklen. Die rechnerische Analyse der Schaufel fand mit Hilfe des Finiten Elemente Programms ABAQUS, in dem das Werkstoffmodell implementiert wurde, statt. Verwendet wurde eine zweidimensionale Netzstruktur. Basierend auf den im Experiment gemessenen Oberflaechentemperaturen wurde in einem ersten Schritt die Temperaturverteilung in der Modellschaufel berechnet. Erst danach war eine Spannungs- und inelastische Dehnungsanalyse moeglich. Ein Vergleich der Experimente mit den Rechnungen unter Verwendung des strukturabhaengigen Werkstoffmodells nach Penkalla zeigte eine gute Uebereinstimmung bei der Lebensdauerprognose. Waehrend bei den Versuchen mit der kurzen Haltezeit das Versagen an der Abstroemkante elastisch abgeschaetzt werden konnte, ist dies fuer die laengere Haltezeit nicht exakt moeglich, da hier den Kriecheffekten eine staerkere Bedeutung zukam. (orig.)

  11. Implementation of new concepts for space HVAC systems in domestic buildings in consideration of cost, consumption and user comfort. Final report; Umsetzung neuer Konzepte der technischen Gebaeudeausruestung im Wohnungsbau unter Beruecksichtigung von Kosten, Verbraeuchen und Nutzerkomfort. Abschlussbericht

    Schmidt, F.; Sucic, D.; Wendler, M.


    The goal of this project was the development of a set of tools for the selection of optimal concepts for HVAC-systems in housing buildings. Several factors are considered. They include technical feasibility, costs for investment, maintenance and operation, energy concumption, environmental impacts and user comfort. It is intended with the help of these tools to identify the most important factors which influence energy consumption and to suggest simple and cost effective measures to reduce energy consumption. Measures include improvements of the envelope, changes in the HVAC-system and its operation according to the needs to the inhabitants of the building. This report describes these components of this tool set which were developed in the frame of the project WohnKomfort. It lists data and rules chosen. In addition we report experiences which we gained with an prototypical implementation. This implementation allows load calculations for more than 60.000 different buildings applying EN 802 (only one zone model) as calculation method. It also supports selection of heating systems for such buildings by offering an evaluation according to user specified criteria including cost, environment and comfort. (orig./MM) [Deutsch] Ziel des Vorhabens war die Entwicklung eines Instrumentariums zur Auswahl optimaler Konzepte fuer technische Anlagen in Wohngebaeuden unter Beruecksichtigung der Faktoren technische Machbarkeit, Erstellungs-, Betriebskosten, Energieverbrauch, Umweltbelastung und Nutzerkomfort. Mit Hilfe dieses Instrumentariums soll es moeglich werden, die Haupteinflussfaktoren fuer den Energieverbrauch anzugeben und Vorschlaege fuer einfache und kostenguenstige Massnahmen zu seiner Reduzierung auf der Seite des Gebaeudes (bauliche Massnahmen) und der Anlage (technische Massnahmen, Nutzerverhalten) anzugeben. In diesem Bericht beschreiben wir die im Vorhaben entwickelten Komponenten des Instrumentariums, die zugrundeliegenden Daten und Regeln sowie Erfahrungen, die

  12. Calculations of an unsteady flow through a hydraulic axial turbine with reference to interaction between stator and rotor; Instationaere Berechnung einer hydraulischen Axialturbine unter Beruecksichtigung der Interaktion zwischen Leit- und Laufrad

    Bauer, C.


    The objective of this study is the development of an algorithm enabling coupling of nonmatching computational grids to carry out calculations of an unsteady flow through a hydraulic axial turbine with reference to interaction between stator and rotor. The algorithm should offer the possibility to operate the computational grids in a fixed position relative to each other as well as in relative movement. Furthermore, the calculation should be feasible with separate grids in parallel and different frames of reference. Employing selected examples this method is investigated in detail the results are compared with performed measurements. The unsteady numerical examination of the coupling process is carried out with different examples; especially the interaction effects between stator, rotor and draft tube of a hydraulic axial turbine are observed. In addition, the effect of tip clearance of the mean flow is described. Extensive model tests using the axial turbine have been performed at the Institute for Fluid Mechanics and Hydraulic Machinery, IHS. Flow time dependent velocities have been measured with a Laser Doppler Velocimeter placed at midspan of the blading. Periodical changes in static pressure have been recorded at different locations near the wall of the turbine casing. These measurements serve as reference for the comparison with results derived from the unsteady calculations. The confrontation of the time-dependent fluctuations of the flow quantities and the calculation of the efficiency of the turbine resulting from the simulation results allow a comparison in absolute terms. (orig.) [German] Fuer die instationaere Berechnung einer hydraulischen Axialturbine unter Beruecksichtigung der Interaktion zwischen Leit- und Laufrad wird ein Algorithmus zum Koppeln von nichtpassenden Berechnungsnetzen entwickelt. Diese Berechnungsnetze sollen zueinander ortsfest sein oder auch eine Relativbewegung zueinander haben koennen. Sie sollen ausserdem und in unterschiedlichen

  13. Fatigue life prediction for integrally cast turbine wheels while taking into account short cracks using the nickel base alloy IN 713 C as an example; Lebensdauervorhersage fuer integralgegossene Turbinenraeder unter Beruecksichtigung kurzer Risse am Beispiel der Nickelbasis-Legierung IN 713 C

    Brandt, U.; Sonsino, C.M.


    The cast alloy IN 713 C (cast condition) frequently used in turbine wheels was used to determine fatigue strength results under quasi-operational conditions within the range of low cycle fatigue with the objective of transferring the initial crack and crack propagation behavior to notched specimens and later to turbine wheels, while taking into account an inhomogeneous stress and strain distribution, respectively. This transferability relates only to results below 600 C, because this temperature occurs in the critical region of the turbine wheel, the hub. (orig.) [Deutsch] Es wurden mit der fuer Turbinenraeder haeufig eingesetzten Gusslegierung IN 713 C (Gusszustand) Schwingfestigkeitsergebnisse und betriebsnahen Bedingungen im Bereich der Niedrigschwingspielzahl-Ermuedung ermittelt, mit dem Ziel das an ungekerbten Proben bestimmte Anriss- und Rissfortschrittsverhalten auf gekerbte Proben und spaeter auf Turbinenraeder unter Beruecksichtigung einer inhomogenen Spannungs-bzw. Dehnungsverteilung uebertragen zu koennen. Die Uebertragbarkeit bezieht sich dabei nur auf die Ergebnisse unter 600 C, weil diese Temperatur im kritischen Bereich des Turbinenrades, der Nabe, auftritt. (orig.)

  14. Wissenstransfer unter dem Gesichtspunkt der Textoptimierung

    Kastberg, Peter


    Fachtexte `gleichen´ Themas aber verschiedener Textsortenzugehörigkeit führte zur Entwicklung eines Analyserasters, das eingesetzt werden kann, um den Prozeß des Transfers von Wissen zwischen Fachtexte verschiedener Fachtextsortenzugehörigkeit aus linguistischer Sicht näher zu beschreiben. Wenn ich ferner...

  15. Charakterisierung der proteasomalen Genregulation unter Biogeneseaspekten


    Das 26S Proteasom ist ein großer Proteinase-Komplex, der aus 32 unterschiedlichen Untereinheiten aufgebaut ist. Das 26S Proteasom ist involviert in die ATP-abhängige De-gradation von ubiquitinierten Proteinen, die eine Vielfalt an zellulären Prozessen wie Signaltransduktion, Stressantwort, transkriptionelle Regulation, Chromosomen-Segregation, DNA-Reparatur, Zellzyklus-Steuerung und die Prozessierung von Peptiden für die MHC I Antigen Präsentation regulieren. Die Prozessierung von Peptiden wi...

  16. Ungarn seit der Wahl: Demokratie unter Druck

    A. Freyberg-Inan; M. Varga


    Die Verfasser zeigen, dass die Orban-Regierung legitime Probleme benennt, wie etwa Ungarns extrem niedrige Beschäftigungsrate, die mit zu den großen wirtschaftliche Schwierigkeiten des Landes beiträgt. Doch packt sie die identifizierten Probleme zu oft auf eine Weise an, die ganz nebenbei dem nation

  17. Being subject to quarantine; Unter Quarantaene

    Ullrich, Sven


    The registration of imports of modules from the People's Republic of China has caused an uncertainty in Europe. The installers now adhere to the wholesalers in order to protect oneself from unpleasant surprises.

  18. Structure and properties of galvanized zinc coatings. According to DIN EN ISO 1461 on untreated structural steels and structural steels with different Si concentrations, with special consideration of the Sandelin and Sebisty effects; Struktur und Eigenschaften von Feuerzinkueberzuegen. Nach DIN EN ISO 1461 auf unberuhigten und verschieden Si-haltigen Baustaehlen unter besonderer Bercksichtigung des Sandelin- und des Sebisty-Effektes

    Schubert, P.; Schulz, W.D. [Institut fuer Korrosionsschutz Dresden (Germany); Katzung, W.; Rittig, R. [Institut fuer Stahlbau Leipzig (Germany)


    The authors investigated the interdependence between the Si content of structural steels and their galvanisation characteristics. Special interest was taken in galvanisation reactivity, the structure of coatings in consideration of the Sandelin effect (>0.035..0.12% of Si) and the Sebisty effect (>0.12.. 0.28% Si) at medium Si concentrations, and the changes in microhardness as a function of phase structure. [Deutsch] Das Ziel unserer Untersuchungen war es, genaue Zusammenhaenge zwischen dem Si-Gehalt von Baustaehlen und deren Verzinkungsverhalten aufzuzeigen. Insbesondere sollte deren Verzinkungsreaktivitaet ermittelt werden, der Aufbau der Ueberzuege unter Beruecksichtigung des Sandelineffektes (>0,035... 0,12% Si) und des Sebisty-Effektes (>0,12... 0,28% Si) bei mittlerem Si-Gehalt sowie der Verlauf der Mikrohaerte in Abhaengigkeit vom Phasenaufbau. (orig.)

  19. The efficacy of N-acetylcysteine to protect the human cochlea from subclinical hearing loss caused by impulse noise: A controlled trial

    Ann-Cathrine Lindblad


    Full Text Available In military outdoor shooting training, with safety measures enforced, the risk of a permanent, noise-induced hearing loss is very small. But urban warfare training performed indoors, with reflections from walls, might increase the risk. A question is whether antioxidants can reduce the negative effects of noise on human hearing as it does on research animals. Hearing tests were performed on a control group of 23 military officers before and after a shooting session in a bunker-like room. The experiments were repeated on another group of 11 officers with peroral adminstration of N-acetyl-cysteine (NAC, directly after the shooting. The measurements performed were tone thresholds; transient-evoked otoacoustic emissions, with and without contralateral noise; and psycho-acoustical modulation transfer function (PMTF, thresholds for brief tones in modulated noise. Effects from shooting on hearing thresholds were small, but threshold behavior supports use of NAC treatment. On the PMTF, shooting without NAC gave strong effects. Those effects were like those from continuous noise, which means that strict safety measures should be enforced. The most striking finding was that the non-linearity of the cochlea, that was strongly reduced in the group without NAC, as manifested by the PMTF-results, was practically unchanged in the NAC-group throughout the study. NAC treatment directly after shooting in a bunkerlike room seems to give some protection of the cochlea.

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

    Finn, Nnenna Adimora; Kemp, Melissa Lambeth


    Clinical debate has arisen over the consequences of antioxidant supplementation during cancer chemotherapy. While antioxidants may impede the efficacy of chemotherapy by scavenging reactive oxygen species and free radicals, it is also possible that antioxidants alleviate unwanted chemotherapy-induced toxicity, thus allowing for increased chemotherapy doses. These contradictory assertions suggest that antioxidant supplementation during chemotherapy treatment can have varied outcomes depending ...

  1. Recovery by N-acetylcysteine from subchronic exposure to Imidacloprid-induced hypothalamic-pituitary-adrenal (HPA) axis tissues injury in male rats.

    Annabi, Alya; Dhouib, Ines Bini; Lamine, Aicha Jrad; El Golli, Nargès; Gharbi, Najoua; El Fazâa, Saloua; Lasram, Mohamed Montassar


    Imidacloprid is the most important example of the neonicotinoid insecticides known to target the nicotinic acetylcholine receptor in insects, and potentially in mammals. N-Acetyl-l-cysteine (NAC) has been shown to possess curative effects in experimental and clinical investigations. The present study was designed to evaluate the recovery effect of NAC against Imidacloprid-induced oxidative stress and cholinergic transmission alteration in hypothalamic-pituitary-adrenal (HPA) axis of male rats following subchronic exposure. About 40 mg/kg of Imidacloprid was administered daily by intragastric intubation and 28 days later, the rats were sacrificed and HPA axis tissues were removed for different analyses. Imidacloprid increased adrenal relative weight and cholesterol level indicating an adaptive stage of the general alarm reaction to stress. Moreover, Imidacloprid caused a significant increase in malondialdehyde level, the antioxidants catalase, superoxide dismutase and glutathione-S-transferase showed various alterations following administration and significant depleted thiols content was only recorded in hypothalamic tissue. Furthermore, the hypothalamic and pituitary acetylcholinesterase activity and calcium level were significantly increased highlighting the alteration of cholinergic activity. The present findings revealed that HPA axis is a sensitive target to Imidacloprid (IMI). Interestingly, the use of NAC for only 7 days post-exposure to IMI showed a partial therapeutic effect against Imidacloprid toxicity.

  2. Evaluation of the Effects of Oral N-Acetylcysteine and a Placebo in Paraclinical and Oxidative Stress Parameters of Patients with Chronic Hepatitis B

    Majid Shohrati


    Full Text Available Background and Aims: The treatment of chronic hepatitis B (CHB is a challenging problem today, and previous study has shown that oxidative stress causes the collective pathophysiological conditions of many hepatopathies, so other new therapeutic approaches are needed. Hence, in this study the paraclinical and oxidative stress parameters of the efficacy of N-acetyl cysteine (NAC as an antioxidant in the treatment of CHB have been evaluated. Methods: In this double-blind placebo-controlled clinical trial study, 43 patients with CHB were enrolled in 2008 in Tehran, Iran. The patients were randomly assigned to receive either 1200 mg/day NAC or a placebo for 45 days. Paraclinical tests and oxidative stress parameters were measured on experimental day 0 and on day 45.Results: Liver function tests, i.e. alanine aminotransferase (ALT, aspartate aminotransferase (AST and alkaline phosphatase (ALP levels were not significantly different in the NAC group and in the placebo group. A reduction in catalase (CAT activity and an increase in glutathione concentration were statistically significant in the NAC group (P < 0.05. Conclusions: According to our results, oral NAC is not an effective adjuvant treatment for patients with CHB, but further research with a larger population is needed for the evaluation of the effectiveness of NAC in these patients.

  3. Effect of cassava-starch coatings with ascorbic acidic and N-acetylcysteine on the quality of harton plantain (Musa paradisiaca

    Carlos Julio Márquez Cardozo


    Full Text Available The effect of coatings was evaluated on the quality ofharton plantain fruits (Musa paradisiaca in the postharvest stage.Solutions for three treatments were prepared from 50 g L-1 cassavastarch (Manihot esculenta with 30 g L-1 glycerol as the plasticizerand 6 g L-1 polyethylene glycol-600®; for anti-browning agents, 6g L-1 ascorbic acid (AA and 8 g L-1 N-Acetyl-Cysteine (NAC wereadded. The fruits were coated by immersion, stored at 18 ± 4°Cand 85% RH. Physicochemical properties were determined at 32days postharvest. The applied coatings decreased the physiologicalweight loss (%WL and resulted in a higher pulp firmness (PF; nosignificant difference was seen with a confidence level of 95% inthe concentration of total soluble solids (TSS, acidity or maturityindex. The skin color was measured by the CIE L*a*b* method, withan average L value of 70 for the fruits coated with the 6 g L-1 AAand 8 g L-1 NAC mixture, while the control fruits had a value of 57.Also, lower a* coordinate values and browning indices were foundfor the epidermis of the coated fruits. The enzymatic activity of thepolyphenol oxidase decreased with the number of postharvest daysfor all of the treatments, being lower for the fruits with the mixtureof anti-browning agents by 27%, as compared to the control. It wasconcluded that the coating mixture containing the anti-browningagents ascorbic acid, 6 g L-1, and N-acetyl-cysteine, 8 g L-1, showeda better effect as an alternative for storing fruits and prolongingthe shelf-life of harton plantain.

  4. The antioxidant n-acetylcysteine reduced necrosis, but exacerbated liver fibrosis induced by chronic alcohol in rats fed via total enteral nutrition

    Despite many years of research, the molecular mechanisms underlying progression of alcoholic liver injury from simple steatosis through steatohepatitis and fibrosis remain in dispute. In the current study male Sprague-Dawley rats (350 g) were chronically fed a high unsaturated fat diet for 120 d usi...

  5. Antioxidative effect of melatonin, ascorbic acid and N-acetylcysteine on caerulein-induced pancreatitis and associated liver injury in rats

    Mukaddes Esrefo(g)lu; Mehmet Gül; Burhan Ates; Kadir Batclo(g)lu; Mukadder Ayse Selimo(g)lu


    AIM: To investigate the role of oxidative injury in pancreatitis-induced hepatic damage and the effect of antioxidant agents such as melatonin, ascorbic acid and N-acetyl cysteine on caerulein-induced pancreatitis and associated liver injury in rats.METHODS: Thirty-eight female Wistar rats were used.Acute pancreatitis (AP) was induced by two i.p. injections of caerulein at 2-h intervals (at a total dose of 100μg/kg b.wt). The other two groups received additional melatonin (20 mg/kg b.wt) or an antioxidant mixture containing L(+)-ascorbic acid (14.3 mg/kb.wt.) and N-acetyl cysteine (181 mg/kg b.wt.) i.p. shortly before each injection of caerulein. The rats were sacrificed by decapitation 12 h after the last injection of caerulein.Pancreatic and hepatic oxidative stress markers were evaluated by changes in the amount of lipid peroxides measured as malondialdehyde (MDA) and changes in tissue antioxidant enzyme levels, catalase (CAT) and glutathione peroxidase (GPx). Histopathological examination was performed using scoring systems.RESULTS: The degree of hepatic cell degeneration, intracellular vacuolization, vascular congestion, sinusoidal dilatation and inflammatory infiltration showed a significant difference between caerulein and caerulein + melatonin (P= 0.001), and careulein and caerulein+ L(+)-ascorbic acid +N-acetyl cysteine groups (P= 0.002). The degree of aciner cell degeneration, pancreatic edema,intracellular vacuolization and inflammatory infiltration showed a significant difference between caerulein and caerulein+ melatonin (P=0.004), and careulein and caerulein + L(+)-ascorbic acid +N-acetyl cysteine groups (P= 0.002). Caerulein-induced pancreatic and liver damage was accompanied with a significant increase in tissue MDA levels (P= 0.01, P= 0.003, respectively) whereas a significant decrease in CAT (P=0.002, P=0.003,respectively) and GPx activities (P= 0.002, P=0.03, respectively). Melatonin and L(+)-ascorbic acid+N-acetyl cysteine administration significantly decreased MDA levels in pancreas (P= 0.03, P=0.002, respectively) and liver (P=0.007, P=0.01, respectively). Administration of these agents increased pancreatic and hepatic CAT and GPx activities. Melatonin significantly increased pancreatic and hepatic CAT (P= 0.002, P= 0.001, respectively)and GPx activities (P=0.002, P= 0.001). Additionally,L(+)-ascorbic acid+N-acetyl cysteine significantly increased pancreatic GPx (P= 0.002) and hepatic CAT and GPx activities (P= 0.001, P= 0.007, respectively)CONCLUSION: Oxidative injury plays an important role not only in the pathogenesis of AP but also in pancreatitis-induced hepatic damage. Antioxidant agents such as melatonin and ascorbic acid +N-acetyl cysteine, are capable of limiting pancreatic and hepatic damage produced during AP via restoring tissue antioxidant enzyme activities.

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

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


    alone. Patients in cardiogenic shock were excluded. Acute CIN was defined as an increase in serum creatinine concentration >25% from the baseline value within a 3-day period. Overall, CIN occurred in 141 (21.9%) patients. The prevention treatment with NAC, NaHCO3, or the combined NAC and NaHCO3 did...... and NaHCO3 (18.7% versus 19.1% versus 9.2% versus 21.3%; P=0.033). CONCLUSIONS: Treatment with NAC or NaHCO3 did not reduce the rate of acute CIN significantly. Combined treatment with NAC and NaHCO3 may reduce the risk of renal dysfunction after 30 days. CLINICAL TRIAL REGISTRATION URL: http......BACKGROUND: Contrast-induced nephropathy (CIN) is a serious condition in patients with ST-segment-elevation myocardial infarction treated with primary percutaneous coronary intervention. We compared the risk of acute CIN and the influence of preventive strategies in patients with ST...

  7. Development and application of a NaNiCl{sub 2}-battery for industrial trucks regarding the requirements cycle life, safety and reliability. Final report; Entwicklung und Erprobung einer NaNiCl{sub 2}-Batterie fuer Flurfoerderzeuge unter besonderer Beruecksichtigung der Aspekte Lebensdauer, Sicherheit und Zuverlaessigkeit. Schlussbericht

    Boehm, H.; Beyermann, G.; Bulling, M.


    Two NaNiCl{sub 2}-battery types including the battery controller and peripheral equipment have been developed for the application in fork lift trucks and driverless transportation. The batteries have been tested and evaluated on bench testing as well as in fork lift trucks and driverless trucks in practical application. The field tests have been performed by the subcontractors Still, Mercedes-Benz and Indumat. All test results have shown that the NaNiCl{sub 2}-battery (ZEBRA-battery) is well suited for the application in industrial traction. A series development together with a cost reduction programme have to be performed ahead of the introduction of the ZEBRA-battery into the market for industrial traction batteries. (orig.) [Deutsch] Im Rahmen des Vorhabens wurden zwei NaNiCl{sub 2}-Batterietypen, eine fuer die Anwendung in Gabelstaplern, die andere fuer den Einsatz in fahrerlosen Transportsystemen (FTS), einschliesslich des Batteriesteuergeraetes und der Batterieperipherie entwickelt. Die Batterien wurden auf Teststaenden im Labor sowie in Gabelstaplern und FTS unter Praxisbedingungen erprobt. Der praktische Einsatz erfolgte bei den Unterauftragnehmern Still, Mercedes-Benz und Indumat. Die Ergebnisse haben gezeigt, dass die NaNiCl{sub 2}-Batterie (ZEBRA-Batterie) fuer die Anwendung in Gabelstaplern und FTS geeignet ist. Insbesondere wurde nachgewiesen, dass die NaNiCl{sub 2}-Batterie im Gegensatz zu anderen Batteriesystemen einen Zweischichtbetrieb von Gabelstaplern ohne Batteriewechsel ermoeglicht. Vor Einfuehrung der ZEBRA-Batterie in den Flurfoerdermarkt muss die Serienentwicklung bei gleichzeitiger Senkung der Herstellkosten durchgefuehrt werden. (orig.)

  8. Solar reactors for freshwater treatment in developing countries with high radiation intensity, with particular regard to part-project No. 1: Microbiology, process conception. Final report; Solarreaktoren fuer die Trinkwasseraufbereitung in Entwicklungslaendern mit hoher Sonnenstrahlungsintensitaet unter besonderer Beruecksichtigung von Teilprojekt 1: Mikrobiologie, Verfahrenskonzeption. Schlussbericht

    Watzke, E.; Roth, M.; Hoffmeier, C.


    Erhoehung der Bakterienabtoetungsraten wird die erhoehte Temperatur des behandelten Wassers in einem isolierten Sammelbehaelter ueber mehrere Stunden gehalten. Ausserdem wurden Trinkwasserentkeimungsgefaesse (TWEG) aus hoch UV-durchlaessigem Glas entwickelt, die ebenfalls zur Trinkwasserdesinfektion verwendet werden koennen. In einem Folgeprojekt werden mit den TWEA Langzeittests unter praxisrelevanten Anwendungsbedingungen in Entwicklungslaendern durchgefuehrt. (orig.)

  9. In situ measurement of flow characteristics of natural saline rock in loose zones for gas and saline solutions in given rock stress conditions. Final report; In-situ-Ermittlung von Stroemungskennwerten natuerlicher Salzgesteine in Auflockerungszonen gegenueber Gas und Salzloesungen unter den gegebenen Spannungsbedingungen im Gebirge. Abschlussbericht

    Haefner, F.; Belohlavek, K.U.; Behr, A.; Foerster, S.; Pohl, A.


    A method and equipment were developed for measuring the extension of loose zones around worked areas in saline rock and for in situ measurement of very small permeabilities and porosities in these zones. The experiments are based on unsteady borehole logs with flowing gases or liquids with special multiple pack systems that enable measurements from 4 cm to 15 m from the cavern contour. The measurements were evaluated by a specially developed software with automatic parameter identification. Permeabilities were identified between 10{sup 14} m{sup 2} and the detection limit of 10{sup 24} m{sup 2} and effective porosities of less than 0.1% at experimental times of several minutes up to several days. The logs were made in 3 mines in Stassfurt rock salt at depths of 700 and 500 m with different geological and geomechanical boundary conditions, worked in different ways and for different periods of time (between a few days and 37 years). Some of the findings were validated by ultrasonic measurements. [German] Fuer die Ermittlung der Ausdehnung von Auflockerungszonen um bergmaennisch aufgefahrene Strecken/Hohlraeume im Salzgestein und zur In-situ-Bestimmung kleinster Permeabilitaeten und Porositaeten in diesen Bereichen wurde ein Verfahren und eine praktikable Versuchsausruestung entwickelt. Diese eignet sich auch fuer Frac-Untersuchungen. Basis der Versuchsdurchfuehrungen sind instationaere Bohrlochuntersuchungen mit Gasen oder Fluessigkeiten als Stroemungsfluid unter Einsatz spezieller Mehrfachpackersysteme. Damit sind Messungen ab 4 cm Abstand zur Hohlraumkontur bis zu 15 m moeglich. Die Versuchsauswertung erfolgt mittels einer speziell entwickelten Software mit automatischer Parameteridentifikation, die die instationaere Stroemung um die Versuchsbohrung raeumlich vollstaendig beschreibt. Permeabilitaeten wurden je nach Abstand zur Hohlraumkontur zwischen 10{sup -14} m{sup 2} und der Nachweisgrenze 10{sup -24} m{sup 2} und effektive Porositaeten bis <0,1% ermittelt, bei

  10. Clinical application of leucocyte scintigraphy with the monoclonal antibody MAK BW 250/183 with special regard to the induction of antimurine antibodies (HAMA); Leukozytenszintigraphie mit dem monoklonalen Antikoerper MAK BW 250/183 in der klinischen Anwendung unter Beruecksichtigung der Induktion von antimurinen Antikoerpern (HAMA)

    Eising, E.G. [Klinik und Poliklinik fuer Nuklearmedizin der Universitaet-GH, Essen (Germany); Reiners, C. [Klinik und Poliklinik fuer Nuklearmedizin der Universitaet-GH, Essen (Germany); Farahati, J. [Klinik und Poliklinik fuer Nuklearmedizin der Universitaet-GH, Essen (Germany); Jacob, M. [Klinik und Poliklinik fuer Nuklearmedizin der Universitaet-GH, Essen (Germany)


    Scintigraphy with the murine antibody MAK BW 250/183 (Scintimun Granulozyt{sup R}) has proven to be a good imaging method to clear up clinical questions concerning acute inflammatory processes. 30 patients with clinical signs of acute inflammation were included in this prospective study to test the clinical usefulness of this tracer and possible negative influences by anti-murine antibodies (HAMA). Side effects or induction of HAMA antibodies couldn`t be observed in any patients. The quality of the obtained images was good in all cases. However, false negative results were obtained in cases on antiphlogistic medication (e.g. cortisone) or with chronic inflammatory diseases. Application of MAK BW 250/183 (Scintimum Granulozyt{sup R}) should be avoided in children due to its relative high radiation dose to bone marrow. False negative results can be found in inflammatory lesions of axial sceleton. On the other hand, the good contrast of bone marrow can be used in patients to diagnose pathologic alterations of bone marrow distribution. (orig.) [Deutsch] Bei erwachsenen Patienten mit dem gezielten Verdacht auf akute entzuendliche Veraenderungen stellt die Anti-Granulozyten-Szintigraphie eine Methode mit relativ guter Bildgebung und Aussagefaehigkeit dar. Zur Ueberpruefung der klinischen Wertigkeit der Anti-Granulozyten-Szintrigraphie mit dem monoklonalen, murinen Antikoerper MAK BW 250/183 (Scintimun Granulozyt{sup R}) wurden 30 Patienten in einer prospektiv angelegten Studie untersucht. Insbesondere wurde hierbei auch die Ausbildung von signifikanten Antikoerpertitern gegen den MAK ueberprueft und deren Einfluss auf die szintigraphische Bildgebung evaluiert. Nebenwirkungen oder die Ausbildung von Antikoerpern (HAMA) wurden bei Patienten innerhalb der Studie nicht beobachtet. Auch die erhaltenen szintigraphischen Aufnahmen waren durchweg gut beurteilbar. Entzuendungen unter Antiphlogistika (insbesondere Cortisonpraeparate) sowie laengerfristig bestehende Entzuendungen

  11. Percutaneous transfemoral placement of a new flexible stent-graft into the thoracic aorta followed by a percutaneous suture-mediated closure of the access site - initial experience; Perkutane transfemorale implantation einer neuen, flexiblen thorakalen Aortenendoprothese unter Verwendung eines perkutanen Nahtsystems zum Gefaessverschluss - erste Erfahrungen

    Manke, C.; Lenhart, M.; Strotzer, M.; Feuerbach, S.; Link, J. [Klinikum der Univ. Regensburg (Germany). Inst. fuer Roentgendiagnostik; Kobuch, R.; Merk, J.; Birnbaum, F. [Klinikum der Univ. Regensburg (Germany). Klinik und Poliklinik fuer Herz-, Thorax- und herznahe Gefaesschirurgie


    To evaluate the transfemoral placement of a new, flexible stent-graft into the thoracic aorta and the suture-mediated closure of the femoral access. Patients and Methods: five patients were treated endovascularly with a stent-graft for an aneurysm (n = 3) or acute dissection (n = 2) of the thoracic aorta via a femoral 24 F sheath. The femoral access site was closed with two suture-mediated closure devices after placement of the stent-graft. Results: the aneurysm or the false lumen was excluded from perfusion by the placement of the stent-graft in all patients. Hemostasis at the femoral access site was successful in all patients with the percutaneous suture device. A minor stenosis of the femoral artery was found angiographically in four patients after suture-mediated closure. Besides a reversible renal failure due to the medically induced hypotension for the treatment of an acutely ruptured aneurysm, no complications resulted from the stent-graft placement or the percutaneous suture. Conclusion: the percutaneous transfemoral placement of stent-grafts in the thoracic aorta using a suture-mediated closure of the access site is technically feasible. Long-term results of the technique have to be awaited. (orig.) [German] Evaluation der transfemoralen Implantation einer neuen, flexiblen thorakalen Aortenprothese unter Verwendung eines perkutanen Nahtsystems zum Verschluss des femoralen Zugangs. Patienten und Methoden: fuenf Patienten wurden wegen Aneurysma (n = 3) oder akuter Dissektion (n = 2) der thorakalen Aorta endovaskulaer ueber eine perkutan eingebrachte 24F-Schleuse mit einem Stentgraft versogt. Der femorale Zugang wurde nach Plazierung der Endoprothese mit zwei perkutanen Nahtgeraeten verschlossen. Ergebnisse: bei allen Patienten fuehrte die Platzierung der Prothese zur Ausschaltung des Aneurysmas oder des falschen Lumens von der Perfusion. Mit der perkutanen Gefae paragraph naht konnte in allen Faellen ein Verschluss des femoralen Zugangs erreicht werden. In

  12. Development of an analysis method for determining chlorinated hydrocarbons in marine sediments and suspended matter giving particular consideration to supercritical fluid extraction; Entwicklung eines Analysenverfahrens zur Bestimmung von chlorierten Kohlenwasserstoffen in marinen Sedimenten und Schwebstoffen unter besonderer Beruecksichtigung der ueberkritischen Fluidextraktion

    Sterzenbach, D.


    diesem Grund soll das gesamte Verfahren und dessen Einzelschritte unter diesem Gesichtspunkt ueberprueft und gegebenenfalls verbessert werden. Fuer die Probennahme von marinen Schwebstoffen soll ein Verfahren erarbeitet werden, das eine effiziente Abtrennung moeglichst kleiner suspendierter Partikel aus Seewasser ermoeglicht. Mit dem entwickelten Analysenverfahren sollen aktuelle Aspekte der Meereschemie zu Quellen, Transport, Verteilung und Verbleib von chlorierten Kohlenwasserstoffen in der marinen Umwelt behandelt werden. (orig.)

  13. Untersuchungen zur Oberflächenspannung von Kohleschlacken unter Vergasungsbedingungen

    Melchior, Tobias


    In the context of CO2-emission-induced global warming, greenhouse gases resulting from the production of electricity in coal-fired power plants gain increasing attention. One possible way to reduce such emissions is to gasify coal instead of burning it. The corresponding process is referred to as Integrated Gasification Combined Cycle and allows for the separation of CO2 before converting a synthesis gas into electrical energy. However, further improvements in efficiency and availability of t...

  14. Experimentelle und numerische Untersuchung magerer Methan-Hochdruckverbrennung unter Mikrogravitation

    Hyvönen, Jari Johannes


    The experimental and numerical examination of laminar lean premixed combustion of methane air mixtures at high pressures under normal and microgravity is the aim of this thesis. The elimination of buoyancy under microgravity is essential for the exact determination of the flammability limit and the burning velocity and furthermore allows the analysis of flame instabilities. First the lean flammability limit for upward combustion of methane was determined by the pressure increase inside the co...

  15. Eine untere Massenschranke fuer Neutralinos aus Supernova-Kuehlung

    Langenfeld, U


    In my diploma thesis I calculate a lower mass bound of the lightest nutralino assuming an additional supernova cooling mechanism. I consider elektron-positron annihilation and nucleon-nucleon bremsstrahlung as cooling processes. These cooling processes must not be too effective because they would destroy the neutrino signal (SN 1987a). From this requirement I derive an upper bound for the emitted energy and as a consequence I get a lower bound for the mass of the lightest neutralino.

  16. Successful upgrading under pressure of time; Unter Zeitdruck erfolgreich modernisiert

    Haas, M. [Sulzer Hydro AG, Zurich (Switzerland); Gislason, G. [Landsvirkjun (Iceland)


    Burfell power station in Iceland is an excellent example of comprehensive upgrading thanks to partnerly relations between customer and supplier. This project has proved that runner replacement should not be treated individually in hydroelectric power plant modernizations, but as part of an overall refurbishing concept. To shorten delivery times, some innovative development and manufacturing methods were introduced. (orig.) [Deutsch] Das Kraftwerk Burfell in Island ist ein Beispiel fuer einen Umbau mit gesamtheitlicher Betrachtung und einer partnerschaftlichen Beziehung zwischen Kunde und Lieferant. Das Projekt hat bewiesen, dass beim Umbau von Wasserkraftwerken ein Laufradersatz nicht isoliert betrachtet werden darf, sondern in ein Gesamtkonzept innerhalb der bestehenden Anlage einzubinden ist. Zur Verkuerzung der Lieferzeiten wurden neue Wege in der Entwicklung und Fertigung der Komponenten beschritten. (orig.)

  17. Dimethylcarbonat als Methylierungsmittel unter phasen-transfer-katalytischen Bedingungen

    Lissel, Manfred; Schmidt, Stefan; Neumann, Beate


    Use of Dimethyl Carbonate as a Methylating Agent under Phase Transfer-Catalysed Conditions Dimethyl carbonate (as well as diethyl, diallyl, dibenzyl carbonate and ethane-1, 2-diyl carbonate) in the presence of potassium carbonate and 18-crown-6 (or Aliqual 336) is a versatile, cheap, and safer reagent for the methylation of a variety of organic substrates.

  18. Vehicles under electricity. Result booklet; Autos unter Strom. Ergebnisbroschuere



    The booklet under consideration reports on the environmental relief of electric-driven vehicles by means of the research project OPTUM 'Potentials of environmental relief of electric driven vehicles - Integrated analysis of vehicle usage and energy economy'. Experts from the Institute for Applied Ecology (Freiburg, Federal Republic of Germany) and the Institute for Social-Ecological Research (Frankfurt (Main), Federal Republic of Germany) are devoted to the following issues: (1) What is the acceptance for electric-driven vehicles?; (2) What is their future market potential?; (3) What are the advantages of electromobility with respect to the climate?; (4) Are their supply shortages concerning major raw materials?.

  19. Veränderung der psychischen Belastung - unter Einbeziehung der Lebensqualität - bei Krebspatienten unter Sport

    Hörtig, Anna


    Dank neuer Diagnoseverfahren zeigt die Inzidenz der Krebserkrankungen einen zunehmenden Verlauf. Durch verbesserte Methoden in der chirurgischen und medikamentösen Therapie wird aus einer ehemals tödlichen, häufig eine chronische Krankheit. Immer mehr Patienten leben jahrelang mit ihrer Erkrankung. Die Erhaltung der Lebensqualität bei diesem steigenden Patientenkollektiv rückt immer mehr in den Fokus der Wissenschaft. Ziele der Forschung auf diesem Gebiet bestehen darin, die Nebenwirkungen de...

  20. Part-body hyperthermia with a radiofrequency multiantenna applicator under online control in 1,5 T MR-tomograph; Teilkoerperhyperthermie mit einem Radiofrequenz-Multiantennen-Applikator unter on-line Kontrolle in einem 1,5 T MR-Tomographen

    Wust, P.; Gellermann, J.; Faehling, H.; Wlodarczyk, W.; Felix, R. [Charite, Klinik fuer Strahlenheilkunde, Berlin (Germany); Seebass, M. [Konrad-Zuse-Zentrum fuer Informationstechnologie, Berlin (Germany); Turner, P. [BSD Medical Corp., Salt Lake City, UT (United States); Nadobny, J. [Charite, Klinik fuer Strahlenheilkunde, Berlin (Germany); Konrad-Zuse-Zentrum fuer Informationstechnologie, Berlin (Germany); Rau, B. [Charite, Medizinische Klinik m.S. Haematologie und Onkologie, Berlin (Germany); Hildebrandt, B.; Schlag, P.M. [Charite, Klinik fuer Chirurgie und Chirurgische Onkologie, Berlin (Germany); Oppelt, A. [Siemens Medical Solutions, Interventional MR, Erlangen (Germany)


    MR-Gantry mechanisch angekoppelt und die Koerperschule zum Monitoring eingesetzt. Dazu mussten Hyperthermie-Antennensystem (100 MHz, 1550 W) und MR-Empfaenger (63,9 MHz) hochfrequenzmaessig (Filter) und elektromagnetisch entkoppelt werden. Die Weiterverarbeitung der MR-Datensaetze erfolgt in einem eigens entwickelten Hyperthermieplanungssystem. Ein Simultanbetrieb von Radiofrequenz-Hyperthermie und MR-System ist bei klinisch relevanten Leistungen moeglich. MR-Datensaetze werden zur diagnostischen Tumordarstellung (Spin-Echo-Standardsequenzen), zur Planung der Hyperthermie (T{sub 1}-gewichtete Gradienten-Echo-Sequenzen in Gegen- und Gleichphasentechnik) und zur Temperaturdarstellung nach der Protonen-Resonanzfrequenz-Methode (PRF-Methode, Phasenauswertung einer Gradienten-Echo-Sequenz mit langer Echozeit) eingesetzt. Bei 33 Patienten mit fortgeschrittenen pelvinen und abdominellen Tumoren wurden ueber 150 Hyperthermiebehandlungen unter MR-Monitoring durchgefuehrt. Bei 70% der Patienten gelang eine Visualisierung temperatursensitiver Daten waehrend der Therapiezeit. Die ausgewerteten Differenzbilder stellen eine Ueberlagerung der tatsaechlichen Temperaturerhoehung und einer (temperaturinduzierten) Perfusionserhoehung dar. Dieser Hybridansatz ermoeglicht es, die Teilkoerperhyperthermie als MR-gesteuerte Intervention fuer die Radiologie zu entwickeln. (orig.)

  1. Investigation and modelling of the alkaline release and transport during coal combustion at elevated pressures. Final report; Untersuchung und Modellierung der Freisetzungs- und Transportvorgaenge von Alkalien bei der Kohleverbrennung unter hohen Druecken. Untersuchungen mit der Hochdruck-Hochtemperatur-Thermowaage, Alkalienanalysen in Rohkohlen und Feuerungsversuche in der Druckwirbelschichtanlage FRED (DMT). Abschlussbericht

    Bonn, B.; Steffin, C.; Busch, U.; Mayer, M.


    Verbrennung unter Druck. Variiert wurden hierzu die Einflussparameter umgebende Gasatmosphaere und Aschezusammensetzung sowie Druck und Aufheizrate. Die Versuche wurden in der DMT Hochdruck-Hochtemperatur-Thermowaage (TGA) und der DMT Druckwirbelschichtfeuerung (DWSF) durchgefuehrt. TGA-Versuche: Als Modelsubstanz fuer Alkalien wurde Natriumchlorid und fuer die Mineralsubstanz der Kohle Metakaolin eingesetzt. Die chemische Eigenschaft (Basizitaet) von Metakaolin wurde durch Zugabe von CaO veraendert. Die allgemein akzeptierte Annahme eines physikalischen Verdampfungsprozesses der Alkalien aus den Kohleaschen konnte in den TGA-Versuchen nicht bestaetigt werden. Vielmehr muss von einer Desorptionsreaktion des Natriumchlorids von der Metakaolin-Oberflaeche ausgegangen werden. Die Desorption von Alkalien wird nicht durch die chemische Zusammensetzung der Mineralsubstanz beeinflusst, dagegen besitzen die Sauerstoffverbindungen in der Gasphase und der Druck einen starken Einfluss. DWSF-Versuche: Die Versuchsanlage wurde betrieben bei einer Wirbelschichttemperatur von 920 C und einem Druck von 7 bar. Die online/in-situ Alkali-Messung beruht auf der Excimer Laser Induced Fragmentation Fluorescence ELIF. Die Alkali-Konzentration wurde variiert durch die Zugabe von Natriumacetat und Natriumchlorid. Als Adsorber von Alkaliemissionen wurde Kaolin eingesetzt. Darueber hinaus wurde der Einfluss der Kalksteinzugabe auf die Alkali-Emissionen untersucht. Die Versuche zeigten u.a., dass die Alkali-Emissionen von Braunkohlen um einen Faktor 50-100 ueber den Alkali-Emissionen von Steinkohlen liegen, und dass die Zugabe von Kalkstein (der zur SO{sub 2}-Minderung eingesetzt wird) zu stark ansteigenden Alkalichlorid-Emissionen fuehrt. (orig.)

  2. Therapeutic effect of N-acetylcysteine on patients with idiopathic pulmonary fibrosis%N-乙酰半胱氨酸辅治特发性肺纤维化的临床疗效观察

    王传海; 李承红; 孔彬


    目的:探讨N-乙酰半胱氨酸( NAC)辅治特发性肺纤维化( IPF)的临床疗效。方法采用按入院顺序随机、对照的方法,将42例IPF患者分为观察组和对照组,每组21例,观察组在糖皮质激素口服常规治疗基础上加用NAC,对照组糖皮质激素口服常规治疗。2组其余基础治疗相同,疗程均为6个月。评价比较2组临床疗效,观察2组治疗前后、肺功能[肺活量(VC)、一氧化碳弥散量(DLco)]、动脉血气分析[pH 值、氧分压(PaO2)、血氧饱和度(SaO2)、二氧化碳分压(PaCO2)]等指标及不良反应等。结果观察组总有效率为80.95%高于对照组的52.38%(χ2=3.857, P 0.05),观察组治疗后VC、DLco下降幅度小于对照组,差异均有统计学意义( t =-2.147, t =-2.083, P均0.05),PaO2、SaO2均降低,且对照组差异有统计学意义( t =2.375, t =2.459, P均0.05),治疗后观察组PaO2、SaO2下降幅度小于对照组,差异均有统计学意义( t =-2.117, t =-3.426, P 均0. 05). After treatment decrease of VC,DLco in observation group was less than those of control group, there were significant difference (t = -2. 147, t = -2. 083, P 0. 05), PaO2,SaO2 were decreased, and the differences in control group were statistically significant ( t =2. 375, t =2. 459, P 0.05),after treatment the decrease of PaO2, SaO2 in observation group was less than observation group ( t = -2. 117, t = -3. 426, P <0. 05). No serious adverse reaction was found in the 2 groups. Conclusion For patients with IPF, the conventional corticosteroid therapy added with NAC can effectively improve the symptoms of IPF, and slow down the decrease of pulmonary function, PaO2 , SaO2 .

  3. Effect of N-acetylcysteine on behavioral changes in rats after administration of methamphetamine%N-乙酰半胱氨酸对甲基苯丙胺中毒大鼠行为改变的影响

    宋健文; 蒋崇良; 王慧君


    目的:探讨N-乙酰半胱氨酸(NAC)对甲基苯丙胺(METH)引起中毒大鼠模型行为改变的保护性作用机制.方法:制备大鼠中毒模型,在METH注射前30 min腹腔注射NAC,应用二氯荧光乙酰乙酸盐(DCFH)作为荧光指标检测大鼠纹状体ROS的含量,以紫外分光光度计检测NOS的活性,以Sams-Dodd的方法给大鼠刻板行为评分,并计算不同组大鼠评分之间的差异.结果:NAC预处理能降低纹状体内ROS的含量(P<0.001)及NOS的活性(P<0.001),减轻METH中毒大鼠精神行为改变,降低了中毒大鼠的刻板行为评分(P<0.001).结论:NAC可能通过逆转METH诱导大鼠纹状体区的氧化失衡状态,减轻氧化应激诱导的精神行为异常改变,产生保护性作用.

  4. N-Acetylcysteine attenuates methamphetamine induced neurotoxicity in rat striatum%N-乙酰半胱氨酸减轻大鼠纹状体甲基苯丙胺神经毒性

    宋健文; 刘增甲; 谭晓辉; 王慧君


    目的 探讨N-乙酰半胱氨酸(NAC)对甲基苯丙胺(METH)中毒大鼠模型纹状体神经毒性的影响及作用机制.方法 制备大鼠中毒模型,在METH前30 min腹腔注射(ip) NAC,应用氯荧光乙酰乙酸盐作为荧光指标检测纹状体ROS的含量,高效液相色谱方法 检测DA浓度,TUNEL方法 观察神经元损害情况,并计算神经元的凋亡率.结果 NAC预处理能降低纹状体内ROS的含量,减轻DA浓度的下降程度,减少神经细胞的凋亡.结论 NAC通过抑制METH诱导纹状体的氧化应激,减轻METH多巴胺能神经毒性.

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

    Skov, Marianne; Pressler, Tacjana; Lykkesfeldt, Jens;


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

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

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


    Objectives: The prothrombin time (PT) assay of factor II+VII+X activity is an important predictor of liver damage in paracetamol poisoned patients. It complicates interpretation of results that the antidote, acetylcysteine (NAC) depresses this activity. The aim was to investigate if NAC influences...

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

    Thorsen, Sixtus; Teisner, Ane; Jensen, Søren Astrup;


    OBJECTIVES: The prothrombin time (PT) assay of factor II+VII+X activity is an important predictor of liver damage in paracetamol poisoned patients. It complicates interpretation of results that the antidote, acetylcysteine (NAC) depresses this activity. The aim was to investigate if NAC influences...

  8. Modulatory effects of N-acetylcysteine on cerebral cortex and cerebellum regions of ageing rat brain Efectos moduladores de la N-acetilcisteína sobre la corteza cerebral y las regiones cerebelosas sobre la del cerebro senescente de rata

    S. Singh Kanwar


    Full Text Available Oxidative stress has been implicated in brain ageing and in age-related neurodegenerative disorders. Since Nacetylcysteine (NAC has recently been shown to prevent oxidative damage in ageing brain, we have examined the effects of this thiolic antioxidant on the age associated oxidative stress related parameters in rat brain regions. The lipid peroxide formation, reduced glutathione (GSH content along with the activities of superoxide dismutase (SOD and catalase were determined in the cerebral cortex and cerebellum brain regions of the young (4 months and older (14 months female rats. The lipid peroxidation was observed to be increased in the cerebral cortex regions accompanied by simultaneous decrease in the GSH content in both the regions of older rats. The SOD activity was reduced in both the regions while catalase was reduced only in cerebellum region of the older rats. Following NAC supplementation (160 mg/kg. b. wt./ day, lipid peroxidation was observed to be reduced which was accompanied by enhanced GSH levels, along with enhanced SOD and catalase in both the brain regions of older rats. Further, in the younger rats the NAC treatment resulted in the decrease of lipid peroxidation in both the regions that was accompanied by the increase catalase activity in cerebral cortex region along with increase in GSH content and SOD in cerebellum regions. Our result suggests that the normal brain ageing is associated with the decrease in antioxidative defense status and the supplementation of thiol antioxidants like NAC may prove helpful in managing the age related brain disorders characterized by compromised antioxidative defense systems.El estrés oxidativo se ha implicado en el envejecimiento cerebral y en los trastornos neurodegenerativos asociados con la edad. Puesto que recientemente se ha demostrado que la N-acetilcisteína (NAC previene el daño oxidativo en el cerebro senescente, hemos explorado los efectos de este antioxidante tiólico sobre los parámetros relacionados con el estrés oxidativo asociado al envejecimiento cerebral en regiones cerebrales de la rata. La formación de peróxidos lipídicos, la reducción en el contenido de glutatión (GSH, junto con las actividades de la superóxido dismutasa (SOD y catalasa se determinaron in las regiones cerebrales corticales y cerebelosas de ratas hembra jóvenes (4 meses y viejas (14 meses. La peroxidación lipídica se observó aumentada en las regiones de la corteza cerebral junto con un descenso simultáneo del contenido en GSH en ambas regiones de las ratas viejas. La actividad de la SOD estaba reducida en ambas regiones mientras que la catalasa estaba disminuida sólo en la región cerebelosa de las ratas viejas. Tras el suplemento con NAC (160 mg/kg de peso/ d��a, se observó que la peroxidación lipídica disminuía, lo que se acompañó de concentraciones aumentadas de GSH junto con aumento de SOD y catalasa en ambas regiones cerebrales de las ratas viejas. Además, en las ratas jóvenes, el tratamiento con NAC produjo una disminución de la peroxidación lipídica en ambas regiones acompañada de un aumento de la actividad catalasa en la región de la corteza cerebral junto con un aumento del contenido en GSH y SOD en la región del cerebelo. Nuestros resultados sugieren que el envejecimiento cerebral normal se asocia con una disminución del estado defensivo antioxidante y que la complementación con antioxidantes tiólicos como la NAC podría mostrarse útil en el tratamiento de los trastornos cerebrales relacionados con la edad y caracterizados por una alteración de los sistemas defensivos antioxidantes.

  9. Comparison of high resolution whole-body MRI using parallel imaging and PET-CT. First experiences with a 32-channel MRI system; Hochaufloesendes Ganzkoerpertumorstaging unter Verwendung paralleler Bildgebung im Vergleich zur PET-CT. Erste Erfahrungen auf einem 32-Kanal-MRT-System

    Schmidt, G.P.; Baur-Melnyk, A.; Reiser, M.F.; Schoenberg, S.O. [Klinikum Grosshadern der Ludwig-Maximilians-Universitaet Muenchen, Institut fuer Klinische Radiologie (Germany); Tiling, R.; Hahn, K. [Klinikum Grosshadern der Ludwig-Maximilians-Universitaet Muenchen, Klinik und Poliklinik fuer Nuklearmedizin (Germany)


    technique in the detection of primary tumor and metastatic disease. Sensitivity in the assessment of lymph node metastases seems to be limited. With the use of parallel imaging (iPAT), dedicated high-resolution whole-body MRI is possible within acceptable scanning times. (orig.) [German] Vergleich der Genauigkeit eines hochaufloesenden Ganzkoerper-MRT-Tumorstagings unter Verwendung paralleler Bildgebung mit den Ergebnissen der PET-CT. Es werden erste Ergebnisse einer Interimsanalyse aus einer prospektiven, geblindeten Studie vorgestellt, in der an 20 Patienten (Durchschnittsalter 59 Jahre, Range 27-77 Jahre) mit unterschiedlichen onkologischen Erkrankungen im Rahmen der klinischen Diagnostik eine Tumor- oder Metastasensuche mit der Ganzkoerper-FDG-PET-CT durchgefuehrt wurde. Bei allen Patienten erfolgte zusaetzlich eine Ganzkoerper-MRT-Bildgebung mit Einsatz der parallelen Bildgebungstechnik (iPAT). Angewendet wurden hochaufloesende koronare T1-gewichtete- und STIR-Sequenzen von 5 Koerperregionen mit einer Matrix von 512 x 512 mm, axiale T2-gewichtete Turbospinechosequenzen (HASTE) der Lunge und des Abdomens sowie kontrastverstaerkte dynamische und statische T1-gewichtete Sequenzen von Leber, Gehirn, Abdomen und Becken. Bei Verwendung eines 32-Kanal-Systems (Magnetom Avanto, Siemens Medical Solutions) mit einem gesamten field of view von 205 cm und freier Tischbewegung konnten alle Patienten in einem Untersuchungsgang vollstaendig von Kopf bis zu den Fuessen gescannt werden. Dabei wurde eine hohe raeumliche Aufloesung erzielt. Die Messzeit betrug ca. 55 min. Zwei erfahrene Radiologen werteten die MRT-Untersuchung, ein Radiologe und ein Nuklearmediziner die PET-CT-Untersuchung, jeweils im Konsensus, aus. Es wurden der Nachweis und das Stadium des Primaertumors oder des Tumorrezidivs sowie von Lymphknoten- und Fernmetastasen bewertet. Als Referenzmethode wurde das durch die PET-CT identifizierte TNM-Stadium herangezogen. Es wurden Metastasen von gastrointestinalen Tumoren (25

  10. Nitrate tolerance impairs nitric oxide-mediated vasodilation in vivo

    Laursen, Jørn Bech; Boesgaard, Søren; Poulsen, Henrik E.;


    Nitrates, Nitrate tolerence, Nitric oxide, acetylcholine, N-acetylcholine, N-acetylcysteine, L-NAME, Rat, Anesthetized......Nitrates, Nitrate tolerence, Nitric oxide, acetylcholine, N-acetylcholine, N-acetylcysteine, L-NAME, Rat, Anesthetized...

  11. Wireless energy transmission through the abdominal wall for operating implanted actuators and recharging implanted energy storages with due consideration to the simultaneous undisturbed transcutaneous transmission of encoded signals for controlling various functions of the implant; Drahtloser Energietransfer durch die Bauchdecke zum Betrieb von implantierten Aktoren und zur Wiederaufladung von implantierten Energiespeichern unter Beruecksichtigung der gleichzeitigen ungestoerten transkutanen Uebertragung von codierten Signalen zur Steuerung verschiedener Funktionen eines Implantats

    Peter, S.


    integrierten Energiespeicher damit geladen werden koennen, ohne Energieleitungen durch die Bauchdecke hindurch fuehren zu muessen. Dieses ziel wurde durch die Entwicklung und Anwendung eines auf die Anforderungen im urologischen Bereich eingesetzten medicinischen Implantats abgestimmten induktiven und damit transkutanen Energietransfer realisiert. Dazu wurde unter anderem ein umfangreiches Simulationsmodell zur Berechnung mit der Finiten-Element-Methode erstellt. Als Resultat ergeben sich eine Reihe von Vorteilen fuer die betroffenen Patienten: vollstaendige Vermeidung von Infektionen die sonst durch eine staendig offene ''Wunde'' in der Bauchdecke, bedingt durch die hindurch tretende Energieleitung, vorhanden waere; hierdurch ergibt sich wiederum der Vorteil, dass die Patienten weniger Medikamente zu sich nehmen muessen und die Kosten fuer eine staendige Wundbehandlung entfallen; weitestgehende Unabhaengigkeit von der stationaeren Energieversorgung im Betrieb des Systems (ueber mehrere Tage keine Notwendigkeit staendig eine Netzsteckdose in der Naehe haben zu muessen), damit geht eine wesentlich gesteigerte Mobilitaet der Patienten einher. Die Entwicklung einer transkutanen Signaluebertragung mit Hilfe von Infrarot bzw. RF Technologie hat die Rueckgewinnung einer willentlichen Steuerung der Miktion erst entscheidend ermoeglicht und beseitigt damit eine der Hauptaengste von betroffenen Patienten, ein fremdbestimmtes und durch ein von kurzen festgelegten Intervallen wiederkehrender Entleerungstaetigkeit (rund um die Uhr) gepraegtes Leben fuehren zu muessen. Die zusaetzliche Abfragemoeglichkeit des Reservoirfuellstandes ermoeglicht dabei eine Kontrolle zu beliebigen Zeitpunkten und fuehrt deshalb zu einer entscheidend verbesserten Planbarkeit der Toilettengaenge. Dies stellte das zweite Ziel dar. Die Kombination des transkutanen Energie- und Signaltransfers fuehrte u.a. zu einem Gesamtsystem, das die Lebensqualitaet der von einer Totaloperation betroffenen

  12. Investigations on the sleep quality of electrosensitive residents near base stations unter homely conditions; Untersuchung der Schlafqualitaet bei elektrosensiblen Anwohnern von Basisstationen unter haeuslichen Bedingungen

    Leitgeb, Norbert


    In this study during a total of 214 nights sleep of 200 volunteers was analyzed. The investigated persons suffered from permanent and severe sleep disturbances and were deeply convinced that the environmental radiofrequency electromagnetic fields (RF EMF) caused their problems. The studies used mobile shields to compare the sleep quality with and without shield including a sham shield. For a predominant number the subjective conviction of volunteers that RF EMF pollution was the cause of their sleep disturbance could be falsified. The pooled analysis resulted in statistically significant placebo-effects for subjective sleep parameters. For 18% of volunteers it could be demonstrated that their belief in shielding improved sleep (placebo-effect). The sleep onset behavior of 9% of the volunteers was statistical significantly affected by RF EMF shielding. The investigations did not indicate adverse health effects of RF EMF emissions in general and from mobile telecommunication fields in particular.

  13. Die Wiedergabe deutscher Abtönungspartikeln im Polnischen unter Satzarten- und Intentionsaspekt



    Modal particles can be strategically used by the speaker to specify the illocutionary content, which can have different consequences on the pragmatic and communicative level. This paper is an attempt to present German and Polish modal particles according to the intention of the speaker and sentence types. This paper gives also an insight into problem of the translation of modal particles.

  14. Sprachstandsdiagnostik im Vorschulalter unter besonderer Berücksichtigung von kognitiven Basiskompetenzen

    Melzer, Jessica


    Background: Language is important for the psychosocial and educational development of a child and is interrelated with cognitive abilities. Language deficits in childhood are associated with many subsequent problems and affect the person concerned through adulthood. The review of language skills in preschool plays a special role. Aim: This dissertation will investigate how language skills can be estimated during the diagnostic process and which cognitive basic competences affect language skil...

  15. Mythologie mal anders – Götter unter Menschen in aktueller Jugendliteratur

    Schrackmann, Petra; von Holzen, Aleta-Amirée


    Die Vermittlung mythischer Geschichten ist englischsprachigen Jugendbüchern aus dem Zeitraum von 2005 bis 2010, in denen jugendliche ProtagonistInnen Göttern und Göttinnen begegnen, ein wichtiges Anliegen. Umgesetzt wird dies einerseits mit in den Text eingeschalteten Nacherzählungen, die in unterschiedlichem Mass Variationen und Umwertungen unterliegen. Andererseits übernehmen die ProtagonistInnen Aufgaben, die klar Variationen mythischer Heldentaten darstellen. In den untersuchten Werken...

  16. Vergleichende Untersuchung zum Einsatz verschiedener Erstbehandlungsmaßnahmen beim neonatalen Kalb unter Praxisbedingungen

    Homberg, Julia


    Ziel dieser Untersuchung war es, den Einsatz von Fruchtwasserabsaugpumpen und das Aufhängen im Rahmen der Erstbehandlung von neugeborenen Kälbern zu vergleichen. Zu diesem Zweck wurde die Vitalität der Kälber post natum beurteilt. Außerdem wurde die Erkrankungshäufigkeit der Kälber in den ersten Lebenswochen ermittelt. Zusätzlich wurde untersucht, ob Störvariablen wie das Geschlecht des Kalbes, die Parität des Muttertieres, die geburtshilfliche Maßnahme und die Jahreszeit einen Einfluss au...

  17. Converter-controlled belt conveyor systems under the difficult conditions; Umrichtergesteuerte Bandanlagen unter schwierigen Bedingungen

    Horz, Michael-Josef [RAG Deutsche Steinkohle, Herne (Germany). Abt. Elektrotechnik unter Tage; Mueller, Uwe [RAG Deutsche Steinkohle, Herne (Germany). Servicebereich Technik- und Logistikdienste


    Panel 572 is located at a depth of 1,200 m in the Girondelle seam at the West mine. The panel has a mean thickness of 2.5 m and is designed as a shearer loader face with a length of 460 m. Coal is conveyed to the shaft by six belts with a total length of about 6 km and a total lifting height of 396 m. The main conveyor belt 1 with an installed power of 3 MW links the panel to a bunker. Conveyor belts 2 to 4 each with 500 kW drive power have operated in a stable manner since the start of working of the panel. Due to in-seam drivage with a selective-cut machine of type AM 85 an area with a marked trough was produced in the coal conveyor road. This area is traversed by belt 5. The planning and control of the conveyor belt in this difficult geological environment impose high demands on drive and control technology. To ensure stable operation under different loads a raft of measures was resolved and implemented. The contribution examines the problem and describes the implemented measures in detail. (orig.)

  18. Geothermal energy - Energy potential under our feet; Geothermie - Energiepotenzial unter unseren Fuessen. Neue Ansaetze zur Nutzungsoptimierung

    Heinzelmann, E. [CST Communication, Science and Technology GmbH, Bern (Switzerland)


    This article reviews new approaches to optimising the use of geothermal energy resources. Switzerland is quoted as being world leader in research into the use of geothermal resources. Work being done at the Swiss Federal Institutes of Technology in Zurich and Lausanne is reviewed. This includes research into the better use of energy-relevant geological structures. This work includes the simulation of thermo-mechanical behaviour and work done on reducing the costs involved in the construction of boreholes for geothermal installations. Uncertainties encountered are discussed and a pilot installation in Lausanne is described which used heat-exchanger piles for foundations. The results obtained are discussed. Also, various tests carried out in the rest of Europe are discussed. A method for the splintering of bedrock is described.

  19. Material properties by continuous elastic straining; Werkstoffverhalten unter zuegiger elastischer Beanspruchung

    Evertz, T. [Salzgitter Flachstahl GmbH, Salzgitter (Germany); Sonne, H.M. [ThyssenKrupp Stahl AG, Duisburg (Germany); Steinbeck, G. [Stahlinstitut VDEh, Duesseldorf (Germany); Engl, B. [MgF Magnesium Flachprodukte GmbH, Freiberg (Germany)


    Within the scope of a common research project of the steel and automotive industry, 20 sheet steels have been investigated to obtain input data for FE-analysis. In detail, characteristical elastic, plastic and fatique values were determined by several testing institutes for a period of 3 years. Knowledge of dependency of Young's modulus from temperature and orientation is important for spring back at the press shop and stiffness of parts for automotive. Young's modulus was determined by tensile tests in delivered state, after prestraining, heat treatment at room temperature and -40 C and 100 C. Young's modulus is dependent from the orientation to rolling direction and can be classified in groups. Young's modulus of ferritic steels is decreased about 10 % by prestraining of 2 % but recovered after annealing at 170 C. Temperature dependency well known from non destructive tests are confirmed. (Abstract Copyright [2004], Wiley Periodicals, Inc.) [German] Im Rahmen eines gemeinschaftlichen Projektes der Stahl- und Automobilindustrie wurden an insgesamt 20 Staehlen fuer Feinblech Kennwerte fuer die FE-Simulation ermittelt. Im Einzelnen handelte es sich um elastische, plastische und zyklische Kennwerte, die ueber einen Zeitraum von 3 Jahren von unterschiedlichen Pruefstellen erarbeitet wurden. Die Bedeutung des temperatur- und richtungsabhaengigen E-Moduls fuer den Automobilbau ist in der Rueckfederung beim Pressen von Blechen und der Steifigkeit von Automobilteilen begruendet. Der E-Modul wurde mit dem Zugversuch fuer den Anlieferungszustand, nach Vorverformung und teilweise nach Waermebehandlung bei Raumtemperatur sowie bei -40 C und 100 C ermittelt. Der E-Modul ist aufgrund der Walzbedingungen richtungsabhaengig und kann in Gruppen zusammengefasst werden. Bereits eine Vorverformung von 2 % verursacht fuer ferritische Staehle eine Verringerung des E-Moduls um ca. 10 %. Nach einer Waermebehandlung bei 170 C erholt sich der E-Modul weitgehend. Die aus zerstoerungsfreien Verfahren bekannte Temperaturabhaengigkeit konnte bestaetigt werden. (Abstract Copyright [2004], Wiley Periodicals, Inc.)

  20. "Ich kam unter die Schweizer": Teaching Switzerland as a Multi-Ethnic Society

    Baumgartner, Karin


    This article describes a five-week module on "Switzerland as a multi-ethnic society" intended to counteract the popular image of Switzerland as a homogenous country concerned mostly with tourism, chocolate, and watches. Instead, the module treats Switzerland through topics such as the definition of identity in a multi-ethnic society, the…

  1. Purchasing motors in the light of full-cost calculation; Beschaffung von Motoren unter der Vollkostenbetrachtung

    Mauchle, P.; Schnyder, G.


    This final report published by the Swiss Federal Office of Energy (SFOE) presents the results of a study made on how full-cost calculation can help define the optimal purchasing strategy for electrical drives. According to the authors, taking total life-cycle costs into consideration also guarantees economical operation and helps avoid unexpected service costs. The report describes the goals of the project and co-operation with industry and users. Factors influencing life-cycle costs are looked at in detail, including investments, installation and operator-training, operation and monitoring as well as maintenance and repair. Also, energy costs are looked at, as are environmental aspects and the disposal of drives taken out of service. The calculation of the economic feasibility of two types of motor is looked at. Sample Calls for Tender are presented and software for the evaluation of offers is briefly discussed.

  2. Untersuchung zur Offenlaufstallhaltung von Pferden unter dem Aspekt des Zusammenhangs zwischen Haltung und Gesundheit

    Szivacz, Barbara


    Investigations of open barn systems of horses regarding the correlation of health and housing system The aim of this thesis was investigating if improved husbandry has a positive influence on the recovery of special health issues. Therefor 600 horse owners were asked to answer an on-line questionnaire about their horses’ behavior and health status. All horses were kept in housing systems, which had been rated positively by the Laufstall-Arbeits-Gemeinschaft (LAG), and had permanent access...

  3. Das ritual der unterwerfung Stefan Nemanjas unter Maunel I. Komnenos (1172

    Vučetić Martin Marko


    Full Text Available This article investigates the ceremonial of the subjection of the Serbian župan Stefan Nemanja to the Byzantine emperor Manuel I Komnenos (1172 and compares it with similar events of the period in question. It argues for a strong influence of western forms of conflict resolution (“deditio” in the ceremonial.

  4. Structure dynamics with regard to non-linear support behavior; Dynamische Strukturberechnung unter Beruecksichtigung nichtlinearen Lagerverhaltens

    Driessen, W. [Technischer Ueberwachungs-Verein Nord e.V., Hamburg (Germany)


    Because of modifications to a feed-water line of a power plant structural calculations of the pipework were performed. As a result of a linear (modal) analysis very high restraint forces on the supports were calculated. In order to reduce conservatisms in the calculation the model was optimized with regard to the support stiffnesses and nonlinear behavior of slide bearings, guides and shock absorbers were taken into account. The main result of the non-linear analysis, which was performed by methods of direct-integration, was that nonlinearity yields evident differences in structural frequencies and in energy dissipation (damping) in comparison to the linear analysis. The high restraint forces on the supports became smaller for most of the supports but at some points the forces of the non-linear analysis were even higher. So the conservatism of the linear analysis is not fully valid for the whole structure. The relevance of the non-linear effects in dynamic piping calculations is shown by comparing the calculation result with measurements which were performed on structures in the plant. (orig.) [German] Im Rahmen der Aenderung der Speisewasserleitung einer Kraftwerksanlage wurde die Struktur neu berechnet. Die Analysen mit einem linearen Modell (modal), das ueblicherweise verwendet wird, ergaben hohe Lasten an Halterungen. Zum Abbau von Konservativitaeten wurde eine realistischere Modellierung durch die Beruecksichtigung des nichtlinearen Verhaltens der in der Anlage befindlichen Gleitlager, Fuehrungen und Stossbremsen in der Berechnung vorgenommen. Die Untersuchungen haben ergeben, dass durch die Nichtlinearitaet das Frequenzverhalten der Struktur und die Dissipation von Energie durch Reibvorgaenge wesentlich beeinflusst werden. Des Weiteren ist festzustellen, dass aus linearen Analysen nicht uneingeschraenkt konservative Ergebnisse gewonnen werden. Die Relevanz der Beruecksichtigung des nichtlinearen Lagerverhaltens bei einer dynamischen Strukturberechnung wird hier anhand eines Vergleiches mit einer der im Rahmen der In-Betrieb-Setzung des Kraftwerks gemessenen Verschiebungen aufgezeigt. (orig.)

  5. Orientierung und Navigation in zoombaren Benutzerschnittstellen unter besonderer Berücksichtigung kognitions-psychologischer Erkenntnisse


    Zoomable User Interfaces (ZUIs) allow access to information-objects in a natural and visual-spatial way. Instead of navigating in abstract hierarchies and structures, the user can navigate in an infinite information landscape by zooming and panning. Informationobjects are therefore organized in space and scale, which allows the user to navigate analogue to the real world. If someone would like to access more information about an object in the real world they simply step closer to it. In a sim...

  6. Heat requirement of greenhouses including latent heat flux; Waermebedarf von Gewaechshaeusern unter Beruecksichtigung des latenten Waermetransportes

    Tantau, Hans-Juergen [Hannover Univ. (Germany). Fachgebiet Biosystem- und Gartenbautechnik


    Unlike buildings, the heat demand of greenhouses is affected also by the evaporation of the respective crop. Due to condensation of water vapour inside the covering material, latent heat is converted into sensible heat and transported outwards through the covering material. The portion of latent heat can increase to more than 50 % of the internal heat transfer and is therefore a significant heat flux, which must be considered in calculations of heat demand. The heat transfer coefficients (U-values), as they are given in literature, are only valid for dry conditions without condensation. In this work, a simplified methodological approach was chosen using heat transfer resistances to consider the latent heat flux and thus, to calculate U-values for greenhouse conditions including condensation. (orig.)

  7. Herstellung, In-line-Einschluss und Charakterisierung lipophiler und hydrophiler Kamillenextrakte unter Einsatz von verdichtetem Kohlendioxid

    Kaiser, Claudia Susanne


    In dieser Arbeit werden die Möglichkeiten der Anwendung von überkritischem CO2 im Bereich der Naturstoffextraktion anhand der Kamille als Modellpflanze untersucht. Kamillenblüten enthalten eine Vielzahl von pharmakologisch wirksamen Inhaltsstoffen mit unterschiedlichsten Eigenschaften im Hinblick auf Polarität und Stabilität und stellen damit eine ideale Matrix dar, um ein breites Spektrum an Einflussgrößen zu untersuchen. Die Optimierung der Extraktionsparameter ergibt hohe Selektivität ...

  8. Hormonprofilveränderungen unter DHEA-Substitution bei Patienten mit erektiler Dysfunktion

    Reiter WJ


    Full Text Available Dehydroepiandrosteron (DHEA ist das verbreitetste Hormon im menschlichen Körper und wird der Gruppe der Steroidhormone zugeordnet. Nach Bildung in der Zona reticularis der Nebennierenrinde wird es mit Hilfe des Leberenzyms Dehydroepiandrosteronsulfotransferase in das Sulfat Dehydroepiandrosteronsulfat (DHEAS umgewandelt, zirkuliert so relativ stabil im Blut und wird in die Sexualhormone Testosteron und Östrogen im Gewebe transformiert. Eine bisher wissenschaftlich nicht abgeklärte Frage ist die Wirkung einer DHEA-Substitution auf die Serumspiegel der Sexualhormone beim Mann. Zu diesem Zweck wurden an allen Patienten mit ED, die an unserer Klinik und in zwei urologischen Kassenpraxen dieser Hormonsubstitution unterzogen wurden, im Rahmen einer prospektiven Studie ein Monitoring der wichtigsten Sexualhormone durchgeführt. Zwischen Oktober 1997 und Februar 2000 wurden 187 Patienten mit einem mittleren Alter von 52,4 Jahren, welche primär unsere Ambulanz oder zwei urologische Kassenpraxen wegen einer ED aufsuchten, nach urologischer und endokrinologischer Abklärung in diese prospektive, offene Studie aufgenommen. Alle Patienten wurden sorgfältig auf medizinische Faktoren untersucht, die einen Einfluß auf endokrinologische Abläufe haben könnten. Jeder Patient wurde mit einer Kapsel DHEA 50 mg 1 x 1 tgl. therapiert und für einen geplanten Studienzeitraum von 6 Monaten in die Studie aufgenommen. Eine statistisch signifikante Veränderung zeigten nur die Östradiolwerte. Dieser Anstieg schon begann 3 Monaten und diese Tendenz wurde bis zum Studienende beibehalten. Es konnte in dieser prospektiven Studie erstmalig in einem großen Patientenkollektiv gezeigt werden, daß sich bei männlichen Patienten mit erektiler Dysfunktion nach Substitutionstherapie mit 50 mg DHEA einmal tgl. eine statistisch signifikante Steigerung der Östradiolwerte, jedoch keine Veränderung der Testosteronwerte nachweisen läßt. Ob nun die DHEA-Wirkung beim ED-Patienten durch zentralnervöse Wirkungsmechanismen oder durch eine periphere Östrogenwirkung zu erfolgt, ist derzeit leider nur hypothetisch und durch weitere Forschungsarbeit abzuklären.

  9. Waste management in underground mining. Colloquium; Abfallentsorgung im Bergbau unter Tage. Tagung

    Frenz, W.; Martens, P.N.; Pretz, T. (eds.)


    The problem of underground waste management is reviewed from various aspects. Technical, legal and ecological problems are outlined with particular emphasis on the aspect of long-term safety. [German] Ziel unserer Veranstaltung ist, die Problematik der untertaegigen Abfallentsorgung aus den unterschiedlichsten Perspektiven zu beleuchten. Sowohl die technische als auch die rechtliche wie auch die oekologische Sichtweise werden aufgezeigt. In technischer Hinsicht werden der aktuelle Stand der Methoden und Fortentwicklungsmoeglichkeiten dargestellt und anhand konkreter Beispiele erlaeutert. Besondere Bedeutung hat dabei die Frage der Langzeitsicherheit. (orig.)

  10. Zertifizierung eines Endometriosezentrums unter besonderer Berücksichtigung von Qualitätsmanagement und Datenerhebung

    Noe GK


    Full Text Available Die Zertifizierung von organ- oder krankheitsspezifischen Zentren ist heute gefordert. Die Prozessnormen unterliegen einer großen Bandbreite und die Anforderungsprofile reichen von Fallzahl bis zum dezidierten Prozessmanagement. Die Motivation zur Zertifizierung liegt zwischen Verbesserung der Marktposition und dem Streben nach optimierter Ablaufstrategie. Häufig treten beim Durchlauf durch den Zertifizierungsprozess unerwartete, in der Regel positive, Effekte auf. Der vorliegende Artikel zeigt diesen Prozess und seine positiven Effekte anhand des Zertifizierungsprozesses eines Endometriosezentrums mit Ausrichtung auf Qualitätsmanagementprozesse und EDV-gestützte Dokumentation in der Versorgung und Nachsorge der Patientinnen.

  11. Unter Krankheitsbedrohung. Vorbemerkungen zu einer Historischen Erforschung der Grossen Epidemien in der Österreichischen Bukowina

    Harieta Mareci-Sabol


    Full Text Available Under Threat of Disease. Introduction to a Historical Study of the Great Epidemics in Austrian Bukovina Like natural disasters, wars and famine, epidemics recorded in Austrian Bukovina, affected people from all layers of society, leaving deep traces in memory and mentality. Considered as divine punishment or attributed to poverty, ignorance and lack of hygiene, they modeled different behaviors, reactions and attitudes, causing panic, tension, isolation, economic decline and, in some cases, depopulation. Information drawn from a variety of sources (from parish and civil registers to newspapers or memories provides an overview of morbid events recorded in Bucovina, from the late XVIIIth century to the early XXth century. Consecutive or recurrent episodes of plague, cholera, diphtheria, typhoid fever and typhus, measles, scarlet, smallpox and influenza have disrupted both rural and urban communities, imposing the imperial authorities, local officials, doctors, priests, teachers, and journalists to initiate some mechanisms for prevention, limitation or eradication of the disease.

  12. Modification of fuel properties under thermal load; Veraenderung von Kraftstoffeigenschaften unter thermischer Belastung

    Lau, Kornelia; Richter, Beate; Schuemann, Ulrike; Crusius, Svetlana; Streibel, Thorsten W.; Harndorf, Horst [Rostock Univ. (Germany). Abt. Analytische und Technische Chemie


    Diesel fuel without FAME and additives as well as rapeseed methyl ester were thermally stressed (150 C) at laboratory conditions. In the course of the performed study, the chemical composition of the fuels and possibly generated residues were analyzed with regards to the influence of oxygen availability and test duration. Therefore, chromatographic methods as GC-MS (Gas Chromatography-Mass Spectrometry) and HP-SEC (High Performance-Size Exclusion Chromatography) have successfully been applied. In the formed solid B 0-residues mainly oxygen-containing aromatic compounds were identified, while the biodiesel samples show mostly decomposition products of the biofuel like carbonic acids and aldehydes. In both fuels an increasing amount of compounds with high molecular weights was observed versus test duration. It is assumed that these components consist of oligo- and polymers with high oxygen content. However, this needs to be proved by further analytical methods. On the basis of these results prospective tailor-made additive packages for the stabilisation of fuels and the prevention of deposits in fuel injection systems, can be developed and applied. (orig.)

  13. Unternehmen unter der Dominanz der Finanzmärkte? Orientierungen aus sozialethischer Perspektive

    Wolf-Gero Reichert


    Full Text Available There is a crucial change in the German financial system and listed corporations: The influence of the financial markets has grown in both fields. Subsequently, shareholders can enforce their interests more efficiently than other stakeholders (e.g. affiliates, NGOs, political communities, and employees. In the paper, diverse explanations for this development are presented and evaluated: disintermediation, financial market capitalism and ‘financialization’. Afterward, the topic is discussed in the perspective of theological ethics. Catholic Social Teaching features no financial ethics, but it includes some thoughts that offer an orientation for economic policy, the concept of an economy in service of the common good, the idea of a cooperation between state, market and civil society and socially anchored entrepreneurship as well as the conception of a serving financial economy. In conclusion, action perspectives are described.

  14. Systematische Entwicklung amorpher Kohlenstoffschichten unter Berücksichtigung der Anforderungen der Blechmassivumformung

    Hetzner, Harald


    Bei der Blechmassivumformung handelt es sich um eine neue Klasse von Umformverfahren, für die im Sonderforschungsbereich/Transregio 73 die ingenieurwissenschaftlichen Grundlagen geschaffen werden. Das Ziel ist es, durch eine Kombination von Verfahren der Blech- und Massivumformung funktionsintegrierte Bauteile ausgehend von flächigen Halbzeugen, vorzugsweise Stahlblechen, kosten- und ressourceneffizient fertigen zu können. Um komplexe Nebenformelemente in der Größe der Blechdicke, z. B. Verz...

  15. Metabolische Veränderungen bei cerebralen Erkrankungen unter Einfluss therapeutischer Maßnahmen.

    Mißler, Jane


    The liver synthesizes a lot of essential substances and works as a detoxification organ by biotransforming toxic compounds, like ammonia. Ammonia is mainly produced by the metabolism of proteins and amino acids. Considering the numerous hepatic functions, chronic and acute liver failure can lead to metabolic disorders. The toxic Ammonia cannot be degraded any longer by the urea cycle and causes high concentrations in blood. This is called hyperammonaemia (HA) and leads to hepatic encephalopat...

  16. A close look at air-conditioner air-filters; Klimaanlagen-Luftfilter unter der Lupe

    Reichert, F.


    This article presents the findings of a long-term study made on air-filters. Results of measurements made according to EN 779 under ideal conditions are discussed and their use as a basis for the assessment of performance in practice is looked at critically. The two-year, long-term study follows up earlier studies on the hygiene of air-conditioning systems. Real-life installations with F7 and F9 filters were tested. Measurement methods used are discussed and the characteristics of the filters with respect to micro-organisms looked at. Various factors considered are examined and alternative filter combinations are briefly discussed. The results are presented in graphical form. EN 779-specific tests made and the results obtained are discussed.

  17. Zur Struktur des deutschen Satzes. Systematische Betrachtung der einzelnen Satzpositionen unter didaktischen Gesichtspunkten

    Dieter Schmid


    Full Text Available Die Struktur, d.h. die Syntax des deutschen Satzes ist möglicherweise das komplexeste Thema der deutschen Grammatik. Es scheint, dass die meisten Fehler in diesem Bereich gemacht werden, und selbst Muttersprachler und Muttersprachlerinnen sind oft unsicher bzgl. der richtigen Wortstellung, insbesondere im Mittelfeld des Satzes. Dieser Aufsatz versucht, Deutschlehrern und -lehrerinnen eine Hilfestellung zu geben, indem er − aufbauend auf das topologische oder Stellungsfeldermodell von Erich Drach (vgl. Musan 2009: 10 − die wichtigsten Stellungsregeln für die verschiedenen Satzelemente angibt. Dies geschieht dadurch, dass alle möglichen „Positionen“ des deutschen Satzes systematisch untersucht werden, eine nach der anderen. The structure, i.e., the syntax of the German sentence is perhaps the most complex topic of German grammar. It seems that most mistakes are made in this area, and even native speakers are often not sure about the correct word order, especially in the middle-field of the sentence. This paper tries to help German teachers by giving them − based on the topological field model of Erich Drach − the most important rules about the correct positioning of the different elements of the sentence. It does so by examining systematically all the possible “positions” of the German sentence, one after the other.

  18. Methane synthesis under mild conditions for decentralized applications; Methansynthese unter milden Bedingungen fuer dezentrale Anwendungen

    Schlueter, Michael [DBFZ Deutsches Biomasseforschungszentrum gGmbH, Leipzig (Germany); Roensch, Stefan


    It is a central aim of the German government to significantly reduce the emission of greenhouse gases in the next years. One possibility to reach this aim is the substitution of fossil fuels, especially natural gas, by fuels from biogenic sources (Bio-SNG). However, it is a drawback of Bio-SNG that the production costs are considerably higher than those of fossil natural gas. This work provides an approach to reduce the production costs of Bio-SNG. It is the aim to reduce the process parameters of the methane synthesis. At the same time, it has to be ensured that high methane yields are achieved even at those mild conditions. A procedure for the optimization of the methanation catalyst activity will be presented. If the catalyst is as active as possible even at mild conditions, it will be possible to produce Bio-SNG cost efficient even in small, decentralized scale.

  19. Production of liquid hydrocarbons using nuclear energy; Erzeugung von fluessigen Kohlenwasserstoffen unter Einsatz von Kernenergie

    Poeppe, N.; Tragsdorf, I.M. [Technische Hochschule Aachen (Germany). Lehrstuhl fuer Reaktorsicherheit und -technik; Kugeler, K. [Technische Hochschule Aachen (Germany). Lehrstuhl fuer Reaktorsicherheit und -technik]|[Forschungszentrum Juelich GmbH (Germany). Inst. fuer Sicherheitsforschung und Reaktortechnik; Kugeler, E.


    In the future, the global demand on liquid hydrocarbons especially for the traffic sector will still increase. To supply the world market with adequate volumes will necessitate the application of alternatively generated fuels in a few decades already. Besides conventional generation processes, where the necessary process heat comes from the combustion of part of the products, the use of nuclear heat is possible to cover the process energy demand. This heat is required in form of steam, electricity and high-temperature heat. Using these techniques the following processes can be attractive: steam flooding of oil deposits, the oil recovery from oil sands and oil shales, the methanol production from natural gas, the coal hydrogenation as well as the production of methanol from biomass. Normally, the volume of recoverable light hydrocarbons can be doubled by applying nuclear energy. The CO{sub 2} emissions during the production process can be avoided and the production costs can be decreased compared to current oil prices. The necessary conversion technologies are well-known and proven in industrial use, some of them for a long-time. The modular high-temperature reactor can be used as a nuclear heat source. This kind of heat source will be sized around 200 MW{sub th}, if a cylindrical core is used. Under these conditions even for a complete loss of the core cooling neither improper overheating of the fuel elements nor a core melt-down can occur. Therefore the retention of radioactive material in the reactor system is assured even for severe accidents. Using an annular core the power can be increased up to 400 MW{sub th} while the system maintains the mentioned safety properties. The nuclear heat is integrated into the process by steam generator, helium heated steam reformer for the steam reforming reaction and by helium-helium heat exchangers. The high-temperature heat exchangers are tested in permanent operation for helium temperatures of 950 C and for powers of 10 MW{sub th}. An extrapolation to commercially necessary sizes of 100 MW{sub th} is considered to be reliable. The mentioned processes can be seen as technically feasible on the basis of previous projects, especially of extensive programs for high-temperature materials. (orig.)

  20. Möglichkeiten der endoskopischen Herzchirurgie unter Verwendung des da VinciTM-Operationsroboters

    Dogan S


    Full Text Available Mit der Einführung des da VinciTM-Operationsroboters steht ein neues Werkzeug zur Verfügung, welches das Spektrum der minimalinvasiven Operationstechniken erweitert und totalendoskopische Operationen am Herzen ermöglicht. Seit Juni 1999 wurden an unserer Klinik 30 roboterunterstützte Eingriffe am Herzen durchgeführt. Das Spektrum der durchgeführten Operationen umfaßt totalendoskopische Bypassoperationen (TECAB mit links- oder rechtsseitigem A. mammaria-Bypass (LIMA oder RIMA zum R. interventricularis anterior (RIVA oder zur rechten Kranzarterie (RCA, aber auch Zweifachbypasseingriffe als sequentieller Mammariabypass zum RIVA und zum R. diagonalis. Sogar bilaterale A. mammaria-Versorgung des RIVA und der RCA ist mit computerunterstützter Telemanipulation erfolgreich realisiert worden. Des weiteren ist bei drei Patienten ein Atrium-Septum-Defekt in totalendoskopischer Technik sowohl mit Direktnaht als auch mit Patchverschluß korrigiert worden. Die durchschnittliche Operationszeit der 13 "closed chest"-Bypasspatienten betrug 354 ± 10 Minuten, die extrakorporale Zirkulationszeit 167 ± 11 Minuten und die Aortenklemmzeit 65 ± 7 Minuten. Außer drei Patienten hatten alle einen unkomplizierten postoperativen Verlauf und wurden in gutem Allgemeinzustand nach Hause entlassen. Bei zwei Patienten nach TECAB war eine Rethorakotomie wegen Blutung bzw. Perikardtamponade erforderlich. Eine Patientin wurde reanimationspflichtig als Folge einer vasoplegiebedingten Hypovolämie. Alle TECAB-Patienten wurden vor Entlassung aus dem Krankenhaus nachangiographiert und zeigten exzellente angiographische Ergebnisse. Wir haben gezeigt, daß computerunterstützte totalendoskopische Einfach- und Zweifachbypassoperationen sowie ASD-Verschlüsse mit dem da VinciTM-Telemanipulationssystem durchführbar sind. Obwohl eine gewisse Lernphase erforderlich ist, sind die initialen klinischen und funktionellen Ergebnisse gut. Die computerunterstützte endoskopische Operationstechnik sowie die Port Access-Kanülierung sind jedoch sehr komplex. Dadurch und durch das schwierigere anästhesiologische Management sind die Eingriffe anspruchsvoll und die Eingriffszeiten gegenüber konventionellen Methoden deutlich verlängert. Alle postulierten Vorteile der roboterunterstützten Technik müssen abgesehen von dem offensichtlichen kosmetischen Aspekt durch weitere Studien näher untersucht werden.

  1. Untersuchungen zum Krankheitsverlauf der Akuten Caninen Polyradikuloneuritis unter Intravenöser Immunglobulintherapie

    Hirschvogel, Katrin


    Treatment of dogs with acute canine polyradiculoneuritis (ACP) is restricted to physical rehabilitation and supportive care. In humans with Guillain-Barré syndrome, the counterpart of ACP, randomized trials show that intravenous immunoglobulin (IVIg) speeds recovery. We hypothesized that dogs would tolerate IVIg well and recover faster from ACP than dogs with supportive treatment only. Sixteen client-owned dogs with ACP were treated with IVIg. Five dogs were identified by a medical record ...

  2. Auswirkungen der Feldenkraismethode - Bewusstheit durch Bewegung - unter besonderer Berücksichtigung psychosomatischer Aspekte

    Busch, Wolfgang


    Die vorliegende Arbeit beschäftigt sich mit den Auswirkungen von Feldenkrais-Bewegungsübungen auf ein Klientel, dass aus freien Stücken an Feldenkraiskursen eines niedergelassenen Feldenkraislehrers teilnimmt, wobei insbesondere gesundheitliche und psychosomatische Aspekte betrachtet werden. Feldenkrais formulierte die theoretischen Grundlagen der Methodik auf einem breiten wissenschaftlichen Fundament verschiedener Fachrichtungen, wie Medizin, Neurobiologie, Psychologie, Physik, Systemtheori...

  3. Abschätzung der Nierenfunktion unter isolierter Hämoperfusion

    Unger, Volker


    Background: Models of isolated and perfused kidneys are used to study physiological and pathophysiological aspects of renal homeostasis in experimental and clinical research, so in transplantation medicine, toxicology. Since physiological and morphological parameters of small laboratory animal kidneys are difficult to compare to human renal parameters, porcine kidney perfusion models have been developed to simulate closer conditions to the human situation. If the organs could be used out of r...

  4. Orale Kontrazeptiva: Hohe Sicherheit unter Berücksichtigung diverser Wechselwirkungen

    Gruber ChJ


    Full Text Available Die Anfänge der Kontrazeption und Familienplanung reichen fast bis an die Anfänge der Menschheitsgeschichte zurück. Viele altertümliche, medizinische Dokumente geben uns über die Entwicklung der Kontrazeption Auskunft. Von einem gewissen Zeitpunkt an hatte man herausgefunden, daß die Ejakulation des Mannes in unmittelbarem Zusammenhang mit dem Zeugen von Kindern stand. Daher beschränkte sich die Kontrazeption auf Maßnahmen, die verhinderten, daß das Ejakulat weiter in die Vagina vordringen konnte. Die allerersten Aufzeichnungen über Pessare findet man im alten Ägypten im Jahre 1850 a.C. Sie wurden aus dem Kot von Elefanten oder Krokodilen hergestellt, vermischt mit Honig, Teebaumöl und Schwefel. Es ist erstaunlich, wieviele dieser Methoden doch einen biologischen Sinn gemacht haben. Ein solches Beispiel wäre die Einführung einer halben Zitrone in die obere Vagina, um die Zervix zu bedecken. Es handelt sich dabei nicht nur um eine Barriere, sondern heute ist bekannt, daß die Zitronensäure spermizid wirkt. Auch die Geschichte der Kondome reicht schon sehr weit zurück. Man verwendete Harnblasen von verschiedensten Tieren oder auch das Caecum von Schafen. Viele kontrazeptive Versuche endeten jedoch tragisch, wie das Schlucken von Arsen, Blei oder Strychnin oder die Anwendung von Gewalt auf das Abdomen der Frauen, um das Kind und alle Organe, die für die Schwangerschaft nötig sind, zu zerstören. In der modernen Zeit hat das ständig akkumulierende Wissen über die Funktion des männlichen und weiblichen Genitaltraktes, sowie das zunehmende Verständnis der molekularen und physiologischen Mechanismen des weiblichen Zyklus dazu geführt, sehr verträgliche und effiziente Formen der Kontrazeption zu entwickeln. Den größten Beitrag hierbei leistete wohl Carl Djerassi, der "Erfinder" der Antibabypille.

  5. Biosorption of heavy metals under anaerobic conditions. Final report; Biosorption von Schwermetallen unter anaeroben Bedingungen. Abschlussbericht

    Kreikenbohm, R.


    The precipitation of heavy metals as hydroxides is the standard technique for the decontamination of waste water streams polluted by these elements. On the other side, progress in research has been made concerning the biosorption onto dead biomass and bioprecipitation supported by physiologically active bacteria. As the aim of this study, a flexible strategy has been envisaged cleaning a waste water with definite heavy metal load underlying the process mentioned above. Suitable bacteria were enriched and the process was tested in a technical plant. As result, a very high efficiency of heavy metal elimination has been found. The field of application covered by the acquired process is identical with the whole range of the waste water streams polluted by heavy metals. In addition, a second stage may be necessary if there are any further contaminants to be removed. (orig.) [Deutsch] Bei der Reinigung von schwermetallhaltigen Abwaessern ist der derzeitige Stand der Technik gegeben durch die Neutralisationsfaellung als Hydroxide, waehrend in der Forschung damit begonnen wurde, Biosorption an devitaler Biomasse oder Biopraezipitation durch physiologisch aktive Bakterien zu untersuchen. Ziel des Vorhabens war die Ermittlung einer flexiblen Strategie fuer die Prozessfuehrung zur Abwasserreinigung bei vorgegebener Schadstoffbelastung auf der Basis des zuletzt genannten Prozesses. Dazu wurden geeignete Bakterien angereichert und das Verfahren in einer Technikumsanlage erprobt. Als Ergebnis wurde bei Zufuhr verschiedener Industrieabwaesser eine sehr hohe Effizienz in der Schwermetallelimination gefunden. Das Anwendungsgebiet des erarbeiteten Verfahrens erstreckt sich auf eine Vielzahl schwermetallbelasteter Abwaesser, wobei - je nach Art der weiteren Inhaltsstoffe - eine zusaetzliche Reinigungsstufe vor- oder nachgeschaltet werden muss. (orig.)

  6. The MR trainer. Lower limbs; Der MR-Trainer. Untere Extremitaet

    Breitenseher, M. [Allgemeines Krankenhaus, Vienna (Austria)


    The book is intended as a guide to MRI of the lower limbs for newcomers from other fields, such as radiology, orthopaedics, sports medicine, rheumatology, and (trauma) surgery. The MR trainer imparts the practical knowledge and insights of a specialist, taking the MRI morphology as a starting point. Special features of the didactic concept: the split-page concept, displaying pictures and schematic illustrations on the right page, and explanatory text on the left page. (orig./CB) [German] Dieses Buch wendet sich an alle Einsteiger in der MRT der unteren Extremitaet aus Radiologie, Orthopaedie, Sportmedizin, Rheumatologie und (Unfall-)Chirurgie. Der MR-Trainer vermittelt das praxisbezogene Anwenderwissen ausgehend von der MRT-Morphologie. Besonderheiten des didaktischen Konzepts: Doppelseitenkonzept, rechts Schemata und Abbildungen, links erklaerender Text; MR-Morphologie als Ausgangsbasis, (nachgeschaltet Indikation, Diagnose/DD,Technik); mit Uebungsfaellen zur Ueberpruefung des Gelernten. Wenn Sie dieses Buch durchgearbeitet haben, haben Sie verstanden - warum bestimmte Untersuchungen so gemacht werden, - wann welche Protokolle gefahren werden, - was Sie tatsaechlich sehen, - was noch normal oder schon pathologisch ist, - welcher klinische Bezug dahinter steht und - wie Sie reagieren muessen. (orig./AJ)

  7. Investigation of hydrogen recombination under natural convection conditions; Untersuchungen zur Wasserstoffrekombination unter Naturkonvektionsbedingungen

    Simon, Berno


    Passive Autocatalytic Recombiners (PAR) are installed inside the containment of nuclear power plants in order to prevent the build-up of flammable mixtures and to mitigate the effects of hydrogen deflagrations, which can occur in the event of a severe accident combined with the release of hydrogen. In order to simulate the operating behaviour of PARs, the computer program REKO-DIREKT is being developed at the Forschungszentrum Juelich in collaboration with the Institute for Reactor Safety and Reactor Technology at the RWTH Aachen. For the validation of the code, data from experimental facilities operated at Juelich are used. This work focusses on the analysis of the chimney effect through the PAR housing as well as the optimization of the chimney model of REKO-DIREKT. Therefore experimental investigations are carried out in the REKO-4 facility under natural convection conditions. This facility is equipped with numerous measuring devices, e.g. katharometers for in-situ measuring of the hydrogen concentration and the optical flow measurement technique Particle-Image-Velocimetry. In preliminary assessments the equipment is being qualified in order to determine the measurement accuracy. In the following experimental investigations, a small-scale PAR is used, that is built in a modular way allowing it to be equipped with different chimney geometries. The experimental results produce a database that shows the central correlation between the hydrogen concentration, the catalyst temperature and the inlet velocity. The results include the variation of the recombiner's chimney height and experiments at different operating pressures. After optimization of the chimney model, the simulation program is validated against experiments in the large-scale facility THAI in Eschborn, which have been performed subsequent to this thesis in the context of the OECD/NEA-THAI project. Finally, the influence of a downward-directed, near-wall flow on the operational behaviour of the small-scale PAR is investigated. The goal is to analyse, whether or not externally induced flow regimes are able to influence the start-up and operational behaviour of PARs. The results show that downward directed flow conditions may influence the operational behaviour and reduce the efficiency of a recombiner, if the flow through the chimney is not prevented by the outlet design.

  8. Ertrag und Qualität von Winterweizengenotypen unter integrierten und ökologischen Anbaubedingungen

    Leithold, Dr. B.; Weber, Prof. Dr. W.E.; Schulz, F.; Leithold, Prof. Dr. G.


    An annually identical assortment of each of 32 winter wheat varieties and lines bred under conventional conditions was tested between 2004 and 2007 both in a conventionally and in an organically managed environment. Previously the assortment had been evaluated with respect to yield and indirect parameters of baking quality. The objective was to obtain evidence for a targeted selection of lines for their later use as bread varieties in organic farming. It was discovered that for...

  9. Status quo der Haltung von Pferden in einer Region Westdeutschlands unter Aspekten des Tierwohlbefindens

    Nover, Matthias


    In this study the circumstances of horse husbandry in a region of Western Germany were gathered under aspects of animal welfare. For this reason a questionnaire based on recommendations and guidelines was created. Within the study 83 horse-keeping farms and 1580 horses were recorded. Results: Farms: The size of the farms differed between 2 and 220 horses. The farms’ plant utilization was 91.7 % on average (median). The recorded farms had often several focuses and were well equipped. ...

  10. Electromobility for everyone? An industry electrified; Elektromobilitaet fuer alle? Eine Branche steht unter Strom

    Winterkorn, Martin [Volkswagen AG, Wolfsburg (Germany)


    The electric car is one of the keys to achieving sustainable mobility - along with more efficient internal combustion engines, intelligent light-weight design and alternative sources of energy such as natural gas and next generation biogenic fuels. The Volkswagen Group is fully committed to electric mobility and is driv-ing the development of the electric car forward using its modular assem-bly strategy, the results of which can already be seen in the XL1 and the Golf blue-e-emotion. Before we are able to produce a practical, afforda-ble ''electric car for everyone,'' however, we face four major challenges: (1) developing the technology (especially the battery), (2) setting up an extensive standardized infrastructure, (3) ensuring an environmentally friendly source of electricity, and (4) driving down costs to a competitive level. All this makes electric mobility the challenge of the century - for the automotive industry and the European industrial community as a whole. It is an issue that concerns us all: manufacturers, suppliers, energy provid-ers, scientists and politicians alike. (orig.)

  11. Ein Lehrbuch über Psychiatrie und Psychotherapie – Geschlechtsunterschiede unter der Lupe?

    Isabella Heuser


    Full Text Available Anke Rohde und An