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Reactive Oxygen Species Scavenger in Acute Intracerebral Hemorrhage Patients: A Multicenter, Randomized Controlled Trial.
Kim, M, Byun, J, Chung, Y, Lee, SU, Park, JE, Park, W, Park, JC, Ahn, JS, Lee, S
Stroke. 2021;(4):1172-1181
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[Figure: see text].
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The effect of N-acetylcysteine and working memory training on glutamate concentrations in the dACC and rACC in regular cocaine users - A randomized proof of concept study.
Schulte, MHJ, Goudriaan, AE, Boendermaker, WJ, van den Brink, W, Wiers, RW
Neuroscience letters. 2021;:136146
Abstract
INTRODUCTION Current treatments for cocaine use disorder (CUD) are not very effective and better treatments are needed. This study investigates the effectiveness of a combined intervention that targets the assumed underlying glutamate pathology in cocaine users. To this end, the combined effects of N-acetylcysteine (NAC) and working memory (WM) training on glutamate concentrations in the dorsal and rostral ACC were investigated in a randomized, double-blind placebo-controlled design. METHODS In this study, 38 regular cocaine-using men were randomized to either 25-days with 2400 mg/day NAC and WM-training or 25 days with placebo with WM-training. Cocaine use, impulsivity, and glutamate concentrations in the dACC and rACC using proton Magnetic Resonance Spectroscopy were assessed at baseline and after treatment. RESULTS Twenty-four participants completed the study, of which 9 received NAC and 15 received placebo. There were no baseline correlations of glutamate concentrations in the dACC or rACC with cocaine use measures or impulsivity. Additionally, there were no effects of NAC, WM-training, or the combination thereof on (changes in) glutamate concentrations in the dACC or rACC. DISCUSSION This randomized proof of concept study could not confirm our hypotheses. Possible explanations are insufficient power and the possible absence of deviant baseline glutamate concentrations in the included participants. Future studies should consider larger samples and a non-using control group to confirm baseline deviations in glutamate in cocaine users.
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A metabolomic analysis of thiol response for standard and modified N-acetyl cysteine treatment regimens in patients with acetaminophen overdose.
Dear, JW, Ng, ML, Bateman, DN, Leroy Sivappiragasam, P, Choi, H, Khoo, BBJ, Ibrahim, B, Drum, CL
Clinical and translational science. 2021;(4):1476-1489
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N-acetylcysteine (NAC) is an antidote to prevent acetaminophen (paracetamol-APAP)-induced acute liver injury (ALI). The 3-bag licensed 20.25 h standard regimen, and a 12 h modified regimen, are used to treat APAP overdose. This study evaluated the redox thiol response and APAP metabolites, in patients with a single APAP overdose treated with either the 20.25 h standard or 12 h modified regimen. We used liquid chromatography tandem mass spectrometry to quantify clinically important oxidative stress biomarkers and APAP metabolites in plasma samples from 45 patients who participated in a randomized controlled trial (SNAP trial). We investigated the time course response of plasma metabolites at predose, 12 h, and 20.25 h post-start of NAC infusion. The results showed that the 12 h modified regimen resulted in a significant elevation of plasma NAC and cysteine concentrations at 12 h post-infusion. We found no significant alteration in the metabolism of APAP, mitochondrial, amino acids, and other thiol biomarkers with the two regimens. We examined APAP and purine metabolism in overdose patients who developed ALI. We showed the major APAP-metabolites and xanthine were significantly higher in patients with ALI. These biomarkers correlated well with alanine aminotransferase activity at admission. Receiver operating characteristic analysis showed that at admission, plasma APAP-metabolites and xanthine concentrations were predictive for ALI. In conclusion, a significantly higher redox thiol response with the modified NAC regimen at 12 h postdose suggests this regimen may produce greater antioxidant efficacy. At baseline, plasma APAP and purine metabolites may be useful biomarkers for early prediction of APAP-induced ALI.
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Efficacy and safety of mesenchymal stem cell in Chinese patients with chronic renal failure: A pilot study in Shandong province, China.
Shao, Z, Meng, X, Meng, F
Pakistan journal of pharmaceutical sciences. 2021;(3(Special)):1227-1231
Abstract
This study designed to evaluate efficacy and safety profile of Mesenchymal stem cells (MSCs) versus Acetyl cysteine (NACys) in the Chinese patients with Chronic renal failure (CRF). The CRF patients having eGFR less than 60ml per minute per 1.73m2 randomly assigned to MSCs (N=100) or NACys (N=100) (1:1) for 8 weeks. MSCs administered as intravenous infusion of marrow-derived autologous MSCs (1 × 106 to 2 × 106/kg) reperfusion, whereas, another group received NACys 600mg orally twice a day for 8 weeks. The efficacy variables include: creatinine; cystatin C; TGF-β levels; oxidants/reactive oxygen species production induced by TGF-β; collagen levels (type 1 and 4); urinary albumin/creatinine ratio and Glomerular area. Safety was also assesed. Both the treatments significantly decreased creatinine, cystatin C and reactive oxygen species from baseline, however, reduction in creatinine, cystatin C, and reactive oxygen species level from baseline was significantly higher in patient treated with MSCs (N=100) as compared to NACys (N=100). Moreover, improvement in renal and systemic functional parameters from baseline was significantly higher in patient treated with MSCs as compared to NACys. Overall, MSCs offer significantly greater improvement in renal function as compared to NACys in Chinese CRF patients.
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Study of the Effects of N-acetylcysteine on Inflammatory Biomarkers and Disease Activity Score in Patients with Rheumatoid Arthritis.
Jamali, F, Ahmadzadeh, A, Sahraei, Z, Salamzadeh, J
Iranian journal of allergy, asthma, and immunology. 2021;(5):574-583
Abstract
Rheumatoid arthritis (RA) is considered as an autoimmune-related condition in which the overproduction of pro-inflammatory cytokines leads to an inflammatory cascade. N-acetylcysteine (NAC) is a potent anti-inflammatory and anti-oxidant agent. We aimed to explore the impact of oral NAC on cytokines activities and clinical indicators in RA patients. In this placebo-controlled randomized double-blind clinical trial, 41 active RA patients were allocated in either NAC (600 mg, twice a day) or placebo group, as add-on therapy to the routine regimen, for 8 weeks. Disease activity score with an erythrocyte sedimentation rate (DAS28-ESR), and serum concentrations of interleukin (IL)-1β and IL-17 were assessed at baseline and end of the trial for all participants in the test and control groups. The reduction of the DAS28-ESR was higher considerably in the NAC group compared to that of the control group. No statistically significant differences were seen in the reduction of IL-1β and IL-17 cytokines between the NAC and control groups. In addition, improvements in the patient global assessment, number of tender joints, number of swollen joints, and the ESR rates were in favor of the NAC group. Our findings reveal that NAC may have a beneficial effect on all of the clinical features of RA. However, non-significant variations in the IL-1β and IL-17 levels suggest an alternative way of NAC effectiveness without influencing the measured cytokines. Nevertheless, these results need to be confirmed by further investigations.
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Safety, Tolerability, and Biologic Activity of AXA1125 and AXA1957 in Subjects With Nonalcoholic Fatty Liver Disease.
Harrison, SA, Baum, SJ, Gunn, NT, Younes, ZH, Kohli, A, Patil, R, Koziel, MJ, Chera, H, Zhao, J, Chakravarthy, MV
The American journal of gastroenterology. 2021;(12):2399-2409
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INTRODUCTION AXA1125 and AXA1957 are novel, orally administered endogenous metabolic modulator compositions, specifically designed to simultaneously support multiple metabolic and fibroinflammatory pathways associated with nonalcoholic fatty liver disease (NAFLD). This study assessed safety, tolerability, and biologic activity of AXA1125 and AXA1957 in NAFLD. METHODS In this multicenter, 16-week, placebo-controlled, single-blind, randomized clinical study in subjects with NAFLD stratified by type 2 diabetes, AXA1125 24 g, AXA1957 13.5 g or 20.3 g, or placebo was administered twice daily. Key metabolism (MRI-proton density fat fraction [MRI-PDFF] and homeostasis model assessment of insulin resistance [HOMA-IR]) and fibroinflammation markers (alanine aminotransferase [ALT], corrected T1 [cT1], keratin-18 [K-18] M65, and N-terminal type III collagen propeptide [Pro-C3]) were evaluated. Safety outcomes included adverse events and standard laboratory assessments. RESULTS Baseline characteristics of the 102 enrolled subjects, including 40 with type 2 diabetes, were consistent with presumed nonalcoholic steatohepatitis. AXA1125 showed consistently greater biologic activity than AXA1957 or placebo. Week 16 changes from baseline with AXA1125 vs placebo: MRI-PDFF -22.9% vs -5.7%, HOMA-IR -4.4 vs +0.7, ALT -21.9% vs -7.2%, K-18 M65 -13.6% vs +20.1%, cT1 -69.6 vs +18.3 ms (P < 0.05), and Pro-C3 -13.6% vs -3.6%. Week 16 changes from baseline with AXA1957 20.3 g: MRI-PDFF -8.1%, HOMA-IR +8.4, ALT -20.7%, K-18 M65 6.6%, cT1 -34.7 ms, and Pro-C3 -15.6%. A greater proportion of subjects treated with AXA1125 achieved clinically relevant thresholds: ≥30% MRI-PDFF, ≥17-IU/L ALT, and ≥80-ms cT1 reductions at week 16. Study products were safe and well tolerated with stable lipid and weight profiles. DISCUSSION Both compositions showed multitargeted activity on relevant NAFLD pathways. AXA1125 demonstrated the greatest activity over 16 weeks, warranting continued clinical investigation in nonalcoholic steatohepatitis subjects.
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A prospective randomized controlled trial comparing simethicone, N-acetylcysteine, sodium bicarbonate and peppermint for visualization in upper gastrointestinal endoscopy.
Mahawongkajit, P, Kanlerd, A
Surgical endoscopy. 2021;(1):303-308
Abstract
OBJECTIVES Early cancer detection is crucial in improving the patients' quality of life and upper gastrointestinal endoscopy (EGD) plays a key role in this detection. Many clearing mechanisms may be applied to create good endoscopic visualizations for the upper gastrointestinal tract using mucolytic agents, antifoaming agents, proteolytic enzymes and neutralizers. The aim of this study is to compare the effects of simethicone, N-acetylcysteine (NAC), sodium bicarbonate and peppermint as pre-medications for visualization of esophagogastroduodenoscopy (EGD). METHODS This study was a single center prospective randomized controlled trial. The patients were randomly allocated to one of four treatment groups. Group A: water; Group B: water with simethicone; Group C: water with simethicone plus NAC 600 mg; Group D: water with simethicone, NAC, sodium bicarbonate and peppermint. RESULTS A total of 128 patients were enrolled and evaluated in this study. Total visibility score (TVS) of Groups A, B, C, and D were 13.4 ± 1.86, 10.5 ± 1.45, 7.15 ± 0.98 and 6.4 ± 1.43, respectively. Group D showed lower TVS than other groups. The procedural durations of Groups C and D were significantly shorter than Group A. The volume of solution for mucosal cleansing of Groups C and D was significantly lower than Groups A and B. CONCLUSIONS The application of simethicone plus NAC is safe, improves endoscopic visualization and requires a minimal amount of mucosal cleansing solution. The addition of sodium bicarbonate and peppermint further improved visualization for the upper and lower gastric body. Thai Clinical Trials Registry (TCTR) with a reference number; TCTR20190501002.
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The effect of N-acetyl cysteine injection on renal function after coronary artery bypass graft surgery: a randomized double blind clinical trial.
Javaherforooshzadeh, F, Shaker, Z, Rashidi, M, Akhondzadeh, R, Hayati, F
Journal of cardiothoracic surgery. 2021;(1):161
Abstract
BACKGROUND This study aimed to compare the effects of N-acetyl cysteine on renal function after coronary artery bypass graft surgery. METHODS In this randomized clinical trial conducted in Golestan Hospital, Ahvaz, Iran, 60 candidates for coronary artery bypass graft surgery were selected and divided into two N-acetyl cysteine and control groups (30 people each). Patients received 3 (2 intraoperative and 1 postoperative) doses of IV N-acetyl cysteine (100 mg/kg) (n = 30) or placebo (n = 30) over 24 h. Prescription times were as follows: after induction of anesthesia, in the Next 4 h, and in the 16 h after on. Primary outcomes were serum levels of BUN and Cr, at baseline,4 and 48 h after surgery. And also need renal replacement therapy (RRT). Secondary outcomes included the hemodynamic variables, Blood products transfusion. RESULTS There were significant differences in BUN between groups at 4 h (P = 0.02) and 48 h after surgery (P = 0.001) There were significant differences in Cr level between groups at 4 h (P < 0.001) and 48 h after surgery (P = 0.001). MAP at different times (at 4 h p = 0.002 and 48 h after surgery P < 0.001) were significantly different between the two groups. There was a significant difference between the two groups in terms of the unit of Packed cell transfusion (P = 0.002) and FFP transfusion (P < 0.001). CONCLUSION In the present study, we found that administration of N-acetyl cysteine can reduce the incidence of acute kidney injury in patients undergoing coronary artery bypass graft surgery and improved kidney functions. TRIAL REGISTRY IRCT20190506043492N3 Registered at 2020.06.07.
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Effect of N-acetylcysteine against Vancomycin-Induced Nephrotoxicity: A Randomized Controlled Clinical Trial.
Badri, S, Soltani, R, Sayadi, M, Khorvash, F, Meidani, M, Taheri, S
Archives of Iranian medicine. 2020;(6):397-402
Abstract
BACKGROUND The proposed mechanism of vancomycin-induced nephrotoxicity (VIN) is indirect production of reactive oxygen species in the kidney tissue. This study aimed to investigate the effectiveness of N-acetylcysteine (NAC), an anti-oxidant agent, in the prevention of VIN. METHODS Patients who received vancomycin for any indication were randomly divided to drug (NAC) and control groups. The patients in the drug group received oral NAC 600 mg every 12 hours for 10 days, starting concurrently with vancomycin. Serum creatinine (SCr) levels and blood urea nitrogen (BUN) as well as creatinine clearance (CrCl) and 12-hour urine volume were recorded at baseline, every other day during the study, and 12 hours after the last dose of vancomycin on the 10th day. Furthermore, the cases of acute kidney injury (AKI; ≥ 0.5 mg/dL or at least 50% increase in serum creatinine from baseline) were recorded in the two groups. RESULTS Over the study period, 84 and 95 patients completed the study in drug and control groups, respectively. SCr and CrCl were significantly lower and higher, respectively, at all-time points (except for baseline) in the NAC compared to the control group. Furthermore, although not statistically significant, 12 cases of vancomycin-induced AKI were observed in the control group (12.63%), while 4 cases (4.76%) were reported from drug group (P = 0.066; relative risk [RR] = 0.377, 95% CI: 0.126-1.124). CONCLUSION NAC has the potential for reduction of VIN. However, more studies are necessary to confirm this effect.
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Protective effect of N-acetylcysteine on oxaliplatin-induced neurotoxicity in patients with colorectal and gastric cancers: A randomized, double blind, placebo-controlled, clinical trial.
Bondad, N, Boostani, R, Barri, A, Elyasi, S, Allahyari, A
Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners. 2020;(7):1575-1582
Abstract
PURPOSE Neuropathy is one of the most prevalent and dose-limiting side effects of platinum chemotherapeutic agents. N-acetylcysteine is an antioxidant thiol which is able to increase whole blood concentration of glutathione, which may be protective against chemotherapy-induced neuropathy. The aim of this study was to evaluate the effect of N-acetylcysteine on neurotoxicity induced by oxaliplatin in patients with gastric or colorectal cancers. METHODS During this randomized, double-blinded, placebo-controlled clinical trial, the preventive effect of N-acetylcysteine effervescent tablets was assessed in comparison with placebo, on neuropathy occurrence. Thirty-two patients with colorectal or gastric cancer randomly received N-acetylcysteine (two 600 mg tablets) or placebo tablets 1 h before receiving oxaliplatin in dose in XELOX (oxaliplatin and capecitabine regimen) for eight courses of chemotherapy. Neuropathy severity was assessed after eight courses of chemotherapy based on National Cancer Institute Common Terminology for Adverse Events (NCI-CTCAE) criteria neuropathy grading scale and also sensory and motor electrophysiological assessment was performed by a neurologist. RESULTS The NCI-CTCAE scale grade of patients in intervention group was significantly lower than placebo group after eight course of oxaliplatin (P = 0.01); however, the sensory electrophysiological assessment result was not significantly different (P = 0.501). No patient in both group had motor electrophysiological changes. CONCLUSION The results of this study showed that N-acetylcysteine could reduce the incidence of the neuropathy induced by oxaliplatin and delay its occurrence in patients with gastric or colorectal cancers.