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BMC Psychiatry May 2022Pediatric bipolar disorder is a highly prevalent and morbid disorder and is considered a prevalent public health concern. Currently approved treatments often pose the... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Pediatric bipolar disorder is a highly prevalent and morbid disorder and is considered a prevalent public health concern. Currently approved treatments often pose the risk of serious side effects. Therefore, this study assessed the efficacy and tolerability of N-acetylcysteine (NAC), in children and adolescents with bipolar spectrum disorder.
METHODS
We conducted a 12-week open-label trial of NAC for treatment of mania and hypomania in children and adolescents ages 5-17 with bipolar spectrum disorder including participants with full and subthreshold manic symptoms, accepting those with and without mixed states with co-occurring depression, and Young Mania Rating Scale scores ≥ 20 and < 40. Symptoms of mania and depression were assessed using the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HDRS), Children's Depression Rating Scale (CDRS), and Clinical Global Impression (CGI) Severity (CGI-S) and Improvement (CGI-I) scales for mania and depression.
RESULTS
This study had a high drop-out rate with only 53% completing all 12 weeks. There was a significant reduction in YMRS, HDRS, and CDRS mean scores from baseline to endpoint. Of the 24 exposed participants, 54% had an anti-manic response measured by a reduction in YMRS ≥ 30% and 46% had a CGI-I mania score ≤ 2 at endpoint. Additionally, 62% of participants had an anti-depressive response measured by a reduction in HDRS ≥ 30%, 31% had an anti-depressive response measured by a reduction in CDRS ≥ 30%, and 38% had a CGI-I depression score ≤ 2 at endpoint.
CONCLUSIONS
These pilot open-label findings in a small sample provide preliminary data supporting the tolerability and safety of NAC in a pediatric population. The findings of this pilot scale study indicating improvement in mania and depression are promising, but require replication with a monotherapy randomized placebo controlled clinical trial and larger sample.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02357290 . First Registration 06/02/2015.
Topics: Acetylcysteine; Adolescent; Antimanic Agents; Bipolar Disorder; Child; Child, Preschool; Humans; Mania; Pilot Projects
PubMed: 35505312
DOI: 10.1186/s12888-022-03943-x -
European Journal of Pharmaceutical... Jun 2024Orally marketed products nintedanib (NDNB) and pirfenidone (PFD) for pulmonary fibrosis (PF) are administered in high doses and have been shown to have serious toxic and...
Orally marketed products nintedanib (NDNB) and pirfenidone (PFD) for pulmonary fibrosis (PF) are administered in high doses and have been shown to have serious toxic and side effects. NDNB can cause the elevation of galectin-3, which activates the NF-κB signaling pathway and causes the inflammatory response. S-allylmercapto-N-acetylcysteine (ASSNAC) can alleviate the inflammation response by inhibiting the TLR-4/NF-κB signaling pathway. Therefore, we designed and prepared inhalable ASSNAC and NDNB co-loaded liposomes for the treatment of pulmonary fibrosis. The yellow, spheroidal co-loaded liposomes with a particle size of 98.32±1.98 nm and zeta potential of -22.5 ± 1.58 mV were produced. The aerodynamic fine particle fraction (FPF) and mass median aerodynamic diameter (MMAD) of NDNB were >50 % (81.14 %±0.22 %) and <5 μm (1.79 μm±0.06 μm) in the nebulized liposome solution, respectively. The results showed that inhalation improved the lung deposition and retention times of both drugs. DSPE-PEG 2000 in the liposome formulation enhanced the mucus permeability and reduced phagocytic efflux mediated by macrophages. ASSNAC reduced the mRNA over-expressions of TLR-4, MyD88 and NF-κB caused by NDNB, which could reduce the NDNB's side effects. The Masson's trichrome staining of lung tissues and the levels of CAT, TGF-β1, HYP, collagen III and mRNA expressions of Collagen I, Collagen III and α-SMA in lung tissues revealed that NDNB/Lip inhalation was more beneficial to alleviate fibrosis than oral NDNB. Although the dose of NDNB/Lip was 30 times lower than that in the oral group, the inhaled NDNB/Lip group had better or comparable anti-fibrotic effects to those in the oral group. According to the expressions of Collagen I, Collagen III and α-SMA in vivo and in vitro, the combination of ASSNAC and NDNB was more effective than the single drugs for pulmonary fibrosis. Therefore, this study provided a new scheme for the treatment of pulmonary fibrosis.
Topics: Animals; Liposomes; Indoles; Acetylcysteine; Pulmonary Fibrosis; Administration, Inhalation; Lung; Mice; Male; Particle Size
PubMed: 38670294
DOI: 10.1016/j.ejps.2024.106779 -
Rationale and evidence for the adjunctive use of N-acetylcysteine in multidrug-resistant infections.European Review For Medical and... May 2023Bacterial multidrug resistance has been a serious issue for healthcare systems in recent decades, responsible for many infections and deaths. Due to the increasing... (Review)
Review
Bacterial multidrug resistance has been a serious issue for healthcare systems in recent decades, responsible for many infections and deaths. Due to the increasing incidence of antimicrobial resistance and scarce treatment options, research is focused on finding possible therapeutic adjuvants able to increase the efficacy of antibiotics. The aim of this article is a review of available evidence on the use of N-acetylcysteine (NAC). MEDLINE/PubMed was searched for appropriate keywords. In vitro and in vivo preclinical studies, clinical studies, reviews, and meta-analyses were retrieved and selected based on relevance. A narrative review article was written, reporting published evidence and the expert opinion of the authors. Among possible adjunctive treatments, NAC has attracted the interest of researchers as a candidate for re-purposing. It is a widely used drug with a good tolerability profile, mainly used as a mucolytic agent, with antioxidant, anti-inflammatory properties and antibacterial activity. NAC acts on different mechanisms and stages of infections, resulting in inhibition of biofilm formation, disruption of preformed biofilms, and reduction of bacterial viability. NAC may be administered as an aerosol in many types of infections, including cystic fibrosis, bronchiectasis and infective flare of chronic obstructive pulmonary disease (COPD), and by the intravenous route in severe systemic infections (including septic shock) such as those caused by carbapenemase (KPC)-producing Klebsiella pneumoniae (Kp) and Carbapenem-Resistant Acinetobacter baumannii (CR-Ab). A rationale exists for using NAC as an adjunctive treatment in multidrug-resistant (MDR) infections, based on in vitro, in vivo and clinical evidence, and future research is needed to identify candidate patients and optimal schedules for specific clinical conditions.
Topics: Humans; Acetylcysteine; Drug Resistance, Multiple, Bacterial; Anti-Bacterial Agents; Expectorants; Pulmonary Disease, Chronic Obstructive; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests
PubMed: 37203858
DOI: 10.26355/eurrev_202305_32342 -
Immunity, Inflammation and Disease Nov 2023Mycoplasma pneumoniae pneumonia (MPP) is a common respiratory tract infectious disease in children. The study aimed to elucidate the therapeutic efficacy of aerosolized...
OBJECTIVE
Mycoplasma pneumoniae pneumonia (MPP) is a common respiratory tract infectious disease in children. The study aimed to elucidate the therapeutic efficacy of aerosolized budesonide and N-acetylcysteine combination therapy for MP infection in children.
METHODS
One hundred and twenty children with MP infection were included and divided into the control group (received aerosol inhalation of budesonide) and the experimental group (aerosolized budesonide and N-acetylcysteine). After treatment, the disappearance time of clinical symptoms and efficacy were contrasted between the two groups.
RESULTS
With the passage of treatment time, the children's cough score of the two groups were gradually reduced. The children in the experimental group got well from the cough faster than the control group, and the difference reached a significant level on the 5th and 7th days. The time required for fever, rale, and cough to disappear in the experimental group was shorter than those in the control group. As the treatment progressed, a gradual decrease in serum interleukin-6, tumor necrosis factor-α, and C-reactive protein values was detected in both groups, and the decrease was more significant in the experimental group. The total effective rate of the experimental group was 98.33%, which surpassed the control group (93.33%).
CONCLUSION
Budesonide and N-acetylcysteine combination therapy in the treatment of MP infection in children has a significant effect, and can quickly relieve the clinical symptoms of children with good safety. It is worthy of widespread clinical use.
Topics: Child; Humans; Pneumonia, Mycoplasma; Budesonide; Acetylcysteine; Cough; Mycoplasma pneumoniae; Treatment Outcome
PubMed: 38018572
DOI: 10.1002/iid3.1068 -
Nutrients May 2023Administering N-acetylcysteine (NAC) could counteract the effect of free radicals, improving the clinical evolution of patients admitted to the Intensive Care Unit... (Randomized Controlled Trial)
Randomized Controlled Trial
Administering N-acetylcysteine (NAC) could counteract the effect of free radicals, improving the clinical evolution of patients admitted to the Intensive Care Unit (ICU). This study aimed to investigate the clinical and biochemical effects of administering NAC to critically ill patients with COVID-19. A randomized controlled clinical trial was conducted on ICU patients ( 140) with COVID-19 and divided into two groups: patients treated with NAC (NAC-treated group) and patients without NAC treatment (control group). NAC was administered as a continuous infusion with a loading dose and a maintenance dose during the study period (from admission until the third day of ICU stay). NAC-treated patients showed higher PaO/FiO ( 0.014) after 3 days in ICU than their control group counterparts. Moreover, C-reactive protein ( 0.001), D-dimer ( 0.042), and lactate dehydrogenase ( 0.001) levels decreased on the third day in NAC-treated patients. Glutathione concentrations decreased in both NAC-treated ( 0.004) and control ( 0.047) groups after 3 days in ICU; whereas glutathione peroxidase did not change during the ICU stay. The administration of NAC manages to improve the clinical and analytical response of seriously ill patients with COVID-19 compared to the control group. NAC is able to stop the decrease in glutathione concentrations.
Topics: Humans; Acetylcysteine; COVID-19; Critical Illness; Glutathione; Dietary Supplements
PubMed: 37405379
DOI: 10.3390/nu15092235 -
Experimental Biology and Medicine... May 2023Acetaminophen (APAP), a widely used antipyretic and analgesic drug in clinics, is relatively safe at therapeutic doses; however, APAP overdose may lead to fatal acute... (Review)
Review
Acetaminophen (APAP), a widely used antipyretic and analgesic drug in clinics, is relatively safe at therapeutic doses; however, APAP overdose may lead to fatal acute liver injury. Currently, -acetylcysteine (NAC) is clinically used as the main antidote for APAP poisoning, but its therapeutic effect remains limited owing to rapid disease progression and the general diagnosis of advanced poisoning. As is well known, APAP-induced hepatotoxicity (AIH) is mainly caused by the toxic metabolite -acetyl--benzoquinone imine (NAPQI), and the toxic mechanisms of AIH are complicated. Several cellular processes are involved in the pathogenesis of AIH, including liver metabolism, mitochondrial oxidative stress and dysfunction, sterile inflammation, endoplasmic reticulum stress, autophagy, and microcirculation dysfunction. Mitochondrial oxidative stress and dysfunction are the major cellular events associated with APAP-induced liver injury. Many biomolecules involved in these biological processes are potential therapeutic targets for AIH. Therefore, there is an urgent need to comprehensively clarify the molecular mechanisms underlying AIH and to explore novel therapeutic strategies. This review summarizes the various cellular events involved in AIH and discusses their potential therapeutic targets, with the aim of providing new ideas for the treatment of AIH.
Topics: Humans; Acetaminophen; Oxidative Stress; Chemical and Drug Induced Liver Injury; Acetylcysteine
PubMed: 36670547
DOI: 10.1177/15353702221147563 -
The European Respiratory Journal May 2023Mucin disulfide cross-links mediate pathologic mucus formation in muco-obstructive lung diseases. MUC-031, a novel thiol-modified carbohydrate compound, cleaves...
BACKGROUND
Mucin disulfide cross-links mediate pathologic mucus formation in muco-obstructive lung diseases. MUC-031, a novel thiol-modified carbohydrate compound, cleaves disulfides to cause mucolysis. The aim of this study was to determine the mucolytic and therapeutic effects of MUC-031 in sputum from patients with cystic fibrosis (CF) and mice with muco-obstructive lung disease (βENaC-Tg mice).
METHODS
We compared the mucolytic efficacy of MUC-031 and existing mucolytics (N-acetylcysteine (NAC) and recombinant human deoxyribonuclease I (rhDNase)) using rheology to measure the elastic modulus (G') of CF sputum, and we tested effects of MUC-031 on airway mucus plugging, inflammation and survival in βENaC-Tg mice to determine its mucolytic efficacy .
RESULTS
In CF sputum, compared to the effects of rhDNase and NAC, MUC-031 caused a larger decrease in sputum G', was faster in decreasing sputum G' by 50% and caused mucolysis of a larger proportion of sputum samples within 15 min of drug addition. Compared to vehicle control, three treatments with MUC-031 in 1 day in adult βENaC-Tg mice decreased airway mucus content (16.8±3.2 7.5±1.2 nL·mm, p<0.01) and bronchoalveolar lavage cells (73 833±6930 47 679±7736 cells·mL, p<0.05). Twice-daily treatment with MUC-031 for 2 weeks also caused decreases in these outcomes in adult and neonatal βENaC-Tg mice and reduced mortality from 37% in vehicle-treated βENaC-Tg neonates to 21% in those treated with MUC-031 (p<0.05).
CONCLUSION
MUC-031 is a potent and fast-acting mucolytic that decreases airway mucus plugging, lessens airway inflammation and improves survival in βENaC-Tg mice. These data provide rationale for human trials of MUC-031 in muco-obstructive lung diseases.
Topics: Adult; Humans; Mice; Animals; Expectorants; Sulfhydryl Compounds; Cystic Fibrosis; Acetylcysteine; Sputum; Lung Diseases, Obstructive; Inflammation; Carbohydrates; Lung
PubMed: 37080569
DOI: 10.1183/13993003.02022-2022 -
Frontiers in Immunology 2023Damage to endothelial glycocalyx (EGCX) can lead to coagulation disorders in sepsis. Heat stroke (HS) resembles sepsis in many aspects; however, it is unclear whether...
INTRODUCTION
Damage to endothelial glycocalyx (EGCX) can lead to coagulation disorders in sepsis. Heat stroke (HS) resembles sepsis in many aspects; however, it is unclear whether EGCX injury is involved in its pathophysiology. The purpose of this study was to examine the relationship between the damage of EGCX and the development of coagulation disorders during HS.
METHODS
We retrospectively collected 159 HS patients and analyzed coagulation characteristics and prognosis of HS patients with or without disseminated intravascular coagulation (DIC). We also replicated a rat HS model and measured coagulation indexes, pulmonary capillary EGCX injury in HS rats. Finally, we evaluated the effect of the antioxidant N-acetylcysteine (NAC) on HS-initiated EGCX injury and coagulation disorders.
RESULTS
Clinical data showed that HS patients complicated with DIC had a higher risk of death than HS patients without DIC. In a rat HS model, we found that rats subjected to heat stress developed hypercoagulability and platelet activation at the core body temperature of 43°C, just before the onset of HS. At 24 h of HS, the rats showed a consumptive hypo-coagulation state. The pulmonary capillary EGCX started to shed at 0 h of HS and became more severe at 24 h of HS. Importantly, pretreatment with NAC substantially alleviated EGCX damage and reversed the hypo-coagulation state in HS rats. Mechanically, HS initiated reactive oxidative species (ROS) generation, while ROS could directly cause EGCX damage. Critically, NAC protected against EGCX injury by attenuating ROS production in heat-stressed or hydrogen peroxide (HO)-stimulated endothelial cells.
DISCUSSION
Our results indicate that the poor prognosis of HS patients correlates with severe coagulation disorders, coagulation abnormalities in HS rats are associated with the damage of EGCX, and NAC improves HS-induced coagulopathy, probably through its protection against EGCX injury by preventing ROS generation.
Topics: Rats; Animals; Acetylcysteine; Endothelial Cells; Glycocalyx; Reactive Oxygen Species; Hydrogen Peroxide; Retrospective Studies; Blood Coagulation Disorders; Heat Stroke; Sepsis
PubMed: 37350963
DOI: 10.3389/fimmu.2023.1159195 -
Italian Journal of Pediatrics Jul 2023To examine the clinical impact of bronchoscope alveolar lavage (BAL) combination with budesonide, ambroxol + budesonide, or acetylcysteine + budesonide in the...
BACKGROUND
To examine the clinical impact of bronchoscope alveolar lavage (BAL) combination with budesonide, ambroxol + budesonide, or acetylcysteine + budesonide in the treatment of refractory Mycoplasma pneumoniae pneumonia (RMPP).
METHODS
Eighty-two RMPP patients admitted to Pediatrics at The First People's Hospital of Zhengzhou were retrospectively evaluated between August 2016 and August 2019. All patients were administered BAL in addition to intravenous Azithromycin, expectoration, and nebulizer inhalation. The medications added to the BLA separated the patients into the Budesonide group, Ambroxol + budesonide group, and acetylcysteine + budesonide group. Analyzed were the variations in laboratory examination indices, improvement in lung imaging, overall effective rate, and adverse responses in the three groups.
RESULTS
The laboratory test indices of patients in all three groups improved significantly relative to pre-treatment levels, and the results were statistically significant. After therapy, there were no significant differences between the three groups in terms of white blood cell (WBC), C-reactive protein (CRP), or erythrocyte sedimentation rate (ESR). Serum lactate dehydrogenase (LDH) and serum ferritin (SF) varied significantly across the three groups (P < 0.05). In the acetylcysteine + budesonide group, the absorption rate of lung imaging lesions and clinical efficacy were superior to those of the other two groups. There were no significant differences between the three groups in the occurrence of adverse events (P > 0.05).
CONCLUSIONS
BLA-coupled acetylcysteine + budesonide was superior to the other two groups in enhancing the effectiveness of RMPP in children, which might increase lung opacity absorption and minimize lung inflammation.
Topics: Child; Humans; Mycoplasma pneumoniae; Acetylcysteine; Retrospective Studies; Budesonide; Ambroxol; Pneumonia, Mycoplasma
PubMed: 37422684
DOI: 10.1186/s13052-023-01491-y -
Ulusal Travma Ve Acil Cerrahi Dergisi =... Jan 2021In burn wound healing, zones of burn, namely zone of hyperemia, the zone of stasis, and zone of coagulation, have crucial importance. These zones have been identified...
BACKGROUND
In burn wound healing, zones of burn, namely zone of hyperemia, the zone of stasis, and zone of coagulation, have crucial importance. These zones have been identified based on the pathophysiology of the burn, and treatment of burn has been improved. The zone of necrosis is treated by excision and repair through grafting. Zone of stasis fully recovers in 24-48 h if the burn treatment is managed well. Otherwise, it may convert to a zone of coagulation. Hyperemia zone is a zone that recovers itself. Recovery of the zone of stasis is very critical in burn treatment. Active oxygen radicals produced due to the hypermetabolism due to burn wounds are known to speed to the process of the zone of stasis converting into the zone of coagulation. The present experimental study aims to evaluate the effects of sildenafil and N-acetylcysteine on the zone of stasis and to establish whether they had any contribution to wound healing in burns.
METHODS
In the present study, 32 four months old female Wistar Albino rats with 200±20 gr body weights were used. The rats were divided into four groups as the sham group (Group 1), the intraperitoneal group (Group 2), Sildenafil group (Group 3, intraperitoneal 10 mg/kg for 10 days), N-acetylcysteine (Group 4, intraperitoneal 100 mg/kg for 10 days). Tissue samples were collected for serum and cytopathology studies of the Malondialdehyde level, glutathione peroxidase, superoxide dismutase, and catalyze enzyme activity. All the rats were sacrificed on the 10th day of the tests edema, hyperemia, epithelial degeneration, necrosis, inflammatory infiltration and fibrosis measurements were made.
RESULTS
When compared with the controls, both of the treatment groups had lower tissue damage scores. MDA level was lower in Group 3 and 4 compared to Group 2 and lower in Group 3 compared to Group 4. SOD, catalase and GPH-Px levels were higher in Group 3 and Group 4 compared to Group 2 and higher in Group 3 compared to Group 4.
CONCLUSION
The results of our study conducted on an experimental burn model created by rats support that Sildenafil and N-acetylcysteine have positive effects, such as decreasing oxidative stress level and increasing wound healing in burns. Further experimental studies are required on this subject.
Topics: Acetylcysteine; Animals; Burns; Female; Oxidative Stress; Rats; Rats, Wistar; Sildenafil Citrate; Wound Healing
PubMed: 33394467
DOI: 10.14744/tjtes.2020.25679