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Where are we with the use of N-acetylcysteine as a preventive and adjuvant treatment for COVID-19?
Di Marco, F, Foti, G, Corsico, AG
European review for medical and pharmacological sciences. 2022;(2):715-721
Abstract
OBJECTIVE As N-acetylcysteine (NAC) is promising as a re-purposed drug for the adjunctive or supportive treatment of serious COVID-19, this article aimed to describe current evidence. MATERIALS AND METHODS A search was performed in PubMed/Medline for "NAC", "viral Infection", COVID-19", oxidative stress", "inflammation", retrieving preclinical and clinical studies. RESULTS NAC is a pleiotropic molecule with a dual antioxidant mechanism; it may neutralize free radicals and acts as a donor of cysteine, restoring the physiological pool of GSH. Serious COVID-19 patients have increased levels of reactive oxygen species (ROS) and free radicals and often present with glutathione depletion, which prompts a cytokine storm. NAC, which acts as a precursor of GSH inside cells, has been currently used in many conditions to restore or protect against GSH depletion and has a wide safety margin. In addition, NAC has anti-inflammatory activity independently of its antioxidant activity. CONCLUSIONS Clinical and experimental data suggest that NAC may act on the mechanisms leading to the prothrombotic state observed in severe COVID-19.
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Autofluorescence and Indocyanine Green in Thyroid Surgery: A Systematic Review and Meta-Analysis.
Barbieri, D, Indelicato, P, Vinciguerra, A, Di Marco, F, Formenti, AM, Trimarchi, M, Bussi, M
The Laryngoscope. 2021;(7):1683-1692
Abstract
OBJECTIVES/HYPOTHESIS To estimate the impact of optical techniques on prevention of post-operative hypocalcemia and hypoparathyroidism after total thyroidectomy. STUDY DESIGN Systematic review and meta-analysis. METHODS A literature search was conducted in Pubmed, EMBASE, SCOPUS, and Cochrane databases. The main inclusion criteria for eligible articles for meta-analysis were patients with benign or malignant thyroid pathologies who underwent total thyroidectomy, utilization of optical techniques to support PGs preservation, the availability of calcium and/or PTH levels. The primary outcome was to evaluate the variation of calcium and PTH levels when adopting optical technologies compared to standard naked-eye surgery. RESULTS In total, 13 papers with 1484 procedures were included. Pooled proportion for short- and medium-term hypocalcemia rates were 8% (95% CI, 5%:11%) and 1% (95% CI, 0%:4%) for optical techniques, while for naked-eye surgery were 15% (95% CI, 9%:23%) and 5% (95% CI, 2%:9%), respectively. CONCLUSIONS Optical technologies reduced short and medium term hypocalcemia compared to conventional surgery. LEVEL OF EVIDENCE NA Laryngoscope, 131:1683-1692, 2021.
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The Modern Western Diet Rich in Advanced Glycation End-Products (AGEs): An Overview of Its Impact on Obesity and Early Progression of Renal Pathology.
Bettiga, A, Fiorio, F, Di Marco, F, Trevisani, F, Romani, A, Porrini, E, Salonia, A, Montorsi, F, Vago, R
Nutrients. 2019;(8)
Abstract
Advanced glycation end-products (AGEs) are an assorted group of molecules formed through covalent bonds between a reduced sugar and a free amino group of proteins, lipids, and nucleic acids. Glycation alters their structure and function, leading to impaired cell function. They can be originated by physiological processes, when not counterbalanced by detoxification mechanisms, or derive from exogenous sources such as food, cigarette smoke, and air pollution. Their accumulation increases inflammation and oxidative stress through the activation of various mechanisms mainly triggered by binding to their receptors (RAGE). So far, the pathogenic role of AGEs has been evidenced in inflammatory and chronic diseases such as chronic kidney disease, cardiovascular disease, and diabetic nephropathy. This review focuses on the AGE-induced kidney damage, by describing the molecular players involved and investigating its link to the excess of body weight and visceral fat, hallmarks of obesity. Research regarding interventions to reduce AGE accumulation has been of great interest and a nutraceutical approach that would help fighting chronic diseases could be a very useful tool for patients' everyday lives.
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Oxidative stress and respiratory system: pharmacological and clinical reappraisal of N-acetylcysteine.
Santus, P, Corsico, A, Solidoro, P, Braido, F, Di Marco, F, Scichilone, N
COPD. 2014;(6):705-17
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Abstract
The large surface area for gas exchange makes the respiratory system particularly susceptible to oxidative stress-mediated injury. Both endogenous and exogenous pro-oxidants (e.g. cigarette smoke) trigger activation of leukocytes and host defenses. These mechanisms interact in a "multilevel cycle" responsible for the control of the oxidant/antioxidant homeostasis. Several studies have demonstrated the presence of increased oxidative stress and decreased antioxidants (e.g. reduced glutathione [GSH]) in subjects with chronic obstructive pulmonary disease (COPD), but the contribution of oxidative stress to the pathophysiology of COPD is generally only minimally discussed. The aim of this review was to provide a comprehensive overview of the role of oxidative stress in the pathogenesis of respiratory diseases, particularly COPD, and to examine the available clinical and experimental evidence on the use of the antioxidant N-acetylcysteine (NAC), a precursor of GSH, as an adjunct to standard therapy for the treatment of COPD. The proposed concept of "multilevel cycle" helps understand the relationship between respiratory diseases and oxidative stress, thus clarifying the rationale for using NAC in COPD. Until recently, antioxidant drugs such as NAC have been regarded only as mucolytic agents. Nevertheless, several clinical trials indicate that NAC may reduce the rate of COPD exacerbations and improve small airways function. The most plausible explanation for the beneficial effects observed in patients with COPD treated with NAC lies in the mucolytic and antioxidant effects of this drug. Modulation of bronchial inflammation by NAC may further account for these favorable clinical results.
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Beneficial effects of diltiazem during myocardial reperfusion: a randomized trial in acute myocardial infarction.
Pizzetti, G, Mailhac, A, Li Volsi, L, Di Marco, F, Lu, C, Margonato, A, Chierchia, SL
Italian heart journal : official journal of the Italian Federation of Cardiology. 2001;(10):757-65
Abstract
BACKGROUND Although in experimental models of coronary occlusion diltiazem administration has been shown to reduce the degree of stunning and of reperfusion injury, the majority of clinical trials has failed to demonstrate significant benefits. The aim of this study was to evaluate the effect of diltiazem, administered before coronary reperfusion, on infarct size, residual myocardial viability and recovery of left ventricular function. METHODS We studied 90 patients admitted within 3 hours of the onset of symptoms of acute myocardial infarction. They were immediately randomized to either intravenous diltiazem (10 mg bolus + 10 mg/hour for 3 days) (group 1, n = 43) or placebo (group 2, n = 47) and subsequently treated with recombinant tissue-type plasminogen activator. All underwent serial echocardiograms upon admission, 4 days post-admission during low-dose dobutamine stress echo, at discharge and after 6 months. We calculated the dysfunction score (1 = hypokinesia, 2 = akinesia, 3 = dyskinesia) on admission and its percent reduction after dobutamine (viability) and at follow-up (recovery). The 12-lead electrocardiograms were continuously monitored for 3 days and coronary angioplasty was performed whenever the residual stenosis was > 60%. RESULTS Upon admission, there were no differences in age, sex, infarct location and size, degree of ST-segment elevation, time from onset of symptoms and dysfunction score. Creatine kinase peaked early in 70% of patients in both groups; the incidences of recurrent ischemia, infarct-related vessel patency and the need for coronary angioplasty were also similar. The creatine kinase peak was significantly higher in group 2 (2931 +/- 2456 vs 1726 +/- 1004 IU/l, p < 0.05). Conversely, in group 1 the residual viability was significantly higher (51 +/- 23 vs 36 +/- 30% improvement in dysfunction score, p < 0.05) and the early recovery of regional function was significantly greater (35 +/- 34 vs 18 +/- 22% at discharge, p < 0.05). On the other hand, the delayed recovery was not significantly different (15 +/- 29 vs 21 +/- 32% from the time of discharge to 6 months of follow-up). CONCLUSIONS Intravenous diltiazem, started before coronary reperfusion, has beneficial effects on the infarct size, residual viability and recovery of regional function. If confirmed by larger trials, these preliminary results suggest the use of diltiazem as adjunctive therapy in patients with acute myocardial infarction and undergoing reperfusion.