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1.
Bisphenol A and Male Fertility: Myths and Realities.
Castellini, C, Totaro, M, Parisi, A, D'Andrea, S, Lucente, L, Cordeschi, G, Francavilla, S, Francavilla, F, Barbonetti, A
Frontiers in endocrinology. 2020;:353
Abstract
Bisphenol A (BPA) represents the main chemical monomer of epoxy resins and polycarbonate plastics. The environmental presence of BPA is widespread, and it can easily be absorbed by the human body through dietary and transdermal routes, so that more than 90% of the population in western countries display detectable BPA levels in the urine. As BPA is qualified as an endocrine disruptor, growing concern is rising for possible harmful effects on human health. This review critically discusses the available literature dealing with the possible impact of BPA on male fertility. In rodent models, the in vivo exposure to BPA negatively interfered with the regulation of spermatogenesis throughout the hypothalamic-pituitary-gonadal axis. Furthermore, in in vitro studies, BPA promoted mitochondrial dysfunction and oxidative/apoptotic damages in spermatozoa from different species, including humans. To date, the claimed clinical adverse effects on male fertility are largely based on the results from studies assessing the relationship between urinary BPA concentration and conventional semen parameters. These studies, however, produced controversial evidence due to heterogeneity in the extent of BPA exposure, type of population, and enrollment setting. Moreover, the cause-effect relationship cannot be established due to the cross-sectional design of the studies as well as the large spontaneous between- and within-subject variability of semen parameters. The best evidence of an adverse effect of BPA on male fertility would be provided by prospective studies on clinically relevant endpoints, including natural or medically assisted pregnancies among men either with different exposure degrees (occupational/environmental) or with different clinical conditions (fertile/subfertile).
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A review of N-acetylcysteine in the treatment of grooming disorders.
Braun, TL, Patel, V, DeBord, LC, Rosen, T
International journal of dermatology. 2019;(4):502-510
Abstract
BACKGROUND Pathologic grooming disorders can lead to clinically significant distress and functional impairment. Studies on treatment of these disorders with selective serotonin reuptake inhibitors (SSRIs) and anticonvulsants have led to inconsistent findings. N-acetylcysteine (NAC) has shown promise in treatment of obsessive-compulsive and related disorders. The objective of this article is to perform an updated review of NAC in the treatment of grooming disorders. METHODS PubMed was searched from inception to October 2017 to identify literature on the use of NAC in the management of trichotillomania, onychophagia, and pathological skin picking. Case reports, case series, and randomized controlled trials were included. Data on study design, dosing regimens, comorbidities, concurrent treatment, and side effects were extracted from the included articles. RESULTS Fifteen articles were included in this review, which consisted of 10 case reports, one case series, and four randomized controlled trials. Dosing of oral NAC ranged from 450 to 2,400 mg per day, and treatment periods lasted from 1 to 8 months. Side effects were uncommon, mild, and usually gastrointestinal in nature, with severe aggression reported in one child. CONCLUSIONS While there are multiple reports of the safety and efficacy of NAC in the treatment of grooming disorders, there are currently few randomized controlled trials on this topic, and more research is needed to develop a formal treatment algorithm. While current data should be considered very preliminary, case reports have demonstrated mostly positive results and a lack of significant side effects. A trial of NAC may be a viable option for pathologic grooming disorders, especially in patients who have failed prior psychologic or pharmacologic treatment.
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3.
N-Acetylcysteine's Role in Sepsis and Potential Benefit in Patients With Microcirculatory Derangements.
Chertoff, J
Journal of intensive care medicine. 2018;(2):87-96
Abstract
OBJECTIVE To review the data surrounding the utility of N-acetylcysteine (NAC) in sepsis and identify areas needed for additional research. DATA SOURCES A review of articles describing the mechanisms of action and clinical use of NAC in sepsis. SUMMARY OF REVIEW Despite many advances in critical care medicine, still as many as 50% of patients with septic shock die. Treatments thus far have focused on resuscitation and restoration of macrocirculatory targets in the early phases of sepsis, with less focus on microcirculatory dysfunction. N-acetylcysteine, due to its anti-inflammatory and antioxidative properties, has been readily investigated in sepsis and has yielded largely incongruous and disappointing results. In addition to its known anti-inflammatory and antioxidative roles, one underappreciated property of NAC is its ability to vasodilate the microcirculation and improve locoregional blood flow. Some investigators have sought to capitalize on this mechanism with promising results, as evidenced by microcirculatory vasodilation, improvements in regional blood flow and oxygen delivery, and reductions in lactic acidosis, organ failure, and mortality. CONCLUSION In addition to its antioxidant and anti-inflammatory properties, N-acetylcysteine possesses vasodilatory properties that could benefit the microcirculation in sepsis. It is imperative that we investigate these properties to uncover NAC's full potential for benefit in sepsis.
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4.
Comparative efficacy of pharmacological interventions for contrast-induced nephropathy prevention after coronary angiography: a network meta-analysis from randomized trials.
Ma, WQ, Zhao, Y, Wang, Y, Han, XQ, Zhu, Y, Liu, NF
International urology and nephrology. 2018;(6):1085-1095
Abstract
BACKGROUND Contrast-induced nephropathy (CIN) is the major complication related to contrast media administration in patients after coronary angiography (CAG). However, inconsistent results have been published in the literature regarding the effects of pharmacological drugs on CIN prevention. We conducted a network meta-analysis to evaluate the relative efficacy of pharmacological interventions for the prevention of CIN. METHODS We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception to July 2017. We included any randomized controlled trials of eleven pharmacological interventions that reported the prevention of CIN. RESULTS We identified 3850 records through database searches, of which 107 studies comprising 21,450 participants were finally identified. Compared with intravenous saline, intravenous saline plus pharmacological drugs including statin [relative risk (RR) 0.57; 95% credibility interval (CrI) 0.39 to 0.83], N-acetylcysteine (NAC) (RR 0.84; 95% CrI, 0.71 to 0.98), vitamin and its analogues (RR 0.66; 95% CrI 0.45 to 0.97), brain natriuretic peptide (BNP) and its analogues (RR 0.46; 95% CrI 0.30 to 0.70), prostaglandin analogues (RR 0.37; 95% CrI 0.18 to 0.76), NAC plus sodium bicarbonate (SB) (RR 0.60; 95% CrI 0.39 to 0.90), and statin plus NAC (RR 0.39; 95% CrI 0.21 to 0.70), have helped to reduce the incidence of CIN in patients after CAG. The top four ranked treatments were statin plus NAC, BNP and its analogues, statin, and vitamin and its analogues, respectively. NAC plus intravenous saline was associated with lower incidence of short-term all-cause mortality than intravenous saline alone (RR 0.62; 95% CI, 0.40 to 0.96; P = 0.03). However, no evidence indicated that any of the pharmacological drugs were associated with a reduced requirement for dialysis and major adverse cardiac and cerebrovascular events (MACCE). CONCLUSIONS Statin plus NAC plus intravenous saline seems to be the most effective treatment for the prevention of CIN in patients after CAG. NAC plus intravenous saline may have a protective role against short-term all-cause mortality. However, none of these drugs has effectively decreased the requirement for dialysis and MACCE.
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5.
Modern Management of Acute Liver Failure.
Khan, R, Koppe, S
Gastroenterology clinics of North America. 2018;(2):313-326
Abstract
Acute liver failure is a rare but life-threatening disease that can lead to progressive encephalopathy, intracranial hypertension, and multiorgan failure. In the developed world, the most common cause remains acetaminophen overdose, but there are still many cases in which there is acute liver failure of unknown etiology. The mainstay of acute liver failure management remains supportive care in the critical care setting. If supportive treatment does not stabilize the disease process, the patient may require emergent liver transplantation. This article summarizes the current management of acute liver failure.
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6.
Free radical scavenging properties of mannitol and its role as a constituent of hyaluronic acid fillers: a literature review.
André, P, Villain, F
International journal of cosmetic science. 2017;(4):355-360
Abstract
Mannitol has both hydrating and antioxidant properties that make it an ideal excipient for use with hyaluronic acid (HA) fillers. This review examines the role of reactive oxygen species in the ageing process and their effects on both endogenous HA and HA products developed for aesthetic use. Evidence is presented to show that the free radical scavenging properties of mannitol provide it with a two-fold mechanism of action when combined with HA fillers: reducing the inflammation and swelling associated with the injection procedure itself, and preventing the degradation of the injected HA by free radicals. Mannitol also has a long- and well-established safety profile in both the food and pharmaceutical industry. Having established the rationale for using mannitol in combination with an HA filler, the products using this strategy are then reviewed. The addition of mannitol to HA fillers is a viable and safe option for improving both short- and long-term HA aesthetic effects.
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7.
Antioxidant treatments for schizophrenia.
Magalhães, PV, Dean, O, Andreazza, AC, Berk, M, Kapczinski, F
The Cochrane database of systematic reviews. 2016;(2):CD008919
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Abstract
BACKGROUND There is accumulating evidence that progressive changes in brain structure and function take place as schizophrenia unfolds. Among many possible candidates, oxidative stress may be one of the mediators of neuroprogression, grey matter loss and subsequent cognitive and functional impairment. Antioxidants are exogenous or endogenous molecules that mitigate any form of oxidative stress or its consequences. They may act from directly scavenging free radicals to increasing anti-oxidative defences. There is evidence that current treatments impact oxidative pathways and may to some extent reverse pro-oxidative states in schizophrenia. The existing literature, however, indicates that these treatments do not fully restore the deficits in antioxidant levels or restore levels of oxidants in schizophrenia. As such, there has been interest in developing interventions aimed at restoring this oxidative balance beyond the benefits of antipsychotics in this direction. If antioxidants are to have a place in the treatment of this serious condition, the relevant and up-to-date information should be available to clinicians and investigators. OBJECTIVES To evaluate the effect of antioxidants as add-on treatments to standard antipsychotic medication for improving acute psychotic episodes and core symptoms, and preventing relapse in people with schizophrenia. SEARCH METHODS We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials which is based on regular searches of CINAHL, BIOSIS, AMED, Embase, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. There are no language, time, document type, or publication status limitations for inclusion of records in the register. We ran this search in November 2010, and again on 8 January 2015. We also inspected references of all identified studies for further trials and contacted authors of trials for additional information. SELECTION CRITERIA We included reports if they were randomised controlled trials (RCTs) involving people with schizophrenia who had been allocated to either a substance with antioxidant potential or to a placebo as an adjunct to standard antipsychotic treatment. DATA COLLECTION AND ANALYSIS We independently extracted data from these trials and we estimated risk ratios (RR) or mean differences (MD), with 95% confidence intervals (CI). We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE. MAIN RESULTS The review includes 22 RCTs of varying quality and sample size studying Ginkgo biloba, N-acetyl cysteine (NAC), allopurinol, dehydroepiandrosterone (DHEA), vitamin C, vitamin E or selegiline. Median follow-up was eight weeks. Only three studies including a minority of the participants reported our a priori selected primary outcome of clinically important response. Short-term data for this outcome (measured as at least 20% improvement in scores on Positive and Negative Syndrome Scale (PANSS)) were similar (3 RCTs, n = 229, RR 0.77, 95% CI 0.53 to 1.12, low quality evidence). Studies usually reported only endpoint psychopathology rating scale scores. Psychotic symptoms were lower in those using an adjunctive antioxidant according to the PANSS ( 7 RCTS, n = 584, MD -6.00, 95% CI -10.35 to -1.65, very low quality evidence) and the Brief Psychiatric Rating Scale (BPRS) (8 RCTS, n = 843, MD -3.20, 95% CI -5.63 to -0.78, low quality evidence). There was no overall short-term difference in leaving the study early (16 RCTs, n = 1584, RR 0.73, 95% CI 0.48 to 1.11, moderate quality evidence), or in general functioning (2 RCTs, n = 52, MD -1.11, 95% CI -8.07 to 5.86, low quality evidence). Adverse events were generally poorly reported. Three studies reported useable data for 'any serious adverse effect', results were equivocal (3 RCTs, n = 234, RR 0.65, 95% CI 0.19 to 2.27, low quality evidence). No evidence was available for relapse, quality of life or service use. AUTHORS' CONCLUSIONS Although 22 trials could be included in this review, the evidence provided is limited and mostly not relevant to clinicians or consumers. Overall, although there was low risk of attrition and selective data reporting bias within the trials, the trials themselves were not adequately powered and need more substantial follow-up periods. There is a need for larger trials with longer periods of follow-up to be conducted. Outcomes should be meaningful for those with schizophrenia, and include measures of improvement and relapse (not just rating scale scores), functioning and quality of life and acceptability and, importantly, safety data.
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Antioxidant capacity of foods for scavenging reactive oxidants and inhibition of plasma lipid oxidation induced by multiple oxidants.
Niki, E
Food & function. 2016;(5):2156-68
Abstract
Unregulated oxidation of biological molecules induced by multiple oxidants has been implicated in the pathogenesis of various diseases. Consequently, the effects of antioxidants contained in foods, beverages and supplements on the maintenance of health and prevention of diseases have attracted much attention of the public as well as scientists. However, recent human studies have shown inconsistent results and failed to demonstrate the beneficial effects of antioxidants. The mechanisms and dynamics of antioxidant action and assessment of antioxidant capacity have been the subject of extensive studies and arguments. In the present article, the antioxidant capacity has been reviewed focusing on two main issues: the capacity of antioxidants to scavenge multiple reactive oxidants and to inhibit plasma lipid oxidation induced by different biological oxidants. It is emphasized that the capacity of antioxidants to scavenge reactive oxidants does not always correlate linearly with the capacity to inhibit lipid oxidation and that it is necessary to specify the oxidant to assess the efficacy of antioxidants, since multiple oxidants contribute to oxidative damage in vivo and the effects of antioxidants depend on the nature of oxidants. A convenient and rapid method using a microplate reader is discussed for assessing the antioxidant capacity against plasma lipid oxidation induced by multiple oxidants including peroxyl radicals, peroxynitrite, hypochlorite, 15-lipoxygenase, and singlet oxygen.
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9.
Treatment of Severe Alcoholic Hepatitis.
Thursz, M, Morgan, TR
Gastroenterology. 2016;(8):1823-34
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Abstract
Alcoholic hepatitis (AH) is a syndrome of jaundice and liver failure that occurs in a minority of heavy consumers of alcohol. The diagnosis usually is based on a history of heavy alcohol use, findings from blood tests, and exclusion of other liver diseases by blood and imaging analyses. Liver biopsy specimens, usually collected via the transjugular route, should be analyzed to confirm a diagnosis of AH in patients with an atypical history or presentation. The optimal treatment for patients with severe AH is prednisolone, possibly in combination with N-acetyl cysteine. At present, only short-term increases in survival can be expected-no treatment has been found to increase patient survival beyond 3 months. Abstinence is essential for long-term survival. New treatment options, including liver transplantation, are being tested in trials and results eagerly are awaited.
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Mechanisms of nitric oxide crosstalk with reactive oxygen species scavenging enzymes during abiotic stress tolerance in plants.
Arora, D, Jain, P, Singh, N, Kaur, H, Bhatla, SC
Free radical research. 2016;(3):291-303
Abstract
Nitric oxide (NO) acts in a concentration and redox-dependent manner to counteract oxidative stress either by directly acting as an antioxidant through scavenging reactive oxygen species (ROS), such as superoxide anions (O(2)(-)*), to form peroxynitrite (ONOO(-)) or by acting as a signaling molecule, thereby altering gene expression. NO can interact with different metal centres in proteins, such as heme-iron, zinc-sulfur clusters, iron-sulfur clusters, and copper, resulting in the formation of a stable metal-nitrosyl complex or production of varied biochemical signals, which ultimately leads to modification of protein structure/function. The thiols (ferrous iron-thiol complex and nitrosothiols) are also involved in the metabolism and mobilization of NO. Thiols bind to NO and transport it to the site of action whereas nitrosothiols release NO after intercellular diffusion and uptake into the target cells. S-nitrosoglutathione (GSNO) also has the ability to transnitrosylate proteins. It is an NO˙ reservoir and a long-distance signaling molecule. Tyrosine nitration of proteins has been suggested as a biomarker of nitrosative stress as it can lead to either activation or inhibition of target proteins. The exact molecular mechanism(s) by which exogenous and endogenously generated NO (or reactive nitrogen species) modulate the induction of various genes affecting redox homeostasis, are being extensively investigated currently by various research groups. Present review provides an in-depth analysis of the mechanisms by which NO interacts with and modulates the activity of various ROS scavenging enzymes, particularly accompanying ROS generation in plants in response to varied abiotic stress.