Brain damage is a complex dysfunction that involves a variety of conditions whose pathogenesis involves a number of mediators that lead to clinical sequelae. For this reason, the identification of specific circulating and/or tissue biomarkers which could indicate brain injury is challenging. This experimental study focused on microRNAs (miRNAs), a well-known diagnostic tool both in the clinical setting and in medico-legal investigation. Previous studies demonstrated that specific miRNAs (miR-21, miR-34, miR-124, miR-132, and miR-200b) control important target genes involved in neuronal apoptosis and neuronal stress-induced adaptation. Thus, in this experimental setting, their expression was evaluated in three selected groups of cadavers: drug abusers (cocaine), ischemic-stroke-related deaths, and aging damage in elder people who died from other neurological causes. The results demonstrated that the drug abuser group showed a higher expression of miR-132 and miR-34, suggesting a specific pathway in consumption-induced neurodegeneration. Instead, miR-200b and miR-21 dysregulation was linked to age-related cognitive impairment, and finally, stroke events and consequences were associated with an alteration in miR-200b, miR-21, and miR-124; significantly higher levels of this last expression are strongly sensitive for ischemic damage. Moreover, these results suggest that these expression patterns could be studied in other biological samples (plasma, urine) in subjects with brain injury linked to aging, drug abuse, and stroke to identify reliable biomarkers that could be applied in clinical practice. Further studies with larger samples are needed to confirm these interesting findings.

https://www.mdpi.com/1422-0067/20/7/1546/pdf

Human Brain Injury and miRNAs: An Experimental Study.

Anabolic androgenic steroids (AAS) are some of the most common drugs used among athletes, frequently in combination with resistance training, to improve physical performance or for aesthetic purpose. A great number of scientific reports showed the detrimental effects of anabolic androgenic steroids on different organs and tissues. In this literature review, we analyzed the AAS-mediated carcinogenicity, focusing on Leydig cell tumor. AAS-induced carcinogenicity can affect DNA transcription through two pathways. It can act directly via the androgen receptor, by means of dihydrotestosterone (DHT) produced by the action of 5-a-reductase. It can also work through the estrogen receptor, by means of estradiol produced by CYP19 aromatase. In addition, nandrolone and stanazolol can activate the PI3K/AKT and PLC/PKC pathways via IGF-1. This would result in cell proliferation in Leydig cell cancer, or magnify cyclin D1 concentration inducing breast cell proliferation. AAS abuse is becoming a serious public health concern in view of the severe health consequences secondary to AAS abuse. The negative role of AAS in supraphysiological dosage impairs the expression of enzymes involved in testosterone biosynthesis. Abnormal synthesis of testosterone plays has a negative effect on the hormonal changes/regulation, and might be involved in certain carcinogenic mechanisms. At the light of this review, it could become very interesting to perform an information campaign more strengthened in gyms and schools in order to prevent male fertility impairment and other tissues damage.

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Anabolic androgenic steroids and carcinogenicity focusing on Leydig cell: a literature review.

Background and objectives: Anabolic-androgenic steroids (AASs) are a group of synthetic molecules derived from testosterone and its related precursors. AASs are widely used illicitly by adolescents and athletes, especially by bodybuilders, both for aesthetic uses and as performance enhancers to increase muscle growth and lean body mass. When used illicitly they can damage health and cause disorders affecting several functions. Sudden cardiac death (SCD) is the most common medical cause of death in athletes. SCD in athletes has also been associated with the use of performance-enhancing drugs. This review aimed to focus on deaths related to AAS abuse to investigate the cardiac pathophysiological mechanism that underlies this type of death, which still needs to be fully investigated. Materials and Methods: This review was conducted using PubMed Central and Google Scholar databases, until 21 July 2020, using the following key terms: “((Sudden cardiac death) OR (Sudden death)) AND ((androgenic anabolic steroid) OR (androgenic anabolic steroids) OR (anabolic-androgenic steroids) OR (anabolic-androgenic steroid))”. Thirteen articles met the inclusion and exclusion criteria, for a total of 33 reported cases. Results: Of the 33 cases, 31 (93.9%) were males while only 2 (61%) were females. Mean age was 29.79 and, among sportsmen, the most represented sports activity was bodybuilding. In all cases there was a history of AAS abuse or a physical phenotype suggesting AAS use; the total usage period was unspecified in most cases. In 24 cases the results of the toxicological analysis were reported. The most detected AASs were nandrolone, testosterone, and stanozolol. The most frequently reported macroscopic alterations were cardiomegaly and left ventricular hypertrophy, while the histological alterations were foci of fibrosis and necrosis of the myocardial tissue. Conclusions: Four principal mechanisms responsible for SCD have been proposed in AAS abusers: the atherogenic model, the thrombosis model, the model of vasospasm induced by the release of nitric oxide, and the direct myocardial injury model. Hypertrophy, fibrosis, and necrosis represent a substrate for arrhythmias, especially when combined with exercise. Indeed, AAS use has been shown to change physiological cardiac remodeling of athletes to pathophysiological cardiac hypertrophy with an increased risk of life-threatening arrhythmias.

https://www.mdpi.com/1648-9144/56/11/587/pdf

Sudden Cardiac Death in Anabolic-Androgenic Steroid Users: A Literature Review.

Even if anabolic androgenic steroid (AAS) abuse is clearly associated with a wide spectrum of collateral effects, adolescents and athletes frequently use a large group of synthetic derivatives of testosterone, both for aesthetic uses and for improving performance. Over the last few years, the development of MicroRNA (miRNA) technologies has become an essential part of research projects and their role as potential molecular biomarkers is being investigated by the scientific community. The circulating miRNAs detection as a diagnostic or prognostic tool for the diagnosis and treatment of several diseases is very useful, because with a minimal quantity of sample (peripheral blood), miRNAs are very sensitive. Even more, miRNAs remain stable both at room temperature and during freeze-thaw cycles. These characteristics highlight the important role of miRNAs in the near future as new tools for anti-doping. The article provides a systematic review and meta-analysis on the role of miRNAs as new potential molecular biomarkers of AAS use/abuse. Particularly, this paper analyzed the "miRNA signature" use as biomarkers for health disorders, focusing on the organ damages which are related to ASS use/abuse. Moreover, this review aims to provide a future prospect for less invasive or non-invasive procedures for the detection of circulating miRNA biomarkers as doping assumption signaling.

Anabolic Androgenic Steroids: Searching New Molecular Biomarkers.

Background and Objectives: Androgens play a significant role in the development of male reproductive organs. The clinical use of synthetic testosterone derivatives, such as nandrolone, is focused on maximizing the anabolic effects and minimizing the androgenic ones. Class II anabolic androgenic steroids (AAS), including nandrolone, are rapidly becoming a widespread group of drugs used both clinically and illicitly. The illicit use of AAS is diffused among adolescent and bodybuilders because of their anabolic proprieties and their capacity to increase tolerance to exercise. This systematic review aims to focus on side effects related to illicit AAS abuse, evaluating the scientific literature in order to underline the most frequent side effects on AAS abusers’ bodies. Materials and Methods: A systematic review of the scientific literature was performed using the PubMed database and the keywords “nandrolone decanoate”. The inclusion criteria for articles or abstracts were English language and the presence of the following words: “abuse” or “adverse effects”. After applying the exclusion and inclusion criteria, from a total of 766 articles, only 148 were considered eligible for the study. Results: The most reported adverse effects (found in more than 5% of the studies) were endocrine effects (18 studies, 42%), such as virilization, gynecomastia, hormonal disorders, dyslipidemia, genital alterations, and infertility; cardiovascular dysfunctions (six studies, 14%) such as vascular damage, coagulation disorders, and arteriosus hypertension; skin disorders (five studies, 12%) such as pricking, acne, and skin spots; psychiatric and mood disorders (four studies, 9%) such as aggressiveness, sleep disorders and anxiety; musculoskeletal disorders (two studies, 5%), excretory disorders (two studies, 5%), and gastrointestinal disorders (two studies, 5%). Conclusions: Based on the result of our study, the most common adverse effects secondary to the abuse of nandrolone decanoate (ND) involve the endocrine, cardiovascular, skin, and psychiatric systems. These data could prove useful to healthcare professionals in both sports and clinical settings.

/pdf/nandrolone-decanoate-use-abuse-and-side-effects-431yzt51uf.pdf

Nandrolone Decanoate: Use, Abuse and Side Effects.

VINCENZO MONDA1,§, ERSILIA NIGRO2,§, MARIA RUBERTO3,§, GIUSEPPE MONDA1, ANNA VALENZANO4, ANTONIO I. TRIGGIANI4, FIORENZO MOSCATELLI4, EMANUELE MONDA1, INES VILLANO1, MICHELE ROCCELLA5, LUCIA PARISI5, ANTONIETTA MESSINA1,* 1Department of Experimental Medicine, Università degli Studi della Campania-Luigi Vanvitelli, Italy 2CEINGE-Biotecnologie Avanzate Scarl, Napoli, Italy 3Department of Medical-Surgical and Dental Specialties; Università degli Studi della Campania-Luigi Vanvitelli, Italy, Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy 4Department of Psychological, Pedagogical and Educational Sciences, University of Palermo, Italy

Synergism or competition between zinc and chromium dietary levels on insulin action mechanism. a method to investigate

GIUSEPPE DAVIDE ALBANO1, FRANCESCO SESSA1, ANTONIETTA MESSINA2, VINCENZO MONDA2, GIUSEPPE BERTOZZI1, FRANCESCA MAGLIETTA1, PASQUALE GIUGLIANO3, GIUSEPPE VACCHIANO4, MARSALA GABRIELLA5, MONICA SALERNO1 1Section of Forensic Pathology, Clinical and Experimental Medicine Department, University of Foggia, Ospedale Colonnello D’Avanzo, Viale Degli Aviatori 1, Foggia, Italy 2Department of Experimental Medicine, Università degli Studi della Campania “Luigi Vanvitelli”, Naples, Italy 3U.O.C., Legal Medicine, Sant’Anna and San Sebastiano Hospital, Palasciano Street, Caserta (Italy) 4U.O.C., Department of Law, Economics and Mathematical Methods, Sannio University, Benevento (Italy) 5Struttura Complessa di Farmacia, Azienda Ospedaliero-Universitaria, Ospedali Riuniti di Foggia, Italy

AAS and organs damage: A focus on Nandrolone effects

Physical activity and modification of lifestyle induce benefits on the health status

Effect of radiofrequency on sympathetic nervous system functioning

One-third of patients with epilepsy do not respond to antiepileptic drugs and may seek complementary and alternative treatment modalities. Dietary therapies, such as the ketogenic diet (KD), the modified Atkins diet, as well as the medium-chain triglyceride and the low glycaemic index diets, have been successfully implemented with some forms of epilepsy and are growing in utilization. The KD is a high-fat, low-protein, low-carbohydrate diet that has been used for various conditions for over a century. Insights into the mechanism of action of these diets may provide more targeted interventions for patients with epilepsy. Knowledge of these mechanisms is growing and includes neuroprotective effects on oxidative stress, neuroinflammation, potassium channels in the brain, and mitochondrial function. In this review, we explain the role of physical exercise and the ketogenic diet on epilepsy.

Monda Vincenzo

Papers

Synergism or competition between zinc and chromium dietary levels on insulin action mechanism. a method to investigate

AAS and organs damage: A focus on Nandrolone effects

Physical activity and modification of lifestyle induce benefits on the health status

Effect of radiofrequency on sympathetic nervous system functioning

Physical Activity, Ketogenic Diet, and Epilepsy: A Mini-Review