Acute myocardial infarction (AMI) is a leading cause of morbidity and mortality. Reperfusion strategies are the current standard therapy for AMI. However, they may result in paradoxical cardiomyocyte dysfunction, known as ischemic reperfusion injury (IRI). Different forms of IRI are recognized, of which only the first two are reversible: reperfusion-induced arrhythmias, myocardial stunning, microvascular obstruction, and lethal myocardial reperfusion injury. Sudden death is the most common pattern for ischemia-induced lethal ventricular arrhythmias during AMI. The exact mechanisms of IRI are not fully known. Molecular, cellular, and tissue alterations such as cell death, inflammation, neurohumoral activation, and oxidative stress are considered to be of paramount importance in IRI. However, comprehension of the exact pathophysiological mechanisms remains a challenge for clinicians. Furthermore, myocardial IRI is a critical issue also for forensic pathologists since sudden death may occur despite timely reperfusion following AMI, that is one of the most frequently litigated areas of cardiology practice. In this paper we explore the literature regarding the pathophysiology of myocardial IRI, focusing on the possible role of the calpain system, oxidative-nitrosative stress, and matrix metalloproteinases and aiming to foster knowledge of IRI pathophysiology also in terms of medicolegal understanding of sudden deaths following AMI.

Neurodegenerative diseases (NDs) represent one of the most important public health problems and concerns, as they are a growing cause of mortality and morbidity worldwide, particularly in the elderly. Despite remarkable breakthroughs in our understanding of NDs, there has been little success in developing effective therapies. The use of natural products may offer great potential opportunities in the prevention and therapy of NDs; however, many clinical concerns have arisen regarding their use, mainly focusing on the lack of scientific support or evidence for their efficacy and patient safety. These clinical uncertainties raise critical questions from a bioethical and legal point of view, as considerations relating to patient decisional autonomy, patient safety, and beneficial or non-beneficial care may need to be addressed. This paper does not intend to advocate for or against the use of natural products, but to analyze the ethical framework of their use, with particular attention paid to the principles of biomedical ethics. In conclusion, the notable message that emerges is that natural products may represent a great promise for the treatment of many NDs, even if many unknown issues regarding the efficacy and safety of many natural products still remain.

Anabolic-androgenic steroids (AAS) are synthetic substances derived from testosterone that are largely employed due to their trophic effect on muscle tissue of athletes at all levels. Since a great number of organs and systems are a target of AAS, their adverse effects are primarily on the following systems: reproductive, hepatic, musculoskeletal, endocrine, renal, immunological, infectious, cardiovascular, cerebrovascular, and hematological. Neuropsychiatric and behavioral effects as a result of AAS abuse are well known and described in the literature. Mounting evidence exists suggesting that in addition to psychiatric and behavioral effects, non-medical use of AAS carries neurodegenerative potential. Although, the nature of this association remains largely unexplored, recent animal studies have shown the recurrence of this AAS effect, ranging from neurotrophin unbalance to increased neuronal susceptibility to apoptotic stimuli. Experimental and animal studies strongly suggest that apoptotic mechanisms are at least in part involved in AAS-induced neurotoxicity. Furthermore, a great body of evidence is emerging suggesting that increased susceptibility to cellular oxidative stress could play a pivotal role in the pathogenesis of many neurodegenerative disorders and cognitive impairment. As in other drug-evoked encephalopathies, the key mechanisms involved in AAS – induced neuropathology could represent a target for future neuroprotective strategies. Progress in the understanding of these mechanisms will provide important insights into the complex pathophysiology of AAS-induced neurodegeneration, and will pave the way for forthcoming studies. Supplementary to abandoning the drug abuse that represents the first step in reducing the possibility of irreversible brain damage in AAS abusers, neuroprotective strategies have to be developed and implemented in future.

Anabolic – androgenic steroids (AAS) were originally developed to promote growth of skeletal muscle. AAS abuse is commonly associated with bodybuilders, weightlifters, and other athletes. The issue of AAS toxicity is not yet completely understood since the adverse effects outline a varied scenario with side effects reported affecting many organs and systems in humans. The true incidence of AAS related medical problems is not known, due to several drawbacks in human studies. The entity of side effects depends on the sex, the dose, the duration of treatment, whether they are taken during exercise training or under sedentary conditions, and the susceptibility of the individuals themselves to androgen exposure partly depending on genetic factors. Both the acute and the chronic effects can lead to toxicity, but generally the serious and even fatal effects depend on the time and the duration of AAS administration. A limitation of human studies is represented by the fact that information about the intake of steroids are, generally, self reported and it is hardly possible to assess the exact dosage. AAS are often used in combination with other dugs or substances, so it is difficult to separate their toxic effects from those caused by the other drugs abused. Hence experimental studies conducted on animal models are mandatory to investigate the mechanisms underlying to AAS toxicity and the organ alterations due to these substances. Finally, clinicians should be aware of the complex and varied pattern of toxicity so as to be able to perform correct diagnoses and treatments.

Background. Myocardial depression in sepsis is common, and it is associated with higher mortality. In recent years, the hypothesis that the myocardial dysfunction during sepsis could be mediated by ischemia related to decreased coronary blood flow waned and a complex mechanism was invoked to explain cardiac dysfunction in sepsis. Oxidative stress unbalance is thought to play a critical role in the pathogenesis of cardiac impairment in septic patients.Aim. In this paper, we review the current literature regarding the pathophysiology of cardiac dysfunction in sepsis, focusing on the possible role of oxidative-nitrosative stress unbalance and mitochondria dysfunction. We discuss these mechanisms within the broad scenario of cardiac involvement in sepsis.Conclusions. Findings from the current literature broaden our understanding of the role of oxidative and nitrosative stress unbalance in the pathophysiology of cardiac dysfunction in sepsis, thus contributing to the establishment of a relationship between these settings and the occurrence of oxidative stress. The complex pathogenesis of septic cardiac failure may explain why, despite the therapeutic strategies, sepsis remains a big clinical challenge for effectively managing the disease to minimize mortality, leading to consideration of the potential therapeutic effects of antioxidant agents.

In December 2017, Law 219/2017, ‘Provisions for informed consent and advance directives’, was approved in Italy. The law is the culmination of a year-long process and the subject of heated debate throughout Italian society. Contentious issues (advance directives, the possibility to refuse medical treatment, the withdrawal of medical treatment, nutrition and hydration) are addressed in the law. What emerges clearly are concepts such as quality of life, autonomy, and the right to accept or refuse any medical treatment – concepts that should be part of an optimal relationship between the patient and healthcare professionals. The law maximizes the value of the patient’s time to decide. Every patient is allowed to make choices for the present (consenting to or refusing current treatment) as well as for the future, conceived as a continuation of the present, and to decide what comes next, based on what he/she already knows. The law identifies three distinct but converging paths towards the affirmation of a care relationship based on reciprocal trust and respect: the possibility to consent to or refuse treatment, the shared care planning, and advance directives. The fundamental point to emerge from the new Italian law is that consensus is an essential connotation of the treatment relationship. Consensus is not limited to the acceptance/rejection of medical treatment but is ongoing. It is projected into the future through shared care planning and advance directives which act as tools for self-determination and the manifestation of the beliefs and preferences of persons unable to express their will. These principles are in line with the idea of appropriate care as evaluated from two different perspectives, one of scientific adequacy and the other commensurate with the individual’s resources, fragility, values, and beliefs. Surely, however, the new law is not the end of the matter on issues such as conscientious objection, which is deeply rooted within the Italian cultural and political debate. In this regard, healthcare institutions and policymakers will be called upon to develop and implement organizational policies aimed at the management of foreseeable conscientious objection in this field.