Italian law on medically assisted reproduction: do women's autonomy and health matter?

BACKGROUND: In Italy in 2004, a very restrictive law was passed on medically assisted reproduction (MAR) (Law 40/2004) that placed Italy at the most conservative end of the European spectrum. The law was widely criticized and many couples seeking MAR brought their cases before the Italian Civil Courts with regard to pre-implantation genetic diagnosis (PGD), donor insemination and the issue of consent. Ten years on, having suffered the blows of the Italian Constitutional Court, little remains of law 40/2004. DISCUSSION: In 2009, the Constitutional Court declared the maximum limit of the number of embryos to be produced and transferred for each cycle (i.e. three), as stated in the original version of the law, to be constitutionally illegitimate. In 2014, the same Court declared as unconstitutional the ban on donor insemination, thus opening the way to heterologous assisted reproduction. Heterologous MAR is therefore perfectly legitimate in Italy. Finally, in 2015 a further ruling by the Constitutional Court granted the right to access MAR to couples who are fertile but carriers of genetic diseases. However, there is still much room for criticism. Many couples and groups are still, in fact, excluded from MAR. Same-sex couples, single women and those of advanced reproductive age are, at the present time, discriminated against in that Italian law denies these subjects access to MAR. The history of Law 40/2004 has been a particularly troubled one. Numerous rulings have, over the years, dismantled much of a law constructed in violation of the rights and autonomy of women and couples. However, a number of troubling issues still exist from what is left of the law and the debate is still open at national and transnational level regarding some of the contradictions and gaps in the law highlighted in this article. Only by abolishing the final prohibitions and adopting more liberal views on these controversial yet crucial issues will Law 40/2004 become what it should have been from the start, i.e. a law which outlines the 'rules of use' of MAR and not, as it has been until now, a law of bans which sets limits to the freedom to reproduce.

Neurotoxicity by synthetic androgen steroids: oxidative stress, apoptosis, and neuropathology: A review.

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.

Multi-phase postmortem CT angiography (MPMCTA): a new axillary approach suitable in fatal thromboembolism.

Postmor tem computed tomography is widely used in the forensic pathology setting as supplementing medico-legal investigations and being capable of providing significant data that affect final conclusions and adding new quality to recording postmortem observations. The integration with angiographic methods [postmortem computed tomography angiography and multiphase postmortem CT angiography (MPMCTA)] allows the examination of the cardiovascular system and it is increasingly being utilised in the field of forensic pathology. However, using the standardised procedure that establishes the femoral vessels on one side of the corpse as an access point to the vascular system, visualisation of the vascular tree below the cannula insertion site is excluded. Consequently, visualisation of the vascular anatomy and morphology of the lower limbs is impossible and lesions such as thrombosis of the superficial and deep venous system may remain elusive. Bearing in mind the high incidence of pulmonary thromboembolism in forensic case studies and the difficulties in postmortem diagnosis, we propose a new axillary approach for MPMCTA that allows the full detection of the vascular system of the lower limbs.

A rare and lethal case of right common carotid pseudoaneurysm following whiplash trauma.

Whiplash trauma from a car crash is one of the most common causes of neck injury, resulting in pain and dysfunction. We report on an unusual case of post-whiplash pseudoaneurysm of the right common carotid artery, which led to acute massive hemorrhage and death days after the initial trauma. A post-mortem computed tomography angiography showed rupture of the pseudoaneurysm of the right common carotid artery with the contrast agent leaking out into the mouth. The subsequent autopsy confirmed a large hemorrhagic clot extending to the right side of the neck and mediastinum. A rupture of the right wall of the oropharynx was identified with massive bronchial hemoaspiration. The case demonstrates a rare but lethal clinical entity, and is important in providing a better understanding of the potentially fatal consequences of minor trauma, such as whiplash injury, and its physiopathological mechanisms. Thus, changing symptoms after a whiplash injury should be carefully evaluated since they can be related to the underlying severe consequences of a rapid hyperextension-hyperflexion of the neck, as in the reported case.

Chronic nandrolone administration promotes oxidative stress, induction of pro-inflammatory cytokine and TNF-α mediated apoptosis in the kidneys of CD1 treated mice.

Nandrolone decanoate administration and strenuous exercise increase the extent of renal damage in response to renal toxic injury. We studied the role played by oxidative stress in the apoptotic response caused by nandrolone decanoate in the kidneys of strength-trained male CD1 mice. To measure cytosolic enzyme activity, glutathione peroxidase (GPx), glutathione reductase (GR) and malondialdehyde (MDA) were determined after nandrolone treatment. An immunohistochemical study and Western blot analysis were performed to evaluate cell apoptosis and to measure the effects of renal expression of inflammatory mediators (IL-1ß, TNF-α) on the induction of apoptosis (HSP90, TUNEL). Dose-related oxidative damage in the kidneys of treated mice is shown by an increase in MDA levels and by a reduction of antioxidant enzyme GR and GPx activities, resulting in the kidney's reduced radical scavenging ability. Renal specimens of the treated group showed relevant glomeruli alterations and increased immunostaining and protein expressions, which manifested significant focal segmental glomerulosclerosis. The induction of proinflammatory cytokine expression levels was confirmed by Western blot analysis. Long-term administration of nandrolone promotes oxidative injury in the mouse kidneys. TNF-α mediated injury due to nandrolone in renal cells appears to play a role in the activation of both the intrinsic and extrinsic apoptosis pathways.

Enzymatic-nonenzymatic cellular antioxidant defense systems response and immunohistochemical detection of MDMA, VMAT2, HSP70, and apoptosis as biomarkers for MDMA (Ecstasy) neurotoxicity.

3,4-Methylenedioxymethamphetamine (MDMA)-induced neurotoxicity leads to the formation of quinone metabolities and hydroxyl radicals and then to the production of reactive oxygen species (ROS). We evaluated the effect of a single dose of MDMA (20 mg/kg, i.p.) on the enzymatic and nonenzymatic cellular antioxidant defense system in different areas of rat brain in the early hours (<6 hr) of the administration itself, and we identified the morphological expressions of neurotoxicity induced by MDMA on the vulnerable brain areas in the first 24 hr. The acute administration of MDMA produces a decrease of reduced and oxidized glutathione ratio, and antioxidant enzyme activities were significantly reduced after 3 hr and after 6 hr in frontal cortex. Ascorbic acid levels strongly increased in striatum, hippocampus, and frontal cortex after 3 and 6 hr. High levels of malonaldehyde with respect to control were measured in striatum after 3 and 6 hr and in hippocampus and frontal cortex after 6 hr. An immunohistochemical investigation on the frontal, thalamic, hypothalamic, and striatal areas was performed. A strong positive reaction to the antivesicular monoamine transporter 2 was observed in the frontal section, in the basal ganglia and thalamus. Cortical positivity, located in the most superficial layer was revealed only for heat shock protein 70 after 24 hr.

A multidisciplinary approach to the investigation of a collapsed building.

Investigating the collapse of a building poses multiple and complex forensic challenges. Large numbers of specialized personnel and equipment are required, as are the combined technical skills of many different kinds of forensic investigators. Forensic pathology teams are integral to these efforts. This report describes the investigation that occurred after a building collapsed in southern Italian location. Several families were still living in small, and abandoned building built in the early 20th century. The buildings were located over cellars 3 meters underground, known locally as "the caves." Eight people were found dead under the debris of one of the collapsed houses and 6 were brought out alive. A team of forensic pathologists and engineers was appointed to investigate the causes of death and of the collapse, respectively. A complete autopsy was performed in every case, along with radiologic assessment and toxicological analysis. Autopsy findings were coded using the Abbreviated Injury Scale and the New Injury Severity Score. Systems for victim identification, arrangements for human remains, management of dead bodies, evaluation of the different patterns of injuries and, finally, detailed identification of the cause of death all played an important role.

Drugs of abuse in pregnancy, poor neonatal development, and future neurodegeneration. Is oxidative stress the culprit?

The abuse of licit and illicit drugs is a worldwide issue that is a cause for concern in pregnant women. It may lead to complications in pregnancy that may affect the mother, fetus, and /or neonate. The effects of any substance on the developing embryo and fetus are dependent upon dosing, timing, duration of drug exposure, and the extent of drug distribution. Teratogenic effects have been described when exposure takes place during the embryonic stage; however drugs have subtle effects, including abnormal growth and/or maturation, alterations in neurotransmitters and their receptors, and brain organization. The mechanisms by which intrauterine exposure to many substances may result in neuronal injury have not been completely elucidated. Oxidative stress and epigenetic changes have been recently implicated in the pathogenesis of long - term adverse health sequelae, and neuro-developmental impairment in the offspring of addicted mothers. Transgenerational epigenetics may also explain the alarming datum that developmental abnormalities, impairment in learning and memory, and attention deficit can occur even in the absence of direct fetal exposure, when drugs are consumed prior to conception. There is a growing body of evidence demonstrating a link between redox state unbalance, epigenetic markers, developmental anomalies, and neurodegeneration. The reviewed literature data uphold redox homeostasis disruption as an important factor in the pathogenesis of drug of abuse- induced neurodegeneration, and highlight the potential for new therapies that could prevent neurodegeneration through antioxidant and epigenetic modulatory mechanisms. This therefore reveals important targets for novel neuroprotective strategies.

The meaning of different forms of structural myocardial injury, immune response and timing of infarct necrosis and cardiac repair.

Although a decline in the all-cause and cardiac mortality rates following myocardial infarction (MI) during the past 3 decades has been reported, MI is a major cause of death and disability worldwide. From a pathological point of view MI consists in a particular myocardial cell death due to prolonged ischemia. After the onset of myocardial ischemia, cell death is not immediate, but takes a finite period of time to develop. Once complete myocytes' necrosis has occurred, a process leading to a healed infarction takes place. In fact, MI is a dynamic process that begins with the transition from reversible to irreversible ischemic injury and culminates in the replacement of dead myocardium by a fibrous scar. The pathobiological mechanisms underlying this process are very complex, involving an inflammatory response by several pathways, and pose a major challenge to ability to improve our knowledge. An improved understanding of the pathobiology of cardiac repair after MI and further studies of its underlying mechanisms provide avenues for the development of future strategies directed toward the identification of novel therapies. The chronologic dating of MI is of great importance both to clinical and forensic investigation, that is, the ability to create a theoretical timeline upon which either clinicians or forensic pathologists may increase their ability to estimate the time of MI. Aging of MI has very important practical implications in clinical practice since, based on the chronological dating of MI, attractive alternatives to solve therapeutic strategies in the various phases of MI are developing.

Amniotic fluid embolism: moving diagnosis through the time. From the mechanical pulmonary vascular occlusion until an immuno - inflammatory pathogenesis?

Amniotic fluid embolism (AFE) is a rare, catastrophic syndrome that presents during labor and delivery or immediately postpartum. Efforts to develop a clinical diagnostic test are ongoing; however the diagnosis still relies on rapid bedside evaluation and depends on the exclusion of other diseases. Classically, the diagnosis was made at autopsy, with the demonstration of squamous cells or debris in the maternal pulmonary vasculature. Clinico-pathological correlations have strengthened the evidence for a role of the immune system in the pathogenesis of AFE and have lead to the development of new laboratory tests, such as the serum tryptase and complement measurements, which should provide scientific support for the presumed immunological mechanism of AFE. Recently, studies on the effects of amniotic fluid (AF) on platelet - neutrophil aggregation and neutrophil/platelet activation have opened new insight in the comprehension of the mechanisms underlying AFE, suggesting that a severe inflammatory response might have a paramount causative role, so opening new diagnostic and therapeutic perspectives. Considering the complex interplay between the different mechanisms involved in the pathogenesis of AFE, the diagnosis still arises from a complex diagnostic puzzle in which clinical, macroscopic, laboratory, histological and immunohistochemical data converge toward AFE.

Advance health care directives and "public guardian": the Italian supreme court requests the status of current and not future inability.

Advance health care decisions animate an intense debate in several European countries, which started more than 20 years ago in the USA and led to the adoption of different rules, based on the diverse legal, sociocultural and philosophical traditions of each society. In Italy, the controversial issue of advance directives and end of life's rights, in the absence of a clear and comprehensive legislation, has been over time a subject of interest of the Supreme Court. Since 2004 a law introduced the "Public Guardian," aiming to provide an instrument of assistance to the person lacking in autonomy because of an illness or incapacity. Recently, this critical issue has once again been brought to the interest of the Supreme Court, which passed a judgment trying to clarify the legislative application of the appointment of the Guardian in the field of advance directives.

Sudden death due to a dissecting intramural hematoma of the esophagus (DIHE) in a woman with severe neurofibromatosis-related scoliosis.

Dissecting intramural hematoma of the esophagus (DIHE) is a rare condition in which intramural hemorrhage can lead to submucosal dissection of the esophageal wall. DIHE is generally considered a benign disease, and the only mortality associated with DIHE has been due to operative intervention or to the presence of another underlying, life-threatening condition. We report, however, a case of sudden death due to the spontaneous rupture of a DIHE that occurred in a 32-year-old woman, affected by neurofibromatosis type 1. She was admitted to the local emergency room, presenting a 24-hour history of sudden onset, severe central chest and interscapular pain associated with dysphagia, odynophagia and vomiting. Her condition worsened and proved fatal within a 6-hour period. A complete autopsy was then conducted, showing a complete dissecting intramural hematoma with laceration of the third superior of the esophagus. We can hypothesize that abnormal variations of gastro-esophageal pressure during ingurgitation and during bolus movement could be predisposing factors in the pathogenesis of the dissection. On the other hand angular kyphoscoliosis deformity may have had play a role as precipitating factor while vomiting in the subject's medical history can then be interpreted as the likely activation phenomenon.

Analytical and quantitative concentration of gunshot residues (Pb, Sb, Ba) to estimate entrance hole and shooting-distance using confocal laser microscopy and inductively coupled plasma atomic emission spectrometer analysis: an experimental study.

The identification of gunshot residues (GSRs) on human body in firearm related fatalities may be essential for the evaluation of gunshot wounds and for the analysis of the shooting distance. The present study introduces the elemental analysis of the GSRs by inductively coupled plasma atomic emission spectrometer analysis (ICP-AES) performed on skin samples. ICP-AES was used to increase the accuracy of the analysis in gunshots fired from long and medium distance. In this experimental study, a series of 50 test shots have been performed in an open space with lateral wind protection. As target we used pig skin cut into 20 cm × 20 cm squares. The firing distances were 0.2, 5, 50, 100 and 150 cm. To exclude environmental contamination, each skin sample was carefully washed with deionized water and dried at room temperature in a closed box before the shooting test. We choose 9×21 and the 7.65 mm calibers handguns, loaded with different ammunitions. At ICP-AES analysis a clearly decreasing trend in the quantity and the concentration of the different elements of GSR by increasing the firing distance for both the guns used in the test was evident for every portion of skin samples analyzed. The analytical results obtained by ICP-AES confirmed very high concentrations of Pb, Sb, and Ba in the close-range shots and low concentrations of these particles in the intermediate and distant shots. In particular, the concentration of Sb, Ba, and Pb was significantly different from loose values when the firing distance was 100-150 cm for both the 9×21 and the 7.65 mm calibers.

Colloid cyst of the third ventricle, hypothalamus, and heart: a dangerous link for sudden death.

Colloid cysts are rare congenital, intracranial neoplasms, commonly located in the third ventricle. Colloid cysts are endodermal congenital malformations. The cysts commonly range in size from 1-2 cm in diameter, although large cysts >3 cm in size have been reported. The components of the cyst include an outer fibrous capsule over an inner epithelium. The epithelium is usually a single layer of mucin-producing or ciliated cells. Such cysts contain mucoid and gelatinous material, which is positive for both Periodic acid Schiff (PAS) and mucicarmen staining. Although colloid cysts usually represent histopathologically benign neoplasms, they can result in sudden, unexpected and potentially lethal complications. The mechanism(s) of death is still a controversial subject and several mechanisms have been postulated to explain the sudden onset of severe symptoms and of fatal rapid deterioration in patients with colloid cysts. In this case, macroscopic and histological findings addressed the diagnosis of colloid cyst of the third ventricle with diffuse myocardial injury (coagulative myocytolysis or contraction band necrosis, CBN) and led us to conclude that acute cardiac arrest due to hypothalamus stimulation in the context of colloid cyst of the third ventricle was the cause of death. As the hypothalamic structures which are involved in neuroendocrine and autonomic regulation playing a key role in cardiovascular control are located close to the walls of the third ventricle which is the most frequent anatomical site of colloid cyst, this may suggest that reflex cardiac effects due to the compression of the hypothalamic cardiovascular regulatory centers by the cyst explain the sudden death in patients harboring a colloid cyst when signs of hydrocephalus or brain herniation are lacking. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4915842848034158.

Fatal pulmonary thromboembolism. A retrospective autopsy study: searching for genetic thrombophilias (Factor V Leiden (G1691A) and FII (G20210A) gene variants) and dating the thrombus.

The accuracy of antemortem diagnosis of pulmonary embolism is within the range of just 10-30%, so representing one of the most frequent missed diagnosis in sudden, unexpected death. We describe 43 fatal cases of pulmonary embolism as confirmed by post-mortem examination. The aim of our study was to verify the systematic search for the most common genetic thrombophilias (Factor V Leiden (G1691A) and FII (G20210A) gene variants) and dating the thrombus. As a whole, 41 patients (95.3%) had at least one risk factor. Pre-existing symptoms are described just before fatal embolism in 18 (41.9%) out 43 patients. In 18 out of 43 (41.9%) it was not possible to find the thrombotic site. In 24 out of the remaining 25 cases the involvement of the deep veins of one leg was shown; in 1 case the thrombus was localised in the inferior caval vein. 10 (41.7%) were iliac vein thromboses, 7 (29.1%) femoral, 2 (8.3%) popliteal, 3 (12.6%) posterior-tibial, 1 (4.1%) anterior-tibial and 1 (4.1%) peroneal vein thromboses. In our cohort of patients, 4 (10%) out of 40 cases carried the 20210A prothrombin gene variant in heterozygosis. One (2.5%) out of 40 carried the Factor V Leiden (G1691A) gene variant in heterozygosis. Patients carrying these gene variants in homozygosis or carrying both were not present in our case-series. We strongly underline the relevance of a complete methodological approach, integrating clinical data by means of autopsy findings and histological study. On the contrary, investigating common inherited thrombophilia is not warranted.

Cardiac beriberi: morphological findings in two fatal cases.

Cardiovascular beriberi is categorized into two main groups, according to its cause: alcoholic and non-alcoholic (dietary). Cardiovascular beriberi can also be divided into a fulminant form (Shoshin beriberi) and a chronic form. Shoshin beriberi is characterized by hypotension, tachycardia, and lactic acidosis and is mainly encountered in non-alcoholic patients in Asian countries, although it has also been seen in alcoholics in Western countries. Due to the complex clinical presentation and to the lack of diagnostic tests, thiamine deficiency is still being missed, especially among non-alcoholics patients. We present two fatal cases of non - alcohol associated cardiac beriberi. An acute myocardial infarction was observed in one case; extensive colliquative myocytolisis (grade 2) was described in the second case respectively. Morphologically, myocardial necrosis and colliquative myocytolysis are the histologic hallmarks of this acute, rare clinical entity. An increase in apoptotic myocytes was demonstrated probably sustaining the cardiogenic shock.

Coronary ostia obstruction after replacement of aortic valve prosthesis.

Aortic valve replacement (AVR) is the gold standard for the treatment of severe symptomatic aortic stenosis. Complications directly related to surgical procedure are relatively infrequent. Coronary ostial stenosis is, generally, referred as late complication. Anecdotal reports concern coronary ostial stenosis as acute complication. A unique fatal case of intraoperative, bilateral coronary ostial obstruction by prosthetic valve leading to an extensive myocardial infarction is reported. Surgeons must have a high level of vigilance regarding the occurrence of acute myocardial ischemia and sudden death soon after AVR.

Immunohistochemical expression of proinflammatory cytokines IL-1ß, IL-6, TNF-α and involvement of COX-2, quantitatively confirmed by Western blot analysis, in Wernicke's encephalopathy.

Selective cerebral vulnerability is a major consequence of Wernicke's encephalopathy (WE), in which focal areas of the brain exhibit symmetrical profound neuronal loss and accompanying gliosis, occurring most frequently in diencephalic regions such as the thalamus and the mammillary bodies. Many processes have been proposed to explain the selective cerebral vulnerability and the focal neuronal cell death in Wernicke's encephalopathy. There are several mechanisms which are common to the pathophysiology of encephalopathies caused by thiamine deficiency (TD). Recently, emphasis is being placed on deficit in mitochondrial oxidative metabolism, oxidative/nitrosative stress, and the release of proinflammatory cytokines such as IL-1ß, IL-6, and tumor necrosis factor-α (TNF-α). Cyclooxygenase-2 (COX-2) plays major roles in regulating brain damage and inflammation. Here we present two fatal cases of non-alcohol associated WE. The immunohistochemical study revealed increased proinflammatory cytokine immunoreactivity in the neurons of the mammillary bodies and medial thalamus, and in the periaqueductal regions, compared with basal constitutive levels of expression in the frontal cortex. Positive (WE cases) and negative (immediate trauma deaths) case-controls were used to confirm the results. TD induced IL-1ß proteins weakly, while moderate increase was observed for TNF-α and IL-6. Immunofluorescence analysis by confocal microscopy confirmed the staining results for immunoreactivity in WE brains. Further, the induction of proinflammatory cytokine protein expression levels was quantified by Western blot analysis.

Anabolic steroid- and exercise-induced cardio-depressant cytokines and myocardial ß1 receptor expression in CD1 mice.

Few animal model studies have been conducted in order to evaluate the impact of androgenic anabolic steroids (AAS) supraphysiological doses on the cardiovascular system and myocardial injury. Twenty-five male CD1 mice (8-10 weeks old; 35g initial body weight) were randomized into three AAS treated groups and two control groups. The AAS mice received intramuscular Nandrolone Decanoate (DECA-DURABOLIN), vehicled in arachidis oil, for 42 days, twice per week, with different dosages, studying plasma lipid analysis, cardiac histopathological features, cardiac ß (1) adrenergic receptor expression, and the effects of the myocardial expression of inflammatory mediators (IL-1ß, TNF-α) on the induction of cardiomyocytes apoptosis (HSP 70, TUNEL), using proteomic and immunohistochemical analysis. The mice had free movements in their animal rooms (two groups) or exercised by running on a motor-driven treadmill the others three groups. Recurring high dose AAS administration and physical training in mice produce significant increase in body weight and for total cholesterol. A moderate increase of the heart weight, cardiac hypertrophy and wide colliquative myocytolysis, were observed in high dose AAS administration and physical training group. The expression of HSP70 and inflammatory cytokine IL-1ß, increased in the three AAS-treated groups. TNF- α showed a more extensive expression in the AAS-high dose group. A significant apoptotic process randomly sparse in the myocardium was described. Our data support the hypothesis that the combined effects of vigorous training, anabolic steroid abuse and stimulation of the sympathetic nervous system, may predispose to myocardial injury.

MDMA toxicity and pathological consequences: a review about experimental data and autopsy findings.

Studies conducted in humans or in animals explored the presence, nature and potential causes of 3,4-methylenedioxymethamphetamine (MDMA) toxicity. According to literature, there are four principal types of such serious toxicity: hepatic, cardiovascular, cerebral and hyperpyrexic. The molecular mechanisms involved in the genesis of these toxic effects are not yet fully clarified, but the oxidative stress, excitotoxicity, and mitochondrial dysfunction appear to be causal events that converge to mediate MDMA-induced toxicity. Studies conducted on animals demonstrated that the acute administration of MDMA elicits cardiovascular responses that are similar to those elicited by d-amphetamine, and that these responses appear to involve catecholaminergic and non-catecholaminergic-dependent mechanisms. Although there is undeniable evidence of MDMA-induced cardiac toxicity, the mechanism responsible remains to be clarified. While many reports both in humans and in animals have demonstrated MDMA-induced liver damage, the underlying mechanism accounting for hepatic toxicity is poorly understood. Various mechanisms may contribute to MDMA-induced liver toxicity, including the metabolism of MDMA, the increased efflux of neurotransmitters, the oxidation of biogenic amines, and hyperthermia. The molecular mechanisms involved in the genesis of these toxic effects are not yet fully clarified, but the oxidative stress, excitotoxicity, and mitochondrial dysfunction appear to be causal events that converge to mediate MDMA-induced neurotoxicity, as measured by loss of various markers of dopaminergic and serotonergic terminals. The evidence is overwhelming that MDMA produces acute and long-lasting toxic anatomic effects in animals and humans. Anatomical and functional MDMA consequences must be better understood.