Synthetic androgen and new psycho-active compounds (smart drugs) abuse and dependance. Neuropathological and toxicological findings, with an approach designed for the future

Self-administration of high doses of synthetic androgen (SA) is widespread among young people, to enhance physical aspect and gain muscle mass. The mechanisms of SA toxicity are not yet completely understood while the adverse effects of SA are known to be complex and likely to arise from effects on several organ systems in humans. Moreover, the negative health consequences of SA have many variable as the sex, dose and the duration of administration and many of the side effects may be reversible. The genomic action of Androgenic Receptors is modulated by a large variety of coregulators, which are proteins that target gene expression by enhancing (coactivator) or restraining (corepressor) transcription. SA may also have direct rewarding or hedonic properties, mediated not so much by their genomic effects (although these may well contribute) but more directly by the effects of SA and their metabolites on plasma membranes. As for other steroids, non-genomic androgen effects typically involve the fast induction of conventional second messenger signal transduction cascades, including increases in cytosolic calcium and activation of protein kinase A, protein kinase C, and MAPK (mitogen- activated protein kinase), leading to diverse cellular effects including smooth muscle relaxation, neuromuscular and junctional signal transmission and neuronal plasticity. Most nongenomic effects involve a membrane receptor, and putative binding sites are described for androgens. The use of AAS among young people has been associated with abuse of additional substances in several cross-sectional survey studies. More often new psychoactive substances that comprise of natural vegetable and synthetic compounds containing both active ingredients such as caffeine, taurine, ephedrine - essentially stimulating substances - and hallucinogenic substances are frequently used in association with SA especially in non athletes frequenting fitness or sport centers. Recently, all over the world the availability of new products sold as “Legal Highs” or “Herbal Highs” (psychoactive compounds not included in the list of Controlled Substances) has been described. This new heterogeneous class of products is also named “Smart Drugs” (SD) and includes several types of preparations such as teas, herbal mixtures, incenses, ambient scents, energetic drinks and food additives. Because of the lack of legal regulations to their marketing, SDs are easily available in common shops such as herbalist shops, in the so- called “Smart Shops” or through e-commerce. It is widely reported that the use of SDs is associated with dissociate mental states and mild psychedelic sensations. Moreover, SDs may induce amphetamine-like effects on both fatigueand mood as well as performance enhancement

Amniotic fluid embolism pathophysiology suggests the new diagnostic armamentarium: β-tryptase and complement fractions C3-C4 are the indispensable working tools

Amniotic fluid embolism (AFE) is an uncommon obstetric condition involving pregnant women during labor or in the initial stages after delivery. Its incidence is estimated to be around 5.5 cases per 100,000 deliveries. Therefore, this paper investigated the pathophysiological mechanism, which underlies AFE, in order to evaluate the role of immune response in the development of this still enigmatic clinical entity. The following databases (from 1956 to September 2014) Medline, Cochrane Central, Scopus, Web of Science and Science Direct were used, searching the following key words: AFE, pathophysiology, immune/inflammatory response, complement and anaphylaxis. The main key word "AFE" was searched singularly and associated individually to each of the other keywords. Of the 146 sources found, only 19 were considered appropriate for the purpose of this paper. The clinical course is characterized by a rapid onset of symptoms, which include: acute hypotension and/or cardiac arrest, acute hypoxia (with dyspnoea, cyanosis and/or respiratory arrest), coagulopathies (disseminated intravascular coagulation and/or severe hemorrhage), coma and seizures. The pathology still determines a significant morbidity and mortality and potential permanent neurological sequelae for surviving patients. At this moment, numerous aspects involving the pathophysiology and clinical development are still not understood and several hypotheses have been formulated, in particular the possible role of anaphylaxis and complement. Moreover, the detection of serum tryptase and complement components and the evaluation of fetal antigens can explain several aspects of immune response

Diagnostics of Coronal Magnetic Fields Through the Hanle Effect in UV and IR Lines

The plasma thermodynamics in the solar upper atmosphere, particularly in the corona, are dominated by the magnetic field, which controls the flow and dissipation of energy. The relative lack of knowledge of the coronal vector magnetic field is a major handicap for progress in coronal physics. This makes the development of measurement methods of coronal magnetic fields a high priority in solar physics. The Hanle effect in the UV and IR spectral lines is a largely unexplored diagnostic. We use magnetohydrodynamic (MHD) simulations to study the magnitude of the signal to be expected for typical coronal magnetic fields for selected spectral lines in the UV and IR wavelength ranges, namely the H I Ly-$\alpha$ and the He I 10830 {\AA} lines. We show that the selected lines are useful for reliable diagnosis of coronal magnetic fields. The results show that the combination of polarization measurements of spectral lines with different sensitivities to the Hanle effect may be most appropriate for deducing coronal magnetic properties from future observations.Comment: 15 pages, 5 figures, Frontiers in Astronomy and Space Sciences, 201

The choice of gadolinium-based contrast agents: a radiologist’s responsibility between pharmaceutical equivalence and bioethical issues

Contrast Agents (CA) are among the most commonly prescribed drugs worldwide, and are used, with a variety of techniques, to increase and intensify the differences between body tissues and to help radiologist make diagnoses in a fast and precise way. In recent decades, advancements in research have resulted in significant improvements in their composition, and have made them safer and better-tolerated by patients; this notwithstanding, although the currently available CA are generally considered to be safe, their use is not completely without risk. The use of CA faces the radiologist with economic considerations, bioethical dilemmas, and possible profiles of professional responsibility. In fact, to achieve the best results in diagnostic imaging, radiologists have to focus on making an appropriate choice of CA, in consideration of efficacy, safety and appropriateness. Moreover, besides by cost/benefit models widely introduced in health management, radiologists are also influenced by their responsibility of appropriate use for the various diagnostic tests and, finally, the choice of best CA to utilise for each individual patient. Thus, the dilemma of choosing between the best and the most cost-effective tests and procedures is occurring more frequently every day. Different variables, such as the patient, examinations, and technology available, can affect the choice of CA in terms of obtaining the highest diagnostic quality, minimum impact on higher-risk patients, and optimisation of used volumes and injection flow

Electron impact polarization expected in solar EUV lines from flaring chromospheres/transition regions

We have evaluated lower bounds on the degree of impact Extreme Ultraviolet/Ultraviolet (EUV/UV) line polarization expected during solar flares. This polarization arises from collisional excitation by energetic electrons with non-Maxwellian velocity distributions. Linear polarization was observed in the S I 1437 A line by the Ultraviolet Spectrometer and Polarimeter/Solar Maximum Mission (UVSP/SMM) during a flare on 15 July 1980. An early interpretation suggested that impact excitation by electrons propagating through the steep temperature gradient of the flaring transition region/high chromosphere produced this polarization. Our calculations show that the observed polarization in this UV line cannot be due to this effect. We find instead that, in some flare models, the energetic electrons can produce an impact polarization of a few percent in EUV neutral helium lines (i.e., lambda lambda 522, 537, and 584 A)

Confocal laser scanning microscope, raman microscopy and western blotting to evaluate inflammatory response after myocardial infarction

Cardiac muscle necrosis is associated with inflammatory cascade that clears the infarct from dead cells and matrix debris, and then replaces the damaged tissue with scar, through three overlapping phases: the inflammatory phase, the proliferative phase and the maturation phase. Western blotting, laser confocal microscopy, Raman microscopy are valuable tools for studying the inflammatory response following myocardial infarction both humoral and cellular phase, allowing the identification and semiquantitative analysis of proteins produced during the inflammatory cascade activation and the topographical distribution and expression of proteins and cells involved in myocardial inflammation. Confocal laser scanning microscopy (CLSM) is a relatively new technique for microscopic imaging, that allows greater resolution, optical sectioning of the sample and three-dimensional reconstruction of the same sample. Western blotting used to detect the presence of a specific protein with antibody-antigen interaction in the midst of a complex protein mixture extracted from cells, produced semi-quantitative data quite easy to interpret. Confocal Raman microscopy combines the three-dimensional optical resolution of confocal microscopy and the sensitivity to molecular vibrations, which characterizes Raman spectroscopy. The combined use of western blotting and confocal microscope allows detecting the presence of proteins in the sample and trying to observe the exact location within the tissue, or the topographical distribution of the same. Once demonstrated the presence of proteins (cytokines, chemokines, etc.) is important to know the topographical distribution, obtaining in this way additional information regarding the extension of the inflammatory process in function of the time stayed from the time of myocardial infarction. These methods may be useful to study and define the expression of a wide range of inflammatory mediators at several different timepoints providing a more detailed analysis of the time course of the infarct

An immunohistochemical study of the diagnostic value of TREM-1 as marker for fatal sepsis cases

Triggering receptor expressed on myeloid cells-1 (TREM-1) is produced and up-regulated by exposure of myeloid cells to lipopolysaccharides or other components of either bacterial or fungal origin, which causes it to be strongly expressed on phagocytes that accumulate in inflamed areas. Because TREM-1 participates in septic shock and in amplifying the inflammatory response to bacterial and fungal infections, we believe it could be an immunohistochemical marker for postmortem diagnosis of sepsis. We tested the anti-TREM-1 antibody in 28 cases of death by septic shock and divided them into two groups. The diagnosis was made according to the criteria of the Surviving Sepsis Campaign. In all cases, blood cultures were positive. The first group was comprised subjects that presented high ante-mortem serum procalcitonin and the soluble form of TREM-1 (s-TREM-1) values. The second group comprised subjects in which s-TREM-1 was not measured ante-mortem. We used samples of brain, heart, lung, liver and kidney for each case to test the anti-TREM-1 antibody. A semiquantitative evaluation of the immunohistochemical findings was made. In lung samples, we found immunostaining in the cells of the monocyte line in 24 of 28 cases, which suggests that TREM-1 is produced principally by cells of the monocyte line. In liver tissue, we found low TREM-staining in the hepatocyte cytoplasm, duct epithelium, the portal-biliary space and blood vessel. In kidney tissue samples, we found the TREM-1 antibody immunostaining in glomeruli and renal tubules. We also found TREM-1 staining in the lumen of blood vessels. Immunohistochemical staining using the anti-TREM-1 antibody can be useful for postmortem diagnosis of sepsis

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

New frontiers in thermal analysis: A TG/Chemometrics approach for postmortem interval estimation in vitreous humor

The coupling of thermogravimetric analysis (TG) associated with chemometrics is proposed as an innovative approach in thanatochemistry in order to develop a new analytical tool using thermal analysis for the characterization of vitreous humor. Vitreous samples were selected from the medicolegal deaths which occurred in casualty and where the death interval is known. Only hospital deaths with no metabolic disorders were taken, and the precise time of death was certified by the treating physician. Samples were analyzed by TG7 thermobalance, and principal component analysis was used to evaluate the results. The TG/Chemometrics outcomes show a clearly distinct behavior according to the postmortem interval, concluding that TG and Chemometrics are capable of predicting the time since death using only a few microliters of vitreous, without any pretreatment and with an hour of analysis tim

Cardiovascular Involvement in Sepsis.

This special issue wants to contribute to a better understanding of cardiac involvement in sepsis. Sepsis is a complex syndrome that has recently been defined as “life-threatening organ dysfunction due to a dysregulated host response to infection”. It should be considered a major public health problem since it affects millions of people worldwide each year, and it accounts for most deaths in critically ill patients. The presence of myocardial dysfunction in sepsis is associated with higher mortality. A great attention has been dedicated to improving our knowledge and understanding of the intricate mechanisms underlying sepsis. However, data from the literature suggest the need to implement strategies to reliably measure sepsis morbidity and mortality. In fact, methods based on analyses of insurance claim data using sepsis-specific codes or separate codes for infection and organ dysfunction are unreliable in informing or measuring the effects of policy changes, and the postmortem diagnosis of sepsis is often elusive since postmortem investigations lack certain pathognomonic macroscopic and histopathological findings. From a morphological and diagnostic point of view, the term “septic disease” has been created to describe the cardiac involvement in the syndrome. However, this definition, rather than describing a morphological finding, was instead referred to the clinical setting. Although in recent years the concept of septic cardiomyopathy has evolved and it involves pathological alterations of myocardial cells in response to the multiplicity of acting mechanism of damage, the importance of structural changes during sepsis is often overlooked. In patients with sepsis, death is usually the result of a progressive multiorgan dysfunction, overlooking the primary infection through the hyperinflammation. The cardiac involvement as fundamental part of septic multiorgan dysfunction syndrome has been discussed for a long time