94 research outputs found

    Association between the intake of cocaine and a strong physical and emotional stress: a case report of a sudden death

    Get PDF
    Cocaine is a powerful sympathomimetic agent, that determines its effects either by inhibiting synaptic re-uptake of noradrenaline or through the direct stimulation of the release of catecholamines from the adrenal gland. Cocaine abuse is associated with various cardiovascular events including ventricular arrhytmias, systemic hypertension, myocardial infarction and left ventricular hypertrophy. These effects are independent of the dose and route of administration of the substance and can be noticeably enhanced by the synergistic action of factors such as stress, smoking and alcoholism. The case that we report has involved a 48 year old man, who died of acute myocardial infarction, which arose as the result of an intake of a large amount of cocaine and a strong physical and emotional stress

    Sudden death in lambda light chain AL cardiac amyloidosis: a review of literature and update for clinicians and pathologists

    Get PDF
    Light chain (AL) amyloidosis is the most common type of systemic amyloidosis, affecting around 10 people per million per year. In Europe, approximately 5000 new diagnosis per year are reported. Deposition of amyloid fibrils derived from antibody light chains are key pathogenic agents in AL amyloidosis. They can be deposited in multiple organs but cardiac involvement carries a major risk of mortality. The prognosis is poor in cases associated with multiple myeloma. The average survival is around 1 year. Up to half of all patients with cardiac amyloidosis die suddenly; 75% ofthose deaths are due to heart failure. Ventricular arrhythmia is also associated with cardiac amyloidosis and unexpected death. It is crucial to make a diagnosis and start treatment at an early stage. Recent data suggest that cardiac amyloidosis has become a treatable and curable condition with a combination of agents targeting multiple steps of the amyloid cascade. ICD implantation may not be as effective for the therapy of light chain (AL) cardiac amyloidosis as supposed earlier. In cases of unexpected and sudden death, autopsy may show unknown conditions and is valuable to assess existing risks for family members. Even after careful autopsy, a proportion of sudden deaths, ranging from 2 to 54%, remain unexplained and this broad range of values is likely due to the heterogeneity of autopsy protocols. Post mortem diagnosis of cardiac amyloidosis still represents a challenge for forensic pathologists. Detailed morphologic study of the heart and a complete histopathologic study are mandatory. Immunohistochemistry is essential for amyloid subclassification. A review of existing literature is performed by the authors and a methodological approach in post mortem diagnosis of light chain AL cardiac amyloidosis is proposed. Both macroscopic and microscopic findings are discussed

    Hypo-Expression of Flice-Inhibitory Protein and Activation of the Caspase-8 Apoptotic Pathways in the Death-Inducing Signaling Complex Due to Ischemia Induced by the Compression of the Asphyxiogenic Tool on the Skin in Hanging Cases

    Get PDF
    The FLICE-inhibitory protein (c-FLIPL) (55 kDa) is expressed in numerous tissues and most abundantly in the kidney, skeletal muscles and heart. The c-FLIPL has a region of homology with caspase-8 at the carboxy-terminal end which allows the molecule to assume a tertiary structure similar to that of caspases-8 and -10. Consequently, c-FLIPL acts as a negative inhibitor of caspase-8, preventing the processing and subsequent release of the pro-apoptotic molecule active form. The c-FLIP plays as an inhibitor of apoptosis induced by a variety of agents, such as tumor necrosis factor (TNF), T cell receptor (TCR), TNF-related apoptosis inducing ligand (TRAIL), Fas and death receptor (DR). Increased expression of c-FLIP has been found in many human malignancies and shown to be involved in resistance to CD95/Fas and TRAIL receptor-induced apoptosis. We wanted to verify an investigative protocol using FLIP to make a differential diagnosis between skin sulcus with vitality or non-vital skin sulcus in hanged subjects and those undergoing simulated hanging (suspension of the victim after murder). The study group consisted of 21 cases who died from suicidal hanging. The control group consisted of traumatic or natural deaths, while a third group consisted of simulated hanging cases. The reactions to the Anti-FLIP Antibody (Abcam clone-8421) was scored for each section with a semi-quantitative method by means of microscopic observation carried out with confocal microscopy and three-dimensional reconstruction. The results obtained allow us to state that the skin reaction to the FLIP is extremely clear and precise, allowing a diagnosis of unequivocal vitality and a very objective differentiation with the post-mortal skin sulcus

    Immunohistochemical evaluation of aquaporin-4 and its correlation with CD68, IBA-1, HIF-1α, GFAP, and CD15 expressions in fatal traumatic brain injury

    Get PDF
    Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide. Our understanding of its pathobiology has substantially increased. Following TBI, the following occur, edema formation, brain swelling, increased intracranial pressure, changes in cerebral blood flow, hypoxia, neuroinflammation, oxidative stress, excitotoxicity, and apoptosis. Experimental animal models have been developed. However, the difficulty in mimicking human TBI explains why few neuroprotective strategies, drawn up on the basis of experimental studies, have translated into improved therapeutic strategies for TBI patients. In this study, we retrospectively examined brain samples in 145 cases of death after different survival times following TBI, to investigate aquaporin-4 (AQP4) expression and correlation with hypoxia, and neuroinflammation in human TBI. Antibodies anti-glial fibrillary acid protein (GFAP), aquaporin-4 (AQP4), hypoxia induced factor-1α (HIF-1α), macrophage/phagocytic activation (CD68), ionized calcium-binding adapter molecule-1 (IBA-1), and neutrophils (CD15) were used. AQP4 showed a significant, progressive increase between the control group and groups 2 (one-day survival) and 3 (three-day survival). There were further increases in AQP4 immunopositivity in groups 4 (seven-day survival), 5 (14-dayssurvival), and 6 (30-day survival), suggesting an upregulation of AQP4 at 7 to 30 days compared to group 1. GFAP showed its highest expression in non-acute cases at the astrocytic level compared with the acute TBI group. Data emerging from the HIF-1α reaction showed a progressive, significant increase. Immunohistochemistry with IBA-1 revealed activated microglia starting three days after trauma and progressively increasing in the next 15 to 20 days after the initial trauma. CD68 expression demonstrated basal macrophage and phagocytic activation mostly around blood vessels. Starting from one to three days of survival after TBI, an increase in the number of CD68 cells was progressively observed; at 15 and 30 days of survival, CD68 showed the most abundant immunopositivity inside or around the areas of necrosis. These findings need to be developed further to gain insight into the mechanisms through which brain AQP4 is upregulated. This could be of the utmost clinicopathological importance

    Regulation of miRNAs as new tool for cutaneous vitality lesions demonstration in ligature marks in deaths by hanging

    Get PDF
    This study aims to demonstrate that the application of miRNA expression in forensic pathology, in cases of hanging, applying the method on skin samples. The proposed investigative protocol allowed us to highlight a different miRNA expression in the skin ligature marks of subjects who died by hanging compared to healthy skin control samples. The results obtained showed an increase in the expression of miRNAs recognized as regulators of the inflammatory response in skin lesions such as miR125a-5p and miR125b-5p. Furthermore, overexpression of additional miRNAs – miR214a-3p, miR128-3p, miR130a-3p, and miR92a-3p – with anti-inflammatory activity was highlighted. It was possible to document a statistical significance to control skin samples only for miR103a-3p (p < 0.05), miR214-3p and miR92a-3p (p < 0.01) The upregulation of miR222-3p and miR150-5p, respectively related to mast-cell activation and neutrophils after the application of traumatic stimuli supports the immunohistochemical data showed in literature. The diagnostic accuracy of miRNAs could expand the range of diagnostic tools available in the assessment of the vitality of a lesion
    • …
    corecore