The link between brain iron homeostasis and neurodegenerative disease has been the subject of extensive research. There is increasing evidence of iron accumulation during ageing, and altered iron levels in some specific brain regions in neurodegenerative disease patients have been reported. Using graphite furnace atomic absorption spectrometry after microwave-assisted acid digestion of the samples, iron levels were determined in 14 different areas of the human brain [frontal cortex, superior and middle temporal, caudate nucleus, putamen, globus pallidus, cingulated gyrus, hippocampus, inferior parietal lobule, visual cortex of the occipital lobe, midbrain, pons (locus coeruleus), medulla and cerebellum (dentate nucleus)] of n=42 adult individuals (71±12 years old, range: 53-101 years old) with no known history or evidence of neurodegenerative, neurological or psychiatric disorders. It was found that the iron distribution in the adult human brain is quite heterogeneous. The highest levels were found in the putamen (mean±SD, range: 855±295μg/g, 304-1628μg/g) and globus pallidus (739±390μg/g, 225-1870μg/g), and the lowest levels were observed in the pons (98±43μg/g, 11-253μg/g) and medulla (56±25μg/g, 13-115μg/g). Globally, iron levels proved to be age-related. The positive correlation between iron levels and age was most significant in the basal ganglia (caudate nucleus, putamen and globus pallidus). Compared with the age-matched control group, altered iron levels were observed in specific brain areas of one Parkinson's disease patient (the basal ganglia) and two Alzheimer's disease patients (the hippocampus).

Forensic toxicology is the study and practice of the application of toxicology to the purposes of the law. The relevance of any finding is determined, in the first instance, by the nature and integrity of the specimen(s) submitted for analysis. This means that there are several specific challenges to select and collect specimens for ante-mortem and post-mortem toxicology investigation. Post-mortem specimens may be numerous and can endow some special difficulties compared to clinical specimens, namely those resulting from autolytic and putrefactive changes. Storage stability is also an important issue to be considered during the pre-analytic phase, since its consideration should facilitate the assessment of sample quality and the analytical result obtained from that sample. The knowledge on degradation mechanisms and methods to increase storage stability may enable the forensic toxicologist to circumvent possible difficulties. Therefore, advantages and limitations of specimen preservation procedures are thoroughfully discussed in this review. Presently, harmonized protocols for sampling in suspected intoxications would have obvious utility. In the present article an overview is given on sampling procedures for routinely collected specimens as well as on alternative specimens that may provide additional information on the route and timing of exposure to a specific xenobiotic. Last, but not least, a discussion on possible bias that can influence the interpretation of toxicological results is provided. This comprehensive review article is intented as a significant help for forensic toxicologists to accomplish their frequently overwhelming mission.

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Summary Objective Thirty percent of patients with epilepsy are refractory to medication. The majority of these patients have mesial temporal lobe epilepsy (MTLE). This prompts for new pharmacologic targets, like ATP‐mediated signaling pathways, since the extracellular levels of the nucleotide dramatically increase during in vitro epileptic seizures. In this study, we investigated whether sodium‐dependent high‐affinity γ‐aminobutyric acid (GABA) and glutamate uptake by isolated nerve terminals of the human neocortex could be modulated by ATP acting via slow‐desensitizing P2X7 receptor (P2X7R). Methods Modulation of [3H]GABA and [14C]glutamate uptake by ATP, through activation of P2X7R, was investigated in isolated nerve terminals of the neocortex of cadaveric controls and patients with drug‐resistant epilepsy (non‐MTLE or MTLE) submitted to surgery. Tissue density and distribution of P2X7R in the human neocortex was assessed by Western blot analysis and immunofluorescence confocal microscopy. Results The P2X7R agonist, 2′(3′)‐O‐(4‐benzoylbenzoyl)ATP (BzATP, 3–100 μm) decreased [3H]GABA and [14C]glutamate uptake by nerve terminals of the neocortex of controls and patients with epilepsy. The inhibitory effect of BzATP (100 μm) was prevented by the selective P2X7R antagonist, A‐438079 (3 μm). Down‐modulation of [14C]glutamate uptake by BzATP (100 μm) was roughly similar in controls and patients with epilepsy, but the P2X7R agonist inhibited more effectively [3H]GABA uptake in the epileptic tissue. Neocortical nerve terminals of patients with epilepsy express higher amounts of the P2X7R protein than control samples. Significance High‐frequency cortical activity during epileptic seizures releases huge amounts of ATP, which by acting on low‐affinity slowly desensitizing ionotropic P2X7R, leads to down‐modulation of neuronal GABA and glutamate uptake. Increased P2X7R expression in neocortical nerve terminals of patients with epilepsy may, under high‐frequency firing, endure GABA signaling and increase GABAergic rundown, thereby unbalancing glutamatergic neuroexcitation. This study highlights the relevance of the ATP‐sensitive P2X7R as an important negative modulator of GABA and glutamate transport and prompts for novel antiepileptic therapeutic targets.

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Background/Aims: To compare biomechanical properties of vaginal tissues between women with and without pelvic organ prolapse (POP) and investigate factors that may influence these properties. Methods: Forty patients submitted to POP surgery and 15 non-POP cadavers were evaluated. The tissue was excised from anterior and posterior middle third vagina. The biomechanical properties considered were stiffness (E) and maximum stress (S_max), and they were evaluated by means of uniaxial tension tests. Results: POP patients were associated with higher values of E (13.1 ± 0.8 vs. 9.5 ± 0.7 MPa; p < 0.001) and S_max (5.3 ± 0.5 vs. 3.2 ± 0.9 MPa; p < 0.001) in the anterior vaginal wall compared to the posterior wall. In contrast, non-POP women presented lower values of E (6.9 ± 1.1 vs. 10.5 ± 1.0 MPa; p = 0.01) and S_max (2.6 ± 0.4 vs. 3.5 ± 0.4 MPa; p = 0.043) in the anterior wall. The occurrence of POP was the only independent predictor of higher values of E and S_max in anterior vaginal samples (p = 0.003 and p = 0.008, respectively). Women with severe anterior vaginal prolapse presented higher levels of E and S_max in the anterior sample compared to those with lower POP stages (p = 0.001 and p = 0.01; respectively). Conclusion: Women with POP present significant changes of biomechanical properties in the vagina.

Tobacco use kills millions of people every year around the world. The current level of 11 metals in tobacco was determined and their transfer rate to cigarette smoke was calculated as the difference between the total metal content in cigarettes and the amount present in its ashes. The metals content was also determined in the lung tissue of smokers and non-smokers in order to evaluate the marks that smoking leaves in this tissue. Metals content in tobacco ranged from less than 1μg/g (Co, Cd, Pb, As and Tl) to several hundreds of μg/g (Al, Mn and Ba). The highest transfer rate from tobacco to cigarette smoke was found for Tl (85-92%) and Cd (81-90%), followed by Pb (46-60%) and As (33-44%). Significantly higher levels of As, Cd and Pb were found in the lung tissue of smokers compared to non-smokers, showing that smoking results in an increase of these metals in the lungs and that they contribute to the carcinogenic potential of cigarette smoke. This study presents important data on current metals content in tobacco and its transference to cigarette smoke and provides evidence of their accumulation in smokers' lung tissue.